American Journal Of Medicine

March 31, 2008 (Chicago) -- An experimental weight loss drug helped dieters shed an average of 14.5 pounds over the course of one year.

Researchers studied more than 800 overweight and obese people on a diet and exercise program; 28% of those given the drug taranabant lost more than 10% of their body weight compared with 8% of those taking placebo.

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"Even losing just 5% of your body weight is important to your health," says researcher Louis Aronne, MD, clinical professor of medicine at Weill-Cornell Medical College and director of the comprehensive weight control program at New York Presbyterian Hospital.

"It will help you lower your risk factors of cardiovascular disease," he tells WebMD.

The findings were presented at the 57th annual scientific session of the American College of Cardiology.

Weight Loss Accompanied by Lower Triglycerides

The one-year study involved 414 patients randomly assigned to take 2 milligrams of taranabant daily and 417 patients given placebo.

Results showed that patients reached their lowest weight about nine months into the study. They were then able to maintain that weight for the rest of the year, Aronne says.

Patients taking taranabant also experienced a rise in levels of HDL"good" cholesterol and a drop in triglyceride levels.

The most common side effects were nausea and diarrhea, but less than 2% of patients dropped out because of these problems.

Taranabant Helps You Resist Food Cravings

Taranabant is a member of the same class of drugs as Zimulti. Taranbant helps people resist food cravings by partially shutting down the cannabinoid system.

Zimulti recently failed to win approval from an FDA advisory panel, mainly because of fears that it could lead to depression and suicidal thoughts in some patients. The drug was previously known as Acomplia.

But at the 2-milligram dose, taranabant was not associated with an increased risk of depression or suicidal thoughts, Aronne says. People taking the drug were also no more likely to suffer from crying, tearfulness, or anxiety than those on placebo.

In fact, irritability was the only psychiatric symptom experienced by more patients taking the 2-milligram dose of taranabant compared with placebo, says Noreen Verbrugge, a spokesperson for Merck Research Laboratories. Merck makes taranabant and sponsored the study.

The study also included patients given a higher dose of taranabant. But due to a high rate of side effects, only the 2-milligram dose will be studied further, she says.

American Heart Association President Dan Jones, MD, dean of the University of Mississippi School of Medicine in Jackson, tells WebMD that much more study is needed. "Weight loss is highly complex," he says, and "every [drug] we have tried to attack it with has been associated with substantial side effects.

"These were all people that were highly motivated to lose weight," Jones says. "I worry that adverse events will be even higher in the real world."

Merck hopes to file an application with the FDA for drug approval in 2008, according to Verbrugge.

View Article Sources

SOURCES:

American College of Cardiology 57th Annual Scientific Session, Chicago, March 30-April 2, 2008.

Louis Aronne, MD, clinical professor of medicine, Weill-Cornell Medical College; director, comprehensive weight control program, New York Presbyterian Hospital.

Noreen Verbrugge, Merck Research Laboratories, Rahway, N.J.

Dan Jones, MD, president, American Heart Association; dean, University of Mississippi School of Medicine, Jackson.

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March 31, 2008 -- Adults being treated for diabetes are just as likely to have a heart attack or stroke or die from cardiovascular causes as people who have had a prior heart attack, new research shows.

They are also twice as likely as non-diabetics to die following a heart attack, the study revealed.

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Researchers say the population study confirms the importance of treating cardiovascular risk factors as aggressively as diabetes in adults with type 1 or type 2 disease.

"Adults who need glucose-lowering drugs are at very high risk for heart attacks and strokes, and they need to be monitored closely for this and treated with appropriate medications," study researcher Tina Ken Schramm, MD, tells WebMD.

Diabetes and Heart Risk

By examining Danish population registries, Schramm and colleagues from Denmark's Gentofte University Hospital followed 3.3 million adults over the age of 30 for five years between 1997 and 2002, including 71,801 people with diabetes and 79,575 who had had a previous heart attack.

Because of the comprehensive nature of the Danish registries, the researchers were able to identify and include all patients in the country with diabetes who were being treated with blood sugar-lowering drugs.

Patients being treated for diabetes had a cardiovascular risk comparable to patients without diabetes who had experienced a previous heart attack.

And compared with people without diabetes or a previous heart attack, the risk of having a heart attack was 11 times greater for women and seven times greater for men with both diabetes and a prior heart attack, Schramm tells WebMD.

"The increased risk was observed at all ages with either type 1 or type 2 diabetes who were receiving insulin or other drugs to reduce levels of sugar in the blood," Schramm notes. "When people with diabetes do have heart attacks, they are twice as likely to die as nondiabetics."

Drugs and Lifestyle Changes

Schramm says patients on insulin or those taking drugs to control their blood sugar should talk to their doctor about also taking low-dose aspirin for their heart, and their blood pressure and cholesterol should be monitored closely and treated aggressively.

In a joint statement issued last week by the American Diabetes Association and the American College of Cardiology, experts concluded that persons with diabetes might need even more aggressive cholesterol lowering than current guidelines suggest.

But many diabetic people remain unaware of their risk, and most are not being treated as aggressively as they should be, Northwestern University professor of preventive medicine Martha L. Daviglus, MD, PhD, tells WebMD.

"Little by little I think people are beginning to understand the dreadful consequences of diabetes, but we have to do more to make patients aware," she says. "It has been considered just another risk factor for heart attack and stroke. We now know that it is much more than this."

Daviglus, who is also a spokeswoman for the American Heart Association, says in addition to aggressive drug treatment, patients need to understand the importance of making lifestyle changes that can lower their cardiovascular risks.

Those lifestyle changes include losing weight, stopping smoking, and exercising regularly.

"We now know that diabetes is a totally reversible risk factor for cardiovascular disease," she says. "That is very important for patients to remember."

View Article Sources

SOURCES:

Schramm, T.K., Circulation, April 15, 2008; online edition.

Tina Ken Schramm, MD, research fellow, department of cardiology, Gentofte University Hospital, Hellerup, Denmark.

Martha L. Daviglus, MD, PhD, professor of preventive medicine, Northwestern University Feinberg School of Medicine, Chicago.

WebMd Medical News: "Cholesterol Testing Not Enough for Some."

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March 31, 2008 -- The antidepressantElavil prevents lung infection in mice with cystic fibrosis, but the dose must be exactly right to avoid harm.

The finding comes from researchers who may have found the key to why the genetic mutation that causes cystic fibrosis leads to the deadly lung-clogging infections that are the hallmark of the disease.

The cystic-fibrosis mutation disables a gene called CFTR (cystic fibrosis transmembrane conductance regulator). Researchers Erich Gulbins, MD, PhD, of Germany's University of Duisburg-Essen and colleagues now find that CFTR dysfunction upsets a delicate chemical balance in the lungs. This results in accumulation of a sticky lipid called ceramide.

As ceramide accumulates, it inflames the lung and kills lung cells. Debris from the dead cells piles up, giving a foothold to dangerous bacteria -- particularly the pseudomonas germs that plague people with cystic fibrosis.

Gulbins' team showed that this happens in mice lacking the CFTR gene. But they could prevent lung inflammation and pseudomonas infection by giving the animals Elavil.

Elavil is commonly used as an antidepressant. The drug works in cystic fibrosis by blocking an enzyme, Asm, that becomes overactive when CFTR isn't working properly.

"Treatment of CFTR-deficient mice with [Elavil] ... normalizes pulmonary ceramide and prevents all pathological findings, including susceptibility to infection," Gulbins and colleagues report. "Normalization of ceramide levels by [Elavil] may represent a new and important strategy to prevent bacterial infection in people with cystic fibrosis."

By blocking Asm, Elavil causes the body to make less ceramide. But Gulbins and colleagues warn that too little ceramide is dangerous. The sticky molecule helps remove bacteria from the airways. Mice with too little ceramide are unable to fight off lung infections.

"Thus any future cystic fibrosis drug targeting the Asm must be carefully titrated to normalize ceramide levels in the lungs of people with cystic fibrosis, but not reduce ceramide concentrations below a critical cellular level that would impair the biological functions of ceramide," they note.

Gulbins and colleagues report their findings in the March 30 online edition of Nature Medicine.

View Article Sources

SOURCES:

Teichgraber, V. Nature Medicine, advance online publication, March 30, 2008.

News release, Nature Medicine.

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March 31, 2008 -- When it comes to saving the life of someone whose heart has suddenly stopped, it may be best for bystanders to keep it simple and use chest compressions.

The American Heart Association is issuing a "call to action" for bystanders who are not trained in conventional CPR to use only their hands, without the rescue breathing, in the crucial moments after they witness an out-of-hospital sudden cardiac arrest, when the heart stops beating.

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CPR stands for cardiopulmonary resuscitation. It's intended to keep blood moving in people whose hearts have stopped and help keep someone alive until an emergency medical team arrives.

Conventional CPR includes two parts. One part is mouth-to-mouth resuscitation, also known as the "breath of life." The second part is chest compressions, when you push down hard and fast on a person's chest, more than once a second, pressing down at least an inch and a half before releasing.

"Many times people nearby don't help because they're afraid that they will hurt the victim and aren't confident in what they're doing," says Michael Sayre, MD, chairman of the AHA's statement writing committee. Sayre is associate professor in the Ohio State University department of emergency medicine in Columbus.

Sayre says that by using what is called hands-only CPR, or chest compressions, "bystanders can still act to improve the odds of survival, whether they are trained in conventional CPR or not."

According to the AHA, more than 300,000 U.S. adults die annually from sudden cardiac arrest outside the hospital.

Hands-Only CPR

The AHA's 2005 recommendations urged bystanders to use compression-only CPR only if they were unable or unwilling to give rescue breaths. This update follows recent studies and the consensus of the AHA's Emergency Cardiovascular Care Committee.

These are the recommendations: If you are witness to a sudden collapse of an adult, call 911 and start chest compressions hard and fast in the middle of the chest.

If the bystander isn't trained in CPR or is not confident in being able to do rescue breaths, then they should only do hands-only CPR until emergency medical assistance arrives or an automated external defibrillator (AED) is available for use.

If the bystander was trained in CPR and is confident in being able to provide rescue breaths with minimal interruptions to chest compressions, then they should give CPR with a 30:2 ratio of chest compressions to breaths or hands-only CPR and continue until an AED is available or emergency medical providers arrive to help.

Newer studies have found that in people with out-of-hospital cardiac arrest, survival numbers were comparable between those who received chest-compression only CPR and conventional CPR.

The researchers also note it could take longer for someone trained in traditional CPR to get it going and that people giving chest compressions alone get to it faster with fewer interruptions.

Hands-Only CPR continued...

Research shows that while bystander CPR can more than double a person's chances of surviving cardiac arrest, in most cities it is performed in only about 27% to 33% percent of the cases. Chest compression-only CPR may help lower bystander reluctance to perform CPR.

The AHA is also recommending changes in the way CPR is taught, streamlining the technique by focusing more on how important chest compressions can be in keeping someone alive until they can get to a hospital.

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Some 94% of sudden cardiac arrest victims die before reaching the hospital, according to the AHA. On average, only 24% of cardiac arrests that occur outside of a hospital have had a bystander perform CPR.

How can you tell if someone's heart has stopped beating? According to the AHA, it's when the person collapses, does not respond to gentle shaking, stops breathing after two rescue breaths, and is still not breathing, coughing, or moving.

If you do give someone CPR, remember to call for help -- 911 -- immediately as it's intended only as a short-term measure until emergency medical help arrives.

The hands-only CPR technique is only for adults whom you have seen collapse outside the hospital. Hands-only CPR is not to be used for children or infants or an adult whose heart has stopped because of non-cardiac causes such as a drug overdose or near drowning. In those cases, the AHA says conventional CPR with breaths is still the best technique to perform. The AHA still encourages people to learn conventional CPR at which time they will also learn how to do compression-only CPR.

That statement and new recommendations are published in the April 29 edition of Circulation.

View Article Sources

SOURCES:

American Heart association: "Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest."

Michael R. Sayre, MD, associate professor, department of emergency medicine, Ohio State University.

News release, American Heart Association.

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March 31, 2008 -- Researchers are six steps closer to finding a genetic fingerprint to identify people particularly susceptible to type 2 diabetes.

To climb the six steps, an international consortium of researchers crunched data from three studies of some 2.2 million single DNA changes across the entire genomes of more than 10,000 people, with replication testing in separate samples of up to 54,000 people.

In the end, Wellcome Trust researcher Eleftheria Zeggini, PhD, and colleagues found six new genetic variations that each increase a person's risk of type 2 diabetes. With the six additions, there are now 16 genetic variations independently linked to type 2 diabetes risk.

None of the 16 gene variations causes diabetes. In fact, each contributes only slightly to diabetes. But the more of these variations researchers find, the closer they are to finding a genetic fingerprint for diabetes risk.

"By combining information from the large number of genes now implicated in diabetes risk, it may be possible to use genetic tools to identify people at unusually high or low risk of diabetes," study researcher David Altshuyler, MD, PhD, of Massachusetts General Hospital, MIT, and Harvard say in a news release. "However, until we know how to use this information to prompt beneficial changes in people's treatment or lifestyle, widespread genetic testing would be premature."

Interestingly, the genetic variant that carried the highest diabetes risk has also been found to predispose men to prostate cancer.

It's hard to know what to make of that association -- other than the fact that this gene is also linked to low blood sugar in fetuses and newborns.

The other five new genes linked to type 2 diabetes risk also offer clues to the cause of diabetes. These genes encode proteins that play roles in:

• Disruption of the normal life cycle of cells
• Pancreatic cancer
• Cell death
• Pancreatic function
• The development of pancreatic stem cells

"Each of these genes, therefore, provides new clues to the processes that go wrong when diabetes develops, and each provides an opportunity for the generation of new approaches for treating or preventing this condition," study researcher Mark McCarthy, MD, of the University of Oxford, England, says in the news release.

Researchers from the U.S. National Human Genome Research Institute participated in the study. The study appears in the March 30 advance online issue of Nature Genetics.

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SOURCES:

Zeggini, E. Nature Genetics, advance online publication, March 30, 2008.

News release, National Human Genome Research Institute.

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