RxPG News : Pharmacology

Advances in treating hip pain to be focus of International Society for Hip Arthroscopy meeting

Sat, 26 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Recent advances in diagnostic imaging techniques and hip arthroscopy procedures are giving physicians and surgeons better tools with which to treat hip pain. The 2009 International Society for Hip Arthroscopy meeting, hosted by Hospital for Special Surgery in New York, brings together leading surgeons from all over the world to take an in-depth look at hip arthroscopy and its potential benefits.

This inaugural meeting by the International Society for Hip Arthroscopy will concentrate on the rapidly changing field of arthroscopic hip surgery, said Robert Buly, M.D., attending orthopedic surgeon at Hospital for Special Surgery and course director of the ISHA meeting. Presentations will be focused on the current research and outcomes data associated with both common and new procedures.

Hip arthroscopy, a minimally invasive treatment option, is an alternative for some patients over open, invasive surgery. Through a few tiny incisions, doctors are able to insert tools to trim bone or repair cartilage. Previously, surgeons only had the option of opening up the entire hip with a large incision and dislocating the hip to access the joint. This procedure can be used to treat patients with femoro-acetabular impingement (FAI), also known as hip impingement, where there is a change in the bony form of the hip joint causing a decreased range of motion and pain, damage to the cartilage within the hip joint, such as labral tears, and other conditions.

It is not uncommon for hip pain due to hip impingement or labral tears to be misdiagnosed. The difficulty in diagnosing the underlying causes of hip pain doesn't affect only professional athletes like Alex Rodriguez, Carlos Delgado or Mike Lowell, who have been in the news for their injuries and subsequent treatment, but week-end warriors and everyday active individuals as well. Hospital for Special Surgery's Center for Hip Pain and Preservation uses the latest imaging technology and arthroscopic techniques to provide those experiencing hip pain with proper diagnosis and treatment.

Research highlights include outcomes data presented by Special Surgery's Dr. Buly and Bryan Kelly, M.D., co-director of the Center for Hip Pain and Preservation at Hospital for Special Surgery and a study by Marc Philippon, M.D., of the Steadman Hawkins Research Foundation in Colorado, on how to assess the ability of a patient to return to sports after arthroscopy. Two imaging advances, one on techniques that allow greater visibility into the hip joint and a second on a method that may identify the earliest onset of arthritis will be presented, as well as a British study on siblings that addresses the genetics underlying hip impingement.

The meeting will take place in New York on October 9 and 10, 2009 at the Roosevelt Hotel on Madison Avenue and 45th Street.

Too many ways to say 'it hurts'

Wed, 29 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO --- There are at least 100 ways to say, It hurts! And that is the problem.

David Cella is on mission -- backed by nearly $10 million in National Institutes of Health funds -- to revolutionize the language of pain, as well as fatigue, depression and anxiety. These are some of the important symptoms researchers measure when they try to figure out if a medical treatment improves the quality of life for a patient with a chronic disease.

Are they in too much pain to unload groceries from the car? Are they too tired or depressed to go out to lunch with a friend? The answers are vital for researchers to know if new treatments are useful or useless.

But the glitch is every group of researchers asks patients different questions to measure their symptoms. Thus, one group's measurement of severe pain or fatigue or depression may be different than another's. Because researchers aren't speaking a common language, doctors and other health care providers can't compare the results across studies to decide which is the best approach. Instead, study results remain separate puzzle pieces that never fit together into a whole picture.

Can you imagine if a doctor wanted to check your hemoglobin and there weren't any numbers to measure whether it was normal? asked Cella , professor and chair of the new department of medical social sciences at Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. When you say a patient's hemoglobin is 11, everybody knows what it means, but nobody knows what a pain of 36 means or a fatigue of 32 because we don't use common measures.

That's about to change. Cella is leading a far-reaching new national project that establishes a common scientific vocabulary. In August, he and colleagues from six other institutions and the NIH will release a set of free publicly available computerized tests for researchers to measure pain, fatigue, depression, anxiety and physical and social functioning. Now there will be a pain measurement of 75, for example, that will mean the same thing to every doctor and scientist.

The new project is called Patient-Reported Outcome Measurement Information System (PROMIS). More than 1,000 researchers have already registered to try the new tools.

Cella's project addresses President Obama's call for greater accountability in medical treatment. In order to have a system that works that way you need a consistent measure of outcomes that people can understand and relate to, Cella said. That's what we have developed.

The lack of a common vocabulary has hurt research, Cella noted. It's a Tower of Babel, a hodge-podge of language. It's a big problem because you can't migrate the results of one study to a broader understanding, he said. We keep having to learn the same things over and over. We are not building on a foundation of knowledge.

Not only have Cella and his team created a new language and tool for researchers, but the PROMIS project also represents a shift in the way researchers evaluate the benefits of treatments. The goal is not just to help people live longer but also live better.

X-rays, CT scans and lab tests may have minimal relevance to the day-to-day functioning of patients with chronic diseases. We help measure directly if people are living better by asking them, Cella said. Sometimes it's as simple as asking, 'Do you think this treatment has made your life better?' That question is surprisingly absent from many studies.

NHLBI stops study of pulmonary hypertension treatment in sickle cell patients

Tue, 28 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped a clinical trial testing a drug treatment for pulmonary hypertension in adults with sickle cell disease nearly one year early due to safety concerns. In an interim review of safety data from 33 participants who completed 16 weeks of treatment, researchers found that, compared to participants on placebo (dummy pill), participants taking sildenafil (Revatio) were significantly more likely to have serious medical problems. The most common problem was episodes of severe pain called sickle cell crises, which resulted in hospitalization. No deaths have been associated with the drug in the clinical trial.

Known as walk-PHaSST, the study was the first multicenter, randomized clinical trial to test the safety and effectiveness of sildenafil for pulmonary hypertension in patients with sickle cell disease, one of the most common genetic blood disorders in the United States. Pulmonary hypertension is a debilitating condition of high blood pressure in the arteries that carry blood to the lungs, which can lead to heart failure and death. Approximately 30 percent of sickle cell disease patients develop pulmonary hypertension, and even mild levels of pulmonary hypertension have been associated with sudden death in people with sickle cell disease.

The increase in sickle cell medical problems is concern enough for us to stop this clinical trial to protect the safety of our participants, said NHLBI Director Elizabeth G. Nabel, M.D. We will continue to look into the possible causes of these preliminary results. In the meantime, we encourage patients with sickle cell disease who are taking sildenafil for pulmonary hypertension to talk with their physicians about the potential risks and benefits of the medication and what actions they should consider, including whether to taper off this medication and how to best manage both sickle cell disease and pulmonary hypertension.

Because the medical problems experienced in walk-PHaSST were complications specific to sickle cell disease, The findings of the walk-PHaSST study should not be applied to other groups of patients with pulmonary hypertension where the drug has been found to be safe and effective, Nabel added.

Researchers are conducting extensive analyses of the study results, which could contribute to recommendations for treating pulmonary hypertension in patients with sickle cell disease. They will prepare reports of their research for publication in peer-reviewed journals.

The NHLBI stopped the study on July 7, 2009, based on the unanimous recommendations of the Pulmonary Complications of Sickle Cell Disease Data and Safety Monitoring Board (DSMB), an independent advisory group that has been monitoring the study since it began. This DSMB is composed of experts in sickle cell disease, lung disease, statistics, and bioethics.

Participants in walk-PHaSST have discussed the preliminary findings of the study with their study clinicians. They have been instructed to taper sildenafil treatment over a period of three to seven days to minimize problems associated with immediate withdrawal from the drug, such as worsening of symptoms of pulmonary hypertension. Researchers will continue to monitor participants and conduct further analyses to assess the findings.

Walk-PHaSST was designed to determine whether sildenafil lessens the symptoms of pulmonary hypertension, such as shortness of breath, by improving heart and lung function, in individuals with sickle cell disease who develop pulmonary hypertension. The primary outcome measure was the results of a six-minute walk test, a standard indicator of a person's heart and lung function. Hence, the name walk-PHaSST reflects the primary test used to assess effectiveness of the treatment (walk test) for Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy. Researchers also evaluated the safety of the drug for sickle cell disease patients through reports of adverse effects and laboratory tests.

Sildenafil is approved by the Food and Drug Administration for use in patients with pulmonary hypertension. In general, the drug treats pulmonary hypertension by relaxing the blood vessels in the lungs to allow blood to flow more easily. Since sildenafil is not FDA-approved to treat pulmonary hypertension in patients with sickle cell disease, the walk-PHaSST study was conducted under an investigational new drug application. The FDA was notified of the termination of the study on July 14.

Walk-PHaSST began recruiting participants in July 2007 and enrolled 74 patients over the age of 19 (average age 45). Participants had sickle cell disease and mild to severe pulmonary hypertension. They were randomly assigned to receive sildenafil or placebo for 16 weeks. Participants could also receive other therapies as needed to manage sickle cell and related complications. After completing the study treatment (or placebo), participants could choose to be part of the open-label follow-up phase of the study and continue to be assessed for up to one year. In the open-label study, participants and clinicians knew that sildenafil was being taken. When the study was stopped, 33 participants had completed the clinical trial.

Researchers found that 38 percent of participants taking sildenafil had serious adverse effects -- primarily sickle cell pain crises -- compared to 8 percent of participants in the placebo group.

Although these preliminary results are disappointing, we expect that the study's results, once fully analyzed, will provide important insights into the role of pulmonary hypertension in sickle cell disease, said Mark Gladwin, M.D., lead investigator of walk-PHaSST and director of the Vascular Medicine Institute at the University of Pittsburgh. Gladwin is also a special volunteer for the NHLBI and was formerly a senior investigator with the Critical Care Medicine Department at the NIH Clinical Center and chief of the NHLBI Pulmonary and Vascular Medicine Branch.

The design of the walk-PHaSST study was based on extensive evidence that sildenafil improves pulmonary hypertension regardless of its cause and on results of a small, open-label, nonrandomized pilot study led by Gladwin while he was at the NIH. The pilot study evaluated 12 sickle cell patients with mild or moderate pulmonary hypertension who were being treated with sildenafil and with hydroxyurea, a drug known to help reduce the numbers of episodes of sickle cell pain crises and acute chest syndrome, as well as hospitalizations and blood transfusions needed. In 2005, Gladwin and his colleagues reported that after about 6 months, sildenafil was well tolerated, decreased pulmonary blood pressure, and increased exercise capacity.

Walk-PHaSST emphasizes the importance of multi-site, blinded, randomized clinical trials to increase our understanding of both the benefits and the potential risks of specific treatments, noted Jonathan C. Goldsmith, M.D., NHLBI project officer of walk-PHaSST. As with all clinical studies, patient safety is paramount.

Walk PHaSST was conducted at the following locations:

Study to assess hip exercises as treatment for osteoarthritis in the knee joints

Wed, 15 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers at Rush University Medical Center are testing a novel regimen of hip-muscle exercises to decrease the load on the knee joints in patients with osteoarthritis. The goal is not only to relieve pain but also, possibly, to halt progression of the disease.

Each time you take a step, a load, or force, is placed on the knee joints. How much load depends not just on your weight, but also on the way you walk and the alignment of your leg, said Laura Thorp, PhD, assistant professor of anatomy and cell biology at Rush Medical College and principal investigator for the study. If we can appropriately alter the gait patterns of patients with osteoarthritis, we can minimize the load and relieve pain.

Ultimately, we're hoping we can prevent the disease from advancing. No treatment currently exists that can stop osteoarthritis from progressing in the knees, other than joint replacement surgery.

Osteoarthritis is the most common form of arthritis and a significant source of disability and impaired quality of life. A higher-than-normal load on the knees during walking is a hallmark of the disease, associated with both the severity of the osteoarthritis and its progression, according to Thorp.

Thorp is enrolling patients with mild to moderate osteoarthritis in their knees in a research study to determine the effectiveness of certain hip exercises in treating the disease. Study participants have their knees x-rayed and undergo an initial assessment in Rush's Human Motion Laboratory to measure the load on their knee joints while walking. Participants then follow a specific regimen of hip exercises for four weeks under the direction of Charles Cranny, clinical manager of outpatient physical therapy.

The exercises focus on strengthening the hip abductor muscles, such as the gluteus medius, a broad, thick, radiating muscle that helps to stabilize the pelvis during ambulation. In patients with osteoarthritis in the knees, these muscles tend to be weak, causing the pelvis to tilt toward the side of the swing leg when walking, instead of remaining level with the ground, which increases the load on the knee joints. Strengthening these muscles helps the pelvis and the knee remain in better alignment, and thereby lessens the load.

After the four weeks of supervised physical therapy, participants are reassessed to determine whether the load on the knees has decreased, and whether the pain has subsided.

The trial continues for another four weeks, with patients exercising at home to determine whether the adjustments in gait can be maintained.

According to Thorp, exercise regimens to date have focused largely on strengthening the quadriceps and hamstring muscles, which stabilize the knee joint but likely do little to correct alignment with the rest of the leg or alter the load on the joint.

Preliminary evidence in the present trial has already shown that a decrease in load is attained with hip-muscle exercises.

By lessening the load on the knees, we can remove one of the major known risk factors for the progression of osteoarthritis, Thorp said.

Study to assess hip exercises as treatment for osteoarthritis in the knee joints

Wed, 15 Jul 2009 03:59:36 PST

Lap-band weight-loss surgery can reverse metabolic syndrome in obese teens

Wed, 01 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) NEW YORK (June 30, 2009) -- A new study of obese adolescents has shown that laparoscopic gastric banding surgery -- the Lap-Band procedure -- not only helps them achieve significant weight loss but can also improve and even reverse metabolic syndrome, reducing their risk for cardiovascular disease and diabetes.

Metabolic syndrome is defined as a cluster of risk factors -- high blood pressure; low levels of HDL or good cholesterol; excessive abdominal fat; and elevated levels of blood sugar, C-reactive protein and triglycerides -- that increase a person's chances of developing cardiovascular disease or diabetes later in life. The single biggest risk factor is obesity, and metabolic syndrome usually improves when a person loses weight.

The study was led by Drs. Ilene Fennoy, Jeffrey Zitsman and colleagues at NewYork-Presbyterian Morgan Stanley Children's Hospital and Columbia University Medical Center and presented at the annual Endocrine Society meeting in Washington, D.C.

An estimated 17 percent of all American adolescents are obese, and increasing numbers of them also have metabolic syndrome, says Dr. Fennoy, a pediatric endocrinologist at NewYork-Presbyterian Morgan Stanley Children's Hospital, clinical professor of pediatrics at the Columbia University College of Physicians and Surgeons and co-author of the study. Until recently, there have been few treatments capable of helping these young patients lose weight, much less improving their lifelong health prospects. The Lap-Band may well be a useful intervention for tackling teen obesity -- which is why it is so important to investigate the procedure's safety and efficacy in this growing population.

In the new study, Dr. Fennoy and her colleagues followed 24 morbidly obese adolescents between the ages of 14 and 17 who underwent the Lap-Band procedure. The study participants either had a BMI of greater than 40 or greater than 35 if already suffering from diabetes or obesity-related illnesses.

Six months after surgery, they noted a significant drop in participants' BMI, waist circumference, and blood levels of C-reactive protein. These indicators continued to improve among the 12 patients being followed up at the one-year point.

Other measures of metabolic syndrome such as blood lipid and sugar levels, the authors reported, came down quickly in the first six months, with less dramatic changes seen one year after surgery.

Of all the bariatric procedures, she says, the Lap-Band is the most benign, with complication rates of less than 1 percent. The device, inserted via minimally invasive laparoscopic surgery, consists of a simple band to make the stomach smaller and a balloon that can be decompressed when necessary, she explains.

Although it is technically reversible, the procedure should be considered a long-term solution for extreme and intractable obesity.

The Lap-Band is the favored bariatric procedure in Europe, while in the U.S., gastric bypass has been the preferred approach. At present, NewYork-Presbyterian Morgan Stanley Children's Hospital/Columbia University Medical Center is one of a few medical centers offering the Lap-Band option in this country.

The Lap-Band procedure, an approved treatment for adults with extreme obesity, has not yet been thoroughly studied in adolescents. Larger, multicenter studies with longer follow-up periods will be needed, Dr. Fennoy says, to validate the findings of the current study.

Increased food intake alone explains the increase in body weight in the United States

Fri, 08 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, the Netherlands: New research that uses an innovative approach to study, for the first time, the relative contributions of food and exercise habits to the development of the obesity epidemic has concluded that the rise in obesity in the United States since the 1970s was virtually all due to increased energy intake.

How much of the obesity epidemic has been caused by excess calorie intake and how much by reductions in physical activity has been long debated and while experts agree that making it easier for people to eat less and exercise more are both important for combating it, they debate where the public health focus should be.

A study presented on Friday at the European Congress on Obesity is the first to examine the question of the proportional contributions to the obesity epidemic by combining metabolic relationships, the laws of thermodynamics, epidemiological data and agricultural data.

There have been a lot of assumptions that both reduced physical activity and increased energy intake have been major drivers of the obesity epidemic. Until now, nobody has proposed how to quantify their relative contributions to the rise in obesity since the 1970s. This study demonstrates that the weight gain in the American population seems to be virtually all explained by eating more calories. It appears that changes in physical activity played a minimal role, said the study's leader, Professor Boyd Swinburn, chair of population health and director of the World Health Organization Collaborating Centre for Obesity Prevention at Deakin University in Australia.

The scientists started by testing 1,399 adults and 963 children to determine how many calories their bodies burn in total under free-living conditions. The test is the most accurate measure of total calorie burning in real-life situations.

Once they had determined each person's calorie burning rate, Swinburn and his colleagues were able to calculate how much adults needed to eat in order to maintain a stable weight and how much children needed to eat in order to maintain a normal growth curve.

They then worked out how much Americans were actually eating, using national food supply data (the amount of food produced and imported, minus the amount exported, thrown away and used for animals or other non-human uses) from the 1970s and the early 2000s.

The researchers used their findings to predict how much weight they would expect Americans to have gained over the 30-year period studied if food intake were the only influence. They used data from a nationally representative survey (NHANES) that recorded the weight of Americans in the 1970s and early 2000s to determine the actual weight gain over that period.

If the actual weight increase was the same as what we predicted, that meant that food intake was virtually entirely responsible. If it wasn't, that meant changes in physical activity also played a role, Swinburn said. If the actual weight gain was higher than predicted, that would suggest that a decrease in physical activity played a role.

The researchers found that in children, the predicted and actual weight increase matched exactly, indicating that the increases in energy intake alone over the 30 years studied could explain the weight increase.

For adults, we predicted that they would be 10.8 kg heavier, but in fact they were 8.6 kg heavier. That suggests that excess food intake still explains the weight gain, but that there may have been increases in physical activity over the 30 years that have blunted what would otherwise have been a higher weight gain, Swinburn said.

To return to the average weights of the 1970s, we would need to reverse the increased food intake of about 350 calories a day for children (about one can of fizzy drink and a small portion of French fries) and 500 calories a day for adults (about one large hamburger), Swinburn said. Alternatively, we could achieve similar results by increasing physical activity by about 150 minutes a day of extra walking for children and 110 minutes for adults, but realistically, although a combination of both is needed, the focus would have to be on reducing calorie intake.

He emphasized that physical activity should not be ignored as a contributor to reducing obesity and should continue to be promoted because of its many other benefits, but that expectations regarding what can be achieved with exercise need to be lowered and public health policy shifted more toward encouraging people to eat less.

Study: Vibration plate machines may aid weight loss and trim abdominal fat

Fri, 08 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, the Netherlands: New research suggests that, if used properly, vibration plate exercise machines may help you lose weight and trim the particularly harmful belly fat between the organs.

In a study presented on Friday at the European Congress on Obesity, scientists found that overweight or obese people who regularly used the equipment in combination with a calorie restricted diet were more successful at long-term weight loss and shedding the fat around their abdominal organs than those who combined dieting with a more conventional fitness routine.

These machines are increasingly found in gyms across the industrialized world and have gathered a devoted following in some places, but there has not been any evidence that they help people lose weight. Our study, the first to investigate the effects of vibration in obese people, indicates it's a promising approach. It looks like these machines could be a useful addition to a weight control package, said the study's leader, Dirk Vissers, a physiotherapist at the Artesis University College and the University of Antwerp in Belgium.

Vissers and his colleagues studied the effects of the Power Plate in 61 overweight or obese people - mostly women - for a year. The intervention lasted six months, after which the scientists advised all the volunteers to do the best they could with a healthy diet and exercise regime on their own for another six months. Body measurements, including CT scans of abdominal fat, were taken at the beginning of the study and after three, six and 12 months.

The researchers divided the volunteers into four groups. One group was prescribed an individually calculated calorie restricted diet. Dietician visits were scheduled every fortnight for the first three months and every month for the second three months. The dieters were asked not to engage in any exercise for the duration of the six-month intervention.

A second group received the same diet intervention, with the addition of a conventional fitness regime. They attended supervised exercise classes twice a week for an hour and were urged to exercise on their own a third time each week. The sessions included group cycling, swimming, running, step aerobics and some general muscle strengthening exercises.

A third group got the diet intervention plus supervised vibration plate training instead of conventional exercise. They were asked not to do any aerobic exercise during the six-month intervention phase. The physiotherapists gradually increased the speed and intensity of the machine each week, as well as the variety and duration of the exercises from 30 seconds for each of 10 exercises to 60 seconds for each of 22 exercises, such as squats, lunges, calf raises, push-ups and abdominal crunches. The average time spent on the machine was 11.9 minutes per session in the first three months and 14.2 minutes in the second three months.

A fourth group got no intervention. There were no significant differences between the groups in obesity and abdominal, or visceral, fat at the start of the study.

Over the year, only the conventional fitness and vibration groups managed to maintain a 5% weight loss, which is what is considered enough to improve health, Vissers said.

During the first six months, the diet only group lost about 6% of their initial body weight, but could not maintain a 5% weight loss in the subsequent six months. The group that got diet plus conventional fitness lost about 7% of their initial body weight in the first six months, but they didn't put much of it back on and by the end of the study, they had managed to keep off a 6.9% loss. The vibration group lost 11% of their body weight during the intervention phase and by the end of the follow-up period they had maintained a 10.5% loss. The control group gained about 1.5% of their original body weight.

The vibration group lost 47.8 square centimetres of visceral fat during the first six months and still had a loss of 47.7 square centimetres at 12 months. Visceral fat shrank by 17.6 square centimetres in the conventional fitness group in the first six months, but by the end of the year, it was only 1.6 square centimetres less than at the beginning. The diet group had a visceral fat loss of 24.3 square centimetres after six months and 7.5 square centimetres after a year.

These are very encouraging results, but it doesn't mean people trying to lose weight can ditch aerobic exercise and jump on the vibration plate instead. They still need a healthy diet and aerobic exercise, but this could be a viable alternative to weight lifting, Vissers said, explaining that the plate works by making muscles rapidly contract, which builds lean muscle mass.

People say vibration machines are fitness for lazy people. It may feel like a short cut, but if it's easy, you are not doing it properly, he added. Supervision in the beginning is imperative and the longer the better. What we see in gyms very often - people just standing on the machine holding the handles - is not going to do anything.

Vissers said further research on a larger group of obese patients is needed to confirm how beneficial the machines are. His team is also planning to study why vibration seems to be more effective than aerobic exercise in trimming visceral fat, including whether increased blood flow to the abdomen and hormonal response to vibration might play a role in more efficient fat breakdown. His study was funded by the Artesis University College of Antwerp.

NC State develops new test method to measure stored heat in firefighter suits

Tue, 14 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) For decades, researchers have evaluated the thermal performance of protective clothing worn by firefighters. A particular area of current interest is how to address the burns received by firefighters when they are not directly in contact with fire - called stored heat burns. Researchers at North Carolina State University have developed a testing apparatus and measurement protocol that allow firefighter suits to be evaluated for their ability to prevent and minimize stored heat burns.

You can compare the burn to when you sit close to a fireplace, and then press down on your jeans and you can feel the heat, says Dr. Roger Barker, professor of textile engineering chemistry and science, and director of the Textile Protection and Comfort Center (T-PACC). Firefighters are getting burns without ever coming in direct contact with the flames. It is a serious issue.

Barker and his colleagues were contacted to develop and evaluate this new test method for stored heat measurement in a two-phase study. During the first phase, sponsored by the National Institute for Occupational Safety and Health, Barker and his team developed a laboratory testing apparatus to conduct the stored energy test which measures transferred and discharged heat in turnout suit materials. The second phase, sponsored by the National Fire Protection Research Foundation, involved using that apparatus to test a variety of firefighter suits and develop a database that will facilitate a new national standard that firefighter suits are measured against and certified.

All firefighter turnout suits are made of three layers - an outer shell, moisture barrier and thermal liner. There are many different combinations of fabrics and barriers used, and reinforcements and reflective trim are attached to the outer shell. Regardless of the combination of materials used, suits must go through a battery of tests to meet the standard set by the National Fire Protection Association, or NFPA.

One of the major objectives of our study was to better understand the role moisture - mostly the sweat from firefighters - plays in transferred and stored heat burns, Barker says. When moisture accumulates in the turnout suit materials, it has a big effect on the thermal properties of those materials and changes its heat capacity and thermal conductivity. These changes affect its thermal protective insulation and ability to store thermal energy.

The stored energy test protocol we developed includes having suit test materials pre-conditioned with moisture - similar to the sweat of a firefighter - in order to determine the effect on transferred and stored heat, Barker adds.

Throughout the development process, various stakeholders - including firefighters, suit manufacturers and members of the NFPA - provided feedback and input to NC State's researchers in order to develop a protocol that met the needs of the firefighters, while understanding the challenges and limitations of the manufacturing process. The NFPA is currently reviewing the protocol supplied by NC State's College of Textiles, and will consider adopting this test method as part of the requirements that manufacturers will need their suits to meet in order to have their suits certified as complying with the NFPA standard.

We know there is no lab test that measures with absolute accuracy what a firefighter encounters, because every fire is a different set of conditions and thermal threats, Barker says. However, we now have a better understanding of the general causes and mechanisms behind transferred and stored heat, and a test method to measure these effects. This research and recommended testing protocol is a major development that could significantly improve the health and safety for firefighters everywhere.

Codeine use and accident risk

Tue, 24 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The risk of being involved in a traffic accident with personal injury is significantly higher among codeine users than non-users. However, sporadic or moderate use of codeine alone does not carry an increased risk, according to a newly published study from the Norwegian Institute of Public Health.

Codeine and tramadol are painkillers in the opiate group, used for mild to moderate pain. In Norway, codeine is included in Paralgin forte and Pinex forte, and tramadol, amongst others, in Nobligan. Norway has a higher consumption of codeine preparations than other European countries.

Earlier studies have given conflicting results when evaluating traffic accident risk linked to the use of codeine and tramadol. In this new study from the Norwegian Institute of Public Health, anonymised data from the Norwegian Prescription Database and Road Traffic Accident Register was used to study whether codeine- or tramadol users have an increased risk of being involved in a traffic accident with personal injury.

During the 33 months of the study, 181 road traffic accidents were registered with personal injury where the driver had been exposed to codeine and 20 after exposure to tramadol. Exposure is defined as the first 7 days after the dispensing of a prescription for a codeine- or tramadol preparation.

The study showed that the risk of being involved in a road traffic accident with personal injury was twice as high in the period after having a prescription for codeine dispensed. For those who had used more than approximately 400 tablets per year, the risk of being involved in a traffic accident was 3 times as large. When the use of other potential impairing medicines was excluded, the risk of accident sank significantly. For sporadic codeine users there was no increased risk of accident. There was not a significantly higher risk for tramadol.

- We have previously seen that large users of codeine preparations often use benzodiazepines (anxiolytics- and hypnotics) or carisoprodol (muscle relaxants /painkillers) in addition. This is an important contributory factor when evaluating the accident risk, says the study's leader Liliana Bachs.

98 of the 181 drivers exposed to codeine who were included in the study had also been dispensed other medicines with abuse potential in the week prior to the accident.

- One can conclude that sporadic or moderate use of codeine alone to a small degree increases the chance of being involved in accidents with personal injury. Simultaneous use of benzodiazepines or carisoprodol gives a clear increase in the risk of accidents, explains Bachs.

Majority of family nurse practitioners have low awareness of influence of marketing by pharmaceutical companies

Tue, 10 Mar 2009 22:47:00 PST

( from http://www.rxpgnews.com ) Family nurse practitioners need to be more aware of the commercial pressures they face as a result of their increased involvement in prescribing, according to a survey published in the March issue of the UK-based Journal of Advanced Nursing.

"Our detailed study of 84 family nurse practitioners (FNPs) showed low awareness of how marketing by pharmaceutical companies affects clinical decisions and creates conflicts of interest" says Dr Nancy Crigger, from William Jewell College, Missouri, USA.

"However they were clear that some marketing activities, promotional items and gifts were less ethical and acceptable than others. For example, gifts that benefited patients and conferences were more acceptable than resort seminars and office equipment."

Dr Crigger, herself a qualified FNP, adds: "The influence of marketing on physician prescribing has been widely researched and this indicates that the more involved physicians are in marketing, the less likely they are to recognise when their clinical judgement has been compromised.

"Our study suggests that the same is now happening to FNPs who have been given greater responsibility for prescribing some types of medication."

Key findings from the survey included:

5% admitted that pharmaceutical reps influenced their prescribing and 26% said they did not, with the vast majority answering sometimes. However they said that other FNP colleagues (18%) and physicians (25%) were more likely to be influenced than them.

41% said they were not influenced by drug company marketing, but 17% said they were. 44% believed their prescribing was positively influenced by marketing rather than negatively, with 10% saying it wasn't.

Two-thirds said that promotional items did not influence their prescribing, with just 1% saying it did. 14% said that pharmaceutical representatives may cross ethical boundaries by giving FNPs gifts, but 42% said they did not.

Nurses were more in favour of education gifts and those that benefited patients. The majority said that educational gifts were ethical and appropriate (49%) and that non-education gifts were not (47%). 51% agreed with gifts that benefited patients and 52% opposed gifts that did not benefit patients.

45% said it was not acceptable or ethical to accept inexpensive gifts but 15% said it was. 59% disagreed with expensive gifts but 7% felt they were acceptable and ethical.

Nurses felt more comfortable attending sponsored events such as lunches and dinners (48%), trips (45%) and conferences (65%), but resort seminars (32%) and happy hour events (21%) were deemed less ethical.

50% felt that events organised by drug companies were more educational than promotional, but 15% disagreed.

62% of respondents accepted samples, 50% educational items, 41% office supplies and 30% office equipment.

41% said that their advanced practice training covered conflicts of interest when it came to drug marketing and 34% said it did not.

The FNPs who completed the 22-item questionnaire were chosen at random from a list of licensed nurses provided by the Missouri State Board of Nursing. 42% of the 200 nurses who were approached responded. Their ages ranged from 25 to 69 (average 47) and they had been in practice for one to 33 years (average 9.4). The majority (82%) were female and 60% served rural populations.

"Our study suggests that pharmaceutical marketing is widespread among FNPs and that FNPs fail to recognise how they are being influenced by this practice and that greater involvement in marketing may reduce their critical assessment of such practices" says Dr Crigger.

"It points to the need for all FNPs to evaluate their personal attitudes and practices concerning the ethical appropriateness of accepting gifts, meals, educational programmes and trips from pharmaceutical companies.

"We believe that prescription decision making should be based on the best interests of patients and on maintaining the trust of the patients and the public.

"Further research is needed to determine the impact of pharmaceutical marketing, but until then we believe that FNPs should avoid situations that could create a conflict of interest."

Mode of activity of recombinant human activated protein C (rhAPC) discovered

Wed, 25 Feb 2009 00:53:29 PST

( from http://www.rxpgnews.com ) Researchers have found a way to block the ability of white blood cells to sprint toward the sites of infection when such speed worsens the damage done by sepsis, the often fatal, whole-body bacterial infection, according to a study published in the journal Blood. The results recommend existing drugs as potential new treatments against sepsis, and suggest improvements in the current treatment that would increase its effect while eliminating a treatment-related risk for internal bleeding.

A simple bacterial infection becomes sepsis, or "blood poisoning," when it gets bad enough to set off system-wide responses from the body's immune defenses and blood-clotting system. It becomes septic shock when bacteria, the toxins they produce and the body's overwhelming immune response cause multiple organ failure. More than 30 percent of patients with severe sepsis die despite advances in critical care, about 250,000 people per year. Physicians currently rely on antibiotics and surgical drainage, but new options are needed.

White blood cells called neutrophils fight infection by swarming toward bacteria to engulf and destroy them with toxic molecules. Because these same molecules also damage human cells, this phase of the immune response is carefully contained and quickly shut down. The massive rush of neutrophils seen in sepsis, however, can overcome these restraints. In between infections, dormant neutrophils drift with the bloodstream until they "realize" they are passing by the part of a blood vessel wall closest to an infection. Proteins on the neutraphil's surface called integrins then unfold and "grab" the surface of the blood vessel wall, resisting the flow. The same proteins then help the neutraphil crawl along the tissue scaffold toward the infection site.

In the current study, a team of researchers at the University of Rochester Medical Center demonstrated for the first time that the only approved sepsis drug treatment, recombinant human activated protein C (rhAPC), has its effect by interfering with specific integrins on neutrophil surfaces, which keeps the cells from moving. Importantly, they also learned that a small protein piece of rhAPC, the "RGD" peptide, is responsible for the treatment's effectiveness against sepsis.

"Our results create the distinct possibility that several drugs already approved as safe in humans may have a second use in sepsis," said Minsoo Kim, Ph.D., assistant professor of Microbiology and Immunology within the David H. Smith Center for Vaccine Biology and Immunology at the Medical Center, and lead author of the article. "That is exciting because it could dramatically increase the pace at which new treatments for sepsis arrive in the clinic."

While the standard approach for decades has been to try to kill bacteria with antibiotics, some newer medications are designed to lessen the body's inflammatory reaction to sepsis. Most of these attempts have failed, but Drotrecogin alpha (brand name Xigris® from Eli Lilly), a genetically engineered (recombinant) form human activated protein C (rhAPC), was shown in a recent study to decrease mortality by about six percent, from 31 percent to 25 percent, in severe sepsis patients. Is the only FDA-approved drug for treating severe sepsis and the drug used in the current study.

Before its approval for use in sepsis, rhAPC was known for its ability to prevent blood clots, and researchers thought initially that this ability explained its efficacy against sepsis. When other anti-clotting agents failed to work the same way, however, researchers began looking elsewhere. Research published by Jerry Nick, M.D., and colleagues at the National Jewish Medical and Research Center (Blood. 2004;104:3878-3885) was the first to suggest that the benefit of rhAPC in sepsis might be explained by its effect on white blood cell migration, not blood coagulation, and several papers followed to confirm the idea. Until the current study, however, no one had been able to show how.

Furthermore, the U.S. Food and Drug Administration earlier this month announced that it was analyzing a report just published in the journal Critical Care Medicine that found Xigris, because of its effect on clotting, may increase the risk of dangerous bleeding in patients with a recent history of hemorrhages. The company argues that the study was flawed, and the drug's label is very clear about bleeding risk. Whatever the case, Jiang and colleagues are excited because their results argue that the part of Xigris that contributes to bleeding has nothing to do with its effect on sepsis, and can be removed.

Halting the Great Migration

In a neutrophil at rest, integrins are kept in a "non-stick" state. When the cell gets ready to move, however, integrins are quickly activated on the cell's "foot," the area where the cell touches the surface it wants to move across. Integrins bind to their partner proteins on the surface, and the neutraphil's cell skeleton contracts to pull itself over the leading-edge integrins. Previous studies in Kim's lab suggest that, without precise, integrin-mediated changes that enable the front end to gain traction, and the tail end to let go, immune cells could not migrate. He studied T cells in his earlier experiment, but the current results suggest the same processes are in play in neutrophils. In the current study, the research team showed for the first time that rhAPC has an effect on sepsis because it directly binds to β1 and β3 integrins on the surface of neutrophils and prevents those integrins from grabbing the surface.

Just as importantly, the team proved that human rhAPC contains the "RGD" three-amino acid chain. This peptide is a key component of several human proteins (e.g. fibronectin) over which neutrophils crawl because it has the right shape to be grabbed by integrin. In the case of rhAPC, its RGD chains grab neutraphil integrins first, taking away their ability to gain traction on surfaces. When the current research team changed the shape of the RGD sequence in rhAPC, the medication could neither bind to integrin nor interfere with the migration of neutrophils toward infection sites. In addition, treatment of septic mice with a single dose of the RGD peptide delivered the same improvement in survival as a dose of whole rhAPC, about 30 percent.

Kim's team tracked the ability of neutrophils to migrate across a glass plate coated with fibronectin. The team placed the neutrophils on the surface and then hit them with a type of molecule produced by bacteria, and toward which neutrophils swarm. The results show that, although neutrophils could sense the bacterial product and had a "desire" in chemical terms to move toward it, they could not in the presence of rhAPC.

Along with Kim, the work was led by Pranita Sarangi, Young-min Hyun, Joseph Hollenbaugh and David Topham within the Department of Microbiology and Immunology at the Medical Center, and by Hung-Li Chung and James McGrath in the Department of Biomechanical Engineering.

Gwendolyn Elphick, Alfred Ayala and Jonathan Reichner led the research at the Department of Surgery at Rhode Island Hospital, as did Walter Biffl in the Department of Surgery at Denver Health Medical Center and Alireza Rezaie in the Department of Biochemistry and Molecular Biology at the Saint Louis University School of Medicine. The work was supported by the National Institutes of Health.

"If, as suggested by our results and the literature, the effects of rhAPC on sepsis are attributable to reduced neutrophil migration, then anti-integrin agents represent a new class of drug candidates for sepsis," Kim said. "An RGD peptide already in clinical trials for cancer has potential against sepsis. We are also using molecular biology techniques to look for protein fragments similar to RGD, but with even greater ability to attach to and shut down activated integrins, and having shed the rhAPC anti-clotting functions that create bleeding risk."

New surgical option for wrist arthritis

Fri, 13 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) NEW YORK (Feb. 13, 2009) -- Breaking a fall, such as a tumble on the sidewalk, with your hands and wrists is everyone's natural reflex. But, if you fall hard enough, you'll often fracture your radius bone, or even one of the smaller wrist bones and wrist ligaments. Left untreated, these injuries could lead to disabling wrist arthritis.

For patients who develop wrist arthritis, a new surgical option known as OCRPRC (OsteoChondral Resurfacing in Proximal Row Carpectomy) is available at NewYork-Presbyterian Hospital/Columbia University Medical Center, where it is offered by one of the orthopedic surgeons who originally developed and described the technique -- Dr. Peter Tang. His research shows that the procedure reduces pain and improves hand function.

I often see patients who had a wrist injury in the past who either did not seek medical attention or whose original injury was not diagnosed. As with most things in medicine, the earlier a diagnosis is made, the better the outcome. So if you continue to have pain after a month, you should make an appointment to see a hand surgeon for an evaluation, says Dr. Tang, who is an orthopedic hand surgeon at NewYork-Presbyterian Hospital/Columbia University Medical Center and assistant professor of orthopedic surgery at Columbia University College of Physicians and Surgeons.

Because the biomechanics of the wrist is both delicate and complex, an alteration in the normal anatomy can lead to arthritis. Once disabling arthritis develops, surgery cannot simply fix the injured structure, but rather must remove the arthritis and improve wrist function. The two most common operations for wrist arthritis are a partial fusion of the small wrist bones (intercarpal fusion) and excision of the first row of carpal bones (proximal row carpectomy, or PRC). There are various reasons to choose one operation over the other, but PRC has a quicker recovery, may be better for older patients, gives equal grip strength to intercarpal fusion, and usually results in more wrist motion.

Once the three carpal bones are removed during the PRC procedure, the capitate bone becomes the point where the wrist articulates with the arm; as such, it is important that the arthritis has not progressed to the capitate bone.

For these patients whose arthritis has progressed, Dr. Tang has adapted a cartilage-grafting technique that is used effectively in sports medicine treatments for cartilage disorders in the knee, ankle and elbow. The results are promising, according to his study in the Journal of Hand Surgery, with improvement in grip strength and decrease in pain levels.

The goal of this new procedure is to give the best possible outcome by improving the cartilage status of the capitate bone. Another plus is that we do not have to take the graft from another part of the body. Even though we take out the three carpal bones for arthritis, there is usually one area of the bones where we can find undamaged cartilage for grafting, says Dr. Tang.

The study followed eight patients who underwent osteochondral resurfacing over 18 months. Preoperatively, seven patients described their pain as moderate to severe, while postoperatively, seven patients described their pain as mild to no pain, and one patient described the pain as moderate. Preoperative grip strength increased from 62 percent of their healthy side to postoperatively, 71 percent. Preoperative Mayo wrist score improved from a score of 51, which rates as poor, to a postoperative score of 68, which rates as fair.

Unexplained chest pain can be due to stress

Mon, 09 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Each year, many people seek emergency treatment for unexplained chest pains. A thesis from the Sahlgrenska Academy, University of Gothenburg, Sweden, indicates several common factors among those affected, including stress at work, anxiety, depression and a sedentary lifestyle.

Chest pain is a common reason for patients to seek emergency treatment. A considerable number of patients are diagnosed with unexplained chest pain, which means that the pain cannot be linked to biomedical factors such as heart disease, or some other illness. The patient group is significant in size, with just over 20,000 patients seeking hospital treatment in 2006, and so far researchers have been unable to identify specific causes for unexplained chest pain.

Many suffer from recurring bouts of pain over several years, while the healthcare services are unable to find out what's causing it, says Registered nurse Annika Janson Fagring, the author of the thesis.

In her thesis, Annika Janson Fagring describes and analyses symptoms among patients with unexplained chest pain. The results show that most of them are middle-aged, and that over a third of those affected were born outside Sweden. The chest pain had a negative impact on the patients' daily life in the form of tiredness, anxiety and fear of death.

The main difference between women and men with unexplained chest pain is that men were more likely to perceive their lives and jobs as being stressful, while women tended more to suffer from symptoms of depressions and anxiety, says Annika Janson Fagring.

The patients, both men and women, experienced more symptoms of depression and anxiety, and work-related stress when compared with a reference group of people who were not suffering from heart disease. The male patients were more physically active in their spare time than the female patients, but compared with the reference group, both the men and the women with unexplained chest pain led a more sedentary lifestyle.

The thesis also looks at the development of symptoms and the prognosis for patients with unexplained chest pain over a period of time, compared with patients suffering from angina and patients who had suffered a heart attack. A register study revealed that from 1987 up until 2000, the number of patients with diagnosed unexplained chest pain increased, and then levelled out. The number of patients with angina increased up until 1994 and has since fallen, while the number of patients who have suffered heart attacks has fallen throughout the whole period examined.

There were fewer deaths among patients with unexplained chest pain a year after they became ill, compared with patients that became ill with angina or suffered heart attacks. Deaths among men a year after falling ill with unexplained chest pain were a third higher compared with men in the rest of the population, while women did not display any increased risk of death.

Annika Janson Fagring says that the thesis shows that it is important to improve knowledge and understanding of the symptoms experienced by patients with unexplained chest pain, in order to be able to offer more individualised care.

ACE 2- Potential treatment for hypertension

Fri, 30 Jan 2009 14:47:36 PST

( from http://www.rxpgnews.com ) Huijing Xia, PhD, a postdoctoral research associate in the lab of Eric Lazartigues, PhD, Assistant Professor of Pharmacology at LSU Health Sciences Center New Orleans, is the lead author on a paper reporting that a recently identified enzyme in the brain plays a critically important role in the central regulation of blood pressure. The LSUHSC research team showed that Angiotensin-converting enzyme 2 (ACE2) helps preserve the function of a key spontaneous reflex involved in blood pressure regulation and confirms its potential as a target for the prevention or treatment of High Blood Pressure. The research is published in the February 1, 2009 issue of the peer reviewed journal, Hypertension, and the cover of the issue features images of ACE2 expression from the Lazartigues laboratory at LSU Health Sciences Center New Orleans.

The LSUHSC researchers had previously identified ACE2 in the mouse brain in areas involved in the central regulation of cardiovascular function. In this study, they wanted to clarify the role it plays.

Beat-to-beat short term regulation of blood pressure is provided by a spontaneous reflex called the baroreceptor reflex. Receptors in the arteries sense blood pressure and relay the information to the central nervous system where a network of brain stem cells adjust vascular resistance and heart rate. Action of a hypertensive hormone – Angiotensin II – is known to interfere with that process.

First, the researchers demonstrated that chronically hypertensive mice showed dramatically decreased baroreceptor reflex sensitivity and ACE2 activity. Following treatment with compounds to block both Angiotensin II receptors, the researchers found that by blocking one of these receptors – AT1Rs – ACE2 activity increased. In order to determine the relationship between AT1Rs blockade and ACE2, as well as the significance of ACE2, the LSUHSC researchers generated a triple-transgenic mouse model with increased ACE2 on a background of chronic hypertension. In this model, they observed that the impaired baroreceptor reflex and other critical functions normalized, as did blood pressure.

"We now have evidence that brain ACE2 plays a critical role in baroreceptor reflex function and , consequently, in the prevention of hypertension," says Dr. Xia.

"Blood pressure" is the force of blood pushing against the walls of the arteries as the heart pumps out blood. If this pressure rises and stays high over time, it can damage the body in many ways. According to the National Institutes of Health, in the United States, about 72 million people have hypertension or High Blood Pressure (HBP). This is about 1 in 3 adults. HBP itself usually has no symptoms. Rarely, headaches may occur. Some people only learn that they have HBP after it causes health problems, such as coronary heart disease, stroke, or kidney failure.

"Beyond our discovery of ACE2, we have now confirmed its potential as a target for the treatment of hypertension and other cardiovascular diseases," concludes Dr. Lazartigues.

Inhibition of protein HipA pevents cell dormancy and bacterial persistence

Thu, 15 Jan 2009 14:31:37 PST

( from http://www.rxpgnews.com ) Bacteria hunker down and survive antibiotic attack when a protein flips a chemical switch that throws them into a dormant state until treatment abates, researchers at The University of Texas M. D. Anderson Cancer Center report in the Jan.16 edition of Science.

"For antibiotics to work, bacteria have to be growing. Dormancy stops everything, allowing some bacteria to persist after treatment," said senior author Richard Brennan, Ph.D., professor in M. D. Anderson's Department of Biochemistry and Molecular Biology.

By demonstrating in detail how the HipA protein freezes bacterial activity, the researchers have opened the possibility of adding a new class of drugs to therapy against chronic and multidrug resistant bacterial infection.

Working in Escherichia coli, the team solved the structure of HipA and several of its protein complexes down to the atomic level, confirming that HipA is a protein kinase - an enzyme that works by transferring phosphate groups to its target molecules.

HipA is a type of protein kinase that is uncommon in bacteria, said lead author Maria Schumacher, Ph.D., associate professor of biochemistry and molecular biology. While other types of phosphorylation occur in bacteria, HipA phosphorylates proteins at their serine or threonine amino acids. This kinase activity is more commonly associated with eukaryotic cells, which make up animals, plants and fungi, and are generally thought to be more complex.

"These 'simple bacteria' are so complex. We're finding that life is sophisticated at all levels," Schumacher said. HipA is active in other types of gram-negative bacteria, which cause significant human bacterial infections.

Inhibitor could make persistent cells 'vanish'

A number of cancer drugs inhibit kinase activity in specific targets.

"If you stop HipA from working, there essentially is no persistence," Brennan said. "We need to see whether kinase inhibitors will bind to and block HipA's active site. If they work, persistent cells, which are already rare, would vanish." Persistent cells are a one-in-a-million-cells occurrence because HipA is normally kept in check by a protein called HipB.

Persistence is common in "biofilms," bacterial colonies that become attached to a surface in a supportive matrix. Drug-resistant biofilms cause about 60 percent of infections in the developed world, the researchers note.

Overexpression of HipA previously had been associated with cell dormancy and bacterial persistence. Evidence had pointed to kinase activity.

Schumacher, Brennan and colleagues demonstrated the molecular details of HipA's role in multidrug tolerance and HipB's role keeping HipA under wraps in a series of experiments:

Using X-ray crystallography to determine and then compare the structures of several HipA complexes, they showed that HipA has a serine/threonine protein kinase fold and that it binds tightly to adenosine triphosphate (ATP), a common characteristic of kinases. Phosphorylation occurs when an enzyme binds to both ATP and to its target protein.
Assays of candidate proteins to identify a target for HipA found that EF-Tu interacts strongly with HipA in the presence of ATP. EF-Tu is the most abundant protein in E.coli and plays an essential role in protein synthesis.
Subsequent experiments and structural analysis of a HipA/EF-Tu peptide complex indicated that HipA phosphorylates EF-Tu, freezing up the bacteria's protein-making machinery and inducing dormancy.
To analyze how HipB normally prevents HipA's function, the team solved the structure of the HipB/DNA/HipA complex. HipB tightly binds two HipA molecules in a sandwich-like structure.
HipB does not block HipA's active site, but inactivates it by forcing it into an "open" position. "Proteins move a lot to function, they open and close - think of a clam shell, for example," Brennan explains. To function, a protein must be able to close down on its target molecules - called substrates. The closed state is the active state.
HipB also might physically sequester HipA from EF-Tu because the HipA/HipB/DNA complex is located in E. coli's nucleoid, far from the bacteria's membrane where EF-Tu is mainly found.

HipA is free to cause trouble when its ties to HipB are broken; an infrequent occurrence which the authors note is likely caused by proteases tugging the smaller and structurally vulnerable HipB protein out of the complex.

Protein kinases often bind to more than one protein, so there are likely multiple targets for the protein in E. coli and other gram-negative bacteria, Schumacher and Brennan said.

Future research will focus on finding other HipA targets in E. coli, and kinase inhibitors will be examined for their ability to affect HipA function. If a promising inhibitor is found, its structure will be solved to clarify its binding mode and how it might be tweaked to bind HipA even better. "Structure-based drug design should provide the best chance at formulating highly specific and effective drugs against HipA," Schumacher said.

Study on spread of antibiotic resistance between bacteria

Sat, 10 Jan 2009 09:25:17 PST

( from http://www.rxpgnews.com ) Scientists have identified the structure of a key component of the bacteria behind such diseases as whooping cough, peptic stomach ulcers and Legionnaires' disease. The research, funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC), sheds light on how antibiotic resistance genes spread from one bacterium to another. The research may help scientists develop novel treatments for these diseases and novel ways to curtail the spread of antibiotic resistance.

Antibiotic resistance spreads when genetic material is exchanged between two bacteria, one of which has mutated to be resistant to the drugs. This exchange is facilitated by a multi-component device known as a type IV secretion system, which acts to transport antibiotic resistance genes from within one cell, through its membrane and into a neighbouring cell.

Type IV secretion systems also play an essential role in transporting toxins or proteins from within bacteria into the cells of the body, causing diseases. Examples of Gram-negative bacterial pathogens using such a device are Helicobacter pylori (which causes peptic ulcers), Legionella pneumophila (which causes Legionnaires' disease), and Bordetella pertussis (which causes whooping cough).

Now, in a paper published in the journal Science, scientists from the Institute of Structural and Molecular Biology (ISMB) at Birkbeck, University of London, and UCL (University College London) describe the structure of the core complex of a type IV secretion system, viewed using cryoelectron microscopy (a form of electron microscopy where the sample is studied at very low temperatures).

"Type IV secretion systems play key roles in secreting toxins which give certain bacteria their disease-causing properties and, importantly, are also directly involved in the spread of antibiotic resistance," says Professor Gabriel Waksman, Director of the ISMB and lead author of the study. "This is why they have become obvious targets in the vast effort required to fight infectious diseases caused by bacteria."

Gram-negative bacteria have a double membrane. At the core of the type IV secretion system is a double-walled chamber which spans the two membranes and opens at one side. Dr Waksman believes this chamber may offer a new pathway for targeting these bacteria.

"If we can inhibit the secretion systems that mediate transfer of antibiotic resistance genes from one bacterial pathogen to another, we could potentially prevent the spread of antibiotic resistance genes," he says. "For those pathogens that use type IV secretion system for secretion of toxins, the system can be targeted directly for inhibition. In both cases, this would have a considerable impact on public health."

Type IV secretion systems were first discovered in Agrobacterium tumefaciens, which uses the system to transfer tumour-inducing DNA into plants, causing "crown gall", which can be devastating to crops such as grape vines, sugar beet and rhubarb. However, crop scientists have been able to successfully exploit this transfer system as a way of introducing new genes into industrial crops, conferring herbicide-resistance and resistance to pathogens.

Genes for 9 health indicators

Sun, 07 Dec 2008 04:59:37 PST

( from http://www.rxpgnews.com ) A new genome-wide study examines genetic variants associated with nine metabolic traits and is the first to draw out novel variants from a population unselected for current disease. The traits are indicators for common disease such as cardiovascular disease, type 2 diabetes, blood pressure, inflammation and lipid levels.

Cohorts are followed throughout their lives, gathering lifelong information about their health: these data will help researchers to dissect the complex causes of common disease, whether genetic or environmental. The current study might indicate genetic variants that influence early development of disease, informing public health measures.

Unlike case-control studies, which make genomic comparisons of apparently healthy people with patients with a specific condition, cohort studies provide long-term information across a population.

The power of studies such as ours lies in their ability to examine these traits for early life events, to reflect the genetic make-up of the wider population and to investigate the relationship between genetic variation and environment over time, says Professor Leena Peltonen, Head of Human Genetics at the Wellcome Trust Sanger Institute and a senior author of the paper. Our study indicates that the environment accounts for around 30% or less of the consequences of the traits. Clearly we have to increase our efforts to understand the genetic factors involved.

The population study looked at a cohort of people born in northern Finland in 1966: the environmental exposure and genetic background of this population is relatively homogeneous and, because the sample includes almost all people born in that year, it reflects the overall composition of the population.

The team looked at more than 360,000 genetic variants in almost 5000 people. These samples were typed to uncover variants associated with levels of triglycerides, high density lipoprotein, low density lipoprotein, glucose, insulin, C-reactive protein, as well as body mass index and blood pressure. Eight 'environmental' factors, including alcohol use, smoking and birth weight, were also included in the analysis.

We found 23 regions of the genome associated with these traits, says Professor Nelson Freimer, University of California, Los Angeles, the other senior author. We were delighted that our study identified 14 that had been described before: it is essential that a study such as this picks up the known variants.

More important, we found nine novel variants: in five of these cases, our knowledge of the role of the gene suggests they are good candidates for important variants.

The research differs from prior investigations in power and study design, which might explain its ability to identify nine previously unknown loci. Five of these associations - HDL with NR1H3 (LXRA), LDL with AR and FADS1/FADS2, glucose with MTNR1B, and insulin with PANK1 - implicate genes with known or postulated roles in metabolism, and are good candidates for further study of the biological role they might play in these conditions.

The comprehensive cohort study also allowed the team adjust for the additional data such as environmental influences and body mass index. Three regions were associated with LDL or insulin when the population was divided into normal or elevated body mass index.

Our population sample allows us to look at gene-environment interactions, explains Professor Chiara Sabatti, University of California, Los Angeles, a co-author of the paper, but we need to examine larger populations in order to validate these. We are only starting to have a glimpse of how the power of modern genetics can work with population data to uncover genes that will be able to help clinical and public health work in the future. We still have many challenges ahead.

Although genetic influences are thought to account for at least half of the variation in each of the traits, the current results explain perhaps one-tenth of that. There remains much more to be discovered.

Work underway, such as The 1000 Genomes Project and wider population studies, will help to determine whether the additional genetic effects lie in many common variants with relatively small effect or in rare variants with a larger effect.

Delays in radiation therapy lead to increased breast cancer recurrence

Mon, 01 Dec 2008 04:59:37 PST

( from http://www.rxpgnews.com ) A new analysis of the National Cancer Institute's cancer registry has found that as many as one in five older women experience delayed or incomplete radiation treatment following breast-conserving surgery, and that this suboptimal care can lead to worse outcomes.

Dr. Heather Taffet Gold of Weill Cornell Medical College and colleagues found that among a nationally representative sample of nearly 8,000 breast cancer registry patients aged 65 and older, almost 1,300 women experienced delayed radiotherapy and approximately 270 had incomplete radiotherapy. Of these women, those with Stage 1 breast cancer had worse health outcomes associated with this less-than-ideal therapy, while those with a precancerous lesion called ductal carcinoma in situ (DCIS) were not as affected.

Timeliness of post-surgical radiotherapy is important in reducing the risk of subsequent recurrence or new breast malignancies in patients with early breast cancer. Delaying treatment by eight weeks or more significantly increased the odds for recurrence, says Dr. Gold, the study's lead author and an assistant professor of public health in the Division of Health Policy in the Department of Public Health at Weill Cornell Medical College. One possible reason for the delays is that the coordination of care can be a challenge as treatment is usually delivered by multiple providers from different specialties, including surgeons, radiation oncologists and medical oncologists.

Stage 1 breast cancer patients with radiation treatment delayed by eight weeks were 1.4 times more likely to have a recurrence or subsequent new primary breast tumor compared with those receiving timely treatment; they also had reduced survival. Patients whose radiotherapy was delayed by 12 weeks or longer were four times more likely to have a recurrence or subsequent new breast tumor. And women who had incomplete radiation treatment for Stage 1 breast cancer -- those who underwent fewer than three weeks of the typical five-to-seven-week regimen -- had a higher rate of overall mortality, with a 32 percent higher likelihood of death.

The researchers also found treatment disparities in subgroups of older women. Older black women were more likely to delay radiation treatment, whereas women living in areas with a high concentration of radiation oncologists were less likely to delay. Additionally, older women living in high-poverty areas were less likely to complete radiation treatment, says Dr. Gold.

The work appears in the latest online issue of the journal Cancer and the Dec. 1, 2008, print issue. Research collaborators include Huong T. Do, M.A., and Andrew W. Dick, Ph.D., senior economist at the RAND Corporation in Pittsburgh, Pa.

The study is based on an evaluation of women aged 65 and older diagnosed with either DCIS or Stage 1 breast cancer from 1991 to 1999 and followed through 2002 in registries of the Surveillance, Epidemiology, and End Results (SEER) Program sponsored by the National Cancer Institute.

This nationally representative, population-based study of older women provided a unique opportunity to study the effects of suboptimal treatment in the community setting. Our findings indicate that radiation treatment should be made easier for all patients to ensure completion and that delays should be minimized. To improve health outcomes following treatment for breast cancer, health care facilities and providers should implement supportive services, such as transportation, and provide educational materials to encourage and ease access to optimal radiation treatment, thereby improving disease-free and overall survival, said Dr. Andrew Dick, senior author on the study.

New method can detect contaminants in life-saving drug

Wed, 19 Nov 2008 15:54:04 PST

( from http://www.rxpgnews.com ) Washington, Nov 18 - A simple, inexpensive method for detecting contaminants in heparin has been devised by Michigan University researchers.

Heparin, a blood-thinning drug, although very effective against clots in veins, arteries and lungs, was under a cloud when contaminated samples caused serious allergic reactions resulting in many deaths.

The method relies on potentiometric polyanion sensors originally developed in Michigan University - researcher Mark Meyerhoff's lab as a tool for detecting heparin in blood.

In the latest work, Meyerhoff and coworkers show that the disposable sensors also can be used to distinguish pure heparin from heparin that is tainted with small quantities of oversulfated chondroitin sulfate -, the culprit in the recent deaths, said an MU release.

'In this technique, the magnitude of the voltage you get from the sensing membrane is dependent on polyion charge density,' Meyerhoff said, 'and because the contaminant has a higher charge density than heparin, the method allows us to detect the contaminant in the presence of excess heparin.'

The new method is simpler and less expensive than analytical methods such as nuclear magnetic resonance - and capillary electrophoresis -, which have been suggested for detection of OSCS contaminants.

Meyerhoff, professor of chemistry, envisions the procedure being used on site in drug manufacturing plants to screen raw materials or finalised, biomedical grade heparin products for contaminants.

The new method was described in Analytical Chemistry.

Novel IBS treatment developed at UB garners $8.5 million for seven-year clinical trial

Thu, 13 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- Irritable bowel syndrome is a chronic, debilitating disorder affecting 25 million people in the U.S -- 14-24 percent of women and 5-19 percent of men.

No reliable and satisfactory medical treatment exists for the full range of IBS symptoms, which can cause severe physical and psychological distress and deprive sufferers of their quality of life.

Based on a successful pilot study of a primarily at-home, self-administered cognitive behavior therapy program, a University at Buffalo behavioral scientist has received $8.5 million from the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) to conduct a seven-year, multi-site clinical trial of the program developed at UB.

The UB trial is the largest IBS clinical trial conducted to date and one of the largest behavioral trials funded by the NIH.

Jeffrey M. Lackner, Psy.D., assistant professor in the department of medicine, UB School of Medicine and Biomedical Sciences, and director of its Behavioral Medicine Clinic at Erie County Medical Center, is principal investigator.

The trial will be conducted at three sites: UB, University at Alabama-Birmingham and Northwestern University. Following a 12-month planning period, 480 patients between the ages of 18 and 70 with moderate to severe IBS will be recruited over the following four years. Participants will be assigned randomly to one of three treatment groups: standard cognitive behavior therapy (CBT), in which patients will receive 10 weekly one-hour sessions with a therapist; home-based CBT plus 4 one-hour therapist sessions over 10 weeks; or education and support.

Participants will be reassessed at five points during the 12 months following the intervention to determine the long-term effectiveness of each treatment.

In the short term, we hope to show that a self-administered version of cognitive behavior therapy for IBS is as effective as standard in-office treatment, but is more efficient, more accessible and less costly to deliver, said Lackner.

In the long term, we hope to show that a self-administered behavioral treatment program maintains its effectiveness over time, can enhance the quality of patient care, improve clinical outcomes and decrease the economic costs of one of the most prevalent and intractable GI disorders.

Lackner noted that the trial addresses a major priority of the NIDDK of improving the quality of care for IBS and the surgeon general's call to develop relatively simple behavioral approaches for enhancing the long-term health of chronically ill Americans.

UB co-investigators are Leonard Katz, M.D., Michael Sitrin, M.D., Susan Krasner, Ph.D., Changxing Ma, Ph.D., and Ann Marie Carosella, Ph.D. Rebecca Firth is project coordinator.

Lackner's early research leading to an NIH-funded pilot study and the current NIDDK award was supported by an Interdisciplinary Research and Creative Activities grant from the UB Office of the Vice President for Research. In addition, the UB School of Medicine and Biomedical Sciences and Office of the Vice President for Research provided bridge funding to sustain Lackner's research between the pilot study and the NIDDK study.

FSU researcher's discovery leads to $1.5 million grant, potential new treatment of liver fibrosis

Fri, 17 Oct 2008 03:59:37 PST

( from http://www.rxpgnews.com ) TALLAHASSEE, Fla. -- The discovery of a protein involved in the life-threatening mechanism of liver fibrosis has helped a researcher at the Florida State University College of Medicine attract a $1.5 million grant from the National Institutes of Health.

Branko Stefanovic, associate professor in the department of biomedical sciences at the College of Medicine, hopes his discovery could lead to treatment methods that may stem the process of liver fibrosis. Cirrhosis, the terminal phase of the disease, kills 26,000 Americans each year -- the ninth leading cause of death in the United States.

Liver fibrosis refers to the accumulation of excess scar tissue in the liver through excess deposits of collagen, a fibrous protein found in skin, bone, and other connective tissues. The formation of scar tissue is a normal bodily response to injury, but in fibrosis the scarring begins to accumulate to unacceptable levels. The process can result from one of multiple causes, the most frequent of which are alcohol abuse and hepatitis C infection.

Fibrosis is difficult to detect until collagen deposits reach a point where the scarring has severely impaired organ function, meaning individuals suffering from the disease typically do not receive any treatment until it's too late.

The capacity of liver cells to regenerate is great, so therefore normally the primary diseases that can lead to fibrosis do not kill the patient, Stefanovic said. What kills the patient is secondary scarring and the replacement of normal liver tissue with scar tissue. Once this happens a liver cannot regenerate anymore.

Stefanovic and his research team made the important discovery of a protein involved in the scar formation process while working on a previous NIH grant. The RNA-binding protein, which Stefanovic has successfully cloned in his lab at the College of Medicine, is found at the place and specific time when the body is making collagen as part of the normal wound healing resulting from the body's efforts to repair injured tissue.

We had evidence of its existence, but we didn't have the protein, Stefanovic said. We had been looking for this particular protein for several years until we used some very sophisticated methods of cloning. When I saw the results of the binding of the protein to our target I knew immediately we had found the right one.''

Stefanovic said he doesn't believe there will ever be a cure for liver fibrosis but that research and development will one day lead physicians to be able to slow down the progress of the disease.

At least if we slow down the chronic process, instead of dying in five years the patient will live 15 years or more,'' he said.

The goal is to suppress excessive collagen synthesis. In order to do that we have to know the molecular mechanisms that regulate manufacture of the protein and then see what has gone wrong when the liver is creating excess collagen.

Then we will be able to find specific points in this process where we can intervene, by designing either a drug of some kind or a therapeutic agent that will allow us to block these key points and slow down the scarring. Cloning of this protein is a major step toward this goal.

'Light' cigarettes occupy most brain nicotine receptors

Fri, 26 Sep 2008 23:34:28 PST

( from http://www.rxpgnews.com ) For decades now, cigarette makers have marketed so-called light cigarettes — which contain less nicotine than regular smokes — with the implication that they are less harmful to smokers' health. A new UCLA study shows, however, that they deliver nearly as much nicotine to the brain.

Reporting in the current online edition of the International Journal of Neuropsychopharmacology, UCLA psychiatry professor Dr. Arthur L. Brody and colleagues found that low-nicotine cigarettes act similarly to regular cigarettes, occupying a significant percentage of the brain's nicotine receptors.

Light cigarettes have nicotine levels of 0.6 to 1 milligrams, while regular cigarettes contain between 1.2 and 1.4 milligrams.

The researchers also looked at de-nicotinized cigarettes, which contain only a trace amount of nicotine (0.05 milligrams) and are currently being tested as an adjunct to standard smoking-cessation treatments. They found that even that low a nicotine level is enough to occupy a sizeable percentage of receptors.

"The two take-home messages are that very little nicotine is needed to occupy a substantial portion of brain nicotine receptors," Brody said, "and cigarettes with less nicotine than regular cigarettes, such as 'light' cigarettes, still occupy most brain nicotine receptors. Thus, low-nicotine cigarettes function almost the same as regular cigarettes in terms of brain nicotine-receptor occupancy.

"It also showed us that de-nicotinized cigarettes still deliver a considerable amount of nicotine to the brain. Researchers, clinicians and smokers themselves should consider that fact when trying to quit."

In the brain, nicotine binds to specific molecules on nerve cells called nicotinic acetylcholine receptors, or nAChRs. When nerve cells communicate, nerve impulses jump chemically across gaps between cells called synapses by means of neurotransmitters. The neurotransmitters then bind to the receptor sites on nerve cells — in the case acetylcholine resulting in the release of a pleasure-inducing chemical called dopamine. Nicotine mimics acetylcholine, but it lasts longer, releasing more dopamine.

"It can cause specific neurons to communicate and thus increases dopamine for an extended period of time," Brody said. "Most scientists believe that's one key reason why nicotine is so addictive."

In an earlier study, researchers determined that smoking a regular, non-light cigarette resulted in the occupancy of 88 percent of these nicotine receptors. However, that study did not determine whether inhaling nicotine or any of the thousands of other chemical found in cigarette smoke resulted in this receptor occupancy. The central goal of the present study was to determine if factors associated with smoking — other than nicotine — resulted in nAChR occupancy.

The authors reasoned that if nicotine is solely responsible for receptor occupancy, then smoking a de-nicotinized cigarette or a low-nicotine cigarette would result in the occupancy of roughly 23 percent and 78 percent of nicotine receptors, respectively, based on the cigarettes' nicotine content.

"That would still be substantial," Brody said.

Fifteen smokers participated in the study. Each was given positron emission tomography (PET) scans, a brain-imaging technique that uses minute amounts of radiation-emitting substances to tag specific molecules. In this case, the tracer was designed to bind to the nicotine receptors in the brain.

The researchers could then measure what percentage of the tracer was displaced by nicotine when the research subjects smoked. In total, 24 PET scans were taken of participants' brains before and after three different conditions: not smoking, smoking a de-nicotinized cigarette and smoking a low-nicotine cigarette.

The PET data showed that smoking a de-nicotinized cigarette and a low-nicotine cigarette occupied 26 percent and 79 percent of the receptors, respectively, which was very close to what the researchers had originally estimated.

"Given the consistency of findings between our previous study with regular cigarettes and the present study — that showed us that inhaling nicotine during smoking is solely responsible for occupancy of brain nicotine receptors," Brody said.

$4.8M NIH grant aids interstitial cystitis research

Fri, 26 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) University of Iowa researchers are ready to find the causes of interstitial cystitis, thanks to a five-year, $4.8 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health. The grant is the largest ever received by the University of Iowa Department of Urology.

Interstitial cystitis is a painful bladder condition that causes excessively frequent urination and associated pain. An estimated 1.3 million Americans have the condition, more than one million of them women, according to an NIH report published in 2007.

Some people with interstitial cystitis can't work because their symptoms are so severe. The condition has been difficult to treat because we don't know the causes, said the grant's principal investigator Karl Kreder, M.D., professor of urology at the University of Iowa Carver College of Medicine.

This NIH grant will allow us to explore inflammatory factors in the bladder and, as some recent evidence suggests, whether interstitial cystitis is a total body condition, said Kreder, who also is director of urodynamics, female and reconstructive urology in the Department of Urology at University of Iowa Hospitals and Clinics.

The funding makes the UI a Discovery Site for the NIH's Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network. In particular, the UI researchers will explore the roles of the pituitary gland and sympathetic nervous system in the inflammatory process. Kreder said the project involves five different, but interrelated, projects and will draw on the UI's Institute for Clinical and Translational Science.

One project, led by Susan Lutgendorf, Ph.D., professor of psychology in the UI College of Liberal Arts and Sciences, examines the hypothalamic pituitary-adrenal axis, which helps regulate temperature, the immune system, mood, sexuality, and energy, as well as reactions to stress and injury.

A second project examining brain pathways that may govern painful syndromes is led by Satish Rao, M.D., Ph.D., UI professor of internal medicine.

Catherine Bradley, M.D., UI associate professor of obstetrics and gynecology, leads a third project that is focused on the epidemiology of interstitial cystitis and categorizes it by pain mapping.

The research is rounded out by two basic sciences projects -- one to develop animal models that mimic the disorder, led by Yi Luo, Ph.D., UI assistant professor of urology, and one, led by Michael O'Donnell, M.D., UI professor of urology, that examines how certain bladder factors may predispose a person to interstitial cystitis.

Triclocarban and triclosan- more risk than benefit?

Sat, 12 Jul 2008 01:39:18 PST

( from http://www.rxpgnews.com ) A new study by UC Davis researchers calls into question the widespread use of two active ingredients -- triclocarban and triclosan -- in personal hygiene products, including anti-bacterial bar and liquid soaps. Using human and animal cell lines, researchers found that triclocarban disrupts reproductive hormone activity and triclosan interferes a type of cell signaling that occurs in brain, heart and other cells.

"Americans spend nearly one billion dollars a year on these products even though recent studies show that they are no better than regular soap and water at reducing the spread of illness. Now we have added evidence that, in some cases, the benefits may not be worth the risks," said Dan Chang, professor emeritus of civil and environmental engineering.

"Manufacturers of products containing triclosan and triclocarban should consider providing cautionary labels. There are new health-related data on these chemicals that consumers should know about, even if the research is in its early stages," Chang said.

The current study was published online in Environmental Health Perspectives , a publication of the National Institute of Environmental Health Sciences, in May.

The authors of the study are part of the UC Davis Superfund Basic Research Program. The group, part of a national network, is charged with assessing and understanding the effects that exposure to environmental substances have on human health.

"We decided to take a look at triclocarban and triclosan because these compounds appeared to be building up in the environment," said Bruce Hammock, an Superfund Basic Research Program investigator and professor of entomology. The compounds are also increasingly being detected in human breast milk and urine, he said.

Triclosan and triclocarban were first introduced for use by surgeons and other operating room personnel to prevent bacterial infections. Today they are inexpensive and readily available, in part because the patents on them have expired. "We are not concerned about limited use in settings with clearly edvident high-value such as in surgical settings. It's the widespread use that is of concern," Hammock said.

Superfund researchers use bioassays to measure the kind of effects a substance might have on living organisms, using animal or human cell lines as proxies for human exposure. The four assays in this study looked at the effects of triclocarban and triclosan. One assay tests a second messenger system broadly used by cells in the peripheral and central nervous systems, a second examines another pathway important in protein synthesis and two assays evaluate the activity of male and female sex hormones (androgens and estrogens).

The first assay involved observing the impact of the chemicals on ryanodine receptors, proteins that serve to keep calcium levels in balance. Calcium is needed for proper cell signaling, especially in brain, heart and muscle cells where these receptors are found. Disrupting these levels could lead to alterations in cell function. Triclosan significantly increased resting calcium levels in the mouse cells used in the assay.

The second assay looked at the impact on aryl hydrocarbon receptors (AhR). Normally, this cell-surface receptor binds a protein that leads to changes in gene expression, the process by which information encoded in the DNA is translated into proteins. Binding of this receptor by the environmental toxin dioxin has been shown to cause everything from birth defects to tumor production. Triclosan exhibited weak activity in the AhR bioassay. Triclocarban exhibited no activity.

Triclocarban had been previously implicated as a new kind of endocrine disruptor in a paper published in December 2007 in Endocrinology by co-author Bill Lasley, professor of obstetrics and gynecology. Lasley's group concluded that, unlike classical endocrine disrupters that bind to cell receptors, triclocarban amplifies the response of naturally occurring sex hormones.

Because of feedback loops in the body, amplification of these hormones could have the effect of depressing natural estrogen and androgen production, potentially impacting fertility and other hormone-dependent processes. In the current study, besides carrying out the AhR assays, co-author Michael Denison repeated Lasley's experiments using a different human cell line. Denison, a professor of environmental toxicology, observed a similar amplification effect.

Given these results, the question for regulators is whether these compounds should be restricted until further testing can be done. To help answer that question, the National Institute of Environmental Health Sciences and the Environmental Protection Agency are sponsoring a scientific meeting for researchers, regulators and industry representatives in October at UC Davis. "We're all getting together to explore where to go from here," Chang said.

Chang said he feels strongly that consumers be provided information about potential hazards, though he is quick to point out that those who are not in high-risk groups may decide to continue their use of triclosan- and triclocarban-containing products. "I have not stopped using my gingivitis-fighting toothpaste. However, if I were a pregnant woman or the parent of a small child, I might check the labels of the products that I use and stop using any that contain those chemicals until we can work this out," Chang said.

Statins can provide some protection against dementia

Thu, 03 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Cholesterol-lowering drugs known as statins have a profound effect on an elite group of cells important to brain health as we age, scientists at the University of Rochester Medical Center have found. The new findings shed light on a long-debated potential role for statins in the area of dementia.

Neuroscientists found that statins, one of the most widely prescribed classes of medication ever used, have an unexpected effect on brain cells. Researchers looked at the effects of statins on glial progenitor cells, which help the brain stay healthy by serving as a crucial reservoir of cells that the brain can customize depending on its needs. The team found that the compounds spur the cells, which are very similar to stem cells, to shed their flexibility and become one particular type of cell.

The new findings come at a time of increasing awareness among neurologists and cardiologists of the possible effects of statins on the brain. Several studies have set out to show that statins provide some protection against dementia, but the evidence has been inconclusive at best. Meanwhile, there is some debate among physicians about whether statins might actually boost the risk of dementia. The new research published in the July issue of the journal

Princeton University survey finds 'pain gap'

Thu, 01 May 2008 03:59:37 PST

( from http://www.rxpgnews.com ) A novel study that attempts to paint the most accurate and detailed description yet of how Americans experience pain has found that a significant portion of the population -- 28 percent -- are in pain at any given moment and those with less education and lower income spend more of their time in pain. Those in pain are less likely to work or socialize with others and are more inclined to watch television than the pain-free.

The study, which appears in the May 3 issue of The Lancet, was prepared by Alan Krueger, a professor of economics at Princeton University, and Arthur Stone, a professor of psychiatry and behavioral science at Stony Brook University. The work is the first of its type, according to the authors, to quantify a pain gap in American society, with the have-nots suffering a disproportionate amount in relation to the haves.

To a significant extent, pain does divide the classes, said Krueger, the Bendheim Professor in Economics and Public Policy. And just how the levels of pain vary among people and across activities -- that has never been found before until now.

Participants with less than a high school degree were found to report twice the average pain rating throughout the day as did college graduates. The researchers also found the average pain rating to be twice as high for those in households with annual incomes below $30,000 as for those in households with incomes above $100,000.

People in households making less than $30,000 a year spend almost 20 percent of their time in moderate to severe pain, compared with less than 8 percent for those in households with income above $100,000 a year, Krueger said.

Pain imposes considerable costs on the health care system and economy. Americans spend billions of dollars each year on painkillers, more than on any other type of medication. And, when workers are suffering, the resulting lost productivity costs business more than $60 billion annually.

Yet, according to Krueger, the phenomenon of pain -- who is in pain and when -- is not well understood.

The authors constructed a new approach in which participants, a representative group of 4,000 Americans, reported their activities and the occurrence and intensity of pain in a diary survey over a 24-hour period. From the data, the researchers could tie the participants' pain to certain activities, demographic characteristics and times of the day. Pain tended to be more frequent when people received medical care or cared for adults.

The researchers did not ask the survey participants to make a distinction between physical and mental pain because all pain, the researchers said, is subjective. Yet clearly, they said, many of the participants were reporting physical pain.

The novelty of this study is the possibility to relate people's pain experiences to their daily activities, wrote Juha H.O. Turunen, a professor in the Department of Social Pharmacy at the University of Kuopio in Finland, in an accompanying commentary.

The study, Turunen noted, may have broad implications for policymakers. Social programs could be constructed to help those who are in pain while caring for relatives. The burdensome life of those caring for their loved ones must be supported by society, he wrote. The differing levels of pain recorded by varying income groups, he said, emphasizes the need for pain preventing measures such as better ergonomics and better availability of occupational health services for jobs with high physical strains.

Workers in blue collar jobs reported higher occurrences and more severe pain than did those in white collar jobs. For blue collar workers, pain was lower when they were off work than when they were working. The 13 percent of people who reported a work-related disability experienced very high rates of pain, and accounted for 44 percent of the total amount of time that Americans spent in moderate to severe pain.

Those in the most pain expressed the least satisfaction with life and health, the authors found. People were more likely to feel pain when they were alone compared with when they were with friends or a spouse. In addition, those in pain spent a disproportionate amount of their time -- almost 25 percent -- watching television, compared with 16 percent for others.

Alarmingly, those in pain were likely to suffer over years, even decades. The pain doesn't go away in many cases, when people stop working, Krueger said. Pain was higher and more common for older individuals, but the amount of pain reported remained relatively constant for individuals from their mid-40s to their mid-70s.

U. Iowa study finds biological link between pain and fatigue

Mon, 07 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) A recent University of Iowa study reveals a biological link between pain and fatigue and may help explain why more women than men are diagnosed with chronic pain and fatigue conditions like fibromyalgia and chronic fatigue syndrome.

Working with mice, the researchers, led by Kathleen Sluka, Ph.D., professor in the Graduate Program in Physical Therapy and Rehabilitation Science in the UI Roy J. and Lucille A. Carver College of Medicine, found that a protein involved in muscle pain works in conjunction with the male hormone testosterone to protect against muscle fatigue.

Chronic pain and fatigue often occur together -- as many as three in four people with chronic, widespread musculoskeletal pain report having fatigue; and as many as 94 percent of people with chronic fatigue syndromes report muscle pain. Women make up the majority of patients with these conditions.

To probe the link between pain and fatigue, and the influence of sex, the UI team compared exercise-induced muscle fatigue in male and female mice with and without ASIC3 -- an acid-activated ion channel protein that the team has shown to be involved in musculoskeletal pain.

A task involving three one-hour runs produced different levels of fatigue in the different groups of mice as measured by the temporary loss of muscle strength caused by the exercise.

Male mice with ASIC3 were less fatigued by the task than female mice. However, male mice without the ASIC3 protein showed levels of fatigue that were similar to the female mice and were greater than for the normal males.

In addition, when female mice with ASIC3 were given testosterone, their muscles became as resistant to fatigue as the normal male mice. In contrast, the muscle strength of female mice without the protein was not boosted by testosterone.

The differences in fatigue between males and females depends on both the presence of testosterone and the activation of ASIC3 channels, which suggests that they are interacting somehow to protect against fatigue, Sluka said. These differences may help explain some of the underlying differences we see in chronic pain conditions that include fatigue with respect to the predominance of women over men.

The study, which was published in the Feb. 28 issue of the American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, indicates that muscle pain and fatigue are not independent conditions and may share a common pathway that is disrupted in chronic muscle pain conditions. The team plans to continue their studies and investigate whether pain enhances fatigue more in females than males.

Our long-term goal is to come up with better treatments for chronic musculoskeletal pain, Sluka said. But the fatigue that is typically associated with chronic widespread pain is also big clinical problem -- it leaves people unable to work or engage in social activities. If we could find a way to reduce fatigue, we could really improve quality of life for these patients.

Study: highly involved patients don't always see better health outcomes

Fri, 22 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Patients who prefer to be highly involved in their treatment don't necessarily have better luck managing chronic health conditions, a new study suggests.

A research team based at the Veterans Affairs (VA) Iowa City Health Care System and the University of Iowa surveyed 189 veterans with high blood pressure to determine the patients' preferences for involvement in their health care. They discovered those who wanted an active role in their treatment had higher blood pressure and cholesterol over a 12-month span than those who wanted a less active role.

The study, published this week in the Annals of Behavioral Medicine, was led by Austin Baldwin, a post-doctoral fellow in the Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) at the VA Iowa City Health Care System and an adjunct assistant professor of psychology in the UI College of Liberal Arts and Sciences.

The intuitive assumption is that the more involved people are with their health, the better they'll be at managing chronic conditions. We found evidence to the contrary, Baldwin said. Those who preferred a more 'patient-centered' or active role actually had higher blood pressure and lipid levels. Those who preferred a 'provider-centered' approach, in which the doctor is more authoritative, did better at managing their blood pressure and lipid levels.

Patients who preferred the most active role averaged a blood pressure of 141 over 79 and a low-density lipoprotein (LDL) cholesterol level of 112, while those who preferred the least active role averaged a blood pressure of 137 over 72 and an LDL of 92. Doctors tell most patients with high blood pressure to aim for a blood pressure less than 140 over 90 and keep LDL cholesterol under 130.

The average participant was 65.8 years old, and 97 percent were men. Participants were recruited from the Iowa City and Minneapolis VA health care systems and four affiliated community-based outpatient clinics as part of a larger hypertension trial. The data were collected in 2004.

The research team offered a couple potential explanations for the results.

One possibility is that patients who wanted an active role were dissatisfied with the relatively passive treatment of taking medication to control their conditions, and therefore may not have followed doctors' orders as well.

They were presumably provided advice and guidance about modifying their lifestyle, but all of these patients were on hypertension medication, and many were on lipid-lowering medications, Baldwin said. For those who want more control over their treatment, a relatively passive treatment like taking medication may not be a good match.

One aspect of the study gave traction to this explanation. Some patients were diabetic. While those who preferred an active role did worse at managing blood pressure and cholesterol, they did slightly better at managing blood sugar (although the effect on managing blood sugar was not statistically significant). Researchers believe that's because managing blood sugar is a more hands-on treatment involving blood sugar tests, diet regulation and sometimes medication.

Another potential explanation is that the patients' role preferences didn't match their doctors' role preferences. While this study did not assess providers' preferences, previous research suggests that a mismatch between patients' and providers' role preferences impacts adherence to treatment recommendations. (See related UI study at

Intensive blood sugar treatment in trial of diabetes and cardiovascular disease changed

Wed, 06 Feb 2008 23:39:37 PST

( from http://www.rxpgnews.com ) The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped one treatment within a large, ongoing North American clinical trial of diabetes and cardiovascular disease 18 months early due to safety concerns after review of available data, although the study will continue.

In this trial of adults with type 2 diabetes at especially high risk for heart attack and stroke, the medical strategy to intensively lower blood glucose (sugar) below current recommendations increased the risk of death compared with a less-intensive standard treatment strategy. Study participants receiving intensive blood glucose lowering treatment will now receive the less-intensive standard treatment.

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study enrolled 10,251 participants. Of these, 257 in the intensive treatment group have died, compared with 203 within the standard treatment group. This is a difference of 54 deaths, or 3 per 1,000 participants each year, over an average of almost four years of treatment. The death rates in both groups were lower than seen in similar populations in other studies.

Chronic pain harms the brain

Tue, 05 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO -- People with unrelenting pain don't only suffer from the non-stop sensation of throbbing pain. They also have trouble sleeping, are often depressed, anxious and even have difficulty making simple decisions.

In a new study, investigators at Northwestern University's Feinberg School of Medicine have identified a clue that may explain how suffering long-term pain could trigger these other pain-related symptoms.

Researchers found that in a healthy brain all the regions exist in a state of equilibrium. When one region is active, the others quiet down. But in people with chronic pain, a front region of the cortex mostly associated with emotion never shuts up, said Dante Chialvo, lead author and associate research professor of physiology at the Feinberg School. The areas that are affected fail to deactivate when they should.

They are stuck on full throttle, wearing out neurons and altering their connections to each other.

This is the first demonstration of brain disturbances in chronic pain patients not directly related to the sensation of pain. The study will be published Feb. 6 in The Journal of Neuroscience.

Chialvo and colleagues used functional magnetic resonance imaging (fMRI) to scan the brains of people with chronic low back pain and a group of pain-free volunteers while both groups were tracking a moving bar on a computer screen. The study showed the pain sufferers performed the task well but at the expense of using their brain differently than the pain-free group, Chialvo said.

When certain parts of the cortex were activated in the pain-free group, some others were deactivated, maintaining a cooperative equilibrium between the regions. This equilibrium also is known as the resting state network of the brain. In the chronic pain group, however, one of the nodes of this network did not quiet down as it did in the pain-free subjects.

This constant firing of neurons in these regions of the brain could cause permanent damage, Chialvo said. We know when neurons fire too much they may change their connections with other neurons and or even die because they can't sustain high activity for so long, he explained.

'If you are a chronic pain patient, you have pain 24 hours a day, seven days a week, every minute of your life, Chialvo said. That permanent perception of pain in your brain makes these areas in your brain continuously active. This continuous dysfunction in the equilibrium of the brain can change the wiring forever and could hurt the brain.

Chialvo hypothesized the subsequent changes in wiring may make it harder for you to make a decision or be in a good mood to get up in the morning. It could be that pain produces depression and the other reported abnormalities because it disturbs the balance of the brain as a whole.

He said his findings show it is essential to study new approaches to treat patients not just to control their pain but also to evaluate and prevent the dysfunction that may be generated in the brain by the chronic pain.

Direct Intraclot Injection of Alteplase - effective treatment for deep vein thrombosis

Tue, 29 Jan 2008 13:25:41 PST

( from http://www.rxpgnews.com ) A novel treatment for blood clots in the legs appears to be safe and effective, according to a pilot study published in the February issue of Radiology. The study found that injecting or “lacing” the clot with a fiber-binding thrombolytic agent effectively treats deep vein thrombosis (DVT) and reduces the risk of subsequent recurrence or bleeding.

“This treatment regimen is able to clear blood clots rapidly and safely, restoring blood flow in the veins of the lower leg, and the results are durable,” said lead author Richard Chang, M.D., chief of the interventional radiology section of the Department of Radiology, Clinical Center, National Institutes of Health (NIH), Bethesda, Md.

DVT is a common and serious health problem in which a blood clot, or thrombus, form in the deep veins, particularly in the lower leg or thigh. Complications occur when the clot breaks off and travels to the lungs, resulting in pulmonary embolism, a potentially fatal condition.

Most patients with DVT are treated solely with anticoagulation therapy (blood thinners) and compression stockings. However, studies have shown that one-third of these patients will suffer from post-thrombotic syndrome, characterized by pain, swelling, or in severe cases by changes in skin color or skin ulceration. Another third are likely to have another clot or pulmonary embolism within five years of their initial DVT.

Treatments with thrombolytic (clot-dissolving) therapy could potentially protect against these occurrences, but can pose a bleeding risk. Therefore, Dr. Chang and colleagues sought to develop a safe, effective and affordable thrombolytic treatment regimen for DVT.

Twenty patients with acute DVT were treated with direct intraclot lacing of the thrombus with a clot-dissolving agent called alteplase and full systemic anticoagulation. Alteplase binds to the clot, so the procedure does not require continuous infusion of the drug, as do some thrombolytic therapies. With this treatment, after lacing one vein segment with alteplase, the interventional radiologist can immediately direct catheters to treat other vein segments to ensure that the entire clot has been adequately treated.

The results of the study showed that blood flow was restored throughout the deep venous system in 16 (80 percent) of the 20 patients during therapy with complete resolution of symptoms in 18 patients (90 percent) after six months of anticoagulation. Alteplase was cleared from the patients’ circulatory system within two hours of treatment, reducing the risk of subsequent bleeding.

There were no serious complications or bleeding during the treatment, and no cases of post-thrombotic syndrome or recurrent clotting during follow-up of 3.4 years.

“With this therapy, pain and swelling resolve rapidly, and, in most cases, the patient is able to resume all normal activity within a week,” said the study’s co-author, McDonald K. Horne III, M.D., from the hematology section of the Department of Lab Medicine, Clinical Center, NIH.

The authors caution that larger clinical trials are required to further support the efficacy of this promising treatment.

Naked mole-rats bear chili pepper heat

Mon, 28 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Pity the tiny naked mole-rat. The buck-toothed, sausage-like rodent lives by the hundreds in packed, oxygen-starved burrows some six feet under ground. It is even cold-blooded -- which, as far as we know, is unique among mammals.

You can feel their pain. But, they can't feel ours.

Evolution has benefited naked mole-rats by ridding them of a body chemical called Substance P, a neurotransmitter released by pain fibers that send signals to the central nervous system in mammals after making contact with things that cause long-lasting, achy pain.

A better understanding of how Substance P works in the strange rodents may lead to new analgesic drugs for people with chronic pain who do not respond well to current medication, according to Thomas Park, associate professor of biological sciences at the University of Illinois at Chicago, and Gary Lewin of the Max-Delbrück Center for Molecular Medicine in Berlin, principal authors of a study appearing Jan. 29 in the free-access journal PLoS Biology.

Park, Lewin and their laboratory teams in Chicago and Berlin used a modified herpes cold sore virus to carry genes for Substance P to the rodents' nerve fibers.

We were able to rescue their ability to feel pain, said Park. His research group restored Substance P and the naked mole-rats' ability to sense the burning sensation other mammals feel when subjected to capsaicin, the active ingredient in chili peppers.

The restored sensitivity was limited to just one rear foot of each tested rodent. They'd pull their foot back and lick it, in response to the stimulus, said Park. Other feet were impervious to the sting of capsaicin.

Capsaicin is very specific for exciting the fibers that normally have Substance P, said Park. They're not the fibers that respond to a pin prick or pinch, but the ones that respond after an injury or burn and produce longer-lasting pain.

But the researchers found that mole-rats remained completely insensitive to acids, indicating a fundamental difference in how their nerves respond to this stimulus.

Acid acts on the capsaicin receptor and on another family of receptors called acid-sensitive ion channels, Park said. Acid is not as specific as capsaicin. The mole-rat is the only animal that shows completely no response to acid.

Park said the research adds to knowledge about the neurotransmitter Substance P.

This is important specifically to the long-term, secondary-order inflammatory pain. It's the pain that can last for hours or days when you pull a muscle or have a surgical procedure, he said.

Park said naked mole-rats provide a new model system that is different from all other animals he has studied.

We're learning which nerve fibers are important for which kinds of pain, so we'll be able to develop new strategies and targets.

Naked mole-rats, native to east-central Africa, developed a protective reaction to acids through evolution. Living in tight underground quarters, the mole-rats exhale high levels of carbon dioxide, which becomes acid when it touches skin and mucous tissue in the nose, eyes and mouth. But the mole-rats have evolved to become desensitized to the stinging pain of acid.

The UIC biologist plans to study other animals, both closely related and unrelated -- such as Alaskan marmots that burrow in high CO2 environments -- to examine how they have evolved similar strategies to cope with acid-rich living conditions.

Use of opioids for pain in ERs on the rise, but racial differences in use still exist

Tue, 01 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) In the last 15 years, use of opioid medications to treat patients with pain-related emergency department visits has improved although white patients were more likely to receive opioids than patients of a different race/ethnicity, according to a study in the January 2 issue of JAMA.

In the 1990s, national attention focused on increasing awareness of the problem of inadequately treated pain. Also, racial and ethnic minority groups appeared to be at higher risk of receiving inadequate treatment for pain in the emergency department, according to background information in the article. National quality improvement initiatives were implemented in the late 1990s, followed by substantial increases in opioid (narcotic agents used for pain relief) prescribing in the United States, but it is unknown whether opioid prescribing for treatment of pain in the emergency department has increased and whether differences in opioid prescribing by race/ethnicity have decreased.

Mark J. Pletcher, M.D., M.P.H., of the University of California, San Francisco, and colleagues examined whether opioid prescribing is increasing in U.S. emergency departments for patients presenting with pain and whether non-Hispanic white patients are more likely to receive an opioid than other racial/ethnic groups. Pain-related visits to U.S. emergency departments were identified using reason-for-visit and physician diagnosis codes from thirteen years (1993-2005) of The National Hospital Ambulatory Medical Care Survey.

During the survey years, pain-related visits accounted for 156,729 of 374,891 (42 percent) emergency department visits. An opioid analgesic was prescribed at 29 percent of pain-related visits. This proportion increased during the study period, from 23 percent in 1993 to 37 percent in 2005. Despite this time trend, the researchers found no evidence that the difference in opioid prescribing by race/ethnicity diminished over time. Averaged over the 13 survey years, opioid prescribing was more likely for pain-related visits made by whites (31 percent) than by blacks (23 percent), Hispanics (24 percent), or Asians/others (28 percent), and there was no evidence of an interaction between the time trend and race/ethnicity during the study period. In 2005, opioid prescribing rates were 40 percent in whites and 32 percent in all others.

Differential opioid prescribing was consistently present across different types of pain, across different levels of pain severity, for visits in which pain was the first or second/third reason for visit, and for two specific painful diagnoses, long-bone fracture and kidney stones. Differences in prescribing between whites and nonwhites were larger as pain severity increased and were particularly pronounced for patients with back pain (48 percent vs. 36 percent, respectively), headache (35 percent vs. 24 percent), abdominal pain (32 percent vs. 22 percent), and other pain (40 percent vs. 28 percent). Blacks were prescribed opioids at lower rates than any other race/ethnicity group for almost every type of pain visit.

Statistical adjustment for pain severity and other factors did not substantially change these differences. Compared with white patients, black patients were 34 percent less likely to receive an opioid prescription; Hispanic patients, 33 percent less likely; and Asian/other patients, 21 percent less likely.

Constipation most common cause of children's abdominal pain

Mon, 17 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) A new study led by a University of Iowa researcher showed that acute and chronic constipation together accounted for nearly half of all cases of acute abdominal pain in children treated at one hospital.

The study also suggests that physicians should do a simple rectal examination for constipation when trying to determine the cause of abdominal pain in children. The findings, which were based on medical records of 962 children ages 4 to nearly 18, appear in the December issue of the Journal of Pediatrics.

Earlier studies have shown that constipation can contribute to abdominal pain in children, but no specific recommendations for diagnosing this contributing factor were made, said Vera Loening-Baucke, M.D., professor of pediatrics at the University of Iowa Carver College of Medicine and the study's lead investigator.

Constipation can be overlooked as the cause of severe or intermittent abdominal pain, as a reporting of symptoms alone does not always establish that a child has constipation, she said. Our study helps to show that constipation frequently causes acute abdominal pain and that a physician should not just ask the parent if the child is constipated because the parent may have not been able to see all the signs of this condition.

Constipation signs include fewer than three bowel movements per week, one or more episodes of stool incontinence per week, passing of stools so large that they obstruct the toilet, retentive posturing (withholding behavior) and painful defecation.

The doctor should perform an abdominal examination and a rectal examination to see if the child is retaining stool, said Loening, who sees patients at University of Iowa Children's Hospital.

Loening said that some doctors shy away from the rectal examination, which involves digitally checking for impacted stool in the lower colon, because they believe it may cause a child mental or physical discomfort. However, the test can be performed safely and explained to children so that they understand its purpose.

It's important for doctors to do a thorough evaluation for abdominal pain, as there are many causes. In addition to constipation, having a cold or sore throat can also cause abdominal pain, for example, Loening-Baucke said.

The study found that 83 (9 percent) of 962 children who had received at least one well-child visit during a six-month period in 2004 at University of Iowa Children's Hospital or University of Iowa Hospitals and Clinics reported acute abdominal pain at that visit or another clinic or emergency visit. Significantly more girls (12 percent of the 962) reported such pain, compared to only 5 percent of boys.

Of the 83 children with acute abdominal pain, 72 were seen in a primary care clinic and 11 were examined after hours in the emergency department. Together, acute constipation (lasting eight or fewer weeks) and chronic constipation (lasting eight or more weeks) accounted for 48 percent of the cases (40 children), making it the most common cause of the pain.

Only 2 percent of the children with pain had a surgical condition such as appendicitis. In addition, doctors could not determine causes for 19 percent of the patients with pain.

While most of the patients reviewed in the study were Caucasian, individuals from all other races were included.

Study shows pine bark naturally reduces osteoarthritis knee pain

Wed, 05 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com )

Affecting more than 10 million Americans, Osteoarthritis of the knee (OA) is one of the five leading causes of disability among the elderly. While OA mainly affects most people over 45, it can occur at any age. A double-blind, placebo-controlled study published in the journal Nutrition Research reveals Pycnogenol, (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, improved physical function by 52 percent in patients suffering from OA.

When OA develops, the cartilage gradually looses elasticity and begins to harden and crack, subsequently becoming more prone to damage and erosion by use or injury and often leads to pain, swelling, a decrease in motion at the joint, stiffness, or the formation of bone spurs (tiny growths of new bone). Current treatments include regular exercise and pain relievers such as NSAIDS and COX-2 inhibitor pills to help ease pain and stiffness. In more severe cases, cortisone shots can help decrease inflammation in the joint and extreme cases consist of joint replacement. There are currently no drugs that treat osteoarthritis directly.

Pycnogenol was chosen due to a history of studies of the extract to alleviate inflammation by inhibiting COX-1, COX-2 and the pro-inflammatory master-switch nuclear factor-kappa B,said lead researcher Dr. Ronald Watson from the University of Arizona. Pycnogenol offers a safe nutritional approach to significantly reduce pain and improve physical function of arthritic joints. It controls inflammation and thus ideally complements existing strategies that comprise delivery of building blocks for replacement of degenerated cartilage.

The study was conducted at the rheumatology department of Mashhad Medical University, Iran. Thirty-five volunteers (average age 42) were randomly assigned a daily dose of Pycnogenol (50mg, 3 times a day) or placebo for three months. Patients were to report arthritic pain using the Western Ontario and McMasters Universities (WOMAC) Osteoarthritis Index after 30, 60 and 90 days. Participants also were instructed to indicate the frequency and dosage of NSAIDS and COX-2 inhibitor usage.

After two months of supplementation, physical function and pain scores improved in the Pycnogenol group. After three months in the Pycnogenol group, there was a reduction of 43 percent in pain, 35 percent in stiffness, 52 percent in physical function subscales and 49 percent composite WOMAC. The placebo group showed no significant scores throughout the entire study. Additionally, further reduction in the number of NSAIDS and COX-2 inhibitor pills and number of days taking medication was noted in the Pycnogenol group.

Pycnogenol's natural anti-inflammatory and antioxidant properties were responsible for delivering these excellent results,said Watson. This study shows that supplementing with Pycnogenol can fight joint inflammation and soothe the pain and stiffness, thus pave the path for cartilage renewal with substances such as glucosamine.

A previous study on Pycnogenol published in the Journal of Inflammation demonstrated that the ingredient effectively prevented inflammation disorders in patients by moderating the immune system response. While the wear and tear is responsible for the initial degeneration of cartilage, the more advanced stage of osteoarthritis involves inflammation. The cells of the cartilage (chondrocytes) respond to mechanical impact by generating pro-inflammatory molecules (cytokines). This process is initiated by the pro-inflammatory master-switch called NF-kappaB. Pycnogenol was shown to lower the sensitivity for NF-kappaB in humans last year.

The cytokines released from chondrocytes recruits immune cells (leukocytes) to the joints where they cause more harm than good. Leukocytes release harmful substances such as free radicals and enzymes that break down connective tissue and speed up the degeneration of cartilage. These processes alike are under control by NF-kappaB, and the effect of Pycnogenol to suppress NF-kappaB will help to limit the damage caused by leukocytes.

Researchers believe this study is the first randomized clinical trial to show Pycnogenol's effectiveness in alleviating the clinical symptoms of knee osteoarthritis. There are several more breakthrough studies on Pycnogenol and osteoarthritis expected to be published next year allowing for development of innovative, natural formulas for joint health.

Additionally, Horphag Research, the exclusive worldwide distributor of Pycnogenol has filed for several patents for Pycnogenol's application for COX-1, COX-2 and treating osteoarthritis.

Smoked cannabis proven effective in treating neuropathic pain

Wed, 24 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Smoked cannabis eased pain induced in healthy volunteers, according to a study by researchers at the University of California, San Diego (UCSD) Center for Medical Cannabis Research (CMCR.) However, the researchers found that less may be more.

In the placebo controlled study of 15 subjects, a low dose of cannabis showed no effect, a medium dose provided moderate pain relief, and a high dose increased the pain response. The results suggest a therapeutic window for cannabis analgesia, according to lead researcher Mark Wallace, M.D., professor of anesthesiology at UCSD School of Medicine and Program Director for the UCSD Center for Pain Medicine.

The paper, to be published in the November issue of the journal Anesthesiology, is the second published study out of the CMCR. Headquartered at UCSD, the CMCR is collaboration between UCSD and UC San Francisco that was funded by a state-funded initiative in 1999 to rigorously study the safety and efficacy of medicinal cannabis in treating diseases.

The study used capsaicin, an alkaloid derived from hot chili peppers that is an irritant to the skin, to mimic the type of neuropathic pain experienced by patients with HIV/AIDS, diabetes or shingles � brief, intense pain following by a longer-lasting secondary pain. The subjects were healthy volunteers who inhaled either medical cannabis or a placebo after pain was induced. The marijuana cigarettes were formulated under NIH supervision to contain either zero, two, four or eight percent delta-9-tetrahydrocannabinol (THC.)

�Subjects reported a decrease in pain at the medium dose, and there was also a significant correlation between plasma levels of THC, the active ingredient in cannabis, and decreased pain,� said Igor Grant, M.D., F.R.C.P.(C), professor and Executive Vice-Chair of the Department of Psychiatry, the director of the CMCR. �Interestingly, the analgesic effect wasn�t immediate; it took about 45 minutes for the cannabis to have an impact on the pain,� he said.

The results, showing a medium-dose (4% THC by weight) of cannabis to be an effective analgesic, converged with results from the CMCR�s first published study, a paper by UCSF researcher Donald Abrams, M.D. published in the journal Neurology in February 2007. In that randomized placebo-controlled trial, patients smoking the same dose of cannabis experienced a 34% reduction in HIV-associated sensory neuropathy pain�twice the rate experienced by patients receiving a placebo.

�This study helps to build a case that cannabis does have therapeutic value at a medium-dose level,� said Grant. �It also suggests that higher doses aren�t necessarily better in certain situations � something also observed with other medications, such as antidepressants.�

The researchers stated that more and larger studies need to be conducted to measure the efficacy of cannabis, noting that medical marijuana could play an important role in treating patients who don�t respond well to the usual pain relievers or can�t tolerate drugs such as ibuprofen or opioids used for severe pain.

�The results of this study might help guide others doing clinical research into pain management,� said Wallace.

Role of a key enzyme in reducing heart disease identified

Wed, 24 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Virginia Commonwealth University researchers have identified the role of a key enzyme called CEH in reducing heart disease, paving the way for new target therapies to reduce plaques in the arteries and perhaps in the future, help predict a patient�s susceptibility to heart disease.

Furthermore, unlike currently available therapies, which prevent or reduce the formation of new plaques, increasing CEH may also reduce existing plaques.

Heart disease results from the formation of plaques in the coronary artery, which supplies blood to the heart. Plaques form when monocytes, which are cells from the blood, enter the wall of the artery and consume large amounts of the �bad� cholesterol, or LDL. The monocytes then become artery-clogging foam cells. The only way for foam cells to get rid of their cholesterol is to make it available to HDL, or �good� cholesterol, for removal. A key enzyme present in the foam cells called cholesteryl ester hydrolase (CEH) regulates the amount of cholesterol that can be removed by HDL.

In this study, led by Shobha Ghosh, Ph.D., an associate professor of internal medicine, pulmonary division in the VCU School of Medicine, the team examined, for the first time, how cells in the artery wall make cholesterol available for removal by HDL. Using transgenic mice, which were fed a high fat and cholesterol-rich diet, the team was able to show that by increasing the removal of cholesterol from the artery clogging foam cells, the mice with the human gene for CEH developed significantly less heart disease.

�Currently the emphasis for managing heart disease is on reducing the �bad� cholesterol or LDL in the circulation. Our study demonstrates that if you can increase the removal of cholesterol from the plaques, even without changing the LDL levels, there is still a significant reduction in the plaques,� said Ghosh.

�These findings not only change the current thinking of managing heart disease but also clearly open avenues for the development of new therapies. By identifying CEH as a new therapeutic target, we expect that in the future patients with heart disease will have more options to aggressively treat heart disease. In addition, by determining the levels of CEH in human blood cells, we hope to be able to predict susceptibility to heart disease in the future,� she said.

According to Ghosh, the team focused their efforts on the examination of macrophage foam cells, which are responsible for storing large amounts of cholesterol and lead to the clogging of the arteries by forming plaques. The findings appear in the October print issue of the Journal of Clinical Investigation.

The team is actively exploring the mechanisms underlying CEH regulation and to determine how its activity can be increased in order to reduce heart disease.

Watching funny shows helps children tolerate pain longer, study finds

Tue, 23 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Watching comedy shows helps children tolerate pain for longer periods of time, according to a study by UCLA's Jonsson Comprehensive Cancer Center and the nonprofit organization Rx Laughter.

The study findings, published in the October issue of the journal Evidence-based Complementary and Alternative Medicine, suggest that humorous distraction could be used in clinical settings to help children and adolescents better handle painful procedures.

Laughter has long been viewed as good medicine, and although there are many programs that bring humor into pediatric hospitals, little research has been done on the utility of humor for children or adolescents undergoing stressful or painful procedures, such as blood draws and treatments for cancer.

Rx Laughter, an organization founded by former television executive Sherry Dunay Hilber that promotes the use of humor in healing, worked with UCLA researchers on the study, which was funded by a grant from Comedy Central. Participants watched funny classic and contemporary films and television programs while undergoing a standardized pain task � in this case, placing their hands in icy-cold water, said Dr. Margaret Stuber, a researcher at UCLA's Jonsson Comprehensive Cancer Center and first author of the study.

The group demonstrated significantly greater pain tolerance while viewing the funny shows, according to the study.

Stuber said that researchers documented submersion times and participants' appraisal of the pain and examined them in relation to humor indicators � the number of times the children laughed or smiled and their ratings of how funny the show was for them.

We found that viewing funny videos increased the tolerance of pain for children but did not change their ratings of the severity of the pain, said Stuber, UCLA's Jane and Marc Nathanson Professor of Psychiatry at the Semel Institute for Neuroscience and Human Behavior. Although they kept their hands in the water longer, they didn't describe the task as any less painful than when they weren't watching the videos. However, this may mean that it simply took longer for the pain to become severe enough to remove their hand.

The number of laughs recorded was not related to either pain tolerance or appraisal, Stuber said.

Eighteen healthy children � 12 boys and six girls between the ages of 7 and 16, with a mean age of 12 � participated in the study. An ice chest was fitted with a plastic mesh screen to separate crushed ice from a plastic mesh armrest placed in 50-degree water. Water was circulated through the ice by a pump to prevent local warming. Participants placed a hand in the cold water to a depth of two inches above the wrist for up to three minutes maximum. Their hands were warmed between tests with warm towels.

Researchers took a baseline measure of submersion duration before the video was viewed, a measurement after and one while participants watched the video. The children left their hands in the icy water significantly longer when watching the funny shows, Stuber said.

Further study is needed to explore the specific mechanism behind the increased pain tolerance, Stuber said.

Since we did not test any other types of distracters, it could be that something equally distracting but not funny would also be effective, she said. However, the results do support the types of interventions being done at children's hospitals across the United States.

Acupuncture reduces pain, need for opioids after surgery

Tue, 16 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. � Using acupuncture before and during surgery significantly reduces the level of pain and the amount of potent painkillers needed by patients after the surgery is over, according to Duke University Medical Center anesthesiologists who combined data from 15 small randomized acupuncture clinical trials.

�While the amount of opioids needed for patients who received acupuncture was much lower than those who did not have acupuncture, the most important outcome for the patient is the reduction of the side effects associated with opioids,� said Tong Joo (T.J.) Gan, M.D., a Duke anesthesiologist who presented the results of the analysis at the annual scientific conference of the American Society for Anesthesiology in San Francisco. �These side effects can negatively impact a patient�s recovery from surgery and lengthen the time spent in the hospital.�

Based on the results of this analysis, Gan recommends that acupuncture should be considered a viable option for pain control in surgery patients.

Patients who received acupuncture had significantly lower risk of developing most common side effects associated with opioid drugs compared with control: 1.5 times lower rates of nausea, 1.3 times fewer incidences of severe itching, 1.6 times fewer reports of dizziness and 3.5 times fewer cases of urinary retention.

Opioids are a class of medications that act on the body much like morphine. While they are effective in controlling pain, the side effects of the drugs often influence a patient�s recovery from, and satisfaction with, their surgery, Gan said.

The results of this study add to the growing body of evidence that acupuncture can play an effective role in improving the quality of the surgical experience, Gan added. Numerous studies, some conducted by Gan, have demonstrated that acupuncture can also be more effective than current medications in lessening the occurrence of post operative nausea and vomiting, the most common side effect experienced by patients after surgery.

�Acupuncture is slowly becoming more accepted by American physicians, but it is still underutilized,� Gan said. �Studies like this, which show that there is a benefit to using it, should help give physicians sitting on the fence the data they need to integrate acupuncture into their routine care of surgery patients.�

Acupuncture has the added benefits of being inexpensive, with virtually no side effects, when done by properly trained personnel, Gan added.

The Chinese have been using acupuncture for more than 5,000 years for the treatment of a variety of ailments, including headaches, gastrointestinal disorders and arthritis. According to Chinese healing practices, there are about 360 specific points along 14 different lines, or meridians, that course throughout the body just under the skin.

�The Chinese believe that our vital energy, known as chi, flows throughout the body along these meridians,� Gan explained. �While healthiness is a state where the chi is in balance, unhealthiness or disease state arises from either too much or too little chi, or a blockage in the flow of the chi.�

Different bodily locations or organs have their own distinct acupuncture points that are the targets for the acupuncturist. For example, a point just below the wrist is the common target for women undergoing breast procedures to prevent nausea and vomiting, another point at the back of the hand is effective in reducing pain.

While it is not completely known why or how acupuncture works, recent research seems to point to its ability to stimulate the release of hormones or the body�s own painkillers, known as endorphins, Gan said. He is now conducting studies to determine the exact mechanism behind acupuncture�s effects.

UI researchers seek to ease children's pain during medical procedures

Mon, 15 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A new system under development by a team of researchers at the University of Iowa will help children better cope with pain during difficult medical procedures.

The system works by using a Web-based software to advise nurses on the best way to distract children from the procedures that cause the pain. The distractions could be anything from having a book read to them, watching a video, talking, or playing a game.

The research team, led by professors Ann Marie McCarthy (left) and Charmaine Kleiber in the College of Nursing and Nick Street in the Tippie College of Business, developed the software after analyzing data from a multi-site research study that observed parents distracting their children, who were undergoing painful procedures.

The study helped the researchers determine how children cope with pain and what distractions worked best to keep their minds off the pain.

Children between the ages of 4 and 10 at the University of Iowa Children's Hospital participated in this study. Data were collected from 542 subjects, all of whom were having an IV line inserted while a video camera recorded the event.

The data was collected by having parents and children complete questionnaires and by analyzing videotapes of the procedures. Members of the research team reviewed the video and graded the children's distress. Children who experienced more pain and had more difficulty coping received higher scores. Children were also able to report how painful the procedure was by using a scale with happy and sad faces on it.

We're now using that data to build software that will determine the best strategy for distracting a child from the procedure, based on what we know about the child and the type of procedure, said Street (left), a Tippie professor of management sciences who mined the data and is developing the software.

The software will also determine the parent's capacity for providing the distraction.

Not all parents are equally cut out for helping their children through medical procedures, said McCarthy, a professor of nursing and chair of the nursing school's Parent, Child and Family Area. Sometimes, it might be best to bring in a distraction coach who has special training to keep children occupied.

The distractions, she said, are anything that takes captures the attention of the child so that they focus on the distraction and not the procedure; reading a book, talking about school, coloring, drawing.

In pain management, one size doesn't fit all, McCarthy said. Some children need intensive distraction, some might need none at all. This software will tell the nurse what group each child should be in and what type of intervention to provide.

McCarthy said the long-term health effects of making it easier for children to cope with pain could be profound.

This is important because more than 4 million children require painful medical procedures, and we know undergoing those procedures can affect health care decisions later in life, said McCarthy. If we can provide a distraction, then the children are more likely to find the event to be less traumatic and are less likely to undergo serious psychological trauma.

The next step in the research will begin in January, when researchers will pilot the software to determine what types of distractions work best with different parents and children. Street said the software asks a brief series of questions of the children and their parents about such things as previous experiences with procedures and pain, parenting styles, and anxiety issues.

Based on the answers and the type of procedure, the software will suggest a distraction strategy to the nurse and recommend whether the parents should do the distracting, or a coach should be brought in.

McCarthy said researchers will observe 580 subjects over 30 months during the next phase of research. The children will be patients at the University of Iowa Children's Hospital in Iowa City, Blank Children's Hospital in Des Moines and Cardinal Glennon Children's Hospital in St. Louis.

Virtual game helps children escape realities of burn unit

Mon, 08 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio -- Nurses and physicians at Nationwide Children�s Hospital are using the latest technology to help young burn victims endure the extreme pain of dressing changes and wound care. Instead of traditional distraction devices, such as books and music, Nationwide Children�s Hospital Burn Center is now using virtual reality games to distract patients while nurses attend to the patients� burn wounds.

�It�s long been known that the actual treatment for a burn is far worse than the actual injury. Initially, the wound has to be cleaned and the dressing applied, and that can be a very painful and lengthy procedure,� said Dr. Catherine Butz, PhD, a psychologist at Nationwide Children�s Hospital and an Assistant Professor at The Ohio State University College of Medicine.

Following this initial treatment, patients must endure subsequent wound care procedures, some of which can be both extensive and painful, depending on the extent of the burn. During these procedures, anxiety often plays a major role in the patient�s pain level.

�Research shows a very strong connection between anxiety and pain,� said Dr. Butz. �Distraction does a great job in decreasing any kind of anxiety that might be associated with the anticipated procedures, so by distracting patients and keeping anxiety at a minimum, procedures tend to go much more smoothly and be much less painful for the child.�

The device, made possible by a donation from the Aladdin Shriner�s Hospital Association for Children, allows patients to escape into a computer-generated world complete with its own environment, creatures and sounds. Patients wear a virtual reality helmet, and once in this new world, they interact in the virtual environment with the help of child life specialists, trained to assist kids through stressful medical treatments.

Since Nationwide Children�s Hospital began using the device in May 2007, it has already resulted in positive feedback from burn patients. Burn nurses report several patients have noticeably improved in terms of their ability to tolerate dressing changes.

In order to better understand the effect on pain, doctors at Nationwide Children�s have launched a study to compare the results of virtual reality pain distraction with traditional distraction techniques, such as watching television, listening to music, counting and deep breathing. Patients will be randomly assigned to receive virtual reality or another pain distraction technique. Following the procedure, they will be asked to gauge their level of pain on a scale of zero to 10. The study will also assess the perspectives of parents and nurses in terms of the child�s pain and level of distress.

The burn program�s goal is to be able to better engage the child in a distraction activity which will hopefully have a beneficial affect on the procedure. An added benefit for patients may be a decrease in the amount of pain and anxiety medications needed. However doctors point out that pain is a very individual experience, and the benefits of virtual reality distraction as well as the level of medication must be determined on a case by case basis.

Cholesterol metabolism links early- and late-onset Alzheimer's disease

Thu, 04 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Oct. 4, 2007 -- Although the causes of Alzheimer's disease are not completely understood, amyloid-beta (A-beta) is widely considered a likely culprit � the sticky protein clumps into plaques thought to harm brain cells.

But now researchers at Washington University School of Medicine in St. Louis have uncovered evidence strengthening the case for another potential cause of Alzheimer's. The finding also represents the first time scientists have found a connection between early- and late-onset Alzheimer's.

In a study published in the Oct. 4, 2007 issue of the journal Neuron, the scientists report that when A-beta is made, a small bit of protein is also released that can regulate cholesterol levels in the brain. The discovery adds weight to the less prominent theory that abnormal brain cholesterol metabolism plays a role in the mental decline seen in Alzheimer's patients.

Our research links two major determinants for early- and late-onset Alzheimer's disease, says senior author Guojun Bu, Ph.D., professor of pediatrics and of cell biology and physiology. And we've shown that the process that links them is implicated in brain cholesterol metabolism.

The report follows closely on another study reporting that statins, widely prescribed cholesterol-lowering drugs, could prevent certain neural changes that signal the progression of Alzheimer's disease. Additional earlier studies support the idea that statins could benefit Alzheimer's patients; however, other studies have found no such protective effect from statins.

The studies of statins and Alzheimer's have generated quite a bit of controversy, Bu says. Those that show positive effects from statins seem to suggest that high cholesterol could increase the risk of Alzheimer's disease. But other evidence contradicts this idea.

In fact, the brain needs a high level of cholesterol, according to Bu. The brain represents only about 2 percent of your body weight, but actually has about 20 percent of your body's cholesterol, Bu says. There is strong evidence that cholesterol is important for synaptic function and is an essential component of cell membranes in the brain, and I believe partial defects in the regulation of cholesterol metabolism in the brain likely contribute to the development of Alzheimer's.

In the current study, Bu and colleagues found an aspect of cholesterol transport and metabolism in the brain was a link between early- and late-onset Alzheimer's disease. Both forms of the disease result in similar brain lesions and have the same symptoms, including difficulties communicating, learning, thinking and reasoning, which suggests they share underlying mechanisms. But until now, no one has been able to identify such a mechanism.

Early-onset Alzheimer's can be traced to mutations in one of three genes, and the gene coding for A-beta's precursor, APP, is one of these. People with mutations in APP nearly always develop Alzheimer's disease, usually at a relatively young age.

The genetic origins of late-onset Alzheimer's, which accounts for 95 percent of cases, have proven harder to pin down. However, studies have shown that people who have a particular mutation in the gene for a cholesterol carrier called apolipoprotein E are far more likely to develop Alzheimer's in old age than those who don't have the mutation.

Bu and colleagues demonstrated that APP and apolipoprotein E have a molecular connection. When APP is cleaved by a specific enzyme in the brain, it releases A-beta plus a small protein fragment. The fragment then can regulate apolipoprotein E, which moves cholesterol in the brain from support cells to neurons.

Past research by others implies that neural synapses, the junctions that nerves use to send impulses and communicate, are particularly sensitive to cholesterol levels and that interfering with cholesterol transport and metabolism could cause loss of synapses and degeneration of nerves.

Cholesterol metabolism in the brain is an understudied area, and our findings could inspire Alzheimer's researchers to look further into the role of the cholesterol pathway, Bu says. Right now, research on Alzheimer's treatment focuses largely on reducing A-beta production or increasing its clearance from the brain. Our study suggests that there could be an alternate way to treat the disease, perhaps by modulating the function of apolipoprotein E and cholesterol in the brain.

Bu and his colleagues plan to screen for compounds that regulate the molecular components that they found to be involved in cholesterol metabolism. They hypothesize that such compounds could work to enhance the brain's cholesterol metabolism and alleviate Alzheimer's symptoms.

Treatment blocks pain without disrupting other functions

Wed, 03 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A combination of two drugs can selectively block pain-sensing neurons in rats without impairing movement or other sensations such as touch, according to a new study by National Institutes of Health (NIH)-supported investigators. The finding suggests an improved way to treat pain from childbirth and surgical procedures. It may also lead to new treatments to help the millions of Americans who suffer from chronic pain.

The study used a combination of capsaicin � the substance that makes chili peppers hot � and a drug called QX-314. This combination exploits a characteristic unique to pain-sensing neurons, also called nociceptors, in order to block their activity without impairing signals from other cells. In contrast, most pain relievers used for surgical procedures block activity in all types of neurons. This can cause numbness, paralysis and other nervous system disturbances.

The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination, or other vital functions of the nervous system. This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major future breakthroughs for the millions of persons who suffer with disabling pain, says Story C. Landis, Ph.D., director of the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH, which funds the investigators' research along with the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institute of General Medical Sciences (NIGMS). NINDS and NIDCR are co-chairs of the NIH Pain Consortium. The study appears in the October 4, 2007, issue of Nature.*

Lidocaine, the most commonly used local anesthetic, relieves pain by blocking electric currents in all nerve cells. Although it is a lidocaine derivative, QX-314 alone cannot get through cell membranes to block their electrical activity.

That's where capsaicin comes in. It opens large pores called TRPV1 channels � found only within the cell membrane of pain-sensing neurons. With these channels propped open by capsaicin, QX-314 can pass through and selectively block the cells� activity.

The research team, led by Clifford J. Woolf, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School and Bruce Bean, Ph.D., at Harvard Medical School, tested the combination of capsaicin and QX-314 in neurons isolated in Petri dishes and found that it blocked pain-sensing neurons without affecting other nerve cells. They then injected the drugs into the paws of rats and found that the treated animals could tolerate much more heat than usual. They also injected the two drugs near the sciatic nerve that runs down the hind leg. The treated rats did not show any signs of pain, and five of the six animals continued to move and behave normally. This showed that the drugs could block pain without impairing motor neurons that control movement.

The drug combination took half an hour to fully block pain in the rats. However, once it began, the pain relief lasted for several hours.

Current nerve blocks cause paralysis and total numbness, Dr. Woolf says. This new strategy could profoundly change pain treatment in the perioperative setting.

The treatment tested in this study is unique in that it uses a type of ion channel (TRPV1 channels) as an avenue to deliver medication. Ion channels are pores in the cell membrane that control the flow of electrically charged ions in and out of cells. I'm not aware of any other strategy that uses a channel within cells to deliver a drug to a select set of cells, Dr. Woolf says. The strategy builds on research done since the 1970's, largely supported by NIH, that shows how electrical signaling in the nervous system results from expression of dozens of different types of ion channels. Some of these ion channels are found only in specific types of neurons.

This project is a nice illustration of how research trying to understand very basic biological principles can have practical applications, says Dr. Bean.This type of treatment has great potential to improve pain treatment during childbirth, dental procedures, and surgery, the researchers say. Surgical pain is the obvious first application for this type of treatment, Dr. Woolf says. However, similar therapies might eventually be useful for treating chronic pain, he adds. Chronic pain continues for weeks, months, or even years and can cause severe problems, and is often resistant to standard medical treatments.

While the researchers focused on finding a treatment for pain, this strategy might also be useful for treating itch from eczema, poison ivy rashes, and other conditions, Dr. Woolf says. Like pain sensations, itch signals come from nociceptors. One problem with the combination treatment is that the capsaicin can cause unpleasant burning sensations until the QX-314 takes effect, Dr. Woolf says. Administering the QX-314 ten minutes before the capsaicin minimized this problem in rats. The investigators are now looking for ways to open the TRPV1 channels without the burning sensations, perhaps by finding an alternative to capsaicin. They also hope to find ways of prolonging the pain relief. Eventually, they might be able to develop pills that will stop pain signals without requiring injections, Dr. Woolf adds.

Women with severe PMS perceive their sleep quality to be poor

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WESTCHESTER, Ill. � Women with severe premenstrual syndrome (PMS) perceive their sleep quality to be poorer in association with their symptoms in the late luteal (premenstrual) phase, despite there being no specific alterations in sleep structure associated with premenstrual symptoms, according to a study published in the October 1 issue of the journal SLEEP.

The study, authored by Fiona C. Baker, PhD, of the Human Sleep Research Program at SRI International in Menlo Park, Calif., and the University of the Witwatersrand in Johannesburg, South Africa, focused on nine women with PMS or premenstrual dysphoric disorder (PMDD) and 12 controls. The subjects, all 18-40 years of age, had laboratory-based polysomnographic recordings at two phases of the menstrual cycle: follicular phase and late luteal phase.

According to the results, women with severe PMS reported a significantly poorer subjective sleep quality during the late luteal phase, but there was no evidence of disturbed sleep based on the polysomnogram specific to premenstrual symptom expression. Both groups of women had increased wakefulness after sleep onset and increased sigma power in the late luteal phase compared with the follicular phase.

There were, however, some group differences in electroencephalographic measures regardless of menstrual phase, including decreased delta incidence and increase theta incidence and amplitude in women with PMS, suggesting the possibility of sleep electroencephalogram trait markers in women with PMS.

�Women with PMS or PMDD commonly report sleep disturbances, but the few studies using conventional polysomnographic measures have produced conflicting results. In this study, we investigated sleep quality and sleep composition using conventional and quantitative electroencephalographic analyses in women with severe PMS, as compared to that of controls,� said Dr. Baker.

Sleep plays a vital role in promoting a woman�s health and well being. Getting the sleep that you need is likely to enhance your overall quality of life. Yet, women face many potential barriers that can disrupt and disturb their sleep. Overcoming these challenges can help them enjoy the daily benefits of feeling alert and well rested.

Experts suggest that most women need about seven to eight hours of sleep each night.

Compared to men, there are many differences in how women sleep. In general, women tend to sleep more than men, going to bed and falling asleep earlier. A woman�s sleep also tends to be lighter and more easily disturbed. Women are more likely to feel unrefreshed even after a full night of sleep.

There are many complex factors that may affect how a woman sleeps. Some of these factors change over time. For example, excessive daytime sleepiness is more common when women are in their 20s and 30s. In contrast, older women appear to adapt better to periods of sleep loss. This difference has been attributed to the many commitments that compete for a young woman�s time. In particular, working moms must balance the demands of their career, family, friends and personal health needs.

Common factors that affect a woman�s sleep include:

Low maternal cholesterol tied to premature birth

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Pregnant women who have very low cholesterol may face a greater risk of delivering their babies prematurely than women with more moderate cholesterol levels, a team led by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), reported today.

In a study published in the October issue of the journal Pediatrics, NHGRI�s Max Muenke, M.D.; Robin J. Edison, M.D., M.P.H.; Kate Berg, Ph.D.; and colleagues from the NIH Clinical Center; Kennedy Krieger Institute, Baltimore; Howard University, Washington; and Greenwood Genetic Center, Greenwood, S.C., confirm previous findings by other groups that very high levels of maternal cholesterol can increase the risk of premature birth. However, in a surprising new twist, the researchers found that low maternal cholesterol levels, which may be related to a woman's genetic makeup, diet or other health factors, also may lead to adverse birth outcomes, including premature birth and low birth weight.

�Based on our initial findings, it appears that too little cholesterol may be as bad as too much cholesterol during pregnancy, but it is too early to extrapolate these results to the general population. More research is needed to replicate this outcome and to extend it to other groups,� said Dr. Muenke, the study�s senior author and chief of the Medical Genetics Branch in NHGRI�s Division of Intramural Research. �For now, the best advice for pregnant women is to follow the guidance of their health care providers when it comes to diet and exercise.�

Premature birth is a major cause of infant death and raises the risk of many potentially disabling conditions, including cerebral palsy, cognitive impairment, blindness, deafness and respiratory illness. Factors contributing to premature birth include maternal genetics, fetal genetics and environmental components, such as nutrition, stress, and infection.

In their study of 1,058 South Carolina women and their newborns, researchers found about 5 percent of the women with cholesterol levels in the moderate range of 159-261 milligrams per deciliter (mg/dl) gave birth prematurely. In contrast, white women with the lowest cholesterol levels � less than 159 mg/dl � had a 21 percent incidence of premature births. Interestingly, no increase in premature births was observed among African American women in the low-cholesterol category. However, full-term babies born to both white and African Americans with low cholesterol weighed 5 ounces less on average than full-term babies born to women with moderate cholesterol.

�The right amount of cholesterol is fundamental for good health, both before and after birth,� explained Dr. Muenke. �During pregnancy, cholesterol is critical for both the placenta and the developing baby, including the brain.�

As in past studies, the new research showed very high cholesterol levels (more than 261 mg/dl) to be a major risk factor for premature birth. About 12 percent of white and African American women with very high cholesterol levels gave birth prematurely.

The study involved pregnant women between the ages of 21 and 34 who were referred to South Carolina clinics for routine prenatal care between 1996 and 2001. According to their medical records, they were all nonsmokers without diabetes who were carrying just one child. It looked at cholesterol levels from their second trimester of pregnancy. Premature birth was defined as delivery before 37 weeks of gestation.

Taking into account the natural rise in maternal cholesterol during pregnancy, researchers examined the effects of maternal cholesterol levels on rates of premature delivery, impaired fetal growth and birth defects. In addition, they analyzed measurements of newborn weight, length and head circumference. No differences were seen in the rate of birth defects, but researchers did detect a trend towards smaller head sizes among babies born to women with very low cholesterol.

�This study sheds important light on the intricate biological mechanisms at work during human gestation,� said NHGRI Scientific Director Eric Green, M.D., Ph.D. �In light of these findings, researchers have a renewed impetus to establish the genetic and environmental causes of low cholesterol levels because of its relevance to pregnancy.�

In the Pediatrics paper, the NHGRI-led research team called for more studies to refine our understanding of cholesterol levels in pregnant women, and to explore the genetic, nutritional and other factors that influence maternal cholesterol. They also pointed out the need for further investigation into the differing impact of low cholesterol levels on the rates of premature delivery in white and African American mothers.

Besides the South Carolina study, Dr. Muenke and his colleagues have undertaken a number of other investigations aiming to determine the role of cholesterol in embryonic development. They have identified genes that impact congenital brain defects and established the role that cholesterol plays in modulating the actions of such genes.

New test could help consumers avoid surprise headaches from chocolate, wine

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers in California are reporting development of a fast, inexpensive test suitable for home use that could help millions of people avoid those �out of the blue� headaches that may follow consumption of certain red wines, cheese, chocolate, and other aged or fermented foods.

The test is designed to detect the presence of so-called biogenic amines, naturally occurring toxins that can trigger a wide range of symptoms in sensitive individuals �from nasty headaches to life-threatening episodes of high-blood pressure.

Existing tests for biogenic amines can take several hours, are cumbersome and require large, expensive instruments found only in laboratories, the researchers say. The new test, based on lab-on-a-chip technology, could produce results within five minutes, they state. It will be described in the Nov. 1 issue of ACS� Analytical Chemistry, a semi-monthly journal.

�These toxins can be a serious health problem and are more common than people think,� says study leader Richard A. Mathies, Ph.D., a chemist with the University of California, Berkeley. �They are hidden in a wide variety of foods. Having a quick, convenient way to identify them will help consumers avoid them or at least limit their intake.�

Biogenic amines include tyramine, histamine, and phenylethylamine, which have been known to cause nausea, headaches, and respiratory disorders. These toxins can be particularly dangerous in people with reduced monoamine oxidase (MAO) activity or those taking MAO inhibitors, an older class of antidepressant medications, because they can potentially interact and cause dangerously high blood pressure. Having a quick testing kit could ultimately save lives in these individuals, Mathies suggests.

The new technique, called portable microchip capillary electrophoresis, involves labeling the sample with a fluorescent dye, separating the components by applying an electric field on a special microchip, and analyzing the pattern of light produced by the sample upon exposure to a laser beam. In the study, Mathies and colleagues used a prototype device to analyze tyramine and histamine concentrations in a variety of wines (both red and white), beer and sake. They found that the device accurately measured the biogenic amines present in the beverages in less than five minutes.

The highest levels of tyramine were found in red wine, and the highest levels of histidine were found in sake, the researchers note. The beer tested contained only small amounts of these biogenic amines, they say.

�Some foods have more biogenic amines than others, but you can�t tell because they aren�t listed on the food labels,� Mathies says. Even a single glass of wine has been known to trigger elevated blood pressure, heart rate and headaches in some people, he notes. �I think that certain foods, especially wines, should indicate their biogenic amine content.�

Besides beverages, the test can be used for a wide range of food products, including cheese, chocolate, fish and even sauerkraut. In addition to being used by consumers in the home, the device could be used by industry as a quick method to monitor or limit the biogenic amine content of foods and beverages, according to the researchers. It can also be used to screen foods that have been deliberately contaminated, they say.

Mathies envisions that the test will eventually be engineered into a PDA or other handheld device that consumers can use at home or in a restaurant to instantly screen a food or beverage sample for the presence of these toxins. More research is needed before this occurs, he says.

The study was funded, in part, by the National Aeronautics and Space Administration. The analyzer was originally developed to look for organic molecules, particularly amino acids, on future explorations of Mars. A version of the sensor has been developed for use in the European Space Agency�s 2013 ExoMars mission, Mathies says.

ACP and APS issue comprehensive guidelines for treating low-back pain

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PHILADELPHIA, Oct. 2, 2007 - The American College of Physicians (ACP) and the American Pain Society (APS) today released joint guidelines on diagnosing and treating low back pain.

About one in four Americans reported having low back pain in the past three months and about l7.6 percent of all adults reported at least one episode of severe acute low back pain within the previous year, according to several studies. Other studies show that most people�s low back pain will improve within one month, regardless of treatment. Treatments range from doing nothing to spinal surgery.

In 2006, ACP and APS convened a multidisciplinary panel of experts to develop questions and the scope of an evidence report on low back pain, to review its results and come up with recommendations for primary care physicians to diagnose and treat low back pain.

The recommendations, published in the Oct. 2, 2007, issue of Annals of Internal Medicine, include an algorithm to guide clinicians in obtaining and interpreting information during the first patient visit and place patients into one of three general categories:

- Nonspecific low back pain (85% of patients fall in this category)- Back pain potentially associated with spinal conditions, such as spinal stenosis, sciatica, vertebral compression fracture - Back pain potentially associated with another specific cause, such as cancer.

The recommendations say that clinicians should not routinely order imaging or other diagnostic tests such as X-rays, CAT scans, and MRIs, for patients with nonspecific low back pain. They should reserve these tests for patients who have severe or progressive neurologic deficits or suspected underlying conditions, such as cancer or infection.

The joint ACP-APS guidelines are designed for primary care physicians and other clinicians and do not address invasive therapies performed by specialists. The American Pain Society will publish a separate guideline covering invasive procedures for low back pain in 2008.

�There are many options for evaluation and treatment of low back pain,� said Amir Qaseem, MD, PhD, MHA, senior medical associate in the ACP Department of Clinical Programs and Quality of Care, and an author of the guidelines. �We wanted to review all the evidence and develop guidance for clinicians and to give our patients a realistic sense of what they can expect when they visit a clinician for low back pain. It is important to tell patients about their expected course based on evidence-based information and advise them to remain active.�

Roger Chou, head of the American Pain Society Clinical Practice Guidelines Program, an author of the guidelines, and the senior author of the two background papers on which the guidelines were based, reviewed evidence for both drug therapies and non-drug therapies for acute and chronic low back pain.

Almost all medications reviewed had some benefits, but they have risks, Chou said. Acetaminophen, for example, is very safe but might not be effective. NSAIDS have gastrointestinal and cardiovascular risks. Opioids and muscle relaxers can provide relief for those with severe pain, but their potential benefits and risks should be weighed carefully.

Patients who prefer not to take medication can benefit from non-drug treatments, such as acupuncture, spinal manipulations and massage therapy. None, however, are proven to be more effective than others to warrant recommendation as first-line therapy.

Treating obstructive sleep apnea, preventing heart attacks and strokes

Fri, 28 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers in Brazil have found that treating patients who suffer from obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) dramatically reduces early indications of atherosclerosis in just months, linking OSA directly to the hardening or narrowing of the arteries. Until now, no study has demonstrated such a direct relationship between the two.

�OSA is independently associated with increased risk of fatal cardiovascular events that can be reversed by treatment with CPAP,� wrote Luciano Drager, M.D., of the University of S�o Paulo Medical School in Brazil.

The research was published in the first issue of the American Journal of Respiratory and Critical Care Medicine for October of 2007, published by the American Thoracic Society.

The researchers selected 24 men with severe OSA and no other comorbidities and randomly assigned them to receive either CPAP therapy or no treatment. After establishing the baseline data for each subject, they then tracked several indicators of pre-clinical atherosclerosis, including carotid intima-media thickness (a measure of arterial plaque), pulse-wave velocity (a measure of arterial stiffness), carotid diameter, C-reactive protein (a marker of inflammation), and catecholamine level (a marker of physical stress) over the course of four months.

�[All markers] were similar across the study period in the control group,� wrote Dr. Drager. �In contrast, the group treated with CPAP had a significant decrease in carotid intima-media thickness, pulse-wave velocity, C-reactive protein, and catecholamines.�

While there is a known association between OSA and risk of myocardial infarctions and strokes, the causal connection between OSA and atherosclerosis as the principle mechanism behind those cardiovascular events has proven difficult to establish.

�The majority of patients with OSA share several risk factors for atherosclerosis, including obesity, hypertension, hypercholesterolemia, insulin resistance, and hyperglycemia,� explained T. Douglas Bradley, M.D., and Dai Yumino, M.D., both of the Sleep Research Laboratory at the Toronto Rehabilitation Institute at the Centre for Sleep Medicine and Circadian Biology at the University of Toronto, in an editorial in the same issue of the journal.

Furthermore, while non-randomized observational trials have suggested that the risk of adverse cardiovascular events is lower among patients who accept treatment by CPAP than in patients who do not accept CPAP therapy, it is possible that this difference may be due to better overall adherence to all prescribed treatments in patients who accept CPAP than in those who do not, as opposed to any direct benefit of CPAP itself.

�Whereas physiological studies suggest that OSA provides a substrate for the development of atherosclerosis, and epidemiological and observational studies suggest an association between OSA and odds of having atherosclerosis, there remains a gap between cause and effect yet to be filled,� wrote Drs. Yumino and Bradley. �Drager and colleagues provide evidence that begins to fill that gap.�

Indeed, after four months of CPAP therapy, carotid intima-media thickness declined by nine percent, which is remarkable in light of the fact that in a large-scale study, patients undergoing cholesterol-lowering pravastatin therapy saw carotid intima-media thickness decline by twelve percent after a full year. Other indicators showed similar magnitudes of improvement.

The researchers put forth a number of potential pathways whereby OSA could contribute to atherosclerosis progression, including inflammation, oxidative stress, lymphocyte activation, and high-density lipoprotein dysfunction. �CPAP treatment could reverse several of these pathways,� they wrote.

Still, the investigators caution that, while they are confident in the biological validity of their results, the rigid inclusion criteria makes it difficult to extrapolate their results to different populations, including women, patients with other co-morbidities and patients with mild to moderate OSA.

'Bad carbs' not the enemy, University of Virginia professor finds

Fri, 28 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The latest common wisdom on carbohydrates claims that eating so-called �bad� carbohydrates will make you fat, but University of Virginia professor Glenn Gaesser says, �that�s just nonsense.� Eating sandwiches with white bread, or an occasional doughnut, isn't going to kill you, or necessarily even lead to obesity, he said.

In an article in the October issue of the Journal of the American Dietetic Association, Gaesser analyzes peer-reviewed, scientific research on carbohydrate consumption, glycemic index and body weight and gives the first detailed review of the literature on the correlation between them. His findings run counter to the current consensus on the effects of �good� and �bad� carbohydrates.

Gaesser, author of �It�s the Calories, Not the Carbs� and other books, found that diets high in carbohydrates are almost universally associated with slimmer bodies. More importantly, Gaesser found that consuming lots of high-glycemic foods is not associated with higher body weights. In fact, several large studies in the United States revealed that high-glycemic diets were linked to better weight control.

�There is no reason to be eating fewer carbs � they�re not the enemy,� says Gaesser, a professor of exercise physiology and director of the kinesiology program in the Curry School of Education.

The description of carbohydrates as �good� or �bad� is based on glycemic index, a measure of the quality of the carbohydrate in terms of how much it raises blood sugar. Foods having a high GI are generally thought to be �bad� because they raise blood sugar more than �good� carbs do. Proponents of the glycemic index claim that this leads to excessive insulin secretion, which can cause weight gain and health problems. Foods such as whole-grain breads are said to offer �good� carbs, because they have a lower GI than white bread, for example. Likewise, a glass of pineapple juice has a high GI compared to apple juice.

Several popular low-carb diets use glycemic index as a key feature for optimum weight control, but it is not a reliable description of carbohydrate quality, Gaesser says. Digestion is a complicated process. It�s very difficult to determine the GI of a whole meal, for instance, so it doesn�t really make sense to use GI or �glycemic load� � the glycemic index multiplied by the quantity ingested � as a guide to eating.

After looking at hundreds of articles on large-scale studies using surveys or randomized, controlled trials, Gaesser says they show that �people who consume high-carb diets tend to be slimmer, and often healthier, than people who consume low-carb diets.� Even high-glycemic foods have a place in the diet, he said, attributing that to the overall higher quality of a high-carb diet, which includes more fiber-rich and other nutritional foods.

Gaesser also looked for a clear association between carbohydrate consumption and illnesses, such as type 2 diabetes, heart disease and cancer. He found no compelling evidence that avoiding carbohydrates with a high GI helps prevent these diseases and others. People with diabetes, as well as very sedentary women who are obese, may benefit from lowering their consumption of foods with a high GI, Gaesser says.

Reducing any part of the diet � carbs or proteins or fats � will result in modest weight loss in the short term, if calorie consumption is reduced, he points out. But for long-term weight maintenance, a high-carb, low-fat diet is still the best bet, he said.

Doctors learn to control their own brains' pain responses to better treat patients

Thu, 27 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Physicians apparently learn to �shut off� the portion of their brain that helps them appreciate the pain their patients experience while treating them and instead activate a portion of the brain connected with controlling emotions, according to new research using brain scans at the University of Chicago.

Because doctors sometimes have to inflict pain on their patients as part of the healing process, they also must develop the ability to not be distracted by the suffering, said Jean Decety, Professor in Psychology and Psychiatry at the University and co-author of �Expertise Modulates the Perception of Pain in Others,� published in the Oct. 9 issue of Current Biology and available Thursday at noon on-line.

�They have learned through their training and practice to keep a detached perspective; without such a mechanism, performing their practice could be overwhelming or distressing, and as a consequence impair their ability to be of assistance for their patients� said Decety, who conducted the study with Yawei Cheng of the Institute of Neuroscience, National Yang-Ming University in Taipei, and colleagues there.

Previous research, including work from Decety�s lab, has shown that the neural circuit that registers pain, is activated if a person sees another person in pain. The response in this circuit, which includes the anterior insula, periaqueducal gray and anterior cigulate cortex, is automatic and may reflect a panic response developed evolutionally as a means of avoiding danger.

The research by Decety and the Taiwanese team shows for the first time that people can learn to control that automatic response.

The team performed its research in Taiwan with two groups of evenly matched men and women with a mean age of 35 and similar socio-economic and educational levels-- a group of 14 physicians and 14 people with no experience in acupuncture. They were tested using a functional MRI.

Brain responses were recorded as individuals from the two groups looked at short video-clips in which people were pricked with acupuncture needles in their mouth regions, hands, and feet. They also watched as the patients were touched with Q-tips. The images appeared in random order.

Among the control group, the scan showed that the pain circuit, which comprises somatosensory cortex, anterior insula, periaqueducal gray and anterior cigulate cortex, was activated when members of that group saw someone touch with a needle but not activated when the person was touched with a Q-tip.

Physicians registered no increase in activity in the portion of the brain related to pain, whether they saw an image of someone stuck with a needle or touched with a Q-tip. However, the physicians, unlike the control group, did register an increase in activity in the frontal areas of the brain--the medial and superior prefrontal cortices and the right tempororparietal junction. That is the neural circuit that is related to emotion regulation and cognitive control.

They also asked the two groups to rate the level of pain they felt people were experiencing while being pricked with needles. The control group rated the pain at about 7 points on a 10-point scale, while the physicians said the pain was probably at 3 points on that scale.

Those findings reflected the prediction the scholars had going into the study.

�It would not be adaptive if this automatic sharing mechanism for pain was not modulated by cognitive control. Think, for instance, of the situations that surgeons, dentists, and nurses face in their everyday professional practices. Without some regulatory mechanism, it is very likely that medical practioners would experience personal distress and anxiety that would interfere with their ability to heal,� the researchers write.

For Decety, this new study also casts light on the mechanisms involved in empathy and empathic concern. The former relies on our capacity to share emotions and feelings with others. If there is too much of an overlap between others and self, such an overlap (reflected by similar neural circuits that automatically and unconsciously resonate between self and other) it could lead to personal distress, which is an aversive reaction. Empathic concern necessitates to regulate our implicit sharing mechanism and frees up processing capacity to act for the sake of the other.

Why don't painkillers work for people with fibromyalgia?

Thu, 27 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich. � People who have the common chronic pain condition fibromyalgia often report that they don�t respond to the types of medication that relieve other people�s pain. New research from the University of Michigan Health System helps to explain why that might be: Patients with fibromyalgia were found to have reduced binding ability of a type of receptor in the brain that is the target of opioid painkiller drugs such as morphine.

The study included positron emission tomography (PET) scans of the brains of patients with fibromyalgia, and of an equal number of sex- and age-matched people without the often-debilitating condition. Results showed that the fibromyalgia patients had reduced mu-opioid receptor (MOR) availability within regions of the brain that normally process and dampen pain signals � specifically, the nucleus accumbens, the anterior cingulate and the amygdala.

�The reduced availability of the receptor was associated with greater pain among people with fibromyalgia,� says lead author Richard E. Harris, Ph.D., research investigator in the Division of Rheumatology at the U-M Medical School's Department of Internal Medicine and a researcher at the U-M Chronic Pain and Fatigue Research Center.

�These findings could explain why opioids are anecdotally thought to be ineffective in people with fibromyalgia,� he notes. The findings appear in The Journal of Neuroscience. �The finding is significant because it has been difficult to determine the causes of pain in patients with fibromyalgia, to the point that acceptance of the condition by medical practitioners has been slow.�

Opioid pain killers work by binding to opioid receptors in the brain and spinal cord. In addition to morphine, they include codeine, propoxyphene-containing medications such as Darvocet, hydrocodone-containing medications such as Vicodin, and oxycodone-containing medications such as Oxycontin.

The researchers theorize based on their findings that, with the lower availability of the MORs in three regions of the brains of people with fibromyalgia, such painkillers may not be able to bind as well to the receptors as they can in the brains of people without the condition.

Put more simply: When the painkillers cannot bind to the receptors, they cannot alleviate the patient�s pain as effectively, Harris says. The reduced availability of the receptors could result from a reduced number of opioid receptors, enhanced release of endogenous opioids (opioids, such as endorphins, that are produced naturally by the body), or both, Harris says.

The research team also found a possible link with depression. The PET scans showed that the fibromyalgia patients with more depressive symptoms had reductions of MOR binding potential in the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.

The study subjects were 17 women with fibromyalgia and 17 women without the condition.

Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage

Wed, 26 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON, Sept. 26 2007 -- Consuming large amounts of caffeine while taking acetaminophen, one of the most widely used painkillers in the United States, could potentially cause liver damage, according to a preliminary laboratory study reported in the Oct. 15 print issue of ACS� Chemical Research in Toxicology, a monthly journal. The toxic interaction could occur not only from drinking caffeinated beverages while taking the painkiller but also from using large amounts of medications that intentionally combine caffeine and acetaminophen for the treatment of migraine headaches, menstrual discomfort and other conditions, the researchers say.

Health experts have warned for years that consuming excess alcohol while taking acetaminophen can trigger toxic interactions and cause liver damage and even death. However, this is the first time scientists have reported a potentially harmful interaction while taking the painkiller with caffeine, the researchers say.

While the studies are preliminary findings conducted in bacteria and laboratory animals, they suggest that consumers may want to limit caffeine intake -- including energy drinks and strong coffee -- while taking acetaminophen.

Chemist Sid Nelson, Ph.D., and colleagues, of the University of Washington in Seattle, tested the effects of acetaminophen and caffeine on E. coli bacteria genetically engineered to express a key human enzyme in the liver that detoxifies many prescription and nonprescription drugs. The researchers found that caffeine triples the amount of a toxic byproduct, N-acetyl-p-benzoquinone imine (NAPQI), that the enzyme produces while breaking down acetaminophen. This same toxin is responsible for liver damage and failure in toxic alcohol-acetaminophen interactions, they say.

In previous studies, the same researchers showed that high doses of caffeine can increase the severity of liver damage in rats with acetaminophen-induced liver damage, thus supporting the current finding.

�People should be informed about this potentially harmful interaction,� Nelson says. �The bottom line is that you don�t have to stop taking acetaminophen or stop taking caffeine products, but you do need to monitor your intake more carefully when taking them together, especially if you drink alcohol.�

Nelson points out that the bacteria used in the study were exposed to �megadoses� of both acetaminophen and caffeine, much higher than most individuals would normally consume on a daily basis. Most people would similarly need to consume unusually high levels of these compounds together to have a dangerous effect, but the toxic threshold has not yet been determined, he says.

Certain groups may be more vulnerable to the potentially toxic interaction than others, Nelson says. This includes people who take certain anti-epileptic medications, including carbamazepine and phenobarbital, and those who take St. John�s Wort, a popular herbal supplement. These products have been shown to boost levels of the enzyme that produces the toxic liver metabolite NAPQI, an effect that will likely be heightened when taking both acetaminophen and caffeine together, he says.

Likewise, people who drink a lot of alcohol may be at increased risk for the toxic interaction, Nelson says. That�s because alcohol can trigger the production of yet another liver enzyme that produces the liver toxin NAPQI. The risks are also higher for those who take large amounts of medications that combine both acetaminophen and caffeine, which are often used together as a remedy for migraine headaches, arthritis and other conditions.

The researchers are currently studying the mechanism by which this toxic interaction occurs and are considering human studies in the future, they say. The National Institutes of Health funded the initial animal and bacterial studies.

Common abdominal pain may be due to a potentially treatable newly recognized inflammatory reaction

Wed, 19 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) JACKSONVILLE, Fla. -- As many as one in four people in westernized countries experience pain or discomfort in their upper abdomen, and physicians have almost nothing to offer except anti-acid medicines, which usually don�t work. Now, in a small but novel study, researchers have found evidence that an abnormal amount of inflammatory cells populates the upper intestine of affected individuals, which suggests a fresh way of understanding the common complaint.

The study, published in the September issue of Clinical Gastroenterology and Hepatology and conducted by researchers in the U.S., Sweden, England, and Australia, may also point to innovative methods to treat the condition and eliminate discomfort.

�Newly-designed, targeted anti-inflammatory medicine aimed at blocking the function of these cells might be very useful, if our results are validated,� says the study�s lead researcher, Nicholas J. Talley, M.D., Chair of Internal Medicine at Mayo Clinic in Jacksonville.

�We are quite intrigued by what we have discovered, because it probably represents a new disease entity, one that might be capable of diagnosis and management,� Dr. Talley says.

The scientists don�t know why inflammatory cells are present in one particular region of the small intestine, the duodenum that connects to the stomach, but they theorize that it could result from an allergic reaction to certain foods. Patients examined did not have infections, celiac disease (an autoimmune reaction to gluten protein), or cancer.

�I believe food intolerance can lead to motor and sensory abnormalities that are perceived as pain and discomfort,� Dr. Talley says. �But we have no evidence yet that this is definitely the case.�

To conduct the study, researchers in Sweden offered endoscopic examinations to 51 Swedish participants who complained of �nonulcer dyspepsia� as well as 49 randomly selected participants who had no pain. Dyspepsia is chronic or recurrent pain, or a feeling of abdominal fullness after eating or nausea, and the nonulcer form means there is not any structural abnormality such as an ulcer. For reasons that are not clear, sensitivity to stomach acid occurs in some of these patients, but acid suppression therapy does not work in two-thirds of patients who try it. There are really very few effective therapies, Dr. Talley says.

During the endoscopy procedure, physicians removed biopsy tissue from several places in the small intestine of participants, and the samples were examined by pathologists who did not know who the samples belonged to.

The researchers found significantly more eosinophil cells in people with nonulcer dyspepsia, compared to the control group population, but these cells were found only in the duodenum, the place in the intestine where most chemical digestion takes place. Eosinophils are white blood cells, part of the immune system, which fight parasites.

The researchers cannot yet say whether duodenal esoinophilia is the cause of the pain or an effect of another factor causing the disorder, although Dr. Talley says �a casual link remains our hypothesis.

�The presence of these cells has been overlooked because no one has used rigorous quantification methods before, and because biopsy examinations of the duodenum are not routinely performed,� he says. �Now we have a new direction to go in.�

Smaller breast reduction surgeries provide health benefits and should be reimbursed

Thu, 13 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (Sept. 13, 2007) -- Smaller-framed women reap significant health and quality-of-life benefits from breast reductions that involve the removal of under 500 grams of tissue per breast, according to a first-of-its-kind study from NewYork-Presbyterian Hospital/Weill Cornell Medical Center and the New York University School of Medicine.

The finding runs counter to the policies of most U.S. health insurance companies, who typically do not reimburse women for these smaller mammoplasties because insurance companies deem them to be only of cosmetic value.

Of course, as plastic surgeons, we know that isn't true -- you can't apply the same number, in terms of the benefits of excised breast tissue, to different-sized women, says co-author Dr. Jason Spector, a plastic surgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and assistant professor of surgery (plastic surgery) at Weill Cornell Medical College.

Smaller women are going to have proportionally smaller breasts, but for their particular frame, their breasts may still be far too large and uncomfortable, Dr. Spector explains.

The study, appearing in the Sept. 15 issue of Plastic and Reconstructive Surgery (already available online), found that breast reductions of less than 500 grams per breast greatly eased women's back, neck and shoulder pain. The procedures also improved their quality of life by allowing them to exercise more, play sports and choose from a wider variety of clothing.

All of the 59 patients in the study had come to the study's co-author, plastic surgeon Dr. Nolan S. Karp of NYU Medical Center, complaining of pain linked to uncomfortably large breasts. Dr. Karp is associate professor of plastic surgery at the NYU School of Medicine.

None of the women in the study had ever undergone any form of breast augmentation before.

On average, the mammoplasties involved the surgical removal of 415 grams of breast tissue per breast (830 grams total), for an average breast reduction of just over 2 cup sizes. Seventeen of the women had less than 750 grams total of breast tissue removed -- an average decrease of 1.7 cup sizes.

Three months and then one year after their surgery, the women were asked about changes in pain and quality of life. They were asked to rate their pain from a score of 1 to 5 (5 being highest).

Scores fell dramatically after the reduction mammoplasties -- in categories including lower-back pain, neck pain, headache and bra-strap grooving.

Women were also greatly relieved that they were more able to engage in healthful activities such as running or playing sports -- demonstrating that breast reduction surgeries have even wider health implications, Dr. Spector says.

None of these findings came as a great surprise to this experienced plastic surgeon.

However, studies like this are needed if we are ever going to reverse the arbitrary ceiling the insurance industry has in place in terms of reimbursing breast reduction surgeries, Dr. Spector explains.

The smaller-framed woman who comes to us complaining of chronic breast-linked pain is not having this procedure done for a 'lift' or any cosmetic purpose, he says. Breast reduction surgeries involve some scarring, general anesthesia, and the usual level of surgical risk. Patients are not taking them lightly.

Dr. Spector is optimistic that reimbursement policies may change, based on the new findings.

This is going to be useful data that patients and other plastic surgeons should be able to turn to as they go back and forth with insurance companies trying to get the procedure approved, Dr. Spector says. Women come in all shapes and sizes, and we're just pointing out that breast reduction -- like many other surgeries -- is definitely not a one-size-fits-all proposal.

Preventing or reducing enlarged heart decreases risk of heart failure

Wed, 12 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (Sept. 10, 2007) -- For high-blood-pressure patients, preventing or reducing enlarged heart (left ventricular hypertrophy or LVH) reduces risk of heart failure. The study is published in the Sept. 4 Annals of Internal Medicine and led by physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City.

An estimated 20 percent of all high-blood-pressure patients, or 12 million Americans, have LVH and are at increased risk of developing heart failure.

While the direct relationship between levels of LVH in patients with high blood pressure and risk of cardiac complications -- including death, heart attack, stroke and atrial fibrillation -- has previously been demonstrated by NewYork-Presbyterian/Weill Cornell researchers (JAMA, 2004 and 2006), the new study is the first to demonstrate that prevention or regression of LVH reduces risk of being hospitalized for heart failure -- and that this relationship exists independent of therapy type and the benefits of blood pressure reduction. The study uses data from the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study conducted between 1995 and 2001.

The message for high-blood-pressure patients is that by preventing or reversing enlarged heart, there is an added benefit, over and above any reduction in blood pressure, of lowering risk for heart failure, says the study's principal investigator, Dr. Peter Okin, director of clinical affairs and professor of medicine in the Greenberg Division of Cardiology at Weill Cornell Medical College and a cardiologist at NewYork-Presbyterian/Weill Cornell.

And, from a public health perspective, our findings suggest that blood-pressure therapy targeted at regression or prevention of LVH may help to blunt the increasing incidence of heart failure, continues Dr. Okin.

Of the 8,479 high-blood-pressure patients without heart failure followed in the new study, 214 were hospitalized for heart failure (2.5 percent). Among these patients, a greater than average reduction of LVH was associated with a 43-percent reduced risk of heart failure, and remained associated with a 36-percent reduced risk after adjusting for other risk factors. Levels of LVH were determined by electrocardiograph (ECG) using Cornell voltage-duration product criteria. (Cornell voltage-duration product, an ECG pattern associated with presence of LVH, was developed at Weill Cornell Medical College in 1992 and is currently in use worldwide.)

Previous studies have shown that hypertension doubles the lifetime risk for developing heart failure in men and triples the risk in women, accounting for 39 percent of new heart failure cases in men and 59 percent of incident cases in women.

All patients in the LIFE study received Losartan- or atenolol-based therapies. In a previous LIFE study paper (Circulation, 2003), Weill Cornell researchers found the angiotensin receptor antagonist drug Losartan had a decided advantage over another anti-hypertensive drug, the beta-blocker atenolol, in reducing LVH.

Depression in women with migraine linked to childhood abuse

Mon, 03 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ST. PAUL, Minn. � Childhood abuse is more common in women with migraine who suffer depression than in women with migraine alone, according to a study published in the September 4, 2007, issue of Neurology�, the medical journal of the American Academy of Neurology.

�This study confirms adverse experiences, particularly childhood abuse, predispose women to health problems later in life, possibly by altering neurobiological systems,� said study author Gretchen Tietjen, MD, with the University of Toledo-Health Science Campus and a member of the American Academy of Neurology.

Researchers surveyed 949 women with migraine about their history of abuse, depression and headache characteristics. Forty percent of the women had chronic headache, more than 15 headaches a month, and 72 percent reported very severe headache-related disability. Physical or sexual abuse was reported in 38 percent of the women and 12 percent reported both physical and sexual abuse in the past. These results for abuse are similar to what�s been reported in the general population.

The association between migraine and depression is well established, but the mechanism is uncertain. The study found women with migraine who had major depression were twice as likely as those with migraine alone to report being sexually abused as a child. If the abuse continued past age 12, the women with migraine were five times more likely to report depression.

�The finding that a variety of somatic symptoms were also more common in people with migraine who had a history of abuse suggests that childhood maltreatment may lead to a spectrum of disorders, which have been linked to serotonin dysfunction,� said Tietjen.

�Our findings contribute to the mounting data that show abuse in childhood has a powerful effect on adult health disorders and the effect intensifies when abuse lasts a long time or continues into adulthood,� said Tietjen. �The findings also support research suggesting that sexual abuse may have more impact on health than physical abuse and that childhood sexual abuse victims, in particular, are more likely to be adversely affected.�

The study also found women with depression and migraine were twice as likely to report multiple types of abuse as a child compared to those without depression, including physical abuse, fear for life, and being in a home with an adult who abused alcohol or drugs.

�Despite the high prevalence of abuse and the increased health costs associated with it, few physicians routinely ask migraine patients about abuse history,� said Tietjen. �By questioning women about their abuse history we�ll be able to better identify those women with migraine at increased risk for depression.�

Metabolic study in mice could lead to 'good cholesterol' boosters

Tue, 07 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers have identified a new player in the control of so-called good cholesterol that circulates in the bloodstream and reduces heart attack risk, according to a report in the August issue of Cell Metabolism, a publication of Cell Press. Should the metabolic pathway uncovered in mice operate similarly in humans, the new discovery could point the way to therapies that protect against heart disease by boosting concentrations of the beneficial high-density lipoprotein cholesterol (HDL-C).

By and large, the medicines now available lower levels of the bad low-density lipoprotein cholesterol [LDL-C], said Weijun Jin of the University of Pennsylvania School of Medicine. There is a great need for methods to raise good cholesterol levels. Our findings suggest there may be multiple places to interrupt the metabolism of HDL-C.

LDL-C can build up in blood vessel walls, increasing the risk of heart disease or stroke. By contrast, HDL-C tends to carry cholesterol away from the arteries to the livera process known as reverse cholesterol transportwhere it is broken down and then eliminated from the body.

Existing LDL-C-lowering drugs such as statins can reduce the risk of heart attack by 20 to 35 percent, Jin said. However, treatment methods that would simultaneously lower bad cholesterol and increase good cholesterol have the potential to work even better. Indeed, researchers believe that increasing HDL-C while lowering LDL-C might cut heart attack risk by as much as 70 percent, he explained.

In the current study, the researchers found that treatments that partially block the activity of liver enzymes called proprotein convertases decreased plasma HDL-C levels in mice. They showed that the metabolic effect of the proprotein convertases depended on yet another factor, an enzyme called endothelial lipase (EL), which breaks down HDL-C. Proprotein convertases normally reduce EL function, they reported. Thus, the loss of proprotein convertase activity leads to an increase in EL and a decline in HDL-C.

Likewise, they showed that increased activity of proprotein convertases in the liver gives a significant boost to the protective HDL-C.

Proprotein convertases are an unexpected new player in HDL-C metabolism, Jin said. By manipulating levels of the enzyme in both directions, we were able to reduce HDL-C to almost nothing or double it. That wide range of effects suggests that it may be theoretically possible to manipulate good cholesterol levels to whatever point you like.

He emphasized, however, that the new findings represent basic research in animals. Further investigation will examine to what extent the pathway is preserved in humans, Jin said. The authors will also look for chemicals capable of modifying the pathway, which could hold promise as new good-cholesterol-boosting drugs.

Older is better -- Top-10 comparison of diabetes drugs give metformin top grade

Tue, 24 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A type 2 diabetes drug taken orally and in widespread use for more than a decade has been found to have distinct advantages over nine other, mostly newer medications used to control the chronic disease, according to a study by researchers at Johns Hopkins.

In their report, published online July 16 in the journal Annals of Internal Medicine, the Hopkins team found that metformin, first approved by the U.S. Food and Drug Administration in 1995 (and sold as Glucophage, Riomet and Fortamet), not only controlled blood sugar levels but also was less likely to cause weight gain and more likely than others to lower bad cholesterol levels in the blood.

Researchers say these health benefits are important because they can potentially ward off heart disease and other life-threatening consequence from diabetes. More than 15 million Americans have type 2 diabetes.

Sometimes newer is not necessarily better, says lead study author Shari Bolen, M.D., an internist at Hopkins. Issues like blood sugar levels, weight gain and cost could be significant factors to many patients struggling to stay in good health, says Bolen, an instructor at The Johns Hopkins University School of Medicine.

In what is believed to be the largest drug comparison of its kind, the scientists showed that all of the commonly used oral medications worked much the same at lowering and controlling blood sugar levels, and were equally safe. But metformin stood out because it offered the same level of effectiveness without lowering glucose measurements too much, and it did so for a lower price.

Metformin was found to lower LDL or bad cholesterol by about 10 milligrams per deciliter of blood, while newer medications studied, such as pioglitazone (Actos) and rosiglitazone (Avandia), or so-called thiazolidinediones, were found to have the opposite effect, increasing levels of the artery-clogging fat by the same amount.

Researchers say the main drawbacks to metformin are digestive problems and diarrhea. Previous reports have found evidence that the medication leads to the buildup of lactic acid in the blood in people with moderate kidney or heart disease, and they note that it should not be prescribed to anyone with either of these conditions. The main advantages to both newer thiazolidinediones were a small increase in HDL or good cholesterol, and less too-low blood sugar levels than three other older, cheaper drugs studied -- glimepiride (Amaryl), glipizide (Glucotrol), glyburide (Micronase, DiabBeta, Glynase PresTab) -- known as second-generation sulfonylureas.

Annual treatment with metformin or the sulfonylureas, they note, costs on average $100, roughly one-fourth the cost of oral diabetes medications FDA-approved since then, including the two newer thiazolidinediones, both approved in 1999. (Their price is expected to drop once generic versions become available.)

When you are dealing with an epidemic like diabetes, it is important for people to weigh their treatment options with their physician and to make informed decisions about which medication best suits their needs, says Bolen.

In the study, Bolen and her colleagues reviewed the scientific evidence from 216 previous studies and compared each drug for its clinical effectiveness, risks and costs. In addition to metformin, the thiazolidinediones and sulfonylureas, drugs included in their analysis were repaglinide (Prandin), miglitol (Glyset), acarbose (Precose), and nateglinide (Starlix).

Among the teams other findings were that glimepiride, glipizide, and glyburide led more frequently to too-low blood sugar levels than the other drugs. The sulfonylureas and acarbose appeared to have no effect on bad cholesterol. And except for metformin and acarbose, drug treatment led to an increase in weight from 2 to 11 pounds.

Researchers also noted the increased risk of heart failure, albeit small (less than three people in a hundred), in people taking thiazolidinediones who did not have a history of heart disease. They also caution that despite recent reports about the potential for increased risk of heart attack from rosiglitazone, there is not yet sufficient information to verify the finding.

Researchers say further studies are needed to compare the long-term effectiveness of one treatment to another and to compare drug effects on quality of life and life expectancy. Additional research will also be needed to compare these findings with results for injectible medications for diabetes, most notably insulin, which was not included in the latest report.

Restless legs genetics on the move

Thu, 19 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) In Germany alone 8 million patients are affected by RLS, which makes it one of the most common neurological diseases. The patients suffer from an urge to move and paresthesia in the legs in the evening and during the night, when they come to rest, which can only be relieved by moving or walking around. The consequence may be severe sleeping disorders, chronic sleep loss and associated with it daytime fatigue. In severe cases the disease may lead to depression and social isolation. The frequency of RLS increases with age: up to ten per cent of over 65 year olds are affected, albeit in very different forms. Children can, however, also contract the disease.

The cause of RLS has so far been completely unknown. More than half of all RLS patients report about other family members who are also affected, so that a genetic component was assumed to be involved in the development of the disease at an early stage. Various groups of scientists have been looking for the genes which might play a role in RLS for years.

A team of scientists from the Institute of Human Genetics of the GSF Research Center, the Technical University of Munich and the Max Planck Institute for Psychiatry have now first identified risk factors which are involved in the development of the disease: under the guidance of Dr. Juliane Winkelmann and Professor Thomas Meitinger DNA chips were used which make it possible to determine 500,000 of the most common variants of the human genome. The distribution of the variants between 400 RLS patients and 1600 test subjects from the normal population was measured. This genome-wide comparison of frequent variants also referred to as genome-wide association study is one of the highlights of genome research this year. Groups of scientists from Germany, Austria and Canada were involved. In all more than 1500 RLS patients and 2500 test subjects from the KORA Study of the GSF, which is conducted by Professor Erich Wichmann, participated in the study.

The genotyping platform at the GSF was partly funded by the National Genome Research Project (NGFN).

The function of the identified genes MEIS1, BTBD9 and LBXCOR1 surprised everybody involved: they are genes which are known in connection with the embryonic development of an organism. During this activity phase they are involved in the pattern formation of the extremities and the central nervous system. The role of these genes in adults will now have to be examined in greater detail.

How soon the knowledge about the genetic risk factors can be implemented in innovative new therapeutic concepts, remains to be seen. In any case new ways have now been opened up for the elucidation of the whole range of genetic and non-genetic causes of this disease. This offers researchers completely new perspectives for gaining an understanding of the cell-biology involved in the development of RLS.

Advice, devices ineffective in preventing worker back pain

Thu, 19 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Back pain is the number one cause of worker-compensation complaints, second only to the common cold in causing lost workdays. Consequently, employers and regulators have pushed training programs to teach specific lifting methods, and some recommend or require the use of assistive devices such as hoists for hospital workers. However, a new review of the research on lifting advice and handling devices has found that they do not prevent work-related back pain.

According to the studies we have so far, it seems that this is not effective, said lead author Kari-Pekka Martimo, of the Finnish Institute of Occupational Health in Helsinki. He and his colleagues examined data from more than 18,000 employees in 11 studies. Some studies looked at advice or assistive devices alone and some looked at combining both, but the combinations did not prove effective either.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The advice and devices did not prevent back pain or reduce disability claims or sick leave.

According to Martimo, one explanation for the negative findings could be that safer lifting techniques do not really exist so teaching particular tactics would be unlikely to help. Another possibility is that elevated risk for back pain might not be related to lifting or moving heavy objects themselves, but to other aspects of work, he said. High stress, for example, might link jobs that require lifting to back pain, rather than the lifting itself.

Alternatively, it could be that the teaching is the problem and that workers do not actually adopt better habits. However, the studies looked at many different training methods and did not find any to have a particular advantage. I dont think its lack of adequate teaching methods, Martimo said. One complication of considering that there is a correct lifting technique that employees should adopt is that when an employee has back pain, theres a tendency to blame the victim because he didnt [use the techniques or devices] correctly.

This study confirms that much of what is happening at the workplace is well-intentioned but probably pointless, said Christopher Maher, associate professor of physiotherapy at the University of Sydney in Australia. We had a pretty good idea that this was the case but this study really does confirm that we need to take a fresh look at the problem, said Maher, who was not involved with the study.

The frustrating thing is that government bodies and employers concentrate on things that do not work, [such as] back belts, education, lifting devices, workplace redesign and no-lift policies, and ignore the only known effective intervention exercise, Maher added. We also know that exercise has health benefits beyond prevention of back pain, so you are getting two health benefits (or more) for the price of one.

Martino concluded, We need more studies and evidence on the chain of events between certain jobs and an elevated risk of back pain. We do not know enough about that chain yet.

Sports hernia repair surgery plus innovative rehab program helps athletes return to play

Sun, 15 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) St. Louis, July 15, 2007 In recent years, sports hernias have sidelined many high-level athletes for months and, occasionally, prevented a return to competitive sports all together. New research at Washington University School of Medicine in St. Louis shows that surgical repair of sports hernias using tension-free mesh, coupled with an innovative rehabilitation program, successfully returned athletes to competition in 93 percent of cases.

Lead investigator L. Michael Brunt, M.D., professor of surgery, presented the study Sunday, July 15 at the annual meeting of the American Orthopaedic Society of Sports Medicine, held in Calgary, Alberta, Canada.

He and his colleagues evaluated the results of 61 sports hernia repair surgeries and a follow-up rehab program to determine how quickly they speed an athletes return to play. The surgeries were performed at Barnes-Jewish Hospital.

Sports hernias have received a lot of attention recently because of some high-profile athletes that have been sidelined with this condition, Brunt says. The benchmark for these athletes is return to play in their sport at the same level they were before the injury. By using the tension-free mesh to strengthen and reinforce the groin and lower abdominal muscles, we found that most athletes were back to their sport within eight weeks of surgery.

A sports hernia is not a true hernia because there is no hole in the abdominal wall through which underlying tissues protrude. A diagnosis can be tricky because symptoms particularly pain in the groin and lower abdomen can masquerade as a groin pull, strained abdominal muscle or other injury.

Those with sports hernias typically experience intense pain only at extreme levels of exertion. The condition is most common among hockey, football and soccer players. Repetitive twisting, turning or kicking motions at high speed are most likely to contribute to the condition.

Usually there is no discomfort walking around but significant pain when an athlete moves from a stationary position to full stride, Brunt says. For a high-performance athlete that can be enough to make a difference in their ability to compete successfully.

Although sports hernias occasionally occur among recreational athletes, it is far more common among those who play professional or college sports. In recent years, quarterback Donovan McNabb (Philadelphia Eagles) has had surgeries to repair sports hernias, as have forward Darren McCarty of the Calgary Flames and Los Angeles Galaxy soccer players Joseph Ngwenya and Benjamin Benditson.

The injury may also be related to changes in strength training. Most athletes focus more on the lower body and less so on the trunk. This lack of balance can create extra stress across the pelvis that is transmitted to the abdomen and the pelvic floor, which may be a factor in the development of a sport hernia, Brunt adds.

On average, the athletes Brunt operated on had experienced symptoms for eight months and most had undergone conservative management and rest during that time. A full 70 percent played at the college or professional level, and 95 percent were men. Because women have a different pelvic structure, they may be less vulnerable to sports hernias, he notes.

The surgery involves a two-inch incision to remove some of the damaged muscle tissue and instead of a primary repair with stitches, tension-free mesh is used to strengthen and reinforce the area. We think the mesh provides considerable support to let the area heal, Brunt says. Because theres no tension on the repair, this helps athletes return to full physical activity faster than surgery with a sutured repair alone.

The rehabilitation protocol used in the study was developed by Ray Barile, an athletic trainer for the St. Louis Blues hockey team. The multistep, graduated program is more structured than others used to return athletes to activity after groin surgery. It starts with early walking and movement and gradually moves athletes to resistance and core muscle building before progressing to speed and functional activities. Athletic trainers, physical therapists and athletes appear to have the most success when they are given well-structured guidelines about what can and cant be expected or allowed at each stage after hernia surgery, Brunt says.

A survey of athletic trainers who treated 21 of the athletes after surgery showed they rated the program highly (average score 4.5/5.0) in its ability to quickly and safely return athletes to their sport.

More recently, Brunt and his colleagues have accelerated the rehabilitation program to help athletes in midseason get back to competition sooner. This has helped some athletes return to play as early as five weeks after surgery. The tension-free nature of the repair helps facilitate a more aggressive progression to full activity, but Brunt cautions that the proper treatment of athletes with sports hernias requires a multidisciplinary approach. This includes sports orthopaedists, physical therapists and surgeons. It is important that physicians who see these athletes understand the entire spectrum of groin injuries and the methods that work best for returning them to competitive play, he says.

Bak protein sets stressed cells on suicide path, researchers show

Thu, 12 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) When a cell is seriously stressed, say by a heart attack, stroke or cancer, a protein called Bak just may set it up for suicide, researchers have found.

In a deadly double whammy, Bak helps chop the finger-like filament shape of the cells powerhouse, or mitochondrion, into vulnerable little spheres. Another protein Bax then pokes countless holes in those spheres, spilling their pro-death contents into the cell.

We found out Bak has a distinct function in regulation of the mitochondrial morphology, says Dr. Zheng Dong, cell biologist at the Medical College of Georgia and the Veterans Affairs Medical Center in Augusta and corresponding author on a paper published this week in Proceedings of the National Academy of Sciences. Bax, on the other hand, is not involved in morphological regulation but needs to be there to puncture holes.

One has to break up, kind of soften, the mitochondria for injury, and the other one actually punches the holes to kill it, says Craig Brooks, MCG graduate student and the papers first author.

Bak and Bax have similar structures and scientists have long suspected they play major, similar roles in programmed cell death, or apoptosis. These two proteins are very important for mitochondrial injury and subsequent apoptosis, says Dr. Dong.

To stress cells, they blocked oxygen supplies and used the common chemotherapeutic agent cisplatin, then documented that filamentous mitochondria became fragmented very early and quickly in apoptosis. Ironically they also found the deadly fragmentation results from Baks interaction with mitochondria-shaping proteins called mitofusins, which help mitochondria keep their filamentous shape in non-stressed cells. Dr. Dong suspects Bak may also play a role in mitofusin regulation in normal, non-stressful conditions.

In fact, the researchers suspect Bak, Bax and the contents they spill into the cell all have roles in keeping a cell functioning until a stressor kicks in.

They probably are both kept in check normally in the cell by other proteins, and when something happens that overwhelms the cell, it activates Bak and Bax to start cell death, says Mr. Brooks. Some of the same proteins, cytochrome c is the big one, are needed for daily mitochondrial function like making energy, but if they are released from the mitochondria, they activate a cell killing or apoptotic pathway, says Dr. Dhong, referencing the contents that spill from punctured mitochondria.

Looking at kidney cells and neurons in a Bak deficient mouse, they also showed that Bak and Bax need each other to successfully spawn cell suicide. If you have Bak but not Bax, the mitochondria still fragment but they dont die; if you have Bax but not Bak, you still have punctures in the mitochondria but with low efficiency, says Mr. Brooks.

Now they want to know exactly how Bak interacts with mitofusins, how the interaction is regulated and how it affects mitochondrial morphology, physiology and pathology. Their long-term goal for better understanding the cell suicide mechanism is developing drugs to block it in the case of a stroke, for example, or induce it to kill cancer.

Insulin sensitizer also serves as energy-conserving signal to the brain

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A fat-derived protein known for its effects on the liver and skeletal muscle might also serve as an energy-conserving signal to the brain during periods of starvation, suggests a new study in the July issue of Cell Metabolism, a publication of Cell Press. The substance, known as adiponectin, acts on the brain to boost appetite and slow energy expenditure in an effort to maintain adequate fat stores during lean times, the researchers report.

Energy homeostasis may be mediated by both short-term regulators, such as gut hormones, and long-term regulators, said Takashi Kadowaki of the University of Tokyo. In this study, we identified, for the first time, a potential long-term regulator that allows energy to be stored efficiently, namely, adiponectin. The findings offer critical insight into adiponectins influence over the central nervous system and suggest that selective inhibition of the chemical in the brain may represent a novel therapeutic strategy for obesity and obesity-linked diseases, he added.

White adipose tissue (WAT) is a major site of energy storage and plays an important role in energy balance, the researchers said. It is also recognized as an important endocrine organ that secretes a number of biologically active signaling proteins, called adipokines. Adiponectin, an adipokine secreted exclusively by WAT, is present at relatively high concentrations in the circulation and has been shown to increase the bodys response to insulin. Studies have also suggested that decreased circulating levels of adiponectin in obesity and type 2 diabetes may contribute to the insulin resistance that characterizes both conditions.

In addition to its peripheral actions on the liver and skeletal muscle, adiponectin has also been reported to have central actions, Kadowaki said. Recently, however, it was reported that adiponectin is undetectable in human cerebrospinal fluid and does not cross the blood-brain barrier, leaving some doubt about its physiological role in the central nervous system, he added.

The researchers now report evidence in mice that adiponectin receptors are present in the hypothalamic region of the brain and that some forms of the chemical enter the cerebrospinal fluid from the blood. Once in the brain, adiponectin enhances the activity of a metabolic enzyme called AMP-activated protein kinase (AMPK) to stimulate greater food consumption. Moreover, the researchers found that adiponectin decreased energy expenditure. They also showed that blood and spinal fluid adiponectin levels in the brain normally increase during fasting and decrease after refeeding, suggesting that adiponectin acts mainly during food shortages.

In adiponectin-deficient mice, AMPK activity in the brain slowed, causing the animals to eat less and expend more energy. That action, in turn, made the animals resistant to becoming obese even on a high-fat diet. Moreover, animals lacking adiponectin lost more fat after 12 hours of fasting than normal mice did.

Blood levels of another fat hormone, leptin, are regulated inversely in relation to serum adiponectin levels, the researchers noted.

Thus, central adiponectin/leptin signals may represent the physiological pathway by which hypothalamic AMPK activity and food intake are stimulated during fasting and suppressed after refeeding, they said. In addition to this short-term regulation of food intake and energy expenditure by adiponectin and leptin, these two adipokines may also participate in the long-term regulation of energy homeostasis. The fundamental roles of leptin and adiponectin seem to be to preserve an adequate fat reserve: leptin acts as a satiety signal, and adiponectin acts as a starvation signal.

Macrochem acquires option to license pexiganan

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WELLESLEY HILLS, Mass., July 10 /PRNewswire-FirstCall/ -- MacroChem Corporation (OTCBB: MACM - News) today announced that it has signed an exclusive option to acquire exclusive worldwide license rights for drug uses of pexiganan, a novel, small peptide anti-infective for topical treatment of patients with mild diabetic foot infection (DFI), from Genaera Corporation (Genaera).

We believe this is a unique opportunity for MacroChem to broaden its product portfolio with a product that has already completed two Phase 3 clinical trials. It also fits our strategic focus and complements our lead product candidate, EcoNail(TM) for treatment of nail fungus currently in a fully enrolled Phase 2 trial and progressing on track with an interim assessment of clinical data later this year after all patients have been treated for twenty four weeks, said Robert J. DeLuccia, President and CEO of MacroChem.

Clinical trials with pexiganan previously conducted by Genaera include two Phase 3 trials submitted in a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in 1998. At that time, outstanding issues with CMC (Chemistry, Manufacturing and Controls) and an FDA request for one additional controlled trial precluded approval.

Mr. DeLuccia further noted, We would be pleased to have pexiganan in our hands since we believe that, if approved, it would be welcomed by physicians and patients for the treatment of diabetic foot infection. In recent years, there have been many advances in the manufacturing of peptides, a better understanding of the treatment of diabetic foot infection, improvements in clinical trial design and execution, and more clarity concerning regulatory requirements for topical anti-infectives with the potential market being even more attractive than before.

He added, There continues to be a very large and growing incidence of diabetes and, as a result, a growing number of diabetic foot infections in the U.S. Diabetic foot ulcers in the approximately 20 million diabetics in the US alone are a major concern and burden to both patients and healthcare system. There is also a lack of effective topical anti-infectives to treat diabetic foot infection. Accordingly, we believe that pexiganan could fill an important unmet medical need for a topical anti-infective treatment and provide a significant commercial opportunity in an addressable market of approximately 3.5 million diabetic foot infections annually.

The option agreement gives MacroChem a 90-day exclusive right to enter into a license agreement with Genaera. MacroChem paid Genaera $250,000 on execution of the option agreement.

Both EcoNail and pexiganan would be developed to treat diseases of the foot predominantly treated by the same prescribing specialists, namely podiatrists. Both products would potentially be of interest to a larger number of physician specialists and primary care physicians as well. EcoNail is the company's patented lacquer which contains the antifungal econazole and MacroChem's enhancer SEPA®. Patients participating in the EcoNail study will receive 48 weeks of treatment and will undergo efficacy assessments using standard criteria of nail appearance and mycology. However, the Company will collect and evaluate 24-week interim data later this year. This trial was specifically designed, with the assistance of well-known onychomycosis experts, to address three important objectives: to assess early signs of efficacy, to maintain robust clinical endpoints in the full study, and, if successful, to facilitate advancement to Phase 3 as soon as possible.

New heart disease risk score will help minimize health inequalities

Fri, 06 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A new score for predicting the risk of heart disease gives a more accurate measure of how many UK adults are at risk of developing the disease and which adults are most likely to benefit from treatment.

The study, published on bmj.com on July 6, estimates that in the general population without pre-existing cardiovascular disease or diabetes, there are 3.2 million adults under the age of 75 in Britain at high risk of developing heart disease. This is lower than previous scores have suggested, but the researchers believe that it is a more appropriate estimate for the UK and will help minimise health inequalities.

The study comes as the governments drugs watchdog, the National Institute for Health and Clinical Excellence, recommends that people with a 20 per cent chance of developing heart disease over the next 10 years should be offered statins.

A persons chance of developing heart disease is estimated using standard risk factors such as age, sex, smoking, blood pressure and cholesterol. This risk score is typically based on equations derived from the US Framingham cohort study.

But the Framingham equations tend to over-predict heart disease risk in the UK population and fail to include measures of deprivation, family history of heart disease, body mass index, and treatment with blood pressure lowering drugs, despite known links between these factors and poor health.

So a team of researchers from The University of Nottingham, Bristol Primary Care Trust, and the Universities of Bristol and Queen Mary, set out to derive a new cardiovascular risk score (QRISK) for the UK and test its performance against the established Framingham score and a new a score used in Scotland called ASSIGN, which includes a measure of social deprivation.

The research has been conducted using data from a general practice research database called QRESEARCH, which is a joint partnership between the University of Nottingham and EMIS, a leading provider of IT systems to GPs.

The researchers tracked the progress of 1.28 million healthy men and women, registered at 318 general practices over a period of 12 years up to April 2007, recording first diagnosis of cardiovascular disease. All the participants were aged between 35 and 74 at the start of the study.

They found that the QRISK score was more accurate than either Framingham or ASSIGN. In patients aged 35-74, Framingham over-predicted cardiovascular disease risk at 10 years by 35%, ASSIGN by 36% and QRISK by 0.4%. QRISK predicted 9% of patients aged 35-74 years to be at high risk compared with 13% for the Framingham equation and 14% for ASSIGN.

Using this more focused tool for risk estimation, the research team estimate that 34% of women and 73% of men aged 64-75 would be at high risk compared with 24% and 86% according to the Framingham equation.

QRISK would also identify a different group of patients than the Framingham equation, with one in ten patients being reclassified into high or low risk, they say. QRISK is likely to provide more appropriate risk estimates of cardiovascular disease risk based on age, sex and social deprivation, write the authors. It is therefore likely to be a more equitable tool to inform management decisions and help ensure treatments are directed towards those most likely to benefit.

In people under 75 years without pre-existing cardiovascular disease or diabetes, QRISK identifies 3.2 million patients at high risk in 2005, compared with 4.7 million from Framingham and 5.1 million from ASSIGN.

They suggest that QRISK should be further tested in other populations, but point out that this is the largest such study to have ever been undertaken, and the first time routine data in a UK general practice population have been used in this way.

Study leader, Professor Julia Hippisley-Cox, of The University of Nottingham, said: QRISK is derived from primary care data for use in primary care, and takes account of social deprivation to better identify patients most at most risk of heart disease and stroke who are most likely to benefit from treatment.

We thank the many thousands of doctors who have enabled this research by freely contributing anonymised data to QRESEARCH, without which this work would not have been possible.

How pain distracts the brain

Thu, 05 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Anybody whos tried to concentrate on work while suffering a headache knows that pain compellingly commands attentionwhich is how evolution helped ensure survival in a painful world. Now, researchers have pinpointed the brain region responsible for pains ability to affect cognitive processing. They have found that this pain-related brain region is distinct from the one involved in cognitive processing interference due to a distracting memory task.

Ulrike Bingel and colleagues at the University Medical Center Hamburg-Eppendorf published their discovery in the July 5, 2007 issue of the journal Neuron, published by Cell Press.

To search for the region responsible for pains ability to usurp attention, the researchers asked volunteers to perform a cognitive task involving distinguishing images, as well as a working memory task involving remembering images. The researchers asked the volunteers to perform the tasks as they experienced different levels of pain caused by the zapping of their hands by a harmless laser beam.

During these tests, the volunteers brains were scanned using functional magnetic resonance imaging (fMRI). In this widely used analytical technique, harmless magnetic fields and radio waves are used to scan the brain to determine blood flow across regions, which reflects brain activity.

The researchers experiments identified a brain region called the lateral occipital complex (LOC) as the cognitive-related area affected by both working memory load and pain. This finding was expected, since the LOC is known to be involved in processing images.

The researchers next sought to identify the brain region by which pain affects the functioning of the LOC. They theorized that the best candidate for this region was one called the rostral anterior cingulate cortex (rACC). This region is known to be involved in the brains processing of pain, and it is part of the anterior cingulate cortex, which plays an important role in executive functions such as attentional control. These structures are located deep in the brain in the region of connection between the two hemispheres.

Indeed, the researchers fMRI scans indicated that the rACC is, indeed, the brain center through which pain influences the LOC. By contrast, they found a working memory load affects the LOC through a different region, the inferior parietal cortex.

The researchers noted that the modulation of visual processing by pain that they observed in their fMRI studies is behaviorally relevant, because as their fMRI scans showed pain affecting the LOC, they also observed a parallel impairment of accuracy in subjects recognition of the images.

Protein's role in lipid absorption may be important to future weight-loss strategies

Thu, 05 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) July 5, 2007 -- Researchers at Washington University School of Medicine in St. Louis have found that a protein absorbs lipids in the upper part of the intestine, and they believe its key role in this process may provide a novel approach for obesity treatment in the future.

Principal investigator Nada A. Abumrad, Ph.D., the Dr. Robert C. Atkins Professor of Medicine and Obesity Research at Washington University School of Medicine, first identified the protein, CD36, that facilitates the uptake of fatty acids. The protein is located on the surface of cells and distributed in many tissues, including fat cells, the digestive tract, heart tissue and skeletal muscle tissue.

Her studies have shown that the intestine makes large amounts of CD36, and that it is important to the absorption of fatty acids. Initially when she compared normal mice that made the protein to genetically altered mice lacking CD36, she couldn't find any net difference in their fat absorption.

But the new study, reported in the July 6 issue of the Journal of Biological Chemistry, reveals the reason it was not possible to identify a difference. Apparently, the intestine has some built-in redundancy.

Normally, CD36 absorbs fatty acids in the upper, or proximal part of the intestine, but when it is absent, lower, more distal, sections of the intestine compensate and absorb the fat.

We think of the intestine as a single organ, but it's really made up of distinct areas that are so specialized it's almost like several organs, Abumrad says. The fat that is not absorbed in the proximal areas ends up being bumped into the distal intestine where different systems absorb it,

Abumrad and her colleagues, including first author Fatiha Nassir, Ph.D., research assistant professor in the Division of Gerontology and Nutritional Science, believe that targeting the upper part of the intestine and interfering with normal CD36 function might be a useful tool in weight loss. The team found that animals that could not make CD36 absorbed fat less efficiently, and as a result they tended to eat less of it.

And the most exciting part for us right now is the fact that these things may apply to humans, Abumrad says. Humans with mutations in the gene that makes CD36 don't seem to process fat normally either.

She learned from the mice that when fatty acids and cholesterol are not absorbed in the proximal part of the intestine, as normally occurs, the distal intestine packages those fats very differently.

The proximal intestine makes molecular packages called chylomicrons, she says. These bundles that contain lipids and proteins transport these molecules from the intestine to other parts of the body. CD36, which is abundant in the proximal intestine, turns out to play a role both in absorbing fatty acids and cholesterol and in packaging these lipids into chylomicron bundles that facilitate their use throughout the body.

When no CD36 was present in the genetically altered mice in Abumrad's study, the lipids were absorbed more slowly since they had to travel to lower, more distal parts of the intestine. And they also were packaged differently. Rather than being bundled into chylomicrons, the lipids were released as parts of smaller particles that are not as easily absorbed by other tissues as the chylomicrons.

For years, Abumrad has studied how CD36 modulates the acute and chronic responses of muscle and fat cells to energy fluctuations and other stresses. Her goal is to translate her findings from rodents into humans, where variations in the CD36 gene are common.

There is evidence that people have different amounts of CD36 and that mutations in the gene are quite common, she says. Those variations are associated with abnormalities of blood lipids, with high levels of fatty acids in the blood, abnormal blood triglycerides and increased risk of diabetes-associated heart disease. It's clear that some of us have different amounts of this protein in different tissues, and some individuals don't have any of it.

Although scientists in Abumrad's laboratory think it may be possible eventually to help people lose weight by interfering with the CD36 protein, they first want to learn more from the mouse. Currently, they work with mice that cannot make CD36 anywhere in their bodies. But because the protein also operates in heart tissue and skeletal muscle, disabling CD36 everywhere can have detrimental effects. So the team is working to develop a new kind of mutant mouse, one that can make CD36 everywhere except in the intestine.

If we find that such a mouse still has delayed absorption of fatty acids and cholesterol and ends up eating less fat, we'll have more evidence that this might be a good approach to use in humans, she says. Block the function of the protein in the intestine, absorb fewer lipids, and since your absorption is delayed, you don't feel as hungry and you eat less.

But until such a mouse is developed, Abumrad's team cannot be certain that blocking the effects of CD36 in the intestine might not also have harmful effects. Interfering with CD36 function to absorb less fat is not necessarily a good thing if it causes problems in the heart, the liver or elsewhere in the body.

SSRI antidepressants do not pose major birth defect risk

Wed, 27 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Boston, MA -- Researchers from Boston Universitys Slone Epidemiology Center have found that certain selective serotonin reuptake inhibitors antidepressants do not appear to increase the risk for most kinds of birth defects. The findings, to be published in the June 28, issue of the New England Journal of Medicine, suggest that individual SSRIs may increase the risk for some specific defects, but these are rare and the absolute risks are small.

The risk of birth defects following antenatal exposure to SSRIs remains controversial. Early studies demonstrated that SSRIs didnt increase risks of birth defects when such defects were studied as a group. However, birth defects are not a single entity and individual defects have distinct causes. And, more recent studies have reported elevated risks for some birth defects.

Using data from the Slone Epidemiology Centers Birth Defects Study, an ongoing program of case-control surveillance of medication use in relation to birth defects, the researchers considered relationships between first trimester SSRI use and the risk of various birth defects among mothers of 9,849 infants with birth defects and 5,860 infants without defects.

The researchers analyzed defects previously linked to SSRI use and found overall SSRI use was not associated with significantly increased risks of craniosynostosis (where connections between skull bones close prematurely), omphalocele (intestines or other abdominal organs protrude from the naval) or heart defects overall.

Analysis of individual SSRIs and specific defects showed significant associations between setraline (e.g. Zoloft) and omphalocele and septal defects (defects in the walls that separate the chambers of the heart) and between the paroxetine (e.g. Paxil) and certain heart defects that interfere with blood flow to the lungs. This last association was also reported in another paper, from the CDCs National Birth Defects Prevention Study, in this weeks NEJM. However, the BU researchers stress that even if a specific SSRI increased rates four-fold, as was observed for some of these associations, the risk of having an affected child would be less than one percent.

Our analyses did not confirm previously reported associations between overall use of SSRIs and a number of birth defects, said lead author Carol Louik, ScD, an assistant professor at the Slone Epidemiology Center at Boston University. Rather our study suggests that risks are limited to specific SSRIs in relation to specific birth defects. Still, it is important to keep in perspective that the baseline risks for these rare defects are small, so even if the modest increased risks we observed are correct, the chances of having a child with such a defect are quite small, she added.

Weight management program cuts diabetes risk, improves BMI in overweight children

Tue, 26 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A family-based weight management program developed by researchers at Yale School of Medicine was more effective at reducing weight, body fat, body mass index (BMI) and insulin sensitivity than traditional clinic-based weight counseling.

Mary Savoye-Desanti, research associate in Yales Department of Pediatrics, will present the findings at a JAMA media briefing in New York on June 26 at 10 a.m. The study will be published in JAMAs June 27 theme issue on chronic diseases of children.

Savoye-Desanti, a registered dietician and certified diabetes educator, and her team conducted the one-year clinical trial of 209 overweight children between the ages of 8 and16 to address the increasing prevalence of childhood obesity, especially in the African American and Hispanic population. The childhood obesity epidemic has also sparked an increase of type 2 diabetes among adolescents.

Savoye-Desanti and colleagues measured the effectiveness of the weight management program Bright Bodies, in comparison to care provided at a pediatric obesity clinic. Bright Bodies was created 10 years ago by Savoye-Desanti and combines nutrition education, behavior modification and exercise tailored to the needs of inner-city children. The study sought to compare changes in BMI, body composition, insulin sensitivity, blood pressure and lipid profiles.

The 105 children randomly assigned to the Bright Bodies program participated in 50 minutes of exercise for two nights per week. The eight to 10-year-old group participated in several games such as relay races, obstacle courses and several other games including Swim Fish Swim. The older group (11- to 16-year-olds) played flag football, basketball and other activities. Both groups played Dance, Dance Revolution by Konami.

The study revealed great differences in BMI, body weight, body fat and percent body fat between the control group and the weight management group. While the average body weight was essentially unchanged among the weight management group, BMI was reduced by 1.7 units and there was an improvement in overall cholesterol. The control group gained an average of 17 pounds and increased their BMI by 1.6 units. Percent and total body fat was reduced in the weight management group and increased in the control group.

Insulin sensitivity, which measures the risk of developing type 2 diabetes, was increased in the weight management group and decreased in the control group. Increased insulin sensitivity is linked to a reduced risk of developing type 2 diabetes.

We have shown that a family-based program that uses nutrition education, behavior modification and supervised exercise can lower BMI, improve body composition and increase insulin sensitivity, said Savoye-Desanti, who stresses that the success of the Bright Bodies program relates to frequent contact between the families and staff members. This is a family problem. The child cant do it alone.

Savoye-Desanti said that while the program was very successful in treating overweight children, the expense incurred in operating such a program is substantial. We will focus future studies on cost-benefit analyses, as this would be helpful for pediatric clinicians or health management organizations that are considering offering similar services to overweight children and adolescents, said Savoye-Desanti.

Community Oncology explores pitched debate over anemia-fighting drugs

Tue, 26 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The June issue of Elseviers Community Oncology takes an in-depth look at the charge that ESAs, generally considered vital to cancer patients quality of life, are overprescribed for profit. Scientists, oncologists, and critics of oncologists are in a heated debate now over the use of ESAs, or erythropoiesis-stimulating agentsdrugs that fight anemia by boosting levels of oxygen-carrying red blood cells and the protein hemoglobin.

Many cancer patients, suffering from fatigue and symptomatic anemia as side effects of their disease and its treatment, are prescribed ESAsalso known as EPO (epoetin alfa, or Procrit) and DARB (darbepoetin alfa, or Aranesp). New datamostly from studies of off-label useson potentially dangerous side effects such as blood clots, and on survival rates, are prompting some scientists to recommend that the US Food and Drug Administration effectively curtail the use of ESAs. Adding fuel to this debate is the fact that the drugs are costly, and some critics have accused oncologists of overprescribing them, swayed by drug company rebates.

The question is whether trained oncologists will be allowed to make the best clinical decision for each patient, or whether rationingwhich isnt based on scientific evidence but on an economic policy tug-of-warbecomes the standard, says Lee S. Schwartzberg, MD, Editor-in-Chief of Community Oncology. The current issue of the journal puts the debate in clear focus.

ESAs are intensively studied medications. After 15 years of well-designed clinical trials, we know that ESAs decrease the need for blood transfusions in cancer patients, increase hemoglobin, and improve quality of life in most patients with chemotherapy-induced anemia, says David H. Henry, MD, an editor of Community Oncology. He adds, Its clear that these drugs cost too much and that any profit from reimbursement should be corrected. But when used on-label, ESAs are safe. Still, the recent studies give us pause. They suggest we need to review all the data in a fair and balanced way. There has been too much emotional distraction.

The June issue of Community Oncology, which serves private practice-based clinicians, contains a point-counterpoint debate, an economic analysis of the cost of ESAs to practices, a report on toxicities from the RADAR project (Research on Adverse Drug Events And Reports) which closely monitors reports to the FDA on drug side effects, a review of ESA clinical studies, the point of view of a payer who plays a key role in ESA prescribing patterns, and a community oncology advocate who says that if insurers jump the gun on policy, both patients and practices could suffer. Its not an exaggeration to say that this controversy has serious implications for the future of cancer care in the United States, notes Dr. Schwartzberg.

More than just bare bones -- New research suggests emotions can affect recovery from hip surgery

Tue, 26 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ST. LOUIS -- A patients emotional state plays a significant role in his or her recovery from hip surgery, suggests Saint Louis University research published this month.

Orthopaedic surgeons typically use two tests to determine if a patient has recovered from hip surgery: one is a clinical measure of hip function given by the doctor, and the second is a questionnaire patients answer that considers a wide variety of factors in determining the overall success of the surgical procedure.

We started out simply looking to see if the results of the two tests were correlated; the one doctors give has been used for decades to evaluate hip function, and the other that the patient answers is much newer, says Berton Moed, M.D., chair of the department of orthopaedic surgery at Saint Louis University School of Medicine. What we found was surprising the clinical test found good-to-excellent results, while the self-test taken by the same patients showed significantly worse recovery.

The disparity, says Moed, can be explained by a section of questions on the self-test not addressed by the clinical test: those dealing with emotional well-being. A patients emotional status was the second-most important factor in determining how well he or she thought recovery was going, Moed found. (Mobility was the first.)

Patients come in for check-ups after their hip surgery and the doctor says, Looks like youre doing fabulously, and they respond, No, Im not. I ache, Moed says. Theyre not doing well, but why It appears to have a lot to do with their emotional state. Its the elephant in the exam room that is, something doctors need to acknowledge is a real issue.

Rather than retool the established clinical test to include an emotional component, Moed says orthopaedic surgeons should make efforts to use both exams for a more comprehensive measure of the patients recovery.

Do we need to look at other interventions besides fixing their hip I think we might have to, he says. That could include bringing in social workers and psychologists to work with the patients in the areas that surgeons, who often are super subspecialists, may not be able to deal with.

Moed says both underlying depression and new depression brought on by the injury and/or surgery could be to blame for slowing a patients recovery.

When an active person is suddenly confined to the bed or to limited activity, it can take a toll, Moed says. Not being able to do the things one used and feeling powerless over it may play a larger role than we thought in how well the patient feels theyre recovering.

While Moed says some patients may be taken aback by the suggestion that they see a psychologist after surgery, he thinks developing better and more customized treatment plans has the potential to help patients recover more fully and not just after hip surgery.

The number one issue is recognition we need to acknowledge that theres more going on with patients than what current clinical tests tell us, he says.

Further legitimization of fibromyalgia as a true medical condition

Mon, 25 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Philadelphia, June 25, 2007 -- Fibromyalgia, a chronic, widespread pain in muscles and soft tissues accompanied by fatigue, is a fairly common condition that does not manifest any structural damage in an organ. Twenty-five years ago, Muhammad B. Yunus, MD, and colleagues published the first controlled study of the clinical characteristics of fibromyalgia syndrome. That seminal article, published in Seminars in Arthritis and Rheumatism, led directly to formal recognition of this disease by the medical community. In the June 2007 issue of Seminars in Arthritis and Rheumatism, Dr. Yunus once again makes an enormous contribution to the field of chronic pain and fatigue by meticulously synthesizing and interpreting the extensive body of scientific literature on fibromyalgia and his own insights into the concept of central sensitivity syndromes (CSS).

Fibromyalgia, affecting approximately 2% of the US population, is an example of a class of maladies called CSS. These diseases are based on neurochemical abnormalities and include irritable bowel syndrome, migraine and restless legs syndrome.

Incorporating a critical review of over 225 publications and the authors broad experience in fibromyalgia and related diseases, Dr. Yunus describes 13 separate conditions that are related to central sensitization (CS), where the central nervous system (spinal cord and brain) becomes extremely sensitized on certain parts of the body, so that even mild pressure or touch would cause much pain. Such hypersensitivity may also be associated with other symptoms such as poor sleep and fatigue.

According to Dr. Yunus, CSS are the most common diseases that are based on real neurochemical pathology and cause real pain and suffering. In some patients stress and depression may contribute to the symptoms but they are all based on objective changes in the central nervous system.

Dr. Norman L. Gottlieb, Editor of Seminars in Arthritis and Rheumatism, believes that this article advances our understanding of fibromyalgia, unifies and advances concepts, and suggests that this and several other common disorders have much in common in terms of their biopsychosocial development. This, hopefully, will expand both clinical and research interest in this group of diseases and lead to advances in therapy for many of them.

In an accompanying editorial John B. Winfield, MD, comments, Without question, Muhammad Yunus is the father of our modern view of fibromyalgia. Yunus, who took a rather more biological approach to fibromyalgia in the past, now emphasizes a biopsychosocial perspective. In my view, this is tremendously important because it is the only way to synthesize the disparate contributions of such variables as genes and adverse childhood experiences, life stress and distress, posttraumatic stress disorder, mood disorders, self-efficacy for pain control, catastrophizing, coping style, and social support into the evolving picture of central nervous system dysfunction vis-a-vis chronic pain and fatigue .Science and medicine now have a rational scaffolding for understanding and treating chronic pain syndromes previously considered to be functional or unexplained. Neuroscience research will continue to reveal the mechanisms of CS, but only if informed through a biopsychosocial perspective and with the interdisciplinary collaboration of basic scientists, psychologists, sociologists, epidemiologists, and clinicians.

Dr. Yunus concludes that CSS is an important new concept that embraces the biopsychosocial model of disease. He advocates further critical studies to fully test this concept which seems to have important significance for new directions for research and patient care involving physician and patient education. Each patient, irrespective of diagnosis, says Dr. Yunus, should be treated as an individual, considering both the biological and psychosocial contributions to his or her symptoms and suffering.

K-State researcher examining why common anti-inflammatory drugs harm intestines

Thu, 21 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) MANHATTAN, KAN. -- New versions of drugs like buffered aspirin and Vioxx could produce fewer harmful side effects thanks to research being done at Kansas State University's College of Veterinary Medicine.

K-State researchers are examining how nonsteroidal anti-inflammatory drugs, or NSAIDs, damage the tissue that lines the gastrointestinal tract. James Lillich, associate professor of clinical sciences, is leading the research. He said NSAIDs are some of the most commonly used prescription and over-the-counter drugs for relieving ailments from headaches to arthritis.

The research being done at K-State will benefit animals like horses that require NSAIDs for ailments related to their athletic activities.

We treat horses the same way we treat humans, and horses get the same side effects, Lillich said.

NSAIDs work by blocking a type of enzyme called cyclooxygenase, or COX, which is needed for healthy cellular function. When tissue becomes inflamed, isoforms of the enzyme produce naturally occurring compounds called prostaglandins, which are responsible for the pain associated with inflammation. Although drugs inhibiting COX-2 reduce inflammation, their targets can spill over and also inhibit the gastrointestinal tract's ability to heal itself, leading to problems like ulcers.

NSAIDs are doing more than just inhibiting COX, Lillich said. You're going to have to deal with side effects with any drug.

In the intestines, healthy epithelial cells move toward damaged cells to repair wounds in a matter of minutes to hours.

The epithelial cells in the GI tract are the barrier between your body and the outside world, Lillich said.

He said NSAIDs inhibit this migration. To find out why, Lillich took an intestinal cell line and exposed it to NSAIDs. He then used wounding assays to assess cell migration over a period of four hours.

Wounding assays are a way we can look at, basically, the behavior of cells, Lillich said.

In the wounding assay, Lillich said cells are seeded on a base that resembles the substance they would normally anchor themselves to in the body. The cells lay themselves out as a flat, single layer, known as a monolayer. The cells are treated with NSAIDs, and then a portion of the monolayer is removed and examined to see the response over a short period of time.

Basically we are looking at cell migration as they move to re-establish the monolayer, Lillich said. We do this over a four-hour time frame, so we know it is migration and not the cells dividing or proliferation.

Lillich and the researchers found something they didn't expect -- that in addition to blocking COX, NSAIDs also are affecting other important enzymes called calpains that are required for cell maintenance. These calpains are vital to white blood cells in epithelial cell migration. Lillich said calpains have become the focus of the research at K-State.

Calpains are a good starting point, because they play important roles for a variety of cells, and you're not just looking at one or two cell types when it comes to ulcer formation, Lillich said. This will teach us about wound healing, cell migration and what the white blood cell does.

Lillich said the research he is doing at K-State will lead to better treatment for patients requiring nonsteroidal anti-inflammatory drugs.

What we're trying to do is get better at drug design, Lillich said. The manufacturers will be able to make drugs that inhibit some isoforms of COX but without inhibiting calpains. Manufacturers will be able to make a drug with fewer harmful side effects.

Diachrome improves blood sugar control in people with type 2 diabetes

Tue, 05 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Nutrition 21, Inc. today announced new published results from a 447 subject, randomized, double-blind, placebo-controlled clinical study that showed Diachrome, a patented combination of chromium picolinate and biotin, significantly improved glycemic control in patients with poorly controlled blood sugar levels who were being treated with oral anti-diabetic medication (OADs). Patients in the treatment group showed significant improvements in glycemic control (A1C) compared with placebo (an absolute decrease of 0.54%). The greatest improvement was seen in those patients with the poorest glycemic control (baseline A1C levels equal to or greater than 10%). These patients saw an additional absolute A1C decrease of 1.76% despite the fact that they were taking one or more OAD medications.The American Diabetes Association's (ADA) recommended goal for type 2 diabetes patients is an A1C level below 7.0%. Lowering A1C by just 1%, especially in patients with poor blood sugar control, can delay or prevent serious complications, reduce diabetes-related deaths and reduce healthcare costs. Uncontrolled, obese and overweight type 2 diabetes patients present an ongoing clinical challenge to health professionals. Prescribing another anti-diabetic medication can increase the risk of unwanted side effects, including weight gain or hypoglycemic events, and could place an added financial burden on the patient, said Cesar Albarracin, MD, lead investigator and a leader in the field of nutritional management of type 2 diabetes. This study shows that adding Diachrome to anti-diabetic medications can help patients reach their blood sugar goal simply, effectively and safely.

Old memory traces in brain may trigger chronic pain

Mon, 04 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO --- Why do so many people continue to suffer from life-altering, chronic pain long after their injuries have actually healed

The definitive answer -- and an effective treatment -- has long eluded scientists. Traditional analgesic drugs, such as aspirin and morphine derivatives, havent worked very well.

A Northwestern University researcher has found a key source of chronic pain appears to be an old memory trace that essentially gets stuck in the prefrontal cortex, the site of emotion and learning. The brain seems to remember the injury as if it were fresh and cant forget it.

With new understanding of the pain source, Vania Apkarian, professor of physiology, and of anesthesiology, at Northwesterns Feinberg School of Medicine, has identified a drug that controls persistent nerve pain by targeting the part of the brain that experiences the emotional suffering of pain. The drug is D-Cycloserine, which has been used to treat phobic behavior over the past decade.

In animal studies, D-Cycloserine appeared to significantly diminish the emotional suffering from pain as well as reduce the sensitivity of the formerly injured site. It also controlled nerve pain resulting from chemotherapy, noted Apkarian, who is a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.

The drug has long-term benefits. Animals appeared to be pain free 30 days after the last dose of a 30-day regime of D-Cycloserine.

The study, funded by the National Institutes of Health, will be published in the journal Pain this fall. (It has been published on-line.)

In some ways, you can think of chronic pain as the inability to turn off the memory of the pain, Apkarian said. Whats exciting is that we now may be relieving what has clinically been the most difficult to treatthe suffering or the emotional component of pain.

Scientists have always tried to understand pain from the viewpoint of sensation, Apkarian said. To control it, they tried to stop the sensory input to the brain. We are saying theres a cognitive memory and emotional component in the brain that seems abnormal. Easing that may have a bigger effect on suffering.

Chronic pain is not caused by a single mechanism, Apkarian noted. Sensory abnormalities in people with chronic pain probably drive this memory abnormality.

About 10 percent of the United States population suffers from chronic pain, of which the majority is back pain.

One of Apkarians studies with rats tried to separately measure their emotional suffering and their physical pain after being treated with the drug. (The rats had chronic pain from a healed limb injury.) The results indicated the animals emotional suffering decreased much more than their physical pain. While the physical pain appeared to be reduced 30 percent their emotional suffering completely disappeared.

Rat are nocturnal animals that prefer to be in the dark and are averse to bright light. Researchers placed the rats in a two-compartment chamber - one side light, one dark. When the rats were in their preferred dark side, scientists mechanically stimulated their sensitive limbs. The rats didnt like that and bolted into the bright chamber, where they remained. Next scientists took the same rats and treated them with DCycloserine. Again, scientists stimulated the rats sensitive limbs. This time, however, the rats remained in the dark chamber.

Their aversive reaction to the stimulation disappeared, Apkarian said.

Based on the animal results, the next step will be to test the drug in clinical trials, Apkarian said.

When we do this in a clinical trial, we expect people to say I still have the pain, but its not bothering me anymore, Apkarian said. We think they will have a physical awareness of the pain, but its emotional consequences will have decreased. He said the drug potentially may lower the amount of standard analgesics people have to use.

In Apkarians previous study, published in late 2006, he revealed that chronic back pain appears in a different part of the brain than the discomfort of burning your finger, for example. With a functional MRI, he found that chronic back pain shows up in the prefrontal cortex. By contrast, the acute sensory pain of the burned finger appears in the sensory part of the thalamus.

Apkarian also found that the longer a person has been suffering from chronic pain, the more activity in the prefrontal cortex. He was able to predict the years of their suffering from the MRI.

Its cumulative memory, he explained. I can predict with 90 percent accuracy how many years they have been living in that pain without even asking them the question.

Detecting cold, feeling pain: Study reveals why menthol feels fresh

Wed, 30 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Scientists have identified the receptor in cells of the peripheral nervous system that is most responsible for the body's ability to sense cold.

The finding, reported on-line in the journal Nature (May 30, 2007), reveals one of the key mechanisms by which the body detects temperature sensation. But in so doing it also illuminates a mechanism that mediates how the body experiences intense stimuli temperature, in this case that can cause pain.

As such, the receptor known as menthol receptor TRPM8 -- provides a target for studying acute and chronic pain, as can result from inflammatory or nerve injury, the researchers say, and a potential new target for treating pain.

By understanding how sensory receptors work, how thresholds for temperature are determined, we gain insight into how these thresholds change in the setting of injury, such as inflammatory and nerve injury, and how these changes may contribute to chronic pain, says senior author David Julius, PhD, chairman and professor of physiology at UCSF.

The methanol receptor, and other temperature receptors discovered in recent years by the Julius lab, offer potential targets for developing analgesic drugs that act in the peripheral, nervous system, rather than centrally, where opiate receptors act, he says.

The finding is a milestone in an investigation the team began several years ago. In 2002, the researchers discovered that the receptor was activated by chemical cooling agents such as menthol, a natural product of mint, and cool air. They reported their discovery, or cloning, of the receptor in Nature (March 7, 2002), hypothesizing that the receptor would play a key role in sensing cold. However, some subsequent papers questioned this theory.

In the current study, the team confirmed their hypothesis by knocking out the gene that synthesizes the receptor, both in sensory neurons in cell culture and in mice. The cells in culture were unresponsive to cooling agents, including menthol. The genetically engineered mice did not discriminate between warm and cold surfaces until the temperature dropped to extremes.

It's been known for years that menthol and related cooling agents evoke the psychophysical sensation of cold somehow by interacting with the aspect of the sensory nervous system that's related to cold detection, says Julius.

The current study, he says -- led by Diana M. Bautista, PhD, and Jan Siemens, PhD, of the Julius lab and Joshua M. Glazer, PhD, of the lab of co-senior author Cheryl Stucky, PhD, of the Medical College of Wisconsin puts that question to rest.

As the mice lacking the gene were not completely insensitive to cold -- they avoided contact with surfaces below 10 degrees C, though with reduced efficiency -- the next step, says Julius, will be to illuminate this residual aspect of cold sensation.

The finding is the latest of a series of discoveries led by the Julius lab on the molecular mechanisms of temperature sensation and pain. In 1997, the lab cloned the gene for the capsaicin receptor, the main pungent ingredient in some chili peppers (Nature, Oct. 23, 1997), and in 2000 reported that, in mice, the receptor triggers the nerves to fire pain signals when they are exposed to high ambient heat or the fiery properties of peppery food. (Science, April 14, 2000). The study demonstrated that capsaicin and noxious heat elicit the sensation of burning pain through activation of the same receptor on sensory neurons.

Most recently, they identified the receptor of isothiocyanate compounds, which constitute the pungent ingredients in such plants as wasabi and yellow mustard. In response to high temperatures, the receptor produces pain and irritation.

All of these studies use natural products to understand pain mechanisms in the periphery of the body, where they are first sensed, says Julius.

Ultimately, pain signals are transmitted from the peripheral nervous system into the body's central nervous system moving through nerves in the spinal cord and brain stem up to the brain, which prompts a response, or feeling. Co-author of the current study Allan Basbaum, PhD, also of UCSF, is a pioneer of research into the mechanism of chronic pain within the central nervous system.

The Julius team's complementary work is focused at the level of the sensory nerve fiber, where the signals are first initiated. We want to know, Julius says, how do you detect these stimuli to begin with How do your sensory nerve endings do this to begin with And what are the biochemical and biophysical mechanisms that account for this

All three receptors the Julius lab has discovered are members of the TRP family of ion channels expressed on sensory neurons. The latest finding adds to the evidence, says Julius, that TRP channels are the principal transducers of thermal stimuli in the mammalian periphery nervous system.

Exercise may slightly boost 'good' cholesterol levels

Mon, 28 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Regular exercise appears to modestly increase levels of high-density lipoprotein, or good, cholesterol, according to a meta-analysis study in the May 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

A low level of high-density lipoprotein cholesterol (HDL-C) is an independent risk factor for cardiovascular disease, the leading cause of death worldwide, according to background information in the article. There is strong evidence that individuals who are more physically active have higher HDL-C levels. Thus, the value of regular aerobic exercise in increasing serum [blood] HDL-C level and in reducing the risk of cardiovascular disease has received widespread acceptance, the authors write. In contrast, results of aerobic exercise studies vary considerably, depending on the exercise program (e.g., duration, intensity or frequency) and characteristics of subjects at baseline.

Satoru Kodama, M.D., of Ochanomizu University, Tokyo, and colleagues performed a meta-analysis of 25 articles reporting the results of randomized controlled trials that were published between 1966 and 2005 and assessed the effects of exercise on HDL-C. To be included in the analysis, the studies had to evaluate aerobic exercise in adults with an average age of 20 or older, specify HDL-C measurements at the beginning and end of the study, have a length of at least eight weeks, and randomly assign some participants to a group of exercisers and others to a control group of non-exercisers.

The 25 articles analyzed included a total of 1,404 participants with an average age range of 23 to 75 years and an average study period of 27.4 weeks. The exercise groups were told to exercise for an average of 3.7 sessions per week at an average of 40.5 minutes each, burning an average of 1,019 calories per week.

In all the studies combined, HDL-C increased by an average of 2.53 milligrams per deciliter in the exercise groups. The minimum amount of weekly exercise that appeared necessary to change HDL-C levels was 120 minutes or 900 calories burned. The effect of exercise was greater in those who had a higher total cholesterol level (220 milligrams per deciliter or greater) and in those with a body mass index of less than 28.

In a previous observational study, every 1-milligram per deciliter increment in HDL-C level was reported to be associated with a 2 percent and 3 percent decreased risk of cardiovascular disease in men and women, respectively, the authors write. If this observation were applied to our results, the increase in HDL-C level by exercise determined by this analysis would, by a rough estimate, result in a cardiovascular disease risk reduced by approximately 5.1 percent in men and 7.6 percent in women. This is potentially of substantial importance in public health, although the effect of reducing cardiovascular risk by increasing HDL-C level might be smaller than that by use of medications such as fibrates or niacin.

Only exercise duration, and not frequency or intensity, was associated with a change in HDL-C levels in the analysis. When the participants exercised for 23 to 74 minutes per session, each 10-minute increase in exercise duration corresponded to a 1.4-milligram per deciliter increase in HDL-C level. This suggests that in improving blood HDL-C values, increasing time per session is better than performing multiple brief exercise sessions when total time for exercise is limited, as is the case for many people, the authors write.

Smokeless cannabis delivery device efficient and less toxic

Tue, 15 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A smokeless cannabis-vaporizing device delivers the same level of active therapeutic chemical and produces the same biological effect as smoking cannabis, but without the harmful toxins, according to UCSF researchers.

Results of a UCSF study, which focuses on delivery of the active ingredient delta-9-tertrahydrocannibinol, or THC, are reported in the online issue of the journal Clinical Pharmacology and Therapeutics.

We showed in a recent paper in the journal Neurology that smoked cannabis can alleviate the chronic pain caused by HIV-related neuropathy, but a concern was expressed that smoking cannabis was not safe. This study demonstrates an alternative method that gives patients the same effects and allows controlled dosing but without inhalation of the toxic products in smoke, said study lead author Donald I. Abrams, MD, UCSF professor of clinical medicine.

The research team looked at the effectiveness of a device that heats cannabis to a temperature between 180 and 200 degrees C, just short of combustion, which occurs at 230 degrees C. Eighteen individuals were enrolled as inpatients for six days under supervision in the General Clinical Research Center at San Francisco General Hospital Medical Center.

Under the study protocol, the participants received on different days three different strengths of cannabis by two delivery methodssmoking or vaporizationthree times a day.

Plasma concentrations of THC were measured along with the exhaled levels of carbon monoxide, or CO. A toxic gas, CO served as a marker for the many other combustion-generated toxins inhaled when smoking. The plasma concentrations of THC were comparable at all strengths of cannabis between smoking and vaporization. Smoking increased CO levels as expected, but there was little or no increase in CO levels after inhaling from the vaporizer, according to Abrams.

Using CO as an indicator, there was virtually no exposure to harmful combustion products using the vaporizing device. Since it replicates smokings efficiency at producing the desired THC effect using smaller amounts of the active ingredient as opposed to pill forms, this device has great potential for improving the therapeutic utility of THC, said study co-author Neal L. Benowitz, MD, UCSF professor of medicine, psychiatry and biopharmaceutical sciences. He added that pills tend to provide patients with more THC than they need for optimal therapeutic effect and increase side effects.

Patients rated the high they experienced from both smoking and vaporization and there was no difference between the two methods by patient self-report of the effect, according to study findings. In addition, patients were asked which method they preferred.

By a significant majority, patients preferred vaporization to smoking, choosing the route of delivery with the fewest side effects and greatest efficiency, said Benowitz.

Reducing cardiovascular disease risk factors when discontinuing hormone replacement therapy

Tue, 15 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Hormone replacement therapy (HRT) has been shown to reduce many cardiovascular disease (CVD) risk factors, but many women have stopped using HRT due to reports from the Womens Health Initiative that HRT may increase the risk of breast cancer and heart disease. In a study published in the June issue of the American Journal of Preventive Medicine, researchers from the University of Pittsburgh Graduate School of Public Health examined whether the increased CVD risk from stopping HRT could be minimized by lifestyle change intervention.

Participants were part of the five-year Women On the Move through Activity and Nutrition (WOMAN) study, a randomized clinical trial of CVD prevention. The focus of this investigation was 240 women who were taking HRT at baseline; 134 of these women were randomized to the lifestyle intervention and the remaining 106 were randomized to the health education group.

Participants were followed for 18 months. At 18 months, 110 (46%) of the women had continued HRT and the remaining 130 had discontinued HRT.

The lifestyle change group significantly decreased weight, Body Mass Index, waist circumference, total cholesterol and LDL-C, had improved fat intake and increased leisure physical activity, when compared to the health education group. In general, HRT discontinuation resulted in an increase in total cholesterol and LDL-C.

In the health education group, HRT discontinuers averaged over 22 mg/dL increase in total cholesterol and LDL-C while HRT continuers averaged less than 4 mg/dL increases. No such differences were observed in the lifestyle change group.

The lead author, Kelley K Pettee, Ph.D. currently a post-doctoral research associate at Arizona State University, states, Considering the controversies regarding HRT, the findings from the present report are timely. These results have important public health implications and suggest that a non-pharmacological lifestyle approach is both safe and effective for CVD risk factor reduction in postmenopausal women, especially those who discontinued HRT use.

She continues, CVD continues to be the leading cause of morbidity and mortality among women in westernized countriesConcern about the possible risks associated with HRT has left women and their heath care providers searching for safe and effective means to reduce CVD risk factors. One potential consequence of diminished HRT use is increased use of pharmacological agents, such as statins and aspirin; however, both are associated with side effects. Based on the findings of the current investigation, special attention should be paid to encouraging lifestyle strategies that are likely to impart more benefit and less risk than drug therapies.

Stenting of abdominal arteries offers welcome relief for 'intestinal angina'

Fri, 11 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) (May 11, 2007ORLANDO, FL)Using catheter techniques perfected in the arteries of the heart, interventional cardiologists are successfully treating chronic mesenteric ischemia, a condition akin to intestinal angina. According to a study reported at the 30th Annual Scientific Sessions of the Society for Cardiovascular Angiography and Interventions (SCAI), May 912, 2007, in Orlando, FL, angioplasty and stenting of clogged arteries in the abdomen successfully restored blood flow to the intestines and relieved painful symptoms in more than 90 percent of patients, without major complications.

Chronic mesenteric ischemia is an ideal condition for treatment with nonsurgical interventions, said David E. Allie, M.D., director of cardiothoracic, vascular and endovascular surgery at the Cardiovascular Institute of the South in Lafayette, LA. Angioplasty and stenting are simple and safe, and many times today can be done as an outpatient procedure.

Chronic mesenteric ischemia can be tricky to diagnose. Patients may suffer nausea, vomiting, or pain after eatingsymptoms often mistaken for gallbladder disease or gastroenteritis. Eventually they may develop a fear of eating and lose large amounts of weight. Surgical treatment of chronic mesenteric ischemia results in death in as many as 15 percent of patients, in part because the procedure is complexit typically takes four to eight hours to performbut also because patients are debilitated by the time the diagnosis is finally made. In about one-third of patients, the diseased artery suddenly becomes completely blocked, gangrene develops in the bowel, and infection spreads throughout the body. More than half of such patients die, even with surgery.

To evaluate the effectiveness of stenting for chronic mesenteric ischemia, Dr. Allie and his colleagues recruited 50 patients with a total of 74 areas of narrowing, or stenosis, in the superior mesenteric or celiac arteries. In most cases, the procedure was performed by passing a catheter from the femoral artery in the groin up through the abdominal aorta and into the arteries supplying blood to the intestines. (In some cases, the catheter was introduced into the brachial artery in the arm and passed downward through the aorta.) A balloon was inflated to expand a large bare metal stent, which was left in place to prop open the artery at the site of the blockage.

Angioplasty and stenting were successful in 96 percent of patients, without major complications. More than 90 percent of patients reported relief of abdominal pain, and a similar percentage reported gaining weight. Fifteen patients (19 percent) later developed renarrowing of the stented artery. Of these, 3 were treated medically and 12 (92 percent) had repeat procedures to reopen the artery, including laser treatment in 8. At 1 year, 91 percent of patients were alive and free of symptoms. Two- and 3-year symptom-free survival rates were 88 percent and 82 percent, respectively.

Dr. Allie said that greater awareness and early diagnosis are critical. We now have the tools for minimally invasive treatment of chronic mesenteric ischemia, he said. Patients and physicians need to know that this condition exists, is common, and is often confused with other conditions of the digestive tract.

Employee health program improves blood pressure, diabetes control

Thu, 10 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON, May 10 Employees who participated in a worksite health program improved blood pressure control by 9 percent and diabetes control by 15 percent, researchers reported at the American Heart Association's 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke.

During three years (200406) of follow-up on 2,100 workers, researchers also found that absenteeism declined significantly at JEA, a municipal utility in Jacksonville, Fla. The number of employees who missed work due to hypertension dropped from 25.8 percent to 15.6 percent, while those who missed work because of diabetes dropped by 66.2 percent (from 50 percent to 16.9 percent).

Workplace accidents also dropped by nearly 70 percent from 83 incidents in 2003 to 25 incidents in 2006. In all, 20 of the 83 incidents in 2003 resulted in lost time away from work, compared to only seven incidents in 2006.

The rising cost of medical care and the utility's predominantly male workforce (median age, 47) contributed to the need for a program that focused on preventing heart and blood vessel disease, said Sharon A. Clark, D.H.Sc., lead author of the study and JEA's health promotion specialist.

With an aging workforce, we were concerned with making a change to the modifiable risk factors for cardiovascular disease for our employees, Clark said.

While safety has long been a priority at the utility, about a dozen employees started the worksite health program in 1989. The workers had been walking along the bridges in Jacksonville's downtown river area during their lunch hours and decided they wanted a more formal exercise facility, Clark said.

They approached the company to create a fitness center, she said. Being a public utility, JEA has to be mindful of where its resources are spent.

The company agreed to provide the space, custodial help and security services, and the employees took out a loan for the equipment. The employees also chose the exercise classes and took over most of the day-to-day administration of what has expanded into seven fitness centers at various company facilities.

Over the years, the company began to notice benefits to helping workers stay fit, Clark said. The program has grown to where it is now part of the company's strategic plan.

For the study, JEA teamed up with its healthcare provider, Blue Cross/Blue Shield of Florida and with Pfizer Global Pharmaceuticals in Jacksonville.

With their help, the company expanded its safety and health program into a comprehensive wellness system that includes live and written health education information, health screenings, coaching and an incentive program to encourage participation.

Researchers, collecting mounds of data during the three years of follow-up, attempted to quantify the effects of lifestyle-changing activities aimed at reducing cardiovascular disease risks such as smoking, excess weight, high blood pressure and diabetes.

The backbone of the program is the Health Risk Assessment (HRA), a screening tool that includes measures of employees' health through blood pressure, blood sugar and cholesterol testing. It also includes a 60-question survey that asks about current health status, family history, daily nutrition, physical activity, the use of alcohol and tobacco, safe habits (such as seat belt usage), stress and depression, use of available medical screening tests and gender-related health questions.

The survey ends by asking questions that measure how willing an employee is to make lifestyle changes related to health and safety, and providing coaching to accomplish that change.

Just knowing about something doesn't make you change, Clark said. So the last part of the HRA is one-on-one coaching.

Employees are asked what they want to change first, such as weight, blood pressure or diabetes control. The coaching, set up through the health insurance company, is structured so that patients can call the same coach repeatedly to build a dialogue.

The researchers also used a Wellness Inventory Survey (WIS) to gather data and provided incentives such as time off or the chance to win prizes for participating in the survey and other aspects of the health and safety program.

The survey includes questions about absenteeism (time away from work due to illness) and presenteeism (unproductive time spent at work due to health or personal situations that make it hard to concentrate).During the study, the percentage of employees with normal blood pressure increased from 28 percent to 37 percent and the percentage with normal blood glucose (sugar) increased from 43 percent to 58 percent. The percentage of non-smokers increased from 86 percent to 89 percent.

Employees also reported feeling better about themselves, with a significant increase in the percentage describing their health status as excellent or very good, jumping 22 percent from 41.7 percent to nearly 51 percent.

We are planning to continue to work with modifiable risk factors because we think it benefits both the employees and the employer, Clark said.

Counseling, coping skills could reduce arthritis disability

Thu, 10 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Arthritis sufferers who undergo psychological counseling and learn skills for coping with pain have less disability and better quality of life, according to a new systematic review.

Living with the pain of arthritis can lead to depression and isolation. Severely afflicted people are often unable to socialize or participate in favorite activities. Limited mobility and loss of fine-motor function can make hard it to perform everyday tasks, like cooking or getting dressed.

Treatment early on aimed at psychosocial issues could make a big long-term difference for people with arthritis, the reviewers say.

This early-intervention approach could have many benefits in terms of preventing problems in coping from developing and [then] becoming entrenched, said review co-author Francis Keefe, Ph.D., of Duke University Medical Center.

The review analyzed 27 randomized controlled trials involving 3,409 patients with osteoarthritis or rheumatoid arthritis to look at how psychosocial interventions affected pain.

The review, which is part of a new series, appears in the May issue of the journal Health Psychology. Each evidence-based review centers on a specific psychological assessment or treatment conducted in the context of a physical disease process or risk reduction effort.

Studies in the review paid the most attention to cognitive-behavioral therapy a treatment based on changing unhelpful patterns of thinking for pain management. An important facet of this therapy was training in specific coping skills, such as using relaxation techniques and pacing daily activities.

Other interventions included biofeedback, stress management, emotional disclosure, hypnosis and psychodynamic therapy.

Counseling and coping skills made the greatest difference in quality of life measures: patients who received the interventions reported a significant decrease in anxiety, depression and psychological disability.

Patients who received psychological treatments also had significant reductions in physical disability and joint swelling, although there was no difference in levels of fatigue or stiffness.

More women (69 percent) participated than men did. The average age was nearly 59 years and 81 percent of the participants were white. Therefore, the results are not universally applicable to men, minority groups or people outside of middle age, the authors say.

The number of study patients that reported reduced pain was not statistically significant, but the authors say that although the effect sizes for pain are smallfor the most part, these effects occur in addition to those produced by standard medical care. The non-drug methods studied are presumed safer than medications, they add, another plus for psychological treatments.

The goal is rehabilitation to reduce disability not a cure for chronic pain, said Patricia Dobkin, Ph.D., an associate professor of medicine at McGill University in Montreal who was not involved with the review. When working in pain clinics, one often notes that even when pain intensity is not reduced significantly, patients can and do learn to live better with their pain, she added.

Given the different approaches and treatment options available to patients with arthritis, Keefe said, If patients begin to develop problems coping with persistent pain, they could ask their health care provider to refer them to a psychologist who specializes in pain coping skills and cognitive behavior interventions.

Over 43 million adults in the United States have an arthritis diagnosis and another 23 million adults report symptoms of arthritis, making the disease the leading cause of pain and disability in the country. Arthritis is also a major contributor to workplace disability.

BEMA Fentanyl demonstrates substantial transmucosal delivery

Mon, 07 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Morrisville, North Carolina, May 7, 2007 -- BioDelivery Sciences International, Inc. (Nasdaq:BDSI) announced the results of a 12 subject, crossover study comparing the absorption of fentanyl from both single and multiple BEMA Fentanyl discs, as well as oral and intravenous doses of fentanyl. The data demonstrates that the absolute bioavailability (i.e. the total amount absorbed from the delivery system) of fentanyl through the BEMA disc was more than 70%, with 50% absorbed through the buccal mucosa (the inner lining of the cheek). The study further demonstrates that equal doses administered as either a single disc or multiple discs produced nearly identical plasma concentrations (i.e. two 200 mcg discs provided nearly equivalent plasma concentrations as one 400 mcg disc, etc.)

These findings follow the Companys April 25, 2007 announcement of statistically significant results with BEMA Fentanyl in treating cancer patients with breakthrough pain in the companys Phase III efficacy clinical trial. BDSI plans to include todays study results, the efficacy trial results and other materials in its planned submission of a New Drug Application (NDA) to the FDA for BEMA Fentanyl. The NDA submission is expected during third quarter of 2007.

BEMA Fentanyl consists of a small, dissolvable polymer disc, formulated with the opioid narcotic fentanyl, for application to the buccal membranes. Upon administration, BEMA Fentanyl is designed to deliver a rapid, reliable dose of drug across mucous membranes. BEMA Fentanyl is being developed for the treatment of breakthrough cancer pain (i.e. episodes of severe pain which break through the medication already in use to control the persistent pain).

Dr. Andrew Finn, Executive Vice President of Product Development for BDSI, stated The results of this study confirm, and are an expansion of, the information obtained in our 2006 pharmacokinetic study which demonstrated that fentanyl absorption from the BEMA delivery system was better than that seen with Actiq®. This study showed that the absolute bioavailability from BEMA Fentanyl and the amount of fentanyl absorbed directly through the buccal mucosa was substantial (70% and 50%, respectively). Although the study announced today was not a direct comparative study, our bioavailability results are greater than those previously reported with Actiq® (50% and 22%), and similar to those previously reported with Fentora (65% and 48%). Given the linear increase in plasma concentrations with increases in dose, and the nearly identical plasma concentrations when a dose is administered as a single disc or with multiple discs, we believe doctors will have the needed flexibility in titrating the dose of BEMA Fentanyl to meet the changing analgesic requirements of patients with breakthrough cancer pain.

Actiq®, marketed by Cephalon, Inc., is the leading fentanyl product for the treatment of breakthrough cancer pain in the U.S. market. Cephalon introduced a second fast dissolving fentanyl product, Fentora, in 2006. The reported combined sales of these products in 2006 were $659 million.

Dr. Mark Sirgo, President and CEO of BDSI, stated These results continue to demonstrate the consistency in the performance of the BEMA delivery system. The principal purpose of a transmucosal delivery system is to have the majority of the drug absorbed through that membrane, thereby allowing for a rapid onset of action while minimizing the amount of drug that is swallowed. Todays results show that the BEMA technology and our BEMA Fentanyl product specifically meet this principle. These results, when combined with the recent announcement of achieving our primary efficacy endpoint in our breakthrough cancer pain Phase III efficacy study, give us continued confidence that the commercial value for BEMA Fentanyl remains on target with our expectations. In addition, we believe these continued positive findings with our BEMA technology lend support to the continued development of other products in the technology, including our next pain product in development, BEMA LA.

Scripps research team sheds light on long-sought cold sensation gene

Wed, 02 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The discovery, reported in the May 3 issue of the journal Neuron, might one day lead to the development of drugs that induce cold sensation as an analgesic, or block it to prevent certain forms of chronic pain associated with cold sensation.

This study represents the first demonstration that a single gene is responsible for most cool temperature sensation, says team leader Ardem Patapoutian, who has joint appointments with the Department of Cell Biology at Scripps Research and the Genomics Institute of the Novartis Research Foundation. Many previous candidates have been postulated to play a role in our ability to sense cool temperatures, but none have withstood the test of genetics, he says.

TRPM8 was first discovered by Patapoutians group and proposed as a key gene controlling cold sensation. To test the hypothesis, the group observed the behavior of mice genetically altered to lack the gene in response to cold stimuli.

When placed in compartments with a temperature gradient, or in an enclosure where they could choose between two temperatures, mice without TRPM8 showed essentially no preference in the temperature range of 18 to 31°C, suggesting their ability to sense this range was completely disabled without the gene. Normal mice, on the other hand, found cold temperature unpleasant, reliably avoiding cold temperatures in favor of warmer areas.

Its pretty amazing that one gene could impact thermal sensation this much, says Ajay Dhaka, a Scripps Research postdoctoral fellow in the Patapoutian lab and lead author on the Neuron paper. It really highlights the importance of the peripheral nervous system and how temperature affects our behavior, he says.

The altered mice also showed little response to the application of acetone to their hindpaw, which causes an unpleasant cold sensation, while the acetone caused normal mice to flick their paw and lick them.

TRPM8 codes for an ion channel found at the tips of sensory neurons, which innervate the skin. When opened, ions flowing through TRPM8 lead to the activation of the sensory neuron, which in turn sends a signal to the brain. The Patapoutian teams results support the idea that activation of TRPM8 by temperature triggers cold sensation. TRPM8 acts as a gate, says Dhaka, At warm temperature it remains closed, but opens when exposed to cool temperature.

The TRPM8-deficient mice did not lose their ability to feel pain in response to extreme cold, as evidenced by responses similar to wild type mice when exposed to -1° C cold plates. This suggests that other genes are responsible for this facet of cold sensation.

Though cold can be unpleasant or painful under certain circumstances, it can also deaden pain, as illustrated by icing an injury to relieve pain. To test this side of cold sensation, the researchers injected the mice with small amounts of a pain-causing chemical, formalin, and then exposed the affected paw area to a cold plate.

Cold temperature clearly reduced the acute pain felt by control mice as shown by a reduction in the response to formalin injection when compared to the amount of time control mice spent flicking and licking their paws when placed on a room temperature plate. In contrast, TRPM8-deficient mice did not receive any acute pain relief from the cold plate suggesting that cold activation of TRPM8 can mediate some of the analgesic effects of cold.

Just how the same sensation can be interpreted as unpleasant under certain circumstances and pleasant in others is still not clear, but is a question the group plans to investigate. It would be really interesting to find out how the brain takes essentially the same signal and, depending on context, interprets it differently, says Dhaka.

MU researchers find statin drugs also may help reduce risk of heart failure, sudden cardiac death

Tue, 01 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBIA, Mo. -- Statin drugs, known primarily for their ability to lower cholesterol, also may reduce the overactive sympathetic nervous system response that contributes to the worsening of heart failure and increases the risk of sudden cardiac death, two University of Missouri-Columbia researchers have found. Heart failure is the leading cause of morbidity and mortality in the United States.

James Fisher, a postdoctoral fellow at MU, and Paul Fadel, an assistant professor of medical pharmacology and physiology in the MU School of Medicine, reported their findings of the effect of the popular statin drugs at Experimental Biology 2007 in Washington, D.C., part of the scientific program of The American Physiological Society.

Heart failure, sometimes called congestive heart failure, is a chronic condition in which the heart can no longer pump enough blood to the rest of the body, causing damage and negatively impacting the quality and duration of life.

In several large clinical trials, cholesterol-lowering statin medications improved survival and other health outcomes in patients with heart failure, an effect that appeared not to be solely due to lowering these patients cholesterol levels. In the search for a possible mechanism to explain this observation, scientists have turned to measures of sympathetic nervous system activity.

The sympathetic nervous system controls blood pressure and heart rate. When a heart begins to fail, the sympathetic nervous system works harder to compensate by helping to maintain heart function, blood pressure and the delivery of needed blood to vital organs and peripheral muscles. While this increased activity is beneficial in the early stages of heart failure, prolonged full-tilt sympathetic nervous system overactivity soon becomes harmful, causing damage to the heart and kidneys.

The largest difference in sympathetic nervous system activity between individuals with and without heart failure can be seen when they are resting, when the body is placing no unusual demands on the heart. An earlier University of Nebraska study found that animals with heart failure characteristics experience a return to normal sympathetic nervous system activity after being treated with statin drugs.

Fisher and Fadel continued the study with humans, treating those with longstanding mild-to-moderate heart failure. The researchers measured sympathetic nervous system activity by placing an electrode in a nerve of the lower leg.

After one month of treatment, all patients had reduced sympathetic nerve activity while resting. Although none of the patients had experienced cholesterol or blood pressure levels elevated enough to require treatment, significant decreases in cholesterol and diastolic blood pressure also were absorbed and considered beneficial for the patients overall health.

Fadel said that the preliminary results are promising and exciting. The findings indicate that short-term treatment with a low level of statin medication significantly lowered resting sympathetic nerve activity, thus lowering a factor known to be associated with increased mortality in heart failure patients, Fadel said.

Does execution by lethal injection involve conscious asphyxiation?

Mon, 23 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Execution by lethal injection may cause death by asphyxiation, and prisoners being executed may be conscious and may experience pain, claim the authors of a new study published this week in PLoS Medicine. Leonidas Koniaris and colleagues from the University of Miami assessed data from two US states that release information on executions together with previously published work on the drugs used in the protocols for lethal injections. They conclude that these protocols may not reliably effect death through the mechanisms intended.

Lethal injection is used for execution in a number of countries, most notably the US and China. The current regimens for lethal injection in the US are based on one drawn up by legislators in Oklahoma, which in turn to appear to have been based on personal opinion rather than independent research. The drugs used are a barbiturate, thiopental (which acts as an anesthetic, but does not have any analgesic effect), a neuromuscular blocker, pancuronium bromide (which causes muscle paralysis); and an electrolyte, potassium chloride (which stops the heart from beating). Each of these drugs on its own was apparently intended by those who derived the protocols to be sufficient to cause death; the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. Following a number of executions in the US, however, it has recently become apparent that the regimen as currently administered does not work as intended. Some p risoners take many minutes to die, and others become very distressed.

The authors concluded that in the current regimen thiopental might not be fatal and might even be insufficient to induce surgical anesthesia for the duration of the execution, and that the doses of potassium chloride used did not reliably induce cardiac arrest. Hence, potentially aware inmates are likely to die through asphyxiation induced by the muscle paralysis caused by pancuronium. The authors conclude that even if lethal injection is administered without technical error, those executed may suffocate, and therefore ''the conventional view of lethal injection as an invariably peaceful and painless death is questionable.''

In a related editorial the PLoS Medicine editors discuss the study's findings and their reason for publishing it in the journal. They state that It is not our intention to encourage further research to improve lethal injection protocols. As editors of a medical journal, we must ensure that research is ethical, and there is no ethical way to establish the humaneness of procedures for killing people who do not wish to die, and note that the data presented by Koniaris and colleagues adds to the evidence that lethal injection is simply the latest in a long line of execution methods that have been found to be inhumane. They argue that the evidence presented in this paper will further strengthen the constitutional case for the abandonment of execution in the US.

Did drug reps encourage doctors to prescribe gabapentin for nonapproved uses?

Mon, 23 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A new study published in PLoS Medicine suggests that so-called detail visits to doctors made by drug company representatives can involve promotion of drugs for non-approved, off-label uses. This may subsequently result in increased prescribing of the drugs for such purposes. Michael Steinman and colleagues from the University of California, San Francisco based their study on visits to doctors made by representatives of the company Parke-Davis between 1995 and 1998 to promote the drug gabapentin.

In the USA, before a company can market a drug to doctors for a specific indication (i.e. the treatment for a particular condition and group of patients), it has to be approved as safe and effective for that use by a government agency, the Food and Drug Administration. Once a drug is approved, doctors are allowed to use it for whatever non-approved indications they think are appropriate, but the drug company cannot actively promote the drug for anything other than its approved use. There have been concerns that companies indirectly try to promote use of drugs for indications that are not approved. One tactic that companies use to sell drugs is detailing. Detailing involves direct visits from company representatives to individual doctors. However, not a great deal is known about detail visits and the effect that they have on doctors' behaviour.

Steinman and colleagues took advantage of an opportunity for researching detailing that came about as a result of a lawsuit, during which drug company documents were subpoenaed i.e. required by the court to be made available. In that lawsuit, it was alleged that Parke-Davis had promoted gabapentin for many non-approved uses. (The company that subsequently took over Parke-Davis eventually made an out-of-court settlement.) During the relevant period of time, the only approved use of gabapentin was for treatment of partial seizures in adults with epilepsy, in combination with other drugs. However, gabapentin was used for many other conditions such as treatment of psychiatric disorders and management of pain. These researchers used the documents to research detailing and the impact it had on doctors' attitudes towards gabapentin.

The documents had been produced by a market research company, which had asked doctors visited by Parke-Davis representatives to fill out a standard form after each visit. The researchers focused on data relating to visits made by a single representative to a doctor or small group of doctors, and collected 116 forms. The researchers classified the information available from the forms, identifying whether the main message related to approved uses of the drug or not; and extracting data relating to whether doctors planned to increase, maintain, or lower, their use of the drug. The majority of the visits studied were to doctors who were not neurologists, so who would be unlikely to be prescribing gabapentin for its approved use. Doctors reported that a substantial proportion of the detail visits contained messages relating to non-approved uses of gabapentin. Although the majority of visits lasted 5 minutes or less, nearly half the doctors stated in the forms that their use of gabapentin would increase in the future, and no doctor said that their use would decrease following the visit. Doctors' stated intention to increase their use of gabapentin was similar whether the main message involved approved or unapproved uses of the drug. In addition, doctors' stated intention to increase their use of the drug was also similar whether the visit was of higher or lower educational value, or of shorter or longer duration.

This research does not establish whether similar activities take place regarding other drugs and drug companies.

Morphine kills the pain, not the patient

Thu, 19 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Professional and public anxieties about the effects of morphine continue to hinder adequate prescribing of this vital painkiller for genuine pain relief, claims a Comment in this week's edition of The Lancet.

Nigel Sykes, of St Christopher's Hospice, London, UK, says that the notorious Dr Harold Shipman's* use of morphine as a murder weapon has further increased disquiet among UK medical professionals.

Dr Sykes claims that the best known fact about morphine among the public and physicians is that it can be addictive, when in fact less than one in 10,000 patients prescribed the drug as part of treatment becomes addicted.

He adds: For physicians, the second best-known fact is that morphine can precipitate respiratory depression. As a consequence, if offered enough confidentiality, clinicians can be readily found who will confess to having shortened the life of their patients to achieve pain control.

The comment goes on to say that it is hardly surprising in light of these points that the media view everyday medical practice for severe pain control as increasing the dosage of morphine until the patient dies.

Dr Sykes welcomes the recent study from the US National Hospice Outcomes Project, which studies morphine/opioid use and survival at the end of life as it provides facts with which to explode the myths about morphine.

The study assessed 725 patients with end-stage cancer, lung disease or heart disease, and found that length of survival was not linked to either absolute or percentage change in dose of morphine or other opioids.

No combination of factors was capable of explaining a variation of more than 8% in survival time, which points to an overwhelming influence of the individual's disease severity.

Only patients who have no experience of opioid treatment are at significant risk of respiratory depression.

Dr Sykes says: A patient with moderate-to-severe chronic pain, malignant in origin or not, who is given the incremental dose-titration practised in pain and palliative care centres is not at such risk. A physician who truly is killing his or her patient in the name of pain relief is not merciful, just incompetent.

He adds: This problem matters because underprescribing of opioids remains a major barrier to effective pain control.

Dr Sykes also expresses his concerns for pain relief in developing countries, saying: If ineffective pain management is still an issue in high-income countries, it is nearly universal in low-income countries where access to morphine is limited or absent, but where most people dying from cancer or AIDS reside.

Tai Chi boosts immunity to shingles virus in older adults, NIH-sponsored study reports

Fri, 06 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Tai Chi, a traditional Chinese form of exercise, may help older adults avoid getting shingles by increasing immunity to varicella-zoster virus (VZV) and boosting the immune response to varicella vaccine in older adults, according to a new study publishsed in print this week in the Journal of the American Geriatrics Society. This National Institutes of Health (NIH)-funded study is the first rigorous clinical trial to suggest that a behavioral intervention, alone or in combination with a vaccine, can help protect older adults from VZV, which causes both chickenpox and shingles.

The research was supported by the National Institute on Aging (NIA) and the National Center for Complementary and Alternative Medicine (NCCAM), both components of NIH. The study's print publication follows its online release in March. The research was conducted by Michael R. Irwin, M.D., and Richard Olmstead, Ph.D., of the University of California at Los Angeles, and Michael N. Oxman, M.D., of the University of California at San Diego and San Diego Veterans Affairs Healthcare System.

One in five people who have had chickenpox will get shingles later in life, usually after age 50, and the risk increases as people get older, says NIA Director Richard J. Hodes, M.D. More research is needed, but this study suggests that the Tai Chi intervention tested, in combination with immunization, may enhance protection of older adults from this painful condition.

Dr. Irwin's research team has demonstrated that a centuries-old behavioral intervention, Tai Chi, resulted in a level of immune response similar to that of a modern biological intervention, the varicella vaccine, and that Tai Chi boosted the positive effects of the vaccine, says Andrew Monjan, Ph.D., chief of the NIA's Neurobiology of Aging Branch.

The randomized, controlled clinical trial included 112 healthy adults ages 59 to 86 (average age of 70). Each person took part in a 16-week program of either Tai Chi or a health education program that provided 120 minutes of instruction weekly. Tai Chi combines aerobic activity, relaxation and meditation, which the researchers note have been reported to boost immune responses. The health education intervention involved classes about a variety of health-related topics.

After the 16-week Tai Chi and health education programs, with periodic blood tests to determine levels of VZV immunity, people in both groups received a single injection of VARIVAX, the chickenpox vaccine that was approved for use in the United States in 1995. Nine weeks later, the investigators did blood tests to assess each participant's level of VZV immunity, comparing it to immunity at the start of the study. All of the participants had had chickenpox earlier in life and so were already immune to that disease.

Tai Chi alone was found to increase participants' immunity to varicella as much as the vaccine typically produces in 30- to 40-year-old adults, and Tai Chi combined with the vaccine produced a significantly higher level of immunity, about a 40 percent increase, over that produced by the vaccine alone. The study further showed that the Tai Chi group's rate of increase in immunity over the course of the 25-week study was double that of the health education (control) group. The Tai Chi and health education groups' VZV immunity had been similar when the study began.

In addition, the Tai Chi group reported significant improvements in physical functioning, bodily pain, vitality and mental health. Both groups showed significant declines in the severity of depressive symptoms.

This study builds upon preliminary research funded by NCCAM and we are delighted to see this rigorous trial of Tai Chi for varicella zoster immunity come to fruition, said Ruth L. Kirschstein, M.D., NCCAM Acting Director.

Kelp Supplementments Implicated in Arsenic Poisoning

Fri, 06 Apr 2007 00:34:24 PST

( from http://www.rxpgnews.com ) A study of herbal kelp supplements led by UC Davis
public health expert Marc Schenker concludes that its medicinal use may cause inadvertent arsenic poisoning and health dangers for consumers, especially when overused. Schenker and two researchers evaluated nine over-the-counter herbal kelp products and found higher than acceptable arsenic levels in eight of them.

The new study, published in the April issue of Environmental Health Perspectives (http://www.ehponline.org/) was prompted by the case of a 54-year-old woman who was seen at the UC Davis Occupational Medicine Clinic following a two-year history of worsening alopecia (hair loss), fatigue and memory loss.

The woman's symptoms had begun with minor memory loss and fatigue. Her primary care physician initially found nothing wrong with the woman and thought the symptoms were related to menopause. With no specific diagnosis or treatment recommendations, the patient started taking a variety of herbal therapies, including a kelp supplement, fish oil, ginkgo biloba and grape seed extract. The kelp supplement was the only herbal therapy she took regularly throughout the course of her illness.

Over a period of several months the woman's short- and long-term memory became so impaired that she could no longer remember her home address. She also reported having a rash, nausea and vomiting, which made it very difficult to work and forced her to leave a full-time job. The woman actually increased her dosage of kelp from two to four pills a day after her doctors still could not find a clear diagnosis.

Subsequent laboratory tests finally revealed arsenic in the patient's blood and urine. At her physician's suggestion, the patient discontinued the kelp supplement. Within weeks, her symptoms disappeared, and within several months arsenic was no longer detected in her urine and its levels had dropped significantly in her blood. She later was referred to the UC Davis Occupational Medicine Clinic as a follow-up to her primary care.

"It's unfortunate that a therapy that's advertised as contributing to 'vital living and well-being' would contain potentially unsafe levels of arsenic," said Schenker, who is a professor of Public Health Sciences and a leading authority on occupational and environmental diseases and respiratory illness. "Concentrations of materials contained in herbal supplements, including both the expected benefits and potential side effects, should be studied, standardized, monitored and accurately labeled."

To assess the concentration of arsenic present in commercially available kelp supplements, the UC Davis investigators purchased nine over-the-counter kelp samples from local health food stores. Included were samples from three different batches of the product consumed by the patient.

The researchers sent the samples to the California Animal Health & Food Safety Laboratory in Davis, which operates in partnership with UC Davis, the California Department of Food and Agriculture and others to provide specialized testing that helps protect both human and animal health. Investigators found detectable levels of arsenic in eight of the nine kelp supplements by using a hydride vapor generation method with an inductively coupled argon plasma spectrometer. Seven of the supplements exceeded the tolerance levels for food products set by the U.S. Food and Drug Administration (FDA).

"Part of the problem," said Schenker, "is that the FDA has limited control over dietary supplements. It can't scrutinize products like herbal kelp before they enter the market, so it has to rely on adverse reports to determine product safety."

He noted that none of the kelp products in the study had labels indicating the presence of arsenic, nor were there any warnings about the potential dangers of ingesting large quantities of the supplement.

Arsenic is a heavy metal that occurs naturally in the environment and as a by-product of some agricultural and industrial activities. Due to high arsenic concentrations in algae and marine micro-organisms, seafood is the highest dietary source of arsenic for consumers. While long term human exposure to arsenic from food sources such as fish does occur, it is usually significantly lower than anything approaching toxic levels. How-ever, dietary supplements, which are largely unregulated, have raised health concerns.

There have been a number of published studies highlighting cases in which the uses of homeopathic remedies to relieve everything from asthma to rheumatoid arthritis have caused arsenic poisoning. Schenker's findings offer a cautionary tale for consumers who use herbal treatments and dietary supplements. The kelp samples analyzed in the study had consistently elevated levels of arsenic, but they were considerably lower than previously documented concentrations found in other herbal remedies.

"What concerns me," said Schenker, "is that chronic exposure to contaminated herbal supplements, even those with moderately elevated concentrations of arsenic, can still be toxic. Consumers won't find such label information on these products, so they could end up like that woman in our study who consumed dangerously high amounts of a toxic substance
without realizing it."

Researchers call for national database of epidural complications

Mon, 02 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers have called for a national database to be set up to identify major complications arising from epidural pain relief after a small number of serious problems were identified during a six-year UK study, according to the April issue of Anaesthesia.

They discovered that 12 of the 8,100 people studied developed major complications after receiving epidural pain relief following an operation. Six developed epidural abscesses, three suffered from meningitis and three had blood clots in the epidural space.

Twelve different anaesthetists sited the epidural catheters and the patients were managed on five different wards after surgery. All the epidural insertions met recommended aseptic techniques to minimise infection.

Although relatively rare, these complications are serious and point to the need for regular surveys to be carried out after epidural pain relief to identify risk factors and the scale of the problem says consultant anaesthetist Dr Iain Christie from Derriford Hospital, Plymouth, UK.

For example, epidural abscesses can cause neurological damage and paralysis of the lower limbs if left untreated.

The survey which took place between 2000 and 2005 gathered information from four key sources.

Researchers looked at the hospitals patient information system to identify patients undergoing surgery and the acute pain service to identify all patients receiving epidural pain relief after surgery.

They also looked at any patients who had received a spinal MRI scan or undergone relevant microbiological investigations within 60 days of surgery.

Before they carried out the survey clinicians were aware of seven patients who had suffered major complications after epidural pain relief during the study period. The survey identified a further five.

Patients have a much better outcome if they are diagnosed and treated before neurological symptoms develop stresses Dr Christie. It is particularly important to monitor leg weakness as this is an important measure of spinal cord health and ensure that patient information systems pick up any infections following discharge from hospital.

The authors point out that other reported cases of epidural abscesses following epidural pain relief indicate that it is not just a local problem.

We would strongly recommend that all acute pain services supervising epidural pain relief after surgery perform a regular survey to identify patients who have suffered one of these complications stresses Dr Christie.

The results should then be stored in a national database to provide a more accurate estimate of the risk of these complications. This register might also identify other relevant risk factors such as MRSA infections.

The Royal College of Anaesthetists started its 3rd National Anaesthesia Audit in September 2006 and says that it plans to report the findings in 2008. We hope that the outcome of this project will be a national register.

MS patients need better socio-economic support as well as medical care

Fri, 30 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) People with multiple sclerosis need much more practical help and better care support, according to a study published in the latest Journal of Advanced Nursing.

Researchers from Kings College London explored the aspirations of 445 patients with different levels of multiple sclerosis (MS), who were taking part in a wider study to evaluate MS specialist nurses.

They believe that their findings could form the basis for developing an MS satisfaction tool, which could be used to assess quality of care in services.

The tool could also identify the gaps in provision that still exist despite the MS guidelines issued by the National Institute for Health and Clinical Excellence, which advises the UK Government on health issues.

29 per cent of those who took part in the survey said that medical treatment was their number one priority when it came to meeting their current needs, but 19 per cent specified socio-economic support, with 67 per cent of those specifying household adaptations, better transport provision and re-housing.

The need for help with financial and employment problems was also identified.

A further 18 per cent pointed to the need for enhanced care provision, including improvements in the availability, accessibility and continuity of health and social care provision.

Respondents felt health care professionals needed greater knowledge about MS and how to manage it and wanted better co-ordinated services with one central point of contact. They also felt that specialist MS nurses had an important role to play.

Nine per cent of respondents wanted more information about MS treatments and services and some felt that families and society needed to improve their understanding of MS and how it affects people.

Seven per cent wanted better access to rehabilitation therapies, notably physiotherapy. Occupational therapy and rehabilitation therapies were also mentioned.

Six per cent wanted non-professional care including support with personal, home and child care and a further three per cent needed help with psychological issues.

The aim of the study was to identify what people with MS needed most and to compare the responses between people with different levels of MS explains lead researcher Dr Angus Forbes.

People with minimal levels of MS rated medical treatment as their highest priority, followed by enhanced care, as did people with severe MS.

Patients with mild MS also rated medical care first, with socio-environmental help and enhanced care in joint second place. But people with moderate MS, rated medical care in second place behind socio-environmental help.

The 714 people taking part in the wider MS study were recruited from seven neurological centres across five English regions.

435 responded to the question What one thing would be most helpful in meeting your current needs in the first questionnaire and 424 responded to the question in the second survey a year later. 270 people answered the question on both occasions.

The average age of the respondents was just over 48 and 69 per cent were female. Average time since diagnosis was just over 11 years and 83 per cent of respondents lived with others.

60 per cent had progressive MS, 29 per cent had relapse-remitting MS. Other forms of MS accounted for 11 per cent of the sample.

More than one in three had moderate MS (35 per cent), followed by severe (28 per cent), mild (20 per cent) and minimal (17 per cent).

Since our research was carried out, the UKs National Institute for Health and Clinical Excellence has produced MS care guidelines which seem to echo the aspirations expressed by the MS patients who took part in our study. But a 2006 study suggested that little had changed, with few health authorities implementing the guidelines says Dr Forbes.

Such deficits are not confined to the UK and have been reported in wider surveys across Europe.

Our survey, which was funded by the MS Society for Great Britain, shows very clearly that peoples needs change as their MS develops.

Developing a needs assessment tool specifically for MS would be an important first step in ensuring that healthcare meets those individual and changing needs, as it would show how well care is currently being provided, identify gaps in provision and point to areas for future research.

Higher trans fat levels in blood associated with elevated risk of heart disease

Tue, 27 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Boston, MA -- High consumption of trans fat, found mainly in partially hydrogenated vegetable oils and widely used by the food industry, has been linked to an increased risk of coronary heart disease (CHD). New York and Philadelphia have passed measures eliminating its use in restaurants, and other cities are considering similar bans. A new study from the Harvard School of Public Health (HSPH) provides the strongest association to date between trans fat and heart disease. It found that women in the U.S. with the highest levels of trans fat in their blood had three times the risk of CHD as those with the lowest levels. The study was published online on March 26, 2007, and will appear in the April 10, 2007 print issue of Circulation: Journal of the American Heart Association.

The strength of this study is that the amount of trans fatty acid levels was measured in blood samples from the study population. Because humans cannot synthesize trans fatty acids, the amount of trans fat in red blood cells is an excellent biomarker of trans fat intake, said senior author Frank Hu, associate professor of nutrition and epidemiology at HSPH.

Clinical trials have shown that trans fatty acids increase LDL cholesterol and lower HDL cholesterol, making them the only class of fatty acids, which includes saturated fat, to have this dual effect. HDL (high-density lipoprotein) is considered a good cholesterol; LDL (low-density lipoprotein) a bad cholesterol.

The researchers, led by Hu and lead author Qi Sun, a graduate research assistant at HSPH, set out to test the assumption that higher trans fatty acid levels in erythrocytesred blood cellswere associated with a higher risk of heart disease among U.S. women. Blood samples collected in 1989 and 1990 from 32,826 participants in the Brigham and Womens Hospital-based Nurses Health Study were examined. During six years of follow-up, 166 cases of CHD were diagnosed and matched with 327 controls for age, smoking status, fasting status and date of blood drawing.

After adjusting for age, smoking status and other dietary and lifestyle cardiovascular risk factors, the researchers found that a higher level of trans fatty acids in red blood cells was associated with an elevated risk of CHD. The risk among women in the top quartile of trans fat levels was triple that of the lowest quartile. Positive associations have been shown in earlier studies based on dietary data provided by the participants, but the use of biomarkers of trans fatty acids is believed to be more reliable than self-reports. This is probably the reason why we see an even stronger association between blood levels of trans fat and risk of CHD in this study, said Sun.

These data provide further justifications for current efforts to remove trans fat from foods and restaurant meals, said Hu. Trans fat intake in the U.S. is still high. Reducing trans fat intake should remain an important public health priority.

Infusion with reconstituted HDL may have some benefit for atherosclerosis

Mon, 26 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Preliminary research suggests that use of reconstituted HDL may have some benefit in coronary atherosclerosis, according to a JAMA study published online March 26. The study is being released early to coincide with its presentation at the American College of Cardiology's annual conference.

There is a strong inverse association between high-density lipoprotein (HDL) cholesterol (the good cholesterol) and risk of coronary atherosclerotic disease, according to background information in the article. Preliminary data have suggested that HDL infusions can reverse atherosclerosis (the progressive thickening and hardening of the arterial walls as a result of fat deposits on their inner lining).

Jean-Claude Tardif, M.D., of the Montreal Heart Institute, University of Montreal, and colleagues with the Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) study assessed the effects of infusion with a reconstituted HDL, CSL-111, on coronary atherosclerosis. CSL-111 consists of apolipoprotein A-I from human plasma combined with soybean phosphatidylcholine (a type of lipid molecule; the combination product) that chemically and biologically resembles HDL. Between July 2005 and October 2006, intravascular ultrasound (IVUS) and quantitative coronary angiography were performed on 183 patients to assess coronary atheroma (plaque deposit) at baseline and 2 to 3 weeks after the last study infusion. Sixty patients were randomly assigned to receive four weekly infusions of placebo (saline), 111 to receive 40 mg/kg of reconstituted HDL (CSL-111); and 12 to receive 80 mg/kg of CSL-111. This highest dosage was discontinued early because of indications it caused a certain elevation in liver function tests, suggesting possible harmful liver effects.

This study showed differences in coronary atheroma volume after 4 weekly infusions of CSL-111 or placebo (-3.4 percent vs. -1.6 percent, -5.3 mm³ vs. -2.3 mm³, respectively), but the differences between these groups were not statistically significant. However, CSL-111 may nevertheless potentially induce some favorable vascular effects as seen in the significant reductions of atheroma volume of 3.4 percent or 5.3 mm³ with active infusions in the analysis comparing follow-up to baseline values. Although the latter finding is not significantly different when compared with placebo and is only suggestive of a possible favorable treatment effect, both the plaque characterization indexes on IVUS and coronary score on quantitative coronary angiography revealed statistically significant differences between CSL-111 and placebo groups that support this analysis, the authors write.

Whether these findings will translate into clinical benefits to patients is not known. Elevation of HDL remains a valid target in vascular disease and further clinical evaluation of HDL infusions with CSL-111 with longer follow-up appears warranted, the researchers conclude.

JAMA. 2007;297:(doi:10.1001/jama.297.15.jpc70004). Available pre-embargo to the media at

Headache-related work absences have a considerable socio-economic effect

Wed, 14 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Eight out of ten people who took part in a study carried out by a specialist headache centre felt they were much less effective at work and 91 per cent said they felt hampered by headaches on a daily basis, according to the March issue of Cephalalgia.

Migraines and tension-type headaches are much more common in peoples forties, when they are often at their most productive, so the socio-economic implications of this chronic disease are considerable says Gabrielle Vinding from the Danish Headache Centre at the University of Copenhagen.

But its not just people who consult specialist services that add to the economic burden, she says. European and American studies suggest that as many as 18 per cent of people suffer lifetime migraines. And the lifetime prevalence of tension-type headaches in Denmark is thought to be as high as 78 per cent.

In Denmark the total cost of all headache disorders is approximately 74 million per million inhabitants per year she points out.

Previous studies have suggested that up to 37 per cent of Danish people have tension type headaches several times a month, 10 per cent have them weekly and up to three per cent have chronic headaches for more than 15 days a month, for most of their life.

55 people took part in the study, which included a structured interview, headache diary and self-administered questionnaire. The survey was carried out over a one-month period and focussed on outpatients paying their first or second visit to the clinic, which has an intake of about 1,000 patients a year.

The participants ranged in age from 20 to 78, with an average age of 41. Median headache frequency in the 30-day period before interview was 15 days and the headache intensity was two on a scale of zero to three.

Headache-related work absences in the previous year ranged from zero to 365 days, with an average of 57 days and a median of 12 days.

Just under one in five patients had been absent from work for more than 60 days because of headaches and 10 per cent had been absent for a full year.

Headaches had also had a profound effect on their lives. 29 per cent had changed their place of work because of their headaches, 46 per cent had ruled out particular jobs and 40 per cent said it restricted their career.

58 per cent said they were dependent on their family and friends and nine per cent had decided not to have any more children.

The survey used the same questions as research carried out in Denmark in 2001 on a cross-section of the general public. That found that nearly a third of people had consulted their family doctor because of a headache and three percent had been hospitalised because of headache.

Although the general population results are predictably lower than our specialist sample, the figures do indicate that headaches can have quite an impact on the work environment says Vinding.

For example, 90 per cent of our employed study subjects had been absent from work in the last year because of a headache, but the figure for the general population was still 12 per cent.

Severe and frequent headache is costly, both in terms of direct and indirect costs concludes Vinding. The socio-economic effects are particularly felt in healthcare services, sick leave and effectiveness in the workplace.

And people suffering from chronic headache also report significant limitations when it comes to work, family and leisure activities.

Prevention, early intervention and effective headache strategies for headache disorders may therefore be highly cost-effective, both for the individual and society.

Women need expanded musculoskeletal care during pregnancy, study finds

Tue, 06 Mar 2007 04:59:37 PST

( from http://www.rxpgnews.com ) (Arlington, Va.) -- Despite the high prevalence of musculoskeletal pain during pregnancy, few women in underserved populations receive treatment for their low back pain, according to a February 2007 study in the Journal of Manipulative and Physiological Therapeutics (JMPT). Moreover, researchers found that pain in a previous pregnancy may predict a high risk for musculoskeletal complaints in future pregnancies.

According to Clayton Skaggs, DC, the studys chief author, 85 percent of women surveyed reported that they had not received treatment for their musculoskeletal pain, and of the small percentage who perceived that their back complaints were addressed, less than 10 percent were satisfied with the symptom relief they obtained.

Based on the findings of this study, doctors of chiropractic and other health care professionals need to expand the musculoskeletal care available during pregnancy, especially in underserved populations, Dr. Skaggs said. As a proactive step, health professionals should consider including back pain screening as part of early obstetrical care to help identify musculoskeletal risk factors and allow for early education and/or treatment.

Researchers surveyed more than 600 women at a clinic that serves predominantly an uninsured, underinsured or Medicaid-insured population. Surveys were offered to all obstetrical patients and were designed to collect information about pregnancy-related pain and quality of life issues. Of those women who responded to the survey, two-thirds reported back pain and nearly half of all women reported pain at two or more locations, including pelvic pain and mid-back pain.

The study findings suggest that pregnant women with back pain are predisposed to sleep disturbances. In the survey, close to 80 percent of women reporting sleep disturbances had back pain, whereas only 8 percent of women without pain reported problems sleeping. More alarming was the significant relationship between reports of musculoskeletal pain and the use of pain medication. Three-fourths of the women who reported pain also described use of pain medication.

We saw a direct association between sleep deficiency and back pain, the authors said. These results raise the question of whether or not the high incidence of pain medication use reflects a lack of education about potential risks of medications or more an inability for the pregnant women to cope with the pain.

The studys authors also found a relationship between pain in a previous pregnancy and pain in the current pregnancy. Similar to the results of other studies, researchers found that 85 percent of women who experienced pain in a previous pregnancy reported pain during their current pregnancy.

Single genetic defect causes early heart disease

Thu, 01 Mar 2007 04:59:37 PST

( from http://www.rxpgnews.com ) A team of researchers from the United States and Iran has identified a genetic mutation that causes early onset coronary artery disease in members of a large Iranian family. The genetic mutation leads to heart disease by causing high blood pressure, high blood levels of bad cholesterol and diabetes, all risk factors for heart disease. Coronary artery disease is the leading cause of death worldwide.

Unfortunately, most of the individuals in this family who carried the mutation died in their early fifties from coronary artery disease that resulted in heart attacks and heart failure, said the research team leader, Richard P. Lifton, a Howard Hughes Medical Institute investigator at Yale University School of Medicine. Our studies identify a single mutation that has quite a large effect on many of the metabolic risk factors for coronary artery disease.

Lifton and his colleagues published their research article in the March 2, 2007, issue of the journal Science. Arya Mani, a cardiologist and member of Liftons laboratory at Yale, was first author of the article. The Yale group collaborated on the studies with researchers at Amir Kabir University of Technology, Azad University and The Social Welfare and Rehabilitation Sciences University, all of which are in Tehran, Iran.

The genetic defect is rare, so the discovery by itself will not provide an explanation for the more common forms of coronary artery disease, which are caused by a constellation of factors, said Lifton. However, he said, understanding the molecular nature of this single genetic defect, which is at the root of a familial form of such a complex disease, offers invaluable clues. Researchers may be able to apply that knowledge to improve understanding of what causes the bodys metabolic machinery to malfunction in the more garden variety forms of heart disease.

According to Lifton, physicians in Tehran had long been aware of the familys tragic struggle with early coronary artery disease. In fact, 23 of 28 blood relatives of the first patient identified with this genetic mutation died from coronary artery disease by an average age of 52. The research team obtained medical records and blood samples from all surviving members of the family. The medical records showed that the family members had a characteristic cluster of symptoms called metabolic syndrome. People with this syndrome have hypertension, high blood lipid levels and diabetes, and they are at much higher risk of developing heart disease.

Dr. Mani identified this family as an example of an extreme outlier of a common disease, said Lifton. Studying extreme forms of common disease has been a longtime theme in our laboratory. Liftons strategy is to pinpoint and analyze the rare genetic traits that cause complex disorders. By understanding the causes of those familial forms of complex diseases such as hypertension, Lifton and others have laid the foundation for identifying the mechanisms that underlie more common forms of the disease.

One of the important features of the Iranian family, Lifton noted, was that affected family members exhibited metabolic syndrome and early coronary artery disease, but unaffected family members were normal. So this told us that the coronary disease was traveling with this cluster of metabolic risk factors, he said. Those risk factors were behaving as though they were being transmitted through the family as a single factor.

When the researchers performed a detailed genetic comparison of affected and disease-free family members, they found that a specific segment of chromosome 12 was the most likely genomic hiding place for this unknown factor. In mapping the six genes present on this small chunk of chromosome 12, they found that the gene for LDL receptor-related protein 6 (LRP6) was present in that region of the chromosome.

They immediately focused on LRP6, tipped off in part by an earlier discovery by HHMI investigator Matthew Warman at Childrens Hospital Boston. In 2001, Warman had shown that members of the LRP gene family were important in bone development. What caught our attention was that multiple people in the Iranian family we were studying had coronary artery disease and unexplained hip fractures at young ages. We had not made much of the hip fractures at the outset, but once we knew that LRP6 was in this small genomic interval that contained the coronary-artery-disease-causing gene, we immediately thought of LRP6 as the likely culprit, said Lifton.

By sequencing the LRP6 gene in affected family members, the scientists found that the mutation caused the substitution of a single amino acid in the protein the gene produced. In contrast, the researchers did not find the mutation when they analyzed large comparison populations of Iranians and Americans. However, the researchers statistical analysis of the family members revealed a high correlation between the presence of the mutation, metabolic syndrome, and osteoporosis.In cell culture studies, Dan Wu, a Yale biochemist, found that the mutation compromised how the LRP6 protein functions in the Wnt signaling pathway. Wnt is at the heart of a key metabolic signaling pathway that is important in embryonic development and contributes to an array of normal physiological processes in adults. Lifton emphasized that the compromised Wnt pathway is intriguing and the pathway will likely become an important research target for understanding coronary artery disease.

For example, now that we know that altered Wnt signaling can lead to multiple components of the metabolic syndrome, this raises the question of whether other mutations in the Wnt signaling pathwayor acquired defects that cause alteration of Wnt pathway activitymight commonly contribute to metabolic syndrome and coronary artery disease, he said.

Basic understanding of how the Wnt pathway malfunctions could lead to new treatments for coronary artery disease. Although its a long way off, we might ultimately develop ways to either disrupt or increase the activity of particular components of the pathway, to prevent development of metabolic syndrome and coronary artery disease, he said.

The discovery that the LRP6 mutation also causes osteoporosis raises the possibility of a linkage with coronary artery disease, said Lifton. There is emerging recognition that osteoporosis and coronary artery disease occur together more often than expected by chance, he said. We have now implicated altered activity of the Wnt pathway in development of both coronary artery disease and osteoporosis. So, one can imagine identifying patients with osteoporosis and coronary artery disease as a way of selecting those who might be particularly interesting to investigate for altered Wnt signaling.

Pharmacist-driven outreach lowers metabolic syndrome rates

Wed, 28 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla., Feb. 28 -- Adults who met with pharmacists or pharmacy students during a community outreach and screening project about metabolic syndrome, returned four months later with lower risk factors for heart disease, researchers reported today at the American Heart Associations 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention.

Metabolic syndrome is a cluster of cardiovascular disease and diabetes risk factors including excess waist circumference, high blood pressure, elevated triglycerides, low levels of high-density lipoprotein (HDL) and high fasting glucose levels. The presence of three or more of the factors increases a persons risk of developing diabetes and cardiovascular disease.

The purpose of our study was to educate people about the metabolic syndrome, because it is not a term used often in the lay public, said Amy M. Franks, Pharm.D., lead author of the study and assistant professor in the College of Pharmacy at the University of Arkansas for Medical Sciences in Little Rock. Our hope was that if we educated people about their individual risks for metabolic syndrome and suggested ways to reduce those risks, we would make a positive impact on heart disease risk in the community.

A group of pharmacists and pharmacy students held individual educational sessions on the metabolic syndrome with 112 people (average age 45 years) employed by a public school in a town near Little Rock.

We did a clinical screening that measured each one of the five risk factors for metabolic syndrome, then sat with each person to talk about their risk and what they could do to lower their overall risk for heart disease, Franks said. When it was necessary, we referred them to their regular healthcare provider to talk about drug therapy or other things they could implement.

Seventy-three of the participants returned four months later to determine if the pharmacists made an impact in health status.

Initially, the researchers found that about 30 percent of study participants had the metabolic syndrome.

When we went back four months later, only 18 percent of them met the criteria for metabolic syndrome, Franks said.

The participants significantly reduced their total cholesterol during the four months, from an average of 197 milligrams per deciliter (mg/dL) to 189 mg/dL. Average systolic (top number) blood pressure dropped from 123 millimeters of mercury (mmHg) to 117 mmHg and diastolic (bottom number) dropped from 79 mmHg to 72 mmHg.

Researchers didnt find significant changes in the amount of exercise or positive dietary changes reported by participants at the four-month assessment; however, at the follow-up, an additional 7 percent of participants reported initiating drug therapy to combat high blood pressure and 12 percent started taking medication to lower triglycerides, Franks said.

The researchers noted particularly significant changes among those at the highest risk for heart disease. While 50 percent of participants had total cholesterol greater than 200 mg/dL at the start of the study, only 41 percent met that high-risk criterion at the four-month mark.

The more striking numbers were in blood pressure, Franks said. When we looked at systolic blood pressure greater than 140 mmHg, 23 percent of the participants met this high-risk criterion at the start and only 14 percent later. And while 26 percent of the participants had a diastolic reading of higher than 90 mmHg at the studys start, only 7 percent had such high diastolic pressures by four months.

The researchers concluded that healthcare providers, including pharmacists, can help combat the components that make up the metabolic syndrome by educating patients and making lifestyle recommendations, Franks said.

McGovern Institute Scolnick Prize awarded to David Julius

Tue, 27 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, MA. Feb 27, 2007 The McGovern Institute for Brain Research at MIT announced today that David Julius, a physiologist at the University of California at San Francisco (UCSF), will be the 2007 recipient of the Edward M. Scolnick Prize in Neuroscience. The Scolnick prize is awarded each year by the McGovern Institute to recognize an individual who has made outstanding advances in the field of neuroscience. Dr. Julius, who a is a professor and vice chair of the Department of Cellular and Molecular Pharmacology at USCF, receives the 2007 prize for his discovery of the molecular receptors for temperature and inflammatory pain.

David Julius has transformed our understanding of temperature perception and pain, says McGovern Institute director Robert Desimone. His work is of great importance for basic neuroscience and medicine, and we are very pleased to honor his groundbreaking contributions through this award.

It has been known for many years that capsaicin, the substance that gives chili peppers their hot taste, interacts specifically with pain sensitive neurons. Building on this observation in a landmark 1997 paper, Dr. Julius was able to identify the molecular receptor for capsaicin and to demonstrate that it is specifically expressed in a subset of sensory neurons, now recognized as key components of the pain pathway. He also showed that the receptor, known as TRPV1, is a heat-sensitive ion channel, with a temperature threshold that corresponds with the point at which we start to perceive warm stimuli as painful.

Dr. Julius has continued to study TRPV1 and related channels, and in more recent work has identified the receptor for menthol, a plant-derived substance that produces a cooling sensation. He showed that the menthol receptor responds to cold temperatures, thereby proving that the TRP family of ion channels constitutes the fundamental mechanism for temperature sensation in mammals.

In addition to explaining how we perceive temperature, Dr. Julius has made major contributions to our understanding of pain. By showing that TRP ion channels are activated by a variety of chemicals that are released by inflamed tissue, as well as noxious chemical agents such as spider toxins and mustard oils, Dr. Julius has established these channels as polymodal receptors that allow us to detect, through pain, the presence of inflammation or injury as well as extremes of temperature. His work has had a great impact not only in basic neuroscience but also in the pharmaceutical industry, where TRP channels have emerged as important potential targets for the development of novel analgesic drugs.

The McGovern Institute will award the Scolnick Prize to Dr. Julius on Monday, May 21st, 2007 at 4:00 pm. Dr. Julius will deliver a lecture entitled From Peppers to Peppermints: Natural Products as Probes of the Pain Pathway, followed by a reception, at the McGovern Institute in the Brain and Cognitive Sciences Complex, 43 Vassar Street (building 46, room 3002) in Cambridge. The event is free and open to the public.