RxPG News : Analgesics

Remitting multiple sclerosis: Natalizumab reduces relapses and disability

Tue, 04 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Taking the new generation anti-inflammatory drug natalizumab for two years lowers the number of remitting multiple sclerosis patients who experience relapses and progression of disability. This is the main finding of a systematic review published in the latest edition of The Cochrane Library.

Multiple sclerosis (MS) is a disease that damages a person's nervous system. The symptoms vary considerably from person to person, but many have a form of the disease in which they feel healthy for a time, and then relapse into periods of ill health. Over time, the disease tends to develop into a permanent disability. The aim of many treatments is to increase the period of remission that MS patients have between each relapse, and to delay the progression to the full disease for as long as possible.

Part of the body's defensive immune system involves a type of white blood cell that actively moves to areas where there is disease or damage. This movement causes the swelling associated with inflammation. Natalizumab, normally abbreviated as NTZ, is an advanced form of medicine that prevents some of these white blood cells passing from blood vessels into the brain. As MS is closely linked to inflammation, the theory is that blocking this passage of cells might help reduce the symptoms.

By searching through the medical literature a team of researchers working in Italy and the UK found three trials that met their inclusion criteria. Together these trials involved over two thousand patients, and showed that after two years of treatment, NTZ reduced the risk of experiencing at least one new bout of disease at two years by about 40%, and the number who had disability progression over the two years was reduced by 25%. MRI brain scans also showed evidence that NTZ had reduced disease activity.

Our analysis indicated that NTZ is well tolerated and safe over a period of up to two years, says study leader Eugenio Pucci, who works at the neurological unit in Macerata, Italy.

Using it, however, is not simple, and two patients in the trials did develop progressive multifocal leukoencephalopathy (PML), a rare and often fatal brain disease caused by the virus named JCV. There wasn't enough data in the original trials to show a definite risk associated with NTZ. However, surveillance programs are in place in several countries watching for any signs of a link. Various factors seem to increase the risk of developing PML, including the number of NTZ infusions a person receives, whether the patient has had previous immunosuppressive treatment and if their blood contains antibodies against JCV, says Pucci.

Consequently Pucci and his colleagues believe that NTZ should be used only by skilled neurologists in MS centres under national or international surveillance programs.

Because of the safety concerns and the considerable cost of using NTZ, Pucci is keen to see further research that will show which category of MS patient would gain most from the medication.

The mark of the beast: tradition or stress?

Wed, 28 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) For a variety of reasons it is important to be able to identify farm animals, horses and small companion animals. Farm animals have generally been marked by branding with hot irons or by ear-tagging, while more recently dogs and cats are being uniquely identified by the implant of a microchip transponder. Horses have traditionally been branded but many countries are now moving towards the use of microchips. Branding is still permitted in Austria and Germany, although the German parliament is currently discussing following the lead of Denmark, which banned the practice in 2009. Similar discussions are taking place in the USA and Australia. The underlying belief is that the use of microchips is more humane but is this really the case? The group of Christine Aurich at the University of Veterinary Medicine, Vienna (Vetmeduni Vienna) has now shown that the short-term differences are far less dramatic than animal rights activists may have us believe but that hot-iron branding has prolonged effects that may negatively affect the welfare of the foals.

Previous work had suggested that branding was significantly more stressful than implanting a microchip but the studies were carried out in adult horses and no investigations had been undertaken in foals, although horses are generally marked as foals. In collaboration with other scientists at the Vetmeduni Vienna, Regina Erber in Aurich's group therefore examined the levels of stress hormones in the saliva of foals when they were branded or when a microchip was implanted in their necks. She also monitored the behaviour, the body temperature and the heart rates of the foals while they were marked and afterwards (changes in heart beat are associated with stress). The results showed that both methods were associated with similar acute levels of stress to the animals: cortisol concentrations in the saliva increased similarly and in each case there was a similar transient increase in heart rate and in aversive behaviour. It seems, then, that the immediate behavioural and physiological changes caused by both methods are extremely similar. Furthermore, they appear at least in part to be caused by handling and fixation of the foals and not by the actual marking procedures.

Not surprisingly, branding caused a skin burn that lasted for about a week. However, branding was also found to be accompanied by a generalized increase in skin temperature that lasted for several days. This is comparable to the response of humans to severe burn injuries. These changes were not found in foals that were not branded but instead marked by means of a microchip. The new results thus show that tissue damage caused by branding in foals is far more pronounced than expected.

Back pain? Move, don't rest!

Mon, 19 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Move if you have back pain, this is the advice of a researcher at the Sahlgrenska Academy, University of Gothenburg. Patients with acute low back pain who were advised to stay active despite the pain fared better than those who were told to adjust their activity in line with their pain.

The thesis looked at 109 patients with acute severe low back pain. They were randomly advised in one of two ways: stay active even though it hurts or adjust your activity to the pain. They were also asked to keep a diary for seven days and to note how many steps they took each day, to what extent they could carry out their day-to-day activities and how they felt physically. They also completed a form to show whether they felt depressed or not.

In spite of having more pain, the group that was advised to be as active as possible recovered more quickly and did not feel depressed at the end of the follow-up.

The other category, who had been advised from the very start to adjust their activity to their pain, were less mobile and felt slightly depressed compared to the patients who were active, says Olaya-Contreras, a researcher at the Sahlgrenska Academy's Department of Orthopaedics.

She believes that this could be because some people who are depressed and in pain experience the pain more acutely. Another explanation could be that the more acute the pain is perceived to be, the less a person wants or is able to move. This, according to Olaya-Contreras, is in line with previous research.

I think that if you're suffering with acute low back pain you should try to remain as active as possible and go about your daily business as well as you can. If you don't keep moving, it's easy to get locked into a downward spiral, as inactivity combined with pain can, in a worst case scenario, turn into long-term disability and an inability to work that, in turn, can lead to depressed mood and more pain.

Olaya-Contreras therefore feels that the health service should introduce a routine investigation to determine the underlying psycho-social causes of patients' back problems. This could measure the degree of perceived depression as well as anxiety and fear of movement.

The results of the investigation and associated discussion could lead to patients taking a more active role and taking responsibility for their treatment, says Olaya-Contreras. I also believe that it can help patients to focus more on the positive resources they themselves have to handle the pain and master various physical movements even though it hurts.

The thesis has been successfully defended.

Pain relief can now be based on solid evidence

Tue, 06 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A Cochrane Review of data relating to about 45,000 patients involved in approximately 350 individual studies has provided an evaluation of the effect you can expect to get if you take commonly used painkillers at specific doses. The review also identifies pain killers for which there is only poor or no reliable evidence. This review will help doctors and patients to make evidence informed decisions of which pain killers to use, and is published in the latest edition of The Cochrane Library.

Acute pain occurs when tissue is damaged either by an injury or as a result of surgery. The pain felt after surgery happens because tissues become inflamed, and giving pain killers is a critical component of good patient care. Managing pain well helps keep a patient as comfortable as possible and aids their recovery.

Working at the Oxford Pain Research Unit at Oxford University, Dr Andrew Moore and colleagues analyzed the findings of 35 Cochrane Reviews of randomized trials testing how well different pain killers work when used against postoperative pain.

Our aim was to bring all this information together, and to report the results for those drugs with reliable evidence about how well they work or any harm they may do in single oral doses, says Moore.

A key finding was that no drug produced high levels of pain relief in all patients. If the first pain killer a person tries doesn't seem to be working, then a doctor should look to find an alternative reliable drug and see if it is more effective in that individual patient. There are plenty of options that have a solid evidence base, says Moore.

The range of results varies considerably between different pain killers. In some cases such as taking 120mg etoricoxib, or the combination of 500mg paracetamol plus 200mg ibuprofen, over 70% of participants with moderate or severe acute pain who took a single-dose achieved good pain relief. With other drugs, such as 1000mg aspirin and 600mg paracetamol taken on their own, only 35% benefitted. The worst was codeine, with only 14% getting significant pain relief. The period over which pain was relieved also varied, from about two hours to about 20 hours.

Pain relief doesn't have to be a mystery. There is a body of reliable evidence about how well 46 different drug/dose combinations work against acute pain, but the review also shows there are many examples of drugs for which there is insufficient evidence, and the drugs in question should probably not be used to treat acute pain, says Moore.

Achieving realistic physical activity goals benefits RA patients

Thu, 25 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers from The Netherlands report that patients with rheumatoid arthritis (RA) who have higher levels of self-efficacy for physical activity are more likely to achieve their physical activity goals. According to the study now available in Arthritis Care & Research, a journal of the American College of Rheumatology (ACR), achievement of physical activity goals is associated with lower self-reported arthritis pain and increased health-related quality of life (HRQOL).

The World Health Organization (WHO) estimates that RA, a chronic autoimmune disease causing inflammation in the lining of joints, affects nearly 1% of the world population. In the U.S., the ACR reports 1.3 million adults suffer with RA. Studies indicate that RA patients cite pain and stiffness as the most limiting factors of their illness, and report lower HRQOL than healthy individuals. RA patients who do not engage in regular physical activity have a more pronounced effect from the disease.

For the current study, Keegan Knittle, MSc, from Leiden University in The Netherlands and colleagues surveyed 106 patients with RA to assess physical activity, motivation and self-efficacy for physical activity, level of arthritis pain, and quality of life. After six months, participants were surveyed again and asked to indicate the extent to which they achieved their baseline physical activity goal. Previous research has shown that self-efficacy, described as one's belief in his or her own capabilities to perform a specific behavior, is associated with increased physical activity participation among RA patients.

Results showed that 75% of participants rated their physical activity goal achievement at 50% or more. Higher levels of self-efficacy for physical activity increased the likelihood that patients would achieve their physical activity goals, and goal achievement had a direct positive effect upon quality of life outcomes. Researchers found that patients who achieved their physical activity goal reported less arthritis pain and greater quality of life. No differences were found between men and women who completed the surveys, or between patients newly diagnosed versus those with RA for 10 years or more.

Knittle concluded, "Our results suggest that an increased focus on self-efficacy enhancement, realistic goal-setting, and techniques that increase the likelihood of goal achievement will assist clinicians and researchers develop interventions that have a positive impact on pain reduction and quality of life outcomes for RA patients."

To help doctors and patients, UB researchers are developing a 'vocabulary of pain'

Tue, 26 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- All over the world, patients with chronic pain struggle to express how they feel to the doctors and health-care providers who are trying to understand and treat them. Now, a University at Buffalo psychiatrist is attempting to help patients suffering from chronic pain and their doctors by drawing on ontology, the branch of philosophy concerned with the nature of being or existence. The research will be discussed during a tutorial he will give at the International Conference on Biomedical Ontology (

He describes the goals of his work in a video interview:

Pain research is very difficult because nothing allows the physician to see the patient's pain directly, says Werner Ceusters, MD, professor of psychiatry in UB's School of Medicine and Biomedical Sciences, and principal investigator on a new National Institutes of Health grant, An Ontology for Pain and Related Disability, Mental Health and Quality of Life.

The patient has to describe what he or she is feeling.

That is a serious shortcoming, Ceusters says, because each patient's subjective experience of pain is different. Descriptions of pain therefore lack the precision and specificity that is taken for granted with other disorders, where biomarkers or physiological indicators reveal what health-care providers need in order to assess the severity of a particular disorder.

If we want to more effectively help people suffering from chronic pain, we need to study a population that is consistent, patients who have features in common, Ceusters says. The problem with pain is, it's very hard to build up a group with the same sort of pain. People don't have the same vocabulary or linguistic capabilities or even the same cultural backgrounds. It's something pain researchers have struggled with for decades, Ceusters says. We need to develop a vocabulary of pain.

That's where ontology comes in.

The philosophical definition of ontology is the study of things that exist and how they relate to each other, says Ceusters, who also is director of the Ontology Research Group of UB's New York State Center of Excellence in Bioinformatics and Life Sciences. I am a person and you are a person so we share something. Suppose I drop dead. What lies on the floor? Is that still a person? If it is no longer a person, is it still the very same thing that was sitting here as a person but now is a corpse?

Ceusters says that in much the same way, definitions of pain and especially of chronic pain need to be much more precise; ontology provides methods of distinguishing among categories and describing data in uniform and formal ways.

While the philosophical approach to ontology naturally has its roots in ancient Greece, a computational approach to ontology began in the latter part of the 20th century, when computer scientists interested in artificial intelligence wanted to create software programs that perform reasoning they way humans do. To do so, they began to draw on ontology.

Here at the University at Buffalo, we excel at combining the two approaches; we have a very strong foundation in the philosophical approach to ontology with Barry Smith, who is a pioneer in contemporary ontology, especially related to biomedical applications, says Ceusters, while we also have a very strong presence in computational approaches, especially to biomedical ontology. These computational approaches allow us to devise systems of communication in which there is a consistent meaning for terms used in different language systems and conceptual frameworks.

With the $793,571 NIH grant, Ceusters and colleagues will study data gathered from thousands of patients in the U.S., the United Kingdom, Sweden, Israel and Germany who suffer from oral and facial pain, including temporomandibular disorder (TMD).

Ceusters will work with his colleagues, including Richard Ohrbach, DDS, PhD, associate professor of oral diagnostic sciences in the UB School of Dental Medicine, to develop an ontology that allows the data to be described in a much more uniform way.

The goal is to integrate the data together so that we have a large pool of data that will allow us to obtain better insight into the complexity of pain disorders, specifically the assessment of pain disorders and how they impact mental health and a patients' quality of life, Ceusters says.

The grant will build on past work that Ceusters conducted with a grant from the Oishei Foundation related to improving the classification, diagnosis and treatment of psychiatric conditions.

Ceusters, who has degrees in knowledge engineering and information science as well as in neuropsychiatry, says that the current effort grew out of his work on that grant and also from a meeting with pain researchers that he attended in 2009.

At that meeting, we discussed how we might build an ontology so that it could represent what pain is and how it relates to body parts and their activities and functions, he says. Our goal is to create a software program that will allow all pain specialists to express themselves in crystal clear terms, he says, We will create a symptom checklist that can be understood by computers. We have to define the terminology of pain. This can only be solved by the kind of ontology we are doing here at the University at Buffalo.

Physiotherapy after surgery best for shoulder problems

Tue, 21 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Most patients who receive physiotherapy after surgery experience that pain is reduced by a half within a few months. Most of them are free of pain after one to two years. This is the conclusion of a thesis presented at the University of Gothenburg, Sweden.

Age-related changes in tissue combined with acute trauma can contribute to shoulder problems. The most common cause of such problems, however, is compression of the tendons in the shoulder due to a reduction in the space available, says Ingrid Hultenheim Klintberg, physiotherapist and researcher at the Institute of Neuroscience and Physiology.

Patients with these symptoms should initially be treated by physiotherapy. Those for whom physiotherapy does not have an adequate effect are offered surgical treatment, in which the space available is enlarged and the tendons repaired, if necessary. The two most common procedures are known as arthroscopic subacromial decompression and rotator cuff repair.

The aim is that the patient should become free of pain, regain muscular strength, regain mobility, and be able to resume work and leisure activities. Patients who undergo either of these two procedures are offered physiotherapy, following a tailored programme of treatment.

The results presented in the thesis show that most patients state that pain and discomfort are reduced by 50%, 3-6 months after the surgery. They had achieved full mobility and muscle strength compared with reference values at the two-year follow up after the surgery, says Ingrid Hultenheim Klintberg.

Follow up 8-11 years after the surgery showed that many of the patients had retained good shoulder function, mobility and strength.

Their quality of life was good and they display the same pattern of physical activity as do Swedish people in general, states Ingrid Hultenheim Klintberg.

The association of alcohol drinking with migraine headache

Mon, 13 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Migraine is a neurovascular disease that affects about 15% of the western population. Compounds in foods and beverages (chocolate, wine, citrus, etc) considered as migraine triggers include tyramine, phenylethylamine and possibly histamine and phenolic compounds. Avoiding those triggers may significantly reduce the frequency of migraines in some patients.

However, only a small percentage of patients in one study became headache-free simply by excluding those foods, epidemiological studies are pointing out that genetic factors may be an underlying cause. Discrepancies in the way people are reacting to wine intake, and whether or not it triggers migraine, may be potentially explained by genetic polymorphisms in specific enzymes related to metabolism Alcoholic drinks are a migraine trigger in about one third of patients with migraine in retrospective studies on trigger factors. Many population studies show that patients with migraine consume alcohol in a smaller percentage than the general population. Research has shown a decreased prevalence of headache with increasing number of alcohol units consumed. The classification criteria of alcohol-related headaches remain problematic.

An excellent paper from The Headache Center in Empoli, Italy by Panconesi A et al (Curr Pain Headache Rep (2011) )15:177-184 summarizes the scientific data relating to alcohol and migraine headaches. The factors that trigger an attack of migraine, or of other headaches as well, are poorly understood. While retrospective studies tend to include alcohol as a trigger for an attack, the authors describe that in a recent prospective study (in which information on the factors that could potentially trigger an attack were collected prior to the migraine attack), menstruation, stress, and fatigue were found most commonly to relate to a subsequent attack, In the present paper, the authors reviewed the role and mechanism of the action of alcohol or other components of alcoholic drinks in relation to alcohol-induced headache. They conclude from their review that reports overestimate the role of alcohol, as well as other foods, in the triggering of migraine.

International Scientific Forum on Alcohol Research members thought that this was a very balanced review of the subject, and that it provided straightforward and sensible advice. Although some individuals surely have the onset of a migraine or other type of headache after the consumption of wine or alcohol, the findings are not consistent (in this study, beer consumption on the previous day reduced the risk of a migraine attack). Forum members suggest that given that subjects reporting migraine headaches have been found to be at increased risk of cardiovascular disease, it would not be appropriate to advise all such sufferers to avoid alcohol. As suggested by the authors of this paper, it may be reasonable for migraine sufferers to drink small amounts of specific types of alcoholic beverages to see if each beverage is tolerated or not. After seeing the effects, and factoring in symptoms from other dietary or lifestyle elements (sleep, stress, dehydration), a reasonable discussion can be carried out with one's physician with respect to commencing or continued alcohol use.

New test could give SLE patients a more tolerable life

Mon, 09 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) At present, it can take up to a year before a patient is diagnosed with SLE. This is because the symptoms are diffuse and are often mistaken for other diseases. However, with this blood-based test, it is possible to determine quickly whether someone has the disease or not, says Christer Wingren, associate professor in Immunotechnology at CREATE Health, Lund University.

The test can also determine how far the disease has progressed. There are three different variants of SLE, and all require different treatment. With current methods, it is often difficult to find out which variant a patient has, which makes it difficult for doctors to prescribe the right medication. A third advantage of the new technique is that it also makes it possible to predict when the disease will become active.

Characteristic of SLE is that the disease goes in waves, or flares. Without warning, the disease can flare up and put the patient out of action for a long time. With our test, we hope to be able to predict when an episode is about to happen and in this way prevent it using the right medication, explains Christer Wingren.

If all goes well, hospitals could start using the technique in two to three years.

The test itself comprises a small chip, smaller than a little fingernail, on which the researchers create a grid pattern, known as an array, using specially selected antibodies. The antibodies serve as 'capture molecules'; by placing a drop of blood on the chip, the antibodies bind the proteins, or biomarkers, in the body. In this way, a unique 'fingerprint' is produced for each patient, which reflects the disease.

In our article, we show which pattern of biomarkers (the 'fingerprint') to look for. From a technical point of view, we get a large number of data signals that say whether the marker is present and in what quantity. These measurements are then entered into a computer, which can present them to the doctors in a way that is easy to understand. It is this fingerprint which doctors could use in the future in clinical practice, explains Christer Wingren, who has spent most of the past decade developing the technique, and the past two years adapting it for SLE in particular.

According to Christer Wingren, a number of researchers around the world have attempted to develop something similar, but without success. The Lund researchers' success in the task is partly due to them having found a way to make the antibodies stable and thus more functional. The method has also become highly sensitive.

In order for the research to benefit patients, a number of key biomarker signatures, which form the basis for the test, have been patented. The findings have also been transferred to a newly started company, Immunovia, which was founded by Christer Wingren and three of his colleagues at the Department of Immunotechnology.

The research has its origins in the cancer research that Christer Wingren and a number of other researchers at the translational cancer centre CREATE Health work on. Together with Carl Borrebaeck, Dr Wingren uses an equivalent technological platform that can detect and diagnose different types of cancer. They have very promising data for predicting breast cancer recurrence and diagnosing pancreatic cancer.

Mount Sinai researchers present critical MS data at American Academy of Neurology meeting

Thu, 14 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers from Mount Sinai School of Medicine will present several key studies at the American Academy of Neurology (AAN) annual meeting, including research providing critical insight into the prognosis and clinical treatment course of people with a certain subtype of Multiple Sclerosis (MS). The meeting is taking place April 9-16 in Honolulu.

In a study titled Evaluation of Progressive Relapsing MS Patients in the PROMISE Trial, Fred Lublin, MD, Saunders Family Professor of Neurology and the Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at The Mount Sinai Medical Center and Michelle Fabian, MD, Neurology Fellow at Mount Sinai School of Medicine, conducted a subanalysis of the PROMISE trial. The clinical trial is a multinational, multicenter, double-blind, placebo-controlled trial evaluating the effects of glatiramer acetate treatment over three years in patients with primary progressive multiple sclerosis (PPMS). PPMS is characterized by steady disease progression, rather than attacks or exacerbations followed by remissions, which people with relapsing-remitting MS experience.

We were able to analyze data from a well-controlled clinical trial to determine the frequency and clinical consequences of the occurrence of relapses in MS patients who initially have a progressive course, said Dr. Lublin. Our data indicate that baseline characteristics and disease progression in PRMS differ from those in PPMS. As such, clinicians should consider evaluating the PRMS subgroup differently from those with PPMS in assessing prognosis and clinical course.

The research team evaluated differences in baseline characteristics and disease progression between patients with PPMS and patients with another subtype called progressive relapsing multiple sclerosis (PRMS) to help determine whether disease prognosis and treatment course should be evaluated differently in these subgroups. People with PRMS have steady disease progression, but also experience exacerbations, or relapses.

Using the data from the PROMISE trial, researchers found that 42 of the 943 PPMS patients in the PROMISE trial had documented relapses over the 53 months of the study, which indicates they could be categorized as PRMS. At the end of the study, the PRMS patients had a larger change in the Expanded Disability Status Scale, a method of quantifying disability in multiple sclerosis (0.92 vs. 0.59) than the PPMS patients, and increased risk for sustained disability progression. These results indicate that there is a definable subgroup that will inevitably convert to PRMS, and that disease progression is more rapid in this group. The data will be presented Thursday, April 14, 2011, at 2:00 PM HST.

Learning from old bones to treat modern back pain

Mon, 28 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) The bones of people who died up to a hundred years ago are being used in the development of new treatments for chronic back pain. It is the first time old bones have been used in this way.

The research is bringing together the unusual combination of latest computer modelling techniques developed at the University of Leeds, and archaeology and anthropology expertise at the University of Bristol.

With Engineering and Physical Sciences Research Council (EPSRC) funding, spines from up to 40 skeletons housed in museums and university anatomy collections are being analysed in the research.

The data generated, on different spine conditions and on how spines vary in size and shape, is playing a key role in the development of innovative computer models. This will enable the potential impact of new treatments and implant materials (such as keyhole spinal surgery and artificial disc replacements) to be evaluated before they are used on patients.

Ultimately, it will also be possible to use the models to pinpoint the type of treatment best suited to an individual patient.

Minister for Universities and Science David Willetts said:

Back pain is an extremely common condition, but everyone has a slightly different spine so developing new treatments can be a real challenge. This investment could significantly improve quality of life for millions of people around the world, so it's fantastic that the research is being carried out in the UK. It's also truly fascinating that old bones and very new technology can come together to deliver benefits for patients.

This is the first software of its kind designed for the treatment of back conditions. The research will also speed up the process of clinical trials for new treatments, which currently can take up to ten years.

The data provided by the old bones will be used to supplement similar data collected from bodies donated to science, which are limited in number and mainly come from older age groups.

The idea is that a company will be able to come in with a design for a new product and we will simulate how it would work on different spines. The good thing about computer models is that we can use them over and over again, so we can test lots of different products on the same model, says Dr Ruth Wilcox, from the University of Leeds, who is leading the project. If we were doing this in a laboratory we would need many new donated spines each time we wanted to test a treatment out.

This computer modelling breakthrough is possible thanks to recent advances in micro-CT (computed tomography) scanning, and to new techniques developed at the University of Leeds enabling data from micro-CT scans to be transformed into sophisticated computer models. Computed tomography (CT) scans use X-rays to build up 3-dimensional images from multiple cross-sectional pictures of body organs or tissues.

The wider the pool of spinal data at our disposal, the more effective the computer models will be in terms of demonstrating the impact of treatments on different back conditions and back types, says Dr Kate Robson Brown from the University of Bristol's Archaeology and Anthropology Department. The computer modelling software should be available for testing newly developed products and treatments in the next few years and along the way this cutting-edge research could even provide new insight into how our ancestors evolved!

Ion channel responsible for pain identified by UB neuroscientists

Fri, 17 Dec 2010 05:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- University at Buffalo neuroscience researchers conducting basic research on ion channels have demonstrated a process that could have a profound therapeutic impact on pain.

Targeting these ion channels pharmacologically would offer effective pain relief without generating the side effects of typical painkilling drugs, according to their paper, published in a recent issue of The Journal of Neuroscience.

Pain is the most common symptom of injuries and diseases, and pain remains the primary reason a person visits the doctor, says Arin Bhattacharjee, PhD, UB assistant professor of pharmacology and toxicology in the School of Medicine and Biological Sciences, director of the Program in Neuroscience and senior author on the paper.

Fifty million Americans suffer from chronic pain, costing between $100-200 billion a year in medical expenses, lost wages and other costs, says Bhattacharjee. The need to understand pain mechanisms remains paramount for human health and for society.

Inflammatory pain can result from penetration wounds, burns, extreme cold, fractures, arthritis, autoimmune conditions, excessive stretching, infections and vasoconstriction.

There are efficacious treatments for inflammatory pain, such as corticosteroids and non-steroidal anti-inflammatory drugs, says Bhattacharjee, but the adverse side effects associated with these drugs limit their long-term use and compromise patient compliance. As a result, there is a great need to understand the cellular processes involved in inflammatory pain to create less toxic, less addictive, analgesic drugs.

Pain-responsive nerve cells, known as nociceptors, are electrical cells that normally respond to pain stimuli. Nociceptors then relay information to the central nervous system, indicating the location, nature and intensity of the ensuing pain. Nociceptors are sensitized during inflammation, their ionic properties are altered and their firing characteristics changes. This sensitization causes a state of hyperalgesia, or increased sensitivity to pain.

Merely touching the inflamed area can be very painful, notes Bhattacharjee. The ionic mechanisms that are chiefly responsible for this inflammatory-mediated change in nociceptive firing had not been clearly identified.

We were able to demonstrate that a certain class of potassium channels is removed from the surface of nociceptive cells during inflammatory signaling. The removal of these ion channels is linked to the hypersensitivity of these nerve cells. We demonstrated that reducing the expression of these channels by gene interference techniques produced a similar nociceptor hyperexcitability.

Bhattacharjee says his team plans to extend their ion channel trafficking studies to in vivo models, using peptide inhibitors to try to prevent the removal of the potassium channels from the surface of nociceptors during inflammation.

We expect to show that maintaining these channels at the surface during inflammation will be effective for pain relief. Successful completion of our studies will provide the impetus for direct human clinical trials.Megan O. Nuwer, PhD, and Kelly E. Picchione, PhD, both in the neuroscience program, are co-authors on the paper.

Laboratory studies show promise for new multiple sclerosis treatment

Thu, 18 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Successfully treating and reversing the effects of multiple sclerosis, or MS, may one day be possible using a drug originally developed to treat chronic pain, according to Distinguished Professor Linda Watkins of the University of Colorado at Boulder.

Watkins and her colleagues in CU-Boulder's department of psychology and neuroscience discovered that a single injection of a compound called ATL313 -- an anti-inflammatory drug being developed to treat chronic pain -- stopped the progression of MS-caused paralysis in rats for weeks at a time.

Lisa Loram, a senior research associate who spearheaded the project in Watkins' laboratory, presented the findings at the Society for Neuroscience's annual meeting held in San Diego this week.

MS is an inflammatory disease where the body's immune system attacks a protective sheath called myelin that encompasses nerves in the spinal cord and brain. As the disease progresses, the myelin develops lesions, or scars, that cause permanent neurological problems.

What happens now with MS drugs is they slow or stop the progression of MS, but they don't treat it, Watkins said. They don't take people back to normal because the lesions caused by MS don't heal.

Watkins, Loram and their colleagues hope to use spinal cord and brain-imaging technology to extend their studies to determine if lesions are being healed in rats that received an ATL313 injection.

If we have a drug that is able to heal these lesions, this treatment could be a major breakthrough in how we treat the symptoms of MS in the future, she said.

The new findings were quite a surprise to Watkins. The team had originally wanted to look at the drug's potential in treating pain associated with MS, because about 70 to 80 percent of MS patients suffer from chronic pain that is not treatable.

What we had originally thought about this class of compounds is that they would calm down glial cells in the spinal cord because their pro-inflammatory activation is what causes pain, she said.

Under normal circumstances glial cells are thought to be like housekeepers in the nervous system, Watkins said, essentially cleaning up debris and providing support for neurons. Recent work by Watkins and others has shown that glial cells in the central nervous system also act as key players in pain enhancement by exciting neurons that transmit pain signals.

What's become evident is that glial cells have a Dr. Jekyll and Mr. Hyde personality, Watkins said. Under normal circumstances they do all these really good things for the neurons, but when they shift into the Mr. Hyde formation they release a whole host of chemicals that cause problems like neuropathic pain and other chronic pain conditions.

They discovered that ATL313 appears to reset the glial cells from an angry activated state to a calm anti-inflammatory state that may heal MS lesions.

National research study to assess new treatment for painful vertebral fractures

Thu, 28 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Physicians at The Medical College of Wisconsin are conducting the KAST clinical trial at Froedtert Hospital to assess the safety and effectiveness of a new vertebral augmentation treatment (Kiva) for painful vertebral compression fractures (VCFs) due to osteoporosis.

Sean Tutton, M.D, associate professor of radiology and surgery at the Medical College, is principal interventional radiology investigator for this multi-institutional, national trial. This prospective, randomized, controlled trial will compare outcomes of the investigational Kiva device using a coil implant with cement, to the current treatment, kyphoplasty using small orthopedic balloons and cement to repair painful fractures of the spine.

The study will evaluate whether the Kiva procedure, using a more elastic implant and less cement placed strategically, will be equally safe and effective to kyphoplasty says Dr. Tutton. It may also demonstrate that the more elastic implant and use of less cement will prove superior to kyphoplasty.

VCFs occur when a vertebra cracks, fractures, or collapses. These fractures are extremely painful and often debilitating. Over 700,000 osteoporosis-related vertebral compression fractures occur each year in the US alone. It is estimated that two-thirds of vertebral compression fractures are never diagnosed because many patients dismiss their back pain as a sign of aging and/or arthritis.

When bones become fragile and brittle from osteoporosis, everyday activities can trigger vertebral compression fractures. Bending to lift an object, missing a curb, or slipping on a wet surface can put the spine at risk of fracture. Multiple vertebral compression fractures significantly changes the structure and shape of the spine and can affect the internal organs and body functions, negatively impacting the overall health of the individual, daily activities, and quality of life.

The primary treatment for VCFs is typically conservative care consisting of bed rest, analgesics, and physical therapy. Interventional treatments for VCFs, include balloon kyphoplasty and vertebroplasty. These treatments aim to stabilize the fractures, providing earlier pain relief, and functional improvement.

Dr. Tutton pointed out that recent studies comparing vertebroplasty to sham procedures have resulted in confusion as they, on first glance, failed to demonstrate significant clinical improvement. When the trials are evaluated more critically, it is apparent that difficulties with patient selection and under-enrollment limited these trials' ability to prove their hypotheses. The prospective randomized FREE trial and recently published Vertos II trial (Lancet) both support the efficacy and safety of kyphoplasty and vertebroplasty. From the available data we know that patients who failed conservative care at four to six weeks and then received vertebroplasty or kyphoplasty experienced significant reduction in pain, earlier resumption of normal activities and most importantly preservation of independence.

Individuals eligible for the KAST study must have one or two osteoporotic spine fractures, be over age 50, and have been unsuccessfully treated by conservative care for at least 6 weeks.

The Kiva System, considered the next generation in the treatment for VCFs, is approved in Europe. The results of the current study will be submitted to the FDA for potential clearance in the US.

New drugs to relieve cancer pain

Mon, 21 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Leicester and the University of Ferrara in Italy have collaborated to develop new drugs which have the potential to relieve cancer pain without causing many of the side effects of current pain-treatments like morphine.

Figures show that 90% of cancer patients experience pain in the final year of their lives and this is a big problem. Currently, the use of drugs like morphine produces side effects such as depressed breathing, drowsiness, constipation and tolerance. Unfortunately tolerance usually results in an increased dose of morphine, which in turn means that patients experience more of these side effects.

Professors David Lambert and David Rowbotham at the University of Leicester, as well as Doctors Guerrini, Calo and Professor Salvadori from the University of Ferrara in Italy, are leading the early experiments of a new group of drugs which may not produce these side effects. The research done at the University of Leicester has been funded by the Leicestershire and Rutland charity Hope Against Cancer.

Professor David Lambert commented:

This work is still at a very early stage but has the potential to change the way we think about making drugs for pain related issues.

The new group of drugs, which were developed in the University of Ferrara and tested by the University of Leicester, is designed to produce pain relief by acting at two targets simultaneously. The two target idea may provide effective pain relief with less tolerance.

Hope Against Cancer has funded this 3-year PhD project at the University of Leicester to look at the long term effects of these new drugs, with a primary focus on drug tolerance.

Nikolaos Dietis, the PhD research student who is currently working on the project, said:

Tolerance to strong painkillers like morphine involves complicated biological processes, aspects of which still remain questionable. Our research may provide some answers by designing new drugs that have multiple roles. We are now studying these drugs to see what they do in the long-term.

Dr Guerrini said:

Pain is a very complicated condition, whose control and relief could be achieved with the use of drugs that act on two different targets in order to obtain pain relief more effectively.

The project at the University of Leicester could lead to further development of these new drugs that could even lead to future trials on cancer patients.

Professor Rowbotham commented:

We need to further refine this work to enable studies to be performed in patients. This may be a relatively long-term process, but it offers a completely new approach to pain management for cancer patients in the future.

Hip exercises found effective at reducing, eliminating common knee pain in runners

Fri, 04 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A twice weekly hip strengthening regimen performed for six weeks proved surprisingly effective at reducing -- and in some cases eliminating -- knee pain referred to as patellofemoral pain (PFP) in female runners.

The study by Tracy Dierks, assistant professor in the Department of Physical Therapy at Indiana University-Purdue University Indianapolis, was based on the theory that stronger hips would correct running form errors that contribute to PFP, even though study participants were given no instruction in gait training. The study used a pain scale of 0 to 10, with 3 representing the onset of pain and 7 representing very strong pain -- the point at which the runners normally stop running because the pain is too great. The injured runners began the six-week trial registering pain of 7 when they ran on a treadmill and finished the study period registering pain levels of 2 or lower; i.e. no onset of pain.

I wasn't expecting such huge reductions, to be honest, Dierks said. We've had a couple of runners who have been at level 2, but the overwhelming majority have been a 2 or below.

PFP, one of the most common running injuries, is caused when the thigh bone rubs against the back of the knee cap. Runners with PFP typically do not feel pain when they begin running, but once the pain begins, it gets increasingly worse. Once they stop running, the pain goes away almost immediately. Dierks said studies indicate PFP essentially wears away cartilage and can have the same effect as osteoarthritis. His study participants showed many of the classic signs of PFP, the most prominent being their knees collapsing inward when running or doing a squat exercise move.

The pilot study thus far involved five runners and a control group that comprised another four runners. Hip strength measurements were taken before and after the runners in the control group maintained their normal running schedule for six weeks. Hip strength measurements were taken for all of the runners before and after the next six-week period in which they all performed the hip-strengthening exercises. The exercises, performed twice a week for around 30 to 45 minutes, involved single-leg squats and exercises with a resistance band, all exercises that can be performed at home. This study is part of an ongoing study involving hip exercises and PFP pain, with 11 runners successfully using the intervention. Dierks said he plans to seek funding to test the exercises on a larger group of runners.

Earlier research had focused on the feet as a possible root of PFP, with studies only recently looking more closely at the hips. Dierks said studies have found an association between PFP in women and weak hips, but his study is the first to test a possible treatment. He noted that PFP is considered multi-factorial, so his study is examining one of several possible causes of the pain.

Osteoporosis drug improves healing after rotator cuff surgery

Wed, 10 Mar 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Tears in the shoulder's rotator cuff, a common sports injury, are painful and restricting. Surgery to repair the damage is successful for pain management, but in many patients it does not result in full recovery of function due to poor healing. New research shows an approved therapy for osteoporosis, Forteo, may speed healing and improve patient outcomes. The preliminary study from Hospital for Special Surgery in New York is being presented at the American Academy of Orthopaedic Surgeons (AAOS) meeting in New Orleans March 9-13.

According to a previous study, only 69 percent of rotator cuff repairs were completely healed when evaluated two years after the surgery, said Scott Rodeo, M.D., co-chief of the Sports Medicine and Shoulder Service at Hospital for Special Surgery and senior author on the study. Although not all of the patients with failed rotator cuff tendon healing had poor clinical outcomes, we wanted to look for ways to further improve patient outcomes.

The rotator cuff is a set of four smaller muscles in the shoulder that rotate the upper arm. A rotator cuff tear happens when the tendon part of the muscle tears away from the bone of the upper arm. The repair surgery reattaches the tendon to the bone, but the success depends on how well the interface between the tendon and bone heals. Much of the time scar tissue forms at that interface, which is not as strong as the original tissue and can lead to a failed repair.

The healing process occurs from both the bone and the tendon, which is made up of collagen, said Carolyn Hettrich, M.D., MPH, fifth year resident in orthopedic surgery at Hospital for Special Surgery and lead author. We knew the drug Forteo is osteogenic and can stimulate bone growth, but we found reports in the literature that it is also chondrogenic, so it can promote cartilage formation as well.

Forteo is a synthetic version of parathyroid hormone, which is the body's primary regulator of calcium and phosphate levels in bone. Recently approved by the FDA, it is prescribed for osteoporosis as it not only stimulates bone growth but it also slows the rate of bone loss.

The researchers hypothesized that because Forteo stimulated both bone and cartilage formation, it might enhance the healing process after rotator cuff surgery. Using a rat model, they performed the surgery and then gave some rats Forteo injections in amounts comparable to human doses.

Initially, at two weeks after the surgery, the repair was not as strong in the rats who received the Forteo. But when the researchers looked at weeks four through eight, the tendon to bone interface in those rats appeared much more like normal tissue. Closer examination showed that not only had those rats that received Forteo produced more bone and cartilage cells, but the organization of the tissue was better and more closely resembled normal tissue. The tendon was also significantly stiffer, a sign of proper healing, at 8 weeks.

The results are positive, but now we want to understand why at week two the tendon wasn't healing as well, said Dr. Hettrich. Our next experiments will look to pinpoint these causes and determine the optimum delivery time of the drug after surgery.

The researchers caution that it would be risky to use Forteo in patients undergoing rotator cuff surgery just yet as further studies are needed. Instead, they encourage patients to talk to their surgeons about other steps they can do to improve healing, such as not smoking after the surgery to optimize their biology.

Athletes who use overhead movements, like baseball or tennis players, are prone to this injury. It is also common in adults over 40 because the tendons begin to degenerate and weaken.

Scientists discover new treatment for chronic pain condition

Mon, 01 Feb 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Scientists at the University of Liverpool have discovered that treating the immune system of patients with Complex Regional Pain Syndrome (CPRS) leads to a significant reduction in pain.

CRPS is an unexplained chronic pain condition that usually develops after an injury or trauma to a limb, and continues after the injury has healed. CPRS I - formerly called Reflex Sympathetic Dystrophy - can arise after any type of injury. CRPS II, previously called causalgia (a term coined in the American Civil War when it was first diagnosed), follows partial damage to a nerve. In some cases the pain can be so severe that patients request amputation, only to find that the pain returns in the stump.

CRPS pain can improve within one year after the injury, but if it is still unchanged after 12 months (longstanding CRPS), then it will often not improve at all. Longstanding CRPS affects about 1 in 5,000 people in the UK.

The team at the Pain Research Institute discovered that a single, low dose infusion of intravenous immunoglobin (IVIG) significantly reduced pain in just under 50 per cent of patients treated, with few adverse effects. The pain relief lasted on average 5 weeks. The results of this study may change the future treatment of patients with CRPS, and have an impact on research in other severe chronic pain areas. Intravenous immunoglobulin treatment for CRPS is currently not available on the NHS.

Although the cause of the syndrome is unknown, precipitating factors include injury or damage to the body's tissue. Changes in the way nerves send messages to the brain about pain may occur at the injury site. These changes may then lead to more changes in the nerves of the spinal chord and brain. All these changes are thought to play a role in causing and prolonging the condition. Conventional pain drugs either don't work, or have considerable side effects.

Dr Goebel, Senior Lecturer in Pain Medicine, explains: In CRPS, the real effect of this treatment in clinic may turn out to be even greater than what we have already seen, because IVIG can be given in higher doses, and repeated treatment may have additional effects. IVIG is normally repeated every four weeks and we are working to develop ways which would allow patients to administer the treatment in their own home.

The discovery is expected to have a real impact on the treatment of other unexplained chronic pain conditions; if one pain condition can be effectively treated with an immune drug, then it is possible that other types will also respond.

The research is published in the journal

Extremity war injuries symposium seeks to improve patient care for wounded warriors

Wed, 27 Jan 2010 05:00:00 PST

( from http://www.rxpgnews.com ) WASHINGTON, D.C. - Since the beginning of Operations Iraqi Freedom and Enduring Freedom, there have been nearly 36,000 battle- injured warriors, of which approximately 82 percent suffer extremity trauma. Many of these injuries are complicated by the effects of improvised explosive devices which cause injury patterns distinct from civilian trauma. Traditional wound-management guidelines simply fall short. In an effort to address the increasing number and severity of extremity war injuries among the nation's warriors serving in Iraq and Afghanistan, the American Academy of Orthopaedic Surgeons (AAOS), the Society of Military Orthopaedic Surgeons (SOMOS), the Orthopaedic Trauma Association (OTA), and the Orthopaedic Research Society (ORS) will bring together the nation's top civilian and military orthopaedic trauma surgeons and researchers for a two-day symposium January 27 - 29 to discuss barriers of return of function and duty and develop treatment principles.

Over the past several years, peer-reviewed orthopaedic research has been an essential element of our continued efforts to encourage researchers to focus on improving the treatment of high-energy extremity war injuries, said Michael Bosse, MD, CAPT, USNR (Ret.), past OTA President and co-chair of the EWI Symposium. The EWI Symposium gives us a valuable opportunity to discuss this type of research and to learn more about helping our military orthopaedic surgeons discover new and innovative ways to best treat these complex injuries. To improve the quality of life for these injured troops, we have to recognize the need for sustained, robust investment in this type of research.

The distinguished service of our military surgeons never ceases to amaze me, noted COL James R. Ficke, MD, current Chairman of the Department of Orthopaedic Surgery and Rehabilitation at Brooke Army Medical Center, the Orthopaedic Surgery Consultant to the US Army Surgeon General, and co-chair of the EWI Symposium. The continued dedication of surgeons and the incredible courage of our patients inspires advances that enhance the treatment, research, and knowledge of blast injuries. The body of research to characterize these injuries demonstrates that the majority of battlefield wounds affect extremities. Extremity wounds are responsible for two-thirds of inpatient hospital and disability costs, and are the main reasons why up to one third of our warriors never fully recover. This underscores the fact that current therapy options are not capable of restoring full function after these devastating injuries.

In January 2006, AAOS, SOMOS, and OTA hosted the first Extremity War Injuries (EWI) symposium in Washington, DC, which defined current knowledge of the management of extremity war wounds and produced a prioritized list of objectives for future research. Now in its fifth year, the EWI symposium will focus on barriers to return of function and duty and will include a session on disaster preparedness and response. The session is co-moderated by Christopher T. Born, MD, Director of Orthopaedic Trauma at Rhode Island Hospital, who will discuss his recent experiences in Haiti after the earthquake disaster.

Tarantula venom-based MD therapy to be advanced by UB scientists' biotech company

Tue, 29 Dec 2009 05:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- University at Buffalo biophysicists have found a protein in tarantula venom that shows promise as a potential therapy for muscular dystrophy (MD). They have formed a start-up biotech company in Buffalo -- Rose Pharmaceuticals -- to advance the drug to clinical trials.

Fredrick Sachs, PhD, professor of physiology and biophysics at the University at Buffalo, and colleagues in his laboratory, discovered the peptide, called GsMTx4.

Therapies for muscular dystrophy are classed as orphan drugs by the FDA, allowing a shorter testing period than normal drugs. Sachs said he anticipates Rose Pharmaceuticals may be able to obtain FDA approval of the peptide for human use within two years.

The new company is named for Rose, the pet tarantula that has been in residence in Sachs' lab for nearly 20 years.

The first target of the peptide is MD, a condition Sachs has been investigating for several years, but the peptide also has potential as a therapy for several other conditions, such as neuropathic pain and atrial fibrillation. Formation of the company was motivated by the goal of finding an MD therapy for the grandson of Sachs' friend Jeffrey Harvey.

The start-up is a collaboration between Sachs, Harvey, Thomas Suchyna, PhD, and Philip Gottlieb, PhD. Suchyna and Gottlieb, UB research scientist and UB research associate professor, respectively, have been working with Sachs at the university for several years to develop the peptide. Their work was supported by a grant from UB's Interdisciplinary Research and Creative Activities Fund.

In collaboration with Eric Hoffman, PhD, director of the Wellstone Muscular Dystrophy Center at Children's National Medical Center in Washington, D.C., the team tested the effect of GsMTx4 on MD mice extensively. Results showed that the drug increased muscle strength and caused no mortality, morbidity or toxicity.

Rose Pharmaceuticals now is concentrating on developing methods to administer the drug. The peptide and its mirror image are covered by U.S. patents obtained by UB's Office of Science, Technology Transfer and Economic Outreach (STOR), and licensed to Rose Pharmaceuticals. Sachs noted that there are no other drugs known to act specifically on mechanosensitive ion channels, the target of GsMTx4.

Unlike most drugs, GsMTx4 seems to generate only positive side effects, said Sachs. In addition to its effectiveness in MD, it inhibits atrial fibrillation, a cardiac arrhythmia that affects 2 million Americans, and for which there currently is no reliable drug therapy.

In a second application, research groups in Korea and UC San Francisco have shown that GsMTx4 can inhibit mechanically induced pain (pain originating in nerve fibers), he said. This therapy is at least half as effective as morphine, but does not act on the brain, only at the site of increased sensitivity. Mark Kristal, PhD, UB professor of psychology, has been collaborating on the pain testing.

GsMTx4 appears to have additional applications. Robert Plunkett, MD., UB associate professor of neurosurgery, has shown that the peptide stimulates neuronal growth, and may be useful for the treatment of Parkinson's disease.

American Academy of Nursing strengthened by induction of palliative care expert

Mon, 09 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) Patricia Berry, PhD, APRN, FAAN, associate professor at the University of Utah College of Nursing was formally inducted into the American Academy of Nursing Saturday as one of the 2009 new Fellows. Berry was nominated for this honor by two current Academy Fellows and was selected by the Academy's 15-member Fellow Selection Committee for her outstanding achievements in the nursing profession. The induction of Berry and 97 other nurse leaders took place during the Academy's Annual Awards Ceremony in Atlanta, GA.

The American Academy of Nursing invites a select group of nursing leaders to become fellows of the academy, said University of Utah College of Nursing Dean and Louis H. Peery Presidential Endowed Chair, Maureen R. Keefe, RN, PhD, FAAN. This honor is indicative of Dr. Berry's numerous contributions to the field of nursing, particularly in the areas of end-of-life care and pain symptom management. According to Keefe, Berry joins a select group of College of Nursing faculty members who have received this distinguished honor.

The Academy is constituted to anticipate national and international trends in health care, and address resulting issues of health care knowledge and policy. Not only is the invitation to Fellowship recognition of one's accomplishments within the nursing profession, but it also affords the chance to work with other leaders in health care in addressing the issues of the day.

In addition to being a certified gerontological nurse practitioner and an advanced practice palliative care nurse, Berry is associate director, education and practice for the University of Utah's Hartford Center of Geriatric Nursing Excellence. With 32 years of experience in hospice and palliative care, Berry has contributed to critical policy, educational, and scientific initiatives to improve the management of pain and symptoms, especially for individuals with life-limiting illness and their families. She is a member of the national faculty for the Geriatric End of Life Nursing Education Consortium (ELNEC) and serves on the research committees of the National Hospice and Palliative Care Organization and the American Board of Nursing Specialties.

By sustaining her commitment to pain and symptom management, especially for older adults at the end of life, Dr. Berry will join other members of the Academy as an important force in disseminating nursing knowledge nationally and internationally, said Regina Fink, RN, PhD, FAAN, AOCN, a research nurse scientist with University of Colorado Hospital and one of Berry's nominators. Added Ginette Pepper, PhD, RN, FAAN, professor, Helen Lowe Bamberger Colby Endowed Chair in Gerontological Nursing, who joined with Fink in nominating Berry, One of the most expensive and agonizing aspects of our health care system is inappropriate care at the end of life. Dr. Berry's voice and expertise will help to further the mission of the Academy and assure the promotion of humane and effective health care.

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

Sat, 26 Sep 2009 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 PST

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

Tue, 14 Apr 2009 04:00:00 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 04:00:00 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.

New surgical option for wrist arthritis

Fri, 13 Feb 2009 05:00:00 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 05:00:00 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.

Delays in radiation therapy lead to increased breast cancer recurrence

Mon, 01 Dec 2008 05:00:00 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.

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

Thu, 13 Nov 2008 05:00:00 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 04:00:00 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.

$4.8M NIH grant aids interstitial cystitis research

Fri, 26 Sep 2008 04:00:00 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.

Princeton University survey finds 'pain gap'

Thu, 01 May 2008 04:00:00 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 04:00:00 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.

Chronic pain harms the brain

Tue, 05 Feb 2008 05:00:00 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.

Naked mole-rats bear chili pepper heat

Mon, 28 Jan 2008 05:00:00 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 05:00:00 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 05:00:00 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 05:00:00 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 04:00:00 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.

Watching funny shows helps children tolerate pain longer, study finds

Tue, 23 Oct 2007 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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.

Treatment blocks pain without disrupting other functions

Wed, 03 Oct 2007 04:00:00 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 04:00:00 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:

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

Mon, 01 Oct 2007 04:00:00 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 04:00:00 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.

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

Thu, 27 Sep 2007 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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.�

Restless legs genetics on the move

Thu, 19 Jul 2007 04:00:00 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 04:00:00 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 04:00:00 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.

Macrochem acquires option to license pexiganan

Tue, 10 Jul 2007 04:00:00 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.

How pain distracts the brain

Thu, 05 Jul 2007 04:00:00 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.

SSRI antidepressants do not pose major birth defect risk

Wed, 27 Jun 2007 04:00:00 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.

Community Oncology explores pitched debate over anemia-fighting drugs

Tue, 26 Jun 2007 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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.

Old memory traces in brain may trigger chronic pain

Mon, 04 Jun 2007 04:00:00 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 04:00:00 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.

Smokeless cannabis delivery device efficient and less toxic

Tue, 15 May 2007 04:00:00 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.

Stenting of abdominal arteries offers welcome relief for 'intestinal angina'

Fri, 11 May 2007 04:00:00 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.

Counseling, coping skills could reduce arthritis disability

Thu, 10 May 2007 04:00:00 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 04:00:00 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 04:00:00 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.

Does execution by lethal injection involve conscious asphyxiation?

Mon, 23 Apr 2007 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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.

Researchers call for national database of epidural complications

Mon, 02 Apr 2007 04:00:00 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 04:00:00 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.

Headache-related work absences have a considerable socio-economic effect

Wed, 14 Mar 2007 04:00:00 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 05:00:00 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.

McGovern Institute Scolnick Prize awarded to David Julius

Tue, 27 Feb 2007 05:00:00 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.

New device safeguards against medication errors at home

Wed, 21 Feb 2007 05:00:00 PST

( from http://www.rxpgnews.com ) CAMDEN -- Patients suffering from chronic illness such as diabetes, congestive heart failure, coronary artery disease, and depression, can take six-to-nine different medications a day oftentimes more. Skipped doses, misinterpretation or labels, or confusion over what pills to take at what time can be fatal.

Larry Shusterman, DO, an internal medicine and geriatrics physician and a former pharmacist, has created a way to stop medication mismanagement through the Medi-Sure Medication Dispensing System, an automated device programmed by a pharmacist and used in the patients home.

Thanks to the services provided by the Rutgers Camden Technology Campus (RCTC Inc.), this innovation is on the fast track to save lives.

This was a device I made out of a desperate attempt to assist patients who ended up requiring emergency room treatment because of medication issues, says Shusterman, a client in the Rutgers-Camden business incubator. I saw a lot of people who were in nursing homes because of medication issues. The usual methods of medicine reminders, like calendars, or pill boxes, just werent working.

Patients who use the Medi-Sure system take their medication at the right time and as instructed 95 percent of the time. Research shows that, in general, medication compliance can be as low as 30 percent.

The Medi-Sure Dispensing System is about the size of a DVD player and is programmed by a pharmacist, who puts medications in cassettes that hold two weeks work of medicine. The pharmacist also programs what times each dose is to be taken and instructions for each medication, such as whether or not the medicine should be taken with food or water.

Then, in the patients home, the Medi-Sure Dispensing System alerts the patient that its time to take their medicine through a verbal recording, and will keep alerting the patient until he or she presses the Get Dose button. The machine then dispenses the pills into a drawer that, once removed, tells the patient any specific instructions about that medicine. When the drawer is returned, the Medi-Sure Dispensing System records the time that the medicine was taken, and creates a log that can be accessed electronically by a health care provider and any family members who have been given permission to view the log. The log also includes crucial information about the medications, from the dosage to what the pills look like since generic version of a medicine can look completely different than the brand-name version.

Medi-Sure Dispensing Systems currently are being used in New Jersey in a range of settings, including independent living facilities, continuing care residences, group and private homes for people with mental disabilities, and through the Living Independently for Elders (LIFE) program at the University of Pennsylvania, which provides patients with additional medical support so they can live at home instead of in a nursing home.

The entire service, which includes hardware, software, reports, and a fee to fill the cassettes, costs about $4 per day less per month than most in-home nursing visits.

Shusterman has been working with RCTC Inc. on the Medi-Sure system, which is a project of his company, Rapid Patient Monitoring. The Rutgers Camden Technology Campus works with entrepreneurs to grow and expand their businesses in Camden by providing them with low-cost office and conference space, technical support services and mentoring for successful startup.

Shusterman started working with the Rutgers-Camden business incubator as a virtual tenant in September 2006 and plans to move into the RCTC Inc. physical facility. Through the Rutgers program, Shusterman has worked with faculty at the Ernesto Mario School of Pharmacy at Rutgers-New Brunswick, who evaluated the product, and with a leading continuing care retirement community in the Delaware Valley. Representatives of both organizations believe that the Medi-Sure system is sound and will be able to keep people in their homes longer than without the system.

Were able to offer companies like Rapid Patient Monitoring amazing services that benefit companies of all sizes, as well as Rutgers, says Peter Gold, CEO of the Rutgers-Camden Technology Campus and associate provost for economic initiatives at Rutgers-Camden. For instance, when a company expands and begins looking for venture capital opportunities or funding, its very valuable for that company to say that theyve already had their product or service assessed by a Rutgers faculty member or by people working in the field.

Theyve been able to provide infrastructure and assistance to take my company to the next level, says Shusterman of the Rutgers Camden Technology Campus. Aside from physical work space, the RCTC has also provided Shusterman with public relations assistance and mentoring from leaders in the fields of pharmacy and business.

Study finds surfing safer than soccer

Tue, 02 Jan 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Providence, RI -- While public perception may frame surfing as a dangerous sport, new research begs to differ. In the first study of its kind, researchers have computed the rate of injury among competitive surfers and found they are less prone to harm than collegiate soccer or basketball players. Led by researchers at Rhode Island Hospital and Brown Medical School, the findings of the study are published in the January 2007 issue of the American Journal of Sports Medicine.

We found that competitive surfing has a relatively low risk of injury 6.6 significant injuries per 1,000 hours of surfing - compared to other sports for which comparable data is available, says lead author Andrew Nathanson, MD, an emergency medicine physician with Rhode Island Hospital's Injury Prevention Center. However, the risk of injury more than doubled when surfing in large waves or over an area with a hard bottom.

The sport of surfing has rapidly grown in popularity since the 1960's, but little is known about surfing injuries especially the relative frequency, mechanisms and risk factors. Nathanson and his research team collected injury data from 32 surfing contests worldwide, both professional and amateur. Documentation of every acute surfing injury sustained during competition was recorded, as well as wave size, mechanism of injury and treatment. Significant injuries were qualified as those that prevented the surfer from surfing for one or more days, resulted in a hospital visit, or required on-site suturing.

Sprains and strains to the lower extremities, particularly the knees, were found to be the most common injuries reported. This is likely due to the aggressive turning and aerial maneuvers, which score highly in competitions, but also appear to place high stress on a surfer's knee, says Nathanson, who is also an emergency physician at The Miriam Hospital and an assistant professor at Brown Medical School, both in Providence, RI.

In contrast, previous studies conducted by Nathanson researching the injuries of recreational surfers found that lacerations and contusions were the most common reported injury these were the second most common injury among contest surfers. Most of these injuries were caused by direct contact between a surfer and a surfboard either their own or another surfer's.

The fact that cuts were found to be less common among surfers during a competition makes sense since it's a more controlled environment compared to a recreational surfing-type atmosphere. In competitions, there are a limited number of surfers in the water during each heat and the skill level is very high. On the other hand, recreational surfers are often trying to catch waves in a dense crowd of surfers of varying abilities, says Nathanson.

The authors note that although age and gender had no bearing on the injury rate, wave size and bottom type, independently, were significantly associated with a great chance of injury.

It would come as little surprise to most surfers that the injury rate more than doubles when surfing in larger surf (overhead) compared to smaller waves, as the energy of waves increases as it grows in height. In addition, a sea floor with a sandy bottom is much more forgiving upon impact than one covered with reefs or rocks, says Nathanson.

The paper cites that establishing an injury rate for surfing is not just of academic or general interest, but also has implications for the insurance industry and for schools that may want to start a surfing team.

The information could also help to predict the needs of medical staff support at contests and aid in the design of safer surfboards and protective equipment such as helmets, Nathanson adds.

To reduce the risk of injury while surfing, Nathanson suggests good physical fitness, seeking local knowledge before paddling out to an unfamiliar break, and being realistic in terms of your ability level and the size of the waves.

Further research is needed to determine if an injury rate can be calculated for recreational surfers and to evaluate the effectiveness of modifications in surfing equipment on reducing the incidence of injury.

Genetic mechanism helps explain chronic pain disorders

Fri, 22 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) CHAPEL HILL - Researchers at the University of North Carolina at Chapel Hill have discovered that commonly occurring variations of a gene trigger a domino effect in chronic pain disorders. The finding might lead to more effective treatments for temporomandibular joint disorder (TMJD) and other chronic pain conditions.

Catechol-O-methyltransferase (COMT), an enzyme that metabolizes neurotransmitters such as epinephrine, norepinephrine and dopamine and that has been implicated in the modulation of persistent pain, as well as cognition and mood, is regulated by a gene, also called COMT. Previous UNC-led research showed that common genetic variants of this gene are associated with increased pain sensitivity and the likelihood of developing TMJD.

Now, the researchers have discovered that specific variants of the COMT gene can dramatically affect the secondary structure of corresponding messenger RNA - which, in turn, leads to alterations in the amount of enzyme crucial for regulating pain processing. The discovery is published in the Dec. 22 issue of Science.

TMJD is a complex pain condition that is frequently associated with other pain conditions such as fibromyalgia syndrome, chronic headaches and irritable bowel syndrome, said Dr. William Maixner, director of the Center for Neurosensory Disorders in UNC's School of Dentistry and a study co-author.

This study has identified a new genetic mechanism that influences an individual's susceptibility to develop chronic pain conditions such as TMJD, Maixner said.

The study was conducted to understand the mechanism by which the identified genetic variants influence enzymatic activity and, ultimately, biological functions such as pain transmission. The researchers found that three major variants of COMT show significant differences in how they code for the secondary structure of messenger RNA, or mRNA. The differences lead to dramatic alterations in protein expression, which substantially influences pain sensitivity in humans.

These findings are clinically important because pain conditions resulting from low COMT activity or elevated catecholamine levels are likely to be susceptible to treatment with pharmacological agents that block beta 2- and beta 3-adrenergic receptors, which mediate COMT-dependent pain signaling, or that control mRNA secondary structure.

Elucidating the genetic mechanisms that mediate pain perception will provide new insights into how chronic pain develops and will ultimately contribute to the identification of unique markers for diagnosing clinical pain conditions, as well as provide novel targets for the development of effective individualized therapeutics for TMJD and related conditions, said Dr. Andrea Nackley Neely, a research assistant professor in the Center for Neurosensory Disorders and the study's lead author.

These data have broad medical and evolutionary implications regarding the analysis of variants common in the human population, Nackley Neely said. It is believed that variants leading to altered protein structure have the strongest impact on gene function. However, this study demonstrates that combinations of common genetic variants that influence mRNA secondary structure may have even stronger effects and, thus, represent another key factor responsible for disease onset and progression.

This study provides additional evidence of a genetic, molecular and physiological basis for pain perception and human pain conditions and should help to remove the stigma associated with conditions such as TMJD and fibromyalgia, said Dr. Luda Diatchenko, an associate professor in the center and the study's chief investigator.

Other researchers were Dr. Inna Tchivileva, a postdoctoral research associate within the Center for Neurosensory Disorders; Kathryn Satterfield, a former research assistant within the center; Dr. Olex Korchynskyi, a former postdoctoral research associate within the UNC-Chapel Hill School of Medicine's Thurston Arthritis Research Center; Dr. Sergei S. Makarov, a former associate professor at the Center for Neurosensory Disorders and the Thurston center and now president and chief executive officer of Attagene Inc.; and Dr. Svetlana A. Shabalina, a staff scientist with the National Center for Biotechnology Information.

Psychological treatments improve outcomes for back pain sufferers

Fri, 22 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Psychological interventions for chronic low back pain are effective, a new review of studies has found. Not only do these approaches improve psychological outcomes such as depression and health-related quality of life, they also reduce patients' experience of pain.

Because this analysis was both more inclusive and more conservative than previous reviews, we have the best evidence to date that these interventions are helpful, said psychologist and review lead author Robert Kerns, Ph.D., of the VA Connecticut Healthcare System.

The review, part of a new article series, appears in the January 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.

To evaluate the effects of psychological interventions on pain-related outcomes, Kerns and his team gathered data from 22 randomized trials published between 1982 and 2003. Trials were limited to adults with nonmalignant low back pain that had persisted for at least three months. However, most patients had been living with pain for much longer. The average duration was seven and a half years.

The studies were not limited to any one psychological approach. Included in the review were behavioral and cognitive-behavioral techniques; self-regulatory techniques such as hypnosis, biofeedback, and relaxation; and supportive counseling.

The review reports on 12 pain-related outcomes, including pain intensity, pain interference, depression, health care use, disability and health-related quality of life.

In the broadest analysis, psychological interventions -- alone or as part of a multidisciplinary approach -- proved to be superior to waiting lists or standard treatments on the entire range of pain-related outcomes.

When the researchers analyzed specific outcomes, they found that the largest and most consistent effect was a reduction in pain intensity.

This was somewhat surprising, Kerns said, because when psychologists first began developing interventions for chronic pain several decades ago, the goal was not to reduce pain but to help patients live with their pain more successfully.

However, a growing body of knowledge suggests that these interventions are actually having a primary effect on people's experience of pain, he said.

The review found that psychological interventions also yielded improvements in health-related quality of life, work-related disability, interference of pain with daily living and depression.

Not all treatments were equally effective. Cognitive-behavioral and self-regulatory treatments seemed to yield the greatest effects, particularly when compared to waiting list control groups. Multidisciplinary approaches that included a psychological component also stood out on some measures, reducing pain interference and work-related disability when compared to other active treatments.

According to Dennis Turk, Ph.D., a professor of anesthesiology and pain research at the University of Washington in Seattle, patients with chronic pain sometimes fail to recognize the value of psychological treatments because they've been set up to expect a cure.

Even the latest and greatest treatments don't cure people with chronic pain, he said. Psychological interventions are not cures, but they do reduce pain and improve function and they are important components in the treatment of people with chronic pain.

Turk added that psychological interventions are also cost-effective when compared to other treatments for chronic low back pain -- a key finding, considering that estimates for treatment-related costs range from $20 billion to $80 billion a year in the United States.

Surgery, opioids, nerve blocks, spinal cord stimulators, implantable drug delivery systems -- every one of those particular alternatives is much more expensive and has poorer or at best equal outcomes compared to rehabilitation programs that include psychological components, said Turk. The paradox is that, despite data on the effectiveness of psychological interventions, insurers are less willing to pay for them.

Getting the word out that these treatments are effective and cost-effective is a challenge that psychologists will have to tackle head-on, Kerns said.

We need to specifically target health care system administrators and third-party payers to try to engage them in a more productive dialogue about the importance of these interventions, he said. We continue to have a huge, very costly problem in our society, but we have an intervention that is effective, and we need to do a better job of creating access to these services.

Pain control is a mind game

Thu, 21 Dec 2006 07:39:51 PST

( from http://www.rxpgnews.com ) 40 pain-free volunteers took part in an experiment funded by the Arthritis Research Campaign using an artificial pain stimulus, and were led to expect reduced pain after the application of a cream which was actually a placebo.

Lead researcher Alison Watson said: "Any medical treatment involves a placebo element; the psychological suggestion that it is going to work. So we theorised that a proportion of any treatment's effectiveness would relate to how much we wanted it to work, believed in it or trusted the person administering it.

"Doctors and nurses can transmit a lot of information about a treatment and its effectiveness through their words and gestures. We know that when people visit their preferred GP the treatment or advice they receive will be more effective than that given by a GP they prefer not to see. Similarly, red pills have been shown to be more effective than green ones; so we wanted to test whether all this was due to expectations of successful treatment and trust in the person giving it."

24 of the volunteers initially received a moderately painful heat stimulus to both arms. The placebo cream was then applied to the skin, but they were led to believe that the cream on one of their arms may be a local anaesthetic.

After the application of the cream, the intensity of the heat stimulus was turned down on one arm without informing the volunteer. Subsequently the intensity was returned to its previous level, but - in contrast to the 16 people in the control group - 67% of the treatment group continued to perceive the heat as less painful.

Alison said: "The expectation of pain relief leads to a release of endorphins, the brain's natural pain killers, which is likely to contribute to a sensation of reward and well-being.

"Interestingly, there was an exact split in the range of responses to the placebo; a third of people reporting a reduction in the pain intensity in the "treated" arm only, another third in both arms and the remainder's intensity-ratings not being influenced by the application of the cream. The different responses can be related to the different levels of pain relief the volunteers expected, which may have allowed their individual suggestibility to influence their assessment of the pain experience.

"Our findings suggest that different individuals may have different styles of placebo response, which is likely to affect how they respond to real treatments too. Understanding these differences could better inform the way doctors and nurses provide treatments in the future.

"It could also facilitate more effective clinical trial design, which could substantially reduce the costs of developing new pain killers for patients with conditions like cancer and arthritis.

"A further, exciting possibility is that we could develop talking and drug-based therapies to enhance people's response to placebos. The experimental methods we're using will allow us to test out such possibilities as a method of treating pain."

Pain relief effectiveness down to mind-set?

Thu, 21 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Research by the Human Pain Research Group at The University of Manchester suggests that people's responses to placebo or 'dummy' pain relief varies according to their way of thinking.

40 pain-free volunteers took part in an experiment funded by the Arthritis Research Campaign using an artificial pain stimulus, and were led to expect reduced pain after the application of a cream which was actually a placebo.

Lead researcher Alison Watson said: Any medical treatment involves a placebo element; the psychological suggestion that it is going to work. So we theorised that a proportion of any treatment's effectiveness would relate to how much we wanted it to work, believed in it or trusted the person administering it.

Doctors and nurses can transmit a lot of information about a treatment and its effectiveness through their words and gestures. We know that when people visit their preferred GP the treatment or advice they receive will be more effective than that given by a GP they prefer not to see. Similarly, red pills have been shown to be more effective than green ones; so we wanted to test whether all this was due to expectations of successful treatment and trust in the person giving it.

24 of the volunteers initially received a moderately painful heat stimulus to both arms. The placebo cream was then applied to the skin, but they were led to believe that the cream on one of their arms may be a local anaesthetic.

After the application of the cream, the intensity of the heat stimulus was turned down on one arm without informing the volunteer. Subsequently the intensity was returned to its previous level, but - in contrast to the 16 people in the control group - 67% of the treatment group continued to perceive the heat as less painful.

Alison said: The expectation of pain relief leads to a release of endorphins, the brain's natural pain killers, which is likely to contribute to a sensation of reward and well-being.

Interestingly, there was an exact split in the range of responses to the placebo; a third of people reporting a reduction in the pain intensity in the 'treated' arm only, another third in both arms and the remainder's intensity-ratings not being influenced by the application of the cream. The different responses can be related to the different levels of pain relief the volunteers expected, which may have allowed their individual suggestibility to influence their assessment of the pain experience.

Our findings suggest that different individuals may have different styles of placebo response, which is likely to affect how they respond to real treatments too. Understanding these differences could better inform the way doctors and nurses provide treatments in the future.

It could also facilitate more effective clinical trial design, which could substantially reduce the costs of developing new pain killers for patients with conditions like cancer and arthritis.

A further, exciting possibility is that we could develop talking and drug-based therapies to enhance people's response to placebos. The experimental methods we're using will allow us to test out such possibilities as a method of treating pain.

Workers' compensation ratings don't accurately predict disabilities

Tue, 19 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) CHAPEL HILL -- A study of settlement decisions in workers' compensation claims for low back pain has found almost no relationship between the rating of the disability's severity when the claim was settlement and reported pain and disability 21 months later.

Findings were counterintuitive: Claimants with higher disability ratings, which suggest higher severity and less ability to work, fared better than those with lower ratings.

The study shows that administrative decisions made at the end of the workers' compensation claim process about the ability of someone to work after back injury has very little predictive validity, said Dr. Norton Hadler, a professor of medicine and microbiology/immunology in the University of North Carolina at Chapel Hill's School of Medicine.

Hadler is a co-author of the paper, which was published in the December issue of the Journal of Pain, with colleagues from St. Louis University and the University of Florida. It was based on administrative records in Missouri of workers' compensation claims for low back pain.

Workers' compensation is an important part of America's health-care system, accounting for 3 percent of an employer's gross income, Hadler said.

Clearly, the rating schemes for workers' compensation are inconsistent, and that fact is stirring enormous pots across the country, Hadler said. If the outcomes from Missouri generalize, then there is a need to reform how disability is determined.

Another paradoxical finding showed that white claimants faired no better than blacks, even though previous reviews found that blacks were much less likely than whites to be diagnosed with a herniated disk or to have back surgery, had less money spent on their care and received lower disability ratings and smaller settlements.

It's one of the more perverse observations in our study, said Hadler. African-Americans were much less likely to be operated on, but the care that the whites got, even though it looks like more care, because it's surgery and it's more expensive, didn't do anything for them.

For their study, the researchers interviewed 580 black and 892 white workers' compensation claimants an average of 21 months after claim settlement to assess how well they were functioning and to determine the contribution of impairment, race and socioeconomic status to their disability ratings.

Hadler said that workers' compensation claims for low back pain represent only 20 to 30 percent of all claims filed but consume a majority of the workers' compensation budget.

The article concludes that the pattern of results suggests that race/ethnicity and other sociodemographic factors influence medical decision making and the outcomes of medical care. Furthermore, the flaws in the system are not distributed evenly but are visited disproportionately on minorities and persons of lower socioeconomic status.

Study explains how NSAIDs halt cancer growth

Fri, 15 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) BOSTON -- Scientists have discovered that induction of a gene known as MDA-7/IL-24 is the molecular mechanism that enables nonsteroidal anti-inflammatory drugs (NSAIDs) to halt the growth of cancer cells, a finding that could eventually lead to the development of targeted cancer treatments.

Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with scientists at Columbia University Medical Center, the new findings provide the answer to the long-puzzling question: How does this popular class of pain killers protect people from developing this deadly disease The study appears in the Dec. 15 issue of the journal Cancer Research.

Although observational studies had previously demonstrated that NSAIDs [such as aspirin, ibuprofen and sulindac] might be effective in the prevention and treatment of several common cancers, it wasnt at all clear how this was happening, explains the studys senior author Towia Libermann, PhD, Director of the BIDMC Genomics Center and Associate Professor of Medicine at Harvard Medical School (HMS). Now, after treating a number of different types of cancer cells in culture with a whole set of NSAIDs, we can point to this single gene which, when upregulated, kills cancer cells while sparing normal, healthy cells.

In recent years, a great deal of attention has focused on the link between inflammation and cancer. As the bodys immune response to tissue damage, acute inflammation serves as a natural defense to guard against injury or infection.

However, in cases of chronic inflammation for example, inflammatory bowel disease certain signaling pathways that modulate the inflammatory processes become stuck in an activated state. Among other outcomes, this course of events leads to the release of molecules that enhance carcinogenesis and tumor progression at the site of the damage.

According to Libermann, it was these observations that originally prompted clinical and epidemiological researchers to begin examining whether routine use of anti-inflammatory agents had any effect on a persons risk of developing several types of cancer, including colorectal cancer, breast cancer and ovarian cancer.

Since then, studies have indeed shown that at clinically relevant concentrations, NSAIDs may be effective in the prevention and treatment of common cancers, he says. These anti-cancer effects have been attributed, in large part, to NSAIDs potential to induce cell death, which appears to stem from the drugs inhibition of the COX (cyclooxygenase) enzymes, the primary mechanism by which NSAIDs guard against pain.

However, adds Libermann, COX inhibition did not appear to be the only anti-cancer pathway being targeted by the compounds. We, therefore, undertook a comprehensive review of NSAIDs in order to decipher the precise molecular mechanisms that were at work.

Using whole genome microarray analysis, Libermann and first author Luiz Zerbini, PhD, a researcher in the BIDMC Genomics Center and Instructor of Medicine at HMS, examined more than 20,000 genes to identify potential mechanisms for cell death induction.

When we analyzed the genes that were upregulated by NSAIDS, one in particular stood out from the rest, says Zerbini. And that was MDA-7/IL-24.

A cancer specific cytokine, MDA-7/IL-24 was already familiar to the investigators as a novel tumor suppressor gene, says Libermann. Viral delivery of MDA-7/IL-24 is currently being evaluated in several clinical trials as a therapeutic agent against various cancers, and enhanced levels of the gene have also been correlated with prolonged survival in patients with non-small lung cancer.

Following their identification of this cytokine, the investigators used an interfering RNA approach to block MDA-7/IL-24 gene expression in cancer cells, thereby demonstrating the necessity of NSAID-mediated induction of the gene to destroy cancer cells. They also used a mouse model of prostate cancer to demonstrate that when MDA-7/IL-24 was blocked, the anti-cancer effects of the NSAIDs were diminished.

Finally, building on their earlier work demonstrating the relevance of GADD45 (Growth Arrest DNA Damage) family members to cancer cell death (as well as previous work by study coauthor Paul Fisher, MPh, PhD, of Columbia University Medical Center) Libermann and Zerbini identified GADD45 alpha and gamma as the critical mediators of this course of events, showing that the ability of NSAIDs to induce apoptosis was dependent on their abilities to induce MDA-7/IL-24 expression, leading to enhanced GADD45 alpha and gamma expression.

Current clinical trials are evaluating a range of NSAIDs for a variety of cancers without any clear vision of the best way to use them, notes Libermann. The fact that upregulation of this single gene MDA-7/IL-24 -- correlated not only with cell death induction of numerous types of cancer but also among various diverse classes of NSAIDs, makes this discovery particularly exciting. The level of MDA-7/IL-24 gene expression in cancer patients may emerge as a new biomarker for monitoring patients responses to certain therapies, and may help determine whether drugs such as NSAIDs are hitting their intended targets.

'Best of both worlds' -- Targeting a single gene could inhibit bone decay and stimulate bone growth

Fri, 08 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) (PHILADELPHIA) -- Researchers at the University of Pennsylvanias School of Medicine have found by targeting the function of a single gene that it is possible to inhibit bone decay while simultaneously stimulating bone formation. This concept may lead to drug treatments for osteoporosis and other bone diseases. Senior author Yongwon Choi, PhD, professor of Pathology and Laboratory Medicine at the University of Pennsylvania and colleagues report their findings in the December issue of Nature Medicine.

Osteoporosis is a major quality of life issue for the millions of senior citizens in the United States and will only become a bigger problem as the population continues to age.

The main challenge is how to prevent bone decay while also encouraging bone growth, said Choi.

The basic principles behind bone metabolism are largely understood, hence a handful of drugs treating osteoporosis are available. Most drugs inhibit osteoclasts, which cause bone decay. But there is also at least one that stimulates osteoblasts, enhancing bone formation. A combined treatment will not only prevent the occurrence of osteoporosis, but also make the quality of bone even better.

Our discovery proves that inhibiting osteoclasts while simultaneously stimulating new bone formation can be done.

Bone health is maintained by the balanced activities of osteoblasts and osteoclasts. The study shows that the inactivation of gene Atp6v0d2 in mice results in dramatically increased bone mass due to defective osteoclasts as well as enhanced bone formation. These findings may provide some clarity into the regulation of bone metabolism and show that targeting the function of a single gene could possibly inhibit bone decay while stimulating bone formation.

We have finally proven the theory that targeting one gene can do both, said Choi. Now that we have demonstrated a new approach that is theoretically attainable, one that combines the best of both worlds, we can go to work on the genes up and down stream from our target gene. If we can find a way to get to our target gene with a drug we may be able to help the millions of seniors with osteoporosis.

Dr. Choi was recently named the 2006 winner of Koreas prestigious Ho-Am Prize for his work in osteoimmunology. The award recognizes scholars and researchers who make outstanding achievements by international standards while encouraging future activities of even higher levels and who also present exemplary models for the academic community. Choi, who is originally from Seoul, South Korea, has been at the University of Pennsylvania since 2001.

Origin of inherited pain disorder pinpointed

Wed, 06 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) The genetic basis for a rare inherited disorder that causes severe burning pain with no warning has been pinpointed by researchers. They found that paroxysmal extreme pain disorder (PEPD) is caused by specific mutations in porelike sodium channels in peripheral nerve cellsa discovery that they said emphasizes the role of such channel disorders in inflammatory pain. Such findings of abnormal function in disease also provide insights into the normal function of such channels, they said.

R. Mark Gardiner, of University College London, and his colleagues published their findings in the December 7, 2006, issue of the journal Neuron, published by Cell Press.

So-called voltage-gated sodium channels are central to the neuron's ability to propagate a nerve impulse. In response to voltage changes in a nerve cell caused by a nerve impulse, these channels snap open, allowing sodium to flow across the cell membrane, further propagating the nerve impulse. Rapid, precise activation and inactivation is key to their normal operation.

In their studies, the researchers sought to understand the basis of PEPD, which is characterized by abrupt paroxysms of pain in the rectum, eye, and jaw. They first performed a detailed genetic comparison of affected and unaffected members of one large family that showed inheritance of the disease. That analysis revealed that mutations that compromise the gene for a component of one particular sodium channel, called SCN9A, were the likely culprit. Further analysis of the gene in 11 affected families and two sporadic cases, indeed, revealed that mutations in SCN9A are responsible for the disease in at least two-thirds of PEPD cases.

Analysis of these mutations revealed that they all disrupted the ability of the sodium channel to rapidly snap shut, prolonging activation of the peripheral nerves in which the channels functioned. What's more, the researchers found, the drug carbamazepineknown to be effective in PEPDacts to correct this abnormality in cultures of neurons.

The researchers also compared PEPD with another inherited pain disorder, primary erythermalgia (PE) that is not alleviated by carbamazepine. PE is also caused by mutations in SCN9A and is characterized by pain in the extremities triggered by exercise or temperature change. In contrast to PEPD, which is caused by mutations that disrupt inactivation the sodium channel, PE arises from mutations that lower its activation threshold.

The researchers concluded that their findings further emphasize the critical role of [this sodium channel] in human inflammatory pain and explain the differential drug sensitivity of PEPD and PE.

Low impact aerobic exercise reduces fatigue in auto-immune conditions says multi-study review

Wed, 29 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Low impact aerobic exercise, such as walking and cycling, can effectively reduce fatigue in adults with chronic auto-immune conditions, according to a research review in the latest issue of the UK-based Journal of Advanced Nursing.

A team led by nurse researcher Dr Jane Neill from Flinders University in Adelaide, examined 162 research studies published between 1987 and 2006, analysing 36 in detail.

They discovered that there was evidence that people with conditions like multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus could benefit from exercise that gradually increased in intensity, duration and frequency.

Fatigue is a major symptom in all three conditions and can cause a range of physical, psychological and social problems says Dr Neill.

Our review showed that aerobic exercise can significantly reduce fatigue and that some behavioural, nutritional and physiological interventions are also very effective.

Studies reviewed by the team tested 38 interventions on more than 1,700 patients. 24 resulted in statistically reduced fatigue or increased vitality levels.

The effective aerobic exercise programmes lasted an average of 12 weeks, with participants exercising for 30 to 60 minutes, three times a week.

Group interventions involved supervised exercise classes, including warm up, low impact aerobic activity and strengthening or stretching exercises before cool down.

Home-based programmes made use of exercise bicycles, walking, cycling, jogging or swimming.

There is good evidence that people experiencing fatigue from chronic auto-immune conditions can benefit from a range of non-medicinal interventions concludes Dr Neill.

Other effective strategies, apart from aerobic exercise, include health education and cognitive behavioural therapy.

Cooling techniques and nutritional supplements such as acetyl-L-carnitine and fish oil showed a number of benefits, but need to be looked at in more detail.

The authors suggest electro-magnetic field devices also warrant further investigation, due to promising results.

But they add that low-cost, low technology interventions that promote self-management of fatigue are probably more appropriate and feasible than those requiring specialised equipment or professional expertise.

They stress that any exercise programmes must be suitable for each individual and take account of issues that affect how people manage their conditions, like reduced mobility, pain, nausea and stress.

Healthcare professionals should ask people about their fatigue and assess each persons symptoms adds Dr Neill. People with fatigue should be encouraged to design their own exercise routines based on awareness of their individual fatigue patterns and daily priorities, while group activities must take account of the changing nature of fatigue over time.

Previous research suggests that 70 per cent of people with multiple sclerosis suffer daily fatigue, 57 per cent of people with rheumatoid arthritis experience fatigue and 81 per cent of those with system lupus erythematosus find fatigue moderately to severely disabling.

Any measures that can reduce peoples fatigue and improve their quality of life are to be welcomed. Our review shows that some interventions have great potential, particularly in the short term, but that more research is needed to measure their long-term effectiveness says Dr Neill.

Hypnosis helps women cope with breast biopsy

Wed, 29 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO -- Radiologists are using an unusual approach, hypnosis, to ease patient pain and anxiety during breast biopsy procedures. A new study from Beth Israel Deaconess Medical Center and Harvard Medical School in Boston found that women who were guided into a state of hypnotic relaxation during biopsy experienced less pain and anxiety during the procedure. The study was presented today at the annual meeting of the Radiological Society of North America (RSNA).

Finding a breast lump or receiving abnormal or inconclusive mammogram results can be highly stressful for a woman. Large-core needle biopsy (LCNB) is an effective diagnostic tool. However, most LCNB procedures are performed in outpatient settings, limiting the use of intravenous drugs to reduce pain and anxiety.

Hypnosis can greatly help women cope with the stress of breast biopsy, said Elvira V. Lang, M.D., associate professor of radiology at Harvard. This is a consumer-driven movement. Already we are seeing the beginning of it.

Dr. Lang and colleagues studied 236 women undergoing LCNB at a university-affiliated medical center. The patients were randomly assigned three types of care during the procedure. Seventy-six women received standard care, 82 women received structured empathetic attention with a person specifically assigned to be responsive to their needs, and 78 women induced self-hypnotic relaxation under instruction from a trained research assistant.

The assistant read a standardized hypnotic induction script that, among other things, instructed patients to roll their eyes upwards, close their eyes, breathe deeply, focus on a sensation of floating and invoke a pleasant setting of their choice with all of their senses.

The researchers then compared several factors, including levels of pain and anxiety and procedure time and cost. All of the patients presented with elevated anxiety. Anxiety increased significantly in the standard care group, did not change in the empathy group and decreased significantly in the hypnosis group. All three groups reported pain during the procedure, but the empathy and hypnosis groups reported significantly less pain than the standard care group.

Procedure time and cost did not differ significantly among the groups even though the empathy and hypnosis groups had an additional assistant. The hypnosis group had the shortest procedure time and the lowest cost.

Dr. Lang attributed the shortened procedure time to the decreased level of stress, not only for the patient, but for the treatment team. The relaxation technique serves to calm and focus everyone involved in the procedure, she noted.

The findings show that nonpharmacologic means can be very powerfulwithout side effects, Dr. Lang said. The results extend prior assumptions about mind-body interventions in that self-hypnotic relaxation can be learned very quickly right on the procedure table without additional cost, challenging the notion that extensive office visits or preparation are necessary.

In addition, through the self-hypnotic relaxation coaching of the research assistant, the patients learned a coping tool that they could take with them and use to relieve anxiety through subsequent waits and work-ups.

This research embraces a holistic approach combining high-tech with high-touch that respects the needs of women during the stressful times of breast biopsy, Dr. Lang said. She added that this method has been successfully applied to a number of other interventional procedures.

This study was supported by the U.S. Army Medical Research and Materiel Command and the National Institutes of Health, National Center for Complementary and Alternative Medicine.

Spacer insertion may offer less invasive option for lumbar problems

Tue, 28 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Implanting a small spacer between lumbar vertebrae during a procedure called interspinous process decompression may be an effective and minimally invasive way to treat spinal stenosis, according to a new report.

The report is published by ECRI, an independent nonprofit health services research agency that produces systematic reviews on medical devices, drugs, biotechnologies, procedures, and health services.

Spinal stenosis is a narrowing of the openings in the vertebrae that contain the spinal cord and nerve roots. The condition, usually caused by age-related degeneration of the spinal disks and osteoarthritis of the spine, may pinch the nerves, resulting in pain or cramping in the legs, buttocks or groin that is aggravated by standing or walking.

The position of the spine typically affects the symptoms: leaning forward reduces the pain, while leaning backward makes it worse. Treatment generally starts conservatively, with physical therapy and pain relievers, and can include epidural steroid injections. Severe cases may require surgery to decompress the spinal cord, which can include fusing two or more of the vertebrae together.

Spacer insertion has a potential role as a less costly alternative to conventional operative procedures when conservative treatments have failed or in situations in which patients are unwilling to consider more invasive surgery. One spacer, X Stop, has been approved by the Food and Drug Administration for use in patients age 50 and older with confirmed lumbar spinal stenosis. XStop was the only spacer addressed in the ECRI report; however, other versions of the spacer are under review.

According to the ECRI analysis, only one randomized controlled trial of the procedure has been reported. A total of 191 patients at nine centers were randomly assigned to undergo either the spacer procedure or to be treated nonoperatively. Results from this study suggest that for some patients, the spacer procedure reduces pain, improves function for up to two years, and reduces the need for laminectomy surgery to remove a portion of a disc.

However, this two-year study does not compare the new procedure to other surgical decompressive procedures or treatments for spinal stenosis and does not provide long enough follow-up to determine how long the spacer will last.

The dearth of randomized control trials is not unusual for new and emerging technologies, said Carol Koman, R.N., a senior clinical writer of ECRIs Health Technology Assessment Information Service. The preliminary data available suggest that the procedure may offer an option for patients whose pain has not responded to conservative treatment, and who are not candidates for more invasive spinal surgery.

To perform the procedure, a spine surgeon makes a one- to two-inch incision over the spine and inserts a small titanium spacer between the spinous processes (the bony wings that stick out) of two adjacent vertebrae and screws the spacer into place. The spacer is intended to keep the spine from bending too far backward, thus preventing the nerve pinching that causes pain. Since local anesthesia and intravenous sedation are used for the procedure, it can be done on an outpatient basis or with a 24-hour hospital stay.

Patients who undergo interspinous process decompression do not need to undergo more invasive forms of spinal surgery, said Paul Anderson, M.D., an associate professor of orthopedic surgery and rehabilitation at the University of Wisconsin-Madison School of Medicine and Public Health.

I see it as an alternative to [such] surgery, not a step before surgery. When it works, patients avoid surgery, Anderson said. He performs the procedure about once a month, and said that about 60 percent of his patients improve with it. Anderson is a consultant for and stockholder in St. Francis Medical Technologies, Inc., the maker of X Stop.

Charges for the procedure are estimated at about $23,000; most surgeries require one or two implants, according to the ECRI report. Several major insurers, including Aetna and Cigna, do not cover the spacer implant procedure. However, in October 2006, the Centers for Medicare and Medicaid Services provided a new technology add-on payment of $4,400 for the X Stop implant when performed during a hospital stay.

Chronic back pain linked to changes in the brain

Tue, 28 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO -- A German research team using a specialized imaging technique revealed that individuals suffering from chronic low back pain also had microstructural changes in their brains. The findings were presented today at the annual meeting of the Radiological Society of North America (RSNA).

The researchers, led by Jürgen Lutz, M.D., a radiology resident at University Hospital, Ludwig-Maximilians University in Munich, Germany, used a technique called diffusion tensor imaging (DTI) to track the movement of water molecules in the brains gray and white matter.

A major problem for patients with chronic pain is making their condition believable to doctors, relatives and insurance carriers. DTI could play an important role in this regard, Dr. Lutz said. With these objective and reproducible correlates in brain imaging, chronic pain may no longer be a subjective experience. For pain diagnosis and treatment, the consequences could be enormous.

Individual water molecules are constantly in motion, colliding with each other and other nearby molecules, causing them to spread out, or diffuse. DTI allows scientists to analyze water diffusion in the tissues of the brain that indicate changes in brain cell organization.

In normal white matter, water diffuses in one main direction, Dr. Lutz explained. But when fiber pathways are developing during childhood or are extensively used, their microstructural organization becomes more organized and complex with measurable changes in diffusion.

Dr. Lutz and colleagues studied 20 patients experiencing chronic back pain with no precisely identifiable cause and 20 age- and gender-matched healthy control patients. DTI was performed to measure the diffusion in several areas of each patients brain.

Compared to the healthy volunteers, the patients with chronic low back pain had a significantly more directed diffusion in the three pain-processing regions of the brain, including the cingulate gyrus, postcentral gyrus and superior frontal gyrus.

Our results reveal that in chronic pain sufferers, the organization of cerebral microstructure is much more complex and active in the areas of the brain involved in pain processing, emotion and the stress response, said co-author Gustav Schelling, M.D., Ph.D. from the Department of Anaesthesiology at Munich University.

The researchers said the findings may help explain the extreme resistance to treatment for chronic low back pain and provide much-needed evidence for individual sufferers. However, it is unclear which occurs first, the chronic back pain or the microstructural changes in the brain.

Its difficult to know whether these are pre-existing changes in the brain that predispose an individual to developing chronic pain, whether ongoing pain creates the hyperactivity that actually changes the brain organization, or if it is some mixture of both, Dr. Schelling said. DTI may help explain whats happening for some of these patients, and direct therapeutic attention from the spine to the brain, he added.

Aching back? Sitting up straight could be the culprit

Mon, 27 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO -- Researchers are using a new form of magnetic resonance imaging (MRI) to show that sitting in an upright position places unnecessary strain on your back, leading to potentially chronic pain problems if you spend long hours sitting. The study, conducted at Woodend Hospital in Aberdeen, Scotland, was presented today at the annual meeting of the Radiological Society of North America (RSNA).

A 135-degree body-thigh sitting posture was demonstrated to be the best biomechanical sitting position, as opposed to a 90-degree posture, which most people consider normal, said Waseem Amir Bashir, M.B.Ch.B., F.R.C.R., author and clinical fellow in the Department of Radiology and Diagnostic Imaging at the University of Alberta Hospital, Canada. Sitting in a sound anatomic position is essential, since the strain put on the spine and its associated ligaments over time can lead to pain, deformity and chronic illness.

Back pain is the most common cause of work-related disability in the United States, and a leading contributor to job-related absenteeism, according to the National Institute of Neurological Disorders and Stroke. By identifying bad seating postures and allowing people to take preventative measures to protect the spine, Dr. Bashir and colleagues hope to reduce back strain and subsequent missed work days.

We were not created to sit down for long hours, but somehow modern life requires the vast majority of the global population to work in a seated position, Dr. Bashir said. This made our search for the optimal sitting position all the more important.The researchers studied 22 healthy volunteers with no history of back pain or surgery. A positional MRI machine was used, which allows patients freedom of motionsuch as sitting or standingduring imaging. Traditional scanners have required patients to lie flat, which may mask causes of pain that stem from different movements or postures.

The patients assumed three different sitting positions: a slouching position, in which the body is hunched forward (e.g., hunched over a desk or slouched over in front of a video game console); an upright 90-degree sitting position; and a relaxed position where the patient reclines backward 135 degrees while the feet remain on the floor. Measurements were taken of spinal angles and spinal disk height and movement across the different positions.

Spinal disk movement occurs when weight-bearing strain is placed on the spine, causing the internal disk material to misalign. Disk movement was most pronounced with a 90-degree upright sitting posture. It was least pronounced with the 135-degree posture, indicating that less strain is placed on the spinal disks and associated muscles and tendons in a more relaxed sitting position.

The slouch position revealed a reduction in spinal disk height, signifying a high rate of wear and tear on the lowest two spinal levels. Across all measurements, the researchers concluded that the 135-degree position fared the best.As a result, Dr. Bashir and colleagues advise patients to stave off future back problems by correcting their sitting posture and finding a chair that allows them to sit in an optimal position of 135 degrees.

This may be all that is necessary to prevent back pain, rather than trying to cure pain that has occurred over the long term due to bad postures, he added. Employers could also reduce problems by providing their staff with more appropriate seating, thereby saving on the cost of lost work hours.

Enbrel first biologic with up to 9 years rheumatoid arthritis safety, sustained efficacy data

Mon, 13 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) THOUSAND OAKS, Calif., November 12, 2006 -- Amgen (NASDAQ: AMGN) today announced that Enbrel? (etanercept) is the first biologic with published data to show improvements in multiple measures of efficacy that were sustained in rheumatoid arthritis (RA) patients completing up to nine years of therapy. These new data are being presented at the American College of Rheumatology (ACR) Scientific Meeting in Washington, D.C.

The current data in Rheumatoid Arthritis suggest that Enbrel is both effective and safe in long-term use, said Mark Genovese, M.D., Stanford University Medical Center, Palo Alto, California. These findings are significant because they provide a degree of reassurance to both the patient and the physician that unexpected safety concerns do not appear to be developing after nine years of use.

ENBREL continues to have a strong safety profile for extended periods of use. In the studies presented at ACR, rates of serious adverse events and serious infections remained low and were consistent with controlled portions from the double-blind phases of the studies. The overall number of observed malignancies (excluding nonmelanoma skin cancers) were similar in type and number to what would be expected in the general population.

Additionally, data showed that 77 early rheumatoid arthritis (ERA) and 280 long-standing rheumatoid arthritis (LRA) patients who completed ENBREL treatment for up to eight years experienced substantial improvements in their ACR scores. Additionally, 73 LRA patients who completed ENBREL treatment for up to nine years experienced similar improvements. ACR scores are a composite measure of improvement in RA symptoms, including joint swelling and tenderness, pain, level of disability, overall patient and physician assessment, and an objective marker of inflammation, such as erythrocyte sedimentation rate.

Data being presented at ACR showed that ENBREL provided sustained improvement in the signs and symptoms of RA, in those patients who continued in the study, regardless of duration of disease. Following eight years of ENBREL therapy: 75 percent of ERA patients and 76 percent of LRA patients achieved ACR 20; 60 percent of ERA patients and 52 percent of LRA patients achieved ACR 50; 35 percent of ERA patients and 26 percent of LRA patients achieved ACR 70. Further, for those patients with LRA who received ENBREL treatment for nine years, 74 percent achieved ACR 20, 41 percent achieved ACR 50, and 22 percent achieved ACR 70.

The ability to perform daily activities is an important goal for many people with RA, and data presented at ACR showed that treatment with ENBREL may help them achieve this goal. Through eight years of treatment with ENBREL, data showed that 73 to 85 percent of patients with ERA and 53 to 72 percent of patients with LRA achieved a clinically significant improvement in the Health Assessment Questionnaire (HAQ) score, a patient questionnaire that measures disability. A clinically significant improvement in HAQ was defined as at least a 0.22 improvement from baseline.

Before I was diagnosed with RA, the pain, stiffness and fatigue stopped me from doing many of the activities I enjoyed, said Gloria Treece, a participant in the study. Since starting ENBREL treatment approximately nine years ago, I'm now able to take part in many activities with my family.

These studies were designed to assess the safety and long-term efficacy of ENBREL in adult LRA patients who have failed to respond to at least one disease-modifying antirheumatic drug, and adult patients with ERA (defined as less than or equal to three years of disease duration). Patients with RA who participated in controlled clinical trials of ENBREL were eligible to enroll in open-label extension studies (LRA, N=644; ERA, N=207).

Antioxidants: New kid on the block for pain relief?

Tue, 07 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio -- Antioxidant-based pain killers may one day become a viable alternative to addictive medications such as morphine.

Researchers found that synthetic antioxidants practically eradicated pain-like behavior in nearly three-quarters of mice with inflamed hind paws.

When it comes to pain killers, there aren't many choices between over-the-counter pain relievers like ibuprofen and aspirin and prescription opiates like morphine, said Robert Stephens, a professor of physiology and cell biology at Ohio State University. He's the lead author of a study examining the effects of antioxidants as pain killers.

We need drugs that fall somewhere between these two extremes, Stephens said. Someone suffering from chronic pain can become dependent on, or even addicted to, heavy-duty pain killers like morphine.

The study appears in a recent issue of the journal Behavioural Brain Research.

Chronic pain is such a formidable problem that, in 2000, Congress passed a bill designating January 1, 2001 as the beginning of the Decade of Pain Control and Research.

Antioxidants neutralize free radicals, substances that damage cells. While our bodies constantly produce free radicals, healthy tissues inactivate these damaging substances and keep their levels in check. It's when free-radical production somehow exceeds the body's natural defenses that problems occur. Researchers have linked this excessive production to diseases like cancer and Alzheimer's.

A handful of studies published in the last 10 years suggest that free radicals may also contribute to chronic pain. Left unchecked, free radicals build up in the body and can further damage already-injured tissue.

An equally small number of studies, including those by Stephens, suggest that antioxidants may fight chronic pain by helping the body to break down free radicals.

Studying the pain-killing effects of antioxidants is an emerging area of research, Stephens said. The FDA hasn't approved antioxidants for the treatment of chronic pain. But down the road we may see some drugs that contain antioxidants.

Stephens and his colleagues first injected one of three different synthetic antioxidants into mice. An additional group of control mice received only saline. The antioxidants used in this study PBN (phenyl-N-tert-butylnitrone), TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxy) and NAC (N-acetyl-L-cysteine) aren't the same as those found in fruits and vegetables, and two, PBM and TEMPOL, are currently only available for scientific purposes. NAC is available as a dietary supplement.

Right now we're trying to show that antioxidants are viable pain killers, Stephens said. Similar work by other researchers suggested that these antioxidants were the best available. And while certain foods likely contain pain-killing antioxidants, these agents have not been systematically tested as pain relievers.

Shortly after the antioxidant or saline injections, the researchers injected formalin, an irritant, into the left hind paw of each mouse. Formalin causes inflammation, which provokes pain-like behavior in mice. Researchers then spent the next 30 minutes studying how much time an animal spent licking and biting its injured paw. This kind of behavior suggests that the animal is in pain or discomfort.

The researchers divided the 30-minute observation session into three distinct periods a five-minute acute phase, when the body first senses and reacts to pain, followed by a 5- to 15-minute period of relative stillness, as the body uses its own mechanisms to try to inhibit the pain, and ending with a 15- to 30-minute period called the tonic phase, during which a mouse starts to again vigorously lick or bite its irritated paw, suggesting that it still feels pain or discomfort.

The three antioxidants significantly reduced the amount of time that mice spent biting and licking their injured paw during both the acute and tonic phases. The researchers reported a 70- to 90-percent reduction in pain-related behaviors during the acute phase, and a 78- to 98-percent reduction in such behavior during the tonic phase.

We were surprised to see such a major decrease in pain in the mice, particularly during the acute phase, Stephens said. The antioxidants seem to preempt pain-like behavior.

Other investigators have given antioxidants to rodents after experimentally inducing pain and have found that the drugs relieve pain to a similar extent.