Researchers have found that a gene region known to play a role in some varieties of adult rheumatoid arthritis is also present in all types of childhood arthritis. The researchers say the responsible gene may be a "master switch" that helps turn on the debilitating disease.

Researchers at The Children's Hospital of Philadelphia reported on the link between the gene region and juvenile idiopathic arthritis (JIA), formerly called juvenile rheumatoid arthritis. The genetic variant is on chromosome 9 in a region housing two genes, TRAF1 and C5. The TRAF1 gene codes for a protein that regulates tumor necrosis factor, a chemical strongly associated with JIA. However, the researchers say further study is needed to determine whether the TRAF1 gene or the C5 gene is altered in the disease.

The study, which appears in the July 2008 issue of Arthritis & Rheumatism, compared 67 Caucasian patients being treated for JIA to 1,952 healthy Caucasian control subjects recruited within the hospital's patient network. While the cause of JIA is unknown, results from this study back up past research that shows arthritis arises in a genetically susceptible individual due to environmental factors.

"There are only a few genes that may act as master switches like this to regulate autoimmune diseases," said Terri H. Finkel, MD, lead author and chief of Rheumatology at Children's Hospital. "This switch we discovered probably has to be an 'ON' gene and when it interacts with other genes and environmental triggers, a child may get juvenile arthritis."

Further research is needed to determine whether the TRAF1 gene or the C5 gene is altered in the disease. 7/2/08

Humira Improves Remission in Crohn’s Disease

An open-label extension study of two large Crohn’s Disease studies – Crohn's trial of the fully Human antibody Adalimumab for Remission Maintenance( CHARM) and Gauging Adalimumab effectiveness in Infliximab Nonresponders (GAIN) – show that patients with moderate-to-severe Crohn's disease who are treated with adalimumab (Humira) achieved a full clinical response and long-term clinical remission.

Patients from CHARM and GAIN were followed through into a non-placebo controlled, ongoing open-label extension trial. Patients from CHARM were followed a total of two years, and patients from the 4-week GAIN study were followed a total of one year.

In the CHARM extension, data demonstrated that three out of four patients (77 percent) taking Humira, who were in remission at the end of the one-year pivotal study, maintained clinical remission for an additional year. The GAIN data showed that, of patients with a clinical response at four weeks, approximately 65 percent remained in clinical response at one year, and 40 percent were in clinical remission at one year.

"Crohn's disease is a life-long condition with no known cure. One of the goals of treatment is to induce and maintain remission, which can help patients with their chronic symptoms," said Remo Panaccione, M.D., Associate Professor, and Director of the Inflammatory Bowel Disease Clinic at the University of Calgary. "In this study, many patients taking Humira during a lengthened treatment period showed clinical response and remission, which translates into improvement of disease symptoms." 5/23/08

New Treatment for Irritable Bowel Approved

Many people with the bloating, cramping, abdominal pain and constipation associated with irritable bowel syndrome (IBS) may soon find relief in the newly approved IBS drug lubiprostone (Amitiza).

In clinical trials leading up to the drug’s FDA approval, University of Michigan Health System researchers found that individuals who were treated with Amitiza were nearly twice as likely to experience improvement in their IBS symptoms compared to individuals who were treated with placebo, says lead author William D. Chey, MD. “Right now, it is the only FDA-approved treatment available that addresses the entire clinical spectrum of symptoms related to IBS [with constipation],” he says.

IBS, an often painful disorder of the lower intestine, affects between 10 to 15 percent of the U.S. population, mostly women. Most patients with IBS tend to fall into two categories: IBS with constipation (IBS-C) or IBS with diarrhea (IBS-D). IBS-C is more common among older adults, while IBS-D tends to be seen more in younger patients.

Amitiza is currently approved only for women, simply because the majority of patients with IBS – and, therefore, the majority of study subjects – are women. But that doesn’t mean the drug doesn’t work for men, says Dr. Chey. “Unfortunately, we just haven’t had enough men represented in these studies to make a firm decision on treatment using this drug,” 5/19/08

Antidepressants May Be Effective Against Inflammatory Bowel Disease

Theories abound about the cause of inflammatory bowel disease – an umbrella term for a group of disorders characterized by inflammation of the digestive system accompanied by abdominal cramps, diarrhea and bleeding from the intestines. New research, appearing in today’s online edition of The Journal of Clinical Investigation, suggests that for some people the cause may be depression and, for those people, antidepressant medications may be effective therapy.

"The gut is intimately connected to the brain, more than any other organ in the body. In fact, the gut contains more nerves than the spinal cord," said Jean-Eric Ghia, lead researcher and a post-doctoral fellow in McMaster University's Intestinal Disease Research Program.

Ghia and his colleagues evaluated mice which had been induced with depressive-like behaviors, then continued to follow them after the animals had been given anti-depressants. The experiment illustrated how the nervous system influences inflammation in the gut.

"Our study shows that depression increases susceptibility to inflammation, and anti-depressant therapies improve not only the depression but also the inflammation in the gut," he said.

The researchers also demonstrated that the vagus nerve - which starts in the brain stem and extends to the gastrointestinal tract - protects against inflammation by releasing nicotine. "In the absence of this nerve, the anti-depressant therapy does not improve inflammation in the gut, suggesting that this nerve is a major link between the brain and the gut," Ghia said.

For patients, he said the findings are significant: They illustrate the close relationship between depression and IBD and indicate selected depressed patients might benefit from novel treatment strategies, such as anti-depressants, the use of highly selective nicotinic stimulant (nicotinic receptors are found in the autonomic nervous system) or nerve stimulation. 5/7/08

Large Study Suggests New Genetic Markers For Crohn's Disease

A large multi-center study, published in the journal Genes and Immunity, has suggested new genetic links to Crohn’s disease as well as further evidence that some people of Jewish descent are more likely to develop it. The study, believed to be the largest of its kind for the genetic roots of inflammatory bowel diseases (IBD), included genetic information from 993 families with IBD, 244 of whom were Ashkenazi Jews

By analyzing common DNA variations known as single nucleotide polymorphisms, or SNPs, the team found evidence for genes causing familial Crohn's disease in the study population specific to Ashkenazi Jewish families with Crohn’s on previously identified areas of chromosomes 1 and 3. They also identified a never-before-identified region of chromosome 13 that was shared by both Jewish and non-Jewish families with the disease. Evidence for chromosomal regions that may be linked to UC on chromosome 2 and 19 for Jewish and non-Jewish families was also noted, according to Steven R. Brant, MD, senior author of the study.

Up to now, Dr. Brant says, no gene regions implicated in IBD were specific to Ashkenazi families, and genetic evidence pointing to why Ashkenazi Jews were more likely to get the disorder was lacking. The two genetic regions identified on chromosomes 1 and 3 were specific to Ashkenazi Crohn’s and unrelated to known IBD genes.

Although further study is needed to narrow down which specific genes are the major players, Dr. Brant says it's already clear that they are in the right "neighborhood" to search for IBD/Crohn’s disease susceptibility genes. 3/31/08

Vaccination Could Treat Hypertension

New research suggests that immunization against angiotensin II – a hormone secreted by the body that causes the muscular walls of the blood vessel to contract – could provide an alternative treatment for high blood pressure.

Although blocking the hormone by daily oral medication is effective for many people, others who could benefit don’t because they fail to take the medication or stop taking it due to adverse side effects. Researchers at Cytos Biotechnology, Schlieren, Switzerland, reporting in The Lancet believe a series of three injections given every four months could circumvent these problems and keep blood pressure under control.

In a study of 72 people with mild to moderate high blood pressure, the researchers gave 48 patients one of two doses of the angiotension II vaccine and the remaining 24 a placebo shot.

Two weeks after the third vaccination, participants receiving the higher vaccine dose showed significant reductions in both systolic and diastolic blood pressure compared to the placebo group – particularly in the early-morning hours when the risk of stroke is the greatest.

The research say further studies are needed before such a vaccination could be made available to patients. 3/24/08

Humira Helps Fistuas in Crohn’s Disease

Newly released results of an 854-patient study of adalimumab (Humira) show the agent is effective for the continued healing of fistulas in Crohn’s disease. Fistulas are ulcers that form tunnels between the intestine and other parts of the body. One of the most painful complications of Crohn’s disease, they can be difficult to treat, often requiring invasive surgery.

In the 56-week, Phase III CHARM trial patients were followed through a second year of Humira therapy in a non-placebo-controlled, ongoing open-label extension trial. Results showed:

* Fistula healing was sustained with Humira treatment. More than half of patients (60 percent) experienced fistula healing at one year with Humira treatment, and 76 percent had continued fistula healing one more year.

* Seventy-one percent had at least a 50 percent reduction in the number of fistulas after treatment with Humira.

* Adverse event rates among patients with fistulas were consistent with those seen in previous trials of Humira in rheumatoid arthritis and Crohn's disease.

* More than half had a high quality-of-life score that correlates to clinical remission over two years.

"Humira’s ability to heal, and keep healed, a majority of fistulas among patients studied reinforces that Humira is an effective and convenient treatment option for severe and active Crohn's disease," says Rebecca Hoffman, MD, divisional vice president, Humira clinical development at Abbott. 3/19/08

Ankylosing Spondylitis Genes Found

A collaboration between U.S. and Australian researchers has led to the discovery of two genes – ARTS1 and IL23R – responsible for ankylosing spondylitis (AS). The discovery – based on work from the largest and most comprehensive genome-wide association scan conducted to date – brings the scientific community closer to fully understanding the disease, say the researchers.

The IL23R gene plays a role in the immune system's response to infection. ARTS1 is involved in processing infectious agents into "bite-size chunks" that can be seen – and fought – by the body's immune system.

Earlier research in twins showed the cause of AS is more than 90 percent genetic. In 1973, a powerful predisposing gene called HLA-B27 was discovered. With the new finding, a large proportion of the genetic risk for AS has now been identified.

Researchers say the new genes, along with HLA-B27, could help physicians identify people at highest risk for AS. The location of the genes and the fact they don't coincide with those of autoimmune diseases, such as rheumatoid arthritis, lupus or juvenile diabetes, helps refute the long-held notion that AS is an autoimmune disease, say the researchers. Rather, AS may actually be an unusual response to infection.

The research, funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, was published in Nature Genetics. 3/14/08

Scientists Test Leukemia Drug for Scleroderma

Physicians at thee U.S. medical centers are studying the effects of the anti-cancer drug imatinib mesylate (Gleevec) to treat patients with scleroderma. The study is the first of its kind to examine whether the drug, which is commonly used to treat leukemia, will treat the skin thickness in scleroderma patients by blocking the pathway that causes the overgrowth of fibrous tissue which characterizes the disease. Patients enrolled in the clinical trial will receive daily oral doses of Gleevec for six months and will be evaluated initially on a weekly basis.

"Based on recent research performed by investigators at the Feinberg School [of Medicine], Gleevec shows potential efficacy in reducing the abnormal skin changes associated with scleroderma," says John Varga, MD, of Northwestern University’s Feinberg School and principal investigator of the study.

“We hope that the use of Gleevec for a sustained period of time will decrease the symptoms of skin hardening, and potentially slow the progression of this devastating disease," says Dr. Varga. 3/10/08

Discovery May Lead to New Treatments for Macular Degeneration

Scientists have won a major battle in the fight against age-related macular degeneration (AMD), a blinding eye disease that affects millions of people. An international team, led by researchers at Sainte-Justine Hospital and the Université de Montréal, has identified the deficient receptor that causes the dry form of AMD.

In the February edition of the medical journal PLoS Medicine, the researchers explain how a deficiency of a receptor for CD36 – a protein that facilitates the update of fatty acids – prevents the evacuation of oxidized lipids in the eye. Those oxidized lipids in turn accumulate and attack the layers beneath and over the retina – thereby causing vision loss.

“Our discovery has important implications for the development of new therapies,” explains lead researcher, Sylvain Chemtob, MD, PhD, one of the paper’s authors. Dr. Chemtob used mice and rat models to pinpoint the scavenger receptor responsible for retinal degeneration typical of dry AMD. “We found that a deficiency in CD36 receptors leads to significant and progressive age-related macular degeneration,” he says. “CD36 deficiency leads to central vision loss – a key feature of dry AMD.”

The authors says the discovery bring them a step closer to treating dry AMD, which could significantly improve the quality of life of seniors who are most affected by this eye disease. 2/25/08

Restless Legs Syndrome Doubles Risk of Stroke and Heart Disease

People with restless legs syndrome (RLS) are twice as likely to have a stroke or heart disease compared to people without RLS, and the risk is greatest in those with the most frequent and severe symptoms, according the largest study of its kind.

The study involved 3,433 men and women enrolled in the Sleep Heart Health Study, a large prospective cohort study of adults age 40 and older designed to investigate obstructive sleep apnea and other sleep-disordered breathing as risk factors for the development of cardiovascular disease. Participants were diagnosed with RLS by detailed questionnaire and asked if they had been diagnosed with a variety of systemic diseases including cardiovascular disease and cerebrovascular disease. Of the participants, nearly seven percent of women and three percent of men had RLS.

RLS is a neurological condition that is characterized by the irresistible urge to move the legs, particularly when at rest. Although the relationship is unclear, RLS is often associated with fibromyalgia and some other forms of arthritis and related conditions.

The new study does not show that RLS causes cardiovascular and cerebrovascular disease, but a number of potential mechanics for such a process exist, says study author John W. Winkelman, MD, PhD, with Harvard Medical School. “In particular, most people with RLS have as many as 200 to 300 periodic leg movements per night of sleep and these leg movements are associated with substantial acute increases in both blood pressure and heart rate, which may, over the long term, produce cardiovascular or cerebrovascular disease.”

Dr. Winkelman says there are limitations to the study, including that the diagnosis of RLS was self-reported by questionnaire rather than by clinical interview. The study was published in the Jan. 1 issue of Neurology.

Bacteria in Cows' Milk May Cause Crohn's Disease

British researchers have found evidence implicating bacteria in cow’s milk in the development of Crohn’s disease, a chronic inflammatory condition of the intestine which, in about 25 percent of cases, is accompanied by arthritis affecting the joints of the arms, legs and/or spine.

The bacterium, called Mycobacterium paratuberculosis, releases a molecule that prevents white blood cells called macrophages from killing E. coli found in the body, the researchers found. E. coli is known to be present in increased numbers in tissues affected by Crohn’s disease.

In cattle, the bacterium can cause an illness called Johne's disease – a condition of diarrhea and wasting. Until now, however, it has been unclear how this bacterium could trigger intestinal inflammation in humans.

The researchers are now beginning clinical trials to assess whether an antibiotic combination can be used to target the bacteria contained in white blood cells as a possible treatment for Crohn's disease.

The study is published in the journal Gastroenterology. 12/12/07

High Blood Pressure Associated with Risk for Mild Cognitive Impairment

High blood pressure appears to be associated with an increased risk for mild cognitive impairment – a condition that involves difficulties with thinking and learning and is considered a precursor to Alzheimer’s disease – according to a report in the December issue of Archives of Neurology.

Researchers at the Columbia University Medical Center in New York followed 918 Medicare recipients 65 older without mild cognitive impairment beginning in 1992 through 1994. All participants underwent an initial interview and physical examination, along with tests of cognitive function, and then were examined again approximately every 18 months for an average of 4.7 years. Individuals with mild cognitive impairment had low cognitive scores and a memory complaint, but could still perform daily activities and did not receive a dementia diagnosis.

Over the follow-up period, 334 individuals – more than a third of those followed – developed mild cognitive impairment. Hypertension was associated with increased risk.

The study’s authors can’t explain exactly how blood pressure affects the risk of cognitive impairment but believe it may be through disease of the blood vessels in the brain, a blood-brain barrier dysfunction or shared risk factors. 12/12/07

Fast-Acting Carbs May Hasten Vision Loss Over Time

A diet high in fast-acting carbohydrates could potentially lead to loss of central vision, one of the first signs of age-related macular degeneration (AMD), according to a study published in the American Journal of Clinical Nutrition. AMD is one of the leading causes of blindness among the elderly.

Researchers made the connection between fast-acting carbs and central vision loss in an analysis of dietary intake and other data from more than 4,000 men and women age 55 to 80 participating in the Age-Related Eye Disease Study (AREDS). Fast-acting carbs are ones which are quickly digested and absorbed, resulting in a rapid rise in blood sugar levels. Examples are white bread, rice, potatoes and pasta, sugars and corn syrups.

Because there is no known cure for AMD, it important to modify risk factors for its development, say the researchers. While it's too soon to recommend dietary “slow carbs” as a preventive strategy for AMD, replacing fast carbs with whole-grain versions of bread, rice and pasta may soon prove to be an early dietary intervention to slow its progression. 12/3/07

Lacking Bacterial Sensor in Gut May Lead to Inflammatory Bowel Disease

New research in mice supports the hypothesis that defects in the innate immune system might underlie some cases of inflammatory bowel disease – a group of disorders characterized by inflammation in the intestine.

In the study, mice lacking a protein known as TLR5 – which senses the bacterial protein flagellin and initiates an inflammatory response – were found to spontaneously develop inflammation of the colon (colitis), whereas normal mice did not spontaneously develop colitis.

Just prior to the onset of colitis, increased numbers of bacteria were detected in the colon, as were very high levels of proinflammatory mediators, which was surprising given that TLR5-deficient mice lack an immune sensor of bacterial flagellin.

This finding, reported in the November issue of the Journal of Clinical Investigation indicate that a deficiency in an immune sensor of bacteria can lead to an increased inflammatory response in the intestine of mice. 11/19/07

Researchers Develop New Method to Diagnose Pulmonary Hypertension

Researchers at the University of Granada have found a developed a noninvasive system for diagnosing pulmonary hypertension, a potentially deadly complication of scleroderma characterized by increased pressure in the pulmonary artery, which carries blood from the from the heart to the lungs where it picks up oxygen. Using ultrasound to measure systolic pressure – the pressure when the heart is contracting – the system enables doctors to make the earliest diagnosis of pulmonary hypertension possible so that they can plan treatment accordingly.

In a study of 41 people with scleroderma, researchers at the university maintained detailed medical records on each patient, including data from blood and respiratory tests. They then performed an echocardiogram on all patients while they were resting and after physical effort on a special bicycle called at bicycle ergometer. From the results of the study, they concluded that there is a group of patients who experience a serious increase of pulmonary artery systolic pressure when exercising and therefore face risks from this serious complication.

Until now, the only way of identifying pulmonary hypertension was to perform a cardiac catheterization, which involves inserting a hollow flexible tube through the jugular vein and saking it directly into the right side of the heart. The technique is not advisable for all patients because of its complexity and risk, the authors say. 11/14/07

Chocolate Provides Sweet Relief for Chronic Fatigue Syndrome Symptoms

If you suffer from chronic fatigue syndrome (CFS), you may find the relief from symptoms in a box of chocolates – at least in the dark variety. A UK study on patients with CFS found that their symptoms were alleviated when they consumed dark chocolate, much more so than when they consumed milk chocolate that had brown dye added to it.

According to the scientists from Hull York Medical School who carried out the study, it is possible that chemicals called polyphenols in dark chocolate boosts levels of serotonin in the brain.

While comparing the symptoms in patients eating 45 grams of milk chocolate (approximately 1 ½ ounces) to those eating 45 grams of dark chocolate (chocolate with high cocoa content and no milk added), it became clear to the researchers that consuming the high-cocoa content dark chocolate were experiencing a significant alleviation of their chronic fatigue symptoms. Two of the patients, who had been off work for six months, managed to get back to work.

Although the study is preliminary, the authors say it couldn’t hurt for CFS patients to consume moderate amounts of dark chocolate. 10/1/07

Staining Technique Diagnoses Dry Eyes

Dry eye syndrome is one of the most common eye problems, affecting an estimated 10 million to 14 million Americans. For some of them, burning, dry, gritty eyes may be little more than a nuisance caused by environmental factor such as pollution. For others, dry eyes signal an autoimmune disease such as rheumatoid arthritis or lupus or a potentially vision-robbing problem. A new test can help doctors tell the difference.

By using a special stain, called lissamine green, which adheres to damaged cells in the eyes, researchers at the University of Texas Southwestern Medical Center at Dallas have found that the severity of the dry-eye condition in patients correlated with where the stain patterns show up. A few properly placed drops can reveal staining patterns that are key to diagnosing dry eye syndrome earlier than other methods, report researchers in the July issue of the journal Eye and Contact Lens. Earlier diagnosis is crucial in giving doctor more treatment options and preventing the disease from getting worse, they say. 8/20/07