January 21, 2008, 8:06 PM CT

A new view of drugs used to treat rheumatoid arthritis

Powerful drugs used to treat patients with rheumatoid arthritis have a profound, previously unrecognized effect on the immune system, breaking up molecular training camps for rogue cells that play an increasingly recognized role in autoimmune diseases like rheumatoid arthritis and lupus.

A team of physicians and researchers at the University of Rochester Medical Center reports that drugs known as anti-TNF compounds which include drugs such as Enbrel, Humira and Remicade affect our B cells, which play a role in a number of autoimmune diseases.

As per a research findings reported in the cutting-edge section of the Jan. 15 issue of the Journal of Immunology, the team observed that anti-TNF compounds help eliminate abnormal B cell activity in patients, raising the possibility that the drugs improve the health of patients in a way no one has realized before.

The most important considerations for any drug are: Is it safe, and does it work? said Ignacio Sanz, M.D., professor of Medicine, Microbiology and Immunology, and one of two rheumatologists leading the research. The answer is certainly yes to both questions for these anti-TNF compounds. The drugs have revolutionized the therapy of patients with rheumatoid arthritis. But it also turns out that, even though millions of patients have been treated with these medications, we really havent understood to a significant degree how they actually work......... Posted by: Mark      Read more         Source

January 2, 2008, 10:39 PM CT

Osteoarthritis and index to ring finger length ratio

Index to ring finger length ratio (2D:4D) is a trait known for its sexual differences. Men typically have shorter second than fourth digits; in women, these fingers tend to be about equal in length. Smaller 2D:4D ratios have intriguing hormonal connections, including higher prenatal testosterone levels, lower estrogen concentrations, and higher sperm counts. Reduction in this ratio has also been associated with athletic and sexual prowess. Whether this trait affects the risk of osteoarthritis (OA), a progressive joint disease linked to both physical activity and estrogen deficiency, has not been examined. Until recently.

Scientists with the University of Nottingham in the United Kingdom conducted a case-control study to assess the relationship between the 2D: 4D ratio and the risk of knee and hip OA. Their findings, featured in the January 2008 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), suggest that having unusually long ring fingers raises the risk for developing OA of the knee, independent of other risk factors and especially among women.

For the study, 2,049 case subjects were recruited from hospital orthopedic surgery lists and a rheumatology clinic in Nottingham. All had clinically significant symptomatic OA of the knees or hips, requiring consideration of joint replacement surgery. Recruited from hospital lists of patients who had undergone intravenous urography (IVU) within the past five years, 1,123 individuals with no radiographic evidence of hip or knee OA, no present hip or knee symptoms, and no history of joint disease or joint surgery served as controls. The study population was comprised of both men and women, with an average age of roughly 67 years for cases and 63 years for controls......... Posted by: Mark      Read more         Source

November 26, 2007, 3:55 PM CT

Link Between Obesity, Poor Bone Health

Being overweight is a known risk factor for heart disease, diabetes and a host of other health conditions. Now, a University of Georgia study reported in the recent issue of the American Journal of Clinical Nutrition finds that obesity may also be bad for bone health.

Scientists conducted advanced three-dimensional bone scans on 115 women ages 18 and 19 with normal (less than 32 percent) and high (greater than 32 percent) body fat. After adjusting for differences in muscle mass surrounding the bone, the scientists observed that the bones of participants with high body fat were 8 to 9 percent weaker than those of normal body fat participants.

"Obesity is an epidemic in this country, and I think this study is critical because it highlights another potential negative health effect that people haven't considered," said co-author of study Richard D. Lewis, professor of foods and nutrition at the UGA College of Family and Consumer Sciences.

Prior studies on bone health and obesity used a two-dimensional bone densitometer that is usually used in osteoporosis screenings. Lewis explained that a notable shortcoming of the bone densitometer is that it does not take into account bone shape and geometry, which have a substantial influence on bone strength. The new study used a three-dimensional imaging technique that measures both the amount of mineral in the bone and its shape and geometry. The study observed that, surprisingly, normal- and high body-fat young adult females have comparable bone strength in a direct comparison that does not account for muscle mass......... Posted by: JoAnn      Read more         Source

November 18, 2007, 9:00 PM CT

Geisinger rheumatologists redesign rheumatoid arthritis care

With the nation collectively spending about $18 billion per year on osteoporosis related bone fractures, Geisinger scientists observed that streamlining the ordering process for osteoporosis bone density scans quadrupled the number of patients who received the exam.

An estimated 10 million Americans suffer from osteoporosis. Like most providers, Geisinger Health System measures the mineral content in the bones of patients who are at high-risk for osteoporosis through DXA scans.

Follow-up exams are commonly needed to assess how the disease has progressed. Geisingers rheumatology department removed some of the steps involved, shifted the responsibility of ordering the exam from the patients primary care provider to the rheumatology staff and made greater use of Geisingers $80 million Electronic Health Record.

Before the change, 18% of patients received the test. After the test, 88% received the scan.

A broken bone from osteoporosis can be excruciating and hard to recover from, said Eric Newman, MD, Geisingers Rheumatology Director. Testing for osteoporosis is the first step in preventing these breaks.

Results of the study were presented at the American College of Rheumatologys annual meeting in Boston recently. Geisinger had four presentations at the meeting, the most ever for the department......... Posted by: Mark      Read more         Source

November 7, 2007, 6:16 PM CT

Golimumab for ankylosing spondylitis

More than half of patients receiving monthly subcutaneous (SC) injections of golimumab (CNTO 148) 50 mg and 100 mg experienced significant and sustained improvements in the signs and symptoms of active ankylosing spondylitis, according to Phase 3 study results presented at the American College of Rheumatology (ACR) annual meeting. At week 14 of the study, 59 percent of patients receiving golimumab 50 mg and 60 percent of patients receiving golimumab 100 mg achieved at least 20 percent improvement in the Assessment in Ankylosing Spondylitis criteria (ASAS 20) compared with 22 percent of patients receiving placebo.

(P < 0.001). Investigators also reported that study subjects receiving golimumab 50 mg or golimumab 100 mg showed significant, sustained improvements in physical function through six months as measured by the Bath Ankylosing Spondylitis Functional Index (BASFI).

Golimumab, Centocor Inc. and Schering-Plough Corporation's next-generation human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, is currently in the most comprehensive Phase 3 development program to date for an anti-TNF-alpha biologic therapy. With ongoing studies for the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, golimumab is being studied as a monthly SC injection and an every twelve-week intravenous (IV) infusion (approximately 30-minutes) therapy......... Posted by: Mark      Read more         Source

November 4, 2007, 2:34 PM CT

Gene Behind Rheumatoid Arthritis

University of Manchester scientists have identified a genetic variant in a region on chromosome 6 that is linked to rheumatoid arthritis (RA), the most common inflammatory arthritis affecting 387,000 people in the UK.

Professor Jane Worthington and her team at the Arthritis Research Campaign (arc) Epidemiology Unit at the University investigated 9 genetic regions identified earlier this year as potentially harbouring DNA variants determining susceptibility to rheumatoid arthritis. Association to one of the variants on chromosome 6 was unequivocally confirmed, reports this week's Nature Genetics (4 November 2007). Eventhough this variant is not located in a gene, Professor Worthington suggests that it may influence the behaviour of a nearby gene: tumour necrosis factor associated protein (TNFAIP3) as this is a gene that is known to be involved in inflammatory processes.

Rheumatoid arthritis, which affects up to 1% of the adult population, is a chronic inflammatory disease that can affect nearly all joints in the body, especially the hands and feet. Complications such as lung disease can occur. In addition, patients with RA are more likely to die from cardiovascular disease and some cancers. Some people respond well to therapy, but most suffer a lifetime of disability......... Posted by: Mark      Read more         Source

October 29, 2007, 10:28 PM CT

New cements to heal spinal fractures

New research could offer hope for victims of the most devastating spinal injuries - typically those caused in car crashes.

Biological cements to repair burst fractures of the spine are being developed and tested in a major new collaborative project between the University of Leeds and Queens University Belfast. The team has been awarded just under 500,000 by the Engineering and Physical Sciences Research Council (EPSRC) to develop and examine the effects of novel cement materials for the therapy of burst fractures.

Bone cements, similar to those used in joint replacement surgery, are already being used to strengthen damaged vertebrae of patients with diseases such as osteoporosis, in a procedure known as vertebroplasty, but burst fractures to the spine, injuries often sustained in major impact accidents and falls, are much more difficult to treat. They account for over 1,000 emergency NHS admissions each year and often require highly complex, invasive surgery and a long stay in hospital.

This type of fracture causes the vertebra to burst apart and in severe cases fragments of bone can be pushed into the spinal cord, says Dr Ruth Wilcox of Leeds Institute of Medical and Biological Engineering. Surgeons may be able to join bone fragments together and stabilize the spine with the use of metal screws and rods, but patients with these injuries are often in a really bad way, so the less invasive the therapy, the better......... Posted by: Mark      Read more         Source

October 21, 2007, 10:00 PM CT

Major genetic breakthrough for ankylosing spondylitis

Research funded by the Wellcome Trust and the Arthritis Research Campaign has identified two genes implicated in the disease ankylosing spondylitis, a common disease primarily causing back pain and progressive stiffness. The research, published online today in Nature Genetics, suggests that a therapy currently being trialled for Crohn's disease may also be applied to this disease.

Ankylosing spondylitis affects as a number of as 1 in 200 men and 1 in 500 women in the UK, typically striking people in their late teens and twenties. Whilst it mainly affects the spine, it can also affect other joints, tendons and ligaments. More rarely, it can affect other areas, such as the eyes, lungs, bowel and heart. High-profile sufferers of the condition include former England cricket captain Mike Atherton.

Now, using a technique known as genome-wide association scanning, scientists led by Professors Lon Cardon, Matthew Brown and Paul Wordsworth, from the Wellcome Trust Centre for Human Genetics at the University of Oxford have analysed DNA samples from 1,000 patients with ankylosing spondylitis and a further 1,500 people unaffected by the disease in search of genetic mutations which, if present, increase a person's risk of developing the disease. The findings from this study were then confirmed by a team at University of Texas (Houston) led by Professor John Reveille......... Posted by: Mark      Read more         Source

October 19, 2007, 4:58 AM CT

What's been causing your knee to ache? Smurfs!

A new clinical trial seeks to predict who is most likely to experience osteoarthritis, and to test whether an experimental therapy can prevent it altogether. Physicians are setting their sights on people who sustain a knee injury, seeking to understand why nearly half of them will later go on to develop osteoarthritis, a debilitating condition that causes pain and disability in more than 20 million Americans each year.

The work is funded by a special class of National Institutes of Health grants awarded to research programs that show promise of quickly translating basic science discoveries into patient therapys. In this case, initial research has shown that an enzyme which controls the response of cells to growth factors may in fact be a major cause of osteoarthritis. The enzymes are called "Smad Ubiquitination Regulatory Factors, or, smurfs, but unlike the small, loveable blue cartoon characters, scientists think that a particular form of these regulatory enzymes, smurf2, might in fact be responsible for Americas leading cause of disability.

We think that smurf2 controls whether or not a cartilage cell matures and calcifies into hard bone, which is a very good thing when turned on in those areas of the body where we are supposed to have hard bone, said Randy Rosier, M.D., Ph.D., professor of Orthopaedics and director of Research Translation in Orthopaedics at the University of Rochester Medical Center. But when smurf2 is active in joint cartilage, it may set off a chain reaction that leads to the steady deterioration of the smooth gliding surface tissue, or cartilage, which comprises the joint surface. When this occurs, the cartilage breaks down and severely damages the weight-bearing surface of a joint. Or, put another way, activation of smurf2 in the joint cartilage appears to significantly contribute to the onset of osteoarthritis......... Posted by: Mark      Read more         Source

October 8, 2007, 3:52 PM CT

Genes That Increase Rheumatoid Arthritis Risk

Scientists in the United States and Sweden have identified a genetic region linked to increased risk of rheumatoid arthritis (RA), a chronic and debilitating inflammatory disease of the joints that affects an estimated 2.1 million Americans. The U.S. arm of the study involved a long-time collaboration between intramural scientists of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other organizations. NIAMS is one of 27 institutes and centers at the National Institutes of Health. The results appeared in the New England Journal (NEJM).

Using the relatively new genome-wide association approach - which makes it possible to analyze between 300,000 and 500,000 single nucleotide polymorphisms (SNPs, or small differences in DNA that are distributed throughout a person's genetic code) - scientists in both countries searched for genetic differences in blood samples from people with RA in comparison to controls. The U.S. group compared 908 samples from patients provided by the North American Rheumatoid Arthritis Consortium (NARAC) - a group of researchers working together to identify the genetic factors that contribute to RA - with those from 1,282 people without RA (controls). The Swedish group compared 676 samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) with 673 controls......... Posted by: Mark      Read more         Source