Poor footwear linked to foot impairment and disability in gout patients


New research shows that use of poor footwear is common among patients with gout. According to the study published today in Arthritis Care & Research, a peer-reviewed journal of the American College of Rheumatology (ACR), gout patients who make poor footwear choices experienced higher foot-related pain, impairment and disability. Gout patients also reported that comfort, fit, support and cost were the most important factors for selecting footwear.

Gout is a type of inflammatory arthritis caused by the crystallization of uric acid within the joints and other tissues. Those with gout experience severe pain and swelling, with the majority of cases affecting the feet. A study published last month in the ACR journal, Arthritis & Rheumatism, shows that doctor-diagnosed gout has risen over the past twenty years and now affects 8.3 million individuals in the U.S. Previous studies have shown that chronic gout contributes to changes in patients' gait parameters, which is consistent with pain avoidance strategy, and likely leads to impaired foot function.

A research team led by Professor Keith Rome from AUT University in Auckland, New Zealand, recruited 50 patients with a history of gout from local rheumatology clinics. Researchers assessed clinical disease characteristics, overall function, foot impairment and disability. The type of footwear worn by patients and factors associated with patient choice of footwear were also evaluated. To determine the suitability of footwear, the team used criteria gauging the adequacy of the footwear from a previous rheumatoid arthritis foot pain study.

"We found that gout patients in our study often wore improper footwear and experienced moderate to severe foot pain, impairment and disability," explains Professor Rome. Roughly 56% of patients made good footwear choices by wearing walking shoes, athletic sneakers, or oxfords. Of the remaining patients, 42% wore footwear that are considered poor and included sandals, flip-flops, slippers, or moccasins; 2% wore boots which are considered average; and none wore high-heeled shoes.

Characteristics of poor footwear included improper cushioning, lack of support, as well as inadequate stability and motion control. Those gout patients who wore poor shoes or sandals reported higher foot-related impairment and disability. More than half of all participants wore shoes that were 12 months or older and showed excessive wear patterns. Factors study participants identified as important for selecting footwear included comfort (98%), fit (90%), support (79%), and cost (60%).

"We found gout patients in our study wore footwear that lacked cushioning, control and stability," concluded Professor Rome. "Many patients' shoes also showed excessive wear and we suggest that proper footwear selection be discussed with gout patients to reduce foot pain and impairment." The authors suggest that further research assessing economically-priced footwear with ample cushioning, adequate motion control and sufficient forefoot width is needed.

More information: "Footwear Characteristics and Factors Influencing Footwear Choice in Patients with Gout." Professor Keith Rome, Mike Frecklington, Peter McNair, Peter Gow, Nicola Dalbeth. Arthritis Care and Research; Published Online: October 3, 2011 (DOI: 10.1002/acr.20582).

Previously unknown cell interaction is key in immune system attacks


Most of the time, the immune system is the body's protector, warding off invading viruses and bacteria before they can lead to infection and disease. But in autoimmune diseases, the immune system does an about face, turning on the body and attacking normal cells.

A major discovery by La Jolla Institute scientist Amnon Altman, Ph.D., and his colleagues, of a previously unknown molecular interaction that is essential for T lymphocyte activation, could have major implications for stopping this aberrantimmune system behavior and the accompanying undesirable immune responses that cause autoimmune diseases and allergies.

"Dr. Altman's finding is a breakthrough in our understanding of the complexbiochemical changes that trigger the immune system's T lymphocytes, which are disease-fighting white blood cells, to mount an immunological attack," said Mitchell Kronenberg, Ph.D., president & chief scientific officer of the La Jolla Institute, an international leader in immunology research. Dr. Kronenberg said the discovery opens the door to the potential development of new therapies for multiple sclerosis, rheumatoid arthritis and a host of other autoimmune diseases by blocking the cellular interaction identified by Dr. Altman, thereby shutting off the unwanted immune attack.

The findings were published online today in the journal Nature Immunology in a paper entitled "A motif in the V3 domain of the kinase PKC-θ determines its localization in the immunological synapse and functions in T cells via association with CD28." The immunological synapse refers to that region of the T cell (also called T lymphocyte) membrane, which contacts antigen-presenting cells to initiate an immune response, and where many of the early activation events take place. La Jolla Institute scientist Kok-Fai Kong, Ph.D., was first author on the paper and Dr. Altman was senior author. Scientists from Japan and Israel also collaborated on the study. 

An important breakthrough at the IRCM associated with osteoporosis


Researchers at the Institut de recherches cliniques de Montréal (IRCM), directed by Dr. Jean Vacher, identified a new gene that modulates bone mass and that could become a risk factor for developing osteoporosis. This scientific breakthrough will be published tomorrow in the scientific journal Cell Metabolism.

Osteoporosis is a "silent" genetic disease characterized by low bone mineral density and deterioration of bone tissue, which leads to increased bone fragility and risk of fracture. In all cases, the disease is caused by an imbalance between the formation and resorption of bone tissue.

"The overall objective of our research is to understand the molecular and cellular mechanisms that determine the balance between bone formation and resorption (breakdown)," explains Dr. Vacher, Director of the Cellular Interactions and Development research unit at the IRCM. "Osteoblasts are responsible for making bones and work in synergy with osteoclasts, which reshape the bone. To gain insight into these complex mechanisms, we are studying the role of new genes that influence osteoclasts and osteoblasts."

The team of researchers recently isolated a gene that modulates osteoclasts. They found, in mice, that a loss of this gene's function leads to a significant increase in the number of osteoclasts, thereby generating an even higher level of bone resorption.

"We identified this gene as a novel modulator of bone mineral density in mice and humans," adds Dr. Vacher. "More importantly, we showed that the human gene could represent a new susceptibility factor for osteoporosis. Hence, this discovery will help identify individuals with a greater predisposition to the disease who could benefit from preventive measures."

According to Osteoporosis Canada, as many as two million Canadians suffer from osteoporosis. One in four women over the age of 50 has osteoporosis, and so does one in eight men over the same age. In addition, 80 per cent of hip fractures are related to the disease. These result in death in up to 20 per cent of cases, and disability in 50 per cent of those who survive.

Mathieu Ferron, graduate student from Dr. Vacher's laboratory, is the article's first author. This research project was conducted in collaboration with scientists at Université Laval in Québec and Washington University School of Medicine in Saint Louis.

Research carried out at the IRCM was funded by the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC). For more information on this discovery, please refer to the article summary published in Cell Metabolism.

Provided by Institut de recherches cliniques de Montreal

Study shows increased Alzheimer's biomarkers in patients after anesthesia and surgery


(Medical Xpress) -- The possibility that anesthesia and surgery produces lasting cognitive losses has gained attention over past decades, but direct evidence has remained ambiguous and controversial. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania provide further evidence that Alzheimer's pathology may be increased in patients after surgery. The new research is published in the October 2011 issue of the journal Anesthesiology.

"We have long sought a clearer picture of the true impact of anesthesia and surgery on the central nervous system," said lead study author Roderic Eckenhoff, MD, Austin Lamont Professor of Anesthesia at Penn. "Although not definitive, this human biomarker study gives some credibility to the notion that anesthesia and surgery produce an inflammatory insult on the brain and accelerate chronic neurodegenerative diseases like Alzheimer's."

Clinical observation of postoperative cognitive dysfunction in patients and studies in animals have long suggested that anesthetics could interact with Alzheimerneuropathology, but the decades-long refractory period, when Alzheimer pathology is developing in the absence of detectable cognitive symptoms, has made research difficult.

With advances in diagnostic tests led by Penn Medicine's Leslie Shaw, PhD, professor of Pathology and Laboratory Medicine, there is now a validated biomarker test that is able to detect the presence of Alzheimer's disease (AD) biomarkers found in cerebral spinal fluid (CSF). This 'signature' combination of Alzheimer's disease indicators – amyloid beta and tau protein – can find disease markers before Alzheimer's symptoms appear and reliably predicts which patients will progress from mild cognitive impairment to full blown Alzheimer's disease. Generally speaking, highly increased CSF tau protein and decreased beta-amyloid are indicative of AD pathology.

To further examine the impact of anesthesia and surgery on CSF in real time, Dr. Eckenhoff and colleagues at Penn set out to analyze the 'signature' indicators of Alzheimer's disease by collecting CSF from patients undergoing routine surgical procedures. A total of 11 patients, all undergoing endoscopic nasal surgery, were included in the study. 

Immune system discoveries earn Nobel in medicine (Update)


Three scientists won the Nobel Prize in medicine on Monday for discoveries about the immune system that opened new avenues for the treatment and prevention of infectious illnesses and cancer.

American Bruce Beutler and French scientist Jules Hoffmann shared the 10 million-kronor ($1.5 million) award with Canadian-born Ralph Steinman, the Nobel committee at Stockholm's Karolinska institute said.

Their discoveries have enabled the development of improved vaccines against infectious diseases. In the long term they could also yield better treatments of cancer, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and chronic inflammatory diseases, award committee secretary Goran Hansson told The Associated Press.

Beutler and Hoffmann were cited for their discoveries in the 1990s of receptor proteins that can recognize bacteria and other microorganisms as they enter the body, and activate the first line of defense in the immune system, known as innate immunity.

Steinman was honored for the discovery two decades earlier of dendritic cells, which help regulate adaptive immunity, the next stage of the immune system's response, when the invading microorganisms are purged from the body.

The discoveries have helped scientists understand why the immune system sometimes attacks its own tissues, paving the way for new ways to fight inflammatory diseases.

"They have made possible the development of new methods for preventing and treating disease, for instance with improved vaccines against infections and in attempts to stimulate the immune system to attack tumors," the committee said.

No vaccines are on the market yet, but Hansson told AP that vaccines against hepatitis are in the pipeline. "Large clinical trials are being done today," he said.

Hansson said he had not been able to reach any of the winners before the announcement.

"Hoffmann for example is traveling in China and is difficult to reach," he said.

Beutler, born in 1957, is professor of genetics and immunology at The Scripps Research Institute in San Diego, California. Hoffmann, 70, headed a research laboratory in Strasbourg, France, between 1974 and 2009 and served as president of the French National Academy of Sciences between 2007-2008.

Steinman, 68, has been affiliated with Rockefeller University in New York since 1970, and heads its Center for Immunology and Immune Diseases. 

Alzheimer's might be transmissible in similar way as infectious prion diseases: study


The brain damage that characterizes Alzheimer's disease may originate in a form similar to that of infectious prion diseases such as bovine spongiform encephalopathy (mad cow) and Creutzfeldt-Jakob, according to newly published research by The University of Texas Health Science Center at Houston (UTHealth).

"Our findings open the possibility that some of the sporadic Alzheimer's cases may arise from an infectious process, which occurs with other neurological diseases such as mad cow and its human form, Creutzfeldt-Jakob disease," said Claudio Soto, Ph.D., professor of neurology at The University of Texas Medical School at Houston, part of UTHealth. "The underlying mechanism of Alzheimer's disease is very similar to the prion diseases. It involves a normal protein that becomes misshapen and is able to spread by transforming good proteins to bad ones. The bad proteins accumulate in the brain, forming plaque deposits that are believed to kill neuron cells in Alzheimer's."

The results showing a potentially infectious spreading of Alzheimer's disease in animal models were published in the Oct. 4, 2011 online issue of Molecular Psychiatry, part of the Nature Publishing Group. The research was funded by The George P. and Cynthia W. Mitchell Center for Research in Alzheimer's Disease and Related Brain Disorders at UTHealth.

Alzheimer's disease is a form of progressive dementia that affects memory, thinking and behavior. Of the estimated 5.4 million cases of Alzheimer's in the United States, 90 percent are sporadic. The plaques caused by misshapen aggregates of beta amyloid protein, along with twisted fibers of the protein tau, are the two major hallmarks associated with the disease. Alzheimer's is the sixth leading cause of death in the United States, according to the Alzheimer's Association.

Researchers injected the brain tissue of a confirmed Alzheimer's patient into mice and compared the results to those from injected tissue of a control without the disease. None of the mice injected with the control showed signs of Alzheimer's, whereas all of those injected with Alzheimer's brain extracts developed plaques and other brain alterations typical of the disease.

"We took a normal mouse model that spontaneously does not develop any brain damage and injected a small amount of Alzheimer's human brain tissue into the animal's brain," said Soto, who is director of the Mitchell Center. "The mouse developed Alzheimer's over time and it spread to other portions of the brain. We are currently working on whether disease transmission can happen in real life under more natural routes of exposure."

More information: "De novo Induction of amyloid-B Deposition in vivo," Molecular Psychiatry.

Provided by University of Texas Health Science Center at Houston (news : web)