A St. Jude Children's Research Hospital study shows that T cells, the body's master immune regulators, do not use simple on/off switches to govern the cellular machinery that regulates their development and function. Rather, they possess sophisticated molecular controls that enable them to adjust their function with exquisite precision. Such subtle adjustment enables T cells to modulate their development and function, including avoiding autoimmunity.
In autoimmune disease, rather than attacking invading microbes, the immune system attacks the body's own organs, tissues or cells. Some 80 autoimmune diseases are known, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis and lupus.
"Among the many mysteries surrounding autoimmune diseases is why they can sometimes take decades to manifest themselves," said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology. "Our findings hint that this delayed onset could be explained by subtle defects in the molecular controls on T cells." Such T cells are white blood cells whose duties include shutting down the immune system when it has done its job and suppressing T cells that can attack the body.
Vignali is the senior author of a report on this work that appears in the advance online publication of the journal Nature Immunology.
The researchers explored the function of T cell receptors, proteins that span the cell membrane of T cells. These receptors receive outside signals that instruct T cells to develop, proliferate and transmit those signals into the cell. The St. Jude investigators sought to understand why T cell receptors need many copies of switch-like components called immunoreceptor tyrosine-based activation motifs (ITAMS). ITAMs are components of the CD3 adaptor proteins that attach to the T cell receptor and help transmit the control signals from the T cell receptor into the cell.
"The ITAMs we studied are little molecular tags inside the cell by which the T cell receptor communicates to the rest of the cell," Vignali said. "The mystery we wanted to address was why the T cell receptor needs 10 ITAMs to do its job. Why not just have a simple on/off switch?"
To explore the role of multiple ITAMs, Jeff Holst, Ph.D., the paper's first author and a St. Jude postdoctoral scientist, used a technique developed in the Vignali lab to produce mice whose T cells have variations in the number and type of functional ITAMs. The technique involved using a virus as a genetic cargo-carrier to transport genes for different combinations of normal and mutant non-functional ITAMs into the mouse cells.
The researchers found that reducing the number of normal ITAMs caused the mice to develop autoimmune disease. However, the investigators also found that some mice with fewer than normal functional ITAMs did not become sick with autoimmune disease. Vignali said this finding suggests that it is not just the number of ITAMs, but also their type that may influence T cell function.
"We theorized that there were two possibilities why the immune system needs so many ITAMs," he said. "One is that the requirement was purely quantitative, and that the ITAMs were there for signal amplification. The second possibility is that different ITAMs do slightly different things - they do have slightly different structures, so maybe they bind to some signaling molecules better than others; and their positions in the T cell receptor are different. So, while our primary observation is that quantity is more important than ITAM type, we also found that type has some influence."
The researchers' analyses of the immune systems of the altered mice indicated that reducing the number of normal ITAMs crippled a process called "negative selection." In this process, the immune system rids itself of immature T cells that might attack the body's own cells, causing autoimmune disease. Vignali said that these findings might provide insight into how autoimmune diseases start.
"One implication of our findings is that a relatively small defect in the efficiency of signal transduction through the T cell receptor could give rise to a subtle failing in negative selection, which gives rise over a long period of time to a few overly active T cells that might initiate autoimmunity," Vignali said. "Clearly from our studies there is the possibility that you don't really need a very big reduction in T cell receptor signal strength to have a defect in negative selection."
The study also showed that different T cell functions required different numbers of functional ITAMs. "We were surprised to find that many ITAMs were required to make T cells divide and expand, but only one or two was required to make T cells secrete cytokines," Vignali said. Cytokines are soluble proteins used by cells of the immune system to communicate and send messages to one another. Vignali said these basic findings represent only the beginning of more detailed studies of the role of ITAMs in T cell function.
"We believe this idea that T cell signaling acts more like a rheostat than an on/off switch offers significant new insights into how T cell development and function is controlled," Vignali said.
Other authors include Haopeng Wang, Kelly Durick Eder, Creg Workman, Kelli Boyd, Zachary Baquet, Karen Forbes and Richard Smeyne (St. Jude); Harvir Singh, Andrzej Chruscinski and Paul Utz (Stanford University School of Medicine, Stanford, Calif.); and Nicolai van Oers (The University of Texas Southwestern Medical Center, Dallas).
This work was supported by the National Institutes of Health, a Cancer Center Support CORE grant and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit stjude/.
Source: Summer Freeman
St. Jude Children's Research Hospital
среда, 19 октября 2011 г.
воскресенье, 16 октября 2011 г.
Protein Involved In Causing Gum Disease, Osteoporosis, Arthritis Identified
Investigators at Hospital for Special Surgery, collaborating with researchers from other institutions, have contributed to the discovery that a gene called interferon regulator factor-8 (IRF-8) is involved in the development of diseases such as periodontitis (gum disease), rheumatoid arthritis and osteoporosis. The study, which was published online August 30, ahead of print, in the journal Nature Medicine, could lead to new treatments in the future.
"The study doesn't have immediate therapeutic applications, but it does open a new avenue of research that could help identify novel therapeutic approaches or interventions to treat diseases such as periodontitis, rheumatoid arthritis or osteoporosis," said Baohong Zhao, Ph.D., lead author of the study and a research fellow in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery located in New York City.
Dr. Zhao initiated the study while working in the laboratory led by Drs. Masamichi Takami and Ryutaro Kamijo at Showa University, Tokyo, where much of the work was performed. Dr. Zhao completed the study and extended the work to human cells during the past year at Hospital for Special Surgery working with Dr. Lionel Ivashkiv.
Specifically, the researchers discovered that downregulation of IRF-8 (meaning that the gene produces less IRF-8 protein) increases the production of cells called osteoclasts that are responsible for breaking down bone. An osteoblast is a type of cell that is responsible for forming bone and an osteoclast is a type of cell that breaks down bony tissue (bone resorption). In humans and animals, bone formation and bone resorption are closely coupled processes involved in the normal remodeling of bone. Enhanced development of osteoclasts, however, can create canals and cavities that are hallmarks of diseases such as periodontitis, osteoporosis and rheumatoid arthritis.
Previous researchers have spent time identifying genes that are upregulated during enhanced development of osteoclasts, such as NFATc1, but few studies have identified genes that are downregulated in the process. To fill this knowledge gap, scientists at Hospital for Special Surgery, collaborating with researchers at other institutions, used microarray technology to conduct a genome-wide screen to identify genes that are downregulated during the formation of osteoclasts. They found that expression of IRF-8 was reduced by 75 percent in the initial phases of osteoclast development.
The researchers then genetically engineered mice to be deficient in IRF-8 and gave the animals x-rays and CT (computed tomography) scans to analyze IRF-8's influence on bone. They found that the mice had decreased bone mass and severe osteoporosis. Experiments demonstrated that this was due not to a decreased number of osteoblasts, but because of an increased number of osteoclasts. The researchers concluded that IRF-8 suppresses the production of osteoclasts.
Tests in human cells confirmed these findings. This included a study that showed that silencing IRF-8 messenger RNA in human osteoclast precursors with small interfering RNAs resulted in enhanced osteoclast production. In other words, decreased IRF-8 means more osteoclasts are produced.
This led the investigators to examine the effect of IRF-8 on the activity of a protein called NFATc1 that was previously reported to interact with IRF-8. They found that IRF-8 inhibited the function and expression of NFATc1. This makes sense given that upregulation of NFATc1 is involved in triggering osteoclast precursor cells to turn into osteoclasts.
"This is the first paper to identify that IRF-8 is a novel key inhibitory factor in osteoclastogenesis [production of osteoclasts]," said Dr. Zhao. "We hope that the understanding of this gene can contribute to understanding the regulatory network of osteoclastogenesis and lead to new therapeutic approaches in the future."
Other authors involved in the study are Masamichi Takami, Ph.D., Atsushi Yamada, Ph.D., Xiaogu Wang, Ph.D., and Ryutaro Kamijo, Ph.D., from Showa University in Tokyo, Japan; Takako Koga, Ph.D., and Hiroshi Takayanagi, M.D., Ph.D., from Tokyo Medical and Dental University and the International Research Center for Molecular Science in Tooth and Bone Disease, both in Japan; Xiaoyu Hu, M.D., Ph.D., and Lionel Ivashkiv, M.D., from Hospital for Special Surgery; Tomohiko Tamura, M.D., Ph.D., and Keiko Ozato, Ph.D., from the National Institutes of Health; and Yongwon Choi, Ph.D., from the University of Pennsylvania School of Medicine.
The work was supported by in part by the High-Tech Research Center Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology in Japan; by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science; and by grants from the U.S. National Institutes of Health.
Source:
Phyllis Fisher
Hospital for Special Surgery
"The study doesn't have immediate therapeutic applications, but it does open a new avenue of research that could help identify novel therapeutic approaches or interventions to treat diseases such as periodontitis, rheumatoid arthritis or osteoporosis," said Baohong Zhao, Ph.D., lead author of the study and a research fellow in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery located in New York City.
Dr. Zhao initiated the study while working in the laboratory led by Drs. Masamichi Takami and Ryutaro Kamijo at Showa University, Tokyo, where much of the work was performed. Dr. Zhao completed the study and extended the work to human cells during the past year at Hospital for Special Surgery working with Dr. Lionel Ivashkiv.
Specifically, the researchers discovered that downregulation of IRF-8 (meaning that the gene produces less IRF-8 protein) increases the production of cells called osteoclasts that are responsible for breaking down bone. An osteoblast is a type of cell that is responsible for forming bone and an osteoclast is a type of cell that breaks down bony tissue (bone resorption). In humans and animals, bone formation and bone resorption are closely coupled processes involved in the normal remodeling of bone. Enhanced development of osteoclasts, however, can create canals and cavities that are hallmarks of diseases such as periodontitis, osteoporosis and rheumatoid arthritis.
Previous researchers have spent time identifying genes that are upregulated during enhanced development of osteoclasts, such as NFATc1, but few studies have identified genes that are downregulated in the process. To fill this knowledge gap, scientists at Hospital for Special Surgery, collaborating with researchers at other institutions, used microarray technology to conduct a genome-wide screen to identify genes that are downregulated during the formation of osteoclasts. They found that expression of IRF-8 was reduced by 75 percent in the initial phases of osteoclast development.
The researchers then genetically engineered mice to be deficient in IRF-8 and gave the animals x-rays and CT (computed tomography) scans to analyze IRF-8's influence on bone. They found that the mice had decreased bone mass and severe osteoporosis. Experiments demonstrated that this was due not to a decreased number of osteoblasts, but because of an increased number of osteoclasts. The researchers concluded that IRF-8 suppresses the production of osteoclasts.
Tests in human cells confirmed these findings. This included a study that showed that silencing IRF-8 messenger RNA in human osteoclast precursors with small interfering RNAs resulted in enhanced osteoclast production. In other words, decreased IRF-8 means more osteoclasts are produced.
This led the investigators to examine the effect of IRF-8 on the activity of a protein called NFATc1 that was previously reported to interact with IRF-8. They found that IRF-8 inhibited the function and expression of NFATc1. This makes sense given that upregulation of NFATc1 is involved in triggering osteoclast precursor cells to turn into osteoclasts.
"This is the first paper to identify that IRF-8 is a novel key inhibitory factor in osteoclastogenesis [production of osteoclasts]," said Dr. Zhao. "We hope that the understanding of this gene can contribute to understanding the regulatory network of osteoclastogenesis and lead to new therapeutic approaches in the future."
Other authors involved in the study are Masamichi Takami, Ph.D., Atsushi Yamada, Ph.D., Xiaogu Wang, Ph.D., and Ryutaro Kamijo, Ph.D., from Showa University in Tokyo, Japan; Takako Koga, Ph.D., and Hiroshi Takayanagi, M.D., Ph.D., from Tokyo Medical and Dental University and the International Research Center for Molecular Science in Tooth and Bone Disease, both in Japan; Xiaoyu Hu, M.D., Ph.D., and Lionel Ivashkiv, M.D., from Hospital for Special Surgery; Tomohiko Tamura, M.D., Ph.D., and Keiko Ozato, Ph.D., from the National Institutes of Health; and Yongwon Choi, Ph.D., from the University of Pennsylvania School of Medicine.
The work was supported by in part by the High-Tech Research Center Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology in Japan; by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science; and by grants from the U.S. National Institutes of Health.
Source:
Phyllis Fisher
Hospital for Special Surgery
четверг, 13 октября 2011 г.
Association Between Rheumatoid Arthritis And Poor Sleep In Women
According to a research abstract that will be presented on Wednesday, June 10, at SLEEP 2009, the 23rd Annual Meeting of the Associated Professional Sleep Societies, symptoms of Rheumatoid Arthritis (RA) negatively affect women's sleep. Sleep is further impaired by pain, depression and poor adherence to RA medications.
Results indicate that length of time since RA diagnosis, RA disease activity, level of pain, depression symptoms and adherence to medications for RA may cause women suffering from the disease to have poor sleep quality.
According to lead author Faith Luyster, PhD, of the University of Pittsburgh, Pa., findings emphasize the need for further research concerning poor RA medication adherence and sleep quality.
"Treating depression in women with RA may not only improve sleep but may also improve pain and adherence to medications," said Luyster.
The study involved 133 women with RA; their average age was 56 years, and they were primarily Caucasian, married, had at least a high school education, were not depressed and had RA for 14.76 years. A majority of participants (71 percent) reported poor sleep quality. Pain and depression were measured through subjective reports, and medication adherence was measured objectively with an electronic medication monitor on medication bottle caps.
Sleep disturbances and depression are more prevalent in women in the general population. According to the American Academy of Sleep Medicine (AASM), women face many challenges that interfere with their sleep quality and duration.
More information about how sleep affects women can be found at sleepeducation/Topic.aspx?id=67
Abstract Title: Sleep Quality in Women with Rheumatoid Arthritis
Presentation Date: Wednesday, June 10
Category: Sleep in Medical Disorders
Abstract ID: 1007
Source:
Kelly Wagner
American Academy of Sleep Medicine
Results indicate that length of time since RA diagnosis, RA disease activity, level of pain, depression symptoms and adherence to medications for RA may cause women suffering from the disease to have poor sleep quality.
According to lead author Faith Luyster, PhD, of the University of Pittsburgh, Pa., findings emphasize the need for further research concerning poor RA medication adherence and sleep quality.
"Treating depression in women with RA may not only improve sleep but may also improve pain and adherence to medications," said Luyster.
The study involved 133 women with RA; their average age was 56 years, and they were primarily Caucasian, married, had at least a high school education, were not depressed and had RA for 14.76 years. A majority of participants (71 percent) reported poor sleep quality. Pain and depression were measured through subjective reports, and medication adherence was measured objectively with an electronic medication monitor on medication bottle caps.
Sleep disturbances and depression are more prevalent in women in the general population. According to the American Academy of Sleep Medicine (AASM), women face many challenges that interfere with their sleep quality and duration.
More information about how sleep affects women can be found at sleepeducation/Topic.aspx?id=67
Abstract Title: Sleep Quality in Women with Rheumatoid Arthritis
Presentation Date: Wednesday, June 10
Category: Sleep in Medical Disorders
Abstract ID: 1007
Source:
Kelly Wagner
American Academy of Sleep Medicine
понедельник, 10 октября 2011 г.
News From The Annals Of Internal Medicine, 18 August 2009
1. Chinese Herbal Remedy Shows Promise for Treating Rheumatoid Arthritis
Rheumatoid arthritis is an autoimmune disease that causes painful and debilitating swelling of the joints. Physicians often prescribe anti-inflammatory drugs such as sulfasalazine for the initial treatment of rheumatoid arthritis. Despite the clinical efficacy of these types of drugs, many patients discontinue treatment due to lack of improvement or adverse events. The Chinese herbal remedy Tripterygium wilfordii Hook F (TwHF) (also known as "lei gong teng" or "thunder god vine") has shown promise in treating autoimmune and inflammatory conditions. Researchers randomly assigned 121 patients to take either TwHF root extract 60mg three times per day or sulfasalazine 1g two times per day for 24 weeks. The researchers used a standard measure of joint involvement to determine treatment outcomes. Many patients in both groups discontinued treatment. However, among those who continued treatment for 24 weeks, improvement was greater with TwHF (67%) than with sulfasalazine (36%) and adverse event rates were similar. The resulst were similar in analyses that adjusted for patient drop-out. Researchers conclude that the rapid improvement in joint symptoms may make TwHF extract an attractive and affordable alternative to anti-inflammatory drugs.
2. Elective Induction of Labor May Reduce Cesareans, Improve Fetal Outcomes
Elective induction of labor, or labor that is induced without medical necessity, is rapidly increasing in the United States. Pregnant women who are at term and their physicians may consider labor induction for several reasons including physical discomfort, scheduling issues, or concerns about maternal or fetal complications. However, many experts discourage the practice because of the widely held belief that it increases the risk for cesarean delivery and other complications. Researchers conducted a systematic review of 11 randomized trials and 25 observational studies to compare the benefits and harms of elective induction of labor and expectant management of pregnancy. The researchers found that elective induction of labor at 41 weeks of gestation and beyond was associated with an approximately 20 percent reduction in the rate of cesarean delivery and a 50 percent reduction in the presence of meconium in the amniotic fluid. These results suggest that outcomes may be better with elective induction of labor. More research should be conducted before elective induction of labor is routinely adopted.
3. China's National Free Antiretroviral Program Has Limited Success, Shows Need for Improvement
In 2002, China began the National Free Antiretroviral Program to provide highly active antiretroviral therapy (HAART) to eligible patients with HIV. To determine the long-term outcomes of the program, researchers collected information on patient deaths and CD4 cell counts for the 48,785 program participants over five years. They found that mortality was highest within the first three months after HAART initiation. After about six months of treatment, death rates decreased to levels similar to those seen in HIV-infected patients who receive HAART in other developing countries. The lower death rates remained stable through year five. However, about half of the patients in the program had CD4 cell counts that suggested treatment failure after five years. The researchers believe that treatment failure may be due to the limited number of drug choices available to these patients. Once resistance developed, patients had few options for other drugs they could take.
Source:
Angela Collom
American College of Physicians
Rheumatoid arthritis is an autoimmune disease that causes painful and debilitating swelling of the joints. Physicians often prescribe anti-inflammatory drugs such as sulfasalazine for the initial treatment of rheumatoid arthritis. Despite the clinical efficacy of these types of drugs, many patients discontinue treatment due to lack of improvement or adverse events. The Chinese herbal remedy Tripterygium wilfordii Hook F (TwHF) (also known as "lei gong teng" or "thunder god vine") has shown promise in treating autoimmune and inflammatory conditions. Researchers randomly assigned 121 patients to take either TwHF root extract 60mg three times per day or sulfasalazine 1g two times per day for 24 weeks. The researchers used a standard measure of joint involvement to determine treatment outcomes. Many patients in both groups discontinued treatment. However, among those who continued treatment for 24 weeks, improvement was greater with TwHF (67%) than with sulfasalazine (36%) and adverse event rates were similar. The resulst were similar in analyses that adjusted for patient drop-out. Researchers conclude that the rapid improvement in joint symptoms may make TwHF extract an attractive and affordable alternative to anti-inflammatory drugs.
2. Elective Induction of Labor May Reduce Cesareans, Improve Fetal Outcomes
Elective induction of labor, or labor that is induced without medical necessity, is rapidly increasing in the United States. Pregnant women who are at term and their physicians may consider labor induction for several reasons including physical discomfort, scheduling issues, or concerns about maternal or fetal complications. However, many experts discourage the practice because of the widely held belief that it increases the risk for cesarean delivery and other complications. Researchers conducted a systematic review of 11 randomized trials and 25 observational studies to compare the benefits and harms of elective induction of labor and expectant management of pregnancy. The researchers found that elective induction of labor at 41 weeks of gestation and beyond was associated with an approximately 20 percent reduction in the rate of cesarean delivery and a 50 percent reduction in the presence of meconium in the amniotic fluid. These results suggest that outcomes may be better with elective induction of labor. More research should be conducted before elective induction of labor is routinely adopted.
3. China's National Free Antiretroviral Program Has Limited Success, Shows Need for Improvement
In 2002, China began the National Free Antiretroviral Program to provide highly active antiretroviral therapy (HAART) to eligible patients with HIV. To determine the long-term outcomes of the program, researchers collected information on patient deaths and CD4 cell counts for the 48,785 program participants over five years. They found that mortality was highest within the first three months after HAART initiation. After about six months of treatment, death rates decreased to levels similar to those seen in HIV-infected patients who receive HAART in other developing countries. The lower death rates remained stable through year five. However, about half of the patients in the program had CD4 cell counts that suggested treatment failure after five years. The researchers believe that treatment failure may be due to the limited number of drug choices available to these patients. Once resistance developed, patients had few options for other drugs they could take.
Source:
Angela Collom
American College of Physicians
пятница, 7 октября 2011 г.
New Way Of Classifying Rheumatoid Arthritis Aimed At Identifying The Disease Earlier
The American College of Rheumatology today announced the release of revised classification criteria (created in collaboration with the European League Against Rheumatism) for rheumatoid arthritis, which will allow the study of treatments for RA at much earlier stages of the disease - before joint damage occurs - ultimately leading to better patient outcomes.
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in the organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
Classification criteria are the standard and accepted means by which researchers define a disease. They allow researchers to define individuals as having or not having a given disease, helping to standardize recruitment into clinical trials and other research studies. Although not intended as criteria for diagnosis in clinical practice, with some additional research, classification criteria may be modified and adopted for such use.
Classification criteria are typically updated as knowledge changes, which is the case with the new RA criteria - published in the College's journal, Arthritis & Rheumatism. The previous criteria were created in 1987. Since that time, new therapies have emerged that can prevent joint damage in people with RA. With these modern therapies, the goal of treatment is to prevent people from reaching the point where their RA is causing chronic damage to their joints.
"The 1987 criteria actually posed a major barrier to the study of treatments designed to prevent joint damage in RA," explains Gillian Hawker, MD; senior author of the new criteria. "Many patients did not fulfill the previous RA classification criteria until their disease was well-advanced, and - in many cases - joint damage had already occurred. This truly limited RA researchers from studying the disease at its earlier phases, which is critical to the development of new treatments to prevent damage."
In 2008, the ACR began a collaborative project with the EULAR to create the first new set of RA classification criteria in over 20 years. To establish the new criteria, researchers completed three phases of work. The first phase (led by EULAR) involved reviewing existing data collected from patients with early arthritis to determine which factors best identified patients who were, according to Daniel Aletaha, MD, MS; lead author of this phase of research, "at a high risk of developing the more persistent and erosive arthritis that we currently consider to be RA." Dr. Aletaha also explains that this phase of research is an important component to the overall project as "all classification criteria need to be built on scientific evidence, either from the literature or - as with these criteria - from extensive analysis of real patient data."
The second phase of work (led by the ACR) was aimed at reaching consensus among practicing rheumatologists on which factors were most important in determining a person's likelihood of developing the chronic joint damage that has been known for many years as the hallmark of RA. "Both scientific evidence and the experience of RA experts needed to be considered in the development of the new criteria to ensure all important factors were identified," explains criteria author Tuhina Neogi, MD, PhD. "Additionally, ensuring the new criteria reflects the opinions of front-line rheumatologists diagnosing and treating patients in clinical practice is key to their ultimate acceptance."
In phase three, researchers integrated the findings from the first two phases of work, refined a scoring system, and determined the optimal cut off point to define the disease. Patients to whom these criteria should be applied must have confirmed presence of joint swelling, indicating synovitis - the inflammation of the synovial membrane, which lines a joint - in at least one joint, and no other possible diagnosis that might better explain the symptoms (such as lupus or gout).
"To be classified as having 'definite RA,' patients must receive a score of six or greater (out of a possible 10)," explains Alan Silman, MD who initiated the project. "The scoring system takes into consideration the number and site/size of involved joints, laboratory tests of inflammation and auto-immunity, and symptom duration."
Researchers continue to make great strides in RA research. The creation of this new set of classification criteria is expected to further accelerate the research being done in this field. The next logical step, according to Dr. Hawker, is to use these classification criteria as the basis for the development of diagnostic criteria for RA, for use by practicing rheumatologists.
"Under the correct circumstances, new knowledge resulting from rheumatology research can quickly move into applicable treatments for patients," explains ACR President Stanley B. Cohen, MD. "We believe these new classification criteria will open the door to more meaningful studies of RA and will eventually lead to changes in the diagnosis and treatment of the disease. This is an important step for RA researchers, practicing rheumatologists and patients."
"2010 Rheumatoid Arthritis Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative initiative."
Daniel Aletaha, Tuhina Neogi, Alan J. Silman, Julia Funovits, David T. Felson, Clifton O. Bingham, III, Neal S. Birnbaum, Gerd R. Burmester, Vivian P. Bykerk, Marc D. Cohen, Bernard Combe, Karen H. Costenbader, Maxime Dougados, Paul Emery, Gianfranco Ferraccioli, Johanna M. W. Hazes, Kathryn Hobbs, Tom W. J. Huizinga, Arthur Kavanaugh, Jonathan Kay, Tore K. Kvien, Timothy Laing, Philip Mease, Henri A. M?©nard, Larry W. Moreland, Raymond L. Naden, Theodore Pincus, Josef S. Smolen, Ewa Stanislawska-Biernat, Deborah Symmons, Paul P. Tak, Katherine S. Upchurch, Jir?‡? Vencovsky??, Frederick Wolfe, and Gillian Hawker.
Arthritis & Rheumatism; Published Online: August 9, 2010 (DOI: 10.1002/art.27584); Print Issue Date: September 2010.
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in the organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
Classification criteria are the standard and accepted means by which researchers define a disease. They allow researchers to define individuals as having or not having a given disease, helping to standardize recruitment into clinical trials and other research studies. Although not intended as criteria for diagnosis in clinical practice, with some additional research, classification criteria may be modified and adopted for such use.
Classification criteria are typically updated as knowledge changes, which is the case with the new RA criteria - published in the College's journal, Arthritis & Rheumatism. The previous criteria were created in 1987. Since that time, new therapies have emerged that can prevent joint damage in people with RA. With these modern therapies, the goal of treatment is to prevent people from reaching the point where their RA is causing chronic damage to their joints.
"The 1987 criteria actually posed a major barrier to the study of treatments designed to prevent joint damage in RA," explains Gillian Hawker, MD; senior author of the new criteria. "Many patients did not fulfill the previous RA classification criteria until their disease was well-advanced, and - in many cases - joint damage had already occurred. This truly limited RA researchers from studying the disease at its earlier phases, which is critical to the development of new treatments to prevent damage."
In 2008, the ACR began a collaborative project with the EULAR to create the first new set of RA classification criteria in over 20 years. To establish the new criteria, researchers completed three phases of work. The first phase (led by EULAR) involved reviewing existing data collected from patients with early arthritis to determine which factors best identified patients who were, according to Daniel Aletaha, MD, MS; lead author of this phase of research, "at a high risk of developing the more persistent and erosive arthritis that we currently consider to be RA." Dr. Aletaha also explains that this phase of research is an important component to the overall project as "all classification criteria need to be built on scientific evidence, either from the literature or - as with these criteria - from extensive analysis of real patient data."
The second phase of work (led by the ACR) was aimed at reaching consensus among practicing rheumatologists on which factors were most important in determining a person's likelihood of developing the chronic joint damage that has been known for many years as the hallmark of RA. "Both scientific evidence and the experience of RA experts needed to be considered in the development of the new criteria to ensure all important factors were identified," explains criteria author Tuhina Neogi, MD, PhD. "Additionally, ensuring the new criteria reflects the opinions of front-line rheumatologists diagnosing and treating patients in clinical practice is key to their ultimate acceptance."
In phase three, researchers integrated the findings from the first two phases of work, refined a scoring system, and determined the optimal cut off point to define the disease. Patients to whom these criteria should be applied must have confirmed presence of joint swelling, indicating synovitis - the inflammation of the synovial membrane, which lines a joint - in at least one joint, and no other possible diagnosis that might better explain the symptoms (such as lupus or gout).
"To be classified as having 'definite RA,' patients must receive a score of six or greater (out of a possible 10)," explains Alan Silman, MD who initiated the project. "The scoring system takes into consideration the number and site/size of involved joints, laboratory tests of inflammation and auto-immunity, and symptom duration."
Researchers continue to make great strides in RA research. The creation of this new set of classification criteria is expected to further accelerate the research being done in this field. The next logical step, according to Dr. Hawker, is to use these classification criteria as the basis for the development of diagnostic criteria for RA, for use by practicing rheumatologists.
"Under the correct circumstances, new knowledge resulting from rheumatology research can quickly move into applicable treatments for patients," explains ACR President Stanley B. Cohen, MD. "We believe these new classification criteria will open the door to more meaningful studies of RA and will eventually lead to changes in the diagnosis and treatment of the disease. This is an important step for RA researchers, practicing rheumatologists and patients."
"2010 Rheumatoid Arthritis Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative initiative."
Daniel Aletaha, Tuhina Neogi, Alan J. Silman, Julia Funovits, David T. Felson, Clifton O. Bingham, III, Neal S. Birnbaum, Gerd R. Burmester, Vivian P. Bykerk, Marc D. Cohen, Bernard Combe, Karen H. Costenbader, Maxime Dougados, Paul Emery, Gianfranco Ferraccioli, Johanna M. W. Hazes, Kathryn Hobbs, Tom W. J. Huizinga, Arthur Kavanaugh, Jonathan Kay, Tore K. Kvien, Timothy Laing, Philip Mease, Henri A. M?©nard, Larry W. Moreland, Raymond L. Naden, Theodore Pincus, Josef S. Smolen, Ewa Stanislawska-Biernat, Deborah Symmons, Paul P. Tak, Katherine S. Upchurch, Jir?‡? Vencovsky??, Frederick Wolfe, and Gillian Hawker.
Arthritis & Rheumatism; Published Online: August 9, 2010 (DOI: 10.1002/art.27584); Print Issue Date: September 2010.
вторник, 4 октября 2011 г.
Knee Arthritis Adversely Affected By Obesity
New studies will help patients better understand the role that obesity plays in knee arthritis and recovery from knee surgery
More than 14 million visits were made to physicians' offices in 2008 by patients with knee problems. Five new studies presented at the 2011 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) look at the effect that obesity has on knee arthritis and a patient's ability to recover from knee surgery.
Does Obesity Cause Irreparable Damage To Knees Despite Weight Loss?
One new study found that while weight loss via bariatric surgery may improve knee pain in obese patients with knee osteoarthritis, there may be permanent damage to the knee from being morbidly obese.
The investigation included 10 morbidly obese patients with knee osteoarthritis who were evaluated before and after bariatric surgery. Patients lost an average of 51 pounds in one year. One year after surgery, knee pain and function improved significantly.
"For a long time people felt there was nothing they could do to mitigate the debilitating effects of knee arthritis, but now we know that surgically-assisted weight loss is a way that folks can help themselves," says Michael S. Sridhar, MD, co-investigator and resident at Emory University. "However, there is probably some element of irreparable damage from being morbidly obese that may constrain the improvement in knee pain despite significant weight loss. Looking at the actual joint surfaces with advanced imaging to assess damage is the exciting next step in studying the evolution of knee arthritis in the obese population."
Are 'Super-Obese' Patients At Greater Risk For Post-Surgery Complications?
Also, two new studies just released examine whether obesity contributes to greater complications after hip and knee replacement surgery. The first study considers patients in the "super obese" category who have a body mass index (BMI) greater than 45. Few studies have examined whether complication rates for total joint replacement (TJR) patients may increase for "super-obese" patients.
This study compared the outcomes after TJR in 137 "super-obese" patients versus 63 non-obese patients.
Ran Schwarzkopf, MD, co-investigator and chief resident, New York University Hospital for Joint Diseases, and his research team found that the number of overall complications were significantly higher for the "super-obese" compared to non-obese. Among "super-obese" patients, each 5-unit increase in BMI over 45 was associated with a statistically significant increased risk of having in-hospital and post-operative outpatient complications or readmission. Also, days to discharge were found to increase by almost 14 percent for each 5-unit increase in BMI over 45.
The second study analyzed complication rates for morbidly obese patients (BMI greater than 40) after TJR. The study reviewed data from 12,355 patients and compared complication rates in morbidly-obese patients versus normal-weight patients.
Led by Richard J. Friedman, MD, FRCSC, co-investigator and Chairman, Department of Orthopaedic Surgery, Roper Hospital, Charleston, SC, the study found that morbid obesity contributed to a significantly higher incidence of complications such as redness around the surgical wound, swelling of the legs, bacterial infections, respiratory disorders, neurologic and gastrointestinal complications and cardiac arrhythmias following total hip and knee replacements.
Will Isolated Weight Loss Improve Knee Pain and Movement?
Another new study just released analyzed the effects of isolated weight loss via bariatric surgery on knee osteoarthritis. The study involved 24 obese patients with knee osteoarthritis who were scheduled to undergo bariatric surgery. Patient weights and knee symptoms were recorded before the surgery and 6 and 12 months after surgery. Patients were not prescribed exercise or physical therapy, anti-inflammatory medications or knee injections post-operatively.
The study found that isolated weight loss following bariatric surgery resulted in significant improvements in knee pain, stiffness and function.
"Other studies have looked at the effect that a combination of weight loss, diet and exercise had on knee arthritis, but it was difficult to say which of these factors contributed the most to reducing knee pain," says Christopher Edwards, co-investigator and a fourth year medical student at the Penn State College of Medicine. "Our study should send a message to patients, health care providers, and payers that weight loss is an important consideration in the treatment of knee arthritis."
Can We Explain the Dramatic Rise in TKR Rates in the US by Population Size and the Obesity Epidemic?
Elena Losina, PhD, co-director, Orthopedics and Arthritis Center for Outcomes Research at Brigham and women's Hospital Associate and Professor of Orthopedic Surgery, Harvard Medical School , led a research team to examine trends in total knee replacement (TKR) utilization and found that it doubled during the decade from 1997-2007. The proportion performed in younger groups tripled. The proportion of obese persons increased by about 15 percent between 1997 and 2007. Such an increase in the obesity epidemic could explain about 20 percent of the increased utilization of TKR. Data suggests that expanding the indications for TKR in younger ages (due to sport-related injuries, obesity and as a consequence, early onset of osteoarthritis) is the likely explanation for the dramatic increase in TKR rates in the US.
Disclosures: The authors for these five studies do not have anything related to disclose.
Source:
American Academy of Orthopaedic Surgeons
More than 14 million visits were made to physicians' offices in 2008 by patients with knee problems. Five new studies presented at the 2011 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) look at the effect that obesity has on knee arthritis and a patient's ability to recover from knee surgery.
Does Obesity Cause Irreparable Damage To Knees Despite Weight Loss?
One new study found that while weight loss via bariatric surgery may improve knee pain in obese patients with knee osteoarthritis, there may be permanent damage to the knee from being morbidly obese.
The investigation included 10 morbidly obese patients with knee osteoarthritis who were evaluated before and after bariatric surgery. Patients lost an average of 51 pounds in one year. One year after surgery, knee pain and function improved significantly.
"For a long time people felt there was nothing they could do to mitigate the debilitating effects of knee arthritis, but now we know that surgically-assisted weight loss is a way that folks can help themselves," says Michael S. Sridhar, MD, co-investigator and resident at Emory University. "However, there is probably some element of irreparable damage from being morbidly obese that may constrain the improvement in knee pain despite significant weight loss. Looking at the actual joint surfaces with advanced imaging to assess damage is the exciting next step in studying the evolution of knee arthritis in the obese population."
Are 'Super-Obese' Patients At Greater Risk For Post-Surgery Complications?
Also, two new studies just released examine whether obesity contributes to greater complications after hip and knee replacement surgery. The first study considers patients in the "super obese" category who have a body mass index (BMI) greater than 45. Few studies have examined whether complication rates for total joint replacement (TJR) patients may increase for "super-obese" patients.
This study compared the outcomes after TJR in 137 "super-obese" patients versus 63 non-obese patients.
Ran Schwarzkopf, MD, co-investigator and chief resident, New York University Hospital for Joint Diseases, and his research team found that the number of overall complications were significantly higher for the "super-obese" compared to non-obese. Among "super-obese" patients, each 5-unit increase in BMI over 45 was associated with a statistically significant increased risk of having in-hospital and post-operative outpatient complications or readmission. Also, days to discharge were found to increase by almost 14 percent for each 5-unit increase in BMI over 45.
The second study analyzed complication rates for morbidly obese patients (BMI greater than 40) after TJR. The study reviewed data from 12,355 patients and compared complication rates in morbidly-obese patients versus normal-weight patients.
Led by Richard J. Friedman, MD, FRCSC, co-investigator and Chairman, Department of Orthopaedic Surgery, Roper Hospital, Charleston, SC, the study found that morbid obesity contributed to a significantly higher incidence of complications such as redness around the surgical wound, swelling of the legs, bacterial infections, respiratory disorders, neurologic and gastrointestinal complications and cardiac arrhythmias following total hip and knee replacements.
Will Isolated Weight Loss Improve Knee Pain and Movement?
Another new study just released analyzed the effects of isolated weight loss via bariatric surgery on knee osteoarthritis. The study involved 24 obese patients with knee osteoarthritis who were scheduled to undergo bariatric surgery. Patient weights and knee symptoms were recorded before the surgery and 6 and 12 months after surgery. Patients were not prescribed exercise or physical therapy, anti-inflammatory medications or knee injections post-operatively.
The study found that isolated weight loss following bariatric surgery resulted in significant improvements in knee pain, stiffness and function.
"Other studies have looked at the effect that a combination of weight loss, diet and exercise had on knee arthritis, but it was difficult to say which of these factors contributed the most to reducing knee pain," says Christopher Edwards, co-investigator and a fourth year medical student at the Penn State College of Medicine. "Our study should send a message to patients, health care providers, and payers that weight loss is an important consideration in the treatment of knee arthritis."
Can We Explain the Dramatic Rise in TKR Rates in the US by Population Size and the Obesity Epidemic?
Elena Losina, PhD, co-director, Orthopedics and Arthritis Center for Outcomes Research at Brigham and women's Hospital Associate and Professor of Orthopedic Surgery, Harvard Medical School , led a research team to examine trends in total knee replacement (TKR) utilization and found that it doubled during the decade from 1997-2007. The proportion performed in younger groups tripled. The proportion of obese persons increased by about 15 percent between 1997 and 2007. Such an increase in the obesity epidemic could explain about 20 percent of the increased utilization of TKR. Data suggests that expanding the indications for TKR in younger ages (due to sport-related injuries, obesity and as a consequence, early onset of osteoarthritis) is the likely explanation for the dramatic increase in TKR rates in the US.
Disclosures: The authors for these five studies do not have anything related to disclose.
Source:
American Academy of Orthopaedic Surgeons
суббота, 1 октября 2011 г.
FDA Announces Dates for Public Meeting on Non-Steroidal Anti-Inflammatory Drugs
The Food and Drug Administration (FDA) has announced a joint public meeting of the agency's Arthritis Advisory Committee
and the Drug Safety and Risk Management Advisory Committee to be held February 16, 17 and 18, 2005.
The committees will discuss the overall benefit-to-risk considerations (including cardiovascular and gastrointestinal
concerns) for COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) and related medicines.
Members of the public are encouraged to participate in this meeting. Interested persons may present data, information or
views, orally or in writing, on issues pending before the committees. Oral presentations from the public will be scheduled
between 1:00 p.m. and 3:00 p.m. on February 17. Time allotted for each presentation may be limited. Those desiring to make
formal oral presentations should register to speak at the meeting before February 4, 2005. No registration is required for
those only planning on attending the meeting.
The three-day meeting will be held at the Hilton Washington DC North, 620 Perry Parkway, Gaithersburg, Md. The proceedings
will start at 8:00 a.m. each day. Agendas and other background materials will be posted online no later than one business day
before the meeting.
For more information regarding this meeting, including contact information for members of the public interested in making
presentations or submitting written comments please CLICK HERE.
Media Inquiries: 301-827-6242
Consumer Inquiries: 888-INFO-FDA
This is an FDA Press Release
and the Drug Safety and Risk Management Advisory Committee to be held February 16, 17 and 18, 2005.
The committees will discuss the overall benefit-to-risk considerations (including cardiovascular and gastrointestinal
concerns) for COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) and related medicines.
Members of the public are encouraged to participate in this meeting. Interested persons may present data, information or
views, orally or in writing, on issues pending before the committees. Oral presentations from the public will be scheduled
between 1:00 p.m. and 3:00 p.m. on February 17. Time allotted for each presentation may be limited. Those desiring to make
formal oral presentations should register to speak at the meeting before February 4, 2005. No registration is required for
those only planning on attending the meeting.
The three-day meeting will be held at the Hilton Washington DC North, 620 Perry Parkway, Gaithersburg, Md. The proceedings
will start at 8:00 a.m. each day. Agendas and other background materials will be posted online no later than one business day
before the meeting.
For more information regarding this meeting, including contact information for members of the public interested in making
presentations or submitting written comments please CLICK HERE.
Media Inquiries: 301-827-6242
Consumer Inquiries: 888-INFO-FDA
This is an FDA Press Release
Подписаться на:
Сообщения (Atom)