Arthritis Information
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Site: MedicineNet Arthritis General
Foot Pain
Title: Foot Pain
Category: Diseases and Conditions
Created: 5/13/2008
Last Editorial Review: 9/1/2010
Health Tip: Snug Shoes Can Damage Feet
Title: Health Tip: Snug Shoes Can Damage Feet
Category: Health News
Created: 8/30/2010 10:10:00 AM
Last Editorial Review: 8/31/2010
Bladder Cancer
Title: Bladder Cancer
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 8/30/2010
Food Better Than Supplements for Cancer Prevention: Expert
Title: Food Better Than Supplements for Cancer Prevention: Expert
Category: Health News
Created: 8/27/2010 10:10:00 AM
Last Editorial Review: 8/30/2010
Does Hope Have a Dark Side?
Title: Does Hope Have a Dark Side?
Category: Health News
Created: 8/26/2010 10:10:00 AM
Last Editorial Review: 8/27/2010
Health Tip: When Hip Pain Signals Bursitis
Title: Health Tip: When Hip Pain Signals Bursitis
Category: Health News
Created: 8/26/2010 10:10:00 AM
Last Editorial Review: 8/27/2010
Long-Term Exercise Can Reduce Vets' Muscle Pain
Title: Long-Term Exercise Can Reduce Vets' Muscle Pain
Category: Health News
Created: 8/26/2010 6:10:00 PM
Last Editorial Review: 8/27/2010
Sacroiliac Joint Dysfunction (SI Joint Pain)
Title: Sacroiliac Joint Dysfunction (SI Joint Pain)
Category: Diseases and Conditions
Created: 10/31/2007
Last Editorial Review: 8/25/2010
Prior Fractures Could Raise Older Women's Odds for Osteoporosis
Title: Prior Fractures Could Raise Older Women's Odds for Osteoporosis
Category: Health News
Created: 8/23/2010 4:10:00 PM
Last Editorial Review: 8/24/2010
Egg Recall: Frequently Asked Questions
Title: Egg Recall: Frequently Asked Questions
Category: Health News
Created: 8/23/2010 9:59:00 AM
Last Editorial Review: 8/23/2010 9:59:19 AM
Parkinson's Disease
Title: Parkinson's Disease
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 8/23/2010
Sham Acupuncture for Knee Arthritis as Effective as the Real Therapy
Title: Sham Acupuncture for Knee Arthritis as Effective as the Real Therapy
Category: Health News
Created: 8/20/2010 8:10:00 PM
Last Editorial Review: 8/23/2010
Site: Arthritis Research & Therapy - Latest Articles
Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort
IntroductionThe objective was to examine the association of baseline demographic and clinical characteristics with sequentially obtained measurements of forced vital capacity (FVC, expressed as a percentage of the predicted value) and to identify predictors of decline rate in FVC over time in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS).
Methods:
To date, 266 patients were enrolled in GENISOS, a prospective, observational cohort of patients with early systemic sclerosis. In addition to pulmonary function tests (PFT), clinical and laboratory data were obtained from each patient. We analyzed 926 FVC measurements utilizing generalized linear mixed models. The predictive significance of baseline variables for the decline rate in FVC was investigated by the interaction term between the variable and follow up time within the first 3 years after enrollment as well as throughout the entire follow up time.
Results:
The cohort consisted of 125 white, 54 African American, and 77 Hispanic patients with average disease duration of 2.5 years at enrollment. The mean follow up time was 3.8 years, ranging up to 11.4 years. A number of baseline variables including antibody status, African American ethnicity, disease type, baseline PFT values, modified Rodnan Skin Score, fibrosis on chest radiograph, lung and skin subscores of Severity Index were associated with serially measured FVC levels. However, only presence of anti-topoisomerase I antibodies (ATA) was associated with lower FVC levels (P<0.001) as well as accelerated decline rate in FVC within the first 3 years of follow up (P=0.02). None of the baseline variables predicted the rate of decline in FVC on long term follow up. However, patients with rapidly progressive ILD were underrepresented in the long term follow up group because the accelerated rate of decline in FVC was associated with poor survival (P=0.001).
Conclusions:
ATA was the only baseline variable, associated with differential FVC levels, predicting the rate of decline in FVC within the first three years of follow up. The association of faster decline in FVC with poor survival further emphasizes the need for identification of predictive biomarkers by collection of genetic information and serial blood samples in cohort studies.
New developments in osteoarthritis. Prevention of injury-related knee osteoarthritis
Purpose of Review: This review presents recent data on knee joint injury as a major cause of osteoarthritis (OA), and promising developments in primary and secondary prevention of OA related to injury. In particular, the role of neuromuscular and biomechanical factors in primary injury prevention and their proposed role in treatment after injury to prevent OA are reviewed and discussed.Recent Findings: Knee OA after injury is common, especially in young adults. There has been an alarming increasing in knee injuries, particularly in females, in the past two decades. Knee OA due to injury estimated at 14-25% a decade ago may be higher now. Convincing level 1 and 2 evidence has shown that the majority of ACL and other injuries are preventable with neuromuscular training programs to improve trunk and core control and lower limb positioning during movement. Mounting evidence supports that neuromuscular function and joint biomechanics are powerful drivers of OA after knee injury. Knee-injured individuals have a host of demonstrable but treatable neuromuscular impairments after injury such as decreased quadriceps strength, decreased trunk control, poor lower limb positioning, proprioceptive deficiencies, and impaired postural control. However, there is limited knowledge of how these factors contribute to early disease, and which is most important.SummaryThere is a strong rationale for interventions targeting neuromuscular and biomechanical factors to prevent knee injury, and a pressing need to disseminate this information widely, especially to school-age and university aged students and sports associations. After injury, there is a need to determine if there are neuromuscular and biomechanical signatures that predispose to OA, and to develop screening tools to identify which knee-injured individuals are at highest risk for future OA development. There is also a strong need to assemble early post-injury cohorts prior to OA development for research in the management of knee injuries, particularly randomized trials that evaluate current treatments in terms of long-term symptoms and structural outcomes. Injury prevention and improved management offer a significant opportunity to prevent knee OA.
High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1beta in osteoarthritic synoviocytes
IntroductionHigh mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL-1beta). The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA).
Methods:
HMGB1 was determined in human synovium using immunohistochemistry, comparing normal to OA. OA synoviocytes were incubated with HMGB1 at 15 or 25 ng/ml in the absence or presence of IL-1beta (10 ng/ml). Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. Matrix metalloproteinase (MMP) activity was studied by fluorometric procedures and nuclear factor (NF)-kappaB activation by transient transfection with a NF-kappaB-luciferase plasmid.
Results:
In the normal synovium, HMGB1 was found in the synovial lining cells, sublining cells, and in the vascular wall cells. The distribution of HMGB1 in OA synovium was similar but the number of HMGB1 positive cells was higher and HMGB1 was also present in infiltrated cells. In normal synovial membrane cells, HMGB1 was found mostly in the nuclei, whereas in OA, HMGB1 was generally found mostly in the cytoplasm. In OA synoviocytes, HMGB1 alone at concentrations of 15 or 25 ng/ml did not affect the production of IL-6, IL-8, CCL2, CCL20, MMP-1 or MMP-3, but in the presence of IL-1beta, a significant potentiation of protein and mRNA expression, as well as MMP activity was observed. HMGB1 also enhanced the phosphorylated ERK1/2 and p38 levels, with a lower effect on phosphorylated Akt. In contrast, JNK1/2 phosphorylation was not affected. In addition, HMGB1 at 25 ng/ml significantly potentiated NF-kappaB activation in the presence of IL-1beta.
Conclusions:
Our results indicate that HMGB1 is overexpressed in OA synovium and mostly present in extracellular form. In OA synoviocytes, HMGB1 cooperates with IL-1beta to amplify the inflammatory response leading to the production of a number of cytokines, chemokines and MMPs. Our data support a pro-inflammatory role for this protein contributing to synovitis and articular destruction in OA.
Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion
IntroductionDiverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA.
Methods:
Patients with PsA (n=38), with psoriasis (n=10) and healthy controls (n=12) were studied. Serum was obtained for testing of Dikkopf-1 (Dkk-1), macrophage-colony stimulating factor (M-CSF), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) by ELISA. Patients with PsA also had bone densitometry, plain radiographs of the hands and feet, and assessment of peripheral blood osteoclast precursors. Radiographs were scored for erosion, joint space narrowing, osteolysis and new bone formation.
Results:
Compared with psoriasis and healthy controls, patients with PsA had higher circulating concentrations of Dkk-1 and M-CSF. In patients with PsA, M-CSF and RANKL, but not Dkk-1, concentrations positively correlated with radiographic erosion, joint space narrowing and osteolysis scores. Mediators of bone remodeling did not correlate with the number of joints with new bone formation or with total hip bone mineral density. Peripheral blood CD14+/CD11b+ cells, and the number of osteoclast-like cells and resorptive pits following culture with RANKL and M-CSF also correlated with radiographic damage scores. Circulating M-CSF concentrations correlated with the percentage of peripheral blood CD14+/CD11b+ cells.
Conclusions:
Systemic expression of soluble factors that promote osteoclastogenesis is disordered in patients with PsA, and may contribute to periarticular bone loss in this disease.
A new tool for detection of type I interferon activation in systemic lupus erythematosus
The Type I Interferon (IFN-I) pathway is activated in SLE and appears to be important in the pathogenesis of the disease. As a result, several clinical trials with anti-IFN monoclonal antibodies have been launched and hold promise to control the disease. Additionally, activation of IFN-I, might be important in prognosis and activity assessment of the disease. Therefore new biomarkers that reflect activity of the IFN-I pathway, and are simple to measure, such as the monocyte CD64 receptor, are expected to have a great impact in the management of SLE, if properly validated.
The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation
IntroductionThe purpose of this study was to evaluate the effects of risedronate (Ris) in the modulation of bone formation in rats with glucocorticoid (GC) - induced osteoporosis by histomorphometric, immunohistochemical and gene expression analyses.
Methods:
We analyzed structure, turnover and microarchitecture, cyclooxygenase 2 (COX-2) levels and osteocyte apoptosis in 40 female rats divided as follows: 1) vehicle of methylprednisolone (vGC) + vehicle of risedronate (vRis); 2) Ris 5[microg]/Kg + vGC; 3) methylprednisolone (GC) 7mg/Kg + vRis; 4) GC 7mg/Kg +Ris 5[microg]/Kg. In addition, we evaluated cell proliferation and expression of COX-2 and bone alkaline phosphatase (b-ALP) genes in bone marrow cells and MLO-y4 osteocytes treated with Ris alone or in co-treatment with the selective COX-2 inhibitor NS-398 or with dexametasone.
Results:
Ris reduced apoptosis induced by GC of osteocytes (41% vs 86%, P<0.0001) and increased COX-2 expression with respect to controls (IHS: 8.75 vs 1.00, P<0.0001). These positive effects of Ris in bone formation were confirmed by in vitro data as the viability and expression of b-ALP gene in bone marrow cells resulted increased in a dose dependent manner.
Conclusions:
These findings suggest a positive effect of Ris in bone formation and support the hypothesis that the up-regulation of COX-2 could be an additional mechanism of anabolic effect of Ris.
Relationship between patient-reported disease severity in osteoarthritis and self-reported pain, function and work productivity
IntroductionUnderstanding the relationship between patient-reported osteoarthritis (OA) severity and other patient-reported outcomes in the real-world clinical setting can provide a basis for appropriate patient management. The objective of this study was to determine how patient-reported OA severity correlates with the patient-reported outcomes including pain, function and productivity.
Methods:
We used the Adelphi disease specific programme (DSP) for OA, a database aggregated from large, multinational, observational studies for specific chronic diseases. Data were obtained based on a 0-100 mm pain visual analogue scale (VAS) and a series of questions including functioning (i.e. activities of daily living) and work productivity. OA severity was rated by the patients based on the question "How bad would you say your arthritis is now?" with potential responses of "mild," "moderate," and "severe." Regression models and chi-square analyses were used to evaluate the relationships between self-reported OA severity and other outcomes.
Results:
Of 998 subjects in the OA DSP U.S. database, 714 (72.5%) agreed to complete the PSC. This sample was predominantly female (61.7%) with a mean age of 63.8+/-12.9 years. Increased OA severity was associated with an older population (P<0.05). With increasing OA severity (mild, moderate, severe), statistically significant differences (P<.05) were observed in increased pain VAS scores (23.5, 50.2, 70.8, respectively), lower functioning outcomes, and a higher percent of overall work impairment due to OA (17%, 37%, 48%, respectively). The increased work impairment at greater severity levels also resulted in higher costs related to lost work productivity, with annual costs due to lost productivity estimated at $6,096, $13,2510, and $17,214 per patient for self-reported mild, moderate, and severe OA, respectively (P<0.05 for pairwise comparisons).
Conclusions:
In the clinical practice setting, patient-reported OA severity was associated with other key patient-reported outcomes and thus may provide an accurate and tangible assessment of patient's perceptions of their disease. Identifying OA patients by their perceived severity level may be of benefit to patients and health-care providers when choosing treatment options aimed at improving pain, function and productivity.
Monocytes/macrophages express CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation
IntroductionMonocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers.
Methods:
CCR9 expression on PB monocytes/macrophages was analysed by flow cytometry and in synovium by immunofluorescence. Chemokine receptor CCR9 mRNA expression was examined in RA and non-RA synovium, monocytes/macrophages from PB and synovial fluid (SF) of RA patients and PB of healthy donors using the reverse transcription polymerase chain reaction (RT-PCR). Monocyte differentiation and chemotaxis to CC chemokine ligand 25/TECK (CCL25) were used to study CCR9 function.
Results:
CCR9 was expressed by PB monocytes/macrophages in RA and healthy donors, and increased in RA. In RA and non-RA synovia, CCR9 co-localised with cluster of differentiation 14+ (CD14+) and cluster of differentiation 68+ (CD68+) macrophages, and was more abundant in RA synovium. CCR9 mRNA was detected in the synovia of all RA patients and in some non-RA controls, and monocytes/macrophages from PB and SF of RA and healthy controls. CCL25 was detected in RA and non-RA synovia where it co-localised with CD14+ and CD68+ cells. Tumour necrosis factor alpha (TNFalpha) increased CCR9 expression on human acute monocytic leukemia cell line THP-1 monocytic cells. CCL25 induced a stronger monocyte differentiation in RA compared to healthy donors. CCL25 induced significant chemotaxis of PB monocytes but not consistently among individuals.
Conclusions:
CCR9 expression by monocytes is increased in RA. CCL25 may be involved in the differentiation of monocytes to macrophages particularly in RA.
Arthritis Research & Therapy evolves: online only from 2011
This article has no abstract.
Rationale of using different biological therapies in rheumatoid arthritis
Due to ongoing developments of novel agents in the field of biological pharmacotherapy, there are now more arrows available in clinicians' quivers for the treatment of rheumatic conditions. As a consequence, however, clear treatment strategies have to be defined in order to guarantee a qualitatively high and individually stage-adapted, state-of-the-art regimen for affected patients. This review summarizes recent evidence regarding the rationale of using different biological therapies to treat rheumatoid arthritis, the most common inflammatory joint disorder after activated osteoarthritis, and draws an actual picture of a possible standardized therapeutic algorithm without claiming exclusive appropriateness.
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