Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
23106505 Effect of Porphyromonas gingivalis on citrullination of proteins by macrophages in vitro. 2013 Sep BACKGROUND: Citrullination of proteins within inflamed periodontal tissues may provide an important link between periodontitis and rheumatoid arthritis. The aim of this study is to determine whether the presence of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) can influence citrullination of proteins by either increasing the amount of local citrullinated protein or influencing the peptidylarginine deiminase (PAD) enzymes found in the monocyte/macrophage population. METHODS: Human peripheral blood monocytes and macrophages were incubated in the presence of live or heat-killed P. gingivalis. Expression of PAD2 and PAD4, PPAD, and citrullinated proteins were assessed by either a combination of real-time polymerase chain reaction, Western blotting, or a colorimetric assay. RESULTS: PPAD was detected only in mononuclear cells incubated in the presence of live P. gingivalis and resulted in increased extracellular citrullination. Endogenous PAD (mRNA and protein) expression was detected in monocytes and macrophages but was not affected by P. gingivalis. CONCLUSION: Although P. gingivalis produces a PAD that can citrullinate extracellular proteins and may contribute to the citrullinated protein load in gingival tissues, it does not appear to affect PAD expression or citrullination by host monocytes or macrophages.
23055010 Acupuncture in the treatment of rheumatic diseases. 2012 Dec Acupuncture has been used for millennia in traditional Chinese medicine as a technique believed to restore the balance of energy in the body caused by disease through the use of needles inserted into specific points or energy channels. This energy is called the de qi. The use of acupuncture for the treatment of pain in musculoskeletal disorders is increasing. Some patients seek alternative therapies because of lack of improvement with conventional treatments. The potential physiological effects of acupuncture on pain relief have been attributed to biochemical processes, such as the release of endorphins into the limbic structures, subcortical areas and brain stem, mechanisms that are also present in placebo-induced analgesia. In addition, pain relief with acupuncture is also associated with patient expectations, beliefs, and interactions with their acupuncturists. In this review, we summarize the latest evidence on the treatment of musculoskeletal conditions including rheumatoid arthritis, fibromyalgia, neck pain, shoulder pain, low back pain, and knee pain with traditional Chinese acupuncture (TCA), electroacupuncture (EA), and the use of moxibustion. Acupuncture is relatively safe, but there are still reports of serious and fatal side effects that must be taken into account when recommending this therapy. Many of the latest trials assessing the benefits of acupuncture in rheumatic diseases found that acupuncture was not better than sham acupuncture, implying that the analgesic effects observed are related to a strong placebo response. While the literature on this topic is extensive, many of the studies lack methodological rigor, and additional large, well-controlled, high quality trials are still needed to determine if acupuncture might be useful in the treatment of chronic rheumatic diseases.
23044001 Resolution of cystic deterioration of the C1-2 articulation with posterior fusion: treatme 2013 May BACKGROUND: The authors previously reported anterior decompression of C1-2 synovial cysts and subsequent posterior fusion in a large series. Although the surgical morbidity and mortality were acceptable, prior reports of stand-alone C1-2 fusion with resolution of cyst compression presumptively by correction of joint instability were intriguing and did not involve the morbidity associated with the transoral procedure. METHODS: Three cases of retroodontoid cysts that resolved after posterior instrumentation and fusion are presented. These cysts were not associated with rheumatoid arthritis. An additional nine cases from the literature in which fusion was performed without cyst extirpation are reviewed. RESULTS: Three patients presented with retroodontoid cysts. Two patients underwent posterior occipitocervical fusion with instrumentation alone. One patient underwent transoral decompression followed by occipitocervical fusion with instrumentation. In this one patient, magnetic resonance imaging performed early after the transoral procedure demonstrated substantial residual cyst. In all cases, follow-up magnetic resonance imaging performed 6-19 months later demonstrated near-complete resolution of the cysts. A literature review was done to find all other similar cases. Demographics, clinical presentation, imaging, and surgical outcome of these cases were analyzed. CONCLUSIONS: In asymptomatic patients with a synovial cyst of the atlantoaxial junction, posterior fusion alone may lead to complete resolution of the cyst; however, in neurologically symptomatic patients with similar lesions, cyst decompression coupled with posterior fusion is recommended to ensure the highest chance of cyst resolution and clinical improvement.
22964232 The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune diseases. 2012 Nov Immunoglobulin G (IgG)-mediated activation of complement and IgG Fc receptors (FcγRs) are important defense mechanisms of the innate immune system to ward off infections. However, the same mechanisms can drive severe and harmful inflammation, when IgG antibodies react with self-antigens in solution or tissues, as described for several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and immune vasculitis. More specifically, IgG immune complexes (ICs) can activate all three pathways of the complement system resulting in the generation of C3 and C5 cleavage products that can activate a panel of different complement receptors on innate and adaptive immune cells. Importantly, complement and FcγRs are often co-expressed on inflammatory immune cells such as neutrophils, monocytes, macrophages or dendritic cells and act in concert to mediate the inflammatory response in autoimmune diseases. In this context, the cross-talk between the receptor for the anaphylatoxin C5a, i.e. C5ar1 (CD88) and FcγRs is of major importance. Recent data suggest a model of bidirectional regulation, in which CD88 acts upstream of FcγRs and sets the threshold for FcγR-dependent effector responses by regulating the ratio between activating and inhibitory FcγRs. Vice versa, FcγR ligation can either amplify or block C5aR-mediated effector functions, depending on whether IgG IC aggregate activating or inhibitory FcγRs. Further, complement and FcγRs cooperate on B cells and on follicular dendritic cells to regulate the development of autoreactive B cells, their differentiation into plasma cells and, eventually, the production of autoantibodies. Here, we will give an update on recent findings regarding this complex regulatory network between complement and FcγRs, which may also regulate the inflammatory response in allergy, cancer and infection.
22936933 Selective inhibitors of phosphoinositide 3-kinase delta: modulators of B-cell function wit 2012 The delta isoform of the p110 catalytic subunit (p110δ) of phosphoinositide 3-kinase is expressed primarily in hematopoietic cells and plays an essential role in B-cell development and function. Studies employing mice lacking a functional p110δ protein, as well as the use of highly-selective chemical inhibitors of p110δ, have revealed that signaling via p110δ-containing PI3K complexes (PI3Kδ) is critical for B-cell survival, migration, and activation, functioning downstream of key receptors on B cells including the B-cell antigen receptor, chemokine receptors, pro-survival receptors such as BAFF-R and the IL-4 receptor, and co-stimulatory receptors such as CD40 and Toll-like receptors (TLRs). Similarly, this PI3K isoform plays a key role in the survival, proliferation, and dissemination of B-cell lymphomas. Herein we summarize studies showing that these processes can be inhibited in vitro and in vivo by small molecule inhibitors of p110δ enzymatic activity, and that these p110δ inhibitors have shown efficacy in clinical trials for the treatment of several types of B-cell malignancies including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). PI3Kδ also plays a critical role in the activation, proliferation, and tissue homing of self-reactive B cells that contribute to autoimmune diseases, in particular innate-like B-cell populations such as marginal zone (MZ) B cells and B-1 cells that have been strongly linked to autoimmunity. We discuss the potential utility of p110δ inhibitors, either alone or in combination with B-cell depletion, for treating autoimmune diseases such as lupus, rheumatoid arthritis, and type 1 diabetes. Because PI3Kδ plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, PI3Kδ inhibitors may represent a promising therapeutic approach for treating these diseases.
22930268 Intracellular BK(Ca) (iBK(Ca)) channels. 2012 Dec 1 The large conductance calcium- and voltage-activated potassium channel (BK(Ca)) is widely expressed at the plasma membrane. This channel is involved in a variety of fundamental cellular functions including excitability, smooth muscle contractility, and Ca(2+) homeostasis, as well as in pathological situations like proinflammatory responses in rheumatoid arthritis, and cancer cell proliferation. Immunochemical, biochemical and pharmacological studies from over a decade have intermittently shown the presence of BK(Ca) in intracellular organelles. To date, intracellular BK(Ca) (iBK(Ca)) has been localized in the mitochondria, endoplasmic reticulum, nucleus and Golgi apparatus but its functional role remains largely unknown except for the mitochondrial BK(Ca) whose opening is thought to play a role in protecting the heart from ischaemic injury. In the nucleus, pharmacology suggests a role in regulating nuclear Ca(2+), membrane potential and eNOS expression. Establishing the molecular correlates of iBK(Ca), the mechanisms defining iBK(Ca) organelle-specific targeting, and their modulation are challenging questions. This review summarizes iBK(Ca) channels, their possible functions, and efforts to identify their molecular correlates.
22912543 B cell depletion in treating primary biliary cirrhosis: pros and cons. 2012 Aug 14 Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease of unknown etiology that affects almost exclusively women. Ursodeoxycholic acid (UDCA) is currently the only approved drug by Food and Drug Administration for patients with PBC. Although the precise pathogenesis of PBC remains unclear, it has been postulated that many cell populations, including B cells, are involved in the ongoing inflammatory process, which implicates, not surprisingly, a potential therapeutic target of depleting B cell to treat this disorder. Rituximab is a chimeric anti-CD20 monoclonal antibody that has been approved for the treatment of lymphoma and some autoimmune diseases such as rheumatoid arthritis. Whether it is effective in the treatment of PBC has not been evaluated. Recently, Tsuda et al([1]) demonstrated that B cell depletion with rituximab significantly reduced the number of anti-mitochondrial antibodies (AMA)-producing B cells, AMA titers, the plasma levels of immunoglobulins (IgA, IgM and IgG) as well as serum alkaline phosphatase, and it was well tolerated by all the treated patients with no serious adverse events. This observation provides a novel treatment option for the patients with PBC who have incomplete response to UDCA.
22666826 Modulation of host cell signaling pathways as a therapeutic approach in periodontal diseas 2012 Mar Recently, new treatment approaches have been developed to target the host component of periodontal disease. This review aims at providing updated information on host-modulating therapies, focusing on treatment strategies for inhibiting signal transduction pathways involved in inflammation. Pharmacological inhibitors of MAPK, NFκB and JAK/STAT pathways are being developed to manage rheumatoid arthritis, periodontal disease and other inflammatory diseases. Through these agents, inflammatory mediators can be inhibited at cell signaling level, interfering on transcription factors activation and inflammatory gene expression. Although these drugs offer great potential to modulate host response, their main limitations are lack of specificity and developments of side effects. After overcoming these limitations, adjunctive host modulating drugs will provide new therapeutic strategies for periodontal treatment.
22664308 The association of psoriasis with autoimmune diseases. 2012 Nov BACKGROUND: Previous studies provide evidence that there is a greater frequency of autoimmune diseases among patients with psoriasis than in the general population. OBJECTIVE: This study examined the association between psoriasis and 21 common autoimmune diseases, specified a priori. METHODS: A retrospective cohort study was conducted among persons who were members of Kaiser Permanente Southern California from 2004 to 2011. A total of 25,341 patients with 2 or more diagnosis codes for any psoriatic disease were evaluated. Five persons not meeting this case definition were matched to each psoriatic patient based on age, sex, and length of enrollment. RESULTS: Patients with psoriasis were more likely to have at least 1 other autoimmune disease (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.5-1.7) and to have at least 2 other autoimmune diseases (1.9; 95% CI 1.6-2.4). Of the 17 conditions evaluated, associations with 14 were found to be statistically significant. The strongest association was with rheumatoid arthritis (3.6; 95% CI 3.4-3.9). LIMITATIONS: Patients with autoimmune conditions are likely to have a greater number of health care encounters, which may result in overascertainment and misascertainment of immune-mediated conditions, although the patients included in the study averaged 5.2 years of observation and the comparison subjects were matched on length of enrollment. CONCLUSIONS: The study suggests a genetic or environmental cause common across autoimmune diseases. Further investigation of individuals with multiple autoimmune diseases may yield important clues about the origin and pathogenesis of the disease.
22634323 Immunological studies on glycated human IgG. 2012 Jun 27 AIMS: To study the immunogenicity of advanced glycation end product (AGE) modified IgG (AGE-IgG) in experimental animals. MAIN METHODS: Human IgG was subjected to in vitro glycation with glucose and the formation of N(ε)-(carboxymethyl)lysine (CML) was evaluated by high performance liquid chromatography (HPLC). The immunogenicity of native and AGE-IgG was investigated by raising polyclonal antibodies against them in rabbits. The induced antibodies were purified on a Protein-A agarose affinity column. Specific binding of antibodies was screened by competitive inhibition assay and band shift assay. Cross reactions of induced antibodies with various proteins or amino acids and their glycated conformers were ascertained by competitive inhibition ELISA. KEY FINDINGS: We detected the CML formation in AGE-IgG. The AGE-IgG was found to be highly immunogenic due to the generation of neo-epitopes on it. Affinity purified antibodies exhibited high degree of specific binding with AGE-IgG in comparison to the native IgG. Antibodies against AGE-IgG exhibited diverse antigen binding characteristics and the glycated conformers of various proteins and amino acids were found to be effective inhibitors of antibody-immunogen interaction in cross reaction studies. Band shift assay reiterated the results obtained by direct binding and competitive inhibition assay. SIGNIFICANCE: The induced antibodies against AGE-IgG resembled the diverse antigen binding characteristics of autoantibodies found in rheumatoid arthritis (RA). IgG modified by AGEs under oxidative stress presents unique neo-epitopes which may be one of the factors for the induction of autoantibodies in RA patients.
22509811 mTORC1 and the regulation of skeletal muscle anabolism and mass. 2012 Jun The mass and integrity of skeletal muscle is vital to whole-body substrate metabolism and health. Indeed, defects in muscle metabolism and functions underlie or exacerbate diseases like diabetes, rheumatoid arthritis, and cancer. Physical activity and nutrition are the 2 most important environmental factors that can affect muscle health. At the molecular level, the mammalian target of rapamycin complex 1 (mTORC1) is a critical signalling complex that regulates muscle mass. In response to nutrition and resistance exercise, increased muscle mass and activation of mTORC1 occur in parallel. In this review, we summarize recent findings on mTORC1 and its regulation in skeletal muscle in response to resistance exercise, alone or in combination with intake of protein or amino acids. Because increased activity of the complex is implicated in the development of muscle insulin resistance, obesity, and some cancers (e.g., ovarian, breast), drugs that target mTORC1 are being developed or are in clinical trials. However, various cancers are associated with extensive muscle wasting, due in part to tumour burden and malnutrition. This muscle wasting may also be a side effect of anticancer drugs. Because loss of muscle mass is associated not only with metabolic abnormalities but also dose limiting toxicity, we review the possible implications for skeletal muscle of long-term inhibition of mTORC1, especially in muscle wasting conditions.
23798298 Lack of exercise is a major cause of chronic diseases. 2012 Apr Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause versus treatment; physical activity and inactivity mechanisms differ; gene-environment interaction (including aerobic training adaptations, personalized medicine, and co-twin physical activity); and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, pre-eclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life.
22373989 A review of 32 free flaps in patients with collagen vascular disorders. 2012 Mar BACKGROUND: Collagen vascular diseases affect multiple organs by the deposition of immunoglobulins along vascular basement membranes. This pathophysiology potentially makes these patients poor free flap candidates, with a possible increased risk of failure. The often concomitant finding of hypercoagulability may also compound the risk. METHODS: A retrospective review was conducted of all free flap reconstructions performed between 2005 and 2009. Of a total of 1251 flaps, 25 patients, who underwent 32 flaps, were identified with connective tissue disorders. These included Sjögren syndrome, Raynaud phenomenon, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, scleroderma, and multicentric thrombocytosis. RESULTS: The mean age of the patients was 51 years, and the average body mass index was 28.1 kg/m(2). Seven patients were on chronic immunosuppression. Flap reconstructions included seven deep inferior epigastric perforator flaps, 21 transverse rectus abdominis musculocutaneous flaps, one gluteal flap for breast reconstruction, and one anterolateral thigh and two radial forearm flaps for head and neck reconstruction. All flaps were performed with a single arterial and venous anastomosis. None had microvascular flap complications. There was one case of postoperative deep vein thrombosis. There were three cases of wound dehiscence and one case of ventral hernia. CONCLUSIONS: Blood vessels and soft tissues are injured by inflammation as the primary target of collagen vascular diseases. The increased incidence for thrombotic events deems them potentially high-risk free tissue transfer patients. The authors demonstrate from their series, however, that there is no increased risk of thrombosis, and this patient population should not be precluded from free flap reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.
22295918 Rotatory subluxation: experience from the Hospital for Sick Children. 2012 Feb OBJECT: Diagnosis and management of atlantoaxial rotatory subluxation (AARS) is challenging because of its variability in clinical presentation. Although several treatment modalities have been employed, there remains no consensus on the most appropriate therapy. The authors explore this issue in their 9-year series on AARS. METHODS: Records of patients diagnosed radiologically and clinically with AARS between May 2001 and March 2010 were retrospectively reviewed. Of 40 patients identified, 24 were male and were on average 8.5 years of age (range 15 months-16 years). Causes of AARS included trauma, congenital abnormalities, juvenile rheumatoid arthritis, infection, postsurgical event, and cryptogenic disease. Four patients had dual etiologies. Symptom duration varied: 29 patients had symptoms for less than 4 weeks, 5 patients had symptoms between 1 and 3 months, and 6 patients had symptoms for 3 months or more. RESULTS: Treatment with a cervical collar was sufficient in 21 patients. In 1 patient collar management failed and halter traction was used to reduce the subluxation. Seven patients underwent initial halter traction, but in 4 the subluxation progressed and the patients required halo traction. A halo vest was placed in 2 patients on presentation because the rotatory subluxation was severe; both patients required subsequent operative fusion. One patient required decompression and fusion due to severe canal compromise and myelopathy. All patients requiring fusion presented with subacute symptoms. CONCLUSIONS: Management of AARS varies due to the spectrum of clinical presentations. Patients presenting acutely without neurological deficits can likely undergo collar therapy; those in whom the subluxation cannot be reduced or who present with a neurological deficit may require traction and/or surgical fixation. Patients presenting subacutely may be more prone to requiring operative intervention.
22242606 Epitope mapping of BP230 leading to a novel enzyme-linked immunosorbent assay for autoanti 2012 May BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by circulating autoantibodies against BP180 and BP230. For BP180, the NC16A domain has previously been identified as the main antigenic target in BP, while data about the diagnostic value of epitopes on BP230 were inconclusive. OBJECTIVES: To identify the most appropriate epitopes on BP230 to be applied in a simple, sensitive, and highly specific enzyme-linked immunosorbent assay (ELISA) for routine detection of serum autoantibodies. METHODS: Ten overlapping linear fragments covering the whole length of BP230 were expressed in Escherichia coli. Based on Western blot analysis with sera from patients with BP (n = 49) and healthy controls (n = 94), the diagnostic performance of the fragments was compared by receiver operating characteristics curve analysis. The BP230-C3 fragment comprising the C-terminal portion (amino acids 2326-2649) was subsequently applied in a novel ELISA. The operating characteristics of this ELISA were analysed by probing sera from patients with BP (n = 118), pemphigus vulgaris (n = 50), rheumatoid arthritis and other inflammatory arthritides (n = 170), and systemic lupus erythematosus (n = 56), and from healthy blood donors (n = 483). RESULTS: Among all the fragments, BP230-C3 provided the best efficiency in serologically diagnosing BP by Western blot. An ELISA employing BP230-C3 revealed a diagnostic sensitivity of 56·8% and specificity of 97·6%. Its diagnostic added value amounted to 4·2% compared with the anti-BP180-NC16A-4X ELISA alone. CONCLUSIONS: Recombinant BP230-C3 is a suitable target antigen for the detection of serum autoantibodies against BP230.
22201856 Osteoarthritis: genetic factors, animal models, mechanisms, and therapies. 2012 Jan 1 Osteoarthritis (OA) is the most common form of joint disease. OA frequently affects knees, hips, hands, and the spine. It is characterized by the progressive destruction of articular cartilage and subchondral bone accompanied by low-grade inflammation that together result in pain and deformity. Recent studies have shed light on the nature of OA genetic susceptibility and confirmed a number of candidate genes involved in the destruction of the synovium, articular cartilage, and subchondral bone in OA pathogenesis. During the progression of OA, there are several cellular changes in joints, including an increase in the number of activated osteoclasts and macrophages and an infiltration of the synovium by activated T-cells and B-cells. Pro-inflammatory mediators (e.g. interleukin IL-1, IL-1beta, IL-6, IL-17, and IL-18, and Tumor necrosis actor-alpha), proteinases (e.g. matrix metalloproteinase 9 and cathepsin K), and regulators of cartilage and bone formation (e.g. BMPs) have been shown to have important roles in OA progression at the molecular level. Studies have suggested that OA shares several common characteristics with rheumatoid arthritis (RA). To systematically understand OA, this review summarizes OA disease genes, mouse models of human disease experimental mouse models, mechanisms of OA pathogenesis, and current OA therapies.
22130326 ANKRD55 and DHCR7 are novel multiple sclerosis risk loci. 2012 Apr Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR) = 1.35; P = 2.3 × 10(-9)). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR = 1.10; P = 0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D'< 0.31; r(2)< 0.011). Our results expand the number of risk genes shared between MS, RA and T1D.
22126919 Radiostereometric analysis of hemiarthroplasties of the hip--a highly precise method for m 2012 Jan OBJECTIVE: Cartilage wear is a feature of osteoarthritis and rheumatoid arthritis. Precise measurements of wear have been difficult. Cartilage wear caused by an artificial articulating joint surface is a well-known feature of hemiarthroplasties. The aim of this study was to demonstrate that radiostereometric analysis (RSA) may be used for three-dimensional measurements of cartilage wear in hemiarthroplasties of the hip. METHOD: We performed a phantom model study to assess the feasibility of a subsequent clinical trial. We showed that the motion of the prosthetic head relative to the pelvis was not influenced by the orientation of the prosthetic head. Twenty-two patients were randomised to treatment with a cemented or an uncemented hemiarthroplasty for an acute femoral neck fracture. Migration of the prosthetic head into the acetabulum was measured using RSA. RESULTS: A mean migration of the prosthetic head into the acetabulum of 0.62 mm was found at 3 months [95% confidence interval (CI): 0.27-0.97] and a further migration of -0.07 mm at 12 months (95% CI: -0.16-0.32). There were no differences between the groups in prosthetic migration or functional outcome. Between three and 12 months, there was no detectable cartilage wear during the first postoperative year. CONCLUSION: Whether the migration during the first 3 months represents a period of bedding in due to a harder opposite surface remains to be shown. RSA may be used for measurement of cartilage wear in hemiarthroplasties of the hip. This study demonstrates a highly precise method for measurements of cartilage wear.
22116994 Membranous glomerulonephritis with the use of etanercept in ankylosing spondylitis. 2011 Dec OBJECTIVE: To report a case of membranous glomerulonephritis with the use of etanercept in a patient with ankylosing spondylitis. CASE SUMMARY: A 60-year-old female with severe ankylosing spondylitis and no history of renal disease was started on etanercept 50 mg subcutaneously once a week after standard treatment modalities failed. She had not been on any nephrotoxic drugs, including nonsteroidal antiinflammatory drugs, for over 1 year. After 2 months of etanercept therapy, the patient presented with anasarca, proteinuria, hypoalbuminemia, and normal serum creatinine. Renal biopsy showed features classic for membranous glomerulonephritis (MGN). Etanercept was discontinued, with resolution of anasarca and proteinuria over the following 3 months. DISCUSSION: Very few cases of MGN in patients with ankylosing spondylitis have been reported in the literature; additionally, MGN following etanercept therapy has not been described in patients with ankylosing spondylitis so far. The exact pathogenesis of etanercept-induced MGN in ankylosing spondylitis is not known. Tumor necrosis factor-α antagonists have been associated with the formation of autoantibodies and induction of lupus-like ailments in patients with rheumatoid arthritis. It is possible that a similar dysregulation of the immune system might have accounted for the development of MGN in this patient. The Naranjo probability scale showed that this patient's MGN was probably associated with etanercept therapy. CONCLUSIONS: In addition to the well-described serious adverse drug events, including serious infections, the use of etanercept in ankylosing spondylitis can be associated with the development of MGN. Health care providers, especially rheumatologists, should be aware of this potentially serious adverse drug reaction.
23279749 The patient acceptable symptom state of chronic musculoskeletal pain measured on a visual 2013 Jan OBJECTIVES: The patient acceptable symptom state (PAccSS) is the value beyond which patients consider themselves well. Our aim was to determine the PAccSS of chronic pain in Moroccan outpatients suffering from chronic rheumatic diseases and to identify contributors to PAccSS. METHODS: A 4-week prospective study of 387 outpatients suffering from chronic rheumatic diseases was carried out. Pain level was evaluated using a 0-100 mm visual analog scale. An anchoring method based on patient's opinion was used. The PAccSS was defined as the 75th percentile of the score for patients who considered their state satisfactory. Pearson's chi-square and binary logistic regression were used to analyze the data. RESULTS: The underlying disease of the patients (mean age 50 ± 13 years; female sex 70%) was rheumatoid arthritis (N = 102), ankylosing spondylitis (N = 100), peripheral osteoarthritis (N = 100), and degenerative back pain (N = 85). The mean disease duration was 7.4 ± 6.7 years. At the time of the study, the level of pain was 44 ± 23 mm. One hundred ninety (49%) patients considered their state as satisfactory, and the PAccSS threshold was 50 mm. Significant contributors to PAccSS were high educational level, high socioeconomic status, higher functional status scores, and shorter term disease duration. CONCLUSION: Half of patients were satisfied of their disease state, while the PAccSS threshold of pain was unexpectedly high. This could be explained by an overestimation of the pain intensity or a Moroccan patients' high tolerance to pain. The main protective factors that contribute to achieving the PAccSS were high educational level, high socioeconomic status, higher functional status, and shorter term disease duration.