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ID PMID Title PublicationDate abstract
18751615 [Lupus like syndrome induced by treatment with anti TNFalpha (infliximab): report of three 2008 Jul Since anti-TNFalpha treatments were introduced in the therapy of rheumatoid arthritis, some cases of patients with drugs induced Lupus during clinical trials with infliximab treatment for rheumatoid arthritis (RA) were reported. We report three cases with history of refractory RA (two patients) and of psoriatic arthritis (one patient) with a diagnosis of Drug Induced Lupus, after treatment with infliximab, with different clinical features such as pericardial and pleural effusion, skin lesions and piastrinopenia and with autoantibody assessment. We also reviewed the development of anti nuclear and anti double-strand DNA antibodies and drug induced lupus in patients treated with anti-TNFalpha agents (infliximab, etanercept and adalimumab).
16627140 Total hip arthroplasty with the porous-coated anatomic hip prosthesis: results at 11 to 18 2006 Apr The authors had previously reported good results with apparent fixation of a series of porous-coated anatomic hips at 2 to 4 years. In a larger series of 133 hips with porous-coated anatomic uncemented components, 91 hips in 82 patients were available for a follow-up of 11 years or greater. Although 3.1% of acetabular cups had migrated or had been revised at 2 to 4 years; at 11 to 18 years, there was 37% lysis, 21.7% migration, and 32.3% revision. For the femur at 2 to 4 years, there was 3.1% migration and 1.5% revision. At 11 to 18 years, there was 27.2% lysis (proximal only), 6.6% migration, and 3.2% revision. Survival analysis for migration or revision for the femoral was 94%, and for the acetabular component, 63%, deteriorating markedly after 10 years.
18625373 Interstitial granulomatous drug reaction to anakinra. 2008 Aug Interstitial granulomatous drug reactions are an uncommon entity presenting as asymptomatic, annular, erythematous to violaceous plaques. The incidence of such reactions has been increasing with the use of biologic agents. We report, to the best of our knowledge, the first such reaction to the interleukin (IL)-1 inhibitor anakinra. Our patient presented with pink dermal plaques and nodules in the periaxillary region which resolved with discontinuation of anakinra and recurred upon restarting anakinra. Biopsy revealed a diffuse dermal infiltrate of lymphocytes and histiocytes with interspersed neutrophils and eosinophils. Fragmentation and degeneration of collagen and elastic fibers was also present. Withdrawal of anakinra led to complete resolution of the lesions. Interstitial granulomatous drug reactions are increasing in frequency and we add anakinra to the list of causative agents.
18465451 Calprotectin (a major leucocyte protein) is associated with the levels of anti-CCP and rhe 2008 May BACKGROUND: Calprotectin is a major granulocyte and monocyte protein, and plasma levels of calprotectin are strongly associated with inflammation in patients with rheumatoid arthritis (RA). OBJECTIVE: To explore the associations between calprotectin and serological, inflammatory, and clinical assessments in a longitudinal study of patients with very early RA. PATIENTS AND METHODS: In 61 RA patients (77% females, mean age 57.9 years, disease duration 132 days), laboratory and clinical assessments were performed at baseline and after 3, 6, and 12 months. RESULTS: Calprotectin levels were higher in patients positive vs. negative for anti-cyclic citrullinated peptide (anti-CCP), immunoglobulin M rheumatoid factor (IgM-RF), and IgA-RF (p<0.001-0.05). The 1-year averaged level of calprotectin correlated significantly with the mean levels of these three serological markers (p<0.05). In multiple regression analyses, adjusting for age, sex, and disease duration, calprotectin was associated with anti-CCP (p = 0.045), and both calprotectin and erythrocyte sedimentation rate (ESR) were associated with IgM-RF (p = 0.003 and 0.03, respectively). Calprotectin correlated significantly with the inflammatory markers at all examinations [C-reactive protein (CRP); r = 0.60-0.70, p<0.001, ESR; r = 0.55-0.57, p<0.001] as well as with the 28-joint disease activity score (DAS28; r = 0.28-0.33, p<0.05). CONCLUSION: This is the first study that shows significant associations between the levels of calprotectin and anti-CCP, IgA-RF, and IgM-RF in very early RA. In addition, significant correlations were found between calprotectin and markers of disease activity.
19928400 [Security of the combined treatment of methotrexate and leflunomide in patients with rheum 2007 Rheumatoid Arthritis (RA) is a chronic disease leading to functional impairment and early mortality. Treatment with disease-modifying antirheumatic drugs have shown to achieve disease remission and improves its evolution. The use of combined therapy should have a biological efficacy, no increased toxicity and have an acceptable dose interval. Also, it should begin its action quickly and be cost-effective. AIMS: to assess the security of the combined treatment with Methotrexate (MTX) and Leflunomide (LF) in patients with Rheumatoid Arthritis (RA) and to evaluate whether the dose and route of MTX administration influence on the toxicity. PATIENTS AND METHODS: Patients with RA who fulfilled ACR criteria and they attended to the Rheumatology Unit at Córdoba Hospital in the last 2 years were assessed. All the patients that received combined treatment with MTX in doses from 7.5 mg to 25 mg weekly orally (PO) or intramuscularly (i.m.) that started LF treatment in doses of 20 mg/day due to disease activity persistence were retrospectively assessed. Patients having at least 6 months of combined treatment were included. Data on treatment and adverse events were collected. They were evaluated at the beginning, at 6 and 12 months of treatment. The presence of adverse events as well as the stop of combined treatment was evaluated at 6 and 12 months of treatment. Adverse events in patients with oral and i.m. MTX treatment and in different doses were compared for the analyses. P<0.05 was considered significant. RESULTS: 62 patients with a mean age of 54 were included. 89% were female and had positive rheumatoid factor and 83% had radiological erosions. Eighty eight percent were in doses of 15 mg MTX, 4.9% with 10 mg and 25 mg at the beginning of LF treatment. Twenty four percent suffered from adverse events and 33% left the medication by 6 months. Among adverse events, 6 patients had diarrhea, 5 increased hepatic enzymes, 3 alopecia, 3 weight loss, and 2 had anemia and leucopenia. Eight patients stopped the medication in 6 months, but only 5 did because of adverse events. There was not significant statistical difference in adverse events between patients with different dose or routes of administration of MTX. CONCLUSIONS: The presence of adverse events in MTX and LF combined treatment was low and it developed during the first 6 months of treatment in our patients. The MTX route of administration and doses did not influence on the toxicity of the combined treatment with LF. The combined therapy seems to be a safe treatment option in RA patients.
17024588 Boswellic acids in chronic inflammatory diseases. 2006 Oct Oleogum resins from BOSWELLIA species are used in traditional medicine in India and African countries for the treatment of a variety of diseases. Animal experiments showed anti-inflammatory activity of the extract. The mechanism of this action is due to some boswellic acids. It is different from that of NSAID and is related to components of the immune system. The most evident action is the inhibition of 5-lipoxygenase. However, other factors such as cytokines (interleukins and TNF-alpha) and the complement system are also candidates. Moreover, leukocyte elastase and oxygen radicals are targets. Clinical studies, so far with pilot character, suggest efficacy in some autoimmune diseases including rheumatoid arthritis, Crohn's disease, ulcerative colitis and bronchial asthma. Side effects are not severe when compared to modern drugs used for the treatment of these diseases.
17127395 The dual personalities of matrix metalloproteinases in inflammation. 2007 Jan 1 Collagen, gelatin, elastin, fibronectin, proteoglycans and vitronectin are just a few proteins which form the "mesh" that holds a multicellular organism together. The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade the extracellular matrix. Over several decades it has been clearly established that MMPs are the key molecules associated with matrix remodeling. The remodeling of this matrix is important for physiological and pathological processes such as pregnancy, wound repair, cancer and arthritis. The identification of new non-matrix MMP substrates involved in inflammation, highlights the diverse role of MMPs. These enzymes can enhance leukocyte invasion and regulate the inflammatory activity of serine proteases, cytokines and chemokines. Interestingly, the MMP family appears to have a "dual personality" in that several MMPs such as MMP-2 and -9 can favour either anti- or pro-inflammatory action, respectively. The extent of this dual functionality of MMPs is yet to be realized. Elucidating these processes may assist in the development of drugs for the treatment of inflammatory diseases such as arthritis, cancer and chronic wounds.
19017993 Anti-inflammatory effects of sphingosine kinase modulation in inflammatory arthritis. 2008 Dec 1 Sphingosine kinase (SphK) is a key enzyme in the sphingolipid metabolic pathway responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P). SphK/S1P play a critical role in angiogenesis, inflammation, and various pathologic conditions. Recently, S1P(1) receptor was found to be expressed in rheumatoid arthritis (RA) synovium, and S1P signaling via S1P(1) enhances synoviocyte proliferation, COX-2 expression, and prostaglandin E(2) production. Here, we examined the role of SphK/S1P in RA using a potent SphK inhibitor, N,N-dimethylsphingosine (DMS), and a molecular approach against one of its isoenzymes, SphK1. We observed that levels of S1P in the synovial fluid of RA patients were significantly higher than those of osteoarthritis patients. Additionally, DMS significantly reduced the levels of TNF-alpha, IL-6, IL-1beta, MCP-1, and MMP-9 in cell-contact assays using both Jurkat-U937 cells and RA PBMCs. In a murine collagen-induced arthritis model, i.p. administration of DMS significantly inhibited disease severity and reduced articular inflammation and joint destruction. Treatment of DMS also down-regulated serum levels IL-6, TNF-alpha, IFN-gamma, S1P, and IgG1 and IgG2a anti-collagen Ab. Furthermore, DMS-treated mice also displayed suppressed proinflammatory cytokine production in response to type II collagen in vitro. Moreover, similar reduction in incidence and disease activity was observed in mice treated with SphK1 knock-down via small interfering RNA approach. Together, these results demonstrate SphK modulation may provide a novel approach in treating chronic autoimmune conditions such as RA by inhibiting the release of pro-inflammatory cytokines.
17028666 Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inf 2006 Sep Interleukin (IL)-6 contributes to a myriad of physiologic and pathophysiologic processes. Among its many physiologic functions, IL-6 plays an active role in immunology, inflammatory responses, bone metabolism, arthritis and neoplasia. Overproduction of IL-6 has been implicated in the disease pathology of several inflammatory and autoimmune disorders, including rheumatoid arthritis, Castleman's disease, Crohn's disease and systemic-onset juvenile idiopathic arthritis. Interception of the IL-6 signaling pathway could thus represent a new treatment option for these diseases, given their refractory status to conventional therapy. Clinical studies with tocilizumab, a humanized monoclonal anti-IL-6 receptor antibody, have been undertaken to explore this option. Current short-term results indicate that tocilizumab dramatically improves disease activity and is well tolerated. Further long-term safety and efficacy studies are needed to confirm the therapeutic benefit of this antibody in inflammatory and autoimmune disorders.
18649465 Semiautomated three-dimensional segmentation software to quantify carpal bone volume chang 2008 Jun Rapid progression of joint destruction is an indication of poor prognosis in patients with rheumatoid arthritis. Computed tomography (CT) has the potential to serve as a gold standard for joint imaging since it provides high resolution three-dimensional (3D) images of bone structure. The authors have developed a method to quantify erosion volume changes on wrist CT scans. In this article they present a description and validation of the methodology using multiple scans of a hand phantom and five human subjects. An anthropomorphic hand phantom was imaged with a clinical CT scanner at three different orientations separated by a 30-deg angle. A reader used the semiautomated software tool to segment the individual carpal bones of each CT scan. Reproducibility was measured as the root-mean-square standard deviation (RMMSD) and coefficient of variation (CoV) between multiple measurements of the carpal volumes. Longitudinal erosion progression was studied by inserting simulated erosions in a paired second scan. The change in simulated erosion size was calculated by performing 3D image registration and measuring the volume difference between scans in a region adjacent to the simulated erosion. The RMSSD for the total carpal volumes was 21.0 mm3 (CoV = 1.3%) for the phantom, and 44.1 mm3 (CoV = 3.0%) for the in vivo subjects. Using 3D registration and local volume difference calculations, the RMMSD was 1.0-3.0 mm3 The reader time was approximately 5 min per carpal bone. There was excellent agreement between the measured and simulated erosion volumes. The effect of a poorly measured volume for a single erosion is mitigated by the large number of subjects that would comprise a clinical study and that there will be many erosions measured per patient. CT promises to be a quantifiable tool to measure erosion volumes and may serve as a gold standard that can be used in the validation of other modalities such as magnetic resonance imaging.
17888205 Efficacy of etanercept in patients with AA amyloidosis secondary to rheumatoid arthritis. 2007 Jul OBJECTIVE: The efficacy of biological therapies in rheumatoid arthritis (RA) is well known, but their hypothetical benefit in amyloid A (AA) amyloidosis secondary to RA still remains to be considered. We evaluated the efficacy and safety of etanercept in serum amyloid A (SAA) 1.3 allele Japanese patients with AA amyloidosis secondary to RA. METHODS: Seven RA patients with histologically confirmed AA amyloidosis and renal involvement who were treated with etanercept were enrolled. They all had the SAA1.3 allele, which has been shown to be a risk factor not only for the association of AA amyloidosis but also for a poor prognosis in Japanese RA patients. Efficacy was assessed as a sustained decrease in RA inflammation and an amelioration of renal function. RESULTS: RA inflammation and AA amyloidosis were improved and stabilized after 43.4 +/- 16.5 weeks. At week 20 the number of tender (p = 0.017) and swollen (p = 0.017) joints, and levels of serum C-reactive protein (p = 0.018) and albumin (p = 0.045) had improved. The values for SAA, serum creatinine, calculated creatinine clearance, and proteinuria also ameliorated. No severe adverse events were observed. One patient eventually had to go on hemodialysis but her tolerance of etanercept remained stable. CONCLUSION: Etanercept can be used safely and effectively in AA amyloidosis secondary to RA with renal involvement, and is of clinical benefit in the short-term, even in patients on hemodialysis. It appears that SAA1.3 allele may be used as a clinical parameter for the introduction of etanercept in Japanese RA with AA amyloidosis.
16972019 Elevated levels of soluble Fas (APO-1, CD95), soluble Fas ligand, and matrix metalloprotei 2007 Mar To investigate serum levels of soluble Fas (sFas), soluble Fas ligand (sFas-L), and matrix metalloproteinase-3 (MMP-3) in patients with active untreated adult onset Still's disease (AOSD). Serum levels of sFas, sFas-L, and MMP-3 were determined by enzyme-linked immunosorbent assays in 20 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. Linear regression was used to evaluate the correlation between clinical activity scores and serum levels of sFas, sFas-L, and MMP-3 in AOSD patients. Significantly higher levels of sFas, sFas-L, and MMP-3 in sera were found in active untreated AOSD patients compared to healthy controls. Serum levels of sFas, sFas-L, and MMP-3 correlated well with clinical activity scores of AOSD patients (r=0.467, 0.694, and 0.798, respectively). There was a significant correlation between CRP values and serum levels of sFas-L as well as MMP-3 (r=0.583 and r=0.582, respectively, both p<0.01), and a positive correlation between serum sFas-L levels and serum MMP-3 levels (r=0.726, p<0.001) in AOSD patients. Significantly higher levels of serum sFas-L were found in AOSD patients than in RA patients. Serum levels of sFas, sFas-L, and MMP-3 fluctuated and were found to be parallel to disease activity of AOSD. sFas, sFas-L, and MMP-3, which were significantly elevated in sera of active untreated AOSD patients and paralleled disease activity, may be involved in the pathogenesis of this disease. Further studies are needed to determine the pathophysiologic role of sFas, sFas-L, and MMP-3 in AOSD.
18383539 Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate 2008 Apr OBJECTIVE: To assess the efficacy, safety, and pharmacology of subcutaneous administration of golimumab in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX). METHODS: Patients were randomly assigned in a double-blinded manner to receive injections of placebo plus MTX or 50 mg or 100 mg golimumab every 2 or 4 weeks plus MTX through week 48. Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. The study was powered to detect a difference in the primary end point when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo. RESULTS: The primary end point was attained. Sixty-one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR20 response at week 16 compared with 37% of patients in the placebo plus MTX group (P=0.010). In addition, 79% of patients in the group receiving 100 mg golimumab every 2 weeks achieved an ACR20 response (P<0.001 versus placebo). Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9% of patients in the combined golimumab groups and in 6% of patients in the placebo group. CONCLUSION: Golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX.
17289759 Magnetic resonance imaging and bone scintigraphy in the differential diagnosis of unclassi 2008 Jan OBJECTIVES: To investigate the value in clinical practice of hand magnetic resonance imaging (MRI) and whole body bone scintigraphy in the differential diagnosis of patients with unclassified arthritis. METHODS: 41 patients with arthritis (> or = 2 swollen joints, > 6 months' duration) which remained unclassified despite conventional clinical, biochemical and radiographic (hands and feet) examinations were studied. Patients who fulfilled the ACR criteria for rheumatoid arthritis (RA) or had radiographic bone erosions were excluded. Contrast enhanced MRI of the wrist and metacarpophalangeal joints of the most symptomatic hand and whole body bone scintigraphy were performed. Two rheumatologists agreed on the most likely diagnosis and the patients were treated accordingly. A final diagnosis was made by another specialist review 2 years later. RESULTS: Tentative diagnoses after MRI and bone scintigraphy were: RA (n = 13), osteoarthritis (n = 8), other inflammatory diseases (n = 11), arthralgias without inflammatory or degenerative origin (n = 9). Two years later 11 of 13 patients with an original tentative diagnosis of RA had fulfilled the ACR criteria while two were reclassified (one to psoriatic arthritis (RF negative + psoriasis); one to non-specific self-limiting arthritis). No patients classified as non-RA at baseline had fulfilled the ACR criteria after 2 years. The presence of MRI synovitis, MRI erosion and bone scintigraphic pattern compatible with RA showed 100% specificity for a diagnosis of RA at 2 year follow-up. CONCLUSIONS: In patients with arthritis unclassified despite conventional clinical, biochemical and radiographic examinations, MRI and scintigraphy allowed correct classification as RA or non-RA in 39 of 41 patients when fulfilment of ACR criteria 2 years later was considered the standard reference.
16356191 Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheu 2006 Many extracellular matrix (ECM) proteases seem to be important in rheumatoid arthritis (RA) and regulation of their transcription levels is a critical mechanism for controlling their activity. We have investigated, therefore, whether the best-characterized single nucleotide polymorphisms (SNPs) affecting transcription of the ECM proteases that have been related with joint pathology are associated with RA susceptibility. Nine SNPs in eight genes were selected by bibliographic search, including SNPs in the genes encoding matrix metalloproteinase (MMP)1, MMP2, MMP3, MMP7, MMP9, MMP13, plasminogen activator, tissue type (PLAT) and PAI-1. They were studied in a case-control setting that included 550 RA patients and 652 controls of Spanish ancestry from a single center. Genotyping was performed by single-base extension. Only two of the nine SNPs showed significant association with RA susceptibility. RA patients showed increased frequencies of the -7351 T allele of the gene encoding PLAT (36.4% versus 32.1% in controls, p = 0.026) and the -1306 T allele of the gene encoding MMP2 (24.5% versus 20.3% in controls, p = 0.013). These two alleles seemed to cooperate according to an additive model with respect to increased RA susceptibility (p = 0.004), and they were the low-expression alleles of the respective SNPs in a PLAT enhancer and the MMP2 promoter. These findings are in agreement with previous data suggesting that these two ECM proteases have a protective role in RA pathology. Confirmation of these associations will be needed to support these hypotheses. The remaining SNPs did not show association, either individually or collectively. Therefore, although regulatory SNPs in ECM proteases did not show any major effect on RA susceptibility, it was possible to find modest associations that, if replicated, will have interesting implications in the understanding of RA pathology.
17520869 T-cell immune response cDNA 7 in allograft rejection and inflammation. 2007 May The membrane protein T-cell immune response cDNA 7 (TIRC7) is transiently expressed in subsets of lymphocytes following antigen stimulation. The importance of TIRC7 in immune activation is demonstrated by the effect of antibodies directed against extracellular domains of TIRC7. In vitro targeting of TIRC7 inhibits proliferation and cytokine expression in human, mouse and rat lymphocytes, and these inhibitory effects have been associated with induction of cytotoxic T-lymphocyte antigen 4 mRNA and protein in the presence of TIRC7 antibodies. In vivo, anti-TIRC7 antibodies prevent kidney transplant rejection in rats and heart allograft rejection in mice. Treatment with an anti-TIRC7 antibody as monotherapy or in combination with TNFalpha blockade inhibits disease progression in collagen-induced arthritis. TIRC7 expression decreases in the peripheral blood of humans who have undergone cardiac transplant prior to clinical rejection, and is therefore a promising noninvasive tool for the prediction of rejection. Thus, targeting of TIRC7 may lead to the development of specific and effective therapeutic and diagnostic approaches by unifying relevant cellular and molecular responses in T- and B-cell subsets, and represents a promising new pathway for immune regulation in transplantation and autoimmune disease.
18534538 Rotational kinematics of a modern fixed-bearing posterior stabilized total knee arthroplas 2009 Jun The purpose of this study was to evaluate the rotational kinematics of a fixed-bearing posteriorly stabilized total knee design in moderate and deep flexion. Three-dimensional kinematics analyses were conducted on 20 knees in 4 weight-bearing positions using 3-dimensional shape-matching techniques. Average maximum skeletal flexion was 138 degrees . Internal tibial rotation was demonstrated in 19 of 20 knees. The average internal tibial rotation in midflexed lunge was 5.5 degrees (-3.8 degrees to 14.1 degrees ) and in maximum flexion kneeling was 4.0 degrees (-3.1 degrees to 10.6 degrees ). Separation of articular surfaces was not identified. In this study, patients with this device demonstrated patterns of rotation similar to those previously reported for both the normal knee and rotating platform designs.
18209096 Synoviocyte stimulation by the LFA-1-intercellular adhesion molecule-2-Ezrin-Akt pathway i 2008 Feb 1 In rheumatoid arthritis (RA), the synovium is infiltrated by mononuclear cells that influence the proliferation and activation of fibroblast-like synoviocytes (FLS) through soluble mediators as well as cell-to-cell contact. To identify receptor-ligand pairs involved in this cross-talk, we cocultured T cells with FLS lines isolated from synovial tissues from RA patients. Coculture with T cells induced phosphorylation of Akt (Ser(473)) and its downstream mediators, GSK-3alpha/GSK-beta, FoxO1/3a, and mouse double minute-2, and enhanced FLS proliferation. T cell-mediated phospho-Akt up-regulation was unique for FLS as no such effect was observed upon interaction of T cells with dendritic cells and B cells. Akt activation was induced by all functional T cell subsets independent of MHC/Ag recognition and was also found with other leukocyte populations, suggesting the involvement of a common leukocyte cell surface molecule. Akt phosphorylation, enhanced in vitro FLS proliferation, and enhanced FLS IL-6 production was inhibited by blocking Abs to CD11a and ICAM-2 whereas Abs to ICAM-1 had a lesser effect. Selective involvement of the LFA-1-ICAM-2 pathway was confirmed by the finding of increased ezrin phosphorylation at Tyr(353) that is known to be downstream of ICAM-2 and supports cell survival through Akt activation. CD28(-) T cells, which are overrepresented in RA patients, have high CD11a cell surface expression and induce Akt phosphorylation in FLS more potently than their CD28(+) counterparts. These findings identify ICAM-2 as a potential therapeutic target to inhibit FLS activation in RA, allowing for a more selective intervention than broad LFA-1 inhibition.
18668556 Increased numbers of circulating polyfunctional Th17 memory cells in patients with seroneg 2008 Aug OBJECTIVE: A distinct subset of proinflammatory CD4+ T cells that produce interleukin-17 was recently identified. These cells are implicated in different autoimmune disease models, such as experimental autoimmune encephalomyelitis and collagen-induced arthritis, but their involvement in human autoimmune disease has not yet been clearly established. The purpose of this study was to assess the frequency and functional properties of Th17 cells in healthy donors and in patients with different autoimmune diseases. METHODS: Peripheral blood was obtained from 10 psoriatic arthritis (PsA), 10 ankylosing spondylitis (AS), 10 rheumatoid arthritis (RA), and 5 vitiligo patients, as well as from 25 healthy donors. Synovial tissue samples from a separate group of patients were also evaluated (obtained as paraffin-embedded sections). Peripheral blood cells were analyzed by multiparameter flow cytometry and immunohistochemistry. Cytokine production was examined by enzyme-linked immunosorbent assay and intracellular cytokine staining using specific monoclonal antibodies. Synovial tissue was examined for infiltrating T cells by immunohistochemical analysis. RESULTS: We found increased numbers of circulating Th17 cells in the peripheral blood of patients with seronegative spondylarthritides (PsA and AS), but not in patients with RA or vitiligo. In addition, Th17 cells from the spondylarthritis patients showed advanced differentiation and were polyfunctional in terms of T cell receptor-driven cytokine production. CONCLUSION: These observations suggest a role of Th17 cells in the pathogenesis of certain human autoimmune disorders, in particular the seronegative spondylarthritides.
16414464 Complications of total shoulder arthroplasty: are they fewer or different? 2006 Jan There has been significant evolution of total shoulder arthroplasty design and improvement in technique over the past 25 years, but there is no information available as to whether this has translated into lower complication rates or different sorts of complications. The purpose of this study was to determine the contemporary complications and their frequency. Between 1990 and 2000, 431 total shoulder arthroplasties were performed with a cemented all-polyethylene glenoid component. Follow-up averaged 4.2 years. Complications were categorized by type as early or late and as minor, major, or major requiring reoperation. In total, 53 surgical complications occurred in 53 patients (12%). Of these, 32 were major complications (7.4%), with 17 of these requiring reoperation. Index complications in order of frequency included rotator cuff tearing, postoperative glenohumeral instability, and periprosthetic humeral fracture. Notably, glenoid and humeral component loosening requiring reoperation occurred in only 1 shoulder. Developing a complication was unrelated to diagnosis, previous surgery, age, sex, humeral head size, or cementing or not cementing the humeral component. Data from the contemporary patient group suggest that there are fewer complications of shoulder arthroplasty and less need for reoperation. Especially striking is the near absence of component revision because of loosening or other mechanical factors. Periprosthetic humeral fractures are more common; the explanation for this warrants further study.