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ID PMID Title PublicationDate abstract
20346237 Adult onset Still's disease: clinical presentation in a large cohort of Italian patients. 2010 Jan OBJECTIVES: To characterise the clinical phenotype of Italian patients with adult-onset Still's disease (AOSD). METHODS: Sixty-six subjects who received a definite diagnosis of AOSD were seen and followed-up at our institution from 1991 to 2009. The diagnosis was made by a senior rheumatologist and confirmed by Yamaguchi's criteria for AOSD. Data regarding clinical manifestations, laboratory and radiographic features, and disease course were collected and compared with those reported in other published series of different ethnicity. RESULTS: The most frequent features were: articular pain (100%), acute phase reactants elevation (100%), elevated serum ferritin (97%), high fever (95%), negative RF and ANA (92%), neutrophilia (82%), skin rash (79%), and overt arthritis (79%). Forty-percent of patients showed a chronic articular disease. Five subjects (8%) experienced severe, life-threatening complications, and 1 patient died. As compared to other North American, North European, Middle Eastern, and Far Eastern cohorts, Italian patients showed significant differences in several epidemiologic, clinical and laboratory features. CONCLUSIONS: Our data show that AOSD is rare in the Italian population, and that its clinical presentation appears to be significantly influenced by the ethnicity of the affected patients. Given its broad differential diagnosis, early recognition of this condition is challenging, but it could become crucial in the setting of severe complications. Beyond the protean manifestations of this disease, a clinical picture of seronegative febrile arthritis and skin rash, concurrent with a marked elevation in serum ferritin should always be mindful of AOSD.
19299715 Functional killer Ig-like receptors on human memory CD4+ T cells specific for cytomegalovi 2009 Apr 1 Although very few CD4(+) T cells express killer Ig receptors (KIR), a large proportion of CD4(+) T cells with a late memory phenotype, characterized by the absence of CD28, does express KIR. Here, we show that KIR expression on CD4(+) T cells is also associated with memory T cell function, by showing that the frequency of CMV-specific cells is higher in CD4(+)KIR(+) than CD4(+)KIR(-) T cells. In addition, engagement of an inhibitory KIR inhibited the CMV-specific proliferation of these CD4(+)KIR(+) memory T cells, but had no detectable effect on cytokine production. Our data reveal that, in marked contrast with CD8(+) T cells, the activity of a subset of CMV-specific CD4(+) T cells is modulated by HLA class I-specific KIR. Thus, the CMV-induced down-regulation of HLA class I may in fact enhance memory CMV-specific CD4(+) T cell responses restricted by HLA class II.
21052564 Pain and ketoprofen: what is its role in clinical practice? 2010 Jul Ketoprofen is a drug belonging to the family of non-steroidal anti-inflammatory drugs (NSAIDs). The present review examines the main available clinical evidence of ketoprofen in the treatment of acute and chronic pain, of both rheumatic and traumatic origin, as well as postoperative pain. Ketoprofen has shown to be an excellent choice of drug for the treatment of chronic pain in patients with osteoarthritis, rheumatoid arthritis or gout, demonstrating a high level of efficacy with good tolerability also in elderly patients. Even in the treatment of acute forms of pain such as bursitis, tendinitis and back pain, ketoprofen compares favourably to other NSAIDs (e.g., ibuprofen and diclofenac) in terms of efficacy. Ketoprofen has been shown to be effective also for the treatment of post-operative pain, particularly in the orthopaedic field, with an efficacy similar to opioids in some studies. In this setting, some evidence indicates that ketoprofen exhibits additional important benefits, showing to be effective in the prophylaxis of heterotopic calcification following hip or pelvic major intervention, without affecting the bone healing process. Moreover, the use of ketoprofen in elastomeric pump in combination with opioids or other NSAIDs has proven to be effective and safe. In conclusion, available data confirm that ketoprofen is effective and well tolerated, through different administration routes, for the treatment of various forms of rheumatic, traumatic and post-surgical pain, and may therefore be considered as a valid therapeutic option for these patients.
19919693 Functional activation of proline-rich tyrosine kinase2 (PYK2) in peripheral blood mononucl 2009 Nov 17 BACKGROUND: Systemic lupus erythematosus (SLE) is a representative systemic autoimmune disease characterized by activated T cells and polyclonally activated B cells that produce autoantibodies. Activation of autoreactive T and B cells plays a pivotal role in the pathogenesis of this disease. A role of focal adhesion kinase (FAK) in the pathogenesis has been suggested. Proline-rich tyrosine kinase2 (PYK2) is structurally related to FAK, however, the functional activation of PYK2 in SLE remains unclear. In the present study, we showed that PYK2 is significantly increased and activated in peripheral blood mononuclear cells (PBMCs) of patients with SLE. In addition, we showed the involvement of PYK2 proteins in the up-regulation of CD40L and CTLA4 expression and PBMC proliferation. METHODS: Freshly isolated PBMCs from 48 SLE patients, 32 patients with rheumatoid arthritis(RA) and 24 healthy individuals were analyzed for the expression and activation of PYK2 by western-blotting and immunocytochemistry. The other isolated PBMCs from patients with this condition were cultured and stimulated with PMA or TyrA9, and then the expression of costimulatory molecules CD40L and CTLA4 was evaluated using flow cytometry, PBMCs proliferation was determined with [3H]-thymidine incorporation (CPM). RESULTS: Compared with RA patients and healthy donors, PBMCs from SLE patients expressed more of both the total PYK2 protein and its activated/phosphorylated form. The increase of activated PYK2 protein in SLE PBMCs was correlated with the complication of nephritis and inversly associated the level of serum complements. In active SLE patients, activation of PYK2 in PBMCs is accompanying the increased cell proliferation and the induced expression of costimulatory molecules CD40L and CTLA4. CONCLUSION: Our findings indicate that phosphorylated PYK2 in SLE PBMCs may induce the expression of CD40L and CTLA4, and subsequently the cell proliferation. PYK2 signaling enhances the autoreactive lymphocyte activation and plays an important role in the pathogenesis of SLE.
20804198 Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2 2010 Sep 23 The discovery and characterization of 7k (BMS-582949), a highly selective p38α MAP kinase inhibitor that is currently in phase II clinical trials for the treatment of rheumatoid arthritis, is described. A key to the discovery was the rational substitution of N-cyclopropyl for N-methoxy in 1a, a previously reported clinical candidate p38α inhibitor. Unlike alkyl and other cycloalkyls, the sp(2) character of the cyclopropyl group can confer improved H-bonding characteristics to the directly substituted amide NH. Inhibitor 7k is slightly less active than 1a in the p38α enzymatic assay but displays a superior pharmacokinetic profile and, as such, was more effective in both the acute murine model of inflammation and pseudoestablished rat AA model. The binding mode of 7k with p38α was confirmed by X-ray crystallographic analysis.
19800762 Sjögren syndrome: advances in the pathogenesis from animal models. 2009 Nov Sjögren syndrome is an autoimmune disease characterized by hyposecretion of the lacrimal and salivary glands, resulting in dryness of the eyes and mouth. Individuals may experience primary Sjögren syndrome or a secondary form accompanying another rheumatic autoimmune disease, such as rheumatoid arthritis or systemic lupus erythematosus. The pathogenic mechanisms of Sjögren syndrome remain largely unknown, in part a consequence of the heterogeneity of the disease. Animal models have shed light on the connections between specific pathways and symptoms, but an ideal system is wanting. Improved disease models will enable a better understanding of Sjögren syndrome, including how immune tolerance is lost and potential therapeutic interventions. Most importantly, an optimal model will enable detection of disease biomarkers, since injury to the salivary glands may precede lymphocytic infiltration. This review aims to characterize available mice models of Sjögren syndrome, including advantages and disadvantages, from the researcher's perspective.
19364934 Long-term course of demyelinating neuropathies occurring during tumor necrosis factor-alph 2009 Apr OBJECTIVE: To report the long-term follow-up (mean, 41 months; range, 25-55 months) of patients with demyelinating neuropathy occurring after tumor necrosis factor-alpha (TNF-alpha) blocker treatment (infliximab [Remicade], etanercept [Enbrel], and adalimumab [Humira]). BACKGROUND: Demyelinating neuropathy is a rare adverse event of anti-TNF-alpha therapy. Improvement usually occurs after drug interruption and/or in association with usual treatments for demyelinating neuropathies. DESIGN: Case report with review of the previously published cases. SETTING: University hospital in Le Kremlin-Bicêtre, France: tertiary reference center for peripheral neuropathies and national reference center for rare peripheral neuropathies (www.nnerf.fr). PATIENTS: Five patients (4 men, mean age, 47 years) who developed a demyelinating neuropathy during anti-TNF-alpha therapy. MAIN OUTCOME MEASURE: Development of neuropathy. RESULTS: Neuropathy developed early (8 months) after treatment introduction. Various clinical patterns were encountered, including pure sensory neuropathy. Immunomodulating treatments were always required for neuropathy control. Chronic demyelinating neuropathy developed either after change of anti-TNF-alpha drug or spontaneously after treatment discontinuation without any drug reintroduction. CONCLUSION: Influence of anti-TNF-alpha treatment continuation on the long-term course of neuropathy is variable, suggesting that anti-TNF-alpha treatment withdrawal is not always necessary for neuropathy control.
19374589 Tumor necrosis factor-alpha alters the modulatory effects of mesenchymal stem cells on ost 2009 Dec Mesenchymal stem cells (MSCs) are characterized by their hematopoiesis-supporting and immunosuppressive capacity, while osteoclasts are main cell components in the endosteal hematopoietic stem cell niche and pivotal players in osteoimmunology. To clarify the association of these 2 kinds of cells, mouse CD11b(+) monocytes were cultured onto MSC layers in the presence or absence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). The results showed that MSCs independently supported osteoclast development and this effect was enhanced by M-CSF and RANKL. Interestingly, tumor necrosis factor-alpha (TNF-alpha)-stimulated MSCs turned to inhibit osteoclast formation and protect tusk slices from osteoclastic resorption. Real-time PCR and ELISA assays demonstrated that osteoprotegerin expression at both mRNA and protein levels in TNF-alpha-stimulated MSCs was up-regulated, at least partially by activating the mitogen-activated protein kinase pathway. Furthermore, TNF-alpha-stimulated MSCs maintained their immunophenotypic, multipotential differentiation and immunosuppressive characteristics. Moreover, MSCs treated with synovial fluid from rheumatoid arthritis patients modulated osteoclast generation in close relation with the TNF-alpha levels. This study suggests that MSCs exhibit dual modulatory function on osteoclasts and the result might shed light on understanding the involvement of MSCs in the inflammatory diseases.
20360734 Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 s 2010 Apr 1 Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
20427474 DBM1285 suppresses tumor necrosis factor alpha production by blocking p38 mitogen-activate 2010 Aug Tumor necrosis factor alpha (TNF-alpha) is a major inflammatory cytokine that plays an important role in the development of various inflammatory diseases. TNF-alpha has been considered as a potential therapeutic target for the treatment of chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease. In this study, we report that cyclopropyl-{4-[4-(4-fluorophenyl)-2-piperidin-4-yl-thiazol-5-yl]pyrimidin-2-yl}amine (DBM1285) is a novel inhibitor of TNF-alpha production. DBM1285 concentration-dependently inhibited lipopolysaccharide (LPS)-induced TNF-alpha secretion in various cells of macrophage/monocyte lineage, including mouse bone marrow macrophages, THP-1 cells, and RAW 264.7 cells. However, LPS-induced mRNA expression of TNF-alpha was not affected by DBM1285 in these cells. Further studies demonstrated that the inhibitory effect of DBM1285 on TNF-alpha production might be mediated by post-transcriptional regulation through the modulation of the p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein kinase 2 (MK2) signaling pathway. We also confirmed that DBM1285 directly inhibits p38 MAPK enzymatic activity. In vivo administration of DBM1285 inhibited LPS-induced increase in the plasma level of TNF-alpha in mice. Whole-blood in vivo target inhibition assay also revealed that DBM1285 attenuates p38 MAPK activity after oral administration in mice. Moreover, DBM1285 suppressed zymosan-induced inflammation and adjuvant-induced arthritis in murine models. Collectively, these results suggest that DBM1285 inhibits TNF-alpha production, at least in part, by blocking the p38 MAPK/MK2 pathway. Furthermore, in vivo results suggest that DBM1285 might be a possible therapeutic candidate for the treatment of TNF-alpha-related chronic inflammatory diseases.
20855873 Functional analysis of recombinant calreticulin fragment 39-272: implications for immunobi 2010 Oct 15 Although calreticulin (CRT) is a major Ca(2+)-binding luminal resident protein, it can also appear on the surface of various types of cells and it functions as an immunopotentiating molecule. However, molecular mechanisms underlying the potent immunobiological activity of cell surface CRT are still unclear. In the present study, a recombinant fragment (rCRT/39-272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed in Escherichia coli. The affinity-purified rCRT/39-272 assembles into homodimers and oligomers in solution and exhibits high binding affinity to various glycans, including carrageenan, alginic acids, and hyaluronic acids. Functionally, rCRT/39-272 is capable of driving the activation and maturation of B cells and cytokine production by macrophages in a TLR-4-dependent manner in vitro. It specifically binds recombinant mouse CD14, but not BAFFR and CD40. It is also able to trigger Ig class switching by B cells in the absence of T cell help both in vitro and in vivo. Furthermore, this fragment of CRT exhibits strong adjuvanticity when conjugated to polysaccharides or expressed as part of a fusion protein. Soluble CRT can be detected in the sera of patients with rheumatoid arthritis or systemic lupus erythematosus, but not in healthy subjects. We argue that CRT, either on the membrane surface of cells or in soluble form, is a potent stimulatory molecule to B cells and macrophages via the TLR-4/CD14 pathway and plays important roles in the pathogenesis of autoimmune diseases.
18974373 CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoiet 2009 Feb 12 Relapse of malignancy after allogeneic hematopoietic cell transplantation (allo-HCT) remains a therapeutic challenge. Blockade of the CTLA4 molecule can effectively augment antitumor immunity mediated by autologous effector T cells. We have assessed the safety and preliminary efficacy of a neutralizing, human anti-CTLA4 monoclonal antibody, ipilimumab, in stimulating the graft-versus-malignancy (GVM) effect after allo-HCT. Twenty-nine patients with malignancies that were recurrent or progressive after allo-HCT, received ipilimumab as a single infusion at dose cohorts between 0.1 and 3.0 mg/kg. Dose-limiting toxicity was not encountered, and ipilimumab did not induce graft-versus-host disease (GVHD) or graft rejection. Organ-specific immune adverse events (IAE) were seen in 4 patients (grade 3 arthritis, grade 2 hyperthyroidism, recurrent grade 4 pneumonitis). Three patients with lymphoid malignancy developed objective disease responses following ipilimumab: complete remission (CR) in 2 patients with Hodgkin disease and partial remission (PR) in a patient with refractory mantle cell lymphoma. At the 3.0 mg/kg dose, active serum concentrations of ipilimumab were maintained for more than 30 days after a single infusion. Ipilimumab, as administered in this clinical trial, does not induce or exacerbate clinical GVHD, but may cause organ-specific IAE and regression of malignancy. This study is registered at (http://clinicaltrials.gov) under NCI protocol ID P6082.
19705046 The potential impact of new National Osteoporosis Foundation guidance on treatment pattern 2010 Jan This analysis of National Health and Nutrition Examination Survey III data describes the prevalence of risk factors for osteoporosis and the proportions of men and postmenopausal women age 50 years and older who are candidates for treatment to lower fracture risk, according to the new FRAX-based National Osteoporosis Foundation Clinician's Guide. INTRODUCTION: Little information is available on prevalence of osteoporosis risk factors or proportions of US men and women who are potential candidates for treatment. METHODS: The prevalence of risk factors used in the new National Osteoporosis Foundation (NOF) FRAX-based Guide to the Prevention and Treatment of Osteoporosis was estimated using data from the third National Health and Nutrition Examination Survey (NHANES III). Risk factors not measured in NHANES III were simulated using World Health Organization cohorts. The proportion of US men and postmenopausal women age 50+ years who are treatment candidates by the new NOF Guide were calculated; for non-Hispanic white (NHW) women, the proportion eligible by the new NOF Guide was compared with that based on an earlier NOF Guide. RESULTS: Twenty percent of men and 37% of women were potential candidates for treatment to prevent fractures by the new NOF Guide. Among NHW women, 53% were potential candidates by the previous NOF Guide compared with 41% by the new guide. CONCLUSIONS: One fifth of men and 37% of postmenopausal women are eligible for osteoporosis treatment consideration by the new NOF Guide. However, fewer NHW women are eligible by the new guide than by the previous NOF Guide.
19753835 [Persistent type 2 lepra reaction (erythema nodosum) and clofazimine-induced lethal entero 2009 Mar INTRODUCTION: Clofazimine enterophathy is a serious complication of clofazimine when used at high doses for treatment of type 2 lepra or or erythema nodosum leprosum. Objective. A woman is presented who had a delayed diagnosis of leprosy, persistent type 2 lepra reaction and lethal clofazimine enteropathy. MATERIALS AND METHODS: A 31-year-old woman presented leprosy symptoms over a 16-year period without medical diagnosis of her disease. During this period, type 2 lepra episodes occurred, but were not accurately diagnosed. These episodes became more severe during her second pregnancy. The patient and her family were interviewed, and her clinical history reviewed. RESULTS: After twelve years of medical consults, lepromatous leprosy was diagnosed, based on perforation of her nasal septum, with a bacterial index of 5. Her husband and a 12-year-old daughter have leprosy symptoms. During multidrug therapy, she presented with repeated type 2 lepra reaction episodes for which she received daily clofazimine 400 mg doses. Two months after this treatment, severe and frequent episodes of intense abdominal pain began to occur. These persisted for more than a year and were managed with in-hospital administration of several classes of painkillers and antispasmodic medication, including morphine. She also presented with sporadic diarrhea, constipation, nausea, weight loss and mesenteric adenopathies. She died finally due to this intestinal condition. No autopsy was performed. CONCLUSIONS: The patient's clinical presentation suggested a clofazimine-induced lethal enteropathy, a complication not previously seen in Colombia. This connection was not recognized by the medical officers that treated the patient.
20187768 The TGF-beta superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of 2010 Jun Macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15), a divergent member of the TGF-beta superfamily is induced by a range of proinflammatory cytokines and oxidized low-density lipoprotein (oxLDL) and is highly expressed in macrophages in atherosclerotic and tumor lesions. MIC-1/GDF15, a major p53 target gene, is largely described to have anti-tumorigenic activity and more recently high MIC-1/GDF15 serum levels in late stage cancer were shown to be the major cause of cancer-associated weight loss. MIC-1/GDF15 serum levels independently predict both atherosclerotic events and severity of rheumatoid arthritis (RA), suggesting serum levels are important in modifying disease expression. Controlling serum levels is the ratio of latent unprocessed MIC-1/GDF15 stromal stores to soluble mature MIC-1/GDF15 generated by the cell. Here, we investigate MIC-1/GDF15 secretion from U937 monocytoid cells and identify novel mechanisms designed to ensure secretion of unprocessed cytokine and creation of latent stromal stores. We find that endogenous MIC-1/GDF15 is secreted as both processed and unprocessed forms. Pulse chase analysis of MIC-1/GDF15 secretion reveals that unprocessed MIC-1/GDF15 precursor is rapidly secreted, while mature MIC-1/GDF15 generated within the cell by intracellular processing is secreted much slower, possibly via an alternate secretory route. The COOH-T 47 amino acids of the propeptide are responsible for rapid secretion of MIC-1/GDF15 precursor and this effect occurs in the trans-Golgi network (TGN)/post TGN compartment. Thus, variations in MIC-1/GDF15 intracellular processing, regulating the presence or absence of propeptide, are a powerful mechanism modulating rate of MIC-1/GDF15 secretion and proMIC-1/GDF15 stromal storage, with major impact on circulating levels of mature MIC-1/GDF15.
20864144 Relation of systemic autoantibodies to the number of extraglandular manifestations in prim 2011 Jun OBJECTIVES: Extraglandular manifestations (EGM) are often seen in patients with primary Sjögren's syndrome and are probably due to a (more) disturbed immune system. Their relation to systemic autoantibodies remains controversial. We hypothesized that positive serology as reflected by the presence of 1 of more systemic autoantibodies is related to the number of EGM. METHODS: To this purpose, all patients, visiting a large nonacademic teaching hospital, with primary Sjögren's syndrome, according to the revised American-European classification criteria of 2002, were retrospectively analyzed. RESULTS: In this group of 65 patients, systemic autoantibodies were abundant: anti-Sjögren syndrome A antigen (SSA) and/or anti-Sjögren syndrome B antigen (SSB) (80%), immunoglobulinM-Rheumatoid factor (IgM-RF) (68%), and anti-nuclear antibodies (ANA) (77%). Their presence was often found together and correlated to the presence of hypergammaglobulinemia. There was a statistically significant correlation between the number of systemic autoantibodies and the total number of EGM (P = 0.025). Anti-SSA was the strongest predictor of the presence of EGM (OR = 4.67, P = 0.024). CONCLUSIONS: These findings indicate that a more disturbed immune system, as reflected by B-cell hyperactivity, with autoantibody formation and hypergammaglobulinemia, is associated with more systemic manifestations in patients with primary Sjögren's syndrome.
19565495 Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy 2009 Jul OBJECTIVE: Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence. METHODS: We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects. RESULTS: We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area. CONCLUSION: The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.
19231014 Surgical management of portal hypertension in Felty's syndrome: A case report and literatu 2009 Apr BACKGROUND/AIMS: Bleeding esophageal varices are a common complication of portal hypertension in patients with underlying liver disease. Often patients with hepatic cirrhosis have hypersplenism with thrombocytopenia and leukopenia. Felty's syndrome is a disorder where patients with rheumatoid arthritis develop splenomegaly, neutropenia, and on rare occasions, portal hypertension without underlying cirrhosis. METHODS: We present a case of a patient with portal hypertension secondary to Felty's syndrome and discuss the importance of recognizing this condition since the treatment of choice is surgical management with splenectomy. A review of the literature and underlying liver histologic features are discussed. RESULTS: Medical and surgical management of patients with Felty's syndrome is different from those with portal hypertension due to cirrhosis. CONCLUSION: Splenectomy is the treatment of choice for complications of portal hypertension in patients with Felty's Syndrome.
19578996 Sjögren syndrome or sjögren disease? The histological and immunological bias caused by t 2010 Apr The current 2002 classification criteria do not cover the broad clinical and immunological heterogeneity of primary Sjögren syndrome (SS), since five of the six criteria focus exclusively on glandular involvement and the remaining criterion is the mandatory presence of anti-Ro/La antibodies. The aim of this study was to analyze the clinical features of patients with a well-established diagnosis of primary SS who do not fulfill the 2002 classification criteria. Five hundred seven patients diagnosed with primary SS (1993 criteria) were consecutively included and followed up. Two hundred twenty-one (44%) patients did not fulfill the 2002 criteria. These patients were older at diagnosis (p < 0.001) and had a lower frequency of parotid enlargement (p = 0.002), fever (p = 0.041), arthritis (p = 0.041), vasculitis (p = 0.050), peripheral neuropathy (p = 0.002), cranial nerve involvement (p = 0.015), raised erythrocyte sedimentation rate ( ESR) levels (p < 0.001), anemia (p < 0.001), leukopenia (p = 0.037), hypergammaglobulinemia (p < 0.001), positive rheumatoid factor ( RF; p = 0.002), and cryoglobulinemia (p = 0.049) in comparison with those fulfilling 2002 criteria. However, there were no significant differences in the prevalence of sicca features, diagnostic tests, overall systemic involvement, antinuclear antibodies , complement levels, development of B-cell lymphoma, or survival. Patients with anti-Ro antibodies had the highest frequencies of systemic features, hematological abnormalities, and altered immunological markers. In conclusion, patients fulfilling the 2002 criteria, who have either a specific histological diagnosis (lymphocytic infiltration) or highly specific autoantibodies (Ro/La), might well be considered to have Sjögren "disease." In contrast, etiopathogenic mechanisms other than lymphocytic-mediated epithelial damage could be involved in patients with negative Ro and negative biopsy, in whom the term Sjögren "syndrome" seems more adequate.
19446580 Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis. 2009 Jun 4 To examine whether grape seed proanthocyanidin extract (GSPE) which is known to act as an antioxidant has therapeutic effect on collagen-induced arthritis (CIA) in mice, an animal model of rheumatoid arthritis. Mice were treated with an intraperitoneal injection of GSPE (10, 50, or 100 mg/kg) or saline. Clinical, histological, and biochemical parameters were assessed. The effects of GSPE on osteoclastogenesis were determined by tartrate-resistant acid phosphatase (TRAP) staining of the inflamed joints and bone-marrow cells cultured with the receptor activator of nuclear factor B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Intracellular levels of hydrogen peroxide were determined using carboxy-dichlorodihydrofluorescein diacetate. GSPE treatment significantly attenuated the severity of CIA in a dose-dependent manner and reduced the histology scores for synovial inflammation, cartilage erosion, bone erosion, and the number of TRAP+ osteoclasts. GSPE treatment significantly reduced the numbers of tumor necrosis factor alpha (TNF-alpha)- or interleukin 17 (IL-17)-producing cells in the synovial tissue and the spontaneous production of TNF-alpha and IL-17 by splenocytes compared with those in the control mice. The serum levels of type-II-collagen-specific IgG2a and plasma levels of 8-isoprostane in the GSPE-treated mice were significantly lower than those in the control mice. GSPE dose-dependently suppressed osteoclastogenesis in vitro. GSPE significantly reduced hydrogen peroxide production by anti-CD3-monoclonal-antibody-stimulated CD4+ splenocytes. These results indicate that intraperitoneal injection of GSPE attenuated CIA in mice. GSPE may be useful in the treatment of rheumatoid arthritis.