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ID PMID Title PublicationDate abstract
19811413 Decreased expression of T lymphocyte co-stimulatory molecule CD26 on invariant natural kil 2009 CD26, a T cell co-stimulatory molecule and dipeptidyl peptidase IV for the degradation of interferon-gamma-induced chemokine, participates in multiple immunopathological roles in leukocyte homing and inflammation. Decreased circulating concentration of soluble (s)CD26 in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis and murine model of arthritis and encephalomyelitis have been reported. In the present study, the plasma concentration of sCD26 and chemokines, and cell surface expression of CD26 on monocytes, CD4+T lymphocytes, CD8+T lymphocytes, CD19+B lymphocytes and invariant natural killer T (iNKT) lymphocytes were analyzed using ELISA and flow cytometry, respectively, in 23 SLE patients and 14 sex- and age-matched control subjects. Although there was no significant difference between plasma concentrations of soluble CD26 in SLE patients with controls (p > 0.05), there was significant elevated Th1 chemokines CXCL10 and CXCL9 but not Th2 chemokine CCL2, and down-regulation in iNKT lymphocytes number and cell surface expression of CD26 on CD4+T and iNKT lymphocytes of SLE patients compared with controls (all p < 0.05). Decreased circulating number of iNKT cells and CD26 on iNKT cells can be important for the immunopathogenesis by exacerbating Th1-related inflammation in SLE.
19444116 Rheumatic manifestations associated with HIV in the highly active antiretroviral therapy e 2009 Jul PURPOSE OF REVIEW: To evaluate the rheumatic manifestations associated with HIV infection in the highly active antiretroviral therapy (HAART) era. RECENT FINDINGS: The overall prevalence of rheumatic manifestations in HIV population is approximately 9% with various clinical features. Anti-TNF agents do not appear to adversely affect the CD4 cell counts or viral load if the HIV infection is well controlled prior to initiation of therapy. SUMMARY: In the HAART era, HIV-infected individuals can be affected by various rheumatic syndromes including arthritis, spondyloarthritis, DILS, vasculitides, connective tissue disease, myopathies, and musculoskeletal diseases. With the use of HAART, the prevalence of spondyloarthritis and Diffuse Infiltrative Lymphocytosis Syndrome has decreased, whereas the musculoskeletal complications of HIV and HAART, such as osteopenia, osteonecrosis, and infection continue to be a concern. With immune restoration, various inflammatory and autoimmune diseases, such as SLE, rheumatoid arthritis, and polymyositis may occur de novo or exacerbate. Most antirheumatic therapies used in HIV-negative individuals appear to be safe and effective in the setting of HIV infection as long as prudent guidelines are followed.
19033264 The effect of plasminogen activator inhibitor-1 -675 4G/5G polymorphism on familial Medite 2009 Jul Familial Mediterranean fever (FMF) is an autosomal recessive disease that is the most common of a rare group of disorders collectively termed familial hereditary periodic fever syndromes, also known as autoinflammatory syndromes. FMF is predominantly affecting people of Mediterranean descent and clinically characterized by intermittent attacks of fever with peritonitis and abdominal pain, pleuritis, arthritis, or erysipelas-like rashes. Amyloidosis due to chronic inflammation progressing to renal failure is one of the most serious potential complications of this disease.Patients with inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis, and conditions with chronic subclinical inflammation, like obesity and diabetes mellitus, are now considered to have an increased risk of atherosclerotic cardiovascular complications. FMF is also an inflammatory disease, and it is accepted that even during attack-free periods significant inflammatory reaction continues. However, whether this inflammatory process causes premature atherosclerosis is not known due to a lack of data.Different studies have investigated the association between the fibrinolytic and inflammatory process parameters. PAI-1 is paracrine secretion of pro- and antiinflammatory cytokines, thereby playing a possible role in the adiposity-related inflammation and atherosclerosis. The patients with IRS have higher values of fibrinogen, factor VII, VIII, Von Willebrand factor and Plasminogen Activator Inhibitor (PAI) compared to control subjects. So that we aimed in this study to investigate whether FMF patients with/without amyloidosis and with M694V homozygote mutation, have increased risk for atherosclerotic cardiovascular complications and to determine the strength of association between MEFV gene-mutation types. To our knowledge, this is the first case control and cross-sectional study in the pediatric age groups.
21063653 Extremely elevated erythrocyte sedimentation rate: etiology at a tertiary care center in S 2010 Nov OBJECTIVE: To evaluate the etiology of extremely elevated erythrocyte sedimentation rate (ESR) in adolescents and adults at a tertiary care center. METHODS: This retrospective, cross-sectional, observational study was carried out at King Abdulaziz Medical City, Riyadh, Saudi Arabia using the Westergren method of determining ESR in adolescents and adults aged >or=12 years. The patients included inpatients and outpatients with medical, surgical, and gynecological problems. During a period from June 2007 to October 2008, consecutive, non-repetitive patients with ESR >or=100 mm/hour were evaluated for possible etiology by checking the electronic and paper data file of each patient. RESULTS: During the study period, out of the 44,366 ESR tests carried out at this center, 1864 (4.2%) had an ESR >or=100 mm/hour belonging to 567 patients. Out of 508 patients fulfilling the study criteria, the main associated causes included: infections (38.6%), autoimmune diseases (15.9%), malignancy (15.4%), miscellaneous causes (10.2%), ischemic tissue injury or trauma (8.7%), and renal diseases (8.4%). Ten common individual causes included: rheumatoid arthritis (7.3%), osteomyelitis (6.9%), tuberculosis (5.5%), trauma (5.3%), lymphoma and sepsis of unknown origin (5.1%) each, urinary tract infection (4.7%), septic arthritis (3.1%), abscesses (2.8%), and pregnancy (2.2%). Fourteen (2.4%) patients had no known cause. CONCLUSION: Most of the patients with extreme ESR elevation have an underlying cause and a focused evaluation of such patients needs to be carried out to reach a diagnosis.
20703489 [IL-1 antagonists]. 2010 Sep Interleukin (IL)-1 plays an important role not only in the mediation of inflammation but also in the destruction of cartilage and bone. Together with TNF-alpha it is one of the most important cytokines in the pathogenesis of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). The first IL-1 antagonist to be approved for RA was Anakinra, an IL-1 receptor antagonist. Anakinra appears to be less effective for RA than TNF blockers. Hence, Anakinra is rarely used for the treatment of RA, but more for the treatment of IL-1-mediated diseases such as autoinflammatory syndromes, adult-onset Still's disease and systemic onset JIA. Two newer IL-1 antagonists have recently been approved for the treatment of CAPS (cryopyrin-associated periodic syndromes): Canakinumab, a fully human IL-1beta antibody, and rilonacept, a fusion protein consisting of the ligand-binding domain of the IL-1 receptor and the IL-1-receptor accessory protein, bound to human IgG1. For RA, there is only one proof-of-concept study to date with canakinumab. There are no prospective data for the treatment of patients with RA who did not respond to or tolerate TNF antagonists; in a retrospective analysis, only 8% of anti-TNF pretreated patients achieved an ACR 20 response.
20065365 Combined preoperative autologous blood donation and intra-operative cell salvage for hip s 2009 Dec PURPOSE: To review records of 161 consecutive hip surgery patients for whom preoperative autologous blood donation (PABD) was used in combination with intra-operative cell salvage (ICS). METHODS: 114 women and 14 men aged 41 to 86 (mean, 64) years underwent 135 primary total hip arthroplasties (THAs), whereas 19 women and 7 men aged 16 to 52 (mean, 35) years underwent 26 rotational acetabular osteotomies (RAOs). Two or 3 weeks before the operation, patients deposited one unit (400 ml) of blood weekly, so long as their haemoglobin levels exceeded 110 g/l (if they had osteoarthritis) or 100 g/l (if they had rheumatoid arthritis). Patients were given oral ferrous sulphate, lactated Ringer's solution, and recombinant human erythropoietin. 800 and 1200 ml of blood were deposited for patients undergoing THA and RAO, respectively. Intra-operatively, ICS was carried out using a continuous autotransfusion system. The blood from ICS was transfused first, and then the blood from PABD was transfused during the latter half of the operation. RESULTS: By combining PABD and ICS, homologous blood transfusion was avoided in all patients, even in those with unexpected massive bleeding during surgery. In 3 patients, one unit of deposited autologous blood was discarded, because they showed no sign of anaemia. The mean total blood loss was almost 1.5 times higher in RAO than in THA patients (1095 vs 1550 ml). In the THA and RAO patients respectively, the mean amount of ICS was 181 and 210 ml, whereas the mean total blood transfusion volume was 975 and 1394 ml. No complications (including infection) related to autologous blood transfusion were observed during PABD, the surgery or the postoperative period. CONCLUSION: Homologous blood transfusion was avoided with the use of PABD and ICS. Preoperative donation of 800 and 1200 ml of blood (combined with ICS) seemed optimal, as only 3 units of blood were discarded.
19380329 Baseline factors associated with congestive heart failure in patients receiving etoricoxib 2009 Jun AIMS: Non-steroidal anti-inflammatory drugs have been associated with increased risk of congestive heart failure (CHF). We aimed to assess the impact of treatment with etoricoxib or diclofenac on risk of CHF relative to baseline risk factors. METHODS AND RESULTS: We performed a multivariate analysis of 34 701 patients with arthritis receiving etoricoxib 60 or 90 mg, or diclofenac 150 mg, daily for a mean of 18 months, to assess the incidence of confirmed, adjudicated CHF events resulting in emergency room visit or hospitalization. Analyses were performed using a Cox proportional hazard model to evaluate the hazard ratio (HR) between the levels of each risk marker for the incidence of CHF. Significant risk markers included history of CHF (HR: 6.69, 95% CI 3.59-12.47; P <0.0001), age > or = 65 years (2.56, 1.65-3.98; P <0.0001), and history of hypertension (1.83, 1.16-2.89; P = 0.0094) or diabetes (1.83, 1.15-2.94; P = 0.0116). Etoricoxib vs. diclofenac was a significant risk factor only when pooling the etoricoxib 90 mg cohorts (1.88; 1.13-3.10; P = 0.0143). Etoricoxib 60 mg did not significantly increase risk vs. diclofenac. CONCLUSION: History of CHF was highly associated with risk for CHF hospitalization. Hypertension, diabetes, and older age also increased risk modestly. There appeared to be a dose-related increase in CHF with etoricoxib compared with diclofenac, which reached statistical significance when the etoricoxib 90 mg groups (osteoarthritis and rheumatoid arthritis) were pooled.
20576225 Clinical application of the CASPAR criteria for psoriatic arthritis compared to other exis 2010 May OBJECTIVES: Psoriatic arthritis (PsA) has been defined as a systemic, chronic, inflammatory arthritis, usually seronegative for rheumatoid factor (RF), associated with cutaneous psoriasis. The exact prevalence of PsA is unknown and its estimation has been difficult, partly due to the lack of a widely accepted classification criteria. Agreed and validated criteria will facilitate comparison between centres and different countries in the areas of epidemiology, outcome studies and therapeutic trials. A number of classification criteria have been published by Moll & Wright (M & W), Bennett's, Vasey and Espinoza (V & E), Fournié's, European Spondyloarthropathy Study Group (ESSG), McGonagle, Gladman and most recently, the CASPAR Study Group. In this paper, we present an audit aiming to assess which of these criteria performs better in clinical practice. METHODS: Sixty-nine (69) patients with evidence of PsA were seen in the clinic as regular outpatients and were assessed as to whether they fulfil any of the 6 existing criteria for PsA: M & W, Bennett's, V & E, Fournié's, ESSG and CASPAR criteria. All items included in the 6 sets of criteria were recorded for each patient based on interview, clinical examination and scrutiny of clinical medical records. By comparing the criteria between themselves as well as the items used in each one of them we tried to assess which one of the criteria was performing best. RESULTS: A total of 69 patients (M/F=24/45; mean age 46.4 years (+/-20.3), and delay in diagnosis of 3.4 years (+/-4.1) was assessed. From those, 9 patients did not fulfil any criteria and excluded from the analysis. From the remaining 60 patients [M/F=21/39; (age 48+/-15.3)], 21 patients (35%) fulfilled all 6 sets of criteria. The remaining 39 patients (M/F=41/59 %; age 47+/-14.9) were further analysed with regards to the feature that did not enable concordance. From those 39 patients, Bennett's criteria were positive in only 4/39 (10.2%), M & W criteria were positive in 12/39 (30.7%), ESSG criteria in 17/39 (43.5%), V & E criteria were positive in 18/39 (46.1%), Fournié's criteria were positive in 31/39 (79.4%) and CASPAR criteria in 35/39 (89.7%). By including family history of psoriasis in the criteria, 11/39 patients (28.2%), who did not fulfil M & W or V & E due to lack of family history of psoriasis as item, met the CASPAR criteria. In addition, some patients who did not fulfil the M & W criteria, since RF positive (7/39; 17.9%), were able to satisfy the CASPAR criteria. CONCLUSIONS: Family history of psoriasis is the main advantage of the new CASPAR Criteria over M & W and V & E. In addition, using the CASPAR criteria, it is possible to make a diagnosis of PsA in a patient who develops inflammatory articular disease even if with RF positive and polyarticular symmetrical arthritis. It is also important to have these classification criteria for the development of recommendations for the optimal treatment of patients with PsA. We believe that the CASPAR criteria, which are simple and easy to use, have high potential to be introduced as the universal classification criteria for PsA. However, further study of the validation of these new criteria is required.
19318800 INI1 and GLUT-1 expression in epithelioid sarcoma and its cutaneous neoplastic and nonneop 2009 Apr The morphological features of epithelioid sarcoma may closely mimic those of epithelial neoplasms, such as squamous cell carcinoma, mesenchymal tumors, such as benign fibrous histiocytoma, and nonneoplastic lesions, such as granuloma annulare. Immunohistochemistry, particularly for epithelial markers and CD34, thus plays a valuable role in the differential diagnosis of epithelioid sarcoma. However, some epithelioid sarcomas may show very focal or even absent expression of such markers and may be difficult to distinguish from various morphological mimics. There is therefore continued interest in the development of new immunohistochemical markers of epithelioid sarcoma. Recently, loss of expression of INI1, a tumor suppressor gene/protein, and expression of GLUT-1, a glucose transporter protein, have been described in epithelioid sarcoma. We examined the utility of immunohistochemistry for INI1 and GLUT-1 in the diagnosis of epithelioid sarcoma and various cutaneous mimics. Twenty-four cases of epithelioid sarcoma, 13 cases of granuloma annulare, 10 cases of rheumatoid nodule, 19 cases of cutaneous squamous cell carcinoma, 7 cases of atypical fibroxanthoma, 9 cases of benign fibrous histiocytoma (dermatofibroma), and 3 cases of nodular fasciitis were immunostained for GLUT-1 and INI1 using commercially available antibodies, heat-induced epitope retrieval, and the Dako Envision detection system. Total or near-total loss of normal constitutive expression of INI1 protein was noted in more than 85% of epithelioid sarcomas, with 19 of 24 cases (79%) showing complete loss of INI1 expression. In contrast, all other cases studied showed uniformly retained expression of INI1. GLUT-1 was positive in 40%-50% of epithelioid sarcomas, all cases of granuloma annulare and rheumatoid nodules, 67% of benign fibrous histiocytomas, and in all squamous cell carcinomas. In contrast, atypical fibroxanthomas and cases of nodular fasciitis were consistently GLUT-1 negative. We conclude that immunohistochemistry for INI1 expression should be included as part of the routine immunohistochemical panel for the diagnosis of epithelioid sarcoma, along with established markers such as wide-spectrum cytokeratins, cytokeratin 5/6, p63, and CD34. In this clinical context, loss of INI1 expression seems to be an entirely specific marker of epithelioid sarcoma and this finding may be of great value in distinguishing CD34-negative epithelioid sarcoma from squamous cell carcinoma and in the distinction of rare cytokeratin-negative epithelioid sarcomas from necrobiotic processes, nodular fasciitis, and benign fibrous histiocytomas. In contrast, there does not seem to be a role for GLUT-1 immunohistochemistry in this differential diagnosis.
20061932 Chronic sclerosing sialadenitis (Küttner tumor) is an IgG4-associated disease. 2010 Feb BACKGROUND: Chronic sclerosing sialadenitis is a fibroinflammatory disease of the salivary glands, characteristically of the submandibular gland. One prior Asian study proposed that chronic sclerosing sialadenitis is a part of the spectrum of IgG4-associated disease. This association has not been confirmed in Western populations. We therefore, investigated the relationship between IgG4 and chronic sclerosing sialadenitis, and compared the histomorphologic features of this condition with those of chronic sialadenitis-not otherwise specified, Sjögren syndrome, and lymphoepithelial sialadenitis. MATERIALS AND METHODS: We evaluated 13 cases of chronic sclerosing sialadenitis and compared them with 15 cases of chronic sialadenitis-not otherwise specified, 8 lip biopsies from individuals with Sjögren syndrome, and 4 cases of lymphoepithelial sialadenitis. Immunohistochemistry for IgG, and IgG4 was carried out. IgG4-positive plasma cells were quantified and the IgG4/IgG ratio was calculated. RESULTS: Seven patients with chronic sclerosing sialadenitis were female and 6 were male. Their mean age was 61 years (range: 27 to 80). Twelve chronic sclerosing sialadenitis cases involved the submandibular gland (bilaterally in 3) and in 1 there was a parotid lesion. Three of these 12 cases had manifestations of IgG4-associated systemic disease. Morphologically these specimens had preservation of lobular architecture, hypercellular interlobular fibrosis, florid lymphoid hyperplasia, and numerous plasma cells. Obliterative phlebitis was observed in 6 cases. The histologic features of chronic sclerosing sialadenitis were reminiscent of autoimmune pancreatitis, and were either not observed or were present only focally in cases of chronic sialadenitis, Sjögren syndrome, and lymphoepithelial sialadenitis.Eleven of 12 evaluable cases showed an increased number of IgG4 plasma cells with a mean of 229/high-power field (HPF) (range 75 to 608) and an overall IgG4/IgG ratio of 0.86 (range 0.5 to 1). The only patient whose biopsy lacked IgG4-positive plasma cells had pathologic evidence of cytomegalovirus infection. Chronic sclerosing sialadenitis cases, in comparison with the other 3 groups studied, showed a significantly higher number of IgG4 positive plasma cells (P<0.05). Patients with chronic sialadenitis-not otherwise specified had a median number of only 16 IgG4-positive plasma cells/HPF (range 2 to 44), with an IgG4/IgG ratio of 0.14 (range 0.02 to 0.28). The Sjögren syndrome patients had a median of 1 IgG4-positive plasma cell/HPF (range 0 to 3), with an IgG4/IgG ratio of 0.02 (range 0 to 0.07). Patients with lymphoepithelial sialadenitis had a median of 0 IgG4-positive plasma cells per HPF. CONCLUSION: Chronic sclerosing sialadenitis has a characteristic morphologic appearance. This morphologic appearance, in conjunction with the elevated IgG4 expression, distinguishes chronic sclerosing sialadenitis from other inflammatory diseases of the salivary glands. Chronic sclerosing sialadenitis belongs to the spectrum of IgG4-related diseases.
19799265 [Anti-HCV and HCV RNA in patients with the primary Sjögren syndrome]. 2009 The subject of study were 104 patients with the primary Sjögren Syndrome (p. Sj. s.) in whom markers of hepatitis C infection were investigated. All the patients fulfilled the criteria of the European Expert Group of the Sjögren Syndrome. Antibodies anti-HCV were found in 20 patients (19.2%) and HCV-RNA found in 5 patients (4.8%). These data were compared with those observed in several European countries and Japan. The following percentages of anti-HCV were observed until now in p.Sj.s. patients: Swedish--2%, Hungarian--6%, Japanese--12%, French--17%, Polish--19% and Spanish--26%. Our patients in whom liver data were available, showed only minor elevations of ALT and AST. International team of experts postulated the delineation of the disease entity: 'HCV-related primary Sjögren syndrome', separate from the p.Sj.s. itself. If this will be substantiated, we can put forward the hypotesis that 'HCV-related p.Sj.s.' may develop in a special subgroup of persons, perhaps genetically predisposed, and is a part of extrahepatic manifestations of HCV infection.
21149398 Markedly increased IL-18 liver expression in adult-onset Still's disease-related hepatitis 2011 Apr OBJECTIVES: First, to investigate the prevalence of liver involvement in adult-onset Still's disease (AOSD) Italian patients; secondly, to measure serum IL-18 concentration and correlate its level to other inflammatory markers and disease activity; and thirdly to characterize the expression level and the cellular source of IL-18 in the liver of a patient with AOSD with hepatitis. METHODS: The clinical charts of 41 consecutive Italian AOSD patients were evaluated with special attention to liver involvement. Serum levels of IL-18 were measured in 21 patients. Finally, the case of a 33-year-old woman with hepatitis where a liver biopsy was obtained and sections stained with antibodies against IL-18 and CD68 is described in detail. RESULTS: Of the 41 AOSD patients, 32 and 39% displayed increased AST level or ALT level, respectively, generally normalizing with steroid treatment, while 41% had evidence of hepatosplenomegaly. Circulating IL-18 levels were significantly higher in those with active disease compared with 85 controls. A correlation was observed between IL-18 serum level and disease activity, serum ferritin level and neutrophil count. IL-18 concentration was markedly increased in the patient with active hepatitis. Intense IL-18 expression was detected within the liver parenchyma and double staining with IL-18 and CD68 clearly showed colocalization of the cytokine with the macrophage marker. CONCLUSION: Macrophage-derived IL-18 might play a central role in the pathogenesis of AOSD. IL-18 serum level is higher in patients with active AOSD and its local, rather than systemic, expression may be responsible for tissue damage in some target organs, such as liver.
20463188 Regulation of disease susceptibility and mononuclear cell infiltration into the labial sal 2010 Aug OBJECTIVE: To investigate how monocyte chemotactic protein-1 (MCP-1) is involved in the pathological process of primary SS (pSS). METHODS: Guanine (G) to adenine (A) single nucleotide polymorphism (SNP) of the -2518 MCP-1 promoter region in pSS and healthy controls was determined by the PCR-restriction fragment length polymorphism technique. Immunohistochemical staining towards MCP-1 and C-C motif chemokine receptor-2 (CCR2), a receptor of MCP-1, of the labial salivary glands of pSS was investigated. Furthermore, the expression of MCP-1 and CCR2 from the cultured primary salivary epithelial cells was studied by RT-PCR, ELISA and western blotting. RESULTS: The genotype and allele frequency of SNP of MCP-1 at -2518 showed that the G/G genotype is low but the presence of allele A as well as the A-allele frequency are high in pSS (n = 52) as compared with healthy controls (n = 164). Immunohistochemistry showed in situ expression of MCP-1 and CCR2 in the ductal structure and infiltrating mononuclear cells (MNCs) of patients with pSS. Primary salivary epithelial cells in vitro from pSS produced MCP-1, which was significantly stimulated by IFN-gamma, as identified by both ELISA and RT-PCR. In contrast to MCP-1, CCR2 expression of primary salivary epithelial cells in vitro was not so changed by IFN-gamma. CONCLUSIONS: MCP-1 is involved in the disease susceptibility of pSS in the Japanese population. MCP-1 interactions with CCR2, which may be facilitated by IFN-gamma, are thought to perpetuate MNC infiltration into the salivary glands of SS.
19394988 [Polymyositis revealing a Sjogren's syndrome]. 2010 Jan INTRODUCTION: Near 10 to 20% of patients with myositis have another systemic, sometimes inaugural, disease. CASE REPORT: A 48-year-old woman was admitted with progressive hypoesthesia in V2 and V3 areas on both sides, difficulties to chew and swallow and then, proximal and axial muscular deficiency, with weight loss. Brain MRI showed gadolinium-enhanced trigeminal nerves and biological tests revealed anti-SSA and anti-Pm/Scl antibodies and a grade IV in Chisholm scoring system on the labial salivary gland biopsy. Neurophysiological studies revealed a myogenic pattern on tibialis anterior muscles and a muscle biopsy confirmed the diagnosis of polymyositis. CONCLUSION: The diagnosis of primitive Sjogren's syndrome was suspected because of the association of bilateral trigeminal neuropathy and anti-SSA and anti-Pm/Scl antibodies.
19056797 Mannose-binding lectin-low genotypes are associated with milder systemic and immunological 2009 Jan OBJECTIVE: To investigate the association of mannose-binding lectin (MBL)-low genotypes with the clinical and immunological expression of primary SS. METHODS: Eighty-one patients with primary SS who fulfilled the 2002 classification criteria were included in the study. MBL2 polymorphisms were investigated by sequence-based DNA typing of the promoter and exon 1. Genotypes 0/0, 0/XA or XA/XA were considered as MBL-low and XA/A, A/0 and A/A as MBL-sufficient. Control groups included 46 patients who exclusively fulfilled the 1993 SS criteria, 114 SLE patients and 104 healthy individuals. RESULTS: Twelve (15%) SS patients had MBL-low genotypes, of whom six (7%) had genotype 0/XA, five (6%) had genotype 0/0 and one (1%) had genotype XA/XA. A higher prevalence of the XA/A genotype (32 vs 17%, P = 0.01) was found in primary SS patients in comparison with SLE patients. No patient with primary SS carrying MBL-low genotypes had purpura, glomerulonephritis or neurological involvement (0 vs 29%, P = 0.025). Immunologically, patients carrying MBL-low genotypes had a lower frequency of anti-Ro/SS-A antibodies (17 vs 55%, P = 0.014), anti-La/SS-B antibodies (8 vs 48%, P = 0.009) and low C4/C3 levels (0 vs 32%, P = 0.016). No patient with primary SS carrying the homozygous MBL-deficient genotype 0/0 had anti-Ro/SS-A or anti-La/SS-B antibodies, low C3/C4 levels or circulating cryoglobulins. CONCLUSION: SS patients with MBL-low genotypes have a less pronounced systemic and immunological disease expression in comparison with those carrying MBL-sufficient genotypes. In primary SS, MBL deficiency may represent a protective factor against the development of more aggressive autoimmune damage.
18292102 Can clinical factors at presentation be used to predict outcome of treatment with methotre 2009 Jan PURPOSE: Methotrexate (MTX) is the first choice conventional disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It is not universally effective, however; although to date it is not possible to predict with any accuracy which patients will respond to treatment. The aim of this analysis was to examine whether clinical and genetic variables could be used to predict response to MTX. METHODS: Patients recruited to the Norfolk Arthritis Register (NOAR), a primary care based inception cohort of patients with inflammatory polyarthritis, were eligible for this analysis if they were commenced on MTX as their first DMARD within 3 months of their baseline visit and had at least 2 years of follow-up data. Outcome on MTX was defined as: (1) stopped for adverse events; (2) stopped for inefficacy or second DMARD added; (3) stopped for other reasons; or (4) remained on MTX monotherapy. Multiple logistic regression was used to establish which variables (including demographics, disease activity and Health Assessment Questionnaire score) predicted stopping monotherapy for inefficacy or adverse event (with those remaining on treatment taken as the referent category). The area under the Receiver Operating Characteristic curves (AUC ROC), were used to determine how accurate the model was at predicting outcome. RESULTS: 309 patients were included in this analysis. At 1 year (2 years), 34 (46) patients had stopped for adverse events and 25 (49) had either stopped monotherapy for inefficacy or had a second DMARD added. 231 (188) patients remained on MTX monotherapy. The strongest predictor of inefficacy at both time points was shared epitope positivity: odds ratios (OR) 5.8 (95% confidence intervals (CI) 1.3 to 25.6) at 1 year, OR 3.0 (95% CI 1.3 to 7.3) at 2 years. High Health Assessment Questionnaire score (OR 1.84 95% CI 1.12 to 3.01) and female gender (OR 2.2, 95% CI 0.92 to 5.28) were associated with adverse events on MTX at 1 year. However, even the most optimal combinations of the factors analysed were only weakly predictive of treatment outcome: AUC ROC for adverse events 0.68 (95% CI 0.58 to 0.78) and for inefficacy AUC ROC 0.71 (95% CI 0.6 to 0.81). CONCLUSIONS: Within this cohort, routine clinical and laboratory factors were poor at predicting outcome of treatment with MTX. Given the major therapeutic advantage to be derived from accurate prediction of treatment outcome, further studies will need to investigate novel biological and other markers.
20658239 Assessment of cardiac and pulmonary function in children with juvenile idiopathic arthriti 2012 Jan Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time (IRT) compared to control. Regarding pulmonary function tests, children with JIA showed significant decrease in FVC, PEF, Pimax, Pemax and DLCO compared to normal controls. This decrease was not related to age, height or weight of these patients. There was significant inverse correlation between lung function parameters and the rheumatoid factor titer, erythrosedimentation rate, disease duration and the duration of methotrexate use (P < 0.01). Despite of an asymptomatic cardiopulmonary status, significant systolic and diastolic functional abnormalities exist in children with JIA. Also, both restrictive and obstructive lung impairments were found.
21122103 Enhancement of antinociception by coadministration of minocycline and a non-steroidal anti 2010 Dec 1 BACKGROUND: Minocycline and a non-steroidal anti-inflammatory drug (NSAID) indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis. METHODS: LPS was injected to BALB/c mice intraperitoneally (i.p.) to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH) limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system. RESULTS: In naïve mice indomethacin (5 to 50 mg/kg) had no significant activity, minocycline (25 to 100 mg/kg) produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg) and a selective COX-2 inhibitor, CAY10404 (10 mg/kg) had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg) or minocycline (50 mg/kg) did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH) limb paw pressure ratios) and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg) or minocycline (50 mg/kg) had no effects on the weight bearing and print area ratios deficits of monoarthritic mice. However, combination of minocycline plus indomethacin restored weight bearing and paw print area ratios of monoarthritic mice similar to that observed in non-arthritic control mice. CONCLUSIONS: Coadministration of indomethacin or a selective COX-2 inhibitor, CAY10404 with minocycline potentiates their effects and results in antinociception against thermal nociception, reduction of thermal hyperalgesia and alleviation of weight bearing deficits in monoarthritic mice at doses where either drug alone has no significant activity. Thus, the coadministration of lower doses of a NSAID or a selective COX-2 inhibitor plus minocycline could be useful in the management of inflammatory pain and arthritis.
20350318 Comparison of serum apolipoprotein A-I between Chinese multiple sclerosis and other relate 2010 Mar 29 BACKGROUND: Serum apolipoprotein (apo) A-I was considered to be an immune regulator and could suppress pro-inflammatory cytokines generated by activated T cell in some autoimmune diseases. However, the change of serum apoA-I levels in multiple sclerosis (MS) patients is unknown. METHODS: In the presentation we performed a study on serum apoA-I levels in the patients with MS. We enrolled some age and gender matched patients with MS, autoimmune demyelinating diseases (Guillain-Barre Syndrome and Clinically Isolated Syndrome), neuroinflammatory diseases (viral encephalitis), autoimmune connective diseases (rheumatoid arthritis and systemic lupus erythematosus) and healthy control groups, and tested their serum lipids levels: total cholesterol (TC), triglyceride (TG), high-density lipoproteins (HDL), apolipoproteinB100 (apoB100), apolipoproteinA-I (apoA-I). RESULTS: For all patients, age had no effect on serum apoA-I levels (P > 0.05). Meanwhile, we proved the highest serum apoA-I levels in MS patients and the lowest serum apoA-I levels in SLE patients. Serum apoA-I levels was significantly elevated in female MS patients (P = 0.033; P < 0.05). CONCLUSION: In short we believed that patients with MS and other autoimmune demyelination had significantly decreased serum levels of apo A-I.
21185665 Bilateral patellar tendon ruptures without predisposing systemic disease or steroid use: a 2012 Jan Simultaneous bilateral patellar tendon rupture occurs rarely and is even rarer in patients without systemic disease or predisposing conditions. We present a case of bilateral, midsubstance patellar tendon ruptures along with a partial anterior cruciate ligament tear from a fall from a standing height in an otherwise healthy adult without any predisposing conditions. Most patients that sustain a tendon rupture have risk factors for tendonopathy including chronic renal disease, systemic lupus erythematosus, rheumatoid arthritis, or exposure to medications (such as corticosteroids or fluoroquinolones). Currently, there are approximately 50 reported cases of bilateral patellar tendon rupture in the scientific literature; however, only a small minority occurred in patients without any predisposing factors. Most of the reports of a bilateral tendon rupture without systemic disease occurred in the inferior pole of the tendon, with only a few of these occurring in the midsubstance. Because of the rarity of this event in a patient without systemic disease, this condition is often misdiagnosed. Emergency physicians should maintain a high degree of suspicion in those patients with concerning clinical and/or radiographic findings.