Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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12931646 | [A case of pulmonary Mycobacterium avium complex disease complicated by interstitial pneum | 2003 Jul | A 45-year-old woman with scleroderma for 15 years duration, rheumatoid arthritis in the past five years, and interstitial pneumonia in the past two years had been followed at OPD. Although sputum had appeared and cough had increased since January 2002, there was no obvious abnormal findings on chest X-ray. Later, as a chest X-ray revealed an infiltrative shadow with cavity in the right lower lung field, we suspected pulmonary tuberculosis and performed the direct smear examination of sputum immediately. As acid-fast bacilli were positive (Gaffky 10) and the polymerase chain reaction (PCR) test was positive for only Mycobacterium avium, we diagnosed the case as pulmonary nontuberculous mycobacterial disease. This case was thought to be pulmonary nontuberculous mycobacterial disease complicated with interstitial pneumonia with collagen vascular disease as a secondary infectious type, and as the cause of the disease, the decrease of the local pulmonary defence mechanism due to pre-existing pulmonary lesions was suspected. | |
12871189 | Regulation of B-cell activation by complement receptors CD21 and CD35. | 2003 | The role of complement in the development and regulation of antibody responses under both healthy and pathological conditions is known for long. Unraveling the elements involved and the molecular mechanisms underlying the events however is still in progress. This review focuses on the role of complement receptors CR1 (CD35) and CR2 (CD21) expressed on B lymphocytes, which interact with ligands generated upon activation of component C3, the major protein of the complement cascade. The binding and possible effects of immune complexes comprising antigen, antibody and complement on B-cell activation are discussed. Results of clinical studies of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis and conclusions drawn from animal models used to investigate various aspects of human diseases are also debated. We discuss similarities regarding the overall structure and certain functions of complement and complement receptors in mice and men however, call the attention to major differences regarding tissue distribution and their role in B-cell functions. | |
12868200 | [Coxibs: highly selective cyclooxygenase-2 inhibitors. Part I. Clinical efficacy]. | 2003 Apr | Slow, time-dependent, irreversible, highly selective inhibitors of COX-2 (coxibs) have been used for the treatment of osteoarthritis and rheumatoid arthritis, as well as other disease entities such as acute pain, fever, neoplastic changes, and Alzheimer's disease, the pathomechanism of which is dependent on the coexisting inflammatory process or overexpression of cyclo-oxygenase (COX) genes. The article presents current state of knowledge about the clinical efficacy of coxibs (celecoxib, rofecoxib) compared to non-selective COX inhibitors. The physiology and pathophysiology of both COX isoforms (COX-1, COX-2) are also discussed. | |
12745458 | Immunohistochemical characterisation of pulmonary hyaline membrane in various types of int | 2003 Apr | AIMS: Hyaline membrane (HM) in diffuse alveolar damage (DAD) pattern is frequently detected in the acute stage of interstitial pneumonia (IP). To determine the exact nature of HM, we investigated immunohistochemically 25 cases of HM-containing IP. METHODS: The cases examined using various kinds of antibodies were four cases associated with rheumatoid arthritis, five with usual interstitial pneumonia, two with dermatomyositis, five with viral infection, one case with progressive systemic sclerosis and eight cases caused by other agents. RESULTS: HM mostly reacted with antibodies to PE10 (SP-A), Factor VIII, KL-6 and EMA and, interestingly, stained for AE1/AE3, CK19, and Hup-1 in some cases, but was negative for PTAH staining. However, the immunoreactivities of HM varied even within the same disease or section. CONCLUSIONS: The immunohistochemical heterogeneity of HM suggests that HM may be formed by different mechanisms in various types of IP. Our findings also suggest that the main components of HM are derived from alveolar epithelial cells and their proteins, some including cytoplasmic element of CK19, and also from serum factors, but not fibrin. The immunohistochemical characteristics of HM in DAD pattern will aid understanding of the significance of HM formation in IP. | |
12689535 | Surgical treatment of de Quervain's disease. | 2003 Mar | OBJECTIVE: The purpose of this study was to evaluate the clinical outcome of surgical treatment of de Quervain's disease. STUDY DESIGN: Prospective study. PLACE AND DURATION OF STUDY: The study was conducted in District Headquarters Hospital, Battagram from December, 2001 to July 2002. SUBJECTS AND METHODS Patients with de Quervain's disease who did not respond to conservative treatment with analgesics, splintage and local steroid injections were operated under local anesthesia and the tendons of abductor pollicis longus and extensor pollicis brevis were released. The patients were followed for a minimum of 3 months to assess the clinical outcome of procedure. RESULTS: Female to male ratio was 9:1. All females were housewives exposed to manual work. Three of them had rheumatoid arthritis. The age range was from 30-50 years with mean age of 38 years. The results of surgical treatment were excellent with 96% patients being completely relieved of symptoms. CONCLUSION: Surgical release of tendons of first dorsal compartment of wrist has excellent results in patients with de quervain's tenosynovitis. | |
12542983 | Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. | 2003 Jan 31 | Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review. | |
24387720 | Factors predicting the response to low-dose methotrexate therapy in patients with rheumato | 2004 Dec | Abstract Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) throughout the world. In Japan, MTX is recommended by the Japanese Ministry of Health, Labour, and Welfare to be given as the second or third DMARD and at a dosage of no more than 8 mg/week. We analyzed the efficacy of MTX in Japanese patients with RA in order to determine whether it is comparable to that in Western countries, where 15-20 mg/week of MTX is used, as well as to elucidate the factors associated with the favorable response to MTX. Around 8 mg/week of MTX was effective in half of the RA patients in the current study, and male sex was the only factor associated with a good response to MTX from a multivariate regression model analysis. Some of the patients who had a poor response to MTX showed an improvement with the addition of bucillamine or prednisolone. For the remaining patients, an increase in the MTX dosage to more than 8 mg/week or the use of biologics such as the anti-tumor necrosis factor (TNF)-α monoclonal antibody may be required. | |
15485011 | Clinical optimization and multicenter validation of antigen-specific cut-off values on the | 2004 Sep | OBJECTIVES: The INNO-LIA ANA Update is a qualitative multiparameter line immunoassay for detection of autoantibodies to several different antigens associated with connective tissue disorders. We sought to optimize and validate the cut-off values for its antigen-specific components: SmB, SmD, RNP-70k, RNP-A, RNP-C, SSA/Ro52, SSA/Ro60, SSB/La, Cenp-B, Topo-I, Jo-1, ribosomal P, and histones. Our aim was to achieve 98% specificity for each of the markers, with respect to differential disease controls, while maintaining sensitivity. METHODS: For optimization, the cut-off value of the different antigen lines was fixed to achieve this specificity using an in-house set of 955 patient samples. Specificity was validated at multiple sites using a different set of 330 samples obtained from 158 apparently healthy blood donors, 100 patients with a variety of infections, 20 each with Wegener's granulomatosis, inflammatory bowel disease, and primary antiphospholipid syndrome, and 12 with psoriatic arthritis. Sensitivity was evaluated, using this optimized cut-off control, in 147 patients with scleroderma, 93 with Sjögren's disease, 40 with systemic lupus erythematosus, 40 with rheumatoid arthritis, 39 with mixed connective tissue disease, and 19 with polymyositis. Sensitivity and specificity of the INNO-LIA ANA Update were determined using the clinical diagnosis as reference. RESULTS: The optimized cut-off values resulted in a specificity 98% or more for all LIA markers except one (histones 97.8%) in the validation set of 330 samples. The sensitivity for each marker tested in 378 samples from the target patient groups was comparable to that reported in the literature. CONCLUSION: The INNO-LIA ANA Update shows uniformly high specificities combined with sensitivities very similar to those of reference assays, in a single test format. | |
15234531 | ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential. | 2004 Jun 15 | Arthropod-transmitted filarial nematodes can survive for in excess of a decade via modulation of the vertebrate host immune system. Although human infection can result in very severe pathology, most infected individuals show remarkably little evidence of this. Analysis of the anti-nematode response indicates that apparently pathology-free individuals have an anti-inflammatory immunological phenotype and it has been suggested that this favours maintenance of host good health. It is considered that parasite-derived molecular secretions contribute to the anti-inflammatory phenotype and we have thus investigated the properties of a filarial nematode glycoprotein secreted in some abundance, ES-62. This molecule shows a plethora of immunomodulatory activities that can be classified as anti-inflammatory. It has been observed in a number of studies that several autoimmune disorders including rheumatoid arthritis (RA) exhibit reduced incidence and severity in geographic regions in which filarial nematodes are transmitted to humans. Furthermore, it has been speculated that these two observations are linked although molecular explanations for such an association have not been forthcoming. Although the aetiology of RA remains unknown a majority of data are consistent with it being mediated via excess pro-inflammatory cytokine production. Given that ES-62 is anti-inflammatory, we hypothesised that it might be able to counter the pathology associated with diseases like RA. Indeed, we found that exposure to ES-62 prevented initiation of collagen-induced arthritis (CIA) in a murine model and also suppressed progression of established disease. Ex vivo analyses demonstrated that these effects correlated with inhibition of TNF-alpha production and inhibition of collagen-specific TH-1 responses. The nematode product was also able to suppress pro-inflammatory cytokine release in vitro in synovial cells derived from RA patients. ES-62 thus constitutes a pathogen-derived immunomodulator with significant therapeutic potential. | |
14550517 | [Common variable immunodeficiency: 17 observations in the adult]. | 2003 Oct | PURPOSE: Common variable immunodeficiency (CVID) is an immune defect characterized by primary hypogammaglobulinemia. Most of the time, clinical manifestations that reveal CVID are recurrent bacterial infections, but auto-immune or granulomatous events may occur. METHODS: This retrospective study was conducted on 17 patients fulfilling the classical CVID definition. Lymphocyte activation level was evaluated in 12 patients through HLA-DR expression on lymphocytes subsets. RESULTS: This study includes 17 patients, 7 men and 10 women. The mean age at the first clinical manifestation is 23 years and the mean age at diagnosis is 39 years. Recurrent upper and lower bacterial respiratory tract infections are common to all patients. Abdominal infection due to Mycobacterium avium-intracellulare complex is found in one patient. Digestive events are dominated by chronic diarrhea caused by giardiasis, nodular lymphoid hyperplasia or villous atrophy. Seven patients developed auto-immune conditions (insulin dependent diabetes, idiopathic thrombocytopenic purpura (ITP), rheumatoid arthritis) and 7 patients have a splenomegaly. Non caseating granulomas in the spleen or in lymph node biopsies are found in 3 patients. Ten patients have a T lymphopenia, 2 have a B lymphopenia, 5 have a CD4/CD8 ratio <1, and 6 have T CD4(+) lymphocytes <400/mm(3). The study of HLA-DR expression on lymphocytes subsets shows that 7/12 patients have activated T CD4(+) and/or CD8(+) cells and these patients have auto-immune or tumoral manifestations. The other 5 patients do not have activated T lymphocytes but present with infectious events only. CONCLUSIONS: Our study allows the separation of patients with CVID according to their T lymphocytes activation level. A patient's classification is necessary to define homogeneous groups of patients to perform genetic and functional studies which will probably reveal heterogeneous molecular abnormalities. | |
12930370 | Hypogalactosylation of serum IgG in patients with coeliac disease. | 2003 Sep | Coeliac disease (CD) is described as an autoimmune enteropathy associated with the presence of IgG and IgA antigliadin and antitransglutaminase autoantibodies. While of diagnostic significance, the role of these autoantibodies in the immunopathogenesis of CD is elucidated. An inappropriate T cell immune response to gluten is also involved in the pathogenesis of CD, as evidenced by autoantibody switching. The N-glycans released from serum IgG of CD patients and three groups of healthy controls, of differing age ranges, were analysed by NH2-high performance liquid chromatography (HPLC). The fucosylated biantennary N- glycans were the most abundant neutral oligosaccharides; in particular, the agalacto form (G0F) showed a mean value of 42% (s.d. +/- 7.4), 30% (s.d. +/- 5.9), 26% (s.d. +/- 4.2) and 35% (s.d. +/- 6.8) for CD patients, healthy children, healthy adults under 40 and healthy adults over 40 years old, respectively. The ratio of asialo agalacto fucosylated biantenna to asialo monogalacto fucosylated biantenna (G0F)/(G1F) for CD patients showed a significant increase compared to healthy children (P < 0.0002), healthy adults under 40 (P < 0.0002) and healthy adults over 40 years old (P < 0.01). Hypogalactosylation was more pronounced for CD patients than for the patients with other autoimmune diseases such as rheumatoid arthritis or psoriatic arthritis. | |
12761187 | Characterization of complement C3 as a glycyrrhizin (GL)-binding protein and the phosphory | 2003 Feb | The physiological interaction between glycyrrhizin (GL) and serum complement C3, and the inhibitory effects of GL, glycyrrhetinic acid (GA), and a GA derivative (oGA) on the phosphorylation of C3 by casein kinase 2 (CK-2), were investigated in vitro. C3 was found to be a GL-binding protein (gbP), because (i) of its high affinity for a GL-affinity HPLC column; and (ii) both GL and GA induce conformational changes in C3. At least four trypsin-resistant fragments (p30, p25, p18, and p15) were detected when the (32)P-labeled C3alpha was digested with trypsin in the presence of 100 micro M GA. Two of these (p25 and p15) were immuno-precipitated with anti-C3a serum. Furthermore, it was found that C3a contains GL-binding domains, because (i) C3a (anaphylatoxin) could be selectively purified from the synovial fluids of patients with rheumatoid arthritis by GL-affinity column chromatography (HPLC); and (ii) purified human C3a has a high affinity for a GL-affinity column. In addition, C3alpha (p115) of C3 was effectively phosphorylated by CK-2 in the presence of poly-Arg (a CK-2 activator) in vitro. This phosphorylation was completely inhibited by 10 micro M oGA, 30 micro M GA, or 100 micro M GL. Taken together, these results suggest that the GL-induced inhibition of the physiological activities of C3a and C3alpha may be involved in the anti-inflammatory effect of GL in vivo. | |
12381511 | Anti-tumour necrosis factor alpha therapy for ankylosing spondylitis: international experi | 2002 Dec | The conventional approach to treatment of patients with spondyloarthritis (SpA), particularly ankylosing spondylitis (AS), has serious limitations, adding a sense of urgency to the evaluation of new treatments for these rheumatic disorders. Tumour necrosis factor alpha (TNFalpha) is a cytokine that has been shown to mediate inflammatory and regulatory activities in SpA and other immune mediated diseases, including other arthritides and inflammatory bowel disease. Positive results have been reported in several international open label and randomised controlled trials of infliximab and etanercept, the two main biological agents targeting TNFalpha, which have included approximately 300 patients with SpA. Specifically, TNFalpha-directed therapy resulted in significant improvements in disease activity, function, and quality of life in these patients, most of whom had AS and received infliximab. Preliminary evidence from open label, long term extension trials suggests clinical benefit with continued use. Serious side effects were rare and consistent with experience from patient groups receiving infliximab or etanercept treatment for inflammatory bowel disease or rheumatoid arthritis. Together, these findings herald an age of more effective treatment of patients with AS with anti-TNFalpha and other emerging biological agents. | |
11886676 | [Infections in joint prostheses: epidemiology and clinical presentation. A prospective stu | 2002 Feb | BACKGROUND: The prosthetic infection is a serious complication due to diagnostic problems. AIM: To determinate epidemiological characteristics, and clinical patterns of infections associated to prosthetic materials to improve the diagnosis and management. PATIENTS AND METHODS: From december 1992 to december 1999, 110 patients with prosthetic infections were prospectively evaluated. Diagnosis was made according to standard microbiological, clinical and radiological criteria. RESULTS: The incidence was 5.1% (110/1,400) prosthetic materials insert in the period of study. The average age was 59.6 years (range 18-79), and the majority of patients 63 (57.2%) were female. Forty-two (38%) suffered a total knee replacement, 29 (26%) a total hip replacement, 1 (1%) shoulder replacement and 38 (34%) autogenous bone gratting. In 29 patients (26.3%) a previous chronic disease had been diagnosed (diabetes, neoplasis, rheumatoid arthritis). Previous use of antibiotics was detected in 58 patients (51%), being ciprofloxacin the most frequently used. An etiological diagnosis was reached in 66 patients (60%), isolated grampositive in 58.2%, gramnegative in 32.8%, fundamentally by Staphylococcus sp. and P. aeruginosa respectively. In 9% anaerobe were isolated. There were early infections in 67 cases, delayed in 25, and late in 18. All the patients had local pain and flogotiv signs as initial findings, whereas 46 (41.8%) developed osteocutaneous fistula and only 5 (4.5%) presented temperature. CONCLUSIONS: Prosthetic infection is a frequent complication after articular replacement, and grampositive cocci predominate as ethilogical agents. Sistemic clinical manifestations are uncommon. | |
14979935 | Anti-alpha-fodrin antibodies do not add much to the diagnosis of Sjögren's syndrome. | 2004 | The presence of anti-alpha-fodrin autoantibodies has been reported to be a highly specific and sensitive test for the diagnosis of Sjögren's syndrome (SjS). We looked (in Nijmegen) for anti-alpha-fodrin, anti-Ro60, and anti-La autoantibodies in a cohort of 51 patients with rheumatic diseases (primary SjS [21], secondary SjS 6, rheumatoid arthritis [RA] 12, systemic lupus erythematosus [SLE] 6, and scleroderma 6) and in 28 healthy subjects, using ELISA, immunoblotting, and immunoprecipitation. The same samples were analyzed with an alternative anti-alpha-fodrin ELISA in Hanover. The Nijmegen ELISA of the sera from primary SjS showed sensitivities of 43% and 48% for IgA- and IgG-type anti-alpha-fodrin antibodies, respectively. The Hanover ELISA showed sensitivities of 38% and 10% for IgA- and IgG-type anti-alpha-fodrin antibodies, respectively. The ELISAs for alpha-fodrin showed six (Nijmegen) and four (Hanover) anti-alpha-fodrin-positive RA sera. IgA and IgG anti-fodrin antibodies were also present in four patients with secondary SjS. The sensitivities of Ro60 and La-antibodies in the Nijmegen ELISA were 67% and 62%, respectively. Unlike anti-alpha-fodrin antibodies, all anti-Ro60 and anti-La positive sera could be confirmed by immunoblotting or RNA immunoprecipitation. Thus, anti-Ro and anti-La autoantibodies were more sensitive than anti-alpha-fodrin autoantibodies in ELISA and were more frequently confirmed by other techniques. Anti-La antibodies appear to be more disease-specific than anti-alpha-fodrin antibodies, which are also found in RA sera. Therefore, the measurement of anti-alpha-fodrin autoantibodies does not add much to the diagnosis of Sjögren's syndrome. | |
14583067 | Balancing gastroprotection and cardioprotection with selective cyclo-oxygenase-2 inhibitor | 2003 | NSAIDs have been the mainstay of treatment in the management of pain and inflammation associated with chronic inflammatory disorders. They are effective. However, complications arising from chronic NSAID use are common and are primarily due to gastrointestinal (GI) toxicity in the form of gastritis, peptic erosions and ulceration and GI bleeds. GI toxicity has been attributed to the blockade of the cyclo-oxygenase (COX)-1-mediated generation of the cytoprotective prostanoids, such as prostaglandin (PG) E2 and PGI2 (prostacyclin). More recently, selective COX-2 inhibitors ('coxibs') were designed to inhibit the production of COX-2-dependent inflammatory prostanoids and to leave intact the cytoprotective COX-1 products. The coxibs, while exhibiting similar efficacy to traditional NSAIDs in controlled clinical trials of their efficacy in chronic inflammatory conditions, such as osteoarthritis and rheumatoid arthritis, have been associated with a reduced incidence of surrogate or actual indices of GI toxicity. However, concerns regarding cardiovascular safety in high-risk patients have evolved. These concerns were driven initially by the concept that inhibition of COX-2-derived endothelial PGI2 without concomitant inhibition of platelet thromboxane A2 would result in increased cardiovascular risk. This was borne out in the Vioxx Gastrointestinal Outcomes Research study of rofecoxib, but not demonstrated in the Celecoxib Long Term Arthritis Safety Study trial. Further elucidation of the relative roles of COX-1- and COX-2-generated prostanoids has enabled a greater understanding of the biology of these pathways. However, it is still not completely clear how this understanding may be appropriately translated into clinical medicine. | |
12924037 | [Is the current treatment of primary and secondary amyloidosis effective?]. | 2003 | BACKGROUND: Retrospective study about results of treatment of patients (pts) with primary (AL) and secondary (AA) amyloidosis is given. 31 pts with systemic forms of amyloidosis have been treated and followed-up in our department since 1993. METHODS AND RESULTS: 6 men and 11 women were in the AL group with the mean age of 59 years. Multiple myeloma was diagnosed in 9 pts, monoclonal gammapathy of undetermined significance (MGUS) was found in 8 pts. The kidneys were affected in all pts, heart in 59% of pts, liver, joints and skin in 26% of pts and polyneuropathy was detected only in 1 pt. Progression of renal insufficiency with decrease of glomerular filtration rate (GFR) was detected in the AL group at the end of follow-up period compared with the initial level (p < 0.05) despite the intensive treatment. The difference did not reach statistical significance in other investigated parameters. Median of survival was 13 months from the assessment of diagnosis. Partial remission of amyloidosis was achieved in 9 pts, stable disease was in 5 pts and in 3 pts the disease progressed. 4 men and 10 women were in the AA group with mean age of 58 years. Underlying disease was rheumatoid arthritis in 7 pts, ankylosing spondylitis in 2 pts, juvenile chronic arthritis in 1 pt, Crohn's disease in 2 pts, eosinophilic fasciitis in 1 pt and chronic abscesses in NK cell deficiency in 1 pt. The kidneys were affected in all pts, bowels and heart in 36% of pts. GFR (p < 0.05) and plasma creatinine (p < 0.01) significantly decreased at the end of follow-up period compared with initial levels. Median of survival was 30 months. Partial remission was achieved in 2 pts, stable disease was in 3 pts and progression was detected in 9 pts despite the use of various treatment regimens. CONCLUSIONS: Both forms of systemic amyloidosis represent severe disease with limited response to treatment. The use of new drugs is promising and could lead to better response to treatment. | |
12755380 | Impact of topoisomerase II inhibition on cytokine and chemokine production. | 2003 Apr | OBJECTIVE AND DESIGN: In systemic inflammatory diseases such as rheumatoid arthritis, cytokines and chemokines are deeply involved in the development of the disease manifestations. Etoposide is a cytostatic drug, known to deplete the monocyte population in mice and rabbits. We have recently shown that suboptimal doses have a disease-ameliorating effect in collagen II induced arthritis in the absence of monocyte depletion. Anti-arthritic properties parallelled with almost total eradication of production of specific collagen II antibodies. The aim of the present study was to investigate ex vivo and in vitro the function of the mononuclear cells and their production of B cell stimulating cytokines following exposure to etoposide, a topoisomerase II inhibitor. MATERIALS AND METHODS: Spleen cells from mice treated during four weeks with etoposide were cultured and the supernatants were analyzed with respect to content of TNF and IL-6. In addition, cells from the murine macrophage cell clone IC-21 were exposed to etoposide and the production of IL-6, using a bioassay, and the production of TNF, MIP-1alpha, RANTES, and IL-1beta, using sandwich ELISAs, was determined. RESULTS: Spleen cells from etoposide-treated mice secreted lower amounts of IL-6 and TNF as compared to the control animals. In addition, in vitro etoposide-exposed macrophages showed reduced capacity to produce TNF, IL-6 and MIP-1alpha. CONCLUSION: Our results indicate that inhibition of topoisomerase II downregulated the function of monocytes. Owing to its immunoregulatory properties, use of etoposide is suggested in treatment of chronic inflammatory diseases. | |
11886959 | Silicone breast implants: correlation between implant ruptures, magnetic resonance spectro | 2002 Feb | OBJECTIVE: To determine the impact of implant integrity on clinical symptoms and antibody status in women with silicone breast implants (SBIs). METHODS: Ninety consecutive women were examined by means of magnetic resonance imaging (MRI) to assess the integrity of their silicone breast implants. The presence of silicone in the liver was estimated by (1)H localized stimulated echo acquisition mode (STEAM) magnetic resonance spectroscopy (MRS). Results were correlated with patients' complaints, as evaluated by a standardized questionnaire, physical examination by a rheumatologist and antibody screening. RESULTS: Breast MRI revealed defects in 24 patients (26.6%); in 13 (54.2%) of these women, silicone was detected in the liver by MRS. Of the 66 patients with MRI-estimated intact implants, 15 (22.7%) had apparent silicone in their liver, arguing for gel bleeding. Clinically, two patients had had rheumatoid arthritis before SBIs, whereas the other patients revealed no typical symptoms of arthritis or connective tissue disease (CTD). The patients with MRS evidence of silicone in the liver had no statistically significant differences in their complaints with the exception of the most frequent symptom, tingling/numbness of the fingers (82.1 vs 51.6%, P=0.006). A positive pattern of antinuclear antibodies (ANA) was obtained in 13 of the 28 MRS-positive patients (46.4%) and in 15 of the 62 MRS-negative patients (24.2%, P=0.033). However, in only one of these 28 ANA-positive patients was a specific weak antibody titre against SS-A detected by ELISA. CONCLUSION: Implant integrity has no major impact on rheumatic symptoms of women with SBIs. This finding supports the standpoint that silicone does not cause either a specific CTD or any other distinct disease entity. However, the moderately increased incidences of ANA-positivity and neuropathy-associated symptoms require explanation. | |
15515415 | Intra-articular treatment of arthritides and activated osteoarthritis with the 5-HT3 recep | 2004 | BACKGROUND: Since the good effect of intra-articular injections of the 5-HT3 receptor antagonist tropisetron in patients with arthritides and activated osteoarthritis has already been demonstrated in pilot studies, the effect of tropisetron is compared with that of methylprednisolone here. OBJECTIVES: In a double-blind study, 34 patients with gonarthritides or activated osteoarthritis (18 patients with rheumatoid arthritis, 16 patients with osteoarthritis) were treated with a single intra-articular injection of 10 mg tropisetron (18 patients) or 40 mg methylprednisolone (16 patients). Before treatment as well as one and three weeks later, the intensity of rest pain and pain following exercise was measured with the visual analog scale (VAS) for pain and the clinical findings in the knee joint were recorded. RESULTS: By means of the intra-articular tropisetron treatment, the inflammatory joint process with arthritides and activated arthroses could be influenced in a similar way as with corticosteroid treatment. No significant differences were detected. CONCLUSION: According to the results presented here, the intra-articular treatment with the 5-HT3 receptor antagonist tropisetron in patients with gonarthritides and activated arthroses was about equally effective as those for treatment with corticosteroids. Therefore, it can be used as an alternative in patients for whom concomitant diseases like diabetes and hypertension make it difficult to use corticosteroids. Whether increasing the tropisetron dose may further improve the results remains to be determined in future studies. |