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ID PMID Title PublicationDate abstract
12687157 Peculiarities of the Rheumatoid Arthritis Pathogenesis and Some Current Approaches to Its 2000 Apr Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases. The present review regards the most important items of RA immunopathogenesis and some of approaches to its treatment. Initiation by a hypothetical antigen causes T lymphocyte activation. T cells stimulate macrophages to produce cytokines, which provide inflammatory and osteodestructive effects, - IL-1, TNF-alpha, GM-CSF, IL-6 and others. TNF-alpha is shown to be of the leading role in the network of the regulatory proteins. The most common patent medication for RA worldwide is the use of anti-inflammatory drugs - steroid and non-steroid. Recent studies suggest relatively prompt involvement of aggressive second line drugs when non-steroid anti-inflammatory treatment is expected to be insufficient, and disease modifying antirheumatic drug use is an integral part of this strategy. Combinations of several drugs are considered to be more effective than monotherapy. A number of immunobiological agents are also being widely used for RA medication - such as recombinant cytokines, especially interferons; oral protein administration-induced tolerance; high doses of immunoglobulins, monoclonal antibodies (mAb) to cell surface antigens and to some cytokines. Employment of non-depleting anti-CD4 mAb have shown promising results. Expedient and efficacious is the use of anti-TNF-alpha agents - mAb and TNF-antagonist TNFR:Fc. Research works are being pursued regarding the mAb-toxin conjugates application within RA treatment as well as gene therapy. Yet the most effective and the least toxic methods are still to be developed.
10340005 [Advances in interleukin-6 therapy]. 1999 Apr Interleukin-6 (IL-6) exhibits multiple biologic activities such as regulation of immunological responses and hematopoiesis, promotion of acute inflammation, and stimulation of some malignant and non-malignant cell growth. The IL-6 receptor system consists of an IL-6 specific binding molecule, IL-6R and a signal transducer, gp130. Following gp130 dimerization, IL-6 activates multiple signaling pathways (Ras dependent MAPk cascade, STAT1-STAT3 heterodimer pathway, and STAT3 homodimer pathway). Several other cytokines including oncostatin M, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and cardiotropin-1 (CT-1) use gp130 as a common signal transducing molecule and therefore have similar biological activities. Two major in vivo functions of IL-6 are reported. Firstly, IL-6 acts as a growth factor of some malignant and non-malignant cells such as malignant plasma cells in multiple myeloma, mesangial cells in the kidney, and keratinocytes. Secondly, IL-6 mediates inflammatory and immune responses in rheumatoid arthritis, Castleman disease, psoriasis, cardiac myxoma, cachexia, and other inflammatory conditions. Recently, a humanized anti-IL-6 receptor antibody was developed. Neutralization of IL-6 activity by the humanized anti-IL-6 receptor antibody may be a new therapeutic approach for IL-6 related diseases such as multiple myeloma, Castleman disease and rheumatoid arthritis.
19078187 Effect of tenidap on metalloproteinase gene expression in rheumatoid arthritis: a synovial 1997 Aug This study evaluated measures of metalloproteinase gene expression in synovial biopsies as a means of differentiating the activities of two antirheumatic therapies: piroxicam and tenidap. Synovial biopsies and quantitative in situ hybridization for stromelysin (STR), collagenase (COL), tissue inhibitor of metalloproteinase-1 (TIMP), and actin mRNA were performed in a subset of patients with rheumatoid arthritis in a larger doubleblind randomized crossover trial comparing 120 mg/day of tenidap for 6 weeks with 20 mg/day of piroxicam for 6 weeks. There were no consistent differences between tenidap and piroxicam on COL or TIMP mRNA expression, but STR mRNA was significantly lower after tenidap compared with piroxicam (p = 0.037). There were no significant associations between measures of local or systemic clinical activity and STR, COL, or TIMP gene expression. However, changes in STR gene expression were significantly correlated with changes in serum C-reactive protein (p = 0.016). Because tenidap and piroxicam are both potent inhibitors of prostaglandin production, the effect of tenidap on STR gene expression may be due to its additional cytokine modulating activity. Clinical trials with data from synovial biopsies may be useful in evaluating the potential for disease-modifying effects of antirheumatic drugs.
11415687 Load dependence in carpal kinematics during wrist flexion in vivo. 1997 Apr OBJECTIVE: The hypothesis tested was that generation of torque at the wrist affects joint kinematics. DESIGN: An in vivo study of normal wrist kinematics during plantar flexion motion against a constant load was undertaken, using a custom-designed instrumented apparatus to track the motion of the hand during the task. BACKGROUND: Despite clinical observations of a relationship between motion-loading and pain in wrists affected by rheumatoid arthritis, there is little published literature on thein vivo kinematics of the normal human wrist under load. METHODS: Ten volunteers with no wrist pathology were tested while generating torques of zero, 1.1 and 2.2 N m in a planar, unidirectional flexion motion. Hand kinematics were computed using the Planar Rigid Body Method algorithm and an 8 degrees angular step size. The finite radius of motion and the range and standard deviation of the residuals to a fitted second-order curve were used as indices of changes in the kinematics. RESULTS: The magnitude of both the range and standard deviation of the residuals were found to increase significantly with torque at the 95% confidence level. CONCLUSIONS: The wrist does not behave like a smooth mechanism when generating torque. Load affects carpal kinematics. RELEVANCE: We propose that fluctuations in the finite radius of motion are the natural kinematic consequence of intercarpal motion known to occur during wrist flexion. Wrist kinematics may be particularly sensitive to load and joint integrity because orchestrated intercarpal motion depends on the soundness of articular and ligamentous structures, the first to be affected in joint degenerating conditions such as rheumatoid arthritis. Thus, wrist kinematics under load may be a key to characterizing joint integrity. In wrist pathologies, simple planar testing of carpal kinematics under reproducible and controlled joint torque conditions may be a useful way to assess joint involvement before the onset of gross dysfunction, and to evaluate treatment outcomes.
11469478 Safety and efficacy of high dose etanercept in treatment of juvenile rheumatoid arthritis. 2001 Jul OBJECTIVE: To evaluate safety and efficacy of high dose etanercept (> 0.8 mg/kg, maximum 25 mg subcutaneously twice weekly) (Enbrel) in children with juvenile rheumatoid arthritis (JRA) and inadequate prior response to standard dose etanercept. METHODS: Retrospective chart review of 8 children (6 girls, 2 boys, mean age 8.4 yrs, range 5-16 yrs). Five children had systemic onset, polyarticular course JRA; 2 had polyarticular onset; and one had pauciarticular onset, polyarticular course JRA. All children had failed at least 3 mo (mean 9 mo) treatment with standard dose etanercept (0.4 mg/kg SC twice a week). All 8 children had increase in the etanercept dose to at least 0.8 mg/kg (mean 1.1 mg/kg, maximum 25 mg SC twice weekly) for a mean of 7 mo (range 3-10 mo). Efficacy of high dose etanercept was evaluated by changes in joint count, laboratory data, and ability to decrease concomitant medication. RESULTS: Improvements in the joint count and laboratory findings (erythrocyte sedimentation rate, hemoglobin and platelet count) were observed in 2 of 8 (25%) children. In these 2, concomitant prednisone was reduced or discontinued. In contrast, no changes in disease activity or laboratory findings were observed in the other 6 children. Overall, high dose etanercept was well tolerated. No laboratory abnormalities were detected and no child withdrew because of adverse events. CONCLUSION: High dose etanercept is safe and well tolerated in children, but efficacy seems limited. In children with unsatisfactory response to standard dose etanercept, an increased dose or treatment prolongation may not offer any additional benefit.
10229415 Pediatric Escola Paulista de Medicina Range of Motion Scale: a reduced joint count scale f 1999 Apr OBJECTIVE: Different instruments are available to measure functional status in juvenile rheumatoid arthritis (JRA); however, none is based on the evaluation of joint range of motion (ROM). We designed and evaluated a ROM scale to be used as a complementary instrument in daily practice with JRA as well as in trials. METHODS: The 10 joint movements of the Pediatric Escola Paulista de Medicina Range of Motion scale (Pediatric EPM-ROM) were derived from 25 initial movements. The selection was based on 2 criteria: (1) consensus among 3 pediatric rheumatologists, one physical therapist, and one occupational therapist; and (2) choice of movements that presented the highest scores in a pilot study involving patients with JRA. The score for each joint ranges from 0 (full movement) to 3 (severe limitation) and the cutoff degrees of motion are, in general, based on the lack of ability to perform some activities of daily living. The test-retest reliability was assessed by administering the scale twice by the same observer, 4 to 10 days apart, always in the morning. The interobserver reliability was evaluated on the same day by 2 independent observers. Cross sectional construct validity was also assessed by correlating the values of some clinical variables with the scores of the Pediatric EPM-ROM scale. RESULTS: The instrument was applied to 34 patients with JRA, 11 systemic, 11 polyarticular, and 12 pauciarticular. The mean EPM-ROM score was 0.57 (SD 0.54, min 0, max 2.05). The test-retest and interobserver correlation coefficients were 0.96 and 0.98, respectively. The Pearson correlation coefficients comparing scores of the Pediatric EPM-ROM scale and other variables were satisfactory: Childhood Health Assessment Questionnaire, r=0.55 (p<0.001); American College of Rheumatology global functional class, r=0.56 (p<0.001); and number of limited joints, r=0.65 (p<0.001). CONCLUSION: Our results provide evidence that the Pediatric EPM-ROM scale is a valid instrument to measure joint ROM in JRA.
10870318 Long-term effects of azathioprine therapy for juvenile rheumatoid arthritis. 2000 Apr BACKGROUND AND PURPOSE: Juvenile rheumatoid arthritis (JRA) can result in disability, growth disturbance, and systemic complications. This study investigated the efficacy and adverse effects of azathioprine (AZA) therapy in children with JRA. METHODS: Data from the medical records of 24 children with JRA treated with oral AZA during the period from 1988 to 1998 were retrospectively analyzed. All 24 patients had received two or more nonsteroidal anti-inflammatory drugs (NSAIDs) and 12 had received disease-modifying antirheumatic drugs (DMARDs) prior to the start of AZA. Of the 24 patients, 21 were corticosteroid-dependent prior to the onset of AZA therapy. The indication for AZA therapy was lack of efficacy of the current treatment regimen. The initial and maximal doses of AZA averaged 1.7 mg.kg-1.d-1 (range, 1-3 mg. kg-1.d-1) and 1.9 mg.kg-1.d-1 (range, 1-6 mg.kg-1.d-1), respectively. The mean duration of treatment was 13 months (range, 4-37 mo). The mean duration of follow-up was 45 months (range, 7-137 mo) from the start of AZA therapy. RESULTS: Fifteen children (62.5%) showed clinical improvement, while the other nine (37.5%) achieved clinical remission. AZA treatment resulted in a more than 50% reduction in the required corticosteroid dose in seven children and complete discontinuation of corticosteroid administration in eight children. None of the patients treated with AZA doses of 1 to 3 mg.kg-1.d-1 developed AZA-related side-effects. Two patients suffered from AZA-related adverse effects due to AZA overdose (6 mg.kg-1.d-1). Both experienced pancytopenia and disseminated infection, which resolved following reduction of the AZA dose to 3 mg.kg-1.d-1. CONCLUSIONS: AZA is an effective and well-tolerated steroid-sparing agent for JRA refractory to NSAIDs or DMARDs.
9833699 Does smoking stimulate rheumatoid factor production in non-rheumatic individuals? 1998 Oct Smoking has been associated with increased incidence of rheumatoid arthritis (RA), joint damage and positive rheumatoid factor (RF). Here we report an analysis of the association between smoking and IgM, IgG and IgA RF in a cohort of non-rheumatic individuals participating in a prospective longitudinal study of the incidence and significance of elevated RF. From the initial cohort of nearly 14,000 randomly selected individuals aged 52-80 years, 109 RF-positive and 187 RF-negative non-rheumatic participants were recruited. All participants were tested for RF at least twice at an interval ranging from 4 to 13 years. Of the RF-negative participants 21.9% were active smokers compared to 34.1% of IgM RF-positive (p=0.035), 20.8% of IgG RF-positive (N.S.) and 34.4% of IgA RF-positive participants (p=0.047). Smoking was most prevalent (44.8%) amongst participants with elevation of both IgM and IgA RF (p=0.008), and smokers were also significantly more likely to have a persistent elevation of RF than non-smokers (p=0.024). These findings indicate that smoking may influence the immune system, leading to increased production of IgM and IgA RF.
10599365 Sulphasalazine. An alternative drug for second-line treatment of juvenile chronic arthriti 1999 Sulphasalazine has been established to be an effective drug for second line treatment of early mild to moderate rheumatoid arthritis. Its application for juvenile chronic arthritis (JCA) is limited so far and controversial results for the efficacy of this therapy have been published. We studied the efficacy and tolerance of the sulphasalazine treatment in 32 patients with JCA (10 with polyarthritis, 21 with pauciarthritis and 1 with systemic form). Our results revealed significant response of the treatment at the end of the 6th month in 24/31 patients (77%). In one patient the treatment was discontinued because of transitory neutropenia at the end of the 1st month. No significant difference was observed between the efficacy of the treatment in the polyarticular and pauciarticular disease, as well as newly-diagnosed cases and those with longstanding disease. From the group of 17 children treated up to the end of the 1st year 88% achieved complete remission. No serious toxic effects were observed, with the exception of two cases with transitory low-grade neutropenia. According to our results sulphasalazine is an effective and well tolerated drug for second line treatment of JCA-patients.
11742208 Adjuvant-induced arthritis: IL-1 beta, IL-6 and TNF-alpha are up-regulated in the spinal c 2001 Dec 21 Adjuvant-induced arthritis (AIA) is a widely used animal model of human rheumatoid arthritis (RA). We have previously shown that increased neuropeptide expression is observed in the spinal cord of AIA rats. To study the potential role of cytokines in the spinal cord of AIA, we wanted to determine whether there are changes of glial and cytokine expression (IL-1 beta, IL-6, TNF-alpha and IFN-gamma) in the spinal cord of AIA rats. Our data indicated that macroglia and MHC class II immunostaining were enhanced, astrocytes expressing GFAP were increased in number and immunostaining intensity. Using in situ hybridization and immunohistochemical methods, both mRNA and protein levels of IL-1 beta, IL-6 and TNF-alpha were significantly increased in the spinal cord of arthritic rats. Increased cytokine expression was presented in the reactive astrocytes and microglia.
10524677 A new spin on an old model: in vivo evaluation of disease progression by magnetic resonanc 1999 Oct OBJECTIVE: To noninvasively examine the pathogenesis of rat adjuvant-induced arthritis (AIA) by magnetic resonance imaging (MRI), and to correlate MRI indices of disease progression with classic inflammatory parameters and histologic evaluation. METHODS: AIA was established in male Lewis rats following subcutaneous injection in the right hindpaw with 0.5 mg of heat-killed Mycobacterium butyricum suspended in light mineral oil. In vivo MRI evaluations of soft tissue and bony changes in AIA rats with matched histopathology were correlated with changes in left hindpaw volumes, circulating leukocytes, acute-phase reactants, and urinary collagen crosslinks throughout the disease process. RESULTS: MRI of arthritic tibiotarsal joints of the uninjected left hindpaws from AIA rats demonstrated 2 distinct phases of disease activity. The first phase, apparent between days 10 and 18, was characterized by periarticular inflammation with marked synovitis, synovial fibroplasia, and distension of the joint capsule into the surrounding tissue. The secondary phase, occurring between days 18 and 30, was marked by continued soft tissue inflammation, periostitis with osteolysis, and periosteal new bone formation progressing to a state of near complete ankylosis by day 30. These 2 phases of disease activity observed by MRI paralleled biochemical, cellular, and histologic markers of disease progression. CONCLUSION: MRI can be used to noninvasively detect, monitor, and quantify the chronic synovitis and progressive destruction of soft tissue and bone in live AIA rats, thereby improving the ability to evaluate disease progression in this preclinical animal model of rheumatoid arthritis.
12089621 [The subclinical involvement of the lung in rheumatoid arthritis: evaluation by high-resol 2001 Pulmonary involvement is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA) and represents a serious complication, being the second cause of death after infection. High-resolution computed tomography (HRCT), owing to its increased sensitivity and diagnostic accuracy respect to the conventional chest radiograph (CXR), allows to detect pulmonary abnormalities in RA patients more frequently than CXR. The aim of this study was to assess pulmonary involvement by HRCT in lifelong non-smoking RA patients without symptoms and clinical signs of pulmonary disease. Seventy-two patients (54 women and 18 men) with a mean age of 56.8+/-10.4 years (range, 40-77 years) and mean duration of disease of 6.9+/-4.7 years (range, 2-12 years) entered the study. 52/72 (72%) were positive for rheumatoid factor (> 20 UI/ml). Standard CXR and HRCT were carried out in each patient. CXR showed a mild interstitial fibrosis in 7 patients (9.7%), whereas HRCT demonstrated pulmonary abnormalities in an higher number of them (22/72 = 30.5%). The most frequent abnormal findings on HRCT were irregular pleural margins (13.8%) and septal/subpleural lines (18%), both compatible with pulmonary fibrosis. Ground-glass opacities were found in 8.3% of the patients. Pulmonary nodules (diameter, range 0,5-2 cm) predominantly located in the subpleural portions of the lung, were demonstrated in the same percentage (8.3%) of patients. Small airway involvement, represented by bronchiectasis/bronchioloectasis, was shown in 15.2% of patients. Subpleural cysts were present in two cases (2.8%). No patient had evidence of honeycombing on HRCT. In conclusion, HRCT is an accurate, non-invasive and safe method of diagnosing lung abnormalities in RA patients without signs and clinical symptoms of pulmonary disease.
9872036 Systemic Penicillium marneffei infection in a child with common variable immunodeficiency. 1998 Nov Penicillium marneffei is rarely pathogenic in humans. Most previously reported cases of P. marneffei infection were from Southeast Asia where patients were usually in an immunocompromised state due to human immunodeficiency virus (HIV) infection. The majority of the patients reported in Western countries were immunocompromised by malignancy, especially Hodgkin's lymphoma. In Taiwan, the first case of P. marneffei infection was reported in 1994 and involved an adult with HIV infection. We report a case of systemic P. marneffei infection in a child with common variable immunodeficiency (CVID). The patient, a 4-year, 5-month-old boy, had a 1-year history of oligoarthritis resembling juvenile rheumatoid arthritis (JRA). He developed a low grade fever (38 degrees C) and hepatosplenomegaly 1 month before admission to the hospital. Although cultures of synovial fluid obtained at the time of onset of oligoarthritis did not grow any organisms, cultures of blood, bone marrow, synovial fluid, and lymph node biopsy samples taken during this admission were positive for P. marneffei. Further immunologic studies revealed a profile characteristic of CVID. The fungal infection was finally eradicated by combined therapy with amphotericin B, fluconazole, itraconazole, and regular immunoglobulin replacement. This case reminds us that JRA or JRA-like arthritis should be differentiated from septic arthritis caused by rare pathogens in immunocompromised patients.
11147755 Serum levels of hyaluronic acid in patients with psoriatic arthritis. 2000 The purpose of this study was to evaluate the serum levels of hyaluronic acid (HA) in a group of patients with psoriatic arthritis (PsA), with special emphasis on the relationships between HA levels and clinical parameters of joint and skin activity. Thirty-four patients with PsA, 34 patients with rheumatoid arthritis (RA) and 49 healthy volunteers participated in the study. Assessment of joint disease in patients with PsA included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory back pain and Schober's test. The current severity of skin involvement was graded according to the Psoriasis Area Severity Index (PASI). Serum levels of HA were measured by a radiometric assay. The mean HA serum levels of patients with PsA and RA were significantly increased in comparison with healthy controls (107 +/- 39.6 microg/dl in patients with PsA, whereas in patients with RA it was 168 +/- 32.4 microg/dl and 36.7 +/- 5.5 microg/dl in healthy controls). A highly significant correlation was found between levels of HA and index of skin involvement, but no association was found between HA levels and clinical parameters of joint severity. We conclude that in this cohort of patients with PsA, HA levels clearly reflected psoriatic skin involvement although it did not correlate with joint disease.
9353148 Local therapy with soluble complement receptor 1 (sCR1) suppresses inflammation in rat mon 1997 Oct Complement activation has been implicated in the pathogenesis of human rheumatoid arthritis. We sought to determine whether inhibition of complement (C) using sCR1 could influence the development and progression of antigen arthritis in the rat, a recognized model of human chronic synovitis. The effect of C inhibition, systemically and locally, on three different stages of disease was examined: (i) prophylaxis, (ii) treatment of established inflammation, and (iii) prevention of antigen-induced flares of disease. Arthritis was assessed by knee swelling and by histological examination. Our results show that intra-articular injection of sCR1 prior to disease onset reduced joint swelling and development of arthritis, whereas systemic administration was ineffective. Treatment of established arthritis with intraarticular sCR1 3 days after disease onset caused a transient reduction in swelling, but treatment 7 days after disease onset had no effect on disease. An intra-articular dose of sCR1 given at the time of disease flares had a small, yet significant effect on knee swelling. We conclude that complement activation is important in the initiation and maintenance of inflammation in antigen arthritis. The potent effect of local C inhibition suggests that C biosynthesis and activation within the joint contributes to inflammation in this model of arthritis.
11832040 [Risk factors for nosocomial infections after total knee replacement]. 2000 Apr OBJECTIVE: To investigate prevalence and risk factors of nosocomial infections in patients with total knee replacement. METHODS: From August 1993 to October 1998, total knee replacement was performed on 363 patients (503 knees). The difference of nosocomial infection rates was statistically analyzed in comparison with different age, primary disease, and associated disease groups. RESULTS: No statistically significant difference was observed in nosocomial infection when compared rheumatoid arthritis with osteoarthritis, bilateral total knee replacement (TKR) with unilateral TKR and different ages. However, the higher nosocomial infection rate was related to the following factors: revision surgery, steroid administration and diabetes urinary infection. 28 female patients demonstrated higher urinary infection rate than that in other systems. CONCLUSIONS: Nosocomial infection rate of TKR in rheumatoid cases is related to steroid administration, accompanying diabetes mellitus, previous knee surgery, aged women and retention of urinary catheter. It is feasible to prevent nosocomial infection by controlling the above-mentioned risk factors.
10708568 Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts ind 2000 Mar 16 The effects of cyclooxygenase (COX)-2 antisense oligodeoxynucleotide (ODN) in induction of adjuvant-induced arthritis were investigated. Female Lewis rats were injected with Mycobacterium butyricum intradermally at the base of tails to induce arthritis. Synthetic 18 mer phosphorothioate ODNs corresponding to the translation initiation site of rat COX-2 mRNA were prepared. The antisense (AS), sense (S), and "scrambled" (Sc) ODNs were intraperitoneally administered. Arthropathy was evaluated with arthritis score, paw edema, and histological examination. Expression of COX-1 and -2 protein and mRNA were examined with immunostaining and reverse-transcription polymerase chain reaction, respectively. COX-2 AS ODN significantly suppressed induction of arthritis in a dose-dependent manner without severe adverse effects, whereas S and Sc ODNs did not show significant inhibitory effects. COX-2 mRNA and protein expression were also suppressed only by COX-2 AS ODN without any alteration of COX-1 expression. These data suggest that selective inhibition of COX-2 with AS ODN may have a therapeutic potency in the treatment of rheumatoid arthritis.
11315918 Expression of angiogenic factors in juvenile rheumatoid arthritis: correlation with revasc 2001 Apr OBJECTIVE: Although increased vascularity was noted in early histopathologic studies of juvenile rheumatoid arthritis (JRA) synovium, the available data on angiogenesis in JRA are very limited. The main purposes of this study were to assess expression of the key angiogenic factors in JRA synovium, and to evaluate a SCID mouse model of JRA as an approach to study in vivo regulation of the expression of these factors in JRA. METHODS: RNase protection assay was used to assess the expression of the key angiogenic factors in fresh JRA synovium and in JRA synovial tissue fragments that had been minced and then implanted into SCID mice. Vascularity of the samples was assessed by immunohistochemical staining for von Willebrand factor. Synovial specimens obtained from patients with osteoarthritis (OA) or other noninflammatory arthropathies were used as controls. RESULTS: Detectable levels of messenger RNA for vascular endothelial growth factor and angiopoietin 1 and their respective receptors, as well as endoglin and thrombin receptors, were present in all JRA tissue specimens studied. The levels of expression of these factors in JRA tissues were significantly higher than those in tissues obtained from patients with OA or other noninflammatory arthropathies. Furthermore, increased expression of the key angiogenic factors in the fresh JRA tissues correlated with the exuberant revascularization of JRA minced tissue fragments implanted into SCID mice. This was in sharp contrast to the poor revascularization of implanted OA tissues. CONCLUSION: JRA synovium is characterized by high angiogenic activity. SCID mouse-human JRA synovium chimeras may provide a good approach to study the in vivo regulation of angiogenesis in JRA.
10648012 Polymorphonuclear elastase-alpha1-proteinase inhibitor (elastase-alpha1 antitrypsin) in pa 2000 Jan OBJECTIVE: To determine whether elastase-alpha1-proteinase inhibitor (E-alpha1PI) complex behaves as an acute phase reactant in inflammatory arthritis. METHODS: E-alpha1PI complex was measured in the plasma of 89 patients with different rheumatic diseases and 28 healthy controls. Correlations were sought between standard indices of disease activity as patients went into remission with the use of disease modifying antirheumatic drugs (DMARD). RESULTS: Compared with levels in 28 healthy controls, E-alpha1PI was significantly higher in 58 patients with rheumatoid arthritis (RA), 14 with ankylosing spondylitis, and 17 with noninflammatory rheumatoid disease. No significant correlations were found between E-alpha1PI and various laboratory and clinical variables of disease activity in RA before introduction of a DMARD. There was a slight decrease in E-alpha1PI over 24 weeks of treatment as other acute phase reactants fell significantly, although this did not reach significant levels. No correlations were found between intra-individual change of E-alpha1PI and different indices of disease activity from Week 0 to Week 24. CONCLUSION: E-alpha1PI complex levels, measured as an index of neutrophil activation, did not correlate with improvement in disease activity in inflammatory arthritis afforded by DMARD.
9558176 Musculoskeletal surgery in psoriatic arthritis. 1998 Apr OBJECTIVE: To determine the probability that patients with psoriatic arthritis (PsA) will require musculoskeletal surgery. To identify factors predictive of surgery in patients with PsA. To determine the clinical outcome of patients with PsA who underwent surgery compared to patients who did not. METHODS: The database of the Psoriatic Arthritis Clinic was searched to identify individuals who had undergone musculoskeletal surgery. Biological and clinical data such as erythrocyte sedimentation rate (ESR), rheumatoid factor, clinical pattern, nail changes, functional class, number of inflamed joints, and radiological damage, as well as health scores such as Arthritis Impact Measurement Scale 2 (AIMS-2), SF-36, and Health Assessment Questionnaire (HAQ) were available for these patients. Patients who had surgery were compared to those who did not. RESULTS: Out of 444 patients with confirmed PsA, 31 had musculoskeletal surgery (6.98%). This probability increased with the duration of PsA. Surgery patients had their first operation at an average of 13.9 years (range 1-46) after onset of joint disease. Age at onset of PsA, clinical pattern, constancy of clinical pattern over time, rheumatoid factor, functional class, symmetry, nail changes, and the time separating the onset of skin disease and the onset of joint disease were not significantly different at the 0.05 confidence level. Patients who had surgery had significantly more radiological damage (p < 0.001) and more actively inflamed joints (p < 0.02) at first assessment than patients who did not. AIMS2, SF-36, and HAQ scores at final review were not statistically different across both groups. CONCLUSION: In our patients the probability of having musculoskeletal surgery for PsA was 7%. It increased with disease duration. Patients had their first surgery after an average of 13 years. The number of actively inflamed joints and the extent of radiological damage at first assessment were highly predictive of subsequent surgery: patients with the highest numbers of severely affected joints, both clinically and radiologically, were more likely to have surgery. "Baseline characteristics" such as ESR, rheumatoid factor, functional class, clinical pattern, nail changes, and symmetry were not predictive of subsequent orthopedic surgery.