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ID PMID Title PublicationDate abstract
8311550 Anti-myeloperoxidase antibodies in patients with rheumatoid arthritis: prevalence, clinica 1994 Jan OBJECTIVES: To determine the prevalence and clinical associations of autoantibodies to myeloperoxidase (MPO) in an unselected series of well-characterised outpatients with rheumatoid arthritis (RA) and to compare the distribution of IgG subclasses of anti-MPO antibodies in these patients with that in patients with systemic vasculitis. PATIENTS AND METHODS: A study was made of 97 patients with RA, who have been seen regularly in this department for up to 20 years, and 29 patients with anti-neutrophil cytoplasmic antibody (ANCA) positive systemic vasculitis. Anti-MPO antibodies were detected using a direct-binding enzyme-linked immunosorbent assay (ELISA) with MPO from human granulocytes as antigen. The IgG subclass of anti-MPO antibodies was determined by ELISA using isotype specific monoclonal antibodies. RESULTS: Anti-MPO antibodies were detected in 12% of patients with RA. Six sera contained IgG anti-MPO antibodies only, 1 IgM only and 5 antibodies of both classes. In the patients with RA the predominant subclasses were IgG1 and IgG3: only 2 sera contained detectable IgG4 antibodies. This was in contrast to patients with vasculitis, in whom most sera contained IgG1, IgG3 and IgG4 anti-MPO antibodies. Anti-MPO antibodies in sera from both patient groups bound only to the native protein. None of the patients studied with RA had evidence of vasculitis affecting the nerves or kidney: three patients (1 positive for anti-MPO antibodies and 2 negative) had cutaneous vasculitis. In the patients with RA, positivity for anti-MPO antibodies was associated with nodules and number of active joints. Three patients with anti-MPO antibodies, and none without, had pulmonary fibrosis. CONCLUSIONS: Twelve per cent of a group of unselected outpatients with RA, but without evidence of major systemic vasculitis, had anti-MPO antibodies in their serum. Positivity for anti-MPO antibodies was more common in patients with nodular disease and lung involvement but not in patients with cutaneous vasculitis. IgG4 sub-class anti-MPO antibodies were present in 90% of sera from patients with ANCA-positive vasculitis and only 2/11 (18%) of anti-MPO antibody containing sera from patients with RA.
1550907 A pharmacokinetic and tolerance study of romazarit in patients with rheumatoid arthritis. 1992 Mar Romazarit is a new drug for which animal pharmacology suggests a disease-modifying action in rheumatoid arthritis (RA). These animal studies predict that plasma romazarit concentrations within the range 50-100 mg l-1 may be required for efficacy in the clinic. Therefore, a pharmacokinetic study was designed to estimate the dosage required to achieve these concentrations in man. Twenty-four patients with RA entered a double-blind controlled assessment receiving either placebo, 100 mg t.i.d., 350 mg b.i.d., or 350 mg t.i.d., for 6 days. Pharmacokinetic profiles were measured after single doses and after the last of the multiple doses. Adverse events were mainly trival and were distributed almost equally between all three treatment and the placebo groups. Plasma romazarit concentrations were not dose-proportional after the single doses. Mean peak plasma drug concentrations were 11.8, 66.7, and 159 mg l-1 at steady state after 100 mg t.i.d., 350 mg b.i.d., and 350 mg t.i.d. The mean urinary recovery of drug-related material (mostly ester glucuronides) was 71 per cent of the dose during the dosage interval. The renal clearance of romazarit glucuronides correlated with creatinine clearance (p less than 0.01). Saturable tubular secretion of glucuronides coupled with reversible glucuronidation would explain these findings. It is predicted that oral doses of 450 mg romazarit given 12-hourly will result in plasma concentrations within the target range of 50-100 mg l-1.
7614782 Increased frequency of the uncommon allele of a tumour necrosis factor alpha gene polymorp 1995 Mar The frequency of the uncommon allele (TNF2) of a polymorphism in the promoter region of the tumour necrosis factor alpha (TNF alpha) gene in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was found to be 3 times that of the normal anglo-saxon population. In SLE patients, this allele was strongly associated with HLA-DR3 expression and was also more frequent in patients who did not have malar rash. Functional studies of normal monocyte cytokine production in vitro showed that this genotype was associated with increased IL-1 alpha protein production but there were no differences in the production of TNF alpha protein.
8103964 Variability in individual responses of 532 patients with rheumatoid arthritis to first-lin 1993 Variability in individual responses to drugs used to treat rheumatoid arthritis was studied in 532 patients under care in seven U.S. rheumatology private practices. Among 15 nonsteroidal anti-inflammatory drugs (NSAIDs), estimated continuation of 1,775 courses was 48% at 12 months and 20% at 60 months. Acetylated salicylates, other than plain aspirin, were continued significantly longer than other NSAIDs. Among second-line drugs, estimated continuation of 50% of courses was 10 months for oral gold, 20 months for hydroxychloroquine, 21 months for penicillamine, 25 months for parenteral gold, 27 months for azathioprine, and more than 60 months for methotrexate and prednisone, the only drugs continued by more than 50% of patients 60 months after initiation.
8660103 Constitutive expression of c-fos and c-jun, overexpression of ets-2, and reduced expressio 1996 May OBJECTIVES: To identify genes that are involved in the development and progression of rheumatoid arthritis (RA). METHODS: We used a multiple gene analysis system and a set of available genes participating in processes such as proliferation, differentiation, tumour progression, and metastasis, to identify their RA related expression. Synovial tissues from 22 patients with RA were evaluated in comparison with those from six patients with osteoarthritis and two patients with non-inflamed joints as controls, using northern blot and reverse transcriptase polymerase chain reaction experiments. RESULTS: Our data confirm the role of c-fos and c-jun as constitutive signal transmitters in solid RA tissues, thus demonstrating the potential of the approach. Activation of both genes persisted through multiple passages of the cells in tissue cultures derived from the synovial lining of RA tissues. There was an increased expression of ets-2 in 30% of RA samples and an up to 30-fold decreased expression of the potential metastasis suppressor gene nm23-H1 in 90% of RA tissues, compared with control tissues. CONCLUSIONS: The data presented show for the first time a significant decrease of nm23-H1 expression in RA, which is possibly involved in local invasiveness, and a strong activation of the ets-2 nuclear oncogene in about one third of RA tissues, which may also be part of a pathway leading to advanced disease stages. The constitutive expression of c-fos and c-jun in RA tissue most probably results from a continuing inflammatory stimulus. These findings with cell cultures suggest an intrinsic activation mechanism of these early response genes in RA.
8168202 [Dot immunobinding assay for detection of three types of rheumatoid factor and its clinica 1993 Aug We set up a dot immunobinding assay method for determination of IgM-, IgG- and IgA-rheumatoid factor (RF) and report here the results in 86 patients with rheumatoid arthritis (RA). It was found that the positive rates of IgM-, IgG- and IgA-RF were 59.7%, 54.7% and 17.4% respectively. The total positive rate was 72.8%. The positive rate using the Latex method was only 43.0%. Our results reveal that dot immunobinding assay for RF is more sensitive than the Latex method. Furthermore, there was a profound correlation of IgG-RF with active stage and the frequency of extra-artivular manifestations in RA patients.
8014929 Depression is not more common in rheumatoid arthritis: a 10-year longitudinal study of 6,1 1993 Dec OBJECTIVE: To determine if depression scores and depressive symptoms are higher in patients with rheumatoid arthritis (RA) than among those with other rheumatic disorders; and to describe norms for the Arthritis Impact Measurement Scale (AIMS) depression scale. METHODS: A 100% sample of all clinic visits of 6,153 consecutive patients with rheumatic disease seen in an outpatient rheumatic disease clinic during a 10-year period. 19,122 AIMS depression scores were utilized. For each patient an average depression score was calculated. Covariates included age, sex, education level, ethnic origin, and number of clinic visits. RESULTS: RA depressive symptoms and depression scores did not differ from all other clinic patients (taken as a whole). Patients with fibromyalgia had significantly more abnormal scores. CONCLUSION: Depression scores are not higher or depressive symptoms more common in patients with RA compared with other clinic patients. By every measure depression is increased in fibromyalgia. The notion that patients with RA have increased depression or are somehow more susceptible to depression is not supported by the data and should be abandoned.
8452582 The measurement of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collage 1993 Mar OBJECTIVE: To compare the levels of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase-TIMP complex in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). This study aims to clarify existing data from previously used enzyme or inhibitor activity assays performed following separation by gel filtration, by using a 1-step enzyme-linked immunosorbent assay (ELISA) for each component. METHODS: Total collagenase, free TIMP, and collagenase-TIMP complex were measured using a newly developed, specific double-antibody sandwich ELISA: RESULTS: Levels of both collagenase and TIMP were significantly higher in RA patients (collagenase 1,560 +/- 150 ng/ml [mean +/- SEM], TIMP 1,610 +/- 130 ng/ml; n = 80) than OA patients (collagenase 420 +/- 90 ng/ml, TIMP 1,050 +/- 60 ng/ml; n = 80), with the difference being especially striking for collagenase. Sixteen RA fluids had detectable levels of collagenase-TIMP complex, compared with only 3 OA fluids. CONCLUSION: The level of total collagenase in SF is greater in RA than OA, while levels of free TIMP show more overlap between the 2 diseases; this may simply reflect the increased inflammation seen in RA, or it may reflect a different disease mechanism.
9082565 [Knee endoprosthesis--determining current status]. 1996 Dec A nationwide survey was performed to evaluate the significance of knee replacement (endoprosthesis) in Germany. All orthopaedic, traumatologic and general surgeons were asked about their preferred surgical techniques, favourite types of prosthesis and related issues. Sledge prostheses have been increasingly preferred to constrained prostheses in the last few years. Unicompartmental prostheses as well as constrained prostheses and high tibial osteotomies are still chosen for special cases. Revisions were most commonly due to patella problems. Patella replacement is popular to prevent this problem. Endoprosthetic knee surgery receives as much endorsement among German surgeons as endoprosthetic hip surgery. An important problem is the increasing costs of the method.
8147925 The mortality of rheumatoid arthritis. 1994 Apr OBJECTIVE: To determine the risk and causes of death and to quantify mortality predictors in patients with rheumatoid arthritis (RA). METHODS: RA patients (n = 3,501) from 4 centers (Saskatoon n = 905, Wichita n = 1,405, Stanford n = 886, and Santa Clara n = 305) were followed for up to 35 years; 922 patients died. RESULTS: The overall standardized mortality ratio (SMR) was 2.26 (Saskatoon 2.24, Wichita 1.98, Stanford 3.08, Santa Clara 2.18) and increased with time. Mortality was strikingly increased for specific causes: infection, lymphoproliferative malignancy, gastroenterologic, and RA. In addition, as an effect of the SMR of 2.26, the expected number of deaths was increased nonspecifically across all causes (except cancer), with a large excess of deaths attributable to cardiovascular and cerebrovascular diseases. Independent predictors of mortality included age, education, male sex, function, rheumatoid factor, nodules, erythrocyte sedimentation rate, joint count, and prednisone use. CONCLUSION: Mortality rates are increased at least 2-fold in RA, and are linked to clinical severity.
8883439 A comparison of the clinical features of hospital out-patients with rheumatoid disease and 1996 Oct Several studies have demonstrated differences between ethnic groups in the severity and pattern of rheumatoid arthritis (RA) and osteoarthritis (OA). The current investigation compared RA and OA in Pakistani and British White Caucasian out-patients in two teaching hospitals. There were 88 RA patients in each setting, matched for age, gender and disease duration. The pattern of OA was sought by recording the details of 44 consecutive new referrals to each clinic. Amongst the RA patients, joint deformity and tenderness were similar, but disability was more severe, ESR higher, anaemia more pronounced and RA latex more often positive amongst the Pakistani patients. X-ray damage was more pronounced amongst the British patients, especially in the feet. The British were also more likely to have rheumatoid nodules and to have undergone disease-modifying treatment or joint surgery. The paradox of more severe indices of disease activity and disability with less X-ray erosion in hands and feet might be explained by the impact of treatment on joint inflammation and the beneficial influence of surgery on disability in the British. The worse X-ray scores in the White Caucasians might indicate a genetic predisposition to radiologically more severe disease. The age of the British OA patients was significantly higher, but this is unlikely to have influenced the striking disparity in the frequency of isolated knee OA, which was significantly greater in the Pakistani patients. Comparison with age- and sex-matched healthy Pakistani subjects suggested that susceptibility to knee OA was strongly associated with body weight, but not with knee bending at prayer or with joint laxity. Amongst the Pakistanis, Heberden nodes, hip involvement and evidence of generalized OA were significantly less, but these observations may have been due to their younger age. The study confirmed differences in the clinical presentation of both RA and OA amongst patients in Pakistan compared with White Caucasians in Britain. Several confounding factors, such as patient recruitment, culture, treatment and age, may have influenced the results, but it remains likely that genetic factors are important.
1316744 Detection of cytomegalovirus antigens in phagocytosed serum complexes from a patient with 1992 Apr A patient with rheumatoid arthritis, vasculitis, peripheral neuropathy, cutaneous ulceration, and digital gangrene was studied. Circulating immune complexes were detected by C1q binding although serum complement levels were within the normal range. Immunofluorescent staining of buffy coat cells with specific antisera showed the presence of IgG and IgM in phagocytosed inclusions but complement C3 was not detected. A monoclonal antibody specific for cytomegalovirus detected antigens in phagocytosed inclusions on one occasion. These results may suggest that cytomegalovirus antigens are a hitherto unidentified component of serum complexes in patients with rheumatoid arthritis and may contribute to the pathogenesis of the vasculitic complications of rheumatoid arthritis by participating in immune complex formation.
1418029 IX 207-887 in rheumatoid arthritis. A double-blind placebo-controlled study. 1992 Sep OBJECTIVE: To determine the efficacy and the safety of IX 207-887 treatment in rheumatoid arthritis. The IX compound [10-methoxy-4H-benzo(4,5)cyclohepta-(1,2-b)thiophene-4-yliden acetic acid] is effective in several animal models of rheumatoid arthritis and has a mechanism of action involving the inhibition of interleukin-1 release. METHODS: A double-blind, controlled trial of 16 weeks' duration comparing placebo with IX at a daily dosage of 800 mg or 1,200 mg (20 patients/group) was conducted. RESULTS: Thirteen patients withdrew from the study, 3 because of lack of efficacy (all in the placebo group) and 10 because of side effects (1 in the placebo group [skin rash] and 9 in the IX groups [skin rash in 5, intestinal disturbances in 2, hepatitis in 1, meningitis in 1]). Intent-to-treat analysis showed a statistically significant difference in the variations of clinical and laboratory parameters between the 3 groups. Between-group comparisons showed an improvement in all these variables in the IX groups versus the placebo group. According to Paulus' criteria, 2 of the 20 placebo-treated patients (10%), 9 of the 20 IX 800 mg-treated patients (45%), and 11 of the 20 IX 1,200 mg-treated patients (55%) were considered responders (P = 0.008). CONCLUSION: The findings of this study suggest that the tolerability of IX is acceptable in rheumatoid arthritis patients, and that IX is an effective slow-acting drug for use in rheumatoid arthritis.
8729772 HTLV-I associated uveitis, myelopathy, rheumatoid arthritis and Sjögren's syndrome. 1995 Dec A 62 year-old white female presented with a 10-year-history of slowly progressive spastic paraparesis, pain and dysesthesia in the lower limbs and sphincter disturbance. A few years after the onset of the neurologic symptoms she developped migratory arthritis with swelling of the knees and pain on palpation of knees and fingers, dry eyes, mouth and skin. Two months before admission she presented bilateral nongranulomatous anterior uveitis. Examination revealed spastic paraparesis with bilateral Babinski sign, a decreased sensation level below L3, decreased vibration sense in the lower extremities, and a postural tremor of the upper limbs. Laboratory work-up disclosed HTLV-I positive tests in the blood and cerebrospinal fluid (CSF), and a mild pleocytosis in the CSF with a normal protein content. Nerve conduction velocity studies were normal. The present case shows the association of uveitis, arthritis and Sjögren's syndrome in a patient with tropical spastic paraparesis/human T-cell lymphotropic virus type I (HTLV-I) associated myelopathy (TSP/HAM), and illustrates the wide spectrum of clinical manifestations which may accompany this infection with this virus.
7586775 Serum erythropoietin and transferrin receptor levels in patients with rheumatoid arthritis 1995 Jul OBJECTIVE: Rheumatoid arthritis (RA) is generally associated with mild anaemia. The role of erythropoietin (EPO) in the pathogenesis of this anaemia of chronic disorders is still a matter of controversy. Therefore, in a multicenter study we investigated the serum EPO concentration in 124 patients with rheumatoid arthritis. METHODS: Patients with uncomplicated iron deficiency and haemolytic anaemia served as the reference group (n = 54). The measurements were performed with a specific and sensitive ELISA: RESULTS: The mean EPO concentration +/- SD of the whole RA group (32.3 +/- 22.2 mU/ml) was elevated above normal. About 40% of the patients had underlying iron deficiency (defined by ferritin values < or = 60 ng/ml) and a significantly higher median EPO concentration than patients with normal iron stores (35.8 mU/ml versus 20.7 mU/ml; p < 0.001). The iron deficiency was associated with lower disease activity, as defined by the C reactive protein. In contrast to the reference group (r = -0.78), there was no significant correlation between EPO and the haematocrit in either RA subgroup, although the values for the RA patients were within the 95% prediction range of the reference group. In addition to the EPO, we investigated the soluble transferrin receptor level as a measure of bone marrow erythropoiesis. The level in iron-replete RA subjects was about 1.6 times higher than in normal persons, reflecting a relatively hypoproliferative erythropoietic activity. CONCLUSION: This study shows that the EPO concentrations in RA are elevated above normal but lower than expected, and that the normal relationship between EPO and the degree of anaemia is impaired.
8082257 [IgG RF analysis of synovial fluid of the knee joints in 35 patients with rheumatic diseas 1993 Dec Rheumatoid arthritis (RA) is an autoimmune disease. IgG RF in the synovial fluid is a significant indicator for the pathogenesis and differential diagnosis of this disease. To now, RF tested by latex agglutination belongs to the IgM type whereas, in the rheumatoid synovial fluid, most of immunocomplex molecules are IgG which bind into a complex. IgG RF was determined by ELISA in the synovial fluid of 35 cases of joint disorders, including 12 cases of RA, 7 cases of reactive arthritis (ReA), 5 cases of osteoarthritis (OA) and 11 cases of non-synovitis (non-S) which were regarded as negative control. The upper limit of OD value +2s was 0.5. Using this standard 7 out of 12 cases of RA were positive. 2 of 5 cases of OA were weakly positive, and only one case of ReA was positive. This suggest that this test is valuable in the diagnosis of RA. We have also observed the relation between IgG RF in synovial fluid and X-ray and arthroscopic findings of the same knee joint. In 5 of 7 cases of positive RA, II-III X-ray changes and II-III cartilage destruction arthroscopic findings were noted, suggesting a relationship between IgG RF in synovial fluid and articular damage.
8033517 Impaired erythropoietin responsiveness in anaemic rheumatoid arthritis patients: potential 1994 May 1. Serum levels of erythropoietin and the immune parameters tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-2, interleukin-6 and interferon-gamma were measured in patients with rheumatoid arthritis. 2. Out of 69 patients, 44 had anaemia with serum haemoglobin concentrations of 10.8 (SD 1.2) g/dl. In these patients erythropoietin levels were significantly higher than in non-anaemic patients [51.97 (SD 23.9) versus 26.06 (SD 11.9) m-units/ml; P < 0.0001; control patients: 18.1 (SD 13.8) m-units/ml]. Mean soluble interleukin-2 receptor activity was elevated in all patients with rheumatoid arthritis [1324 (SD 715) units/ml; control patients: 480 (SD 75) units/ml; P < 0.001] and was significantly higher in the anaemic group than in the non-anaemic group [1562 (SD 662) versus 696 (SD 402) units/ml; P < 0.0001]. The serum activity of soluble interleukin-2 receptor showed an inverse correlation with haemoglobin (r = 0.79; P < 0.0001) and a positive correlation with erythropoietin (r = 0.70, P < 0.0001). 3. Elevated serum tumour necrosis factor-alpha levels were found in 19 anaemic patients [20.6 (SD 9.1) pg/ml]. Concentrations of tumour necrosis factor-alpha in serum showed an inverse correlation with haemoglobin (r = 0.57, P < 0.001) and a positive correlation with erythropoietin (r = 0.46, P < 0.05). Interleukin-6 was detected in seven anaemic patients [21 (SD 14) pg/ml] and interleukin-2 activity in three anaemic patients (12, 16 and 14 units/ml, respectively). Interferon-gamma was not detected in any of the patients investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
8422212 Reporting of age data in clinical trials of arthritis. Deficiencies and solutions. 1993 Jan 25 OBJECTIVE: We studied recent nonsteroidal anti-inflammatory drug (NSAID) randomized control trials of arthritis to identify the age and number of older people (> or = 65 years) and to document the way information on age was presented. We hypothesized that older people, who are most likely to take NSAIDs are underrepresented and underreported. STUDY SELECTION AND DATA EXTRACTION: All NSAID articles (n = 1008) in MEDLINE between September 1987 and May 1990 were identified. Eighty-three trials employing NSAIDs in a randomized control trial of arthritis reported in 73 articles were identified and studied in detail for age-related information. RESULTS: A total of 9664 subjects with a female-to-male ratio of 2.3:1 were enrolled. Forty-four trials studied osteoarthritis (53.0%), 37 studied rheumatoid arthritis (44.6%), and two studied both conditions (2.4%). More than half of the studies reviewed included people 65 years of age or older, only 207 people in this older age group could be identified (2.1%). While there was inclusion of the 'young-old' (65 to 74 years of age), only 14 of the 9664 people studied were between 75 and 84 years of age, and no one 85 years or older could be identified. The inclusion of the young-old is documented by the weighted mean age that ranged from 59.6 to 64.9 years for patients with osteoarthritis (mean, 62.9; SD, 1.67) and from 47.4 to 53.0 years (mean, 49.9; SD, 2.16) for those with rheumatoid arthritis. CONCLUSION: We demonstrate that older people, who represent a high proportion of the population treated with NSAIDs in practice, are generally omitted from drug trials. Recommendations designed to improve the reporting of age information to make clinical trials more informative and applicable to older people are presented.
10149943 Wrist arthrodesis by intramedullary rod fixation: a valuable technique. 1992 Apr Arthrodesis of the wrist with intramedullary rod fixation is a simple technique that provides the opportunity for performing concomitant procedures. Iliac bone graft usually is not required with this technique, as the intramedullary rod is a load-sharing construct that allows compression at the fusion site and facilitates union. Rod removal usually is optional, and the long intramedullary beam effect of the rod can function as an internal splint if fibrous or hypoplastic union occurs. Early mobilization is possible, sometimes with only minimal splinting. The results with use of this technique over a ten year period of time in ten wrists (nine patients) with endstage radiocarpal joint instability are reported.
1372282 Cell-free CD5 in patients with rheumatic diseases. 1992 Jan Since an increased frequency of CD5+ B cells has been reported in rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS), and the expression of the molecule was reduced on the T cells of some SS patients, we hypothesised that there would be an accelerated turnover of CD5 in these disorders. We describe a novel enzyme-linked immunosorbent assay for measuring cell-free (CF) CD5, using rabbit F(ab')2 anti-CD5 antibody as capture agent and monoclonal anti-CD5 antibody as revealing agent. It was established that CF-CD5 was detectable in RA and SS sera, as opposed to sera from patients with ankylosing spondylitis and normal controls. The level of CF-CD5 did not correlate with rheumatoid factor in RA patients but was significantly higher (P less than 0.05) in SS patients with extraglandular manifestations than in those with glandular disease. Three of the latter patients with significantly increased levels of CD5-negative T cells did not have a particularly high proportion of CF-CD5 in these sera.