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ID PMID Title PublicationDate abstract
9506573 Long-term outcome of autoimmune disease following allogeneic bone marrow transplantation. 1998 Mar OBJECTIVE: To investigate the long-term outcome of autoimmune disease following allogeneic bone marrow transplantation (BMT), and its relationship to hemopoietic chimerism. METHODS: Three previously described patients with rheumatoid arthritis (RA) who underwent allogeneic BMT for therapy-related severe aplastic anemia and 1 new patient with psoriasis who received BMT for chronic myeloid leukemia (CML) were followed up. Molecular studies were performed to assess hemopoietic and immune reconstitution in 3 cases. RESULTS: In 2 of the RA patients, the RA remained in remission without treatment, with nonprogressive disease, 11 and 13 years after BMT. The third patient with RA had a relapse 2 years after BMT, although the previously aggressive disease subsequently ran an attenuated course with treatment-free remission for the last 11 years. Comparison with other cases of RA suggests that graft-versus-host disease may influence the long-term outcome, perhaps through ongoing inhibition of the immune system. In the patient with psoriasis, BMT was followed by remission, but the psoriatic rash recurred and arthropathy developed 12 months later. The psoriasis and arthropathy remained active 4.5 years post-BMT, although the CML remained in remission. Molecular studies in the 2 patients whose RA remained in continued remission and in the patient with psoriasis that relapsed confirmed complete donor hemopoietic reconstitution. CONCLUSION: Long-term followup of autoimmune disease after allogeneic transplantation confirmed cure of the autoimmune disease in some, but eventual relapse in others. The occurrence of relapse despite complete donor hemopoietic reconstitution is evidence for the development of de novo, as opposed to persistent, disease, and is possibly related to intrinsic susceptibility of the transplanted stem cells or to host factors. There may be a relationship between remission of autoimmune disease and graft-versus-host reaction. These findings have relevance for the evolving application of stem cell transplantation as a therapy for autoimmune diseases.
10342649 Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Prote 1999 Mar OBJECTIVES: patients with rheumatoid arthritis (RA) are reported to have in their sera raised levels of antibody specific to Proteus mirabilis. The aim of the study was to verify this and to determine an explanation for it by investigating the frequency of P. mirabilis urinary tract infection in RA patients and matched controls. METHODS: freshly voided urine was examined for the presence, number and identity of infecting bacteria. The levels of antibody in blood and in urine of the IgM, IgA and IgG classes to the common O serotypes of P. mirabilis and the antigens to which they reacted were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: analysis of urine from 76 patients with RA and 48 age- and gender-matched healthy controls showed that only two (4%) of the control urines but 25 (33%) of those from the RA patients were infected. The commonest infecting organism in the RA patients' urine was Proteus mirabilis which occurred twice as frequently as Escherichia coli. Proteus mirabilis was found in 52% of the infected urines of the RA patients and was always detected as a pure growth and usually in insignificant (< 10(4)/ml) numbers. It is highly improbable that this finding was the outcome of differences in age, physical ability or medication between the RA and control patient groups. Comparison of antibody levels to P. mirabilis by ELISA showed RA patients had raised (P < 0.0001, P = 0.001, P = 0.0063) levels of IgA, IgG and IgM respectively in their sera and raised (P < 0.0001, P < 0.0001, P = 0.0001) levels of IgG, IgM and IgA respectively in their urine compared with the control group. It was not possible to detect an antibody reacting to a P. mirabilis antigen that was specific to the RA patients. CONCLUSION: the results confirm that RA patients have raised levels of antibody to P. mirabilis not only in blood but also in urine and suggest that this arises because RA patients have an asymptomatic, non-significant P. mirabilis bacteriuria more frequently or more prolonged than control patients. This may be the trigger for their RA condition.
11197696 New variations in human OX40 ligand (CD134L) gene. 2000 Dec We found three new variations in the OX40 ligand (OX40L, CD134L) gene and its 5' upstream region. -921 (G-->A) at 5' upstream region, -19 (C-->G) at 5' untranslated region, and 202 + 25 (G-->T) at intron 2 were identified. -921 (G-->A) and 202 + 25 (G-->T) were detected in a substantial proportion of healthy Japanese individuals and were considered to be single nucleotide polymorphisms (SNPs). -19 (C-->G) was detected in only one healthy individual. There was no association between these variations and the presence of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).
10466645 Ipsilateral total shoulder and elbow arthroplasties in patients who have rheumatoid arthri 1999 Aug BACKGROUND: The data on seventeen patients with rheumatoid arthritis who had been managed with ipsilateral total shoulder and elbow arthroplasties were analyzed to determine whether the operative technique, the presence of total shoulder and total elbow prostheses in the same upper extremity, or complications of the arthroplasties affected the result in each joint or the overall functional outcome of the upper extremity. METHODS: Seventeen patients with rheumatoid arthritis who were managed with a total of eighteen ipsilateral total shoulder and elbow arthroplasties were evaluated. The most recent physical examination was at an average of six years and six months (range, two years and one month to fourteen years) postoperatively. Radiographs, including 40-degree oblique and axillary radiographs of the shoulder as well as anteroposterior and lateral radiographs of the elbow, were made at an average of six years and eleven months (range, two years and two months to twenty-two years and eleven months) postoperatively. The radiographs of the shoulder were examined for loosening of the glenoid component, glenohumeral subluxation, and radiolucency at the bone-cement or bone-implant interface. The functional results of the total shoulder arthroplasties were evaluated with use of the rating systems of Neer et al. and Cofield. The Mayo elbow-performance score was used to evaluate elbow function. A rating system was also developed to assess the overall function of the upper extremity, including pain and motion of both the elbow and the shoulder. With this system, the overall function of the upper extremity was rated as excellent, good, fair, or poor. RESULTS: Evaluation of the shoulders revealed substantial relief of pain and an increase in active elevation. On radiographic evaluation, eight glenoid and five humeral components were considered to be loose. There were no reoperations. According to the rating system of Neer et al., eight shoulders had a satisfactory result and eight had an unsatisfactory result with limited active abduction. Limited-goals rehabilitation was successful after one shoulder arthroplasty and unsuccessful after another. There were two type-B periprosthetic humeral fractures. There was also substantial relief of pain in the elbows as well as an increase in the extension-flexion arc; the pronation-supination arc was sufficient for tasks of daily living. There was no radiographic loosening. Two elbows had an avulsion of the triceps, and two had aseptic loosening (one of which also had a worn bushing); all four needed a reoperation. One other elbow had persistent ulnar neuritis. The average interval between the arthroplasties was two years and eight months when the shoulder was replaced first and three years and five months when the elbow was replaced first. The interval between the joint replacements and the sequence of the joint replacements were not found to influence the outcome. Function of the extremity was improved by replacement of either the shoulder or the elbow alone; however, it improved significantly only when both joints were replaced (p = 0.03). According to combined clinical outcomes scores, there were nine excellent outcomes, four good outcomes, four fair outcomes, and one poor outcome after ipsilateral total shoulder and elbow arthroplasties. CONCLUSIONS: When there is severe arthritis of both the shoulder and the elbow, consideration should be given to replacing both joints in order to obtain optimum functional and clinical outcomes. The possibility of fracture of the humeral shaft necessitates an alteration of the technique for ipsilateral total shoulder and elbow arthroplasties.
9328776 Predictors of physician frustration in the care of patients with rheumatological complaint 1997 Sep Recent studies of the doctor-patient relationship have shown that certain patients are perceived as frustrating or difficult by their doctors; however, little is known about the characteristics of these patients that elicit this dissatisfaction. As part of a larger study of rheumatology clinic patients with fibromyalgia or rheumatoid arthritis (N = 68) we used stepwise multiple regression to select the factors most associated with physician frustration while controlling for the effects of other variables. Variable domains included demographics, psychiatric diagnoses, personality factors, functional disability, disease state, and trauma history. These domains as well as individual variables within these domains were systematically evaluated for their unique contribution to the prediction of physician frustration as measured by the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ). Initial bivariate correlates of physician frustration included marital status, current dysthymia and agoraphobia, lifetime panic disorder and obsessive-compulsive disorder, adult rape and physical abuse, somatization disorder, physical and social disability, the presence of fibromyalgia, as well as neuroticism, illness impact, and perceived loss of control. The best multivariable model for estimating frustration magnitude included somatization disorder, perception of lack of control over illness, and a lifetime history of obsessive-compulsive disorder. These factors explained 48% of the variance in DDPRQ score. Physicians in this study were most frustrated with patients who had ongoing preoccupation with multiple medically unexplained physical symptoms as well as the perception of greater impact and lack of control over their illness. These findings suggest that treatment of somatization in patients with chronic symptoms may decrease physician frustration.
9914217 Genetics of susceptibility to chronic experimental encephalomyelitis and arthritis. 1998 Dec The recent developments in genetic techniques and the development of more appropriate animal models for rheumatoid arthritis and multiple sclerosis make it possible to use a new approach for understanding these complex diseases. Thus it is now meaningful to address the question of which genes are causing the diseases. Several new associations with loci outside the MHC region have now been identified in models for both rheumatoid arthritis and multiple sclerosis. Some of these are shared between diseases - for example loci on mouse chromosome 3 (experimental allergic encephalomyelitis, collagen-induced arthritis and Theiler's encephalomyelitis) and rat chromosome 4 (collagen-induced arthritis and the experimental allergic encephalomyelitis induced by myelin oligodendrocytic glycoprotein).
10513510 Development of the Joint Protection Behavior Assessment. 1999 Jun OBJECTIVE: To develop an observational assessment of the use of joint protection (JP) methods by people with rheumatoid arthritis (RA). METHODS: Subjects with and without RA were videotaped performing a kitchen activity to identify the range of JP and non-JP methods used. Behavior codes were developed for these. Seven rheumatology occupational therapists reviewed and scored behaviors as correct, partially correct, or incorrect JP methods. Test-retest and interrater agreement studies were conducted. RESULTS: The Joint Protection Behavior Assessment (JPBA) demonstrated good content validity (kappa = 0.46 to 1.00), test-retest reliability (P < 0.0001), and interobserver agreement (kappa = 0.68 to 0.88). Construct validity was supported by significant correlations with hand impairment and function variables. CONCLUSION: The JPBA is a reliable and valid assessment of the use of JP methods by people with mild to moderate hand and upper limb joint involvement, which can be used to evaluate the effectiveness of JP education programs.
9125254 Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of sever 1997 Apr OBJECTIVE: To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy. METHODS: A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay. RESULTS: Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (+/- SD) pANCA log titers (103 +/- 5.6 versus 27 +/- 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA-associated nephropathy. CONCLUSION: Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.
9120516 Use of topical NSAIDs in patients receiving systemic NSAID treatment: a pharmacy-based stu 1997 Feb Topical non-steroidal anti-inflammatory drugs NSAID account for two-thirds of the most frequently prescribed NSAIDs in Germany. Nevertheless, the extent of use and the benefit of local NSAIDs are viewed critically. We described the use of topical NSAIDs in people with systemic NSAID therapy. The study population consisted of 526 people with an average age of 57 years; two-thirds of the patients were women. We observed that the elderly (60 years and older) and patients with osteo- and/or rheumatoid arthritis had an increased likelihood of being treated with both topical and systemic NSAIDs. We suggest that the frequent use of topical NSAIDs in these patients is based on their supportive therapeutic effect rather than on their efficacy. Further research is needed in order to investigate the potential beneficial effects of topical NSAIDs in NSAID therapy.
10073501 Production and elimination of hyaluronan in rheumatoid arthritis patients: estimation with 1999 Feb OBJECTIVE: To evaluate the benefit of determining the maximal elimination rate (Vmax) and the endogenous production of hyaluronan (HYA) in relation to the basal HYA concentration (c0) in rheumatoid arthritis (RA) patients; and to evaluate the compatibility of a new model for HYA kinetics, taking renal elimination into separate account in the overall clearance of HYA from the blood. METHODS: The calculations of production and elimination of HYA were based on the HYA loading test, which was performed in 21 patients with RA and 15 healthy controls. A blood sample was drawn before the loading test, followed by an intravenous (i.v.) injection of HYA as a single bolus dose of 7.5 mg. Blood samples were taken regularly during the next 60 minutes. A theoretical model with computational analysis of the data collected was used for calculating HYA production and elimination. RESULTS: Patients with RA had significantly higher c0 than healthy controls, although in 10 of 21 patients c0 was within the normal range. The RA patients also had higher Vmax than healthy controls, but the difference was not significant. The calculated production of HYA was increased in RA patients (P = .001) and correlated with c0 (P < .0001). The new model for HYA kinetics, in which the renal elimination was taken separately into account, proved to be more compatible than the previous model. CONCLUSION: The HYA loading test can help determine whether the increased serum level of HYA in RA patients is due to a high production or reduced elimination of HYA or both.
11212175 The influence of synovial fluid on adenovirus-mediated gene transfer to the synovial tissu 2001 Jan OBJECTIVE: To determine the effect of synovial fluid (SF) from rheumatoid arthritis (RA) patients on adenovirus type 5 (Ad5)-mediated gene transfer to synoviocytes, and to explore new strategies for vector development based on the neutralization data obtained. METHODS: SF was derived from 63 randomly selected R4 patients. Ten samples were used to study the effect of SF on Ad5-mediated gene transfer in synoviocytes. IgG and <100-kd fractions were purified from these 10 SF, and their effect on gene transfer was determined. Neutralizing activity against wild-type Ad5 (wt-Ad5), wt-Ad26, wt-Ad34, wt-Ad35, and wt-Ad48 was tested in the SF from the remaining 53 patients. RESULTS: Seven of 10 SF samples inhibited Ad5-mediated gene transfer. Purified antibodies exhibited inhibition patterns similar to those seen with unfractionated SF. In 5 of 10 SF samples, low molecular weight fractions inhibited gene transfer at low dilutions. Neutralization of wt-Ad35 by SF from RA patients was less frequent than neutralization of other wt-Ad tested (4% versus 42-72%; n = 53). CONCLUSION: SF from 70% of the RA patients contained neutralizing antibodies that hamper Ad5-mediated gene transfer to synoviocytes. The activity of neutralizing antibodies may be circumvented in the majority of RA patients when vectors based on an Ad35 backbone are used.
9693349 Graphic representation of illness: a novel method of measuring patients' perceptions of th 1998 Jul BACKGROUND: Health outcome is multi-faceted, and for both research and clinical practice, greater knowledge of its facets is required. The Pictorial Representation of Illness and Self Measure (PRISM) was developed as a simple, rapid measure of the current impact of illness and symptoms on the individual. METHODS: The PRISM task was completed by 26 outpatients with rheumatoid arthritis participating in a larger study of psychosocial correlates of arthritis, which included assessment of disease variables, functional impairment, pain, depression and patients' appraisals of their illness. In the PRISM task, the patient was asked to imagine that a small board represents his/her life and a fixed disk on the board represents his/her 'self'. The task was to place another (Illness) disk on the board to represent the current importance of illness in the patients' life. The main outcome measure was the distance between the Self and Illness disks. FINDINGS: Only 2 patients had difficulty understanding the task. PRISM distance did not correlate with any disease variables. It correlated inversely with pain, functional impairment and depression, and positively with coping resources. PRISM distance correlated with perceived control over illness and negatively with awareness of illness. INTERPRETATION: PRISM is an innovative measure, simple and well accepted by patients. It appears to measure what in German is termed leidensdruck, the burden of suffering due to illness. It offers a promising measure of an intangible but important health outcome, hitherto neglected, applicable to research interventions and clinical practice.
10804043 Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. 2000 Apr Celecoxib is a cyclo-oxygenase (COX) inhibitor that exhibits relative in vitro and ex vivo selectivity for COX-2 over COX-1. Results of randomised double-blind multicentre studies indicate that celecoxib is superior to placebo and has similar efficacy as conventional nonsteroidal anti-inflammatory drugs (NSAIDs) in improving the signs and symptoms of osteoarthritis and rheumatoid arthritis. Analgesic efficacy and improvements in functional status are apparent within 2 weeks of starting therapy and are maintained throughout treatment. Available data suggest that celecoxib has analgesic efficacy in patients with postsurgical dental pain, although this is yet to be confirmed. In patients with osteoarthritis of the knee, celecoxib 100 and 200 mg and naproxen 500 mg twice daily were similarly efficacious and superior to placebo. Once and twice daily celecoxib dosage regimens provided comparable efficacy. Improvements in physical function paralleled those in pain relief. Celecoxib also has efficacy in treating the signs and symptoms of osteoarthritis of the hip. The effects of celecoxib were not diminished in elderly patients with osteoarthritis of the hip or knee. All dosages of celecoxib (100 to 400 mg twice daily) and naproxen 500 mg twice daily produced significant anti-inflammatory and analgesic effects in patients with active rheumatoid arthritis. In patients with stable rheumatoid arthritis, celecoxib 200 mg twice daily showed sustained symptomatic improvements similar to those of twice daily slow-release diclofenac 75 mg over a 24-week period. Celecoxib was well tolerated in clinical trials. Upper gastrointestinal complications occurred in significantly fewer patients treated with twice daily celecoxib 25 to 400 mg than in those receiving comparator NSAIDs. There was no evidence of a dose relationship in endoscopic ulcer development and incidences in celecoxib and placebo recipients were lower than in those receiving twice daily naproxen 500 mg or ibuprofen 800 mg 3 times daily. CONCLUSIONS: Celecoxib is the first COX-2 specific inhibitor approved for use in osteoarthritis and rheumatoid arthritis. Celecoxib produces significant improvements in pain and inflammation and these effects are maintained during treatment for up 24 weeks in clinical trials. Studies indicate that celecoxib has similar efficacy to conventional NSAIDs in relieving pain and improving functional status, but is associated with a lower incidence of upper gastrointestinal ulceration and complications. This promising gastrointestinal safety profile, together with sustained symptomatic relief, places celecoxib as a useful alternative for the treatment of osteoarthritis and rheumatoid arthritis, particularly in patients at high risk of developing gastrointestinal events. Although data are encouraging, its place in acute pain states remains to be established.
9267314 Increased alkaline phosphatase isoforms in autoimmune diseases. 1997 Aug We found significant increases in ALP and ALP isoform band 10 in the serum of patients with early insulin-dependent diabetes, rheumatoid arthritis, and in those with multiple sclerosis during periods of disease exacerbation as compared with healthy controls. The ALP isoforms were assayed by isoelectric focusing. Our data suggest that the increase in ALP and ALP-10 closely reflects the abnormal activation of T lymphocytes that is common in autoimmune diseases, and that the source of the ALP-10 is activated T lymphocytes. ALP-10 is a sensitive but nonspecific marker of an active autoimmune process and appears to have the ability to detect abnormal T-cell activation. ALP-10 may be a useful test in the screening for autoimmune disorders.
10483692 [Pharmacological and clinical effectiveness of a fixed phytogenic combination trembling po 1999 Besides the well-known nonsteroidal antiinflammatory drugs (NSAID) for the treatment of rheumatic pain herbal medicine can also be applied successfully. Plants with antirheumatic efficacy include Fraxini cortex, Populi cortex/folia and Solidaginis herba. This review focuses on pharmacological and clinical efficacy of a combination of Fraxinus cortex, Populus cortex/folia and Solidago herba. Antiinflammatory and analgetic properties were shown in pharmacological tests. Clinical studies conducted in the indications of the different subtypes of rheumatic diseases such as rheumatoid arthritis or osteoarthritis pointed out a similar efficacy compared to NSAID applied in average dosages. Even the rate of adverse effects of the herbal combination was half of that registered in NSAID treated patients within the clinical studies.
9002041 The sensitivity of different analytical methods to detect disease susceptibility genes in 1997 Jan Our aim was to compare the sensitivity of 4 analytical methods to detect linkage to a known disease susceptibility locus, HLA-DRB1, in 100 rheumatoid arthritis sibling pair families with incomplete parental genotype information. Genotypes for the HLA-DRB1 and HLA-A loci were analyzed using (1) identity-by-descent (IBD), considering inheritance of maternal and paternal alleles separately; (2) maximum likelihood score-IBD (MLS-IBD), which infers missing parental genotypes; (3) identity-by-state (IBS), which does not require parental genotypes; and (4) transmission disequilibrium test (TDT), which uses affected offspring with a heterozygous parent. Due to the small number of informative meoisis for HLA-DRB1, the IBD analysis was not significant for linkage (p = 0.014). HLA-A was more informative (p = 0.0002). The MLS-IBD method for HLA-DRB1 (p = 0.00004) and HLA-A (p < or = 0.00001) was significant. Using IBS both loci gave highly significant evidence of linkage, (p < < 0.00001). The TDT detected HLA-DRB1*0401 as the allele associated with RA; no HLA-A allele was associated. Thus, sib pair families with limited parental genotypes can be used to detect disease susceptibility loci, but when selecting the method of analysis the informativeness of the markers should be taken into account.
9764613 Modulation by proinflammatory cytokines of Fas/Fas ligand-mediated apoptotic cell death of 1998 Oct Synovial cell hyperplasia is a characteristic of patients with RA. Excessive proliferation of RA synovial cells is, in part, responsible for the synovial cell hyperplasia. In addition, synovial cell death that would reduce synovial cell number may be defective, leading to the hyperplasia. Thus, the defective control of cell death as well as cell proliferation may be of central importance in the pathogenesis of RA. In this study we analysed effects of proinflammatory cytokines on Fas/Fas ligand (FasL)-induced synovial cell apoptosis, and evaluated apoptosis-associated protein expression in the synovial cells in patients with RA. RA synovial cells expressed Fas antigen and lymphocytes infiltrating into RA synovium expressed FasL. Apoptotic synovial cells were detected within the sublining layer of RA synovium. Anti-Fas MoAb induced apoptosis of RA synovial cells in vitro, and proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-1beta, but not IL-6 or IL-8, inhibited the anti-Fas-induced apoptosis accompanying up-regulation of Bcl-2 protein expression and reduced expression of CPP32 and ICH-1L. Immunohistochemical study revealed that CPP32 and ICH-1L were expressed weakly in the RA synovial lining cells compared with osteoarthritis (OA) synovial lining cells. Thus, we found that although RA synovial cells could die via apoptosis through Fas/FasL pathway, apoptosis of synovial cells was inhibited by proinflammatory cytokines present within the synovium. Inhibition of apoptosis by the proinflammatory cytokines may contribute outgrowth of synovial cells that leads to pannus formation and the destruction of joints in patients with RA.
9923167 Dimensions of the Center of Epidemiological Studies-Depression Scale for people with arthr 1998 Dec The aim of this study was to investigate the factor structure and to conduct an item analysis of the Center for Epidemiological Studies-Depression Scale (CES-D) among people with arthritis from the UK. This 20-item self-report scale was designed by Radloff in 1977 to measure depressive symptomatology in the general population. Data were drawn from a national study and collected through self-administered questionnaires mailed to participants, each of whom had a confirmed diagnosis of arthritis. Reliability and structure of the scale were examined using standard item analysis, internal consistency (Cronbach alpha), and principal components analysis. A four-dimensional structure was identified: Self-worth, Depressed Affect, Positive Affect, and Somatic Disturbance; three items loaded on two factors and were excluded from consideration. Comparisons with previous studies indicated some differences in the subscales and showed that, in this sample, two subscales might be artifacts of measurement. In samples of people with arthritis from the UK, use of the total score may not reflect accurate depressive symptomatology and the subscale scores should be used with caution.
11248511 HPLC determination of adenosine in human synovial fluid. 2001 Mar A high-performance liquid chromatographic method has been developed for the quantitative determination of adenosine in human synovial fluid. The method is simple, rapid and, overall, selective. No interference with the components of the biological matrix was observed in these chromatographic conditions. An ODS (250 x 4.6 mm) 5 microm column was used with an isocratic elution of a phosphate buffer-acetonitrile mobile phase. Detection was carried out on a UV detector at 260 nm. Calibration curve was found to be linear in the 0.7--70 microg ml(-1) range. Linear regression analysis of the data demonstrates the efficacy of the method in terms of precision and accuracy. The precision of this method, calculated as the relative standard deviation (RSD) of the recoveries (1.57--2.21%), was excellent. The limits of quantitation (LOQ) and detection (LOD) were respectively 0.7 and 0.2 microg ml(-1). The method was applied to some samples of synovial effusion from patients affected by rheumatoid arthritis. The concentrations of adenosine which were found were included in the range of the calibration curve.
10555886 Tacrolimus (FK506) in the treatment of severe, refractory rheumatoid arthritis: initial ex 1999 Nov OBJECTIVE: To determine if tacrolimus (FK506) has potential as a therapeutic agent in patients with severe and/or refractory rheumatoid arthritis (RA). METHODS: Twelve patients with RA who had severe and active disease and had failed an average of 5.3 disease modifying antirheumatic drugs (DMARD) were treated with tacrolimus 2-6 mg/day in an open label study. Patients were assessed monthly with respect to RA outcomes and drug related toxicities. RESULTS: Of the 12 patients, 7 were able to complete 6 months of treatment. In these 7 patients, significant improvements were seen in tender joint count (from 26.4 +/- 4.2 to 11.7 +/- 3.2; p = 0.007), swollen joint count (from 17.7 +/- 2.5 to 4.1 +/- 1.3; p = 0.001), and other RA outcomes. All 7 patients achieved the 20% response criteria of the American College of Rheumatology (ACR), and 5 of 7 patients met the ACR 50% response criteria. The other 5 patients withdrew in the first 3 months of treatment due to gastrointestinal symptoms (3), chest pain (1), and neuropathic pain (1). Serum creatinine levels were unchanged in all patients, and hypertension was not seen. CONCLUSION: Tacrolimus was tolerated by only 7 of 12 patients, but in 5 of these 7 patients with severe and refractory disease, the clinical responses were very good.