Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12788002 The St. Leger total knee replacement--a 7-year clinical assessment and survivorship analys 2003 Jun The St. Leger total knee replacement was developed with the aim of producing an affordable prosthesis which contained the best known features of current designs and also allowed ease of instrumentation. We present the medium term clinical and radiographic outcome and survivorship of the prosthesis. From 1992 to August 1994, 150 St. Leger total knee replacements were performed on 53 male and 72 female patients. Mean age was 67 (Range: 40-86). Sixty-nine percent of operations were for osteoarthritis and 30% for rheumatoid arthritis. Patients were reviewed at 1, 4 and 7 years postoperatively by an independent assessor. One hundred and twenty-three patients were assessed at 4 years and 83 patients at 7 years. The American Knee Association Scores revealed 84% excellent or good, 9% fair, and 7% poor results at 7 years. No patients complained of severe pain, 90% had mild or no pain, 10% had moderate pain. Eighty nine percent of patients were satisfied with their outcome. There were five complications requiring revision: infection (2), loosening (1), valgus instability (1) and knee stiffness (1). Survivorship analysis revealed 95% (95% CI +/-7.2%) survival at 7 years. Total knee replacement using the St. Leger knee prosthesis has comparable results to other condylar knee systems that cost almost twice the price.
15309279 [Lead poisoning after ingestion of ayurvedic drugs]. 2004 Aug 15 HISTORY AND CLINICAL FINDINGS: A 60-year-old woman suffering from rheumatoid arthritis and taking methotrexate was admitted with recurrent episodes of nausea, vomiting, constipation, loss of appetite, myalgia and backache, sternal chest pain, costal and jaw pain. On examination the epigastrium was tender to palpation and nonrigid. INVESTIGATIONS: Laboratory tests showed normocytic anemia (with a hemoglobin concentration of 8.6 g/dl), elevated blood urea and creatinine levels, hyponatremia, hypochloremia, hemolysis and polychromasia, anisocytosis, poikilocytosis and basophilic stippling of several red cells. On gastroscopy an ulcer was excluded, ultrasound scan of abdomen, X-ray of chest and pelvis showed no abnormalities. The electrocardiogram showed a right bundle branch block and left anterior hemiblock. DIAGNOSIS, TREATMENT, AND COURSE: In the differential diagnosis of anemia with basophilic stippling and abdominal discomfort, lead poisoning was found. Whole-blood lead concentration was markedly raised to 852 micro g/l (normal < 100 micro g/l). Lead poisoning was the result of the use of ayurvedic drugs during a period of 7.5 months prior to admission to the authors' hospital. CONCLUSION: Heavy metal poisoning, especially lead poisoning, should be considered in the differential diagnosis in patients with unspecific clinical symptoms taking traditional Indian remedies.
12180722 Methotrexate, hydroxychloroquine, and intramuscular gold in rheumatoid arthritis: relative 2002 Aug OBJECTIVE: The use of disease modifying antirheumatic drugs (DMARD) for rheumatoid arthritis (RA) is predicated on the expected value of the treatment course. Most clinical data are generalized from randomized controlled trials (RCT), which may result in estimates that are discordant with clinical experience and cannot address the effects of sequence of drugs. We computed estimates of relative DMARD effectiveness from a large observational database using area under the curve (AUC) data. METHODS: We examined data collected over a 20 year period on 1160 patients who were followed at the Wichita Arthritis Center. We utilized Health Assessment Questionnaire (HAQ) disability index data to quantify the effect of methotrexate (MTX), hydroxychloroquine (HCQ), and injectable gold (gold) on subsequent patient outcome. Using an AUC analysis, we compared length of treatment course, total disability averted, annual disability averted, and percentage of possible disability averted across drugs, and examined differences between first courses of therapy in DMARD naive patients and subsequent courses of the same and different DMARD in patients. RESULTS: Patients treated with MTX, HCQ, and gold improved at a rate of -0.33, -0.18 and -0.38 annualized HAQ area units, respectively. Since duration taking drug was greatest for MTX, then HCQ, then gold, the cumulative improvement was greatest with MTX (-1.07) versus gold (-0.74) versus HCQ (-0.47) in disability unit years. All 3 drugs were better cumulatively with earlier disease (MTX-1.74 for < 1 yr vs -0.95 for > 1 yr; HCQ -0.68 vs -0.43; gold -1.71 vs -0.49). A second trial of the same drug was far less effective than the first course. On a percentage of possible improvement basis, these drugs were nearly equal since HCQ is given to less severely affected patients. CONCLUSION: MTX is the most effective DMARD of these 3 because of the length the therapeutic segment. In terms of disability averted, none of the agents decrease disability by more than 25% of the theoretically possible improvement. We documented that effectiveness of RA treatment is a function of drug sequence, duration of disease, whether it is a first or second course, and severity of disease. None of these clinically relevant observations have emerged from clinical trials. These methodologic approaches provide important quantitative comparative data and will be useful in further assessment of the relative effectiveness of present and future DMARD.
15638052 Prevalences of rheumatoid arthritis in Roman Catholic nuns and the general female populati 2004 Nov OBJECTIVE: To evaluate the influence of lifestyle factors on the prevalence of rheumatoid arthritis (RA) by comparing Roman Catholic nuns and the general female population. METHOD: RA prevalence in the general population was evaluated using a standardized telephone survey in 1857 homes taken at random. Individuals who reported an inflammatory joint disease were contacted by a rheumatologist of our unit, missing data were collected from the general practitioner or rheumatologist with the patient's permission, and if necessary a physical examination was done by a rheumatologist. The 9 largest Roman Catholic nun communities in Brittany were screened using the same standardized questionnaire administered face-to-face; nuns who reported an inflammatory joint disease were interviewed and examined by rheumatologists. In both populations, RA was diagnosed when (1) the rheumatologist of our unit who interviewed the patient considered the RA classification criteria positive and (2) the rheumatologist who examined the patient gave a diagnosis of RA independently from RA classification criteria. RESULTS: Data were available for 1706 adult females in the general population and 721 nuns. Of the 20 nuns who reported RA or polyarthritis, 11 received a diagnosis of RA (prevalence 1.52%). The prevalences adjustedfor the French population after 40 years were 1.66% (95% confidence interval, 0.84-2.44) and 1.33 (0.27-2.40) among the nuns and the general female population, respectively. CONCLUSION: Although our nun population was too small for definite conclusions, we found no evidence of a difference in RA prevalence among nuns and the general female population in Brittany.
15552511 Quantitative documentation of benefit/risk of new therapies for rheumatoid arthritis: pati 2004 Sep Assessment of benefit/risk of therapies for any disease is best conducted according to quantitative data. In many diseases, such as hypertension or hyperlipidemia, a single quantitative measure serves as a "gold standard" for patient status, but no single measure can serve as a "gold standard' for all individual patients with rheumatoid arthritis (RA). Therefore, indices such as the American College of Rheumatology (ACR) Core Data Set and Disease Activity Score (DAS), are used in clinical trials and other clinical research. These indices include 3 types of measures, which are derived from a health professional [joint counts, global]; a laboratory [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]; or a patient questionnaire [physical function, pain, global]. In most standard clinical care, the majority of clinicians do not collect joint count or patient questionnaire data at most visits. Therefore, assessment and management of most patients with RA is conducted empirically, with the only quantitative data from laboratory tests. Measures on a patient self-report questionnaire of physical function, pain, and global status, are as informative as joint counts, radiographic scores, laboratory tests, or any measure by a health professional to document status, estimate prognosis, and monitor responses to therapies. We suggest that quantitative measurement may be incorporated into standard clinical care most easily and effectively by asking each patient to complete a simple 1-page questionnaire at each visit to a rheumatologist.
15184406 Nocardia arthritidis sp. nov., a new pathogen isolated from a patient with rheumatoid arth 2004 Jun Two different bacterial strains with different drug susceptibilities were isolated from the sputum and an inflammatory discharge from a swelling in the left thigh of a patient with rheumatoid arthritis. Both bacterial strains were provisionally assigned to the genus Nocardia on the basis of their morphological and chemotaxonomic characteristics and were further studied in order to establish their taxonomic status. One strain (IFM 10034) was identified as Nocardia farcinica on the basis of its physiological characteristics. The other strain, which was designated Nocardia sp. strain IFM 10035(T), revealed a unique pattern of phenotypic properties that distinguished it from other representatives of established Nocardia species. Comparative 16S rRNA gene sequence studies of Nocardia sp. strain IFM 10035(T) also showed that the bacterium was closely related to the species Nocardia beijingensis. Determination of DNA-DNA relatedness, however, indicated that Nocardia sp. strain IFM 10035(T) could be delineated from N. beijingensis. The genotypic and phenotypic data combined indicated that the bacterium merits description as a new Nocardia species. The name proposed for the new species is Nocardia arthritidis sp. nov., the type strain being IFM 10035(T) (NBRC 100137(T), JCM 12120(T), DSM44731(T)). The present study suggests that Nocardia infections can be caused by multiple species of the bacterium.
12740669 Doppler echocardiographic evaluation of ventricular function in patients with rheumatoid a 2003 May Cardiac involvement in rheumatoid arthritis (RA) has been reported previously. However, evaluation of ventricular function in this disease by the use of recently proposed Doppler echocardiographic methods has not been reported before. Thus, the aim of this study was to evaluate ventricular function by measurement of myocardial performance index (MPI) and transmitral flow propagation velocity (TFPV). Thirty-two patients with long-standing RA and 32 control subjects (mean ages 52 +/- 11 and 50 +/- 10 years, respectively) participated in this study. Systolic function was assessed by subjective evaluation of wall motion for both ventricles and by fractional shortening for the left ventricle (LV). LV diastolic function was evaluated by standard pulsed-wave Doppler echocardiography, MPI and TFPV. Right ventricular (RV) function was evaluated by MPI. No subject had signs or symptoms of clinically overt heart failure. Systolic function was normal in all subjects. Among the echocardiographic indices of LV diastolic function the peak E velocity, E velocity/A velocity ratio, isovolumetric relaxation time, MPI and TFPV in the RA group were significantly different from those of the controls ( P < 0.05). However, we did not observe a significant difference in RV echocardiographic indices between the two groups. Our results show that there is LV diastolic dysfunction in patients with long-standing RA. The lack of a history of cardiotoxic antirheumatic drug use among our patients suggests that this abnormality is due to RA itself.
15593223 CC and CXC chemokine receptors mediate migration, proliferation, and matrix metalloprotein 2004 Dec OBJECTIVE: To explore the potential involvement of the chemokine system in synoviocyte-mediated tissue destruction in rheumatoid arthritis (RA), we studied the expression profile of chemokine receptors and their function in the migration, proliferation, and matrix metalloproteinase (MMP) production of cultured fibroblast-like synoviocytes (FLS) from RA patients. METHODS: The presence of CC and CXC chemokine receptors on cultured FLS was studied at the messenger RNA (mRNA) level by reverse transcriptase-polymerase chain reaction and at the cell surface expression level by flow cytometry. Variations in cytosolic calcium influx induced by chemokine stimulation were assessed by flow cytometry on Fura Red-preloaded FLS. Two-compartment transwell chambers were used for FLS chemotaxis assays. Cell growth was measured by a fluorescence-based proliferation assay. Gelatinase and collagenase activities were determined by a fibril degradation assay and zymography. RESULTS: FLS constitutively expressed the receptors CCR2, CCR5, CXCR3, and CXCR4, both at the cell surface and mRNA levels, but failed to express CCR3 and CCR6. Significant intracytosolic calcium influx was observed on FLS challenged with monocyte chemotactic protein 1 (MCP-1), stromal cell-derived factor 1alpha (SDF-1alpha), and interferon-inducible protein 10 (IP-10). Stimulation with MCP-1, SDF-1alpha, IP-10, and monokine induced by interferon-gamma enhanced the migration and proliferation of FLS. These chemokines, in addition to RANTES, increased in a dose- and time-dependent manner the gelatinase and collagenase activities in cell-free supernatants of cultured FLS. Interestingly, the chemokine-mediated up-regulation of MMP activities was significantly abrogated by the presence of anti-interleukin-1beta, but not anti-tumor necrosis factor alpha, blocking antibodies. CONCLUSION: These data suggest that through modulation of the migration, proliferation, and MMP production by FLS, the chemokine system may play a more direct role in the destructive phase of RA than is currently suspected, and thus emphasize the relevance of chemokines and their receptors as potential therapeutic targets in this disease.
15709316 A comparative study on the utility of telehealth in the provision of rheumatology services 2004 Dec INTRODUCTION: There is a critical shortage of specialty rheumatology services in Canada. The impact is felt more in rural and northern regions than on urban areas of the country. In response to the need, this study was conducted to compare the satisfaction of referring physicians with rheumatology services through conventional visiting specialty clinics; email consults and regularly scheduled videoconference. METHODS: Three rural communities of similar size and availability of physician services were assigned to one of the following means of providing outreach rheumatology services: visiting rheumatologist clinics, email access to rheumatologist and scheduled videoconference consults. A case based pre/post test, and post satisfaction questionnaire were administered to the primary care physicians in these communities. Patient outcomes, and physician ability and confidence in managing specific arthritis problems, were measured. RESULTS: Physicians responded positively to all methods of rheumatology service provision. The videoconference group were the most positive. The reasons were: immediate feedback to referring physician and patient, effective case based learning and transfer of knowledge, and improved accessibility. CONCLUSION: Videoconference is preferred to visiting clinics and email as a method for rheumatology services to rural/northern communities. It is cost effective and there is knowledge transfer between the rheumatologist and the referring physicians.
11774145 Analysis of arthroscopically assisted ankle arthrodesis. 2002 Jan PURPOSE: Evaluation of an arthroscopically assisted ankle arthrodesis technique for clinical and radiographic union, function, and patient satisfaction. TYPE OF STUDY: Retrospective analysis and review of the literature. METHODS: Twenty-one patients with a mean age of 52.7 years who underwent arthroscopic ankle arthrodesis were examined at an average follow-up time of 34 months. The mean duration of symptoms was 4.4 years. The most common diagnosis for patients who underwent arthrodesis was post-traumatic arthritis (19 of 21) with 1 patient having a diagnosis of avascular necrosis of the talus and the other patient having rheumatoid arthritis. All patients described severe mechanical pain as the most important reason for undergoing the procedure. RESULTS: Fusion occurred in 20 of 21 patients. The average time to clinical and radiographic union was 8.9 weeks. Nine patients were graded as excellent; no pain, limp, or occupational restriction, and a stable fusion. Eleven were graded as good; mild pain, occasional limp, or occupational restriction with a stable fusion. One was graded as poor; failed union and pain. The failure had extensive avascular necrosis involving approximately 50% of the talus as a preoperative diagnosis. CONCLUSIONS: The advantages of the arthroscopic technique include a high fusion rate, decreased time to fusion, and decreased cost. There are considerable advantages to the arthroscopic technique in appropriately selected patients with no or mild angular deformity and no avascular necrosis greater than 30% of the talus. There is a substantial reduction in time to fusion in the arthroscopic procedure compared with published reports on open procedures for ankle arthrodesis. While this procedure is not indicated in all instances, selected patients with disabling ankle arthrosis may be more appropriately treated with an arthroscopic arthrodesis than by open surgery.
12759300 The "X-Ray RheumaCoach" software: a novel tool for enhancing the efficacy and accelerating 2003 Jun BACKGROUND: Precise diagnosis and follow up treatment of rheumatoid arthritis (RA) requires objective quantification, which is still lacking. For this purpose, radiological analyses are considered to be the most appropriate method. OBJECTIVE: To develop computer assisted quantification software that is particularly applicable to joint scoring in rheumatic disorders. METHODS: 3914 radiographs from hands and feet of 190 patients with RA were collected, expertly examined, analysed, and statistically evaluated. Radiographs were quantified using the conventional Larsen score and the "X-Ray RheumaCoach" (XRRC) software. The XRRC is a Java stand alone application which can support and accelerate, but not fully automate, the scoring procedure in RA. The scorer can apply both the Larsen and the Ratingen-Rau scores. RESULTS: Compared with conventional scoring procedures, the XRRC software accelerated quantification time by approximately 25%. The program, which is now available on the internet free of charge, ran stably and proved to be a consistently valuable tool. CONCLUSIONS: Compared with conventional scoring methods, the XRRC software offers several advantages: (a) structured data analysis and input that minimises variance by standardisation; (b) faster and more precise calculation of sum scores and indices; (c) permanent data storing and fast access to the software's database; (d) the possibility of cross calculation to other scores; (e) "user friendly" technology and a dedicated help program; (f) fast access and data transfer through the internet if desired; and (g) reliable documentation of results in a specially designed printout.
14516037 Arthroscopic synovectomy of the wrist in rheumatoid arthritis. 2003 Sep We analysed the results of arthroscopic synovectomy of the wrist in 18 patients (19 wrists) with rheumatoid arthritis who had not responded to conservative treatment. The patients' symptoms were assessed using visual analogue scales for pain and satisfaction. Standard posteroanterior radiographs which were taken pre-operatively and at final follow-up were analysed using a modified Larsen scoring system (normal, 0; total destruction, 40). The mean follow-up period was 29.2 months (24 to 45). The mean pre-operative pain score was 8.58 which decreased to 3.58 one year after surgery and increased again to 4.42 at final follow-up. This suggested a gradual increase in pain with time. The mean satisfaction score was 6.26. The mean modified Larsen's score was 9.8 pre-operatively and 13.9 at final follow-up, which demonstrated the slow progression of degenerative changes. Arthroscopic synovectomy for rheumatoid arthritis of the wrist allows effective pain relief and high patient satisfaction, although any prolonged benefits will require long-term follow-up.
12910969 [Two cases of rheumatoid arthritis developed after polymyositis]. 2003 Jun We report two cases of rheumatoid arthritis (RA) who later had developed after polymyositis (PM). The first patient was 64-year old male who experienced muscular weakness of the four limbs in proximity 10 years ago. He was diagnosed as PM because of the elevated serum CK and the myogenic pattern of EMG, and his symptoms were improved by treatment with corticosteroid. He started to complain polyarthralgia 2 years ago, followed by interstitial pneumonia, pleuritis and skin ulcer. He was admitted because of exacerbated polyarthralgia, multiple subcutaneous nodules, skin eruption and fever. The level of serum CK was within normal range but CRP was elevated and CH 50 was decreased. The laboratory examination showed positive cryoglobulin and high titer of rheumatoid factor, but anti-Jo 1 antibody was negative. The hand X-ray showed bone erosions in bilateral wrist joints. Skin biopsy revealed leukocytoclastic vasculitis. Based on these findings, he was diagnosed as malignant RA. He was successfully treated with methylprednisolone pulse therapy, cyclophosphamide and prostaglandin E 1. The second patient was 77-year old male with pneumoconiosis who experienced muscular weakness of the four limbs in proximity 4 years ago. He was diagnosed as PM based on his clinical and laboratory findings and was treated with temporary corticosteroid. He started to have polyarthralgia last year, and he was admitted because of increasing arthralgia after the treatment of pulmonary tuberculosis. The level of serum CK was slightly elevated due to hypothyroidism, and CRP was highly elevated. Rheumatoid factor and cryoglobulin were positive, but anti-Jo 1 antibody was negative. The hand X-ray showed bone erosions in bilateral wrist joints. Crystals of pyrophosphate calcium was observed in knee joints. He was diagnosed as RA associate with pseudogout. His symptoms were relieved with corticosteroid, salazosulfapyridine and anti-tuberculous therapy. These two cases had altered their clinical features from PM to definite RA, and both had pulmonary complications. Previous reports described the cases of RA followed by PM, most of which were induced by such drugs as D-penicillamine, but the cases of PM who later had developed RA are extremely unusual. The overlapped cases of RA and PM tend to highly associate with pulmonary lesions.
15105912 "Like a virgin": Absence of rheumatoid arthritis and treponematosis, good sanitation and o 2004 Jan OBJECTIVES: This study was conducted to test several hypotheses: 1. That rheumatoid arthritis and syphilis were New World diseases, only transmitted to the Old World subsequent to the passages of Christopher Columbus; 2. To indirectly test the hypothesis that lead poisoning was prevalent in Roman Italy by looking for its byproduct, gout; 3. To test the hypothesis of compromised sanitation in ancient Italy, on the basis of spondyloarthropathy frequency; and 4. To assess variation of trauma frequencies in ancient Italy, by examining frequency of focal periosteal reaction. METHODS: Skeletons from sites ranging from the Bronze Age to the Black Plague epidemic of 1485-1486 were macroscopically evaluated for focal periosteal reaction and for the cardinal signs of rheumatoid arthritis, treponemal disease, gout and spondyloarthropathy. RESULTS: Examination of 688 individuals revealed low frequency of focally distributed periosteal reaction (bumps) in sites dated from the 3400-700 years before present, sharply increasing in the 15th century. Diffuse periosteal reaction was present only as isolated occurrences secondary to hypertrophic osteoarthropathy and sabre shin reaction was notably absent. Erosive disease was uncommon and always oligoarticular in distribution. No marginal erosions were present, with the exception of an isolated metatarsal with classic overhanging edge sign of gout. Subchondral erosions, peripheral joint fusion and axial skeletal involvement identified spondyloarthropathy frequencies of 1-3%, independent of the antiquity of the site. CONCLUSIONS: Italy, prior to Columbus was like a virgin. Rheumatoid arthritis and treponemal disease (specifically syphilis) were not present, further supporting the contention that they are New World-derived diseases. Periosteal signs of minor trauma were rare prior to fifteenth century plague times. This suggests a potential role of domestic (as opposed to outside environment activities) in is development. The hypothesis for a role of lead poisoning in the demise of the Roman Empire is falsified by the rarity of gout. The frequency of spondyloarthropathy was significantly below that found in sanitarily challenged populations, suggesting high standards of hygiene in ancient Italy.
12115180 Necessary role of phosphatidylinositol 3-kinase in transforming growth factor beta-mediate 2002 Jun OBJECTIVE: Rheumatoid arthritis is a disease that, pathologically, is characterized by the progressive growth and invasion of the synovial pannus into the surrounding cartilage and bone. Many cytokines, including transforming growth factor beta1 (TGFbeta1), have been implicated in this process, but their mode of action is incompletely understood. The goal of the present study was to better understand the downstream signaling pathways of TGFbeta in fibroblasts. METHODS: The role of phosphatidylinositol 3-kinase (PI 3-kinase) was determined by chemical inhibition with LY294002 or wortmannin. Activation of protein kinase B (Akt), c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases (ERKs) was evaluated by Western blot analysis using phospho-specific antibodies. RESULTS: Exposure of fibroblasts to TGFbeta rapidly induced activation of a kinase, Akt, that is known to inhibit apoptosis by a variety of pathways. Activation of Akt was blocked by the specific PI 3-kinase inhibitor, LY294002, indicating that TGFbeta-mediated phosphorylation of Akt was dependent on PI 3-kinase activation. This activation pathway was relatively selective for Akt, since inhibition of PI 3-kinase failed to substantially modify activation of ERKs or JNKs in synovial fibroblasts. Inhibition of the PI 3-kinase/Akt pathway resulted in impaired proliferation of synovial fibroblasts and partial attenuation of the protective effect of TGFbeta on Fas-mediated apoptosis. CONCLUSION: TGFbeta exerts its growth and antiapoptotic effects on fibroblasts, at least in part, by activation of the PI 3-kinase/Akt pathway.
15334458 In vivo imaging of protease activity in arthritis: a novel approach for monitoring treatme 2004 Aug OBJECTIVE: Sensitive noninvasive strategies for monitoring treatment response in rheumatoid arthritis (RA) would be valuable for facilitating appropriate therapy and dosing, evaluating clinical outcome, and developing more effective drugs. Because different proteases are highly up-regulated in RA and contribute significantly to joint destruction, in the present study we investigated whether such enzymes are suitable in vivo imaging biomarkers for early evaluation of treatment response in a murine model of RA. METHODS: Using a protease-activated near-infrared fluorescence (NIRF) imaging "smart" probe, we examined the presence and distribution of fluorescence in arthritic joints of mice with collagen-induced arthritis by both noninvasive fluorescence imaging and histology. Proteases that target the Lys-Lys cleavage site, including cathepsin B, activate probe fluorescence. Treatment monitoring data were obtained following methotrexate (MTX) therapy. RESULTS: Twenty-four hours after intravenous injection of the protease sensor, affected toes and paws of arthritic mice showed significantly higher fluorescence intensity than did toes and paws of healthy mice. Fluorescence from the protease probe and cathepsin B antibody histologic staining were localized in the vast majority of cells in the inflamed synovium. In arthritic animals treated with MTX (35 mg of MTX/kg 48 hours prior to probe injection), a significantly lower fluorescent signal (inflamed paws 50%, inflamed toes 70%) was observed as compared with untreated arthritic animals. CONCLUSION: Protease-activated NIRF probes are sensitive means of imaging the presence of target enzymes in arthritic joints and can be used for early monitoring of treatment response to antirheumatic drugs such as MTX.
15201943 [The safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid 2004 Jan The safety profile of interleukin-1 receptor antagonist (anakinra) has been studied with randomised, placebo-controlled trials involving 2932 patients affected by rheumatoid arthritis. The most frequently reported adverse events were represented by injection site reactions (71%) and headache (13.6%). No statistically significant difference in the incidence of infections was observed among the patients treated with the interleukin-1 receptor antagonist and the patients receiving placebo. In particular, the incidence of serious infections was 1,8% in rheumatoid arthritis patients on anakinra therapy and 0,7% in patients on placebo. The reported serious infections consisted of pneumonia, cellulitis, bone and joint infections, bursitis. No case of opportunistic infections or tubercolosis was observed. The results of clinical studies suggest that anakinra is a new well-tolerated drug for the treatment of patients affected by rheumatoid arthritis.
12124854 Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 2002 Jul OBJECTIVE: To evaluate the extent of and risk factors for bone loss in a population-based cohort of patients with rheumatoid arthritis (RA) receiving conventional health care. METHODS: In a longitudinal study, clinical data were collected and bone mineral density (BMD) measurements were performed at baseline and after 2 years. Dual-energy x-ray absorptiometry was used for hip and spine BMD measurements. At baseline, patients received advice about lifestyle adjustments and calcium and vitamin D supplementation; during the followup period they were treated with antirheumatic and bone-sparing drugs, according to clinical judgment. RESULTS: After a mean +/- SD of 2.2 +/- 0.2 years, 366 (298 women, 68 men) of the 488 patients who were examined at baseline were reexamined. At that time, 47.9% were current users of corticosteroids and 37.0% were using antiresorptive drugs (hormone replacement therapy, bisphosphonates, or calcitonin). The mean BMD reduction was -0.64% in the femoral neck, -0.77% in the total hip, and -0.29% in the spine at L2-4. BMD was increased at all measurement sites in current users of antiresorptive drugs (0.16-1.64%) but was decreased in patients using calcium and vitamin D alone (-1.99% to -1.39%) and in patients not using any osteoporosis treatment (-1.20% to -0.43%). Current use of corticosteroids was independently associated with increased risk for BMD loss in the total hip (odds ratio [OR] 2.63, 95% confidence interval [95% CI] 1.38-5.00) and spine at L2-4 (OR 2.70, 95% CI 1.30-5.63), whereas current use of antiresorptive drugs was associated with decreased risk for bone loss in the total hip (OR 0.43, 95% CI 0.20-0.89). CONCLUSION: Results of this population-based, 2-year followup study indicate that adequate management of patients with RA, addressing both the rheumatic disease and osteoporosis, protects against bone loss.
14576993 Efficacy of imatinib mesylate (STI571) treatment for a patient with rheumatoid arthritis d 2003 Oct We report on an 80-year-old man with rheumatoid arthritis (RA) who presented with chronic myelogenous leukemia (CML). Five years after the onset of RA, the CML diagnosis was made. The patient was treated for CML with 300 mg of imatinib mesylate (STI; signal transduction inhibitor 571) for 8 weeks. Laboratory tests showed that the C-reactive protein level, percentage of cells exhibiting the Philadelphia chromosome (Ph1), WBC count, and Lansbury index for RA all dropped respectively from 7.5 mg/dl to 1.0 mg/dl, 74.9% to 1%, 25, 100/microl to 9900/microl, and 51% to 14%. Administration of imatinib mesylate is felt to be effective in treating not only CML but also RA in the active stage.
15084914 Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthrit 2004 Apr Two autoimmune murine models--proteoglycan (aggrecan)-induced arthritis (PGIA) and collagen-induced arthritis (CIA)--were developed in parent strains, F1 and F2 hybrids of major histocompatibility complex (MHC)-matched (H-2) BALB/c x DBA/2 and MHC-unmatched (H-2/H-2) BALB/c x DBA/1 intercrosses. The major goal of this comparative study was to identify disease (model)-specific (PGIA or CIA) and shared clinical and immunologic loci in 2 types of genetic intercrosses. Qualitative (binary/susceptibility) and quantitative (severity and onset) clinical trait loci were separated and analyzed independently or together with various pathophysiologic/immunologic traits, such as antigen-specific T- and B-cell responses and cytokine production. The major quantitative trait locus (QTL) was the MHC on chromosome 17, which was especially dominant in CIA. In addition, chromosomes 3, 5, 10, and X contained shared clinical loci in both models, and a total of 8 QTLs (clinical traits together with immunologic traits) were colocalized in PGIA and CIA.