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

ID PMID Title PublicationDate abstract
7833891 [Severe laryngeal involvement in rheumatoid arthritis requiring permanent tracheostomy]. 1994 A 72-year-old woman with severe rheumatoid arthritis developed atlantoaxial subluxation requiring surgery. Tracheal intubation was performed during the procedure. Gradually worsening dysphonia and dyspnea developed postoperatively. Laryngoscopy showed palsy of both vocal cords and coalescence of the arytenoid cartilages. Despite surgical treatment, permanent tracheostomy was required. There is evidence that laryngeal involvement is common but usually subclinical or mild in rheumatoid arthritis patients. Tracheal intubation can cause the laryngeal lesions to flare. Clinical manifestations are nonspecific and sometimes misleading (e.g., cough or pharyngeal and laryngeal pain). Direct laryngoscopy and computed tomography of the larynx allow evaluation of the lesions of the different components of the larynx. The case reported herein demonstrates that rheumatoid arthritis patients should be screened for laryngeal involvement by history and ENT examination and that any laryngeal abnormalities should be reported to the anesthesiologist if tracheal intubation is planned.
8797705 HTLV-I arthropathy and Sjögren syndrome. 1996 Human T-cell lymphotropic virus type I (HTLV-I) was initially detected as the causative agent of adult T-cell leukemia (ATL). However, recent studies have revealed that HTLV-I may disrupt the immune system and lead to the development of rheumatoid arthritis and Sjögren syndrome. A current study in our laboratory has revealed that HTLV-I tax gene, known as the transregulatory gene, contributes not only to the induction of synovial cell hyperplasia but also the immune response, both in vivo and in vitro. In this report, the role of HTLV-I in the pathogenesis of chronic destructive arthropathy and Sjögren syndrome is discussed.
7639809 Effects of cyclophosphamide on the development of malignancy and on long-term survival of 1995 Aug OBJECTIVE: To examine the effects of cyclophosphamide (CYC) on the development of malignancies and on the long-term survival of patients with rheumatoid arthritis (RA). METHODS: We used a longitudinal cohort design in which 119 patients (76 women and 43 men) with refractory RA who were treated with oral CYC between 1968 and 1973 were compared with 119 control patients with RA (matched for age, sex, disease duration, and functional class) who were evaluated during the same time period but did not receive CYC. RESULTS: There was increased risk of malignancy in the CYC-treated group, with 50 cancers found in 37 patients in the CYC group compared with 26 cancers in 25 of the control patients (P < 0.05). The relative risk of cancer for those treated with CYC was 1.5 (95% confidence interval 0.93-5.5). Nine of the malignancies in the CYC group were bladder cancers and 19 were skin cancers, compared with no bladder cancers and 6 skin cancers in the control group. The total dose of CYC was higher in those who developed cancer, particularly in those with bladder cancer. Three of the bladder cancers occurred 14, 16, and 17 years after CYC had been discontinued. CONCLUSION: The risk of malignancy, particularly bladder cancer, in RA patients treated with oral CYC continues even 17 years after discontinuation of the drug.
7955531 Induction of multinucleated giant cells from rheumatoid arthritis (RA) synovial adherent c 1994 Nov To determine the effects of signalling through the DR molecule on synoviocytes from RA patients, the synovial adherent cells were incubated with anti-DR antibodies. After 24 h incubation, we found the formation of multinucleated giant cells in that culture. These multinucleated giant cells showed characteristics of monocyte-macrophage lineage cells and precursor of osteoclasts. Cyclohexamide inhibited the formation of multinucleated giant cells, but not the aggregation of synovial cells, suggesting that newly synthesized proteins are associated with the cell fusion. These results revealed a new mechanism in multinucleated giant cell formation.
8522321 Proliferation enhancement by spontaneous multiplication of chromosome 7 in rheumatic synov 1995 Dec Mosaic trisomy of chromosome 7 is known to occur in a variety of non-neoplastic hyperproliferative disorders. In long-term cell cultures established from rheumatic synovium with mosaic trisomy 7, we observed a continuous increase in the proportion of cells with trisomy 7 to over 50% by the 10th in vitro passage. Simultaneous in situ hybridization with a repetitive chromosome-7-specific DNA probe and fluorescent Ki-67 labelling showed a strong correlation between trisomy 7 and an elevated proliferation index in cultured rheumatic synovial cells. Moreover, we observed a fraction of rapidly proliferating cells with up to eight copies of chromosome 7 as the sole cytogenetic change. Frequent somatic pairing of centromeres of two chromosomes 7 in interphase nuclei suggests either atypical non-disjunction with a persisting centromere or selective endoreduplication of chromosome 7.
1578350 Aloe vera and the inflamed synovial pouch model. 1992 Mar Administration of air under the skin produced a pouch wall that closely resembled a synovium in that the inner lining was made up of macrophages and fibroblasts. Administration of 1% carrageenan directly into the 7-day-old air pouch produced an inflammation characterized by an increased number of mast cells in pouch fluid as well as an increase in wall vascularity. A punch biopsy weight of the pouch wall did not reveal an increase in 1% carrageenan-treated animals. However, a 10% Aloe vera treatment of carrageenan-inflamed synovial pouches reduced the vascularity 50% and the number of mast cells in synovial fluid 48%. The pouch wall punch biopsy weight was increased by A. vera, which was verified by histologic examination of the inner synovial lining. Aloe vera stimulated the synovial-like membrane, as evidenced by an increased number of fibroblasts, suggesting that A. vera stimulated fibroblasts for growth and repair of the synovial model. The synovial air pouch can be used to study simultaneously the acute anti-inflammatory and fibroblast stimulating activities of A. vera.
10155685 Wrist arthroplasty with the trispherical total wrist prosthesis. 1995 Jan The clinical results and long-term implant survival of wrist arthroplasty with the Trispherical total wrist prosthesis was evaluated in patients with inflammatory arthritis. Using the Hospital for Special Surgery wrist scoring system, the clinical evaluation of 35 Trispherical total wrist arthroplasties showed an excellent result in 20, good result in 8, fair result in 3, poor result in 2, and failed result requiring revision in 2 wrists at an average follow-up of 9 years. Cumulative implant survival in 67 consecutive Trispherical total wrist arthroplasties was 97% at 5 years and 93% at 10 and 12 years postoperatively. Patient satisfaction with wrist arthroplasty using the Trispherical prosthesis was excellent. We attribute the favorable long-term results obtained with the use of this prosthesis to its inherent design that allows for accurate restoration of the center of rotation of the wrist.
7614981 Altered T lymphocyte signaling in rheumatoid arthritis. 1995 Jun Synovial and peripheral blood T cells from patients with rheumatoid arthritis are functionally deficient. This may be secondary to their reduced cytokine (e.g. interleukin-2) synthesis. We have investigated the possibility of an alteration in pathways common to interleukin-2 production and proliferation in peripheral blood T cells from patients with active rheumatoid arthritis. Intracellular calcium levels ([Ca2+]i) were analyzed by flow cytometric methods in Indo1-loaded T cells. These were purified by negative selection from patients or age/sex-matched controls, and stimulated with phytohemagglutinin-P or anti-CD3. Rheumatoid [Ca2+]i responses to both stimuli were reduced (p < 0.005). Patient cell samples included a larger proportion of non-responding cells, but even in the responsive population the magnitude of the response in rheumatoid cells was impaired compared with those in normal cell samples (p < 0.0001) for both stimuli. Proliferation responses were also impaired (p < 0.005), and there was a positive correlation between the paired [Ca2+]i elevation and proliferative responses for both stimuli. CD2 and CD3 expression were normal, and the proportions of CD4, CD8 and CD45RO and CD45RA subsets were also unaffected by disease. Thus a signaling defect downstream of CD2 or CD3 surface molecules may contribute to functional deficiencies in rheumatoid T lymphocytes. This effect is not due to non-steroidal anti-inflammatory drugs which some patients were taking. We have demonstrated similar alterations in [Ca2+]i responses and proliferation in a smaller study of patients with inflammatory bowel disease, indicating that such changes might be present in other chronic inflammatory states.
8003058 Preferential utilization of a novel V lambda 3 gene in monoclonal rheumatoid factors deriv 1994 Jun OBJECTIVE: To further our understanding about the molecular genetics of rheumatoid factor (RF) in rheumatoid arthritis (RA). METHODS: The heavy and light chain variable region (V) genes of 5 new human monoclonal IgM RFs were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide termination method. RESULTS: The results reveal the recurrent usage in two RA patients of a novel V lambda 3 germline gene, designated Humlv3c93. Specifically, in 2 of 3 RFs (C93 and D53) from one patient, the light chains in the V lambda gene-encoded region were identical to each other and to the light chain of an RF (H4) from another patient. Serologically, the light chains of these 3 RFs were classified as members of the V lambda 3b sub-subgroup. Each of the RFs was encoded by a different VH gene. Both C93 and D53 bound specifically with human and rabbit IgG, whereas H4 was monospecific for rabbit IgG. CONCLUSION: Since the lv3c93 gene is not homologous to any reported V lambda sequence from natural autoantibodies, it is possible that lv3c93 may represent a disease-specific RF-related V lambda gene. Moreover, the amino acid sequence CSGGSCY in the third complementarity-determining regions of 2 of the RF heavy chains is encoded by the DLR2 gene segment and has been found previously in 2 other RA-derived RFs, and thus may play a significant role in antigen binding.
8350328 Variability of immunologic and clinical features in patients with rheumatoid arthritis stu 1993 Jun Disease activity measures in patients with rheumatoid arthritis (RA) are influenced by many factors. Bedrest has been long recognized to effect decreased disease activity. In addition, most patients note maximal levels of pain and stiffness in the early morning hours with improvement in the afternoon. Cytokines and hormones with circadian rhythms may also contribute to variability in disease status during the day. Our purpose was to investigate variability of clinical and immunologic measures over a 24-h period of hospitalization in patients with RA. Production of rheumatoid factors and immunoglobulins, joint counts and questionnaire evaluations were measured 3 to 6 times over a 24-h period of hospitalization in 10 patients with RA who were not receiving steroids or second line drugs. Total joint counts were significantly decreased as soon as 4 h after admission, and continued to decrease during the 24-h period of observation. Significant decreases in mononuclear cell proliferation and antibody synthesis were also observed. Our findings are consistent with the presence of decreased levels of immunostimulatory mediators in hospitalized patients especially during late afternoon or evening hours.
7942201 Bovine bone grafting in occipito-cervical fusion for atlanto-axial instability in rheumato 1994 Bovine bone chips (Surgibone) were used in occipito-cervical fusion in nine patients with atlanto-axial instability due to rheumatoid arthritis. The patients were examined with CT 12-15 months after surgery. Graft resorbtion was observed in one patient. The other 8 patients showed preserved grafts, in most cases the grafts appeared to be in contact with the underlying bone. One patient was revised, and at the grafted site a bony bridge was found. In conclusion, the use of bovine chips in posterior occipito-cervical fusion will not lead to predictable bone union. However, there seem to be exceptions to that rule.
10146960 Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs). 1993 Feb Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of the symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), sprains and strains, sports injuries and menstrual disorders, and have a small role in the management of patent ductus arteriosus in the neonate. In patients with RA, symptom relief through use of NSAIDs is firmly established, although it remains unclear whether they influence the course and outcome of the disease. For the average patient with RA taking NSAIDs, the attributable risk of hospitalisation with gastrointestinal problems related to NSAIDs is 1.3 to 1.6% annually and risk of death is 0.15%. Associations of therapy with risk are greatest with age, corticosteroid use and previous NSAID-related gastrointestinal adverse effects, and less marked with disability and high NSAID dose. These are important data in attempting to balance risk of therapy with clinical efficacy in an individual patient, and assessing the cost-effectiveness of prophylaxis. Although half of all NSAID consumption is for control of pain associated with degenerative conditions, their superiority over simple analgesics in osteoarthritis is poorly documented. This finding supports the use of the simple analgesic paracetamol (acetaminophen) as the preferred therapy of osteoarthritis, especially when its lower cost and low incidence of adverse effects are taken into consideration. Consistent differences in clinical effectiveness of individual NSAIDs have not been demonstrated, although unpredictable interpatient variation in response to individual agents is of considerable clinical importance, and a more expensive NSAID may prove cost effective for some patients. Cost effectiveness can be improved by a self-adjusted dosage regime which also leads to lower overall drug consumption. The adverse gastrointestinal effects of these drugs account for about 30% of the overall cost of arthritis treatment, and although studies to date have been too limited to assess the relative risk of gastrointestinal toxicity of the different NSAIDs reliably, ibuprofen appears to be one of the least hazardous, and azapropazone one of the most hazardous. Although the effectiveness of prophylaxis with H 2-antagonists and with prostaglandin E 1 analogues (prostaglandin-E 1 analogues) has been established, estimates of cost-benefit ratios are widely divergent. To establish the most cost-effective therapy with NSAIDs, more data are required to establish multivariable risk profiles for identification of patients at particular risk, the optimal drug, and its optimal dosage and duration of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
8630115 Elevated nitric oxide production in rheumatoid arthritis. Detection using the fasting urin 1996 Apr OBJECTIVE: To develop a simple method for assessing endogenous nitric oxide (NO) production applicable to routine clinical practice in rheumatology. METHODS: NO production was assessed in patients with rheumatoid arthritis (RA) as serum nitrate levels and as the urinary nitrate:creatinine ratio in morning samples of urine following an overnight fast. The influence of dietary intake of nitrate on these measurements was investigated in healthy volunteers. The clinical value of the urinary nitrate:creatinine ratio was validated in patients with infectious gastroenteritis, in whom its production is known to be increased. RESULTS: Urinary nitrate:creatinine ratios were significantly elevated in patients with RA (average 3-fold elevation over controls; P < 0.005) or infectious gastroenteritis (average 10-fold elevation, P < 0.001). Serum nitrate was significantly elevated only in patients with infectious gastroenteritis (P < 0.001). Dietary intake of nitrate had no significant influence on the fasting morning urinary nitrate:creatinine ratio in the healthy volunteers, showing that this parameter is a useful indicator of endogenous NO production.
8083264 Outcome after flap cover for exposed total knee arthroplasties. A report of 25 cases. 1994 Sep The long-term functional result of exposed total knee arthroplasty, treated by flap cover, is presented and the results compared with those of a randomly selected control group. The wound was successfully covered and the prosthesis was preserved in 76% of cases, but the final functional score was not as good as in those with primary wound healing.
7774100 Abnormal T cell receptor V beta gene expression in the peripheral blood and synovial fluid 1995 Jan OBJECTIVE: The aim of this study was to assess T cell receptor V beta-gene expression in the peripheral blood and synovial fluid of rheumatoid arthritis patients. METHODS: Cytometric analysis was performed on peripheral blood and synovial fluid lymphocytes from 12 patients using a restricted set of V beta-specific monoclonal antibodies (to V beta 5.1-3, V beta 6.7 and V beta 8). In 5 patients the expression of the V beta 1 through V beta 20 gene families was also analysed, using a recently described method based on a one-side-specificity polymerase chain reaction coupled to reverse dot hybridization. RESULTS: Cytometric analysis failed to show any consistent difference in the expression of V beta 5, 6 and 8 between the two compartments on the one hand, or between the peripheral blood of normal individuals and patients on the other hand. The PCR/dot hybridization method did not demonstrate a significant difference in the V beta repertoires between peripheral blood and synovial fluid samples from arthritis patients. However, in all patients the V beta 6, 13 and/or 14 families were expressed to a high level, so that these families frequently represented over 40% of the V beta 1-20 repertoire in both compartments, instead of the approximately 20% seen in normal peripheral blood samples. CONCLUSION: We conclude that V beta 6, 13 and 14 are overexpressed in both the peripheral blood and synovial fluid of rheumatoid arthritis patients compared to normal samples.
8311549 Decreased axial bone mineral density in perimenopausal women with rheumatoid arthritis--a 1994 Jan OBJECTIVES: Although periarticular osteoporosis is a well-recognised phenomenon in rheumatoid arthritis (RA), there is considerable controversy over whether RA is associated with more generalised osteoporosis. The aetiology of this bone loss is probably multifactorial, including both life-style risk factors and disease-related determinants. Population-based studies on bone mineral density (BMD) in RA have not previously been conducted, and the purpose of the present cross-sectional population-based study was to determine whether patients with RA are at an increased risk of having osteoporosis. Furthermore, the determinants of BMD in RA patients were investigated. METHODS: BMD at the spine and femoral neck was measured in 143 women with RA. The control group consisted of 1611 women with no disease or taking any drugs known to affect bone metabolism. The study population was a random stratified sample from the Kuopio Osteoporosis Study, which included all perimenopausal women aged 47-56 years residing in Kuopio Province, Eastern Finland in 1989 (n = 14,220). The mean age of the patients at the time of densitometry was 53.7 years. RESULTS: The mean (SD) spinal and femoral neck BMD was significantly lower in patients with RA compared with controls [spine: 1.067 (0.161) v 1.129 (0.157) g/cm2, p < 0.001; femoral neck: 0.851 (0.136) v 0.932 (0.123) g/cm2, p < 0.001]. Analysis of variance showed that at the spine the difference was significant only in patients having corticosteroid treatment, whereas at the femoral neck patients with non-steroid treatment also had significantly lower BMD. When confounding factors were corrected, no significant difference could be found between non-steroid and corticosteroid treated patients with RA, suggesting that the independent effect of corticosteroids on BMD is only minimal. Multiple regression analysis found age, weight and functional grade to be significant predictors of spinal BMD (R2 = 0.403, p < 0.001). In the femoral neck weight, cumulative corticosteroid dose and functional grade were significant predictors of BMD (R2 = 0.410, p < 0.001). CONCLUSIONS: RA is associated with generalised osteoporosis. The physical impairment and body weight are the major determinants of both spinal and femoral bone mass in RA patients. The cumulative corticosteroid dose was also a significant determinant of femoral neck BMD. However, the independent effect of corticosteroids is questionable because the use of corticosteroids may be an indicator of more severe disease.
8849379 The systemic effect of intraarticular administration of corticosteroid on markers of bone 1996 Feb OBJECTIVE: To assess the effects of intraarticular (IA) corticosteroid use on bone metabolism in patients with rheumatoid arthritis (RA). METHODS: Levels of the bone turnover markers, serum osteocalcin (BGP) and urinary pyridinoline (PYD), were monitored in RA patients for 4 weeks following a single IA administration of xylocaine alone or in combination with triamcinolone acetonide. RESULTS: Levels of the bone resorption marker, PYD, did not show any significant change, whereas BGP levels were drastically decreased 1 day after IA administration of corticosteroid, and then returned to pretreatment levels by day 14. The efficacy of IA corticosteroid treatment lasted for 4 weeks. CONCLUSION: Our results suggest that IA administration of corticosteroid has no net effects on bone resorption and only a transient systemic effect on bone formation. IA corticosteroid administration may be better for bone metabolism than continuous use of orally administered corticosteroid.
8835569 Interruptions in rheumatology subspecialty care among patients with rheumatoid arthritis. 1995 Dec OBJECTIVE: To identify factors associated with interruptions in care from rheumatologists among patients with rheumatoid arthritis (RA). METHODS: A person-time analysis was used to examine the association of medical insurance status, income, health status, treatment by a primary care physician, and presence of comorbid conditions with interruptions in rheumatology subspecialty care in a cohort of 161 patients with RA followed prospectively for up to 10 years. An interruption was defined as a 6-month period during which a patient was not treated by a rheumatologist. Each patient had at least one interruption. RESULTS: Interruptions in rheumatology care occurred more commonly during periods when patients reported no medical insurance coverage than when they had medical insurance coverage (relative risk, RR = 1.49; 95% confidence interval, CI = 1.05, 2.11). Interruptions in care were more common during intervals in which patients reported at least a 40% improvement in functional disability (RR = 1.30; 95% CI = 1.03, 1.63), but interruptions were not associated with either absolute or relative changes in pain or global arthritis status. Interruptions in rheumatology care also occurred more commonly during periods when patients reported seeing a primary care physician (RR = 2.07; 95% CI = 1.71, 2.50), and when they reported having a comorbid condition (RR = 1.37; 95% CI = 1.06, 1.77). Income was not associated with interruptions in care. CONCLUSION: Lack of medical insurance and short term improvements in functional disability are associated with interruptions in rheumatology care among patients with RA. Patients also appear to substitute primary care for care from rheumatologists. These associations suggest that potential strategies for enhancing continuity in rheumatology care might include the promotion of universal insurance coverage and the development of informational programs for patients.
1566139 Polyarticular pseudosepsis in rheumatoid arthritis. 1992 Apr Three patients with longstanding seropositive rheumatoid arthritis had fever and marked synovial fluid leukocytosis in multiple joints. No infectious agents were found in synovial fluid or blood, and the patients recovered uneventfully without prolonged antibiotic therapy. Acute, severe exacerbations of synovitis in patients with rheumatoid arthritis may simulate a septic process and involve multiple joints.
8024963 Operative treatment of the rheumatoid shoulder. 1994 Mar Rheumatoid arthritis can affect almost any joint. Shoulder involvement typically occurs late in the disease process and usually after other joints have manifested arthritic change. Any of the four shoulder articulations can be involved: scapulothoracic, acromioclavicular, sternoclavicular, and glenohumeral. In addition to bony involvement, many of the soft tissues of the shoulder joint can be affected. Early operative treatment includes synovectomy with or without bursectomy, which is indicated prior to radiographic evidence of arthritis. Early synovectomy provides for a slowing of the progression of the disease process. Patients who have incapacitating pain with loss of range of motion can benefit from total shoulder replacement. Most patients experience pain relief and some restoration of motion. The restoration of normal range of motion is dependent on anatomic reconstruction of the glenohumeral joint. Factors that can affect the range of motion include rotator cuff tears and the general health status and motivation of the patient. Although there is a 30% to 80% incidence of radiographic lucencies with nonconstrained prostheses, their presence does not indicate the need for revision surgery. Occasionally, there is medialization of the glenohumeral joint with central bony losses of the glenoid. The surgeon should try to bone graft the defect and lateralize the components. If there is massive medialization of the glenoid that is not reconstructable, then a hemiarthroplasty is the procedure of choice.