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ID PMID Title PublicationDate abstract
10852255 Randomized double blind trial of an ayurvedic plant derived formulation for treatment of r 2000 Jun OBJECTIVE: To evaluate RA-1, a standardized plant extract formulation, traditionally considered a safe, effective antiarthritic in the Asian-Indian Ayurvedic medicinal system. METHODS: One hundred eighty-two patients with active-on-chronic rheumatoid arthritis (RA) participated in a 16 week randomized, double blind, placebo controlled, parallel efficacy clinical drug trial in Pune, India. Tenderness, pain, swelling, and several other efficacy measures were assessed by (1) ACR core set 20% and 50% improvement; (2) ACR 20% improvement response. An intent-to-treat analysis was performed; p<0.05 considered significant. RESULTS: Seventeen patients withdrew (active = 9; placebo = 8); none withdrew due to drug toxicity. An unprecedented placebo response (often p<0.001 in within-group change) was observed. The active RA-1 group remained numerically superior at all evaluation timepoints. RA-1 demonstrated few significant differences: (1) increased proportion with 50% reduction in swollen joint count (95% CI approximately 1.52, 29.90) and swollen joint score (95% CI approximately 0.91, 28.73); (2) reduced rheumatoid factor (95% CI approximately -303.7, -2.72); 39% in the RA-1 group versus 30% placebo showed ACR 20% improvement (95% CI approximately -5.48, 24.59). Only minor side effects were seen, with no significant differences by treatment group. CONCLUSION: In a trial with sufficient power, RA-1 revealed efficacy that was not significantly superior to the strong placebo response, except for improvement in joint swelling. Further, the effect on RF and good safety profile led to an open label phase.
10529125 The safety and efficacy of cyclosporine (Neoral) in rheumatoid arthritis. 1999 Oct OBJECTIVE: To assess the safety and efficacy of cyclosporine (Neoral), its steroid sparing effect, and its usefulness in combination therapy with methotrexate (MTX) in the treatment of refractory rheumatoid arthritis (RA). METHODS: All patients given cyclosporine for refractory RA over a 21 month period were included in an open, prospective study. Patients were reviewed initially fortnightly then monthly with clinical evaluation and serum creatinine. There were no restrictions on the use of other disease modifying agents, nonsteroidal antiinflammatory drugs, or corticosteroids. RESULTS: Forty-six patients with severe RA were included in the study, 33 (72%) female and 13 (28%) male, with a mean age of 54.8 years (range 20-74). At the completion of the study 30 (65%) were still taking cyclosporine at a mean dose of 2.94 mg/kg/day for a mean duration of 10.5 months. Thirteen patients discontinued cyclosporine due to side effects, most commonly gastrointestinal, and 3 due to inefficacy. Thirty-seven of the 46 patients were taking prednisolone at the start of the study at a mean dose of 10.36 mg/day, which decreased to 7.068 mg/day at the end of the study (p < 0.001). Thirty patients used cyclosporine in combination with MTX. The mean dose of MTX decreased from 15.08 to 13.67 mg/wk (p = 0.02). The mean serum creatinine increased by 13% from 74 to 83.7 micromol/l. Patients who continued therapy had a shorter duration of disease, with a mean of 9.93 years compared to 15.73 years in those who stopped therapy (p = 0.004). CONCLUSION: Cyclosporine (Neoral) was a safe and effective therapy in this population of patients with RA refractory to standard therapy. We observed a significant steroid sparing effect and have shown that combination therapy with MTX does not increase side effects and allows for a decrease in MTX dose. Renal function is not adversely affected if guidelines are followed.
11196523 Surfing the Net--information on the World Wide Web for persons with arthritis: patient emp 2001 Jan OBJECTIVE: In the past few years access to the Internet has become readily available. Patients are increasingly seeking and obtaining health information through the Internet, most often the World Wide Web (WWW). We assessed the content, authorship, and scope of the information available on WWW in relation to rheumatoid arthritis. METHODS: In an attempt to replicate use by the average person, a broad search of the Internet was conducted for the phrase "rheumatoid arthritis" using WebCrawler, a commonly used search engine. All the "hits" were critically assessed after visiting and collecting information from the respective Web sites in relation to relevance, scope, authorship, type of publication, and financial objectives. RESULTS: The search returned 537 hits. We evaluated 531-2 did not exist, 2 could not be contacted, one was not in English, and one required a membership to access. The 531 hits originated from 388 Web sites. Only 198 (51%) were considered to be relevant and 7 (2%) were of doubtful relevance. Thirty-four (17%) were posted by an individual, 57 (28%) by a nonprofit organization, 104 (51%) by a profit industry, and 10 (5%) by universities. Ninety-one (44%) promoted alternative therapies, the most common including cetyl-myristoleate, colloidal minerals, Pycnogenol, shark cartilage, and Tahitian Noni. Of the 107 sites with financial interests, 76 (71%) promoted alternative medicine. The first 100 hits only identified about a third of the nonprofit organizations or university owned Web pages. CONCLUSION: Many sites easily accessed by consumers appear to be profit based companies advertising an alternative product claimed to be effective for many conditions. These findings emphasize the need for critical evaluation of Web site contents.
11276798 Celecoxib clinical profile. 2000 Dec Celecoxib is the first COX-2-specific inhibitor approved for relief of the signs and symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA), as well as for treatment of familial adenomatous polyposis. For both OA and RA, celecoxib has been shown to be significantly superior in efficacy to placebo and similar in efficacy to traditional non-steroidal anti-inflammatory drugs. Its advantage, however, is its gastrointestinal (GI) safety. Randomized clinical trials as well as long-term outcomes studies have demonstrated that the GI safety profile of celecoxib is superior to that of traditional NSAIDs and similar to that of placebo. Additionally, the renal and cardiovascular safety of celecoxib has also become apparent, as well as its efficacy, tolerability and safety in the elderly population.
9034987 Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythemato 1997 Feb OBJECTIVE: To investigate the difference in acute phase protein responses between patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and spondyloarthropathies (SpA). METHODS: Circulating levels of cytokines inducing the production of acute phase proteins such as interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha, and of cytokine inhibitors such as TNF soluble receptors (TNF-sR55 and TNF-sR75) and IL-1 receptor antagonist (IL-1ra), were measured in 2 cohorts of patients. The first cohort included 52 patients with SLE and 22 with RA, and the second included 21 with SLE, 20 with RA, and 18 with SpA. An examination at the time of blood collection and the Systemic Lupus Activity Measure (SLAM) index were used to assess disease activity in patients with SLE. Serum levels of IL-6 were measured using a biological assay, and concentrations of IL-1 beta, TNF-alpha, TNF-sR55, TNF-sR75, and IL-1ra were assessed by immunoassays. RESULTS: Although C-reactive protein (CRP) levels were significantly lower in SLE than in RA or SpA, the concentrations of circulating IL-6 or TNF-alpha were higher in SLE. The most striking observation was that TNF-sR levels were significantly higher in SLE than in RA or SpA. The TNF-alpha: TNF-sR ratio was also significantly lower in SLE than in RA. TNF-sR55 and TNF-sR75 levels correlated with disease activity in SLE. CONCLUSION: The weak acute phase protein response in SLE may be explained by a decreased ratio between inducing cytokines and their inhibitors. In addition, TNF-sR may prove a useful biological marker for the followup of SLE, where acute phase protein response is generally low during disease exacerbations.
9184268 Adverse drug reactions and debrisoquine/sparteine (P450IID6) polymorphism in patients with 1997 May OBJECTIVE: To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions. METHODS: Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions. A sample of 60 patients with rheumatoid arthritis and 62 patients with localized back pain served as controls. The P450IID6 phenotype was determined for each of the fibromyalgia patients. RESULTS: Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of them reported side effects. Analgesics were used by 122 patients and 22 (18%) had experienced adverse effects. Statistical differences in the frequency of adverse effects were found with antidepressant drugs in the fibromyalgia group, compared with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35 patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52) indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log M.R. = -2.30) to 4.99 (log M.R. = 0.70). CONCLUSIONS: The problem of adverse drug reactions in fibromyalgia patients does not appear to correlate with the PM phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered xenobiotic detoxification attributable to this PM phenotype would have a significant role in the development of fibromyalgia.
11085806 Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial 2000 Nov OBJECTIVE: To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA). METHODS: The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points. RESULTS: BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication. CONCLUSION: Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs.
9643572 Intravascular lymphomatosis--an indolent or aggressive entity? 1998 May Intravascular lymphomatosis (IVL) is a rare malignancy characterized by neoplastic proliferation of lymphoid cells within the lumens of arteries, small veins and capillaries. We report four patients with IVL and review the recent world literature, relating to incidence, clinical features and possible therapy. In these cases diagnosis was established coincidentally in one patient after prostatectomy. This patient eventually had central nervous system involvement. In two other patients IVL was diagnosed from skin lesions. In the fourth case the diagnosis was established at post-mortem examination, where involvement of most organs was evident but particularly kidneys, myocardium, gastrointestinal tract and lymph nodes. Therapy was given to three patients, but the disease progressed in two and they both died with evidence of central nervous system involvement, while the third patient has had a good partial response to combination chemotherapy but has relapsed within two months of completing chemotherapy. As evident from our patients and the literature review IVL has a variable clinical course and currently, there appears to be no effective therapy for this rare disorder.
9486836 Meningoencephalocele associated with Tripterygium wilfordii treatment. 1997 Jul We treated a male infant with occipital meningoencephalocele associated with the taking of Tripterygium wilfordii. The infant was delivered normally at 38 weeks of gestation with a huge cystic mass protruding from the occiput. He was diagnosed with occipital meningoencephalocele and cerebellar agenesis. His mother had taken T. wilfordii for rheumatoid arthritis early in her pregnancy. T. wilfordii is a herbal medicine used for rheumatoid arthritis and male contraception. Since its toxicity is high and its use during pregnancy is restricted, it is the most likely cause of this infant's anomalies.
9058671 Herpes zoster encephalomyelitis associated with low dose methotrexate for rheumatoid arthr 1997 Mar We describe herpes zoster encephalomyelitis occurring 9 days after the onset of cutaneous zoster in an elderly patient taking low dose weekly methotrexate without concomitant prednisolone.
10395320 Induction of the p16INK4a senescence gene as a new therapeutic strategy for the treatment 1999 Jul Synovial tissue affected by rheumatoid arthritis is characterized by proliferation, which leads to irreversible cartilage and bone destruction. Current and experimental treatments have been aimed mainly at correcting the underlying immune abnormalities, but these treatments often prove ineffective in preventing the invasive destruction. We studied the expression of cyclin-dependent kinase inhibitors in rheumatoid synovial cells as a means of suppressing synovial cell proliferation. Synovial cells derived from hypertrophic synovial tissue readily expressed p16INK4a when they were growth-inhibited. This was not seen in other fibroblasts, including those derived from normal and osteoarthritis-affected synovial tissues. In vivo adenoviral gene therapy with the p16INK4a gene efficiently inhibited the pathology in an animal model of rheumatoid arthritis. Thus, the induction of p16INK4a may provide a new approach to the effective treatment of rheumatoid arthritis.
11718154 Leflunomide and rheumatoid arthritis: new preparation. Neither the safest nor the most eff 2001 Apr (1) There is no consensus on the reference disease-modifying antirheumatic drug. Three drugs are often prescribed as a first line option: methotrexate for its efficacy, and sulfasalazine and hydroxychloroquine for their lesser adverse effects. (2) Leflunomide, an immunosuppressive drug, is approved in the European community for oral treatment of rheumatoid arthritis, as a slow-acting antirheumatic agent. (3) The clinical file answers only some practical questions. (4) At a dose of 10-20 mg/day, patients start to notice the efficacy of leflunomide after 4-8 weeks. (5) One of the two available trials versus methotrexate shows that the latter is significantly more effective than leflunomide on clinical end points. The other trial, which was smaller, showed no difference between the treatments. Another trial showed no difference in clinical efficacy between leflunomide and sulfasalazine. (6) Leflunomide was more often associated with severe adverse events than methotrexate or sulfasalazine: elevated transminase levels, haematological disorders and cutaneous reactions. (7) Leflunomide is teratogenic in animals. The summary of product characteristics recommends a two-year period between conception and the end of leflunomide treatment. (8) The two-week half-life of the active metabolite of leflunomide is a major disadvantage when adverse effects occur.
10790435 Induction and suppression of collagen-induced arthritis is dependent on distinct fcgamma r 2000 May 1 Receptors for immunoglobulin (Ig)G (FcgammaRs) are important for the antibody-mediated effector functions of the immune system. FcgammaRI and FcgammaRIII trigger cell activation through a common gamma chain, whereas FcgammaRII acts as a negative regulator of antibody production and immune complex-triggered activation. Here we describe the in vivo consequences of FcgammaR deficiency in a mouse model of human rheumatoid arthritis. FcRgamma chain-deficient mice on arthritis-susceptible DBA/1 background were immunized with collagen for induction of collagen-induced arthritis. The DBA/1 mice lacking FcRgamma chain were protected from collagen-induced arthritis in contrast to wild-type mice, although both groups produced similar levels of IgG anticollagen antibodies. In comparison, DBA/1 mice lacking FcgammaRII developed an augmented IgG anticollagen response and arthritis. These observations suggest a crucial role of FcgammaRI and FcgammaRIII in triggering autoimmune arthritis.
11565191 The antiproliferative effect of mizoribine on rheumatoid synovial fibroblast mediated by i 2001 Feb In order to investigate the mechanism of anti-rheumatic action of mizoribine (MZR), antiproliferative effect of MZR on synovial fibroblasts obtained from rheumatoid arthritis (RA) patients were examined. To examine the effect of MZR on DNA synthesis, total radioactivity of 3H-thymidine (3H-TdR) incorporated into the synovial fibroblasts was measured. Also quantification of DNA fragmentation of synovial fibroblasts in the cultured supernatant and cell associated Bcl-2 protein, which is suspected of interfering with apoptosis, were performed with enzyme-linked immunosorbent assay. MZR suppressed 3H-TdR incorporation into synovial fibroblasts in a dose dependent fashion. Significant inhibition (P < 0.01) was attained at the concentration of more than 1 microgram/ml of MZR. However, induction of DNA fragmentation which is characteristic of apoptosis, were observed at only 10 micrograms/ml of MZR over 72 h-incubation significantly. In terms of the Bcl-2 expression of synovial fibroblasts, up to 10 micrograms/ml of MZR has no effect on the expression of this protooncogene bcl-2 expression. These results suggest that MZR might suppress the growth of rheumatoid pannus by inhibition of synovial fibroblast proliferation partially through the induction of apoptosis of synovial fibroblast without modulating Bcl-2 expression.
9766153 Clinical presentation of sarcoidosis in The Netherlands an epidemiological study. 1998 Aug BACKGROUND: Patients suffering from sarcoidosis may present with a wide range of symptoms. The aim of this study was to make an inventory of the clinical presentation of the sarcoidosis population in the Netherlands. METHODS: Symptom inventory questionnaires were sent to all members of the Dutch Sarcoidosis Society. Of these 1755 sarcoidosis patients, 1026 (58%), (age 46.7 +/- 11.6, female 63%) completed the questionnaire. RESULTS: Familial sarcoidosis was reported by 170 patients (16.3%). In 57% of the cases the first diagnosis was sarcoidosis. Other diagnosis included rheumatoid arthritis (5.1%) and tuberculosis (4.8%). Treatment with systemic corticosteroids was reported by 565 patients (55.1%). The most frequently reported symptom was fatigue (71%), followed by dyspnea (70%), arthralgia (52%), muscle pain (39), chest pain (27%), and general weakness (22%). Moreover, 26% of patients suffered from disease-related tension and strain. No relationship was found between the reported symptoms and treatment with corticosteroids. CONCLUSIONS: Sarcoidosis patients suffered from a broad range of persistent physical symptoms. In this study fatigue appeared to be the most commonly reported symptom. Intervention programs should focus on physical health as well as psychosocial aspects such as teaching patients how to cope with the disease.
10677975 [Total knee replacement of severe flexion contracture deformities greater than 60 degree]. 1997 Jul The technique of total knee arthroplasty for the patients with severe flexion contractures of more than 60 degrees is not clear. Recently, We have performed 37 total knee arthroplasties in 23 patients with flexion contracture of more than 60 degrees (average 77.97 degrees). Among them, 14 knees (37.9%) with flexion contracture of more than 90 degrees, and 7 knees (18.0%) with 90 degrees flexion fusion deformities. Significant improvements occurred after averaged 4.3-year follow-up. Complications occurred in four patients: three had transient peroneal-nerve palsy, and one had temporary circulatory disturbance of the lower extremity. They recovered after conservative therapy. We consider that severe flexion contracture of more than 60 degrees is not a contraindication of TKR. Staged bone resection and thoroughly soft-tissue release of the posterior capsule and collateral ligament balance were the critical procedure. If necessary, additional distal femoral condyle resection with posterior cruciate ligment sacrifice can be considered.
11574988 Tumor necrosis factor inhibitors: new options for treating rheumatoid arthritis. 2001 Sep There is accumulating evidence that tumor necrosis factor plays a major role in the pathogenesis of rheumatoid arthritis. Recent biotechnological advances have allowed for the development of agents that directly target TNF, a proinflammatory cytokine. In the last 2 years, the U.S. Food and Drug Administration and the European Union's Commission of the European Communities have approved two biological agents for the treatment of refractory RA, etanercept and infliximab. Etanercept is a fusion protein, composed of the Fc portion of immunoglobulin G1 and the extracellular domain of a TNF receptor (p75). Infliximab is a chimeric monoclonal antibody composed of murine variable and human constant regions. In placebo-controlled trials, both agents have proven to be effective and well tolerated in RA patients.
11021173 [A case of rheumatoid arthritis associated with autoimmune hemolytic anemia due to weekly 2000 Aug A 57-year-old woman was found to have rheumatoid arthritis (RA) in 1996. Treatment with different immunoregulatory agents, including actarit and bucillamine, produced no improvement. Therefore, combined therapy with methotrexate (MTX) (5 mg/week oral) and low-dose prednisolone (PSL) (5 mg/day) was started in April 1997. Sulindac and famotidine were also administered. In August 1997, she was admitted to our hospital because of palpitations and shortness of breath due to severe anemia. Results of laboratory studies were hemoglobin, 2.9 g/dl; reticulocyte count, 225/1000; and haptoglobin, less than 10 mg/dl. The direct and indirect Coombs'tests were positive. A diagnosis of autoimmune hemolytic anemia (AIHA) was made on the basis of the laboratory findings. Treatment with high-dose PSL (50 mg/day) was started, and the anemia improved. The hemoglobin level increased to 6.0 g/dl within the 1st week and to 12.6 g/dl 6 weeks later. We believe that the most likely explanation for this anemia was the low-dose MTX because the anemia appeared soon after treatment was started.
11020469 Electrophoretic study of tartrate-resistant acid phosphatase isoforms in endstage renal di 2000 Nov The objective of this study was to identify the isoform, type-5a or type-5b, responsible for increased tartrate-resistant acid phosphatase (TRAP) activity in endstage renal disease (ESRD) and TRAP protein in rheumatoid arthritis (RA). We studied 24 sera each from healthy, ESRD and RA subjects. Type-5 TRAP activity and protein were quantitated by immunoassays. Isoform expression was determined by computerized imaging of non-denaturing polyacrylamide gels (PAGE) stained for TRAP activity. Other biochemical markers included: intact parathyroid hormone (iPTH), total and bone-specific alkaline phosphatase (TAP, BAP), N-telopeptides of type-I collagen (NTx), and free pyridinoline (Pyd). Isoform 5a was normal in both ESRD and RA. Isoform 5b was elevated in ESRD only. Serum TRAP activity correlated with both isoforms 5a and 5b in RA, but only with 5b in ESRD. TRAP protein assays did not correlate with PAGE assays for 5a or 5b. TRAP activity, but not protein, correlated with BAP and NTx in RA sera. Both TRAP activity and protein correlated with iPTH, TAP and Pyd in ESRD sera. Increased TRAP activity in ESRD was due to increased osteoclastic isoform 5b and related to bone turnover. Increased TRAP protein in RA was suspected, but not proven, to be isoform 5a and not related to bone turnover. Heterogeneity of serum TRAP and preferential expression of isoforms has clinical significance in different diseases including ESRD and RA.
10779216 Non-Helicobacter pylori ulcer disease in rheumatoid arthritis patients receiving long-term 2000 Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are considered the major causes of peptic ulcer. If ulcers are not attributable to H. pylori, most are thought to be attributable to NSAIDs. We have previously reported that rheumatoid arthritis (RA) patients taking NSAIDs long term (NSAIDs group) are more likely to develop gastric ulcers, which commonly occur in the gastric antrum. In addition, the morphology of gastric ulcers in the NSAIDs group differs from that in the non-NSAIDs group (control group), in whom NSAIDs are not involved in the occurrence of gastric ulcers. In this study, we compared gastric ulcers in the NSAIDs group with those in the control group in terms of H. pylori infection. The positive rate of H. pylori in gastric ulcers was significantly lower in the NSAIDs group than in control group (53.6% vs 91.5%). At the ulcer site they were seen significantly less often in the antrum than in either the angle or body of the stomach (35% vs 100%) in the NSAIDs group. On the other hand, the H. pylori-positive rate for ulcers in the antrum did not differ significantly from that in the angle and body of the stomach (81.8% vs 93.8%) in the control group. These findings suggest that H. pylori plays little role in antral ulcers in those taking NSAIDs.