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ID PMID Title PublicationDate abstract
10580457 Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: 1999 Nov 24 CONTEXT: In vitro studies have shown that celecoxib inhibits cyclooxygenase 2 (COX-2) but not COX-1, suggesting that this drug may have anti-inflammatory and analgesic activity without adverse upper gastrointestinal (GI) tract effects that result from COX-1 inhibition. OBJECTIVE: To test whether celecoxib has efficacy as an anti-inflammatory and analgesic with reduced GI tract mucosal damage compared with conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial lasting 12 weeks, with follow-up at weeks 2, 6, and 12, from September 1996 thorugh February 1998. SETTING: Seventy-nine clinical sites in the United States and Canada. PATIENTS: A total of 1149 patients aged 18 years or older with symptomatic rheumatoid arthritis who met inclusion criteria were randomized; 688 (60%) of these completed the study. INTERVENTIONS: Patients were randomized to receive celecoxib, 100 mg, 200 mg, or 400 mg twice per day (n = 240, 235, and 218, respectively); naproxen, 500 mg twice per day (n = 225); or placebo (n = 231). MAIN OUTCOME MEASURES: Improvement in signs and symptoms of rheumatoid arthritis as assessed using standard measures of efficacy and GI tract safety as assessed by upper GI tract endoscopy before and after treatment, compared among treatment groups. RESULTS: All dosages of celecoxib and naproxen significantly improved the signs and symptoms of arthritis compared with placebo. Maximal anti-inflammatory and analgesic activity was evident within 2 weeks of initiating treatment and was sustained throughout the 12 weeks. The incidence of endoscopically determined gastroduodenal ulcers in placebo-treated patients was 4 (4%) of 99, and the incidences across all dosages of celecoxib were not significantly different (P>.40): 9 (6%) of 148 with 100 mg twice per day, 6 (4%) of 145 with 200 mg twice per day, and 8 (6%) of 130 with 400 mg twice per day. In contrast, the incidence with naproxen was 36 (26%) of 137, significantly greater than either placebo or celecoxib (P<.001). The overall incidences of GI tract adverse effects were 19% for placebo; 28%, 25%, and 26% for celecoxib 100 mg, 200 mg, and 400 mg twice per day, respectively; and 31 % for naproxen. CONCLUSION: In this study, all dosages of celecoxib were efficacious in the treatment of rheumatoid arthritis and did not affect COX-1 activity in the GI tract mucosa as evidenced by less frequent incidence of endoscopic ulcers compared with naproxen.
10073585 The hemispherical Harris-Galante acetabular cup, inserted without cement. The results of a 1999 Feb We studied the results for 168 available hips from a series of 324 consecutive primary total hip arthroplasties that had been performed with insertion of a Harris-Galante-I acetabular component without cement. The acetabulum had been reamed in a so-called line-to-line manner, and the cup had been fixed with one to four screws. A femoral component with a modular alumina-ceramic head had been inserted with cement in all hips. The median duration of follow-up was 112 months (range, 101 to 131 months). Of the original 324 hips, 109 could not be included in the clinical and radiographic follow-up because the patients had died and thirty could not be included because the patients were not available for examination. Seventeen hips had had a revision of the acetabular cup: five, because of infection; five, because of dislocation; three, because of aseptic loosening; and four, because of technical failure. This left 168 hips for clinical and radiographic follow-up; of these, fifteen had had a revision of the femoral component only. Of the remaining 153 hips, which had not had a revision, 147 (96 percent) were considered by the patient to have a satisfactory, good, or excellent result. One hip was found to have a loose cup on radiographic evaluation and was therefore considered to have failed, but the clinical function was good. We concluded that, with an overall rate of aseptic loosening of 1 percent (four of 324) after an intermediate (ten-year) duration of follow-up, use of this cup has good results.
9068596 Comparative evaluation of three assay systems for automated determination of hemoglobin A1 1997 Mar We evaluated three newly introduced systems for automated determinations of hemoglobin (Hb) A1c, which allow the processing of large amounts of samples in a routine clinical laboratory. We compared these methods--the Variant HPLC, the Hi-Auto A1c analyzer system, and the Roche immunoassay--with the Diamat HPLC system. All showed good precision and good concordance with the Diamat HPLC. The reference range for Hb A1c has to be determined by the laboratory for each assay system. Interference study showed no statistically significant influence of anemia, polycythemia, rheumatoid factor, or chronic hemodialysis, although individual Hb A1c values can be influenced by polycythemia (when measured with the Hi-Auto A1c analyzer) and by chronic hemodialysis (when measured with the Variant HPLC). HPLC was not suitable for measuring Hb A1c in the examined cases of hemoglobin variants; assaying fructosamine seems to be better for monitoring these patients.
10491362 Presentation of autoantibody to proliferating cell nuclear antigen in patients with chroni 1999 Oct OBJECTIVES: To study the association of antibodies to proliferating cell nuclear antigen (PCNA) in patients with chronic hepatitis B (HBV) and C (HCV) virus infection. METHODS: Sera from 243 patients with chronic HBV infection; 379 patients with chronic HCV infection; 80 patients with systemic lupus erythematosus (SLE); 28 patients with rheumatoid arthritis; 15 patients with Sjogren's syndrome; eight with polymyositis; eight with primary biliary cirrhosis; and 33 healthy control subjects were tested for the presentation of anti-PCNA antibodies by enzyme linked immunosorbent assay (ELISA) and immunoblotting using recombinant PCNA as antigen. The distribution of immunoglobulin isotypes of anti-PCNA antibody was measured by ELISA assay. RESULTS: By ELISA, anti-PCNA antibodies were detected in 30 (12.3%) patients with chronic HBV infection, 71 (18.7%) patients with chronic HCV infection, and five (6.3%) patients with SLE. The inhibition of binding with these sera by purified PCNA was shown to exceed 71%. By immunoblotting, the frequency of anti-PCNA in patients with chronic HBV and HCV infection was 17 of 243 (7%) and 41 of 379 (11%), respectively. Absorption studies on indirect immunofluorescence showed the typical nuclear speckled staining pattern by anti-PCNA sera was abolished by preincubation of sera with PCNA. Anti-PCNA antibody was not detected in sera from patients with autoimmune diseases except SLE. Anti-PCNA antibodies in patients with chronic HBV and HCV infection were predominantly IgG. CONCLUSION: These data suggest that anti-PCNA antibody are also present in patients with chronic HBV and HCV infection. Anti-PCNA antibody may not be specific for SLE.
9527748 Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different r 1998 Jan AIM: To test the evidence for a difference in analgesic efficacy and adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) given by different routes. METHODS: Systematic review of published randomised controlled trials. Relevant trials were comparisons of the same drug given by different routes. Presence of internal sensitivity was sought as a validity criterion. Analgesic and adverse effect outcomes were summarised, and synthesised qualitatively. RESULTS: In 26 trials (2225 analysed patients), 8 different NSAIDs were tested in 58 comparisons. Fifteen trials (58%) compared the same drug by different routes. Drugs were given by intravenous, intramuscular, intrawound, rectal and oral routes in postoperative pain (14 trials), renal colic (4), acute musculoskeletal pain (1), dysmenorrhoea (1), and rheumatoid arthritis (6). Five of the 15 direct comparisons were invalid because they reported no difference between routes but without evidence of internal sensitivity. In all 3 direct comparisons in renal colic, intravenous NSAID had a faster onset of action than intramuscular or rectal. In 1 direct comparison in dysmenorrhoea, oral NSAID was better than rectal. In the 5 direct comparisons in postoperative pain, results were inconsistent. In 1 direct comparison in rheumatoid arthritis, intramuscular NSAID was better than oral. Injected and rectal administration had some specific adverse effects. CONCLUSION: In renal colic there is evidence that NSAIDs act quickest when given intravenously. This may be clinically relevant. In all other pain conditions there is a lack of evidence of any difference between routes. In pain conditions other than renal colic, there is, therefore, a strong argument to give oral NSAIDs when patients can swallow.
11354865 Patella resurfacing in total knee replacement: functional evaluation and complications. 2001 Three different knee replacements, with three trochlear designs, were prospectively evaluated clinically and radiographically for patellar function and presence of patellar complications. They included the Insall-Burstein (IB) I and the IB-II (posterior cruciate ligament substituting) and the Meniscal Bearing Knee (MBK; posterior cruciate ligament recession). The trochlea of the IB-I was short and shallow with an anterior sharp edge of the intercondylar box (later modified to a smoother edge) and the femoral component had a prominent "shoulder." In the IB-II the trochlea was deeper to allow for soft tissue clearance. In the MBK the trochlea was more prolonged, with R and L components and the "shoulder" was less prominent. In all the cases the patella was resurfaced with an all polyethylene dome prosthesis. Knees with tibiofemoral problems were excluded. From the data of the present study the following conclusions can be drawn: (a) The most frequent problem was impingement (clunks) with the early version of the IB-I. Smoothening of the anterior edge significantly reduced the incidence of clunks to 5% in the modified IB I. (b) With the IB-II deepening the trochlea for soft tissue clearance improved the degree, not the incidence of clunks (4.5%), compared to the modified IB I. (c) With the MBK clunks were very rare and patellar function improved. (d) Throughout the three series patellar stress fractures and instability were rare and loosening or wear not evident. (e) Normal function (including stairs ascending and descending) can be expected in over 80% of category A patients. (f) Of the various radiological parameters only patella baja was correlated with symptoms in the IB prostheses. (g) We still prefer the dome design because is more tolerant and with cold flow may better conform to the trochlea increasing contact area.
11109595 [Non-steroidal anti-inflammatory agents with selective inhibitory activity on cyclooxygena 2000 Nov INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the production of primary prostanoids by blocking the access of arachidonic acid to the active site of the cyclooxygenases (COXs). Because the prostanoids produced by COX-1 appear to play a physiological role (protection of the gastric mucosa, platelet aggregation, vascular homeostasis, maintenance of renal sodium-water balance) while those produced by COX-2 seem mainly to intervene in the inflammatory response and in certain processes associated with cell proliferation, the hypothesis has been put forward that the NSAIDs that are selective COX-2 inhibitors should theoretically be capable of maintaining NSAID therapeutic properties but also have fewer adverse side effects due to the maintenance of prostaglandin production at normal physiological levels. CURRENT KNOWLEDGE AND KEY POINTS: The hypothesis of COX isoenzyme selectivity has led to a proposed classification for COX inhibitors: 1) COX-1 selective inhibitors (low-dosage aspirin); 2) COX non-selective inhibitors (the majority of classified NSAIDs, which when administered over the long term, e.g., in cases of rheumatoid arthritis, cause duodenal ulcers in 20% of cases and gastric hemorrhage in 1-4% of cases/year); 3) COX-2 preferential inhibitors (meloxicam and nimesulide, which have fewer gastric side effects than standard NSAIDs, but which are not risk-free at high doses); 4) COX-2 selective inhibitors (celecoxib and rofecoxib). Preliminary clinical studies have shown that COX-2 selective inhibitors are as efficient as standard NSAIDs and have fewer adverse digestive side effects, thereby confirming the interest of this proposed classification. In the UK, the aforementioned studies have led to the commercialization of rofecoxib for the treatment of pain and osteoarthritis, while celecoxib has been introduced in medical practice in the USA and other countries for the treatment of rheumatoid arthritis and osteoarthritis. FUTURE PROSPECTS AND PROJECTS: Various epidemiological and laboratory studies have indicated that NSAIDs may be able to reduce the risk of cancer (colorectal cancer in particular) and Alzheimer's disease due to their inhibitory activity on COXs, especially COX-2. The therapeutic contribution of COX-2 specific inhibitors has to be more fully evaluated, particularly as these agents could delay the healing of duodenal ulcers and interfere with several COX-2-induced physiological functions. It is therefore suggested that until further information becomes available, this new class of NSAIDs should be used with caution in certain patient populations.
11466388 Evidence of IL-18 as a novel angiogenic mediator. 2001 Aug 1 Angiogenesis, or new blood vessel growth, is a key process in the development of synovial inflammation in rheumatoid arthritis (RA). Integral to this pathologic proliferation are proinflammatory cytokines. We hypothesized a role for IL-18 as an angiogenic mediator in RA. We examined the effect of human IL-18 on human microvascular endothelial cell (HMVEC) migration. IL-18 induced HMVEC migration at 1 nM (p < 0.05). RA synovial fluids potently induced endothelial cell migration, but IL-18 immunodepletion resulted in a 68 +/- 5% decrease in HMVEC migration (p < 0.05). IL-18 appears to act on HMVECs via alpha(v)beta(3) integrin. To test whether IL-18 induced endothelial cell tube formation in vitro, we quantitated the degree of tube formation on Matrigel matrix. IL-18, 1 or 10 nM, resulted in a 77% or 87% increase in tube formation compared with control (p < 0.05). To determine whether IL-18 may be angiogenic in vivo, we implanted IL-18 in Matrigel plugs in mice, and IL-18 at 1 and 10 nM induced angiogenesis (p < 0.05). The angiogenesis observed appears to be independent of the contribution of local TNF-alpha, as evidenced by adding neutralizing anti-TNF-alpha Ab to the Matrigel plugs. In an alternative in vivo model, sponges embedded with IL-18 or control were implanted into mice. IL-18 (10 nM) induced a 4-fold increase in angiogenesis vs the control (p < 0.05). These findings support a novel function for IL-18 as an angiogenic factor in RA and may elucidate a potential therapeutic target for angiogenesis-directed diseases.
9619890 Comparison of IgA-alpha1-antitrypsin levels in rheumatoid arthritis and seronegative oligo 1998 Apr Serum complexes between IgA and alpha1-antitrypsin (IgA alpha1AT) have been found at raised levels in early rheumatoid arthritis (RA), where they appear to be associated with more erosive disease. We have now measured the levels of these complexes in the sera and synovial fluid of patients with RA and seronegative oligoarthritis to determine whether there is a relationship between complex levels and joint inflammation, and if bacterial stimulation of the mucosa is associated with complex formation in seronegative oligoarthritis. IgA-alpha1AT complexes were measured in patients with RA (n = 75) and seronegative oligoarthritis, with or without definite reactive arthritis (n = 28), using a newly developed sandwich ELISA. The results were compared with serum levels from healthy volunteers (n = 30). IgA and alpha1AT were also measured using ELISA and radial immunodiffusion (RID) techniques, respectively. IgA-alpha1AT complex levels in the sera of RA patients [mean = 25.6 arbitrary units (au)] were significantly higher (P = 0.0034) than those in patients with seronegative oligoarthritis (mean = 12.36 au) and healthy controls (mean = 8.08 au). There was no evidence for the inflamed joint being the source of IgA-alpha1AT complexes since synovial fluid levels were lower than corresponding serum levels, although higher amounts were found in RA than seronegative oligoarthritis (12.84 au vs 4.11 au, P = 0.01). Serum levels of IgA and alpha1AT were similar in RA and seronegative oligoarthritis patients, and were higher than in normals. There was a significant correlation between complex and serum IgA levels in RA (r = 0.49, P < 0.001) and seronegative oligoarthritis (r = 0.53, P < 0.001) patients, although no relationship was found with alpha1AT levels. There was no correlation with other markers of the acute-phase response (C-reactive protein, erythrocyte sedimentation rate), nor with any clinical markers. In RA patients, serum complex levels were significantly higher in seropositive than seronegative patients (30.75 vs 16.48 au, P = 0.03), and we have demonstrated that a small amount of alpha1AT may be complexed with IgA rheumatoid factor. Our data suggest that the formation of IgA-alpha1AT complexes is not associated with inflammation per se, and does not appear to be related to bacterial stimulation of the mucosal immune system in patients with seronegative oligoarthritis.
11153989 Infection after shoulder arthroplasty. 2001 Jan Between 1972 and 1994, 2279 patients underwent primary shoulder arthroplasty (2512 shoulders) and 194 patients underwent revision shoulder arthroplasty (222 shoulders) at the authors' institution. Of these, 18 patients with primary shoulder arthroplasties (19 shoulders) and seven patients with revision shoulder arthroplasties (seven shoulders) were diagnosed with deep periprosthetic infection. Additionally, during this period, seven patients (seven shoulders) with primary shoulder arthroplasties and one patient (one shoulder) with a previously revised shoulder arthroplasty were referred to the authors' institution for treatment of deep periprosthetic infection. Two patients (two shoulders) were excluded because of incomplete medical records and with component removal performed elsewhere. The average time from arthroplasty to the diagnosis of infection was 3.5 years (range, 0-14.8 years). The patients were divided into four groups on the basis of treatment. Group I comprised 20 patients (21 shoulders) who underwent resection arthroplasty. Six of the 21 shoulders had additional episodes of infection. Group II comprised six patients (six shoulders) who underwent debridement and prosthetic retention. Three of the six shoulders failed this treatment with subsequent reinfection and underwent a resection arthroplasty. Group III comprised two patients (two shoulders) who had removal of the prosthesis, debridement, and immediate reimplantation. One patient underwent resection arthroplasty 9 months after direct exchange because of reinfection. Group IV comprised three patients (three shoulders) who had removal of the prosthesis, debridement, and delayed reimplantation. Reinfection has not occurred in any of these patients. At final followup, patients with a prosthesis in situ had better pain relief and shoulder function than patients treated with resection arthroplasty. Delayed reimplantation may offer the best hope for pain relief, eradication of infection, and maintenance of shoulder function.
9561020 [Differential diagnosis of fever of unknown origin. A case of adult onset Still disease]. 1998 Jan BACKGROUND: A case of Still's disease in the adult, an uncommon seronegative rheumatoid arthritis-like disease with prominent systemic features is reported. This case did not show the typical clinical features and appeared like a fever of unknown origin. CASE REPORT: A 60 year-old female was admitted to the hospital for high fever occurred two months before without other important clinical symptoms and signs. Laboratory tests and morphologic images were negative for infectious diseases, tumours and immunological disorders. The course of the disease worsened and an hepatic failure threatened the patient life. The onset of many other typical clinical features, i.e. joints pain, characteristic skin rash, splenomegaly, throat pain, serositis and weight loss, led us to make a sure diagnosis and to save the patient with steroid therapy.
10513808 Differential regulation of rheumatoid synovial cell interleukin-12 production by tumor nec 1999 Sep OBJECTIVE: To investigate the roles of tumor necrosis factor alpha(TNFalpha) and the CD40-CD154 interaction in interleukin-12 (IL-12) production by rheumatoid synovial cells (SC). METHODS: Levels of IL-12 (p40 and p70) in synovial tissue and culture supernatants of SC from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS) were assayed by enzyme-linked immunosorbent assay. Effects of anti-CD154 and anti-TNFalpha antibody on spontaneous and lipopolysaccharide (LPS)-stimulated IL-12 production by SC were examined. Effects of immobilized anti-CD3 treatment and depletion of CD4+ T cells on IL-12 production were also tested. CD154 expression by synovial T cells and intracellular IL-12 production during culture were analyzed by flow cytometry. RESULTS: IL-12 p40 and p70 levels in RA synovial tissue and spontaneous IL-12 p40 production by SC from RA patients were significantly higher than the levels in OA and AS patients. Spontaneous IL-12 production by SC from RA patients significantly decreased after depletion of CD4+ T cells from SC or after application of anti-CD154 antibody, but not by treatment with anti-TNFalpha antibody. Anti-CD3 antibody stimulation increased spontaneous IL-12 p40 production and CD154 expression by synovial T cells. The increment of IL-12 p40 production by anti-CD3 was abrogated by anti-CD154 antibody. IL-12 p40 production was also increased by LPS stimulation. LPS-stimulated IL-12 production was inhibited by anti-TNFalpha antibody, but not by T cell depletion and anti-CD154 antibody treatment. The TNFalpha inhibitor rolipram inhibited LPS-stimulated IL-12 p40 production by RA SC more strongly than spontaneous production. TNFalpha restored LPS-stimulated IL-12 production that had been inhibited by rolipram. CONCLUSION: IL-12 production in RA is regulated by 2 different pathways. One pathway is T cell dependent, predominantly through a CD40-CD154 interaction, while the other is T cell independent, mediated through TNFalpha. Inhibition of IL-12 production by interference with CD40-CD154 interaction and TNFalpha production may be a potential therapeutic strategy for treating RA.
11299060 B lymphocyte involvement in ankylosing spondylitis: the heavy chain variable segment gene 2001 The synovial membrane (SM) of affected joints in ankylosing spondylitis (AS) is infiltrated by germinal center-like aggregates (foci) of lymphocytes similar to rheumatoid arthritis (RA). We characterized the rearranged heavy chain variable segment (VH) genes in the SM for gene usage and the mutational pattern to elucidate the B lymphocyte involvement in AS. Cryosections from an AS-derived SM were stained for B and T lymphocytes. B cells were isolated from different areas of a focus. The rearranged VH genes were amplified by semi-nested polymerase chain reaction (PCR) using oligonucleotides specific for the six different VH families and heavy chain joining segments (JHs). PCR products were cloned and sequenced.Fifty-nine of 70 different heavy chain gene rearrangements were potentially functional. Most of the rearranged genes were mutated (range, 1-15%). Thirty of 70 products had a mutational pattern typical for antigen selection. Most of the rearranged VH genes belonged to the VH3 family (54%), consistent with data from healthy donors and patients with RA, while VH4 genes, in contrast to RA, were identified less frequently (10%) and VH5 genes were over-represented (11%). In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34 were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used (11%). One VH1-derived and one VH3-derived B cell clone were expanded. CDR3 were shorter and more variable in length than in RA. Comparable with RA and reactive arthritis, there is a biased repertoire of selected VH genes, whereas the panel of represented genes is different and less clonal expansion was observed.
11509092 Micronutrients: oxidant/antioxidant status. 2001 May Potentially damaging species (reactive oxygen, nitrogen and chlorine species) arise as by-products of metabolism and as physiological mediators and signalling molecules. Levels of these species are controlled by the antioxidant defence system. Several components of this system are micronutrients (e.g. vitamins C and E) or are dependent upon dietary micronutrients (e.g. CuZn and Mn superoxide dismutase). The antioxidant defences act as a coordinated system where deficiencies in one component may affect the efficiency of the others. Oxidative stress may be an important factor in infection if micronutrients are deficient.
9557878 Inflammation-induced expression of sialyl LewisX is not restricted to alpha1-acid glycopro 1998 Feb Acute and chronic inflammation-induced expression of sialyl LewisX has already been shown to occur on alpha1-acid glycoprotein. We now demonstrate that this phenomenon is not restricted to alpha1-acid glycoprotein but also occurs on two other acute-phase proteins. ie on alpha1-antichymotrypsin and on haptoglobin. The level of expression of sialyl LewisX on these proteins was lower than on alpha1-acid glycoprotein, in all likelihood because alpha1-acid glycoprotein is the only acute-phase protein containing tetraantennary glycans. No expression of sialyl LewisX was detectable on alpha1-protease inhibitor, a protein with a high diantennary glycan content. Non-sialylated LewisX was not detectable on these major acute-phase proteins in any of the conditions studied. This indicates that the majority of the a3-linked fucose residues are present as sialyl LewisX on alpha1-acid glycoprotein, alpha1-antichymotrypsin and haptoglobin. The absolute contribution to the total phenotype in plasma of protein containing this determinant in a multivalent form was highest for alpha1-acid glycoprotein. This leads us to propose that alpha1-acid glycoprotein is, among the acute-phase proteins studied, the one with the highest potential for interference with the extravasation of leukocytes by binding to the selectins.
11892915 VX-745. Vertex Pharmaceuticals. 2001 Aug VX-745, a lead anti-inflammatory candidate, small-molecule inhibitor of mitogen-activated protein kinase (MAPK), is under development by Vertex Pharmaceuticals Inc in association with Kissei Pharmaceutical Co Ltd for the potential treatment of rheumatoid arthritis (RA) [214928]. VX-745 was introduced by Vertex as a potential antiinflammatory drug for the treatment of RA in a pilot phase II trial initiated in November 1999 [346067]. In June 2000, phase II trials were still ongoing [371819] and in January 2001, Vertex initiated a randomized, double-blind, placebo-controlled phase II trial in adult patients with RA, with the objective of evaluating clinical response rates, self-reported patient health assessments and pharmacodynamic markers of drug activity [395083]. During the 33rd Annual Meeting of the American Chemical Society in May 2000, VX-745 was reported to be active against several isotypes of p38 MAPK, including p38alpha, p38beta and p38gamma [368149]. The targeting of p38 MAPK by VX-745 was associated with the suppression of the release of inflammatory mediators, including interleukin (IL)-1beta and tumor necrosis factor (TNF)alpha, known to be implicated in exacerbating the pathophysiology of RA [273648], [368149], [371548], [372054], [408713].
11130454 Molecular mimicry: a critical look at exemplary instances in human diseases. 2000 Apr Molecular mimicry, the concept that antigenic determinants of microorganisms resemble antigenic determinants of the host, is frequently cited as a plausible mechanism to account for the association of infection and autoimmune disease. Based on analogous sequences of amino acids or on cross-reactions of monoclonal antibodies, numerous examples of such mimicry have been reported. There are, however, no clear examples of a human disease caused by molecular mimicry.
10380836 The prevention of corticosteroid-induced bone loss with intermittent cyclical etidronate. 1999 A prospective, randomised, double-blind, placebo controlled primary prevention trial was undertaken in 28 patients commencing low to moderate doses of corticosteroids for the first time. Patients were randomised to intermittent cyclical etidronate (400 mg daily for 2 weeks) and calcium (500 mg daily for 11 weeks) or intermittent cyclical placebo with calcium. After 52 weeks of treatment, lumbar spine BMD increased by 1.8% in the etidronate group, while it decreased by 3.7% in the placebo group. The differences in bone loss rate were statistically significant (p<0.01) at both 6 and 12 months. Similar trends were observed at the proximal femur, but differences were not statistically significant. These results suggest that intermittent cyclical etidronate therapy is effective in the primary prevention of corticosteroid-induced bone loss at the lumbar spine.
11339517 Meloxicam in acute episodes of soft-tissue rheumatism of the shoulder. 2001 Mar OBJECTIVE: This double-blind, randomised trial compared the efficacy and safety of meloxicam vs piroxicam in patients with soft-tissue rheumatism of the shoulder. SUBJECTS: 599 outpatients at 88 centres in 9 countries. TREATMENT AND METHODS: Oral meloxicam 7.5 mg, meloxicam 15 mg or piroxicam 20 mg, once-daily for 14 days. The primary efficacy endpoint was the assessment of pain on day 7 relative to day 1. RESULTS: Once-daily treatment with meloxicam 7.5 or 15 mg was comparable to piroxicam. A significantly higher proportion of meloxicam-treated patients had pain relief within day 1 or day 3. The incidence and intensity of adverse events was comparable between the treatment groups, although fewer patients in the meloxicam groups withdrew due to adverse events. There were no apparent differences between the two meloxicam doses. CONCLUSIONS: Treatment with meloxicam was at least as effective as treatment with piroxicam, with a favourable global tolerability for both doses of meloxicam.
9418628 Periprosthetic fractures of the tibia associated with total knee arthroplasty. 1997 Dec One hundred two periprosthetic tibial fractures associated with total knee arthroplasty were identified in 29 men and 73 women. Eighty-three fractures occurred postoperatively, and 19 occurred intraoperatively. Fractures were classified into four types based on location and proximity to the prosthesis. There were 61 Type I fractures, occurring at the tibial plateau; 22 Type II fractures, occurring adjacent to the prosthetic stem; 17 Type III fractures, occurring distal to the prosthetic stem; and two Type IV fractures, involving the tibial tubercle. Fracture types were additionally classified by whether the prosthesis appeared to be radiographically well fixed (A) or loose (B) at the time of fracture, or whether the fracture occurred intraoperatively (C). The majority of postoperative Types I and II fractures were Types IB and IIB, and these were treated most successfully with revision surgery. Types IIA, IIIA, and IVA fractures were managed successfully by the usual principles of tibial fracture treatment. Type IC fractures usually were managed by intraoperative fixation, Type IIC by bone grafting or external immobilization and weightbearing restrictions, and Type IIIC by conventional fracture management. This classification system provides a guide for determining the appropriate treatment for tibial fractures associated with total knee arthroplasty.