bluuebunny/crossref_metadata_2025_split huggingface dataset:
The comparative efficacy and toxicity of second‐line drugs in rheumatoid arthritis results of two metaanalyses
Authors: Felson David T. , Anderson Jennifer J. , Meenan Robert F. 
Published: February 2007

AbstractWe performed 2 metaanalyses of placebo‐controlled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D‐penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second‐line drugs most commonly used to treat rheumatoid arthritis (RA). For the efficacy study, we applied a set of inclusion criteria and focused on trials which provided information on tender joint count, erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials that contained 117 treatment groups of interest, and for each drug, we combined the treatment groups. For each outcome, results showed that AUR tended to be weaker than other second‐line drugs. The results of the 3 outcome measures were synthesized into a composite measure of outcomes, and AUR was significantly weaker than MTX (P = 0.006), injectable gold (P < 0.0001), DP (P < 0.0001), and SSZ (P = 0.009) and was slightly, but not significantly, weaker than antimalarial agents (P = 0.11). We also found heterogeneity among antimalarial agents, in that patients treated with chloroquine did better than those treated with hydroxychloroquine. We found little difference in efficacy between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial should contain at least 170 patients per treatment group to successfully differentiate between more effective and less effective (e.g., AUR) second‐line drugs. None of the reported interdrug comparative trials we reviewed were this large.For the toxicity study, our inclusion criteria captured RA trials which reported the proportion of patients who discontinued therapy because of drug toxicity and the total proportion who dropped out. We found 71 clinical trials that contained 129 treatment groups. The average proportion who dropped out and the average proportion who dropped out because of drug toxicity were computed for each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of them did so because of drug toxicity. Injectable gold had higher toxicity rates (P < 0.05) and higher total dropout rates (P < 0.01) than any other drug; 30% of goldtreated patients dropped out because of side effects versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low rates of toxicity; the rate for MTX was imprecise because of discrepancies between trials. Thus, of the commonly used second‐line drugs, AUR is the weakest, and injectable gold is the most toxic. Agents introduced in the future will be compared with these drugs. If a curative drug is not found, large multicenter trials or data synthesis from multiple drug trials may be necessary to identify new treatment regimens that have promise.
Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis
Authors: Pelletier Jean‐Pierre , Mineau FrançOis , Faure Marie‐Pierre , Martel‐Pelletier Johanne 
Published: February 2007

AbstractLevels of tissue inhibitor of metalloproteases (TIMP) and plasminogen activator (PA)/plasmin were measured and the distribution of PA was studied by immunohistochemical techniques in cartilage and synovium samples from dogs subjected to sectioning of the anterior cruciate ligament of their right knees and sham operation of their left knees (controls). Twenty‐three animals were divided into 3 groups and killed at 2, 4, or 8 weeks after surgery. The levels of PA and plasmin were found to be significantly elevated in the osteoarthritic (OA) knee cartilage and synovium at all times after surgery, except for levels of PA in the OA cartilage at 2 weeks. There was a positive correlation between the levels of PA and plasmin in the synovial membrane (r = 0.64, P < 0.001). In OA knees, the presence of high levels of total and active collagenase was detected in cartilage and in synovium. The levels of these 2 forms of collagenase showed a positive correlation both in cartilage (r = 0.65, P < 0.001) and in synovium (r = 0.77, P < 0.001). The levels of TIMP in cartilage from OA and sham operated knees were similar. Although the TIMP level was increased in the OA synovium, it was found only in trace amounts in cartilage. Immunohistochemical studies revealed that both forms of PA, urokinase‐type PA and tissue‐type PA, and TIMP were present in OA tissues. In the synovium, they were found mainly in monocyte/macrophages, synovial lining cells, and blood vessel cells. In OA cartilage, PA was present only at the superficial level in chondrocytes and in cartilage matrix, whereas TIMP was present in chondrocyte lacunae throughout the full thickness of the cartilage. TIMP was also detected in the superficial level of cartilage from sham operated knees. The results of this study indicate that in OA tissues, there are conditions that favor the synthesis and activation of metalloproteases. PA and plasmin are likely to play an important role in the physiologic activation of metalloproteases, although they are probably not the only system involved in this process. The lack of increased TIMP levels in the OA cartilage, in the presence of increased metalloprotease activity, is also a possible contributing factor in the enzymatic degradation of this tissue.
Specificity of antibodies to type II collagen in rheumatoid arthritis
Authors: Terato Kuniaki , Shimozuru Yasunori , Katayama Kou , Takemitsu Yoshiharu , Yamashita Izumi , Miyatsu Makoto , Fujii Katsuyuki , Sagara Mitsusada , Kobayashi Shiegeto , Goto Makoto , Nishioka Kusuki , Miyasaka Nobuyuki , Nagai Yutaka 
Published: February 2007

AbstractTo reassess the role of autoantibodies to type II collagen in the pathogenesis of diseases, we studied antibodies from patients with rheumatoid arthritis (RA) and from patients with relapsing polychondritis for species specificity and collagen type specificity, using an improved enzyme‐linked immunosorbent assay. Antibodies were found in the sera of 15% of the RA patients and 50% of the relapsing polychondritis patients, as well as in the cartilage of 69% of the RA patients examined. Reaction with both homologous and heterologous type II collagens was common. Analysis of 19 selected RA sera revealed that autoantibodies were generally associated with specific antibodies to some species of heterologous type II collagen. In contrast, antibodies found in 4% of the non‐RA controls were specific for either bovine or chick type II collagen. These findings indicate that autoantibody formation in RA and relapsing polychondritis may occur as a result of an immune response to heterologous type II collagen. However, since RA and relapsing polychondritis patient sera differed in their reactivity with the cyanogen bromide‐digested peptides, it is possible that the clinical manifestation of collagen autoimmunity might be influenced by the epitope specificity of the antibodies.
Use of molecular cloning methods to map the distribution of epitopes on topoisomerase I (Scl‐70) recognized by sera of scleroderma patients
Authors: D'Arpa Peter , White‐Cooper Helen , Cleveland Don W. , Rothfield Naomi F. , Earnshaw William C. 
Published: February 2007

AbstractWe report the initial molecular characterization of the autoimmune response against DNA topoisomerase I (topo I; Scl‐70). Sera from 36 patients with scleroderma and 4 healthy control subjects were studied using 6 subcloned portions of topo I. Twenty‐three sera recognized at least 2 independent epitopes on the molecule. Therefore, anti‐topo I, like other non‐organ‐specific autoantibodies characterized to date, is polyclonal and multifocal. The cloned protein should prove suitable for sensitive early detection of anti‐topo I in the clinical setting.
Synergistic, additive, and antagonistic effects of interleukin‐1β, tumor necrosis factor α, and γ‐interferon on prostaglandin e, hyaluronic acid, and collagenase production by cultured synovial fibroblasts
Authors: Meyer Frank A. , Yaron Ilana , Yaron Michael 
Published: February 2007

AbstractThe effects of binary combinations of the recombinant human cytokines, interleukin‐1β (rHuIL‐1β), tumor necrosis factor α (rHuTNFα), and γ‐interferon (rHuγ‐IFN) on the production of prostaglandin E (PGE), hyaluronic acid (HA), and collagenase by human synovial fibroblasts in culture were investigated. All 3 were stimulated by rHuIL‐1β and rHuTNFα alone, but not by rHuγ‐IFN. Stimulation with rHuIL‐1β and rHuTNFα occurred at femtomolar and picomolar concentrations, respectively, and maximal stimulation by rHuIL‐1β was several times greater than that by rHuTNFã. Stimulation of PGE and collagenase production with rHuIL‐1β or rHuTNFα was depressed by rHuγ‐IFN, depending on the concentration used. In contrast, stimulation of HA production with rHuIL‐1β or rHuTNFα was unaffected or increased somewhat with rHuγ‐IFN. Combinations of rHuIL‐1β and rHuTNFα had marked synergistic effects on PGE and collagenase production. However, when rHuIL‐1β effects were maximal, rHuTNFα had an additive effect. These cytokines had only additive effects on HA production, however, and when rHuIL‐1β effects were maximal, rHuTNFα produced no further stimulation. These data suggest that the secretory activities of synovial fibroblasts can be influenced by a combination of cytokines and is dependent on the type of cytokine present and its concentration.
Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma‐linolenic acid
Authors: Pullman‐Mooar Sally , Laposata Michael , Lem Diana , Holman Ralph T. , Leventhal Lawrence J. , Demarco Deborah , Zurier Robert B. 
Published: February 2007

AbstractWe administered borage seed oil (9 capsules/day) for 12 weeks to 7 normal controls and to 7 patients with active rheumatoid arthritis. The therapy provided 1.1 gm/day of γ‐linolenic acid (GLA). GLA administration resulted in increased proportions of its first metabolite, dihomo‐γ‐linolenic acid (DGLA), in circulating mononuclear cells. The ratios of DGLA to arachidonic acid and DGLA to stearic acid increased significantly in these cells. Significant reductions in prostaglandin E2, leukotriene B4, and leukotriene C4 produced by stimulated monocytes were seen after 12 weeks of GLA supplementation. The antiinflammatory effects of GLA administration observed in animal models, and the apparent clinical improvement experienced by 6 of 7 rheumatoid arthritis patients given borage seed oil in this open, uncontrolled study may be due in part to reduced generation of arachidonic acid oxygenation products.
Renal disease in chronic arthritis of childhood. A study of urinary N‐acetyl‐β‐glucosaminidase and β2‐microglobulin excretion
Authors: Malleson Peter N. , Lockitch Gillian , Mackinnon Murray , Mahy Marguerite , Petty Ross E. 
Published: February 2007

AbstractUrinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N‐acetyl‐β‐glucosaminidase and/or β2‐microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P < 0.0001). Abnormalities of either N‐acetyl‐β‐glucosaminidase or β2‐microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow‐acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflammatory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long‐term consequences of this abnormality remain to be elucidated.
D‐penicillamine‐induced lupus erythematosus
Authors: Enzenauer Raymond J. , West Sterling G. , Rubin Robert L. 
Published: February 2007

AbstractWe describe a patient who presented with polyarthritis, pleurisy, rash, and a positive antinuclear antibody result after 5 years of D‐penicillamine therapy. D‐penicillamine‐induced antinuclear antibodies were mainly high‐titer IgG directed against the (H2A‐H2B)‐DNA complex. Weak IgM activity with H1 and H2B was also observed. Withdrawal of D‐penicillamine therapy resulted in improvement in clinical symptoms and gradual resolution of serologic abnormalities.
Amyloidosis in behçet's syndrome
Authors: Yurdakul Sebahattin , Tüzüner Nüket , Yurdakul Ibrahim , Hamuryudan Vedat , Yazici Hasan 
Published: February 2007

AbstractWe investigated the frequency of amyloidosis in 99 consecutive patients (65 men and 34 women) with Behçet's syndrome. Rectal biopsies performed on all patients showed no amyloidosis by polarizing microscopy. The results of urinalyses were normal in all patients. Among 1,130 patients registered in our Behçet's syndrome outpatient clinic, 5 were found to have systemic amyloidosis, all of the AA type.
Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis
Authors: Fries James F. , Singh Gurkirpal , Lenert Leslie , Furst Daniel E. 
Published: February 2007

AbstractLevels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued.
Diffusing capacity of the lung and nifedipine in systemic sclerosis
Authors: Sfikakis Petros P. , Kyriakidis Michael , Vergos Constantine , Papazoglou Sotirios , Georgiakodis Fotis , Toutouzas Pavlos , Sfikakis Paul 
Published: February 2007

AbstractLung involvement in systemic sclerosis may be due in part to a functional abnormality of the pulmonary vasculature. To investigate the possible role of a pulmonary vasospastic process in this disorder, 21 non‐smoking patients who had no evidence of cardiac disease or pulmonary hypertension were evaluated with pulmonary function tests prior to administration of nifedipine, 30 minutes after a single oral dose of nifedipine (20 mg), and after 4 weeks of treatment with nifedipine (10 mg 3 times daily). Treatment with nifedipine did not significantly change any of the pulmonary function values, except for the carbon monoxide diffusing capacity (DLCO). The linear trend between the individual DLCO values at baseline and their changes immediately following the initial 20‐mg dose of nifedipine (r = −0.603, P = 0.02) and after 4 weeks of treatment (r = −0.636, P = 0.01) showed that the lower the DLCO value at baseline, the greater the improvement caused by nifedipine. These findings support the hypothesis of a potentially reversible pulmonary vasospasm in systemic sclerosis and suggest that nifedipine may be useful in the treatment of lung disease in these patients; however, further studies are needed.
Evidence for impaired t cell dna methylation in systemic lupus erythematosus and rheumatoid arthritis
Authors: Richardson Bruce , Scheinbart Lee , Strahler John , Gross Laura , Hanash Samir , Johnson Marcia 
Published: February 2007

AbstractProcainamide and hydralazine inhibit T cell DNA methylation and induce autoreactivity in cloned CD4+ T cells. These drugs also induce an autoimmune syndrome, suggesting a possible relationship between DNA hypomethylation, T cell autoreactivity, and certain autoimmune diseases. To test this relationship, DNA methylation was studied in T cells from patients with rheumatoid arthritis and patients with systemic lupus erythematosus, and was found to be impaired. These results support a relationship between DNA hypomethylation and some forms of autoimmune disease.
Spontaneous rheumatoid‐like arthritis in a line of mice sensitive to collagen‐induced arthritis
Authors: Bouvet Jean‐Pierre , Couderc Jacques , Bouthillier Yolande , Franc Brigitte , Ducailar Annie , Mouton Denise 
Published: February 2007

AbstractTwenty‐eight percent of 13‐month‐old male mice of the high antibody responder line of Biozzi's selection I (HI) spontaneously developed a long‐lasting inflammatory arthritis. This disease was clinically and histologically similar to human rheumatoid arthritis. The synovium of joints and some tendons was hypertrophied, with thickening of the synovial cell layer and infiltration by polymorphonuclear and mononuclear leukocytes. In some cases, synovial pannus formation led to destructive damage of articular cartilage and bone. Rheumatoid factor and antinuclear, anti‐DNA, and anti‐type II collagen (CII) antibodies were often found in the sera of both arthritic mice and clinically normal littermates. The presence of CII autoantibodies in this line of mice suggests that a potentially harmful anti‐CII T cell autoimmunity can also develop spontaneously and lead to joint damage. Moreover, HI mice are also susceptible to collagen‐induced arthritis, while a closely related mouse line (HII) is resistant to both diseases. These data support the hypothesis that collagen‐induced arthritis is pathogenetically related both to this spontaneous arthritis and to rheumatoid arthritis.
Treatment of psoriatic arthritis with oral 1,25‐dihydroxyvitamin D3: a pilot study
Authors: Huckins David , Felson David T. , Holick Michael 
Published: February 2007

AbstractWe conducted a 6‐month open‐label trial in which 10 patients with active psoriatic arthritis received 2 m̈g of oral 1,25‐dihydroxyvitamin D3 daily. Statistically significant improvement was noted in the tender joint count and physician global impression. Of these 10 patients, 4 had substantial (≥50%) improvement, and 3 had moderate (≥25%) improvement in the tender joint count. Two patients were unable to receive therapeutic doses because of hypercalciuria. High‐dose vitamin D may be a useful therapeutic agent for psoriatic arthritis.
Clinical and pathologic studies of twenty‐six patients with penetrating foreign body injury to the joints, bursae, and tendon sheaths
Authors: Reginato Antonio J. , Ferreiro Jose Luis , RiesterO'Connor Carolyn , Barbasan Ceferino , Arasa Javier , Bednar John , Soler Juan 
Published: February 2007

AbstractForeign body synovitis has been neglected in the rheumatology literature. We describe 26 patients in whom arthritis, bursitis, or tenosynovitis appeared within 1 day to 7 years after an initial injury by a penetrating foreign body. Twenty‐two patients presented with acute synovitis, which was followed by chronic or recurrent inflammation mimicking septic arthritis, osteomyelitis, monarticular juvenile rheumatoid arthritis, bone tumor, or apatite deposition disease. Foreign bodies were not seen in 5 inflammatory synovial fluids studied, but were seen in the synovium or periarticular tissues of 17 patients. Excisional biopsy was required in most patients for precise diagnosis and treatment.
Autoantibody to th ribonucleoprotein (nucleolar 7–2 rna protein particle) in patients with systemic sclerosis
Authors: Okano Yutaka , Medsger Thomas A. 
Published: February 2007

AbstractWe studied sera of 371 consecutive new patients with systemic sclerosis (SSc; scieroderma) who were first evaluated during 1984–1988. All sera were tested for antinuclear antibodies by immunofluorescence staining using HEp‐2 cells as substrate. We excluded 219 sera showing dark nucleoli and screened for antibodies to Th in the remaining 152 sera by immunoprecipitation of a 32P‐labeled HeLa cell extract. Fifteen (4.0%) of 371 sera were anti‐Th+. Anti‐Th antibodies were present in 14 (8.4%) of 167 SSc patients with limited cutaneous involvement, in 1 of 167 with diffuse cutaneous involvement, and in 0 of 37 with SSc overlap syndrome. Among 244 controls with other connective tissue diseases, anti‐Th was detected in only 3 patients, all having primary Raynaud's phenomenon of 2 years duration. In the subgroup with SSc with limited cutaneous involvement, the 14 anti‐Th+ patients had a significantly greater frequency of puffy fingers, small bowel involvement, and hypothyroidism, and a significantly lower frequency of arthralgia and/or arthritis. Their cumulative survival rate from the time of onset of symptoms was lower than that for anti‐Th— patients (78% versus 91% at 10 years), primarily due to 3 deaths from pulmonary arterial hypertension (2 from primary pulmonary hypertension and 1 from pulmonary hypertension secondary to pulmonary interstitial fibrosis). Serum anti‐Th antibodies are present almost exclusively in patients with SSc with limited cutaneous involvement or in those with primary Raynaud's phenomenon whose disease may evolve to SSc with limited cutaneous involvement, and these antibodies may identify those patients who are at greater risk for reduced survival.
Increased expression of type VI collagen genes in systemic sclerosis
Authors: Peltonen Juha , Kähäri Leena , Uitto Jouni , Jimenez Sergio A. 
Published: February 2007

AbstractThe expression of type VI collagen genes in affected skin from patients with systemic sclerosis (SSc) was examined by in situ hybridizations with a human α2(VI) collagen sequence‐specific complementary DNA. Five patients with diffuse, rapidly progressive SSc of recent onset (less than 12 months) were studied. The results showed increased expression of α2(VI) collagen messenger RNA transcripts in the skin of scleroderma patients compared with that in the skin of normal subjects. These findings indicate that alterations in the expression of type VI collagen genes, similar to those previously described for types I and III collagen, are present in the affected skin of SSc patients. These alterations may result in excessive tissue accumulation of type VI collagen and may play a role in the progressive skin induration and sclerosis that are prominent features of SSc.
Androgen replacement therapy in male patients with rheumatoid arthritis
Authors: Cutolo Maurizio , Balleari Enrico , Giusti Massimo , Intra Ettore , Accardo Silvano 
Published: February 2007

AbstractA hypogonadic condition characterized by low serum testosterone levels has been identified in male patients with rheumatoid arthritis (RA). Seven men with active RA were treated daily for 6 months with oral testosterone undecanoate plus a nonsteroidal antiinflammatory drug in an attempt to evaluate the immunologic response, the overall clinical response, and the sex hormone response to such replacement therapy. At the end of the 6 months, there was a significant increase in serum testosterone levels (P < 0.05), an increase in the number of CD8+ T cells, and a decrease in the CD4+ :CD8+ T cell ratio. The IgM rheumatoid factor concentration decreased significantly (P < 0.05). There was a concurrent significant reduction in the number of affected joints (P < 0.05) and in the daily intake of nonsteroidal antiinflammatory drugs (P < 0.01). The well‐known immunosuppressive action of androgens probably contributed to our findings in these RA patients.