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ID PMID Title PublicationDate abstract
11695254 Pharmacokinetic and pharmacodynamic aspects of the ideal COX-2 inhibitor: a rheumatologist 2001 Nov The ideal cyclooxygenase-2-specific inhibitor (coxib) would demonstrate efficacy comparable or superior to the best non-steroidal anti-inflammatory drug (NSAID) and, in addition to being substantially less gastrotoxic than the safest conventional NSAID, would have limited or no cardiovascular or renal toxicity and be generally tolerated as well as placebo. The contribution of the pharmacokinetic properties of a coxib to achieving this goal has been overlooked to some degree for available coxibs. Maximizing synovial compartment exposure while minimizing systemic exposure may deliver tolerability benefits, particularly with respect to rates of hypertension and cardiovascular and thrombotic adverse effects.
9340956 [Hemochromatosis arthropathy--an early manifestation of genetic hemochromatosis]. 1997 May Recent studies have shown a high frequency of genetic hemochromatosis in the Caucasian population. In addition, the well known organ involvement of genetic hemochromatosis was evident; more than 50% of patients develop a typical arthropathy which may result in severe physical disability. Among approximately 5000 patients referred to the rheumatology outpatient clinics of Bad Nauheim and Frankfurt with different rheumatologic diagnoses, 11 patients with typical signs of hemochromatotic arthropathy were identified. In none of those cases had the diagnosis "genetic hemochromatosis" been previously established. These patients had been treated for rheumatoid arthritis and other rheumatologic disorders over several years. All showed severe organ dysfunction due to iron overload, resulting in a reduced life expectancy. This investigation shows that knowledge of the typical signs of hemochromatotic arthropathy could lead to an earlier diagnosis of genetic hemochromatosis which is necessary to prevent the complications of iron overload in those patients.
9113543 Effect of tourniquet use on blood loss and incidence of deep vein thrombosis in total knee 1997 Apr Tourniquet time and its relationship to blood loss and deep vein thrombosis were studied in 80 cases of unilateral total knee arthroplasty. These data were part of a prospective multicenter double-blind study on thromboprophylaxis for knee surgery. This study reports on the cases done at one institution in which the tourniquet was used in three different ways: group 1, no tourniquet use; group 2, limited tourniquet use for cementing time only; group 3, tourniquet use throughout the whole case. Blood loss was significantly related to tourniquet time (P = .0001). The incidence of deep vein thrombosis was not related to the tourniquet group (P = .9).
9048213 Molecular mechanisms involved in the association of HLA-DR4 and rheumatoid arthritis. 1997 Feb Susceptibility to developing rheumatoid arthritis (RA) maps to a highly conserved amino acid motif located in the third hypervariable region of different HLA-DRB1 chains. This motif, namely QKRAA, QRRAA, or RRRAA, helps the development of RA by an unknown mechanism. The QKRAA motif predisposes to more severe disease than the QRRAA or RRRAA motifs. The QKRAA motif carries particular properties: it is a strong B- and T-cell epitope, it shapes the T cell repertoire, it is overrepresented in protein databases, and it is a binding motif for bacterial and human 70-kDa heat-shock proteins. In this article, we propose different models to explain how the QKRAA motif might contribute to RA.
10693878 Preference for nonsteroidal antiinflammatory drugs over acetaminophen by rheumatic disease 2000 Feb OBJECTIVE: Because there is controversy regarding the efficacy of acetaminophen in rheumatic diseases and because apparently safer nonsteroidal antiinflammatory drugs (NSAIDs) are being produced, we surveyed rheumatic disease patients about their preferences for these agents to determine the degree to which one type of therapeutic agent is preferred over the other. METHODS: In 1998, we surveyed by mailed questionnaire 1,799 patients with osteoarthritis (OA), rheumatoid arthritis, or fibromyalgia who were participating in a long-term outcome study. Patients who had taken acetaminophen rated the effectiveness of acetaminophen, compared its effectiveness with that of NSAIDs, and then rated their overall satisfaction with acetaminophen compared with NSAIDs when both effectiveness and side effects were considered. RESULTS: Two-thirds of study participants had taken acetaminophen. About 37% of patients who had taken acetaminophen found it to be moderately or very effective and about 63% indicated that it was not effective or was only slightly effective. One-fourth of the patients found acetaminophen and NSAIDs to be equally effective, but >60% found acetaminophen to be much less effective or somewhat less effective. About 12% preferred acetaminophen to NSAIDs. When both effectiveness and side effects were considered together, 25% of the patients had no preference, 60% preferred NSAIDs, and 14% preferred acetaminophen. CONCLUSION: There was a considerable and statistically significant preference for NSAIDs compared with acetaminophen among the 3 groups of rheumatic disease patients. Although this preference decreased slightly with age and was less pronounced in OA patients, the preference was noted among all categories of patients and was not altered by disease severity. If safety and cost are not issues, there would hardly ever be a reason to recommend acetaminophen over NSAIDs, since patients generally preferred NSAIDs and fewer than 14% preferred acetaminophen. If safety and costs are issues, then the recommendation of the American College Rheumatology that acetaminophen be tried first seems correct, since 38.2% found acetaminophen to be as effective or more effective than NSAIDs.
9858433 Kininogen-kallikrein-kinin system in plasma and saliva of patients with Sjögren's syndrom 1998 Dec OBJECTIVE: To evaluate variables of the kininogen-kallikrein-kinin system (KKKS) simultaneously in plasma and saliva of patients with Sjögren's syndrome (SS). METHODS: We studied a group of 20 female patients with SS aged 37-75 years, 7 with primary SS (SS1) and 13 with SS secondary to rheumatoid arthritis (SS2), and 20 healthy individuals. Total kininogen and high and low molecular weight kininogen (HKg and LKg, respectively) levels were evaluated by ELISA. The activity of plasma and tissue kallikreins was determined by enzyme activity on selective chromogenic substrates. RESULTS: The plasma levels of total kininogen, HKg, and LKg, and the activity of plasma kallikrein observed in patients were not significantly different from controls. The tissue kallikrein-like activity in plasma and the active tissue kallikrein in saliva were significantly increased in patients with SS, whereas the total salivary tissue kallikrein activity in patients was not significantly different from controls. The concentration of protein in the saliva of patients was significantly increased, and a positive correlation between salivary protein levels and the active tissue kallikrein was observed. CONCLUSION: Comparisons between the total and the active tissue kallikrein in saliva of patients with SS showed that most of the tissue kallikrein was in its active form. In addition, we observed a concomitant increase of the tissue kallikrein-like activity in plasma. These results suggest increased activation of the KKKS in plasma and saliva of patients with SS.
10946307 Reduction of inflammatory cytokines and prostaglandin E2 by IL-13 gene therapy in rheumato 2000 Sep 1 The rheumatoid arthritis (RA) joint is characterized by an inflammatory synovial pannus which mediates tissue destruction. IL-13 is a cytokine that inhibits activated monocytes/macrophages from secreting a variety of proinflammatory molecules. The aim of this study was to examine whether gene therapy-delivered IL-13 could reduce the production of key proinflammatory mediators in RA synovial tissue (ST) explants. Adenoviral vectors encoding the genes for human IL-13 (AxCAIL-13) and bacterial beta-galactosidase were generated and examined for protein production. Vectors were used to infect RA ST explants and RA synovial fibroblasts, and conditioned medium (CM) was collected at various times for analysis by ELISA and competitive immunoassay. AxCAIL-13 decreased the production of RA ST explant proinflammatory IL-1beta by 85% after 24 h. Likewise, TNF-alpha levels were decreased by 82 and 75% whereas IL-8 levels were reduced 54 and 82% after 24 and 48 h, respectively, in RA ST explant CM. Monocyte chemotactic protein-1 concentrations were decreased by 88% after 72 h in RA ST explant CM. RA ST explant epithelial neutrophil-activating peptide-78 concentrations were decreased 85 and 94% whereas growth-related gene product-alpha levels were decreased by 77 and 85% at 24 and 48 h, respectively, by AxCAIL-13. Further, IL-13 significantly decreased PGE2 and macrophage inflammatory protein-1alpha production. These results demonstrate that increased expression of IL-13 via gene therapy may decrease RA-associated inflammation by reducing secretion of proinflammatory cytokines and PGE2.
9061460 Investigation into the concanavalin A reactivity, fucosylation and oligosaccharide microhe 1997 Jan 24 alpha 1-Acid glycoprotein (AGP) exists as an heterogeneous population of glycosylated variants (glycoforms) in plasma. The concentration of AGP increases some 2-5 fold in certain pathophysiological states exemplified by the chronic inflammatory disease, rheumatoid arthritis (RA). Moreover, the expressed glycosylation pattern alters in such conditions, indicating functional significance that is likely to be related to the oligosaccharide heterogeneity. We have investigated the heterogeneity of AGP glycosylation using the technique of high pH anion-exchange chromatography (HPAEC). AGP was isolated from the blood of RA sufferers, partially separated by Concanavalin A (Con A) affinity chromatography into bound and non-bound fractions and was enzymatically deglycosylated. Chromatography on the pellicular HPAE resin at pH 13 separated the released oligosaccharides and allowed a comparison of profiles in terms of branching and fucosylation. Results demonstrate an abnormal RA AGP glycosylation, with a tendency towards tri- and tetra-antennary oligosaccharides and enhanced fucosylation, in addition to the possible existence of penta-sialylated RA AGP glycoforms.
9771211 Linkage of cytokine genes to rheumatoid arthritis. Evidence of genetic heterogeneity. 1998 Jun OBJECTIVE: To investigate linkage of candidate disease susceptibility genes to rheumatoid arthritis (RA) in affected sibling pair families stratified for specific clinical features. METHOD: Two hundred RA affected sibling pair families were genotyped for informative microsatellite markers mapping within or less than 3cM from: INF alpha, INF gamma, INF beta, IL1 alpha, IL1 beta, IL1R, IL2, IL6, IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, alpha 1 anti-trypsin, and alpha 1 anti-chymotrypsin, using fluorescence based automated technology. Linkage was examined by defining allele sharing sibling pairs. This was assessed by maximum likelihood-inheritance by descent methods. RESULTS: An increase in allele sharing was seen for IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INF gamma in sibling pairs with an affected male (LOD 0.96, p = 0.03) and most significantly for IL2 in sibling pairs where one or both were persistently seronegative (LOD 1.05, p = 0.02). CONCLUSION: Weak evidence of linkage of RA to IL5R, IFN gamma, and IL2 has been detected in clinical subsets of sibling pairs suggesting that RA is a genetically heterogeneous disease.
11307127 The efficacy of intra-articular analgesia after total knee arthroplasty in patients with r 2001 Apr The pain relief provided by intra-articular injection of morphine plus bupivacaine after total knee arthroplasty (TKA) plus partial synovectomy in patients with rheumatoid arthritis was compared with pain relief after TKA alone in patients with osteoarthritis. There were lower pain scores, a much smaller requirement for systemic analgesics, longer duration until the first requirement of systemic analgesics, and improvement in the range of motion of the knee joint in the patients who received intra-articular injection of analgesics. There was more pronounced postoperative analgesia in the patients with rheumatoid arthritis than in the patients with osteoarthritis in the study groups that received intra-articular injection of analgesics.
9635455 Cervicomedullary compression: an unrecognized cause of vocal cord paralysis in rheumatoid 1998 Jun Cervicomedullary compression (CMC) from traumatic, infectious, or congenital processes of the atlanto-axial joint is a known cause of vocal cord immobility. Cervicomedullary compression can also occur from destructive arthritic changes and inflammatory pannus formation at the occipito-atlanto-axial joint in patients with rheumatoid arthritis (RA). We present findings suggesting that CMC in patients with RA is an unrecognized cause of vocal cord immobility. Previously, vocal cord immobility in patients with RA has been assumed to be cricoarytenoid arthritis with joint fixation. We report 3 patients with RA and radiographically demonstrated CMC with vocal cord immobility. One patient had bilateral vocal cord immobility and airway obstruction; 2 patients had unilateral cord paralysis and contralateral paresis without airway compromise. All patients had myelopathy and neck pain in addition to brain stem symptoms. All patients underwent transoral-transpharyngeal decompression of the anterior craniocervical junction with subsequent posterior fusion. These patients demonstrated full return of vocal cord function within 3 months of decompression. We propose that CMC is a cause of vocal cord paralysis in patients with RA that may go unrecognized without appropriate imaging studies of the skull base and physician awareness of symptoms of occipito-atlanto-axial subluxation and/or basilar invagination with brain stem compression. Our results demonstrate that CMC in RA is a potentially reversible cause of vocal cord paralysis.
9259419 Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovia 1997 Aug OBJECTIVE: To establish whether the clinical efficacy of pulse methylprednisolone (MP; 1,000 mg intravenously) is related to the modulation of proinflammatory cytokines within the peripheral blood, synovial membrane, or synovial fluid compartments. METHODS: Eighteen patients with active rheumatoid arthritis (RA) were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients, 10 knees) were obtained before and at 4 and 24 hours after MP therapy. Interleukin-1beta (IL-1beta), IL-8, and tumor necrosis factor alpha (TNFalpha) were measured by enzyme-linked immunosorbent assay and biologic assays; prostaglandin E2 (PGE2) was measured by competitive radioimmunoassay. In 10 patients, arthroscopically directed synovial biopsies were obtained before and at 24 hours after treatment, at disease relapse (4 patients), and after retreatment (1 patient). Membranes were stained by immunohistochemical techniques with monoclonal antibodies against TNFalpha, IL-8, IL-1beta, and the IL-1 receptor antagonist protein (IL-1Ra). RESULTS: MP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of TNFalpha in the lining and sublining regions of the synovial membrane, as well as substantial decreases in the levels of TNFalpha in serum and synovial fluid. There was also reduced IL-8 expression in the synovial lining, as well as reduced synovial fluid IL-8 levels. No effect on synovial membrane IL-1beta and IL-1Ra or synovial fluid IL-1beta and PGE2 was found. CONCLUSION: MP therapy rapidly reduces IL-8 and TNFalpha levels in the synovial compartment, with cytokine changes in the serum and synovial fluid reflecting the changes in the synovial membrane. Alterations in TNFalpha expression in the synovial membrane correlated with clinical response to, and subsequent relapse after, MP therapy.
10566565 The safety profile, tolerability, and effective dose range of rofecoxib in the treatment o 1999 Oct Nonsteroidal anti-inflammatory drugs. (NSAIDs) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders. This 8-week, double-masked, placebo-controlled trial was undertaken to assess the safety profile, tolerability, and effective dose range of once-daily rofecoxib, a COX-2-specific inhibitor, in the treatment of rheumatoid arthritis (RA). After a 3- to 15-day washout of prior NSAID therapy, 658 patients were randomly allocated to receive placebo or rofecoxib 5 mg, 25 mg, or 50 mg once daily. Safety profile, tolerability, and efficacy were evaluated after 2, 4, and 8 weeks of therapy. Six hundred fifty-eight patients (168, 158, 171, and 161 in the placebo and 5-mg, 25-mg, and 50-mg rofecoxib groups, respectively) were enrolled at 79 clinical centers in the United States. Mean age was 55 years, mean duration of RA was 10 years, and 506 (77%) of the 658 patients were female. All groups had similar baseline demographic characteristics. Patients taking rofecoxib 25 and 50 mg showed significant clinical improvement compared with those taking placebo; 43.9% in the rofecoxib 25-mg group and 49.7% in the rofecoxib 50-mg group completed the treatment period and achieved an American College of Rheumatology 20 response (P = 0.025 and 0.001 vs. placebo, respectively). The 5-mg dose of rofecoxib did not differ significantly from placebo. Patients in the rofecoxib 25- and 50-mg groups showed significant improvement in key individual efficacy measurements, including patient global assessment of pain, patient and investigator global assessment of disease activity, and Stanford Health Assessment Questionnaire Disability Index (P<0.05 vs placebo). Compared with placebo, significantly fewer patients in the 25-mg and 50-mg rofecoxib groups discontinued therapy because of lack of efficacy (P = 0.02 and P = 0.032, respectively). Our results show that rofecoxib 25 and 50 mg once daily was effective and generally well-tolerated in patients with RA.
10493666 Prolactin locally produced by synovium infiltrating T lymphocytes induces excessive synovi 1999 Sep OBJECTIVE: To elucidate the role of prolactin (PRL) produced in joints as part of the pathological response of rheumatoid arthritis (RA), we studied PRL production and prolactin receptor (PRLR) expression in RA synovium and its effects on RA synovial cell functions. METHODS: Proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells was estimated by ELISA, Western blotting analysis, and zymography. Expression of PRLR by RA synovial cells and local production of PRL were estimated by reverse transcription polymerase chain reaction and immunohistochemical staining. RESULTS: PRL enhanced RA synovial cell proliferation. Production of proinflammatory cytokine and MMP was augmented and production of tissue inhibitor of metalloproteinases (TIMP)-1 was inhibited by PRL treatment of RA synovial cells, suggesting that PRL enhances total collagenase activity in the joints. PRLR was exclusively expressed on fibroblast-like synovial cells and lymphocytes infiltrating into the synovium in patients with RA. Both synovium infiltrating T lymphocytes and, to a lesser extent, fibroblast-like synovial cells synthesized PRL, suggesting that PRL acts as a paracrine as well as autocrine activator of RA synovial cell functions. Stimulation of synovial cells by PRL induced rapid translocation of STAT-5 from cytoplasm into nuclei of RA synovial cells, suggesting that transcriptional regulation of RA synovial cell functions by PRL affects STAT-5. Inhibitors of PRL release, such as bromocriptine, inhibited proliferation of proinflammatory cytokines and collagenases by RA synovial cells. CONCLUSION: Our findings emphasize the importance of PRL, locally produced by infiltrating T lymphocytes, for aberrant synovial cell functions in RA, and suggest possible clinical application of PRL inhibitors.
9044084 A rare case of embolizing cardiac tumor: rheumatoid nodule of the mitral valve. 1997 Jan We report the case of a 65-year-old woman with rheumatoid arthritis who was admitted with a stroke. Echocardiographic examination revealed a multilobule, highly mobile tumor on the posterior leaflet of the mitral valve. Surgical exploration showed a tumor infiltrating the valve, the annulus, and the adjacent left ventricular wall, which required complete valve resection. Histologic study demonstrated typical characteristics of a rheumatoid nodule.
10616232 Personality and social attitudes in chronic fatigue syndrome. 1999 Oct One hundred one chronic fatigue syndrome (CFS) patients attending a specialist CFS clinic were compared with 45 rheumatoid arthritis (RA) patients on a range of standardized questionnaire measures, to investigate whether CFS patients are characterized by particular personality traits or social attitudes. No differences were found between CFS and RA patients in measures of perfectionism, attitudes toward mental illness, defensiveness, social desirability, or sensitivity to punishment (a concept related to neuroticism), on either crude or adjusted analyses. Alexithymia scores were greater in the RA patient group (p<0.05). Social adjustment, based on subjective assessment of overall restriction in activities and relationship difficulties, was substantially poorer in the CFS group (p<0.001). This was highly associated with depressive symptoms, but remained significant even after adjusting for depressive symptomatology. There was no evidence from this study of major differences between the personalities of CFS patients and RA patients. The stereotype of CFS sufferers as perfectionists with negative attitudes toward psychiatry was not supported.
10832004 Peripheral and central nervous changes in patients with rheumatoid arthritis in response t 2000 Aug It has been observed that patients with rheumatoid arthritis (RA) respond differently to repetitive painful stimulation. The present study investigated whether this is related to the peripheral or central nervous nociceptive system. EEG-derived potentials and the negative mucosal potential (NMP) from the respiratory epithelium were recorded in response to painful intranasal stimulation with gaseous CO(2). Differences between groups (12 RA patients, 12 controls) were found when stimuli were presented at short intervals. While the NMP did not differ between groups, patients had larger cortical responses to the first stimuli of a series of painful stimuli. This may indicate that in RA central nervous changes of nociceptive processing are present.
9751468 Effects of intravenous regional administration of methylprednisolone plus mepivacaine in r 1998 To evaluate the subjective and objective response to intravenous regional administration of a glucocorticoid (IVRAG) on rheumatoid arthritis (RA), twenty RA-patients received, in a randomised, double-blind crossover and placebo-controlled fashion, either 50 mg methylprednisolone in mepivacaine 0.25% or mepivacaine (placebo) in one hand only using a Bier-block technique. The other hand was given the opposite. One week later the procedure was repeated but the previous placebo hand was now treated with the glucocorticoid. About 50% of the patients experienced a subjective improvement at 1 and 6 weeks. After one week a significant reduction was recorded in grip diastasis with no difference between the glucocorticoid and the placebo. In the other outcome measures (grip strength, handvolume, rest pain, and movement provoked pain) no differences were recorded between the glucocorticoid and placebo. At six weeks a significant reduction in grip diastasis and movement provoked pain as well as a significant increase in grip strength were noted. Hand volume was unchanged. IVRAG is a safe, easy and well-tolerated technique. The beneficial results are probably due to both a systemic and a regional effect. The findings of benefit in both hands at the end of one week seem to suggest that mepivacaine can give some short term improvement.
9418617 The Insall Award. Total knee replacement with posterior cruciate ligament retention in rhe 1997 Dec A series of patients with rheumatoid arthritis underwent total knee replacement with posterior cruciate ligament retention and was observed a minimum of 6 years and a mean of 8.2 years. A group of patients with osteoarthritis with an identical prosthesis and a group of patients with rheumatoid arthritis with a posterior stabilized implant served as controls. In the rheumatoid arthritis group with posterior cruciate ligament retention, there was an increased incidence in posterior instability and recurvatum deformity, resulting in an increased revision rate. Those patients undergoing revision for instability had a higher incidence of recurrent synovitis, and at revision the posterior cruciate ligament was grossly absent with a Grade 1 synovial reaction. In patients with rheumatoid arthritis undergoing total knee replacement, a posterior stabilized prosthesis rather than a posterior cruciate ligament sparing prosthesis should be used.
9805545 [Interstitial granulomatous dermatitis and paraneoplastic rheumatoid polyarthritis disclos 1998 Sep INTRODUCTION: Interstitial granulomatous dermatitis is a histological entity usually associated with systemic auto-immune conditions or malignant lymphoproliferation. Its spontaneous regression after surgical treatment of a lung cancer suggests an eventual paraneoplasic variant. OBSERVATION: A 62 year old male patient, a smoker, was hospitalized for weakness, pruritus and symmetrical arthritis of small and large joints. Numerous rheumatoid nodules were located on the extensor aspects of the involved joints. During hospitalization, he developed an inflammatory plaque located on a thigh, which showed histologic features consistent with the diagnosis of interstitial granulomatous dermatitis. He had elevated E.S.R., blood eosiniphilia, and the search for antinuclear antibodies and antineutrophilic leukocyte cytoplasm antibodies (ANCA), of the p-ANCA type, was positive. A lung C.T. scan showed a cavitary tumor. Surgical removal of this tumor evidenced a bronchial squamous cell carcinoma. Four week after surgery, clinical signs and eosinophilia disappeared. After 6 months, ANCA became undetectable. DISCUSSION: Parallelism between the evolution of the cutaneous and articular symptomatology and of the cancer are diagnosis of paraneoplastic rheumatoid arthritis and paraneoplastic interstitial granulomatous dermatitis. Paraneoplastic rheumatoid arthritis is very unusual and this is the first reported case of simultaneously occurring paraneoplastic interstitial granulomatous dermatitis.