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ID PMID Title PublicationDate abstract
10381046 Survivorship in a population based cohort of patients with Sjögren's syndrome, 1976-1992. 1999 Jun OBJECTIVE: Sjögren's syndrome (SS) has been associated with development of lymphoid malignancies and other significant medical complications, but the effect of SS on survival in a population based sample has not been reported. We analyzed survival in an incidence cohort of patients diagnosed with SS in residents of Olmsted County, Minnesota, USA, between 1976 and 1992. METHODS: All records of physician diagnosed SS were reviewed, as well as all records from patients diagnosed with xerostomia and keratoconjunctivitis sicca, and records of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. The case definition for SS required 2 of 3 criteria: keratoconjunctivitis sicca, xerostomia, or serologic abnormality. Confounding illnesses were excluded. All patients were white. RESULTS: Of the 74 cases of SS identified, 50 (67%) had primary SS and 24 (33%) secondary SS. An average of 7.2 years of followup was available for patients with primary SS and 9.9 years for patients with secondary SS. Compared with the general population, patients with SS had increased mortality (p = 0.04). When patients with primary and secondary SS were studied separately, increased mortality was found in patients with secondary SS (p < 0.005) but not primary SS (p = 0.86). CONCLUSION: In this population based cohort, patients with primary SS did not have increased mortality. However, mortality may have been increased in patients with secondary SS, the majority of whom had RA.
9196874 Pleurisy in primary Sjögren's syndrome: T cell receptor beta-chain variable region gene b 1997 Mar Pleurisy with or without effusion has not been considered to be associated with primary Sjögren's syndrome (SS), but rather to represent a manifestation of the underlying disorder, usually rheumatoid arthritis in secondary SS. We describe a patient with primary SS who presented with pleural effusions (PE) as an initial manifestation. Serological studies of paired serum and PE specimens demonstrated the occurrence of local immune reactions in the pleura, including the production of rheumatoid factor and anti-SS-A antibody, the formation of immune complexes, and activation of complement. In addition, the analysis of T cell receptor beta-chain variable (V beta) regions in the PE revealed the overexpression of a number of V beta gene products, including V beta 2 and V beta 13 that have previously been shown to be over-represented in the salivary glands of patients with SS. Thus, our report not only calls for an awareness of pleurisy as an extraglandular manifestation of primary SS, but suggests that a common biased T cell response might play a critical role in the pathogenesis of the glandular as well as extraglandular manifestations.
11161972 Modification of the Fc region of a primatized IgG antibody to human CD4 retains its abilit 2001 Feb Keliximab, a Primatized IgG1 CD4 mAb, was reconfigured to an IgG4 antibody. The gamma4 constant region was further modified by substituting glutamic acid for serine at position 235 in the CH2 domain (IgG4-E), to remove residual binding to Fcgamma receptors, and substitution of serine with proline at position 228 in the hinge region (IgG4-PE) for greater stability. Pharmacokinetic analysis in rats gave a t(1/2) of approximately 4 days for IgG4-E and 9 days for IgG4-PE, consistent with a greater stability of the IgG4-PE molecule. The effects on T cell subsets were assessed in chimpanzees given escalating doses of IgG4-PE: 0.05 mg/kg on Day 16, 1.5 mg/kg dose on Day 43, and 15 mg/kg on Day 85. Receptor modulation was observed at the two highest doses, but no depletion of T cells at any dose. The in vitro and in vivo results demonstrate the potential of this IgG4-PE mAb for use in human trials.
9489829 Divergent cytokine production profile in Behçet's disease. Altered Th1/Th2 cell cytokine 1998 Feb OBJECTIVE: To determine Th1/Th2 cell response cytokine production profile in Behçet's disease (BD). METHODS: Interleukin 2 (IL-2), interferon-gamma (IFN-gamma) and IL-12 (Th1 cell response), and IL-4, IL-10, and IL-13 (Th2 cell response) cytokine production from anti-CD3/anti-CD40 stimulated peripheral blood mononuclear cells (PBMC) were measured by ELISA. RESULTS: PBMC from patients with BD produced higher levels of IL-4, IL-10, and IL-13 (Th2 cell response), almost normal levels of IL-2 (Th1 cell response), but highly deficient IFN-gamma and IL-12 (Th1 cell response). The additions of exogenous recombinant IFN-gamma to the anti-CD3 stimulated PBMC dramatically changed this pattern with enhanced IL-12 and concomitantly decreased IL-4 and IL-10 production. CONCLUSION: The immune system in BD may be characterized by a divergent cytokine production profile of mixed Th1/Th2 (Th0) cell type; IFN-gamma is critical in modulating the IL-4, IL-10, and IL-12 cytokine network pathway in this disease.
9058670 Rheumatoid factor positive, oligoarticular onset juvenile rheumatoid arthritis. 1997 Mar We describe 2 children with oligoarticular onset juvenile rheumatoid arthritis (JRA) with early erosive disease. Both patients were rheumatoid factor (RF) positive, but neither had HLA-DR4. These findings suggest RF is associated with early erosive disease, independent of HLA-DR4. RF positive oligoarticular onset JRA should probably be recognized as a separate subgroup of JRA.
10360201 Stomatognathic function in juvenile rheumatoid arthritis and in developmental open-bite su 1999 Jan Patients affected with juvenile rheumatoid arthritis present clear radiological alterations of the condyles of the temporomandibular joint (TMJ) due to the inflammatory process, with a prevalence ranging from 17 percent to 63 percent. This work is a comparison between a group of subjects with juvenile rheumatoid arthritis presenting signs and symptoms of TMT dysfunction and a group of the same age not suffering from any rheumatic morbidity, but presenting an open bite > 3 mm. The aim is to verify whether the open bite can induce an alteration in mandibular function comparable to that observed in juvenile rheumatoid arthritis. Statistically significant difference is found in the juvenile rheumatoid arthritis group only regarding spontaneous and provoked muscle pain and the lateral opening deviations of the mouth, but mostly the two groups seem alike and present the same stomatognathic pattern.
11696466 Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib. 2001 Nov 6 BACKGROUND: In comparing aspirin, nonselective nonsteroidal antiinflammatory agents (NSAIDs), and cyclooxygenase (COX)-2 inhibitors, variation in platelet inhibitory effects exists that may be associated with differential risks of cardiovascular (CV) thrombotic events. Among the randomized, controlled trials with the COX-2 inhibitor rofecoxib, one study demonstrated a significant difference between rofecoxib and its NSAID comparator (naproxen) in the risk of CV thrombotic events. A combined analysis of individual patient data was undertaken to determine whether there was an excess of CV thrombotic events in patients treated with rofecoxib compared with those treated with placebo or nonselective NSAIDs. METHODS AND RESULTS: CV thrombotic events were assessed across 23 phase IIb to V rofecoxib studies. Comparisons were made between patients taking rofecoxib and those taking either placebo, naproxen (an NSAID with near-complete inhibition of platelet function throughout its dosing interval), or another nonselective NSAIDs used in the development program (diclofenac, ibuprofen, and nabumetone). The major outcome measure was the combined end point used by the Antiplatelet Trialists' Collaboration, which includes CV, hemorrhagic, and unknown deaths; nonfatal myocardial infarctions; and nonfatal strokes. More than 28 000 patients, representing >14 000 patient-years at risk, were analyzed. The relative risk for an end point was 0.84 (95% CI: 0.51, 1.38) when comparing rofecoxib with placebo; 0.79 (95% CI: 0.40, 1.55) when comparing rofecoxib with non-naproxen NSAIDs; and 1.69 (95% CI: 1.07, 2.69) when comparing rofecoxib with naproxen. CONCLUSIONS: This analysis provides no evidence for an excess of CV events for rofecoxib relative to either placebo or the non-naproxen NSAIDs that were studied. Differences observed between rofecoxib and naproxen are likely the result of the antiplatelet effects of the latter agent.
18031101 Risks and benefits of low-dosage cyclosporin in rheumatoid arthritis. 1997 May The effects of cyclosporin on the activity of rheumatoid arthritis have mainly been investigated in patients with active, refractory, long-standing disease. The data obtained in these trials suggest that cyclosporin is not only a symptomatic treatment for rheumatoid arthritis but can also be considered a disease-modifying antirheumatic drug (DMARD), since it seems to be capable of slowing the progression of cartilage and bone damage due to rheumatoid arthritis. The trials conducted so far have led to a better understanding of cyclosporin toxicity and, therefore, to better monitoring of patients in order to avoid it. The reasons for studying the role of cyclosporin in patients with early, active and potentially severe rheumatoid arthritis are the poor prognosis of the disease despite the use of the presently available DMARDs, and the hypothesis that the drug is more efficacious and better tolerated in early rheumatoid arthritis. A new classification of antirheumatic drugs proposes that disease-controlling antirheumatic therapies decrease inflammatory synovitis and prevent structural joint damage or significantly reduce its rate of progression. However, few existing drugs meet these criteria. The 12-month results of a disease-controlling antirheumatic therapy clinical trial with a blinded radiological end-point, named GRISAR (Gruppo Reumatologi Italiani Studio Artrite Reumatoide) comparing cyclosporin with conventional DMARDs in patients with early rheumatoid arthritis provide strong evidence that cyclosporin offers better control of ongoing joint damage than do conventional DMARDs.
10773968 Outcomes in patients with incipient undifferentiated arthritis. 2000 Jan OBJECTIVE: To determine outcomes in patients with onset within the last year of peripheral inflammatory arthritis that does not meet classification criteria for any specific disease. METHODS: Symptoms and laboratory tests were evaluated at baseline and 14 to 60 months later in 43 patients, 32 women and 11 men, with a mean age of 50 years. RESULTS: At baseline, a presumptive clinical diagnosis was made in 16 of the 43 patients. Diagnoses at last follow-up were undifferentiated inflammatory arthritis in seven cases, mild rheumatoid arthritis in 18, psoriatic arthritis in two, Sjögren's syndrome in two, lupus in one, and paraneoplastic syndrome in one. The remaining 12 patients were free of inflammatory joint symptoms; three had symptoms of osteoarthritis and nine were asymptomatic. Factors present at baseline and predictive of progression to definite rheumatoid arthritis were a positive test for rheumatoid factor, presence of an HLA DRB1*04 allele, and a presumptive clinical diagnosis of rheumatoid arthritis. CONCLUSION: 55% of our patients developed a specific inflammatory joint disease, and 42% developed rheumatoid arthritis, which was consistently mild. Resolution of all inflammatory joint symptoms occurred in 28% of cases. A number of clinical laboratory, and genetic findings of use for predicting the outcome of undifferentiated arthritis were identified.
24441205 Cognitive-behavioral therapy: a psychoeducational treatment approach for the American work 1998 Rheumatoid arthritis is a systemic autoimmune disorder affecting nearly 2.1 million Americans. This condition often leads to chronic pain, inflammation, joint destruction, feelings of helplessness, maladaptive coping, depression and activity limitations. For those individuals with rheumatoid arthritis and chronic arthritic pain, the role of the worker has become difficult to maintain. Research suggests that cognitive-behavioral intervention reduces chronic arthritic pain, decreases disease activity and improves coping skills in individuals with rheumatoid arthritis. To be effective, cognitive-behavioral techniques must be practiced on a regular basis. The literature suggests that the American worker with rheumatoid arthritis would greatly benefit from work-site wellness programs that provide cognitive-behavioral intervention as a 'reasonable accommodation'. Occupational therapy practitioners can help to advance the positive effects of this psychoeducational intervention by providing 'booster treatments' to clients after formal treatment sessions have ceased.
11605814 Clinical characteristics of juvenile rheumatoid arthritis in Taiwan. 2001 Sep This study aimed to investigate the clinical features of juvenile rheumatoid arthritis among Taiwan children. The medical records of 228 children who had juvenile rheumatoid arthritis treated in the Chang Gung Medical Center in Taiwan from 1978 through 1998 were retrospectively reviewed. A total of 146 boys and 82 girls (M:F ratio, 1.8:1) were included in this study. Clinical and laboratory data of these patients were collected from medical charts. Pauciarticular onset (56%) was the most common type of juvenile rheumatoid arthritis, followed by polyarticular (36%) and systemic (8%) type. The positive rate for rheumatoid factor, human leukocyte antigen B27, and antinuclear antibody were 9.2%, 55.2%, and 16.2%, respectively. Uveitis was observed in 5.7% of patients. Compared with previous reports in other regions and populations, remarkably different features of juvenile rheumatoid arthritis were found in this study, which included a higher prevalence among boys than girls, a high positive rate of human leukocyte antigen B27, and a low rate of uveitis.
23119817 Study of Auditory function in Rheumatoid Arthritis. 2001 Oct Rheumatoid Arthritis may affect the auditory function and is a subject of debate. The exact etiopathogenesis is not known. However there is evidence of rt of synovial joints of ossicles. Rheumatoid Arthritis may involve the Aoditory system by producing conductive hearing loss, abnormal otoadmittance and sensorineural hearing loss. Patients with pre-existing ear disease were not included in the study. In the present study, effcet of Rheumatoid Arthritis on auditory function is observed. The Study was carried out on 25 patients of classical or definite Rheumatoid Arthritis and 16 controls at M.Y. Hospital, Indore.
11096206 Psoriasis in a patient with juvenile rheumatoid arthritis. 2000 A 20-year-old woman had polyarticular-onset type of juvenile rheumatoid arthritis with a chronic and destructive course since 6 years of age. She had developmental retardation, deformity and disability. Asymptomatic erythematous scaly plaques developed on the trunk. A skin biopsy specimen revealed psoriasis. This is the first report of psoriasis developing in a patient with juvenile rheumatoid arthritis.
9309198 Cytokines in juvenile rheumatoid arthritis. 1997 Sep Most data concerning the role of cytokines in chronic arthritides have been obtained in adult rheumatoid arthritis. In this paper we review the available evidence regarding the role of the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor in juvenile rheumatoid arthritis, focusing in particular on the differences among the various onset types. Results from the analysis of cytokine expression may provide the basis for the use of specific anticytokine treatment. Recent clinical trials in adult rheumatoid arthritis have demonstrated the feasibility and clinical usefulness of these treatments.
9490502 [The interrelation of the expression of HLA class I and II proteins and of the costimulato 1997 It has been presumed that: 1) rheumatoid arthritis (RA) is a genuine model of activation of the peripheral natural killers (NK); 2) methods of NK separation can cause their activation, and therefore only peripheral mononuclear cells were used. The aim of this research was to study the role of cytolysis of HLA-I, HLA-DR, and costimulatory proteins CD11a and CD16 expressed on resting and activated peripheral NK cells. A total of 74 healthy volunteers (HV) and 74 RA patients were compared before corticosteroid or gold treatment. Two-colour immunofluorescence and cytofluorimetric analysis, cytotoxic test against the target K 562 cells (class I negative) before and after incubation of PMC with monoclonal antibodies (MoAB) to HLA-I (E3D8), HLA-DR (ICO-1), CD11 (ICO-11), PXx63 Ag8.653 as control, and also incubation with recombinant alpha 2-IFN were used. VEP-13 MoAB was used for CD16 determination. Compared with HV PMC, the RA PMC showed a statistically significant increase of activated NK lymphocytes (CD11a+DR+ and CD16+DR+ by 2.03 and 1.96 times, resp.), and increased level of expression of HLA-I, HLA-DR, and CD16 on CD11a+ lymphocytes, resulting in significantly diminished cytolytic activity (CA) by 1.9 times. A short-term incubation with alpha 2-IFN (100 U/ml, 1 h) increased the level of expression of HLA- and costimulatory proteins and the CA of the HV PMC, while the RA PMC did not react. HV peripheral NK are concluded to be mainly resting cells, and the RA peripheral NK are mainly the activated ones. Only using the level of expression of HLA-DR on CD11a lymphocytes, as a ranking criterion, allowed to reveal two types of correlation between the CA and immunocytological parameters of PMC. The first type: in HV, the CA correlated positively (P < 0.025) with the percentage of CD11a+CD16+, and with levels of expression of HLA-I (P < 0.025) and CD16 (P < 0.025) expressed on CD11a lymphocytes (5-9.5 MFI DR--the mean fluorescence intensity of HLA-DR). The second type: the CA positively correlated (P < 0.05) with the percentage of CD11a+CD16-, and with levels of expression of HLA-DR (P < 0.05) and CD11a (P < 0.05) expressed on CD11a lymphocytes (12.4-16 MFI DR). In RA patients with a "normal" density expression of HLA-DR on CD11a lymphocytes (up to 14 MFI) there exists a mixed type: the CA correlated positively (P < 0.05) with the percentage of CD11a+CD16+, and with levels of expression of HLA-DR (P < 0.05) and CD11a (P < 0.05) expressed on CD11a lymphocytes. In RA patients with a very high density expression of HLA-DR on CD11a lymphocytes (VH-DR group, 18-26 MFI) the CA correlated negatively with the percentage of CD11a+CD1 6+ (P < 0.05), and with levels of expression of HLA-DR (P < 0.025) and CD11a (P < 0.025) expressed on CD11a lymphocytes. The anti-HLA-I,-DR, -CD11a MoABs strongly inhibit the Ca in HV- and RA-PMC. However, in the VH-DR group the anti-DR MoAB stimulates the CA from 27.06 +/- 10.25 up to 41.69 +/- 14.23%. Thus, activated peripheral CD11a+CD16+ lymphocytes suppress the CA of other NK.
10608725 Thrombotic thrombocytopenic purpura in a patient with rheumatoid arthritis treated by plas 1999 Nov Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, and neurologic symptoms. TTP is associated with many diseases and several therapeutic drugs. We report the rare case of a patient with rheumatoid arthritis who developed TTP that was not associated with drug therapy, 18 months after the onset of rheumatoid arthritis. She recovered from the TTP following daily sessions of therapeutic plasma exchange (TPE) with fresh frozen plasma replacement and glucocorticoid therapy. Recent pathogenic mechanisms are reviewed as they relate to von Willebrand factor. In this report of the rare association of TTP with rheumatoid arthritis, an immediate relationship is likely because both are of an immune nature. Awareness of the possible development of TTP in rheumatoid arthritis is important for early diagnosis and treatment.
9746862 Pathogenesis and mechanisms of inflammation in the childhood rheumatic diseases. 1998 Sep The presence of CD4+ cells in the synovium of children with juvenile rheumatoid arthritis has led to the generally accepted hypothesis that aberrant activation or regulation of acquired immunity is central to the pathogenesis of this family of diseases; however, this hypothesis remains unproven, and, indeed, a specific role for T cells in the process of chronic synovitis in rheumatoid disease has yet to be identified for either adults or children. In contrast, processes associated with innate immunity are undeniably involved in the pathophysiology of chronic synovitis in both rheumatoid arthritis and juvenile rheumatoid arthritis. The presence of neutrophils in the synovial fluid, complement activation, and immune complex accumulation in the synovial fluid and serum all indicate an active inflammatory process. It is reasonable to hypothesize, therefore, that there are important clues to the cause of juvenile rheumatoid arthritis to be gleaned from a more careful study of inflammation or innate immunity. This review will focus on the roles of complement, immune complexes, and the vascular endothelium in the pathogenesis of juvenile rheumatoid arthritis. In so doing, it will reexamine the dogma of the central role of the T cell in juvenile rheumatoid arthritis disease pathogenesis and offer new paradigms with which to understand this and other rheumatic diseases of childhood.
11157861 Muscarinic acetylcholine receptor antibodies as a new marker of dry eye Sjögren syndrome. 2001 Feb PURPOSE: The authors investigated whether circulating autoantibodies against M(3) muscarinic acetylcholine receptors (mAChRs) could be a new marker for diagnosis for primary and secondary Sjögren syndrome (SS) dry eye. METHODS: Enzyme-linked immunosorbent assay (ELISA) using both rat exorbital lacrimal gland acinar cell membranes and synthetic 25-mer peptide as antigens was used to determine autoantibodies against acinar cells and M(3) mAChRs. Also, nitric oxide synthase (NOS) activity was assessed to determine the biological effect of these autoantibodies in relation to the M(3) mAChR. RESULTS: Sera from dry eye primary SS (pSS) or secondary SS (sSS) patients tested by ELISA recognized membrane lacrimal gland acinar cells antigens and the synthetic 25-mer peptide, corresponding to the second extracellular loop of human M(3) mAChRs. Moreover, the IgG fraction and the corresponding affinity-purified anti-M(3) peptide autoantibodies from the same patients were able to activate NOS coupled to lacrimal gland M(3) mAChRs. As controls, IgG and sera from women without dry eye with or without rheumatoid arthritis and from normal control subjects gave negative results on ELISA and biological assay; thus demonstrating the specificity of the reaction. CONCLUSIONS: Autoantibodies against mAChR may be considered among the serum factors implicated in the pathophysiology of the development of pSS dry eyes and could be a new marker to differentiate SS dry eyes from non-SS dry eyes.
17039088 Worsening of arthritis with antiretroviral therapy: the coexistence of rheumatoid arthriti 2001 Feb The observation of remission occurring in several rheumatoid arthritis (RA) patients who subsequently became infected with human immunodeficiency virus (HIV) suggested that these diseases are mutually exclusive. Subsequent case reports of progression of destructive rheumatoid arthritis, even with depleted CD4 cell counts, seemed to imply that active RA may be independent of CD4 lymphocyte number and function. We report an HIV-infected individual who developed rheumatoid arthritis, which rapidly worsened with the initiation of antiretroviral therapy. The worsening disease course correlated with the increase in CD4 cell count and with the decrease in HIV viral load, perhaps suggesting a central role for the CD4 cells in the pathogenesis of rheumatoid arthritis in this particular patient. Among the therapeutic options to consider in such a patient, indomethacin and hydroxychloroquine may offer additional benefit of inhibiting viral replication. The cautious use of methotrexate with several limitations is possible, although sulfasalazine (to which our patient responded) may be a safer option.
18031119 Current status of gene therapy for rheumatoid arthritis. 1999 Feb Despite the high prevalence of the disease, at present little effective pharmacological treatment of rheumatoid arthritis is available. Novel approaches utilising biological agents have resulted in the development of new antiarthritic and antiinflammatory agents, such as tumour necrosis factor-alpha (TNFalpha)-specific antibodies and interleukin-1 receptor antagonist (IL-1ra). Local gene therapy not only allows the pharmaceutical use of these biologicals, but also allows for continuous drug supply, which is necessary for chronic diseases like rheumatoid arthritis. We discuss the basics of rheumatoid arthritis therapy, candidate genes and possible gene transfer methods. A current clinical gene therapy trial is focusing on the IL-1 system using IL-1ra as a transgene. The transfer system, clinical protocol and preliminary results are described. After treatment of 11 patients we feel that gene therapy will offer potential as a new avenue to treat rheumatoid arthritis.