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ID PMID Title PublicationDate abstract
8777853 Ultrasonography is a nonspecific method in the evaluation of joints. 1996 Mar Two cases of unilateral abnormal ultrasonographic findings in the hip joints are introduced. The correct diagnoses were detected by radiography after the failure of intra-articular glucocorticoid injections given as first aid. Ultrasonography (US) has poor specificity, since all phenomena causing effusion into the joint cavity may be detected as abnormal by US, and may include stress fractures and malignant myeloma, as we show here. In the case of an abnormal ultrasonographic finding in a joint, the recent radiological status should also be considered.
8629827 Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rh 1996 Feb BACKGROUND: In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. Methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of methotrexate proved to have an adverse effect on bone metabolism, especially on osteoblast activity. OBSERVATIONS: Methotrexate osteopathy is a relatively unknown complication of low-dose methotrexate treatment. We describe three patients treated with low-dose oral methotrexate in whom signs and symptoms were present that were similar to those found in children treated with high doses of methotrexate. All three patients had a triad of severe pain localized in the distal tibiae, osteoporosis, and compression fractures of the distal tibia, which could be identified with radiographs, technetium Tc 99m scanning, and magnetic resonance imaging. CONCLUSIONS: Methotrexate osteopathy can occur in patients treated with low doses of methotrexate, even over a short period of time. As pain is localized in the distal tibia, it is easily misdiagnosed as psoriatic arthritis of the ankle, but the diagnosis can be correctly made by careful investigation and use of imaging techniques. The only therapy is withdrawal of methotrexate. It is important that more physicians become aware of this side effect of methotrexate therapy, which can occur along with arthritic symptoms.
8120407 Production of interleukin-1 receptor antagonist, inflammatory chemotactic proteins, and pr 1994 Feb 15 This study analyzes the effects of the T cell cytokines IL-4 and IFN-gamma on the spontaneous and stimulated production of IL-8, MCP-1, IL-1 receptor antagonist (IL-1ra), and PGE by synoviocytes from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells from both sources constitutively released IL-8 and MCP-1, but no IL-1ra or PGE. Stimulation with IL-1 beta or TNF-alpha massively increased chemokine production and induced the generation of PGE and low amounts of IL-1ra. The constitutive or cytokine-stimulated release of IL-8 was inhibited by IFN-gamma, but not by IL-4. The constitutive or IL-1 beta-stimulated release of MCP-1, by contrast, was markedly enhanced by IL-4 and IFN-gamma. Both cytokines, however, had only borderline effects on the release stimulated by TNF-alpha. The yield of IL-1ra was strongly enhanced by IFN-gamma in all cases, whereas the effect of IL-4 was pronounced only in IL-1 beta-stimulated OA synoviocytes. IL-4, on the other hand, markedly decreased the release of PGE, which was less susceptible to IFN-gamma. The observed effects on chemokines, IL-1ra expression, and PGE release by synoviocytes suggest that IFN-gamma and IL-4 are important regulatory elements in the inflamed synovium and may exert anti-inflammatory effects.
7535359 Localization of the alpha v subfamily of integrins and their putative ligands in synovial 1995 Jan OBJECTIVE: The lining cell layer of the synovium proliferates strongly in rheumatoid arthritis. It has been suggested that it has a central role in the destruction of cartilage. We have analyzed the structure of the extracellular matrix and the adhesion molecules of normal, osteoarthritic and rheumatoid lining cell layer. METHODS: We localized the alpha v integrin subunit and its 4 putative partner beta subunits in synovial samples by using indirect immunofluorescence. The specimens were also analyzed by confocal microscopy. Indirect immunofluorescence was also used to analyze the ligands of alpha v integrins, namely fibronectin and vitronectin. RESULTS: The alpha v integrin was abundant in the lining cell layer of normal and osteoarthritic synovia, whereas it was not expressed in the proliferating rheumatoid lining cell layers. A similar expression pattern was found for beta 5 subunit, suggesting that it is the major partner for alpha v. However, also some alpha v beta 1 and alpha v beta 3 heterodimers may be present. The confocal microscopy revealed the presence of both alpha v beta 5 positive and negative lining cells. The putative ligands for alpha v integrins, namely fibronectin and vitronectin were found in the lining cell layer of all the synovial specimens. CONCLUSION: In spite of the proliferation of the lining cell layer in rheumatoid inflammation, the extracellular matrix stays very similar to that in normal and osteoarthritic synovium, whereas the pattern of the adhesion receptors is completely altered.
1581469 Relationship between interleukin 6, agalactosyl IgG and pristane-induced arthritis. 1992 IL-6 titres in sera and peritoneal exudate fluids (PEF) derived from pristane injected DBA/1 and CBA/Igb mice were measured. Arthritic DBA/1 mice had significantly higher serum IL-6 titres than nonarthritic or normal mice at 160 days post pristane injection. By contrast, although both arthritic and non-arthritic CBA/Igb mice had higher serum IL-6 titres than normal mice, there was no significant difference in serum IL-6 titre between these two groups at day 200-230. In both strains of mice, the IL-6 titres in PEF were more than 10 times serum levels regardless of arthritis. As previously reported for CBA/Igb mice, agalactosyl IgG levels are raised in pristane injected DBA/1 mice and the percentage is higher in arthritic animals than that in non-arthritic mice. An association between serum agalactosyl IgG levels and PEF IL-6 in pristane injected DBA/1 was demonstrated. Moreover, the injection of recombinant IL-6 into normal mice increased their serum agalactosyl IgG levels. However, it is considered that IL-6 is not the only factor involved in the production of agalactosyl IgG.
7983651 Rheumatic diseases in China: ILAR-China study comparing the prevalence of rheumatic sympto 1994 Aug OBJECTIVE: To determine the prevalence of rheumatic diseases in Han Chinese in north and south China. METHODS: Samples of 4192 adults in the Beijing (north) and 5057 in the Shantou (south) areas, based on village administration registers, were studied. The same questionnaire was administered by doctors who then examined those with rheumatic symptoms. One observer (QYZ) took part in both studies. RESULTS: The prevalence of definite rheumatoid arthritis (RA) was 0.34% (95% CI; 0.20-0.51) in the north and 0.32% (0.16-0.47) in the south. Ankylosing spondylitis (AS) was noted in 0.26% of both samples (95% CI; 0.11-0.42 north and 0.14-0.40 south). Only 3 cases of systemic lupus erythematosus (SLE) in the north and one in the south were identified. General rheumatic pain was reported more frequently in the north. Lumbar problems were recorded on examination 5 times more frequently in the north than in the south [men, 25%:5.3%; women 38%:6.5%] and knee problems 10 times more frequently [men, 24%:1.8%; women, 36%:3.4%] in the north. The difference was greatest in the 55 to 64 year age group. CONCLUSION: The prevalence of RA was similar to that in other rural populations and Japan, but only half that reported from other industrialized communities. The prevalence of AS was similar to that in most Caucasian populations. SLE was too infrequent to establish a prevalence with confidence, but did not differ from that in other populations. A study is planned in the south to assess the contribution of interobserver error and/or differences in cultural response to the north/south differences observed in the prevalence of general rheumatic symptoms and back pain.
7528189 Inflamed joints of patients with rheumatoid arthritis contain T cells that display in vitr The immunopathology of inflamed joints in patients with RA is thought to result from an antigen-driven T-cell response. The antigen(s) responsible for the activation of synovial T cells, however, are as yet unidentified. In this study, we tested SF as a potential source of (auto)antigen(s). Five of 15 IL-2-expanded T-cell lines generated from SF cells of RA patients displayed a proliferative response to autologous SF. Five CD4+CD8-alpha beta TCR+SF-reactive T-cell clones obtained from responder T-cell lines were studied in more detail. Three T-cell clones from one RA patient were found to recognize epitopes in autologous SF in the context of DR4(Dw4), and two T-cell clones of another RA patient responded to autologous SF in the context of the HLA-DPB1*0401 gene product. The two DP-restricted clones and one of the DR-restricted clones did not proliferate to 50 SF samples of other RA patients, whereas the remaining DR-restricted clones responded to one allogeneic sample. Sequence analysis demonstrated that the latter clones expressed identical V beta 6.9 + TCR beta chains. This was also found for the (V beta 19+) DP-restricted clones. Proliferation of SF-reactive T cells was not only obtained with SF of the joint that had contained the T cells, but also with autologous SF of other affected joints. Together, these findings indicate that epitopes able to stimulate synovial T cells differ among RA patients, but may be similar within multiple joints of an individual patient. The presence of T cells able to respond to SF antigens in inflamed joints suggests that these T cells play an active role in the pathogenesis of RA.
1525326 Leukemia, lymphoma, and multiple myeloma following selected medical conditions. 1992 Sep The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.
8621791 CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by auto 1996 May 1 Clonal expansion of CD4+ T cells is a characteristic finding in patients with RA and is only infrequently found in patients with psoriatic arthritis and healthy controls. Expanded CD4+ clonotypes are present in the blood, infiltrate into the joint, and persist over years. We have not addressed the question of whether the expanded clonotypes have unique functional and phenotypic properties which may explain the preferential in vivo expansion in RA. In contrast to most CD4+ T cells, expanded clonotypes lacked the expression of the CD28 and CD7 cell surface molecules. Accordingly, the subsets of CD4+ CD28- (9.7 vs 1.7, P = 0.00002) and CD4+ CD7- T cells (21.5 vs 12.26, P = 0.018) were increased in RA patients compared with age-matched normal individuals. Despite the lack of CD28 expression, clonally expanded CD4+ T cells were not anergic but proliferated in response to immobilized anti-CD3 and could be maintained in tissue culture. In vivo expanded CD4+ T cells were autoreactive to ubiquitously distributed autoantigens. They responded in an autologous mixed lymphocyte reaction, and T cell clones isolated from selected patients proliferated to autologous peripheral blood adherent cells. These data suggest that in RA patients selected CD4+ T cells which share the CD7- CD28- phenotype escape from peripheral tolerance.
7618560 Quantification of the volume of articular cartilage in the metacarpophalangeal joints of t 1995 Aug OBJECTIVE: Cartilage loss is central to the development of joint failure in arthritis. However, radiographic assessment of cartilage loss is highly unreliable. This study examined the accuracy and reproducibility of a noninvasive technique for quantifying the volume of articular cartilage in the metacarpophalangeal joints of the hand by use of three-dimensional (3D) MR imaging. SUBJECTS AND METHODS: Eight metacarpophalangeal joints (four normal, one rheumatoid arthritic, and three normal cadaveric) each were imaged three times with a 1.5-T clinical MR imaging scanner with a small partial volume coil and a fat-saturated 3D spoiled gradient-echo sequence optimized for delineating articular cartilage. The volumes of cartilage over the metacarpal and phalangeal surfaces were quantified by summing the voxels within segmented 3D reconstructions of the images. Cartilage volumes in the three cadaver joints also were estimated by scraping cartilage off the articular surfaces and measuring water displacement in graduated cylinders. These values were used as the gold standard for assessing the accuracy of cartilage volume quantification by MR imaging. RESULTS: The fat-saturated sequence discriminated the articular cartilage from adjacent joint structures with high contrast and high spatial resolution. Cartilage volumes determined by MR imaging for the different subjects ranged from 115 microliters to 222 microliters for metacarpal cartilage and from 34 microliters to 86 microliters for proximal phalangeal cartilage. Accuracy errors for quantifying cartilage volume by MR imaging were -1.8% (95% confidence interval, -3.5% to -0.7%) for metacarpal cartilage and 9.1% (4.3% to 14.7%) for proximal phalangeal cartilage. Reproducibility errors were 5.2% (95% confidence interval, 2.9% to 7.6%) and 9.9% (5.4% to 15.1%), respectively. CONCLUSION: Fat-suppressed T1-weighted 3D MR imaging provides sufficient contrast and spatial resolution to allow accurate and reproducible quantification of articular cartilage volume in the metacarpophalangeal joints of the hand. This technique may be useful for monitoring cartilage loss in patients with arthritis.
8103699 Suspected cutaneous drug toxicity in rheumatoid arthritis--an evaluation. 1993 Sep Cutaneous toxicity from drugs used to treat RA is a major perceived problem. Over a 2-yr period we have prospectively reviewed 114 patients with a suspected adverse cutaneous reaction to anti-rheumatic drugs. In 71 (62%), the rash was thought to be unrelated to drug therapy. This group included 10 in whom the rash had resolved before review (usually < 1 week), 38 with a rash related to their rheumatoid disease and 23 with eruptions unrelated to either drugs or arthritis. Forty-three (38%) patients had rashes thought to be related to their drug therapy. Gold therapy (both oral and intramuscular) was implicated most frequently (31 patients). However, the majority of these (23) had a pityriasiform/discoid eczematous eruption that responded to potent topical steroids occasionally with a reduction in gold dosage. In this sample it was possible to continue drug therapy in 82% of patients with what were initially thought to be cutaneous adverse drug reactions. Careful evaluation should allow a majority of patients to continue drug therapy from which they are often gaining benefit.
8285810 A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the tr 1994 Jan 24 BACKGROUND: To study the relation between reported drug performance in published trials and support of the trials by the manufacturer of the drug under evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of arthritis. METHODS: All randomized control trials of NSAIDs published between September 1987 and May 1990 identified by MEDLINE were reviewed. If an article met the following criteria (n = 61), it was selected: trials involving adult patients with osteoarthritis or rheumatoid arthritis (n = 180), use of nonsalicylate NSAIDs marketed in the United States (n = 101), randomized control trial (n = 81), duration of the trial 4 or more days (n = 78), and use of an efficacy outcome measure (n = 61). Reviewers, "blinded" to manufacturer status, evaluated the narrative interpretation of results and extracted numeric data on efficacy and toxicity. Manufacturer-associated trials were defined as those that acknowledged an association with a pharmaceutical manufacturer. Because of the scarcity of non-manufacturer-associated trials (n = 9), we report only on the manufacturer-associated articles. RESULTS: Fifty-two publications (85.2%) representing 56 trials were associated with a manufacturer. The manufacturer-associated drug was reported as comparable with (71.4%) or superior to (28.6%) the comparison drug in all 56 trials. These narrative claims of superiority were usually justified with trial data. Of the trials identifying one drug as less toxic (n = 22), the manufacturer-associated drug's safety was reported as superior to the comparison drug in 86.4% of cases. Justification for the narrative interpretation of the trial findings regarding less toxicity was provided in only 12 (54.5%) of 22 trials. CONCLUSION: The manufacturer-associated NSAID is almost always reported as being equal or superior in efficacy and toxicity to the comparison drug. These claims of superiority, especially in regard to side effect profiles, are often not supported by trial data. These data raise concerns about selective publication or biased interpretation of results in manufacturer-associated trials.
8312806 [The effect of kobazol and atsizol on the proliferation of mononuclear cells]. 1993 Sep The authors studied the new imidazole-containing drugs cobazole and acizole for their effects on the proliferation of mononuclear cells from donors and patients with rheumatic arthritis. Acizole was found to produce no effects on mononuclear cell proliferation, whereas cobazole inhibited only the increased spontaneous proliferation of mononuclear cells in patients with rheumatic arthritis, which was due to a higher activity of nonspecific T-suppressor lymphocytes.
7550958 Retrograde intramedullary nailing for ankle arthrodesis. 1995 Jul This is a retrospective study of retrograde intramedullary rodding for ankle arthrodesis in 19 ankles in 16 patients. The preoperative diagnosis of 16 patients was diabetic neuropathic arthropathy in seven patients, rheumatoid arthritis in three patients, post traumatic arthrosis in three patients, paraplegia with fixed equinovarus of the foot in two patients, and avascular necrosis of the talus in one patient. Retrograde intramedullary rodding for ankle arthrodesis was done as a salvage procedure in each patient. Fourteen of the 19 ankles had radiographic evidence of solid arthrodesis. In the four patients with five ankles with pseudarthrosis, no case was clinically significant. There was one deep infection and one broken rod. Thirteen of the 16 patients are ambulatory, and nine required either an ankle-foot orthosis or shoe modification. The standard method of ankle fusion using crossed cancellous screws is the procedure of choice because it preserves the subtalar joint. Retrograde intramedullary rodding for ankle arthrodesis should be considered for patients with significant posttraumatic arthrosis and bone loss following distal tibial plafond fractures, concomitant subtalar arthrosis, severe osteopenia, such as in patients with rheumatoid arthritis, or neuropathic arthropathy.
8943731 Gene knockout mice as investigative tools in pathophysiology. 1996 Aug An overview is given of the phenotype of mice with distinct deletions of genes for cytokines and some related proteins, which occur either naturally or as a result of homologous recombination. The use of such knockout mice for investigation of the pathophysiology of experimental disease is summarized. Understanding of the role of a given cytokine in pathogenesis has therapeutic implications, as the pathology may be prevented or attenuated by inhibition of the synthesis, release or activity of that cytokine.
7798190 Preparation and characterization of human rheumatoid arthritic synovial fluid phospholipas 1994 Jul We prepared human rheumatoid arthritic synovial fluid phospholipase A2 (PLA2) [EC 3.1.1.4] from insect cells infected with a recombinant baculovirus. The PLA2 DNA was designed, changing the original codons to those used frequently in the polyhedrin gene. Sixteen oligo-deoxynucleotides ranging from 40 to 70 nucleotides were chemically synthesized and then assembled to form the whole PLA2 gene. The gene thus synthesized was then placed under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus. The recombinant virus was infected into Spodoptera frugiperda cells. The infected cells secreted protein having PLA2 activity into the culture medium. The enzyme level in the medium reached about 3 mg/liter on day 4 after infection. The secreted protein was purified to a single band of 14,000 Da on SDS-PAGE, by means of cation exchange chromatography and reverse-phase HPLC. N-terminal amino acid sequence analysis revealed that the recombinant protein was recognized and cleaved at the signal sequence in the insect cell. The purified enzyme had almost the same specific enzyme activity, substrate specificity, pH optimum, Ca2+ ion dependency, and kinetic values as those of the natural enzyme.
8050206 Do mesangial immune complex deposits affect the renal prognosis in membranous glomerulonep 1994 May Patients with rheumatoid arthritis who develop membranous glomerulonephritis associated with gold or penicillamine therapy have been shown to get better when the drugs are discontinued, whereas up to 50% of patients with idiopathic membranous glomerulonephritis develop renal failure. A feature of the lesion in rheumatoid disease is the presence of mesangial immune complex deposits in addition to the basement membrane deposits of classical idiopathic membranous glomerulonephritis. To determine whether the presence of mesangial immune complexes indicates a different renal outcome in membranous glomerulonephritis we studied 3 groups: group A 10 patients with rheumatoid arthritis and drug induced membranous glomerulonephritis with mesangial immune complex deposits, group B 14 patients with idiopathic membranous glomerulonephritis with additional mesangial immune complex deposits and group C 25 patients having classic idiopathic membranous glomerulonephritis with deposits solely in the glomerular basement membrane. After median follow up of 72 months, nephrotic range proteinuria resolved in all cases in group A after drug withdrawal, 93% of group B, but only 60% of group C (groups A + B vs C, X2 = 7.8, p < 0.01). Serum creatinine remains less than 500 mumol/l in all patients in group A, 93% of group B, but only 64% of group C (groups A + B vs C, X2 = 7.6, p < 0.01). Mesangial immune complex deposits were predominantly of the IgM isotype in both the rheumatoid and idiopathic membranous group. The presence of mesangial immune complex deposits suggests either a different pathogenesis or host responsiveness to that found in classic idiopathic membranous glomerulonephritis, and predicts a more favourable renal outcome.
8200991 Defining the genetic origins of three rheumatoid synovium-derived IgG rheumatoid factors. 1994 Jun A major diagnostic marker in most rheumatoid arthritis (RA) patients is the rheumatoid factor (RF), an autoantibody that binds to the Fc region of IgG. To delineate the Ig genes and the underlying mechanism for RF production in RA patients, we applied a systematic approach to define the genetic origins of three IgG RFs derived from the synovial fluid of two RA patients. The results show that two of three IgG RF have substantial numbers of somatic mutations in their variable (V) regions, ranging from 13 to 23 mutations over a stretch of 291-313 nucleotides, resulting in a frequency of 4.4-7.8%. However, one IgG RF has only one mutation in each V region. This result indicates that an IgG RF may arise from a germline gene by very few mutations. The mutations occur mainly in the complementarity-determining regions (CDRs), and the mutations in the CDRs often lead to amino acid substitutions. Five of the six corresponding germline V genes have been found to encode either natural autoantibodies or autoantibodies in other autoimmune disorders; and three of the six V genes have been found in fetal liver. Taken together with other results, the data show that (a) several potentially pathogenic RFs in RA patients arise from natural autoantibodies, and (b) only a few mutations are required to convert the natural autoantibodies to IgG RFs.
8574963 Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates au 1996 Feb The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.
8098938 Effects of inoculation with attenuated autologous T cells in patients with rheumatoid arth 1993 Apr Injection of attenuated autoimmune T cells, T cell vaccination, has been used successfully in the prevention and treatment of experimental animal autoimmune disease. In order to determine whether such a procedure might be applied in rheumatoid arthritis (RA), a phase I study was conducted in thirteen RA patients with a mean disease duration of 12.8 years. All patients received a subcutaneous injection of attenuated autologous T lymphocytes from a CD4 positive clone (n = 4) or line (n = 9) isolated from synovial tissue (n = 3) or synovial fluid (n = 10). No toxic side effects were observed. On the average the patients showed a slight decrease in disease activity which was most marked at 8 weeks after the injection. Specific immune reactivity against the injected T cells was not detected, with the possible exception of one patient who was vaccinated with a clone selected in vitro with antigen and whose disease had begun one year earlier. In this patient a clear decrease in disease activity occurred, which was associated with a decrease in mitogen-induced proliferation of her peripheral blood mononuclear cells and in titres of serum rheumatoid factors. The results of this study show that inoculation of RA patients with autologous T cells is technically feasible and non-toxic, and may be associated with clinical and immunological effects. The data suggest that the potential of T cell vaccination should be further explored in diseases with defined antigen reactivity.