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ID PMID Title PublicationDate abstract
9228317 Long-term results of the treatment of severe osteoarthritis and rheumatoid arthritis with 1997 We undertook a clinical and surgical study with evaluation of the long-term results (average 5 years, range 1-9 years) of 193 stabilized posterior cemented total knee replacements (TKRs) type Insall-Burstein in patients with severe osteoarthritis (OA) and rheumatoid arthritis (RA), carried out consecutively by the same surgeon from January 1986 to January 1995, at our COT Unit at the Central Military Hospital "Gomez Ulla" in Madrid, in collaboration with the Departments of Traumatology and Morphological Sciences of the University of Alcala de Henares (Madrid). The principal purpose was to examine the success rate of this type of prothesis implanted during primary surgery, according to severity of the case. Six methodology protocols were produced in this study (exploratory, surgical technique in primary surgery, revision surgery, rehabilitation, evaluation and clinical revisions), and satisfactory statistical results (SPSS/PC+) were obtained with the three scales of evaluation: Harris Galante, The Hospital for Special Surgery and Knee Society. These were: 90.5% +/- 0.8% excellent and good results for the OA series, and 83.9% +/- 5% for the RA series. The analysis of survival after long-term monitoring was also statistically significant, with a 96.95% survival rate. Complications arose in 3.10% of cases (6 revisions: 4 aseptic loosenings and 2 loosenings due to infection), which were treated with a constrained prosthesis, and in cases of infection with an arthrodesis. After undertaking a comparative study with other series, we conclude that the Insall-Burnstein stabilized posterior total knee prosthesis, is an excellent Primary replacement associated with long-term survival in patients with a severe degree of articular destruction and functional incapacity, and we give some specific recommendations to reduce complications.
10079291 Identification of the gene variations in human CD22. 1999 Apr CD22, a member of the immunoglobulin superfamily, is a B-cell transmembrane glycoprotein that acts as an accessory-signaling component of the B-cell antigen receptor (BCR). Recent evidence indicating the role of CD22 as a negative regulator of BCR signal transduction prompted us to test the possibility that genetic variations of human CD22 may be associated with autoimmune diseases. In this study, variation screening of the entire CD22 coding region was performed, and possible association with rheumatic diseases was tested, using the genomic DNA from 207 healthy Japanese individuals, 68 patients with systemic lupus erythematosus (SLE), and 119 patients with rheumatoid arthritis (RA). Through the variation screening, seven non-synonymous and four synonymous substitutions were identified. In addition, single base substitutions were found in two introns flanking exon-intron junctions. Among these variations, Q152E substitution within the second extracellular domain was observed with a marginally higher frequency in the patients with SLE (3/68, 4.4%) than that in healthy individuals (1/207, 0.5%) (P=0.048. SLE vs healthy individuals), although this difference was no longer significant after correction for the number of comparisons (Pc=0.62). No significant association was observed between any of the variations and RA. These findings indicate that a number of genetic variants are present in CD22, and suggest that CD22 could be considered a candidate for the susceptibility genes to autoimmune diseases.
10565376 Fasting in healthy individuals and adaption to undernutrition during chronic disease. 1998 Jul During long-term fasting, gluconeogenesis from amino acids was thought to lessen, when ketone bodies from lipolysis became a major fuel source. Thus, muscle mass is conserved. However, recent studies show that this adaptation does not occur in chronic undernourishment. In cancer, chronic undernutrition without disease, and HIV infection, carbohydrate utilization is high. Enhanced hepatic glucose production occurs in active inflammatory bowel disease and in underweight cancer patients. Repletion of tissue after undernutrition is energetically inefficient because of enhanced diet induced thermogenesis (following anorexia nervosa) and decreased fat, and increased protein, oxidation (in tuberculosis).
11394898 Expression of ID family genes in the synovia from patients with rheumatoid arthritis. 2001 Jun 8 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by aggressive proliferation of synovial tissue leading to destruction of cartilage and bone. To identify molecules which play a crucial role for the pathogenesis, we compared mRNA expression pattern of RA synovium with that of osteoarthritis (OA), using the differential display. From the panel of differentially expressed genes, ID1 (inhibitor of differentiation 1) was considered to be particularly relevant to the pathogenesis of RA, because Id family genes have been shown to play a role in cell proliferation and angiogenesis. To examine whether the up-regulation of these genes is consistently observed in the patients with RA, mRNA levels of ID1 and ID3 in the synovial tissues from 13 patients with RA and 6 patients with OA were semi-quantitatively analyzed by RT-PCR. Mean mRNA levels of ID1 and ID3 were significantly elevated in RA synovia compared with OA by 8.6-fold (P = 0.0044) and 3.3-fold (P = 0.0085), respectively. Immunohistochemistry revealed striking staining of Id1 and Id3 in the endothelial cells, suggesting a possible role of Id in severe angiogenesis observed in RA. The expression of Id family genes in the synovium constitutes a new finding of particular interest. Their functional role as well as their contribution to the genetic susceptibility to RA requires further investigation.
10450517 On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheuma 1999 Jun The specific role of the tumor necrosis factor (TNF)/TNF receptor (TNFR) system in disease pathogenesis still remains an unresolved puzzle. Recent studies in transgenic and knockout animals, where the pathogenic influence of genetically perturbed TNF expression has been evaluated, indicate that several pathways of TNF/TNFR action may contribute independently or in concert to initiate, promote or downregulate disease pathogenesis. Evidently, organ-specific inflammatory or autoimmune pathology may ensue due to sustained activation by TNF of innate immune cells and inflammatory responses, which may consequently lead to tissue damage and to organ-specific chronic pathology. However, more cryptic functions of this molecule may be considered to play a significant part in the development of TNF-mediated pathologies. Direct interference of TNF with the differentiation, proliferation or death of specific pathogenic cell targets may be an alternative mechanism for disease initiation or progression. In addition to these activities, there is now considerable evidence to suggest that TNF may also directly promote or downregulate the adaptive immune response. It is therefore evident that no general scenario may adequately describe the role of TNF in disease pathogenesis. In this article, we aim to place these diverse functions of TNF/TNFRs into context with the development of specific pathology in murine models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease.
10415622 Disease activity related catecholamine response of lymphocytes from patients with rheumato 1999 Jun 22 In patients with chronic rheumatic diseases, a decreased density of beta 2-adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) could be demonstrated negatively correlating with various disease activity parameters. The aim of the present study was to determine the impact of this decrease on catecholamine response of PBMC from patients with rheumatoid arthritis (RA) in vitro. PBMC from 17 patients with RA and 6 healthy blood donors (HD) were investigated. The effects of epinephrine (E) and norepinephrine (NE) on PBMC proliferation were studied using cells activated with phytohemagglutinin (PHA) and monoclonal anti-CD3-antibodies (OKT3), respectively. The results revealed that lymphocytes of patients with RA showed a significantly reduced influence of catecholamines on PBMC function. In RA patients with high disease activity only, a shift to alpha 1-adrenergic-mediated catecholamine effects upon PBMC reactivity could be observed. The study demonstrates the intricate relationship between PBMC reactivity and catecholamine effects that is mediated via alpha- and beta-adrenergic receptors due to disease activity. In this respect the altered catecholamine response of PBMC from patients with RA may contribute to the pathogenic process of RA.
9495573 Myocrisin-mediated oxidative stress. 1997 Dec 10 This study reports on the ability of myocrisin to mediate in the production and detoxification of oxidants (principally hydrogen peroxide) in the monocyte in-vivo and in-vitro. The hydrogen peroxide produced by the monocyte derived from rheumatoid arthritis patients being treated with myocrisin was found to be 14.9 +/- 1.6 nmoles/10(6) cells and is elevated above levels found in monocytes obtained from patients either being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (11.3 +/- 0.4 nmoles/10(6) cells; P < 0.01) or normal healthy volunteers (11.2 +/- 1.2 nmoles/10(6) cells; P < 0.01). A comparative study on glutathione (GSH) oxidation indicated that levels of monocyte GSH were elevated in myocrisin-treated patients (2.4 +/- 0.49 mmol/l) over normal healthy volunteers (0.83 +/- 0.18 mM; P < 0.01) and that levels of monocyte diglutathione (GSSG) were depressed (myocrisin, 0.97 +/- 0.41 micromol/l; normal, 5.71 +/- 0.73 micromol/l; P < 0.01). The non-inhibition of glutathione reductase and the inhibition of glutathione peroxidase by gold provides the link between these two observations. Thus, gold therapy would seem to elevate monocyte hydrogen peroxide, increase monocyte reduced glutathione and decrease plasma glutathione peroxidase activity. Subsequently, the data from this small group of patients (n = 10) provides an indication that, in-vivo, myocrisin contributes to an increase in oxidative stress.
10949061 Evidence-based data on pain relief with antidepressants. 2000 Jul This structured review addresses the issue of whether antidepressants have an antinociceptive (analgesic) effect for chronic pain independent of their antidepressant effect. In order to answer this question, human acute pain studies, individual placebo-controlled studies for the treatment of specific chronic pain syndromes, and metaanalytic studies were reviewed and placed into table format. Analysis of this evidence led to the following conclusions: The evidence was consistent in indicating that overall antidepressants may have an antinociceptive effect in chronic pain, and that these drugs were effective for neuropathic pain. There was also some evidence that these drugs could be effective for psychogenic or somatoform disorder-associated pain. This evidence also strongly suggested that serotonergic-noradrenergic antidepressants may have a more consistent antinociceptive effect than the serotonergic antidepressants. Finally, this evidence indicated that antidepressants could be effective for pain associated with some specific pain syndromes, such as chronic low back pain, osteoarthritis or rheumatoid arthritis, fibrositis or fibromyalgia, and ulcer healing. Possible reasons for the conflicting results of studies in this area are presented, and problems that could limit the validity of the conclusions of this review are discussed.
10374416 HLA-DRB1 genes in 5 rheumatic disease multi-case families. 1998 Mar OBJECTIVE: To detect HLA-DRB1 (DR1-10) alleles in 5 families with multi-case rheumatic diseases, and to study the possible influence of DRB1 genes in the pathogenesis of rheumatic diseases. METHODS: Sequence-Specific Primer PCR (PCR-SSP) method was used to examine HLA-DRB1 alleles. Totally 36 members of 5 families and 166 healthy people were involved in this study. The results were assessed by Chi-square test. RESULTS: The HLA-DRB1 allele frequency in the patients and their relatives was similar. No significant difference was found. But DR4 allele frequency in the patients (90.9%) and their relatives (68%) was much higher than that in normal controls (16.8%) and the difference was statistically significant (P < 0.0001). In family 4, two RA patients have different DRB1 alleles, while in family 5, two patients have the same DRB1 alleles, one developed SLE and the other developed RA. CONCLUSIONS: DR4 is closely related to rheumatoid arthritis. The nelatives of RA patients may be at greater risk to develop RA than individuals without family history. Some patients had the same DRB1 allele but developed different rheumatic diseases. This suggested that there might be some common pathways in genetic predisposing of rheumatic diseases. On the other hand, only a few patients with the same DRB1 allele developed rheumatic diseases during their life, so other factors besides DRB1 gene might also be involved in the pathogenesis of rheumatic diseases.
9255107 Gelatinase B in chronic synovitis: immunolocalization with a monoclonal antibody. 1997 Jul Gelatinase B is a matrix metalloproteinase (MMP-9) involved in the remodelling of extracellular matrices of connective tissues. With the use of specific monoclonal antibodies against human gelatinase B, the producer cell types were pinpointed in histopathological sections of a number of arthritic diseases. In cases of acute joint trauma, chondromatosis, villonodular synovitis and a cyst of a bursa, high numbers of strongly immunopositive neutrophils were observed in addition to weaker staining macrophages. Activated macrophages with giant cell morphology clearly stained with the gelatinase B-specific monoclonal antibody in the case of villonodular synovitis and in an epidermoid cyst. However, in the sections from patients with rheumatoid arthritis, no immunostaining was seen. In other cases of chronic synovitis, however, within the lymphocyte nodular aggregates a strong gelatinase B expression was observed in morphologically identified dendritic cells. In conclusion, gelatinase B production in joint disease seems to be predominantly by neutrophils and cell types of the macrophage/antigen-presenting cell lineage.
10852253 Interleukin-1beta induces elevation of spermidine/spermine N1-acetyltransferase activity a 2000 Jun OBJECTIVE: To investigate polyamine metabolism in rheumatoid synovial adherent cells stimulated by interleukin- 1beta (IL-1beta). METHODS: Synovial adherent cells obtained from patients with rheumatoid arthritis (RA) were cultured and incubated in the presence or absence of human recombinant IL-1beta at a concentration of 10 ng/ml for 24 h. The cellular contents of polyamines as well as the activities of spermidine/spermine N1-acetyltransferase (SAT) and ornithine decarboxylase (ODC) were measured. RESULTS: Polyamines in synovial adherent cells decreased significantly after 24 h incubation in the absence of IL-1beta. However, in the presence of IL-Ibeta, putrescine and N'-acetylspermidine increased significantly. No significant difference was observed between the amount of spermidine in synovial adherent cells incubated with and without IL-1beta. Spermine and N8-acetylspermidine in synovial adherent cells incubated with IL-1beta decreased significantly more than in synovial adherent cells incubated without. SAT activity reached a peak 12 h after the addition of IL-1beta and then decreased, while the ODC activity did not increase. SAT activity was elevated by the addition of IL-1beta in a dose dependent manner. CONCLUSION: An increase in the putrescine level in rheumatoid synovial adherent cells as a result of the elevation of SAT activity induced by IL-1beta may play a role in RA.
11176875 Prospects for autoimmune disease: Research advances in rheumatoid arthritis. 2001 Feb 7 Rheumatoid arthritis (RA) is a common chronic inflammatory disease associated with progressive destruction of diarthrodial joints, substantial morbidity and economic burden, and a shortened lifespan. Significant progress has been made in understanding the pathogenesis of RA, and increasingly effective therapies have been introduced, including anti-tumor necrosis factor alpha agents. Advances made in the past quarter century will pale in comparison to those anticipated for the next 25 years, including delineation of the genetic basis of disease susceptibility and severity, genetic definition of disease subtypes that differ in severity and response to therapy, and prompt initiation of effective individualized treatment based on genetic and environmental assessment. Reconstructive surgery will become increasingly unnecessary and the morbidity, economic burden, and mortality due to RA will be reduced substantially.
9028735 A nonradioactive method of in situ hybridization that uses riboprobes and paraffin-embedde 1997 Feb Current research into cytokine production in tissue sections relies on the detection of cytokine proteins using a variety of immunohistochemical methods. The disadvantages of this technique are that precise localization to a particular cell is difficult and it is uncertain whether the cells detected by this method are the origin or target of the cytokine or rather have nonspecifically absorbed the secreted cytokine. This question can be clarified using in situ hybridization, but current techniques are insensitive, poorly localizing, or time consuming. Biotin-labeled riboprobes were generated from cDNA fragments sandwiched between two RNA polymerase promoters (SP6 and T7 RNA polymerases) using a commercial riboprobe generation kit containing biotin-labeled UTP. The in situ hybridization technique was used to demonstrate cytokine mRNA in a range of tissues containing an inflammatory infiltrate and with a range of cytokine probes. This technique of in situ hybridization was combined with immunohistochemistry using an immunoalkaline phosphatase technique to show the powerful combination of these two techniques. The biotin-labeled riboprobes were sensitive enough to detect a range of cytokine mRNAs in a variety of tissue sections. The technique can be completed over a 24-h period and produces a stable color product that can be stored for long periods and can be quantitated using image analysis techniques. This technique was performed on paraffin-embedded tissue as well as cryosections and allowed for the detection of mRNA in archival tissue. It was also successfully combined with immunohistochemical techniques to determine simultaneously the localization of a cytokine product in particular cell lineages. A nonradioactive method for in situ hybridization using biotin-labeled riboprobes is described; it is capable of detecting mRNA products from a range of genes in a variety of tissue samples. An amplification step in the method enhances the sensitivity to a level that approaches that of radioactive methods, while maintaining the speed, safety, and simplicity of an immunoperoxidase detection system. The ability to use paraffin-embedded tissue with this method allows for improved tissue architecture and examination of archival tissue. These features should ensure greater use of in situ hybridization techniques in future research studies.
10092165 Muscle relaxation training and quality of life in rheumatoid arthritis. A randomized contr 1999 The purpose of the study was to investigate the effects of supervised muscle relaxation training in individuals with rheumatoid arthritis (RA). Sixty-eight participants were allocated at random either to a muscle relaxation training group or to a control group. Every participant was evaluated for health-related quality of life, muscle function, pain, and disease activity. The training group exercised 30 minutes, twice a week for 10 weeks, while no intervention was made in the control group. The results indicated improvements in the training group regarding self-care according to the Arthritis Impact Measurement Scales 2, and in recreation and pastimes according to the Sickness Impact Profile-RA (p < 0.05) directly after the intervention. Mobility and arm function (p < 0.01) according to the Arthritis Impact Measurement Scales 2, and muscle function of the lower limbs (p < 0.05) were improved after six months. No improvements remained after twelve months. It thus seems that 10 weeks' relaxation training might have some short-term influence in individuals with RA.
10795218 Pearls of the plain film. 1999 Sep Three case presentations from a general rheumatologic practice show the importance of the plain x-ray in making the diagnosis of arthritis. Clinical history, physical examination, and the plain x-ray are likely to provide the diagnosis most often over laboratory and more technologically advanced imaging studies for arthritis.
9499517 [10 years follow-up of athrodeses of the hindfoot joints and upper ankle joint]. 1997 Nov PURPOSE: What is the clinical and radiographic outcome of arthrodeses at the hindfoot and at the ankle more than 10 years postoperatively? METHODS: Between 1968 and 1988, 155 arthrodeses (ankle joint, triple arthrodeses, subtalar, pantalar and talonavicular arthrodeses) were performed on 147 patients. Indications for arthrodesis were posttraumatic arthritis, congenital deformity, idiopathic degenerative arthritis and rheumatoid arthritis. A variety of internal fixation devices or no internal fixation were used. 79 patients with 82 arthrodeses were reexamined clinically and radiographically, after 11.1 years on average. Static and dynamic foot print measurements were recorded with a capacitive sensor system. Another 26 patients with 27 arthrodeses replied to a questionnaire. RESULTS: Subjectively, the average pain score improved significantly. The overall function score improved only slightly. Results were inferior in the talonavicular arthrodesis. Radiographic evaluation revealed bony union in only 59 percent of the arthrodeses, one third at the talonavicular joint. Secondary degenerative arthritis of the foot and ankle occurred in 107 joints of the 82 feet. Evaluation of dynamic foot pressure measurements revealed an overall prolonged weightbearing on the midfoot region. CONCLUSION: An unacceptably low rate of bony union in some locations, a high incidence of secondary degenerative changes at neighboring joints, and a persistent abnormality of the plantar weightbearing pattern in the operated feet demonstrate unsatisfactory results with the techniques used more than 10 years ago. We now recommend stable internal fixation with optimum adaptation of the bone surfaces of the arthrodesis.
11759231 [Clinical experience with TNF-blockers]. 2001 Oct Recently, biologic agents have become available for the treatment of rheumatoid arthritis. Such agents, the so-called TNF blockers, selectively inhibit TNF alpha, a dominant proinflammatory cytokine. They allow good suppression of the disease activity in many patients. Even in nonresponders to conventional disease modifying antirheumatic drugs (DMARDs) a good response may be achieved. The anti-erosive effect appears to be excellent. Major advantages are the fast response and good overall safety. Constitutional symptoms often disappear rapidly, which may contribute substantially to the gain in quality of life. Efficacy and safety are maintained even in long-term use. Because of certain risks and high costs TNF-blocking agents should be reserved for patients who respond poorly to conventional DMARDs or do not tolerate them.
9671990 Modelling the major histocompatibility complex susceptibility to RA using the MASC method. 1998 To explain the association between HLA-DRB1 gene and rheumatoid arthritis (RA), two main hypotheses have been proposed. The first, the shared epitope hypothesis, assumes a direct role of DRB1 in RA susceptibility. The second hypothesis assumes a recessive disease susceptibility gene in linkage disequilibrium with DRB1. To investigate these two hypotheses, we analysed data on the HLA-DRB1 and TNF-LT loci in 49 affected sib-pairs. We used the Marker Association Segregation Chi-square (MASC) method in which the genotype distribution of markers among index cases and the haplotype sharing in affected sib-pairs are jointly taken into account. With DRB1 data alone, both hypotheses were shown to fit but with analysis of TNF data, both hypotheses were strongly rejected. Thus the TNF data provided additional information for a better understanding of genetic susceptibility to RA than was previously possible using only HLA-DR data. A theoretical standpoint is addressed here on the advisability of using different linked markers in a candidate region for modelling the contribution of this region in disease susceptibility.
10880256 Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis. 2000 Jul Interleukin (IL-)17 is a T cell-derived pro-inflammatory cytokine produced by RA synovium. We studied the role of IL-17 in the synovium cytokine network to determine whether it can influence the inflammatory and destructive pattern characteristic of RA. Herein, we investigated whether the production and action of MMP-1 and its inhibitor TIMP-1 could be modulated by IL-17 in the presence of pro-inflammatory cytokine (IL-1) and anti-inflammatory cytokines (IL-4, IL-13, IL-10). The effect of the blockade of endogenous IL-17 on the secretion of MMP-1 and TIMP-1 by RA synovium and matrix destruction was also studied. IL-17 increased the spontaneous production of MMP-1 by synoviocytes five-fold. IL-1 was more potent since it increased MMP-1 production nine-fold. Addition of IL-4, IL-13 and IL-10 to synoviocyte cultures reduced the spontaneous production of MMP-1 and induced TIMP-1 production by synoviocytes stimulated with IL-17 or/and IL-1beta. In the presence of anti-IL-17 blocking mAb, MMP-1 production and collagenase activity by RA synovium was reduced by 50% and associated with a 50% reduction in type I collagen C-telopeptide fragments (CTX) released in the supernatants, demonstrating the direct contribution of IL-17 in destruction. IL-17 and its producing T cells appear to contribute to the inflammatory process involved in the rheumatoid lesion.
9410920 Functional CD40 ligand is expressed by T cells in rheumatoid arthritis. 1997 Nov 1 CD40 ligand (CD40-L), a member of the tumor necrosis family of transmembrane glycoproteins, is rapidly and transiently expressed on the surface of recently activated CD4+ T cells. Interactions between CD40-L and CD40 induce B cell immunoglobulin production as well as monocyte activation and dendritic cell differentiation. Since these features characterize rheumatoid arthritis (RA), the expression and function of CD40-L in RA was examined. Freshly isolated RA peripheral blood (PB) and synovial fluid (SF) T cells expressed CD40-L mRNA as well as low level cell surface CD40-L. An additional subset of CD4+ RA SF T cells upregulated cell surface CD40-L expression within 15 min of in vitro activation even in the presence of cycloheximide, but soluble CD40-L was not found in SF. CD40-L expressed by RA T cells was functional, since RA PB and SF T cells but not normal PB T cells stimulated CD40-L-dependent B cell immunoglobulin production and dendritic cell IL-12 expression in the absence of prolonged in vitro T cell activation. In view of the diverse proinflammatory effects of CD40-L, this molecule is likely to play a central role in the perpetuation of rheumatoid synovitis. Of importance, blockade of CD40-L may prove highly effective as a disease modifying therapy for RA.