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ID PMID Title PublicationDate abstract
9082938 Macrophage cathepsin L, a factor in the erosion of subchondral bone in rheumatoid arthriti 1997 Mar OBJECTIVE: To test the hypothesis that the proteinase cathepsin L is involved in the subchondral bone lesions found in chronic rheumatoid arthritis (RA). METHODS: The medial tibial plateaus from 4 control cases and 30 patients diagnosed as having end-stage RA were examined immunochemically for cathepsin L. RESULTS: RA lesions include large groups of mononuclear cells, many of which are rich in cathepsin L. Since these mononuclear cells contained the CD68 glycoprotein and, in the electron microscope, displayed an irregular cell surface, cytoplasmic vacuoles, lysosomes, and phagosomes, they were identified as belonging to the macrophage family. The lesions were classified into 2 main patterns, both displaying these cathepsin L-rich cells, which, in at least 1 of the 2, were closely associated with bone degradation. CONCLUSION: The cathepsin L-rich macrophages are sufficiently numerous to be considered a major factor in producing the erosion of subchondral bone found in chronic RA lesions.
10489838 Subclinical alveolar bleeding in pulmonary vasculitides: correlation with indices of disea 1999 Jul Haemosiderin-laden alveolar macrophages are a common finding in patients with alveolar bleeding. Iron-positive macrophages, suggestive of subclinical alveolar bleeding, were found to be fairly common in bronchoalveolar lavage (BAL) fluid in primary systemic vasculitis but uncommon in collagen vascular diseases (CVDs) and rheumatoid arthritis (RA). To substantiate the impression that subclinical alveolar bleeding may be a feature distinguishing between these disorders, fibreoptic bronchoscopy and BAL were performed in 49 patients with active Wegener's granulomatosis or Churg-Strauss syndrome and 44 patients with CVDs or RA, all of them without clinically manifest alveolar bleeding. The percentage of iron-positive cells was compared with clinical and radiological findings. Only a minority of the CVD and RA patients had iron-positive alveolar macrophages; the 95th percentile of the median number of such cells was 5%. Fifty-three per cent of the patients in the vasculitis group had >5% iron-positive cells, with individual counts ranging up to 95%. Patients with iron-positive macrophages had more extensive disease, more frequent microhaematuria, a higher antineutrophil cytoplasmic antibody titre, a higher myeloperoxidase concentration in the BAL fluid and somewhat more frequent low-attenuation opacities in pulmonary high-resolution computed tomography than the patients with a low iron-positive cell count. In conclusion, subclinical alveolar bleeding was, indeed, a common finding in antineutrophil cytoplasmic antibody-associated vasculitis, which distinguished these disorders from lung disease due to collagen vascular diseases or rheumatoid arthritis. Its association with indices of disease activity, although weak in this cross-sectional study, merits a longitudinal study of its value for the long-term monitoring of vasculitis patients.
10464548 Activation of progelatinase B in synovial fluids of patients with rheumatoid arthritis, wi 1999 Jul OBJECTIVE: To clarify whether stromelysin-1 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are involved in the modulation of activation of progelatinase B in the synovial fluid of patients with rheumatoid arthritis (RA). METHODS: Gelatinases in the synovial fluid of patients with RA were analyzed by gelatin zymography. Concentrations of stromelysin-1 and TIMP-1 were measured using a specific sandwich enzyme linked immunosorbent assay. RESULTS: Forty-three rheumatoid synovial fluids containing progelatinase B were examined to clarify whether the enzyme was activated by incubation. Incubation at 37 degrees C caused the conversion of progelatinase B to the active form in 22 of the 43 synovial fluids. The levels of both stromelysin-1 and TIMP-1 were determined for each group and the concentration ratio of stromelysin-1/TIMP-1 in the synovial fluids of each group was highly correlated to the activation of progelatinase B. CONCLUSION: The balance between the concentrations of stromelysin-1 and of TIMP-1 in the synovial fluid appears to determine whether the progelatinase B molecule causes conversion into the active form.
11759230 [Rheumatoid arthritis: new developments in the pathogenesis with special reference to syno 2001 Oct Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is mainly characterized by synovial hyperplasia, pathological immune phenomena and progressive destruction of the affected joints. Various cell types are involved in the pathogenesis of RA including T cells, antigen presenting cells, and endothelial cells. Recent experimental evidence suggests that the CD40/CD154 system might play an important role in the development of RA. Our experimental approach focuses on RA synovial fibroblasts (RA-SF) that are able to destroy articular cartilage independent of inflammation. To elucidate the specific role of those cells in RA pathophysiology the following questions are currently addressed: 1. Which mechanisms do activate the RA-SF? 2. How do the activated RA-SF attach to the cartilage? 3. How do RA-SF destroy cartilage and bone? Which mechanisms do activate the RA-SF? The process of activation is poorly understood. It is unclear, how far the synovial hyperplasia of RA resembles tumor diseases. Along this line some contradictory results exist concerning the role of the tumor suppressor protein p53. Some investigations could show the expression of p53 in the synovial lining including p53 mutations in RA synovium and in RASF, while other research groups could not confirm these data. Our group has demonstrated that the tumor suppressor PTEN was less expressed in the synovial lining of RA than in normal synovium, but no PTEN mutations could be found in the RA-SF. In addition, the in vivo and in vitro expression of the anti-apoptotic molecule sentrin suggests a functional resistance of RA-SF to undergo apoptosis. Although it is still unclear, whether certain viruses or viral elements are involved in the pathogenesis of RA (cause, consequence or coincidence?), certain viruses could play a role in the pathogenesis of RA. The endogenous retroviral element L1 was found to be expressed in the synovial lining, at sites of invasion as well as in RA-SF grown in vitro. Moreover, the data indicate that after the initial activation of L1 downstream molecules such as the SAP kinase 4, the met-protoonocogene and the galectin-3 binding protein are upregulated. How do the activated RA-SF attach to the cartilage? It has been suggested that integrins mediate the attachment of RA-SF to fibronectin rich sites of cartilage. Intriguingly, other adhesion molecules such as the vascular cellular adhesion molecule-1 (VCAM) and CS-1, a splice variant of fibronectin, are synthesized by RA-SF. By binding to these adhesion molecules, lymphocytes that express the integrin VLA-4 could be stimulated and thereby maintain the inflammatory process. Osteopontin is an extracellular matrix protein, which is associated with matrix adhesion and metastasis in tumors. In RA synovium, osteopontin was detectable in the synovial lining and at sites of invasion. How do RA-SF destroy cartilage and bone? The destruction of cartilage and bone in RA is mediated by matrix metalloproteinases (MMPs) and cathepsins. MMPs exist as secreted and as membrane bound forms. In vitro models are being developed to simulate the invasive process of RA-SF. In an in vitro model developed in our laboratory, the treatment of RA-SF with anti-CD44 or anti-interleukin-1 (IL-1) minimized matrix degradation of RA-SF. On the other hand, co-culture of RA-SF and U937 cells as well as application of interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) increased the invasiveness of RA-SF. Gene transfer of bovine pancreas trypsin inhibitor (BPMI) or interleukin-10 (IL-10) reduced the invasion of RA-SF, while transduction of interleukin-1 receptor antagonist (IL-1Ra) was chondroprotective. Double gene transfer of IL-10 and IL-1Ra resulted in both inhibition of invasion and chondroprotection.
10513801 Function and health-related quality of life: results from a randomized controlled trial of 1999 Sep OBJECTIVE: To assess the efficacy of leflunomide or methotrexate compared with placebo in improving function and health-related quality of life in patients with active rheumatoid arthritis (RA), and to examine correlations between response status (as defined by the American College of Rheumatology [ACR] response criteria) and improvement in these measures. METHODS: This 52-week, multicenter, doubleblind, controlled trial compared responses to the Health Assessment Questionnaire (HAQ), modified Health Assessment Questionnaire (MHAQ), Problem Elicitation Technique (PET), Medical Outcomes Study Short Form 36 (SF-36), and questions regarding work productivity among 3 treatment groups (leflunomide, methotrexate, and placebo). Improvement in the PET top 5 and SF-36 scales and component scores were compared with ACR response rates. RESULTS: Clinically meaningful and statistically significant (P<0.0001) improvement in measures of function and heath-related quality of life (MHAQ scores, all scales and disability index of the HAQ, weighted top 5 score of the PET, 5 of 8 scales and physical component score of the SF-36, and work productivity) was seen during treatment with leflunomide in comparison with placebo. Methotrexate administration resulted in significant improvements (P<0.05) in comparison with placebo in the MHAQ scores, HAQ disability index, weighted top 5 score of the PET, physical component score of the SF-36, and bodily pain scale. Compared with methotrexate, leflunomide administration resulted in significantly (P<0.01) more improvement in the MHAQ scores, 5 of 8 scales and disability index of the HAQ, weighted top 5 score of the PET, and 2 of 8 scales and physical component score of the SF-36. Improvements in the PET score, SF-36 physical component score, and work productivity correlated with the ACR responder rates of > or =20% and > or =50% improvement. CONCLUSION: Significant improvements in function and health-related quality of life occurred in patients with RA during treatment with leflunomide or methotrexate. These findings were clinically meaningful and correlated with the ACR response status.
11037876 The mechanism of taurine chloramine inhibition of cytokine (interleukin-6, interleukin-8) 2000 Oct OBJECTIVE: Taurine chloramine (Tau-Cl) has been shown to inhibit the production of proinflammatory cytokines (interleukin-6 [IL-6] and IL-8) by fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients. The present study was conducted to elucidate the mechanism of inhibitory action exerted by Tau-Cl. METHODS: The effects of Tau-Cl on 1) the transcription of genes coding for IL-6 and IL-8, and 2) the activity of nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors, which are crucial for the transcription of these cytokine genes, were investigated in FLS isolated from the synovial tissue of RA patients. FLS were cultured in vitro for 3-6 passages and stimulated with recombinant human IL-1beta (1 ng/ml) in the presence of either Tau or Tau-Cl, which were added simultaneously with the stimulus at concentrations of 250 microM or 500 microM. The relative expression of IL-6 and IL-8 messenger RNA (mRNA) was evaluated after 4 hours of stimulation, using competitive reverse transcriptase-polymerase chain reaction. The DNA binding activity of NF-kappaB and AP-1 was examined 30 minutes and 2 hours after cell stimulation, respectively, using electromobility gel shift assay. RESULTS: IL-1beta triggered a significant rise in the activity of transcription factors NF-kappaB and AP-1, followed by an elevation of cytokine IL-6 and IL-8 mRNA expression. Tau-Cl, but not Tau, reduced IL-1beta-triggered cytokine mRNA expression, exerting stronger inhibitory activity on the levels of IL-6 than on those of IL-8. Importantly, Tau-Cl also diminished the activity of NF-kappaB and, to a lesser extent, that of AP-1 transcription factor. Neither IL-1beta nor Tau-Cl affected the activity of octamer transcription factor 1. CONCLUSION: Tau-Cl inhibition of IL-6 and IL-8 synthesis in FLS from RA patients results from the ability of this compound to diminish the activity of the major transcriptional regulators (NF-kappaB and AP-1), which subsequently reduces the transcription of these cytokine genes.
11064596 [A case of hemophagocytosis syndrome with excessive Fe and ferritin concentration in serum 2000 Aug Investigation in the present case began with a high serum Fe concentration. The routine method for determining serum Fe concentration in our hospital is direct photoscopic assay. When we assayed serum Fe concentration by a deproteinization method, it showed a higher value. We also measured serum ferritin concentration, and suspected that high ferritin interfered with serum Fe concentration. We checked the dose-dependent effect of ferritin on serum Fe determination. The present case, a 64-year-old female, showed a reduction of Plt count, and an elevation of LDH, CRP and so on, meeting most of the criteria for hemophagocytosis syndrome. Bone marrow smears revealed phagocytosis of blood cells. The present case had been followed for rheumatoid arthritis and medicated with oral iron pills. In her liver and spleen, high amounts of Fe had accumulated, and excessive Fe was being released into the blood by any trigger, such as infection, stress, cytokine activation, and/or HPS.
9417261 [Tumors of the craniocervical junction. II. Morphological and radiological aspects with sp 1997 Oct Tumours of the craniocervical junction (ccjct) vary considerably in respect of survival times and cure rates. Correct localisation and tissue diagnosis are decisive for selecting the most suitable treatment. To do so one must be familiar not only with the clinical symptoms but also with the imaging features and the possible differential diagnoses of the individual tumour. In a second part of this overview we present the morphological and imaging features of the tumours occurring at the ccjct, and discuss in addition their epidemiological aspects.
9228548 Generation of kinins in synovial fluid from patients with arthropathy. 1997 Jun An enzyme-linked immunosorbent assay method is described for the measurement of kinin formation in synovial fluid from patients with rheumatoid and osteoarthritis (RA and OA). Basal kinin concentrations were less than 6 ng/ml in synovial fluid collected in the presence of inhibitors of kinin forming (kininogenase) and kinin metabolising (kininase) enzymes. During incubation of synovial fluid in the presence of kininase inhibitors alone, kinins were produced rapidly over the first 10 min, but production ceased completely within 30 min due to inhibition of the endogenous kininogenases; the rate of kinin generation during the early rapid phase correlated well with the plateau kinin concentration. Plateau kinin levels in synovial fluid from 15 patients with OA and RA ranged from 98 to 427 ng/ml, with a median value of 148 ng/ml. This study demonstrates clearly that synovial fluid from arthritis patients has the capacity to produce kinins. Although the number of patients was small, the amount of kinin generated in vitro varied over a wide range and a relationship between intra-articular kinin formation and clinical features may become apparent in a larger group of patients. The technique could also be used to investigate other biological systems in which a role has been proposed for kinins.
10023134 Synovial T cell receptor heterogeneity in early arthritis. 1999 Mar Rheumatoid arthritis (RA) has been postulated to result from a synovial immune response to an unidentified antigen(s), which should be mirrored by the T cell response. Here we investigate the T cell receptor (TCR) repertoire in the synovial tissue of patients with arthritis of early to moderate duration. We developed a nested polymerase chain reaction (PCR) technique to examine the TCR repertoire of small biopsy specimens, and show that the method is highly sensitive. We apply this technique to synovial biopsies obtained from the knee joints of patients with early to moderate duration arthritis (average duration of arthritis 1 year, range 0. 02-2.75 years). We examined biopsies from 5 normal individuals, 32 RA patients, 7 patients with seronegative spondyloarthropathy (Sp), and 12 patients with undifferentiated arthritis (UA). TCR message was detectable in 4/5 normals, 15/32 RA, 5/7 Sp, and 8/11 UA biopsies, with sampling error likely accounting for most negative biopsies. The average numbers of TCR Vbetas detected per TCR-positive biopsy were 5.0 +/- 3.7 for normals, 12.7 +/- 8.4 for RA, 18.0 +/- 7.4 for Sp patients, and 14.4 +/- 10.2 for UA. Examination of TCR messages by single-stranded conformational polymorphism analysis showed similar proportions of dominant clones in the normals compared with the patients with inflammatory arthritis. Sequence analysis was performed on 33 dominant clones from 16 patients. Sequence alignment of the third hypervariable regions showed some evidence of disease-specific sequence clustering for Sp, while some RA sequences showed similarity to previously described motifs. These data indicate greater TCR heterogeneity in early Sp and UA compared with normal synovium. Disease-specific TCR sequences may occur in early RA and Sp.
10211890 Wegener's granulomatosis associated with renal cell carcinoma. 1999 Apr OBJECTIVE: To determine the frequencies and types of malignant neoplasms occurring before or simultaneously with the diagnosis of Wegener's granulomatosis (WG), and to test for the presence of "Wegener's autoantigen," proteinase 3 (PR3), in malignant tissues from WG patients to ascertain whether an association exists between malignancy and WG. METHODS: A retrospective statistical analysis was performed on the medical records of 477 patients with WG as compared with a control group of 479 patients with rheumatoid arthritis (RA). A murine monoclonal antibody was used to test malignant tissues for the presence of PR3. RESULTS: A malignant neoplasm was found in 23 patients in the WG group and in 18 patients in the control group. The odds ratio for malignant neoplasm in the WG group was 1.79 (P = 0.0876, 95% confidence interval [95% CI] 0.92-3.48). Seven patients with renal cell carcinoma were found in the WG group compared with 1 patient in the control group, for an odds ratio of 8.73 (P = 0.0464, 95% CI 1.04-73.69). Simultaneous occurrence of cancer and WG was observed in 14 patients with WG compared with 1 control patient, for an odds ratio of 18.00 (P = 0.0059, 95% CI 230-140.67). Furthermore, the diseases occurred simultaneously in 5 of the 7 patients with both WG and renal cell carcinoma, but not in the single patient in the control group with RA and renal cell carcinoma. PR3 could not be detected in any of the 8 malignant tissue samples (4 renal cell carcinomas) investigated in the patients from the WG group. CONCLUSION: The close temporal association between renal cell carcinoma and WG suggests that malignancy is, in some cases, a trigger for the development of WG. However, since PR3 was not found in malignant tissues from the WG patients, the immunopathologic mechanisms leading to autoimmunity and vasculitis remain unclear.
10323450 p53 overexpression in synovial tissue from patients with early and longstanding rheumatoid 1999 May OBJECTIVE: The p53 tumor suppressor gene is overexpressed in synovial tissue (ST) from patients with longstanding rheumatoid arthritis (RA), and may contain somatic mutations. The aim of this study was to determine p53 expression in ST from RA patients in different stages of the disease, compared with disease controls. METHODS: ST biopsy specimens were obtained from the knee joints of 31 RA patients in varying disease phases, 8 patients with reactive arthritis (ReA), 10 patients with inflammatory osteoarthritis (OA), and 6 control patients (4 with meniscus pathology, 2 with vascular insufficiency). ST was also obtained from the clinically uninvolved knee joints of 9 RA patients. Expression of p53 was determined by immunohistology with DO1 monoclonal antibody (mAb) in all patients and by Western blot analysis with DO7 mAb in a subgroup of the patients. RESULTS: The p53 protein was detected by immunohistology in 10 of the 13 patients with early RA (duration <6 months) and in 12 of the 14 patients with longstanding RA (duration >5 years). The p53 protein was also demonstrated in clinically uninvolved knee joints. Western blots revealed immunoreactive p53 in ST extracts from all RA patients. Expression of p53 was about twice as high in ST from patients with longstanding RA as in early RA samples, but the difference did not reach statistical significance. Small amounts of p53 were also detected in ST from ReA and OA patients, although the expression in RA synovium was significantly higher. Immunohistologic analysis of normal ST gave negative results for p53. CONCLUSION: This study shows that p53 overexpression is specific for RA, compared with OA and ReA. This phenomenon is probably secondary to increased production of wild-type p53 protein in response to DNA damage and secondary to somatic mutations caused by the genotoxic local environment in inflamed ST. Of interest, p53 overexpression can also be found in the earliest stages of RA and in clinically uninvolved joints.
10427794 Meloxicam-induced liver toxicity. 1999 Apr We report the case of a female patient with rheumatoid arthritis who developed acute cytolytic hepatitis due to meloxicam. Recently introduced in Belgium, meloxicam is the first nonsteroidal antiinflammatory drug with selective action on the inducible form of cyclooxygenase 2. The acute cytolytic hepatitis occurred rapidly after meloxicam administration and was associated with the development of antinuclear antibodies suggesting a hypersensitivity mechanism. This first case of meloxicam related liver toxicity demonstrates the potential of this drug to induce hepatic damage.
9125248 Characteristic epitope recognition pattern of autoantibodies against eukaryotic ribosomal 1997 Apr OBJECTIVE: To define the epitope-recognition pattern and the fine specificity of the autoantibody response to protein L7 in patients with rheumatic diseases. METHODS: The epitope-recognition pattern was studied by enzyme-linked immunosorbent assay utilizing overlapping fragments of L7. The fine specificity was examined by binding inhibition and isoelectric focusing. RESULTS: We observed a disease-specific epitope-recognition pattern of anti-L7 autoantibodies. There was one immunodominant epitope that was recognized by all anti-L7-positive sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc). Additional recognition of minor epitopes was observed; it arises by intramolecular epitope spreading and was correlated with disease activity in SLE patients. SSc patients differed from SLE and RA patients in that their sera did not recognize certain minor epitopes. The major epitope was recognized by high-affinity autoantibodies of limited heterogeneity. Minor epitopes were recognized by heterogeneous low-affinity autoantibodies. CONCLUSION: The anti-L7 autoantibody response is oligoclonal. Additional B cell clones are activated by antigen during active phases of disease.
11340750 Leflunomide: new antirheumatic drug. Effect on pregnancy outcomes. 2001 Apr QUESTION: I am treating a 34-year-old woman with rheumatoid arthritis. She began taking the new drug leflunomide (Arava) 6 months ago and had good clinical response. She is now planning her first pregnancy. What should she do? ANSWER: Leflunomide is a new and effective disease-modifying antirheumatic drug. Animal studies have shown an increased rate of malformations and fetal death in various species, but there are no data on pregnancy outcomes in humans treated with leflunomide. Since the drug has a prolonged and unpredictable elimination half-life, it should be stopped during pregnancy. The manufacturer recommends that patients who wish to become pregnant be treated with cholestyramine, which enhances elimination.
11748261 Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treati 2001 Dec Immune and inflammatory systems are controlled by multiple cytokines, including ILs and INFs. These cytokines exert their biological functions through Janus tyrosine kinases and STAT transcription factors. One such cytokine, IL-6, has been proposed to contribute to the development of rheumatoid arthritis (RA). We found that STAT3 was strongly tyrosine phosphorylated in synovial tissue of RA patients, but not those with osteoarthritis. Blockade of the IL-6-gp130-JAK-STAT3-signaling pathway might therefore be beneficial in the treatment of RA. We show here that the mRNA for the endogenous cytokine signaling repressor CIS3/SOCS3 is abundantly expressed in RA patients. To determine whether CIS3 is effective in treating experimental arthritis, a recombinant adenovirus carrying the CIS3 cDNA was injected periarticularly into the ankle joints of mice with antigen-induced arthritis or collagen-induced arthritis (CIA). Periarticular injection of CIS3 adenovirus drastically reduced the severity of arthritis and joint swelling compared with control groups. CIS3 was more effective than a dominant-negative form of STAT3 in the CIA model. Thus, induction of CIS3 could represent a new approach for effective treatment of RA.
11014356 Mesenchymal cells expressing bone morphogenetic protein receptors are present in the rheum 2000 Sep OBJECTIVE: To evaluate the presence of cells of an early mesenchymal lineage, as judged by the expression of bone morphogenetic protein receptors (BMPRs), in the joints of normal individuals and patients with rheumatoid arthritis (RA). METHODS: Synovial fluids, single cell suspensions of cultured fibroblast-like synoviocytes (FLS), and synovial tissues were examined by immunohistology with antibodies to BMPR type IA (BMPRIA), BMPRIB, and BMPRII and then quantified using computerized image analysis. Other antibodies were evaluated by cytofluorography. RESULTS: In primary cultures of joint effusions from patients with RA and other forms of inflammatory arthritis, there were large adherent cells with the appearance of either fibroblasts or stromal cells that stained with antibodies to mesenchymal elements-CD44, type I collagen, alpha-actin, and vimentin-but not with antibodies to hematopoietic markers. These cells proliferated rapidly, expressed BMPRIA and BMPRII, and soon became the predominant cells in culture. They were retained through multiple passages and persistently displayed surface vascular cell adhesion molecule 1. Immunohistochemical analysis of cultured RA FLS (passages 3, 4, and 6; n = 6) revealed that 11.6% were BMPR-positive, while only 2.0% of osteoarthritis FLS (passage 4; n = 3) were BMPR-positive, and 1 normal synovial culture had no BMPR-positive cells. In all RA synovial membranes examined (n = 9), BMPRI- and BMPRII-expressing cells were identified in the intimal lining and were also scattered in the subintima. These cells constituted approximately 25% and approximately 7% of the cells in each area, respectively. Double immunostaining showed no coexpression of BMPR-positive cells with CD68, CD34, or CD3. Cells expressing BMPR were not seen in any normal synovial samples (n = 4). Strong staining for BMPR was identified on cells at the invasive front of the pannus and at sites of cartilage erosion. CONCLUSION: The inflamed RA joint contains BMPR-positive mesenchymal cells. Their origin is still speculative, but since their counterparts in the bone marrow are essential for osteoclastogenesis, support lymphocyte development and maturation, and protect T cells and B cells from programmed cell death, the BMPR-positive cells may be essential elements in the pathogenesis of RA and other inflammatory forms of chronic synovitis.
10415590 Hormonal regulation of tumor necrosis factor-alpha, interleukin-12 and interleukin-10 prod 1999 Jun 22 Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) frequently develop and progress in settings in which sympathoadrenomedullary and gonadal hormone levels are changing, e.g., during pregnancy, postpartum period, menopause, estrogen administration. This paper addresses the view that adrenal and gonadal hormonal deficiency facilitates excessive macrophage production of TNF-alpha and IL-12 that characterizes RA, whereas excessive estrogen action is suggested to play an essential role in the production of IL-10 in patients with SLE. Disease activity in SLE, in contrast to RA, appears to be associated with high-level production of IL-10, relative to the proinflammatory cytokines, TNF-alpha and IL-12. Accumulating data suggest that novel therapeutic approaches may ultimately be developed from continued investigation of the role of the neuroendocrine factors in RA and SLE.
10381037 Correlation between radiation dose, synovial thickness, and efficacy of radiosynoviorthesi 1999 Jun OBJECTIVE: To correlate the therapeutic efficacy of radiosynoviorthesis (RSO) to radiation doses achieved. METHODS: In 20 patients with known rheumatoid arthritis, radiosynoviorthesis was performed in 36 joints. Arthritis disease activity was assessed by "blood pool scintigraphy" (n = 29) score after injection of 370 MBq 99mTc-MDP, before and at 1, 2, and 5 months after the RSO in 12 patients. For semiquantitative measurements, a region-of-interest technique was applied. Synovial thickness and response to the RSO were evaluated by joint ultrasonography. Pain levels were evaluated semiquantitatively. Dosimetry (n = 20) was calculated using planar quantification according to the MIRD scheme. RESULTS: The mean radiation absorbed dose of 186Re-sulfate to the whole body was 5.3+/-2.7 cGy, liver 10.0+/-8.1 cGy, spleen 20.3+/-22.9 cGy, kidneys 9.4+/-11.4 cGy, and at the injected joints of the shoulder 120.5+/-32.2 Gy, hand 130.0+/-12.6 Gy, elbow 83.6+/-38.7 Gy, and talar/subtalar joint 84.1+/-30.7 Gy. In 7 cases, where mandatory immobilization of the joint was not possible, the dose to the lymph nodes (n = 25) was 25.9+/-53.8 Gy (maximum 189 Gy) and to single lymph nodes 14.6+/-11.2 Gy (maximum 63 Gy). The reduced doses to the synovia (at 40% leakage) were: 169Er-citrate 73.10+/-25.25 Gy; 90Y-citrate 59.25+/-46.45 Gy; 186Re-sulfate 65.40+/-32.55 Gy. In cases of complete immobilization, the dose to the lymph nodes was negligible: 169Er-citrate (n = 7), whole body dose 0.4 cGy, lymph nodes 2.3 Gy, finger joints 132.3+/-34.3 Gy; 90Y-citrate (n = 6), whole body dose 15.5 cGy, liver dose 26.5 cGy, splenic dose 11.9 cGy, kidney dose 67 cGy, joint knee joint dose 130.1 Gy. Regarding therapeutic effect, mean reduction of the 99mTc-MDP blood pool activity was 41% at first month, 48% at second month, 48% at the fifth month, 48% in larger joints, and 63% in finger joints. Three and 6 months after RSO, sonography showed a mean reduction in synovial swelling: in the knee joint 1.67 and 4.38 mm, respectively; in the larger joints (shoulder, elbow, hand, talar/subtalar) 0.88/1.93 mm; and in finger joints 0.53/1.76 mm. Clinically, best results were observed in the finger joints. CONCLUSION: 1. We observed a significantly higher radiation absorbed dose to the lymph nodes and lower dose to the synovia in the absence of joint immobilization. Immobilization of the joint is essential. 2. At 2 months after treatment, a significant reduction of blood pool activity and synovial swelling was observed, with further improvement in the following months, especially in the finger joints. 3. There is a strong correlation between the reduction of blood pool activity, synovial swelling, and improvement of pain.
10220815 [Connective tissue diseases in the hospital outpatient service in Lomé (Togo)]. 1999 Jan PURPOSE: There have been few studies of connective tissue diseases in Africa. METHODS: A retrospective study was conducted in order to describe the various connective tissue diseases and their semiological profile in patients attending the dermatology and rheumatology units at Lomé hospital. RESULTS: Clinical examinations showed that eighty-four (0.2%) out of the 34,169 patients were suffering from connective tissue diseases. Diseases that were encountered were the following: scleroderma (18 cases), systemic lupus erythematosus (four cases), discoid lupus erythematosus (15 cases), rheumatoid arthritis (29 cases), polymyositis and dermatomyositis (16 cases), juvenile rheumatoid arthritis (one case), giant cell arteritis (one case). Raynaud's syndrome was present in six out of the 18 patients suffering from scleroderma. Nephrotic syndrome was observed in a patient suffering from systemic lupus erythematosus. A septicemia caused this patient's death. Two patients suffering from polymyositis had cancer. No etiology was found in the 14 other patients. Hip involvement was present in two patients suffering from rheumatoid arthritis. Patients with rheumatoid arthritis had no systemic involvement (nodulitis, vasculitis). CONCLUSION: Our results are in agreement with those of previous studies on connective tissue diseases in Africa. However, further studies are required to better understand the epidemiological and semiological profiles of connective tissue diseases in Africa.