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ID PMID Title PublicationDate abstract
9195531 Multiple bursitis in systemic sclerosis. 1997 Jun Bursitis is a common clinical entity usually induced by trauma and infection. It often occurs in inflammatory diseases such as gout and rheumatoid arthritis. We describe a patient with systemic sclerosis who developed multiple bursitis in the later stage of the disease.
11525197 [Radiation-induced cataract: physiopathologic, radiobiologic and clinical aspects]. 2001 Aug Cataractogenesis is a widely reported late effect of irradiated crystalline lens. In this review the authors discussed the different aspects of radiation cataract pathogenesis, and the different mechanisms involved in the lens opacification, particularly the epithelium modifications such as epithelial cell death. The authors also reported the influence of radiation exposure on cataract formation following total body irradiation (TBI) and autologous or allogeneic bone marrow transplantation for hematologic malignancies. Moreover, the radiobiological parameters are not studied for the crystalline lens of human. We applied for the first time the linear-quadratic (LQ) and biological effective dose (BED) concept to TBI data. The calculated value of alpha/beta of 1 Gy is in the range of the values reported for the other late responding tissues. The other risk factors for cataract development after TBI such as age, gender, central nervous system boost, long-term steroid therapy and heparin administration are discussed. In terms of cataract or sicca syndrome prevention, numerous compounds have been successfully tested in experimental models or used for the prevention of radiation-induced xerostomia in patients treated for head and neck cancer. However, none of them has been clinically evaluated for ocular radiation late effects prevention. In this report the authors discussed some of the radioprotectors potentially interesting for radiation-induced cataract or sicca syndrome prevention.
24383692 "Inverse wrap": an improved implantation technique for virus-transduced synovial fibroblas 2001 Jun Abstract The SCID mouse model for rheumatoid arthritis (RA) is an established and reliable approach to examining the distinct mechanisms operative in RA synovium, and evaluating novel gene therapy strategies. However, serum concentrations of circulating gene therapy products following gene transfer are frequently too low to allow detection. This problem stimulated us to develop a novel implantation technique to improve the yield of these soluble gene products. Synovial fibroblasts from patients with RA were cultured, passaged, and transduced with Ad5 sTNFRp55:Ig. sTNFRp55:Ig production was confirmed by ELISA, and then cells were implanted into SCID mice using a novel implantation strategy in which pieces of human cartilage were engrafted into a fibroblast-saturated inert sponge. Thereafter, the sponges were implanted under the skin of the mice instead of under the kidney capsule, as in the original approach, allowing co-implantation of larger pieces of cartilage together with higher numbers of adenovirus-transduced RA synovial fibroblasts. The improved implantation technique not only resulted in a reduction in the number of mice needed in each experiment by approximately 60%, and a reduction of the time taken for surgery by about 50%, but also considerably enhanced the serum concentrations of the gene product sTNFRp55-Ig, allowing detection of the soluble TNF receptor p55 by standard ELISA. In summary, the improved implantation technique for the SCID mouse model for RA results in more economic animal treatment, and facilitates the detection and quantification of circulating gene products following adenovirus-based gene transfer into synovial fibroblasts.
11201912 Cataract surgery in children with uveitis. 2001 Jan PURPOSE: To report the technique and postoperative results of cataract surgery in children with uveitis. METHOD: Between 1988 and 1998, nine children (age range: 2.5-11 years) who developed secondary uveitic cataract and underwent cataract extraction were studied retrospectively. Seven children had juvenile rheumatoid arthritis and two had chronic anterior uveitis of unknown etiology. The surgical technique was lensectomy and wide anterior vitrectomy with limbal approach, lysis of anterior synechiae and in some cases, peripheral iridectomy. Postoperative aphakia was corrected with soft contact lenses in all patients. Follow-up ranged from 6 months to 6 years. RESULTS: Postoperatively, visual acuity in all patients improved and final visual acuity ranged from 20/70 to 20/25. Significant intraoperative complications did not occcur in any patient. One boy with juvenile rheumatoid arthritis developed cystoid macular edema 1 month postoperatively, which was successfully managed. He also developed hypertonia 1 year later, which was also successfully managed. Seven of the nine children had fewer and milder relapses of uveitis after surgery. CONCLUSION: Cataract surgery, using the lensectomy-vitrectomy technique in children with uveitis, is a safe technique with a relatively small percentage of postoperative complications and good functional results.
11052469 Glucocorticoid-induced osteoporosis: pathogenesis and management. 2000 Glucocorticoid- (GC-) induced osteoporosis and an increased risk of fractures are one of the most serious problems for patient using long-term GC therapy, such as those with rheumatoid arthritis, autoimmune diseases, inflammatory bowel diseases, bronchial asthma, and chronic lung diseases. GCs are known to affect both bone formation and resorption. In rheumatoid arthritis, the etiology of bone loss is multifactorial, including local inflammation around joints, release of bone-absorbing cytokines, physical inactivity, and malnutrition, in addition to the use of GC. Two guidelines have been published, by the American College of Rheumatology Task Force in 1966 and by the UK Consensus Group in 1998. Both guidelines recommend that patients 'receiving GC therapy at doses of 7.5 mg/day of prednisolone or more for 6 months or longer should have their bone mineral density measured and begin preventive therapies. Calcium and vitamin D supplements, sex hormone replacement, and weight-bearing exercise are the first-line therapies. For patients who are unable to take sex hormone replacement therapy (HRT), bisphosphonates are recommended by both guidelines. In this article, we briefly summarize the pathogenesis of GC-induced osteoporosis and its prevention and treatment.
10328576 Biologic agents in the treatment of inflammatory rheumatic diseases. 1999 May In 1998, further details on the treatment of patients with rheumatoid arthritis with biologic agents became available. Biologic agents with established efficacy, e.g., the chimeric tumor necrosis factor-alpha monoclonal antibody cA2, were tested in combination with methotrexate (MTX), with evidence of synergistic effects. These trials revealed new, important information on the incorporation of tumor necrosis factor-alpha blocking agents into a treatment regimen of rheumatoid arthritis using established disease-modifying antirheumatic drugs and innovative biologic agents. Clinical trials testing new agents, e.g., T-cell receptor peptides in a double-blind, placebo-controlled fashion represented new developments with regard to T cell-directed treatment principles. In addition, new developments in the preclinical phase are discussed.
9510087 Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta 1998 Mar 1. The effects of antimalarial drugs on the intracellular signaling leading to activation of the phospholipase C and phospholipase A2 pathways and the induction of proinflammatory cytokines have been studied in mouse macrophages. 2. Both chloroquine and quinacrine, and to a lesser extent hydroxychloroquine, inhibited arachidonate release and eicosanoid formation induced by phorbol diester. This inhibition was due to that of the activation of the arachidonate-mobilizing phospholipase A2. 3. All three antimalarials potently inhibited arachidonate release induced by zymosan. They also inhibited the zymosan-induced formation of inositol phosphates, which hints that an inhibitory effect at the phospholipase C level might explain the inhibition of the response to zymosan. 4. Quinacrine, and to a lesser extent chloroquine, has an inhibitory effect on the lipopolysaccharide- or zymosan-induced expression of interleukin 1beta and tumor necrosis factor alpha, both at the mRNA and protein levels. This, in particular, has important implications for the mode of action of these compounds in rheumatoid arthritis.
9467582 Cytosolic autoantigens in lymphocytic hypophysitis. 1998 Feb Lymphocytic hypophysitis was first recognized postmortem, then by biopsy, but detection of antipituitary autoantibodies by immunofluorescence has proved unsatisfactory. Immunoblotting has the dual advantages of increased specificity and identification of the mol wt of autoantigens. Sera from 115 patients and 52 normal subjects were immunoblotted against human autopsy pituitary cytosolic proteins. Among the neurosurgical cohort (30), 10 patients had biopsy-proven lymphocytic hypophysitis, and 20 had hypopituitarism secondary to tumor. There were 22 cases with suspected hypophysitis; 47 with either Hashimoto's, Graves', or Addison's diseases; and 15 with rheumatoid arthritis. Antipituitary autoantibodies reactive to a 49-kDa pituitary cytosolic protein were found in 70% of biopsy-proven lymphocytic hypophysitis, 55% of suspected hypophysitis, 42% of Addison's disease, 20% of pituitary tumors, 15% of patients with thyroid autoimmunity, 13% of rheumatoid arthritis patients, and 9.8% of normal subjects. Reactivity to a 40-kDa cytosolic protein was also found in 50% of patients with biopsy-proven disease. These 49- and 40-kDa autoantigens are conserved across species and are not exclusive to pituitary tissue. Immunoblotting has demonstrated antipituitary autoantibodies to 49- and 40-kDa cytosolic proteins in biopsy-proven cases of lymphocytic hypophysitis.
17353592 Juvenile rheumatoid arthritis: The Saudi Experience. 1997 Jul We retrospectively studied the charts of 115 Arab children with juvenile rheumatoid arthritis (JRA), all of whom satisfied the American College of Rheumatology (ACR) criteria for JRA. They were followed between 1978 and 1993 at King Faisal Specialist Hospital and Research Centre and King Khalid University Hospital in Riyadh, Saudi Arabia. All patients were followed up for at least 18 months. The female to male ratio was 1.2:1, and the mean age of onset of the disease was six years. Ninety of the patients were Saudis and the remainder were Middle Eastern Arabs. The mode of onset was systemic in 44%, polyarticular in 30%, and periarticular in 26%. Chronic uveitis was found in only two of the children (1.7%). Antinuclear antibody (ANA) was determined in 96 patients and was positive in 29 (30%). Amyloidosis was not detected in this study population. The clinical and laboratory manifestations of this disease are presented. This review shows that the spectrum of clinical presentation differs in Arab children from those in the West. Systemic and polyarticular onset subtypes were more common, and the incidence of uveitis and amyloidosis was lower. Whether this reflects a genuine difference in the pattern of the disease, or is due to bias in referral pattern, remains to be detected. The answer is currently being sought through an ongoing prospective study.
12167974 [Rheumatoid arthritis: frequency of hospitalization and evaluation of economic burden]. 2001 About 10% of the Italian general population is affected by rheumatic diseases (RD). Due to their chronic and disabling nature, RD are cause of an annual economic burden evaluated in about 17,000 billions italian lire. In Italy, rheumatoid arthritis (RA) affects nearly 400,000 people. One hundred RA patients answered to a questionnaire concerning hospitalization during the first ten years of disease. Seventy-two patients needed hospitalization with a total of 147 hospital admissions. Eleven patients were admitted thrice to the hospital, 53 patients twice, and 8 patients only once with a mean number of hospital admissions per patients of 1.8. Hospitalization costs were calculated on the basis of the cost of the DRG for RA and inferred for the total population of Italian RA patients. The result was about 350 billions italian lire. Two methods were used in order to evaluate the economic impact of RA including both direct and indirect costs. First, internationally accepted criteria for cost assessment were applied to the Italian system. Second, different evaluations were performed by the authors. With the first method, direct and indirect costs were 3,000 and 3,500 billions Italian lire, respectively. With the second method, based on a more precise assessment of costs including the costs of wager from a reduction or cessation of work, the total costs for RA was between 3,100 and 3,600 billions Italian lire. Since psychological and social problems often influence patients with RA in relation to their families and society, the issue of intangible costs has also been addressed.
19078342 Influence of hormonal events on disease expression in patients with the combination of sys 1999 Feb The concurrent presence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) ("rhupus" or "rufus") has been described in the literature. However, it has not been clear to what extent and under what circumstances clinical disease expresssion can undergo transitions from one disease to the other. We postulated that major hormonal events might have an influence on disease expression in such patients and conducted a retrospective study of 1507 patients with RA and 893 with SLE. In this population, 13 patients were identified as having convincing clinical diagnoses of both RA and SLE. Although 6 of these 13 patients had symptoms and signs of RA and SLE concurrently during their entire illness, 7 patients had clearly identifiable transitions from SLE to RA, and in one of these patients the reverse occurred as well. Of the 7 transitions from SLE to RA, 5 were associated with menopause (3 of these patients were receiving hormone replacement therapy) and the other 2 occurred in the postpartum period. The one change from RA to SLE in this series occurred during pregnancy. Thus, pregnancy, the postpartum period, and menopause can modulate disease expression in patients with both SLE and RA. It is speculated that, in patients with an autoimmune predilection, a high-estrogen environment (premenopause, pregnancy) favors the clinical expression of SLE, whereas a low-estrogen environment favors more RA-like disease, possibly because of the immunomodulatory effects of sex-steroids. The clinical implication is that in the management of patients with autoimmune diseases such as SLE and RA, hormonal alterations could result in changes in disease expression that might necessitate changes in treatment.
24383776 Osteoclast differentiation factor induces synovial macrophage-osteoclast differentiation i 2001 Dec Abstract The aim of this study was to clarify the role of osteoclast differentiation factor (ODF) and osteoprotegerin (OPG) in synovial macrophage-osteoclast differentiation. Synovial macrophages were cultured in the presence of macrophage-colony-stimulating factor (M-CSF) and/or ODF. OPG was added to cocultures of synovial macrophages and UMR106. The cultures on glass coverslips were stained with osteoclast-associated markers, tartrate-resistant acid phosphatase (TRAP), and vitronectin receptor (VNR), as well as macrophage-associated markers CD11b and CD14. Functional evidence of osteoclast formation was determined by a resorption pit assay. To investigate whether rheumatoid arthritis (RA) synovial cells expressed messenger RNA (mRNA) for ODF, OPG, and the receptor activator of NF-κB (RANK), we performed a polymerase chain reaction (PCR) analysis. The addition of M-CSF or ODF alone induced TRAP-positive multinucleated cell formation. Resorption pits were rarely detected with M-CSF alone. ODF was capable of inducing bone resorption and enhancing osteoclastogenesis, as well as bone resorption in the presence of M-CSF. In the coculture system, both osteoclast formation and bone resorption were inhibited by OPG in a dose-dependent manner. In all experiments, synovial cells, including macrophages and fibroblasts, expressed the mRNA for RANK, ODF, and OPG. Our findings suggest that ODF plays a role in regulating RA synovial macrophage-osteoclast differentiation, and that synovial cells might have the ability to produce ODF. OPG might be further developed as a new strategy for treating bone destruction in RA joints.
10992726 Secondary renal amyloidosis in adult onset Still's disease: case report and review of the 2000 Jul We report a 25-year-old Korean woman with Adult onset Still's disease (AOSD) presented with renal amyloidosis, which had developed four years after disease onset. We successfully treated her with prednisolone, colchicine and cyclophosphamide. A review of the literature uncovered about 10 cases, most of which were treated by various regimens that resulted in poor outcomes. Renal amyloidosis should be suspected in patients with AOSD who have unexplained proteinuria. Although the mechanism of renal amyloid deposition is not well known, earlier histopathologic diagnosis and choice of regimen may affect prognosis.
10366102 Polymorphic haplotypes of the interleukin-10 5' flanking region determine variable interle 1999 Jun OBJECTIVE: To determine the distribution of the interleukin-10 (IL-10) 5' flanking region haplotypes in children with arthritis and in controls, and to investigate the functional significance of each haplotype. METHODS: Sequence-specific oligonucleotide probing was used to determine haplotype frequency. Transient transfection studies were used to investigate the transcription of reporter genes driven by each haplotype. Whole blood cultures were performed to assess IL-10 production by each genotype. RESULTS: Patients with arthritis involving >4 joints were more likely to have a genotype with an ATA haplotype than those whose arthritis remained restricted to <4 joints. This ATA haplotype was associated with lower transcriptional activity than the GCC haplotype (P = 0.02), and the ATA/ATA genotype was associated with lower IL-10 production under lipopolysaccharide stimulation than other genotypes (P < 0.02). CONCLUSION: The results of this study demonstrate the functional significance of the ATA haplotype and reveal a significant association of genotypes containing this haplotype with extended oligoarthritis.
11407305 A role for parathyroid hormone-related protein in the pathogenesis of inflammatory/autoimm 2001 Jun Our increased understanding of the critical role of cytokines in chronic inflammatory/autoimmune diseases has led to the recent development of effective anti-cytokine treatments. In particular, agents blocking the function of TNF-alpha, a cytokine first identified as an endotoxin-inducible mediator of tumor cell necrosis, are now licensed for the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease. However, TNF-alpha is but one member of a cytokine network that is responsible for mediating these inflammatory disorders. Therefore, as our understanding of the pathophysiologic role of other members of this inflammatory network increases, other cytokines may similarly be identified as effective targets for treatment. In this article, we will review evidence which suggests that parathyroid hormone-related protein (PTHrP), a peptide which, like TNF-alpha, was first identified because of its effects in the setting of malignancy, may in fact serve an important non-neoplastic, physiologic function by mediating the inflammatory/autoimmune host response. Data identifying PTHrP as a member of the cytokine network induced in multi-organ inflammation and rheumatoid arthritis will be summarized, initial evidence comparing the therapeutic efficacy of PTHrP- vs. TNF-alpha-blockade in the treatment of endotoxemia will be reviewed, and potential future areas of research, including assessment of the effects of PTHrP blockade in the treatment of RA, will be discussed.
9713902 Evidence supporting an association between the DRB1 gene and schizophrenia in Japanese. 1998 Jul 27 The authors attempted a replication of earlier studies that detected an association of HLA-DR4 and DR1 with schizophrenia. Japanese patients with schizophrenia (n = 266, DSM-III-R criteria) and Japanese controls (n = 283) were genotyped for DR1 and DR4 alleles using a combination of group-specific polymerase chain reaction (PCR) amplification and PCR-restriction fragment length polymorphism. Significant positive association with HLA-DR1 [odds ratio (OR) = 1.87, corrected p = 0.04] and a negative association with HLA-DR4 (OR = 0.63, corrected p = 0.02) was noted. DR1 and DR4 were independently associated with schizophrenia. The association of the DR1-positive/DR4-negative genotype with schizophrenia was modest (OR = 2.60, 95% confidence intervals = 1.38-4.89, corrected p = 0.008). Thus, these findings support an association of the HLA DRB1 gene locus with schizophrenia in the Japanese population. Since both DR4 and DR1 are positively associated with rheumatoid arthritis, our findings are not simply consistent with the known negative association between schizophrenia and rheumatoid arthritis.
11361219 The influence of mannose binding lectin polymorphisms on disease outcome in early polyarth 2001 May OBJECTIVE: To determine whether variant alleles of the mannose binding lectin (MBL) gene causing low serum concentrations of MBL are associated with increased susceptibility to rheumatoid arthritis (RA) and erosive outcome in an inception cohort of patients with early polyarthritis. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 68 Danish patients with incident early polyarthritis observed for one year. The associations between MBL and specific HLA-DRB1 genotypes and disease outcomes were analyzed. RESULTS: Among the patients with early polyarthritis 7.4% (5/68) and 41.2% (28/68) were homozygous and heterozygous for MBL variant alleles, compared with 2.8% (7/250) and 34.4% (86/250) of healthy controls (p = 0.09), while the corresponding figures in the patients with RA were 10% (5/50) and 42% (21/50) (p = 0.03), and in the patients with erosive RA 18.8% (3/16) and 35.3% (6/16), respectively (p = 0.004). Patients with early polyarthritis homozygous for MBL variant alleles had an increased risk of having erosive RA at inclusion by a factor of 4.7 (p = 0.02) and after one year by a factor of 3.6 (p = 0.04). MBL deficiency was associated with increased levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) at inclusion (p < 0.05). HLA-DRB1 alleles were not found to be associated with disease outcome. CONCLUSION: MBL variant alleles appear to be weak susceptibility markers for RA, and patients with early polyarthritis and homozygous for MBL structural variant alleles have a higher risk of developing early erosive RA. These findings, together with the positive association between MBL variant alleles and the increased serum levels of IgM RF and CRP, point at the MBL gene as a relevant locus in the pathophysiology of RA.
11053070 Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogen 2000 Nov OBJECTIVES: (a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality. METHODS: Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls. RESULTS: High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL(3) cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL(3), was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL(3) cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant. CONCLUSION: Raised levels of LDL(3) and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.
9093587 The clinical patterns of arthritis in children with familial Mediterranean fever. 1997 Jan We studied the clinical patterns of arthritis in 133 children with familial Mediterranean fever (FMF) over 5.5 years. Six clinical patterns were noted. The commonest was recurrent monoarticular arthritis as seen in 95 children (71%), mainly affecting the knee and ankle joints. This type followed two different courses: acute (< 1 month) and chronic (> 1 month). In 18 (14%) children, both knee or ankle joints were simultaneously and symmetrically involved: here too the course was either acute or chronic. Five (4%) children developed symmetric polyarthritis similar to juvenile rheumatoid arthritis (JRA). Six (4%) children developed asymmetric oligoarticular arthritis similar to acute rheumatic fever (ARF). The small joints of the hands (SJH) were involved in seven (5%) children, and the small joints of the feet in one. One child developed sacroiliitis similar to ankylosing spondylitis (AS). Between attacks, the joints were normal. Overall, outcome was good: residual damage of the hip joint occurred in one patient and of the shoulder in another. Although the clinical presentation and course of FMF arthritis are diverse, delineating these clinical patterns may help with earlier recognition and treatment. The low incidence of residual articular damage in this study may be related to the use of colchicine prophylaxis.
10323491 Anticomplement activity of triterpenes from Crataeva nurvala stem bark in adjuvant arthrit 1999 Apr Adjuvant arthritis is widely used as an experimental model for rheumatoid arthritis and inflammation. It is useful in the evaluation of anti-inflammatory drugs. Lupeol is a naturally occuring triterpene isolated from Crataeva nurvala stem bark, and its ester lupeol linoleate was synthesized. The effects of lupeol and lupeol linoleate on the development of complement in adjuvant arthritis in rats were studied and compared with those of indomethacin. The effect of lupeol linoleate in reducing the foot-pad thickness and complement activity in arthritic rats was even greater than that of unesterified lupeol and indomethacin. Because complement is highly involved in inflammation, the results suggest that the anti-inflammatory activity of triterpenes may be due to their anticomplementary activity.