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ID PMID Title PublicationDate abstract
15683847 FK506 ameliorates spontaneous locomotor activity in collagen-induced arthritis: implicatio 2005 Mar FK506 (tacrolimus), an immunosuppressive drug, improves quality of life (QOL) for patients with rheumatoid arthritis (RA). However, the mechanism of FK506 behind the improvement in QOL is still uncharacterized. To explain the improvement of QOL by FK506, we investigated the effect of FK506 on spontaneous locomotor activity in rats with collagen-induced arthritis (CIA). CIA was induced in 7- to 8-week-old female Lewis rats by immunization with bovine type II collagen. After initiation of paw inflammation (paw swelling, histopathological analysis), CIA rats were therapeutically administered FK506 or methotrexate (MTX) from day 15. Therapeutic treatment with FK506 ameliorated spontaneous locomotor activity without suppressing paw inflammation in CIA rats from day 27. FK506 also improved hyperalgesia and grip strength from day 27. Therapeutic treatment with MTX did not improve spontaneous locomotor activity, and simultaneously did not recover hyperalgesia or grip strength in CIA rats. Our results indicate that spontaneous locomotor activity in CIA rats correlates mainly with hyperalgesia and muscle strength, but not paw inflammation, implying that therapeutic treatment with FK506 ameliorates spontaneous locomotor activity via improvement of hyperalgesia and muscle strength in CIA rats.
16207319 Protective effect of vasoactive intestinal peptide on bone destruction in the collagen-ind 2005 Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by the presence of inflammatory synovitis accompanied by destruction of joint cartilage and bone. Treatment with vasoactive intestinal peptide (VIP) prevents experimental arthritis in animal models by downregulation of both autoimmune and inflammatory components of the disease. The aim of this study was to characterize the protective effect of VIP on bone erosion in collagen-induced arthritis (CIA) in mice. We have studied the expression of different mediators implicated in bone homeostasis, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), receptor activator of nuclear factor-kappaB (RANK), receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), IL-1, IL-4, IL-6, IL-10, IL-11 and IL-17. Circulating cytokine levels were assessed by ELISA and the local expression of mediators were determined by RT-PCR in mRNA extracts from joints. VIP treatment resulted in decreased levels of circulating IL-6, IL-1beta and TNFalpha, and increased levels of IL-4 and IL-10. CIA-mice treated with VIP presented a decrease in mRNA expression of IL-17, IL-11 in the joints. The ratio of RANKL to OPG decreased drastically in the joint after VIP treatment, which correlated with an increase in levels of circulating OPG in CIA mice treated with VIP. In addition, VIP treatment decreased the expression of mRNA for RANK, iNOS and COX-2. To investigate the molecular mechanisms involved, we tested the activity of NFkappaB and AP-1, two transcriptional factors closely related to joint erosion, by EMSA in synovial cells from CIA mice. VIP treatment in vivo was able to affect the transcriptional activity of both factors. Our data indicate that VIP is a viable candidate for the development of treatments for RA.
15710254 [Evolution of Sjögren syndrome associated with hepatitis C virus when chronic hepatitis C 2005 Feb Hepatitis C virus is one of the most likely candidates as a potential pathogenic agent causing Sjogren's syndrome (SS) in a subset of patients. Nobody has until now described the evolution of SS associated with HCV when chronic hepatitis C is treated with antiviral therapy, interferon being an auto-immunity inductor. This is the purpose of our study. METHODS: Prospective study of 12 patients with a HCV-associated SS defined as certain according to the first european criteria and treated with interferon or interferon/ribavirin for their chronic hepatitis C. RESULTS: More than fifty percent of these patients developed a severe immunological complication especially when they were treated with interferon alone. Ribavirin may have had a protective role on interferon-mediated immunological complications. These complications went on after cessation of therapy. Sicca syndrome was improved only in the patients treated with the association (in 50% of the cases), but these patients also had a sustained virological response. It is difficult to tell if this improvement was due to the hepatitis C virus eradication or ribavirin treatment. CONCLUSION: Hepatitis C virus is implicated in the development of SS in a specific subset of patients for which we can propose the term SS "secondary to HCV" and this disease is not utterly benign especially after the introduction of interferon therapy. Ribavirin when associated with interferon gives a significative sustained virological response and could lower the incidence of immunological interferon-mediated complications with a favorable outcome of sicca syndrome.
16221495 Role of complement and B lymphocytes in Sjögren's syndrome-like autoimmune exocrinopathy 2006 Mar Sjögren's syndrome (SjS) is a human autoimmune disease characterized by the loss of exocrine function as a result of a chronic immune attack directed primarily against the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes). NOD.B10-H2b mice manifest many features of SjS, exhibiting exocrine gland dysfunction concomitant with leukocyte infiltration of the salivary and lacrimal glands. Recent studies have shown that both SjS patients and NOD.B10-H2b mice exhibit increased B lymphocyte survival, B cell hyper-reactivity and hyper-gammaglobulinemia with high production of autoantibodies. To study the possible influence of complement on the development and expression of SjS-like disease of the NOD.B10-H2b, we have utilized a prophylactic treatment with CVF known to interfere with the action of complement C3 factor. NOD.B10-H2b mice, injected with CVF starting at 10 weeks of age, a time when leukocyte infiltration is expected to begin, failed to develop salivary dysfunction out to 24 weeks of age, a time when reduced salivary flow rates are known to occur in non-treated animals. Concomitant with retention of salivary exocrine function, CVF-treated mice showed reduced levels of leukocytic infiltration, reduction of anti-nuclear autoantibodies and major alterations in the B lymphocyte profiles while maintaining general pathophysiological measures of disease. These data suggest that C3 plays a significant role in development and onset of SjS-like disease, yet additional studies need to be carried out to identify the precise mode of action.
17348248 Simultaneous complication of multiple myeloma with Sjögren syndrome. 2006 Dec We report a 72-year-old female case of IgG-kappa type multiple myeloma (MM) simultaneously complicated with Sjögren syndrome (SS). She also presented marked hyperamylasemia of salivary-type isozyme. Although she had received sequential chemotherapy completed with high-dose therapy with autologous hematopoietic stem cell transplantation, she died of relapse fifteen months after the initial diagnosis. Various autoantibodies indicated that her sicca symptoms were due to true SS and not caused by MM cell infiltration to exocrine glands. MM cells appeared to produce amylase that fluctuated correspondingly to the disease status of MM. To our knowledge, this is the first English report of simultaneous complication of SS and MM referring to hyperamylasemia. Accumulation of this rare clinical manifestation is important to elucidate the pathogenesis of MM under condition of immunological disorder caused by SS.
16276517 Involvement of human intracisternal A-type retroviral particles in autoimmunity. 2005 Nov Prior studies have linked retroviruses to various arthropathies and autoimmune diseases. Sjögren's syndrome (SS), a systemic autoimmune disease, is characterized by aggressive infiltration of lymphocytes into the salivary and lacrimal glands, resulting in destruction of the glands and dry mouth and eyes (sicca syndrome). The infiltrating lymphocytes in SS may become overtly malignant, and thus, the incidence of lymphoma is greatly increased in SS patients. A human intracisternal A-type retroviral particle type I (HIAP-I) has been isolated from persons with SS. HIAP-I shares a limited number of antigenic epitopes with human immunodeficiency virus (HIV), but is distinguishable from HIV by morphological, physical, and biochemical criteria. A substantial majority of patients with SS or systemic lupus erythematosus (SLE) have serum antibodies to the proteins of this human retrovirus. Fewer than 3% of the normal blood donor population have antibodies to any HIAP-associated proteins. A second type of a human intracisternal A-type retrovirus, HIAP-II, was detected in a subset of patients with idiopathic CD4 lymphocytopenia (ICL), an AIDS-like immunodeficiency disease. Most HIAP-II positive ICL patients were also antinuclear antibody positive. Reviewed here are additional studies from several laboratories suggesting that HIAP or related viruses may be involved in SLE and other autoimmune conditions. Additionally, results of comprehensive surveys of autoimmune patients to determine seroreactivity to HIAP, and other human retroviruses, including HIV and human T-lymphotropic virus type I, are reported.
16089294 [The effect of interferon-gamma in collagen-induced arthritis in mice shows a mechanism of 2005 Collagen-induced arthritis (CIA) is an animal model for human rheumatoid arthritis. CIA is induced in the mouse by immunization with collagen type II in complete Freund's adjuvant (CFA). As a result of this immunization, mice will develop an autoimmune disease that is characterized by an inflammatory and destructive affection of the joints. IFN-gammaR KO mice have an increased susceptibility to CIA as compared to wild-type control animals: they developed arthritis with a significant earlier disease onset and a higher disease incidence and score. The results indicate that IFN-gamma acts as a disease-protective factor in CIA. The disease-protective effect of IFN-gamma in CIA appeared to be due to CFA that was used for the induction of CIA, and more precisely to the presence of killed mycobacteria in this adjuvant. The killed mycobacteria in CFA elicited in mice an extramedullar myelopoiesis and an expansion of Mac-1+ cells that was strongly inhibited by endogenous IFN-gamma. Parts of the expanded Mac-1+ splenocytes were precursor cells for osteoclasts, they migrated to the joints after challenge with SDF-1, where they found to differentiate into mature osteoclasts who are responsible for bone destruction. The mechanism of expansion, migration and osteoclast activation occurred in IFN-gammaR KO as well as in wild-type mice, but was much more pronounced in the mutant mice. Thus, the use of IFN-gammaR KO mice has exposed a new mechanism in the pathogenesis of autoimmune arthritis in mice. These findings may have important clinical perspectives.
16357763 Garibaldi's rheumatism. 2005 Aug Giuseppe Garibaldi, the charismatic 19th-century Italian revolutionary leader, had complaints of recurrent and often persistent rheumatic pain starting in his early 40s. Symptoms continued until his death at 74, with progressive disability. His diagnosis is uncertain, but rheumatoid arthritis is most likely. Garibaldi coped successfully with his rheumatic illness during most of his military and political career, but eventually became bedridden and dependent.
16752740 [Natural gas-steam-thermal springs in combined therapy of osteomuscular system diseases]. 2006 Jan The article describes effects of unique thermal springs of Yangan-Tau mountain in patients with locomotor diseases. Effects of gas, steam and thermal factors of the water from the above springs were studied in patients with rheumatoid arthritis who took baths in the sanatorium Yangan-Tau. Changes in the cytokine profile of the patients were analysed.
15862805 Effect of celecoxib, a cyclooxygenase-2 inhibitor, on the pathophysiology of adjuvant arth 2005 Apr 25 We investigated the efficacy of celecoxib, a specific cyclooxygenase (COX)-2 inhibitor, on arthritic pathophysiology and confirmed its gastric safety in adjuvant-induced arthritis rats. Results were compared with those for loxoprofen, a non-selective COX inhibitor. Arthritis was induced by injection of 1 mg of Mycobacterium butyricum in 50 microl of liquid paraffin into the left footpad of Lewis rats. The drugs were given by twice daily oral administration for 10 days beginning 15 days after adjuvant injection, with celecoxib at 0.01-3 mg/kg/day and loxoprofen at 0.01-3 mg/kg/day. Celecoxib significantly inhibited paw swelling, hyperalgesic response, and joint destruction (radiographic and histopathological findings) in these arthritic rats. These effects of celecoxib were superior to those of loxoprofen. Further, the administration of loxoprofen (3 mg/kg/day) caused significant gastric lesions, whereas celecoxib at the same dose did not. These results suggest that COX-2-mediated prostaglandins may play an important role in the progression of pathophysiology in this model and that celecoxib may be a useful therapeutic agent for the treatment of rheumatoid arthritis, with greater safety than non-selective COX inhibitors.
16981296 Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic a 2006 Nov OBJECTIVE: To compare the prevalence of cardiovascular diseases and their risk factors between patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) and control subjects. METHODS: Data for patients continuously enrolled in an integrated outcomes database between January 1, 2001, and December 31, 2002, with International Classification of Diseases, 9th Revision codes of 714.x (RA), 696.0 (PsA), or 720.0 (AS) were evaluated in this cross-sectional comparative study. Control groups were established for each patient group (1:4 ratio) by matching on the basis of age, sex, geographic region, and length of time in plan. Age- and sex-adjusted prevalence of cardiovascular comorbidities and risk factors were calculated; the prevalence ratio of the comorbidities and risk factors for the patient groups compared with the control population were estimated. Use of selected cardiovascular medications was also compared between patient and control groups. RESULTS: The RA, PsA, and AS cohorts comprised 28,208, 3066, and 1843 patients, respectively. The prevalence ratio of ischemic heart disease (1.5, 1.3, 1.2), atherosclerosis (1.9, 1.4, 1.5), peripheral vascular disease (2.4, 1.6, 1.6), congestive heart failure (2.0, 1.5, 1.8), cerebrovascular disease (1.6, 1.3, 1.7), type II diabetes (1.4, 1.5, 1.2), hyperlipidemia (1.2, 1.2, 1.2), and hypertension (1.3, 1.3, 1.3) were higher in patients than controls. For RA, PsA, and AS, use of angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics, nitrates/vasodilators, anticoagulants, and antihyperlipidemia agents was significantly higher in patients than controls. CONCLUSION: Cardiovascular diseases and their risk factors were more common in patients with RA, PsA, and AS than in matched controls.
16942002 Hand arthritis in systemic lupus erythematosus: an ultrasound pictorial essay. 2006 A small minority of systemic lupus erythematosus (SLE) patients may develop a deforming arthritis, typically with a non-erosive (Jaccoud's) pattern, although erosive features indistinguishable from rheumatoid arthritis may also occur. High-resolution ultrasonography (HRUS) allows detailed 'real time' imaging of joint and tendon morphostructural changes involving the hand in patients with several rheumatic diseases. The main aim of this pictorial essay is to provide the first descriptive HRUS and power Doppler (PD) findings of joint and tendon involvement of the hand and wrist in patients with SLE arthritis. Seventeen patients with SLE and hand involvement were examined. HRUS of the wrist, 2nd and 3rd MCP joints, 3rd PIP joint and 2nd, 3rd and 4th finger flexor tendons were studied in the dominant hand for each patient. Sixteen (94%) patients had joint effusion or synovial hypertrophy in the wrist. Twelve (71%) patients had joint effusion or synovial hypertrophy in 2nd or 3rd MCPJs. Eight (47%) patients had erosion at 2nd or 3rd MCPJs. In three cases erosions were not present radiologically. Eleven (65%) patients had evidence of tenosynovitis. In SLE, HRUS with PD detects a high prevalence of inflammatory pathology in the tendons and synovium of the hand and wrist, and a high prevalence of MCP joint erosions. HRUS offers a sensitive, real-time and readily repeatable assessment of soft-tissue, inflammatory and bony changes in SLE hands.
15708944 Psoriatic arthritis treatment: biological response modifiers. 2005 Mar In recent years there has been a surge of interest in the treatment of chronic inflammatory disorders as a result of the development and application of targeted biological therapies. The elucidation of the overlapping cellular and cytokine immunopathology of such diverse conditions as rheumatoid arthritis (RA), Crohn's disease, and psoriasis points to specific targets for bioengineered proteins or small molecules. Similar to clinical trials in RA, trials in psoriatic arthritis (PsA) have shown excellent clinical results with the tumour necrosis factor (TNF) blockers, etanercept, infliximab, and adalimumab in a variety of domains including the joints, quality of life, function, and slowing of disease progress as evidenced radiologically. In addition, these agents have shown benefit in domains more unique to PsA, such as the skin lesions of psoriasis, enthesitis, and dactylitis, pointing out the similar pathogenesis of the disease in the skin, the tendons, and the synovial membrane. This therapy has been generally safe and well tolerated in clinical trials of PsA. Other logical candidates for targeted therapy in development include other anti-TNF agents, costimulatory blockade agents that affect T cell function, blockers of other cytokines such as interleukin (IL)-1, 6, 12, 15, or 18, and B cell modulatory medicines. Also, it will be useful to learn more about the effects of combining traditional disease modifying drugs and the newer biologicals.
17108524 Information technology in clinical research in rheumatology domain. 2006 The development of a functional clinical database of rheumatic diseases represents an essential step in the process of acquiring the necessary epidemiological and other information on disorders under study. In 1999-2005 the Institute of Rheumatology in cooperation with the EuroMISE Center has developed the Clinical database/National Register of selected systemic inflammatory rheumatic diseases inclusive of a bank of sera and DNA. Aims of this phase of the pilot research were gathering clinical, laboratory, genetic, pharmaco-and socio-economic data in a representative sample of patients with systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, mixed connective tissue disease; rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis. In 2002 the preset number of over 2000 registered patients had been achieved with collaboration of 34 territorial and 20 institutional rheumatologists in the whole covering the majority of the Czech Republic. Based on experiences gathered, the systems for other related studies are being developed and implemented using modern information technologies.
15716976 Identification of epistasis through a partial advanced intercross reveals three arthritis 2005 May Identification of genes controlling complex diseases has proven to be difficult; however, animal models may pave the way to determine how low penetrant genes interact to promote disease development. We have dissected the Cia5/Eae3 susceptibility locus on mouse chromosome 3 previously identified to control disease in experimental models of multiple sclerosis and rheumatoid arthritis. Congenic strains showed significant but small effects on severity of both diseases. To improve the penetrance, we have now used a new strategy that defines the genetic interactions. The QTL interacted with another locus on chromosome 15 and a partial advanced intercross breeding of the two congenic strains for eight generations accumulated enough statistical power to identify interactions with several loci on chromosome 15. Thereby, three separate loci within the original QTL could be identified; Cia5 affected the onset of arthritis by an additive interaction with Cia31 on chromosome 15, whereas the Cia21 and Cia22 affected severity during the chronic phase of the disease through an epistatic interaction with Cia32 on chromosome 15. The definition of genetic interactions was a prerequisite to dissect the Cia5 QTL and we suggest the partial advanced intercross strategy to be helpful also for dissecting other QTL controlling complex phenotypes.
16958499 Infections and inflammatory conditions of the cervical spine in children. 2006 Because infections and inflammatory disorders of the cervical spine are uncommon in children and adolescents, diagnosis and treatment are frequently delayed. Intractable pain, limitation of neck motion, and neurologic compromise may occur as the result of these pathologic processes. It is important to identify these symptoms for early diagnosis and treatment of conditions such as bacterial and tuberculous infections, intervertebral disk calcification, juvenile rheumatoid arthritis, and Grisel's syndrome.
16995415 [Regulation of osteoclast activity: a new approach in the therapy of bone diseases]. 2006 Bone remodelling is process of constant resorption and formation of a bone. Osteoclasts are the cells responsible for bone resorption. Deregulation of osteoclast differentiation, activity or function can cause severe diseases, such as osteoporosis, osteopetrosis or rheumatoid arthritis. Advances in molecular biology of osteoclasts and osteoimmunology open new approaches for the specific and efficient therapy.
16216119 Fat intake and composition of fatty acids in serum phospholipids in a randomized, controll 2005 Oct 10 BACKGROUND: We have previously reported that rheumatoid arthritis patients, who adopted a modified Cretan Mediterranean diet, obtained a reduction in disease activity and an improvement in physical function and vitality. This shift in diet is likely to result in an altered intake of fatty acids. Therefore, the objective of the present study was to examine the dietary intake of fatty acids, as well as the fatty acid profile in serum phospholipids, during the dietary intervention study presented earlier. RESULTS: From baseline to the end of the study, changes in the reported consumption of various food groups were observed in the Mediterranean diet group. The change in diet resulted in a number of differences between the Mediterranean diet group and the control diet group regarding the fatty acid intake. For instance, a lower ratio of n-6 to n-3 fatty acids was observed in the Mediterranean diet group, both assessed by diet history interviews (dietary intake) and measured in serum phospholipids. Moreover, the patients in the Mediterranean diet group that showed a moderate or better clinical improvement during the study (diet responders), had a higher reported intake of n-3 fatty acids and a lower ratio of n-6 to n-3 fatty acids compared to the patients with minor or no improvement. Also the fatty acid profile in serum phospholipids differed in part between the diet responders and the diet non-responders. CONCLUSION: The changes in the fatty acid profile, indicated both by dietary assessments and through fatty acids in s-phospholipids may, at least in part, explain the beneficial effects of the Cretan Mediterranean diet that we have presented earlier.
17041989 Clinical and psychological outcomes of patient education in rheumatoid arthritis. 2005 OBJECTIVE: Evidence that patient education improves outcome in self-selected patients is often based on studies using patients with a mixture of diagnoses (primarily osteoarthritis) and where the education is delivered in a community setting. This study explored whether hospital outpatients with rheumatoid arthritis (RA) who were offered a self-management programme showed a similar response. METHODS: A randomized controlled trial was undertaken of either observation or observation plus an educational intervention of five sessions (12.5 hours) designed to enhance self-management. Pain and self-efficacy for pain were the primary outcome measures. These and other standardized assessments were made at 0, 4, 8 and 36 weeks for a variety of psychological and disease states. Knowledge of RA and its treatment was measured at 0 and 4 weeks using a multiple-choice questionnaire. RESULTS: Sixty-eight of 79 randomized patients provided adequate data. In those randomized to be offered education, knowledge of RA and its treatment increased by 18% compared to 9% in controls (p = 0.058). Self-efficacy for pain improved between weeks 0 and 4 by 10.3% (p = 0.015) in those offered education, and by 14.1% in those who were offered and accepted education (p = 0.001) but the difference from controls was not maintained after four weeks. There were no significant differences between groups in pain or in any of the remaining variables. Most patients reported that the education had been helpful. CONCLUSIONS: Patients offered education gained knowledge and reported personal benefit, but only improved in self-efficacy for pain and only for a short time. RA patients drawn from hospital outpatient clinics and allocated to an educational intervention may not gain changes in health status as measured by the instruments employed in this study.
16273778 Complexities in the quantitative assessment of patients with rheumatic diseases in clinica 2005 Sep Quantitative measurement has led to major advances in the diagnosis, prognosis and management of chronic diseases. Quantitative measures in rheumatic diseases differ from measures in many chronic diseases in several respects. There is no single "gold standard," such as blood pressure or cholesterol, in the diagnosis, management, and prognosis of any rheumatic disease. Laboratory tests are limited; for example, in rheumatoid arthritis > 40% of patients or more have a normal erythrocyte sedimentation rate (ESR). Formal joint counts have poor reliability and are not performed at most visits of most patients. Radiographs are rarely read quantitatively, except in formal clinical trials. The optimal quantitative measures to monitor status and assess long-term prognosis are often derived from patient self-report questionnaires. Quantitative measures may reflect disease activity, e.g., swollen joint counts or C-reactive protein (CRP), long-term damage, e.g., radiographic damage, or poor outcomes, e.g., work disability and premature death. Disease activity measures used in clinical trials are primarily surrogates for long-term outcomes. As there is no single "gold standard" measure, indices of multiple measures are used in patient assessment. Indices used in rheumatoid arthritis assess primarily disease activity, but separate indices have been developed to assess disease activity versus damage in patients with ankylosing spondylitis, systemic lupus erythematosus, and vasculitis.