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ID PMID Title PublicationDate abstract
11874843 Anticardiolipin antibodies in rheumatoid patients treated with etanercept or conventional 2002 Apr OBJECTIVE: To assess the occurrence of anticardiolipin antibodies (ACA) (as well as of anti-DNA antibodies) in patients with rheumatoid arthritis treated with etanercept or combination therapy. METHODS: Eight patients treated with etanercept 25 mg twice weekly were studied for a period of 85 weeks. A control group of 39 patients with rheumatoid arthritis undergoing combination treatment (methotrexate (MTX) + cyclosporin A or MTX + chloroquine) were studied for the same period of time. The occurrence of anticardiolipin antibodies (ACA-IgG) and anti-DNA was examined, together with the possible occurrence of infections due to bacteria capable of inducing B cell activation. RESULTS: In 5/8 patients receiving etanercept an increase of ACA-IgG was seen, while anti-DNA became positive in 3/8 patients. A nasal or bronchial infection due to Staphylococcus aureus (Staph aureus) or a urinary tract infection due to E coli, occurred in all five cases. Antibiotic treatment produced a return to normal of ACA-IgG, and also of anti-DNA, in all cases except one. The infectious agent was eradicated in all subjects but one. In the control group Staph aureus was found in the nasal swab in 10/39 subjects; ACA-IgM (followed by ACA-IgG) appeared at the same time as infection occurred in 6/10, while no infection related to the increased ACA-IgM was recorded in the other four. CONCLUSIONS: Bacterial DNA, especially that enriched in CpG motifs, is a powerful immunostimulant that may, in some cases, lead to ACA or anti-DNA positivity, once tumour necrosis factor alpha is blocked. Eradication of the infections leads to a rapid decrease of ACA-IgG and of anti-DNA levels.
15583764 [Benefits of breastfeeding and women's health]. 2004 Nov OBJECTIVE: To review breastfeeding benefits for the women's health. SOURCES OF DATA: Lilacs, MEDLINE, SciELO, BIREME, Cochrane Library and Google were searched for the keywords: breastfeeding and breast cancer, ovarian cancer, osteoporosis, rheumatoid arthritis, lactation amenorrhea, post natal period, and women's health. Single articles published between 1990 and 2004 were considered, as well as remarkable ones prior to this period. SUMMARY OF THE FINDINGS: There are a few articles published on the topic, even though, the existing literature reveals that there is a positive relationship between breastfeeding and decreased risk of breast cancer, cancer of the ovarian epithelium, and osteoporosis leading to hip fracture. Some studies suggest the effect of breastfeeding on the decreasing risk of rheumatoid arthritis, others mention the relation between breastfeeding and faster loss of weight gained during the gestational period. Several studies show how breastfeeding interferes on the onset of postnatal menstruation and consequent birth spacing. CONCLUSIONS: Breastfeeding provides important benefits for the women's health, such as reduced risk of breast and ovarian cancer, decreased risks of hip fractures and contribution to the increase of birth spacing.
14579030 [New biological therapeutic options for the treatment of RE: inhibition of costimulatory m 2003 Oct After approval of TNF and interleukin-1 inhibiting agents for treatment of refractory rheumathoid arthritis, new agents inhibiting interleukin-6 and costimulatory pathways are entering clinical phase I and II trials. Blockade of costimulation by using a CTLA4 immunoglobulin fusion protein (CTLA4Ig), which inhibits the interaction between CD 28 and CD80/86, has been studied in humans and was demonstrated to be well tolerated and efficacious. A monoclonal antibody to the IL-6 receptor (MRA) blocks bioactivity of IL-6 and also showed favorable effects in first clinical trials. Drug safety data on both substances revealed no severe toxicity or increased incidence of severe infections. For the first time combinations of biological substances like CTLA4Ig and etanercept were demonstrated to be effective and showed no evidence for an increased rate of severe infectious complications. Encouraged by data on these two agents there is substancial hope for a broadened therapeutic armentarium of biological agents in refractory rheumatoid arthritis.
12810927 Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production by cultur 2003 Nov OBJECTIVE: To clarify the pharmacological action of an anti-rheumatic agent T-614, we investigated its effects on immunoglobulin (Ig) production by cultured B cells and Ig secretion from synovial tissues of patients with rheumatoid arthritis (RA) using SCID mice engrafted with human RA tissue (SCID-HuRAg). METHODS: Murine B cells were prepared from mouse spleen by a T-cell depletion method. The cells were cultured with lipopolysaccharide (LPS) and/or interleukin 4 (IL-4) in the absence or presence of T-614. Human B cells were isolated from peripheral blood of healthy donors and the Ig production was induced by co-culture with autologous T cells and anti-CD3 antibody. SCID-HuRAg was prepared according to our previous method. T-614 was orally administered to the mice once daily for 4 weeks starting on the fourth week after the implantation. Then, peripheral blood was obtained and the implanted tissues were removed. Igs in the culture media or the sera were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In murine B-cell cultures, T-614 significantly decreased not only the IgM production stimulated with LPS but IgG1 production induced by LPS and IL-4. Regarding human B cells stimulated with T cells, it also inhibited IgM and IgG production. In SCID-HuRAg mice, high concentrations of polyclonal human IgG were detectable in the sera of all mice. A significant decrease in the IgG level was observed in the T-614-treated group compared with the control group. CONCLUSIONS: We showed that T-614 inhibited Ig production by the cultured B cells and also decreased the high level of human IgG observed in SCID-HuRAg mice. These results may support its effect on plasma Ig in RA patients and provide insights into the mechanisms of its anti-rheumatic effect.
15540421 [Effect of small-dose glucocorticoids on the course of early rheumatic arthritis]. 2004 The study was undertaken to evaluate the effect of small-dose glucocorticoids (GCs) in combination with essential drugs used in early rheumatic arthritis (RA) on the clinical and laboratory activity and progression of joint destruction. Sixty-two patients aged 18-63 years who had active RA (its history being 1.5 to 24 months) and had not received basic therapy before were given methotrexate (MT) in a dose of 7.5-10.0 mg/week. Prednisolone (P) was randomly used in a dose equal or more than 10 mg/day). The efficiency of treatment was evaluated every 3 months by the ACR criteria 20/50/70. X-ray study of the hand and foot joints (the Larsen procedure by erosion calculations) was performed and the serum levels of C-reactive protein (C-RP) and interleukin-6 (IL-6) were measured before and 12 months after therapy. In the MT group, the patients' mean age was 52.0 +/- 10.5 years, the history of RA was 8.4 +/- 6.8 months; 82% of the patients were seropositive in terms of rheumatoid factor; the DAS 28 index was 5.2 +/- 0.8; in the P+MT group, the above parameters were 51.9 +/- 11. 7 years, 9.1 +/- 6.0 months, 83%, and 5.4 +/- 0.8, respectively (p > 0.05). Throughout one-year follow-up, the patients whose parameters corresponded to ACR 70 were more in the P+MT group than in the MT group (p < 0.05). The level of IL-6 and C-RP significantly decreased only in the P+MT group. There was a significant in the Larsen scores in both groups. A much fewer number of new erosions was revealed in the P+MT group than that in the MT group. According to the ACR 70 criteria, the efficiency of treatment with small-dose GCs was much higher than that in MT monotherapy. The small doses of GCs significantly lowered the laboratory activity of RA (C-RP, IL-6) and the occurrence of erosions.
12790266 Effect of methotrexate on male fertility. 2003 May QUESTION: Several men with psoriatic arthritis have asked whether the methotrexate they take for rheumatoid arthritis will affect their fertility or the outcome of any of their partners' future pregnancies. What is known regarding risks to fertility and to fetuses? ANSWER: To date, there are no reports of adverse pregnancy outcomes among men exposed to methotrexate before conception. Opinions in the literature differ on the effects of methotrexate on male fertility. Several case reports and studies report no effect; others report reversible sterility. One limitation to several of these studies is the concurrent administration of other chemotherapeutic agents. Small studies reporting on methotrexate use with no other agents suggest no increased infertility. Motherisk is currently following men who are taking methotrexate alone for psoriatic arthritis to see whether it affects fertility.
12822080 [Radiolunate arthrodesis in rheumatoid wrist--the modified Chamay technique with broadenin 2003 May AIM: Radiolunate arthrodesis (RLA) has become an established surgical technique for stabilising wrists destroyed by RA. Our modified surgical technique with special osteosynthesis material has enabled the spectrum of indications to be expanded to include stage IV a--sagittal instability. METHOD: 44 radiolunate arthrodeses were carried out from 10.96 to 6.98. 19 (43.2%) satisfied the criteria for correction RLA with correction of sagittal instability. All (100%) of the 19 radiolunate arthrodeses were included in a follow-up examination, and all were examined clinically and radiologically at specified intervals. The mean follow-up is 22.8 months. RESULTS: Correction of the lunate drift in the sagittal plane was successful. The radiolunate angle was reduced from a mean 23.7 degrees before surgery to 9.3 degrees afterwards. The lunate drift in the frontal plane, which is shown by the ulnar translation index (UTI) was corrected from an average of 0.35 before surgery to 0.30 afterwards. Restoration of the carpal height by bone grafting from a mean preoperative CHI of 0.47 to 0.50 after surgery was achieved. We discovered one failure, thus the consolidation rate dropped to 94.7%. CONCLUSION: Since the capitate is the centre of rotation and movement at the wrist, a stable central pivot is essential, and correction of sagittal instability is particularly important. This demand can also be met by our modified radiolunate arthrodesis.
14685719 [Phlegmon of the forearm due to therapy with Anakinra (interleukin-1 receptor-antagonist)] 2003 Dec INTRODUCTION: Biological modifiers (BM) are very effective in a high percentage of patients with rheumatoid arthritis being resistant to disease modifying antirheumatic drugs (DMARD). In the beginning, the therapy with the BMs was thought to be of low risk. However, due to the increase of application, a few lethal septical complications have been reported. CASE REPORT: A 38 year old male with rheumatoid arthritis and insulin deficiency diabetes mellitus achieved remission under the therapy with Anakinra within three days. Due to a spontaneous disrupture of the finger extensor tendons operative revision was performed. A phlegmon from the dorsum of the hand to the cubita was found five months after resection of a septical cubital bursa. CONCLUSION: The very effective suppression of the immune system by the BMs should not lead to noncritical therapy in patients with history of infections of bone, joints and soft tissue, because inactive organism may start growing and lead to undetected lethal sepsis.
14971874 Worsening of obstructive sleep apnoeas in a patient with rheumatoid arthritis treated with 2004 Feb We report on a case of an adult patient treated for rheumatoid arthritis with infliximab, a chimerical monoclonal antibody to TNFalpha. Apart from this, the patient also showed clinical signs of obstructive sleep apnea syndrome that was confirmed by polysomnographic study. After infliximab treatment, additional sleep studies revealed an increase in the number of apneic events and SaO2 dips suggesting that TNFalpha plays an important role in the pathophysiology of sleep apnea. Thus, clinical recognition of sleep disordered breathing should be taken into account when rheumatoid arthritis patients are to be treated with infliximab.
15517626 Association of reduced CD4 T cell responses specific to varicella zoster virus with high i 2004 Nov OBJECTIVE: To examine whether the high incidence of herpes zoster in patients with systemic lupus erythematosus (SLE) is associated with the frequency of memory T cells specific to varicella zoster virus (VZV). METHODS: Whole blood samples from 47 subjects [24 patients with SLE, 11 with rheumatoid arthritis (RA) as a disease control, and 12 healthy negative controls] were stimulated with VZV antigen, stained for surface CD4 and CD8 and intracellularly stained for the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), and IL-10, followed by flow cytometry analyses. Correlations of VZV-specific T cell frequencies with the clinical status of patients were analyzed. RESULTS: Percentage of IFN-gamma-positive CD4 T cells was significantly lower in patients with SLE (0.043 +/- 0.009%) than in RA (0.102 +/- 0.019%) and healthy controls (0.126 +/- 0.025%) upon VZV stimulation. A similar pattern was seen in TNF-alpha-positive CD4 T cell responses. These low frequencies of VZV-specific CD4 T cells in patients with SLE were significantly related with disease activity (r = -0.435, p = 0.043). CONCLUSION: These data suggest that the high incidence of herpes zoster in patients with SLE was related to the intrinsic defects in controlling VZV reactivation, and thus VZV-specific CD4 T cell frequency could be another practical risk factor of herpes zoster in patients with SLE.
15005257 Malignant lymphoma associated with rheumatoid arthritis, developing shortly after initiati 2004 Feb We report a patient with rheumatoid arthritis (RA) who developed malignant lymphoma of the diffuse large B-cell type in the right submandibular region shortly after initiation of oral methotrexate (MTX). Despite cessation of MTX, the lymphadenopathy did not regress, and only reached complete remission after 3 courses of CHOP therapy followed by irradiation. In this patient highly active RA itself was considered to be the main cause of malignant lymphoma, and MTX might have contributed to the development by modifying the immune system. When RA is highly active, MTX should be used carefully because of the possible development of malignant lymphoma as well as other serious complications.
15577739 Factors underlying chronic inflammation in rheumatoid arthritis. 2004 Nov Rheumatoid arthritis (RA)is a debilitating chronic inflammatory disease whose characteristic pathology includes swollen, painful, and deformed joints. In recent decades, both clinical and basic scientific research have tried to determine the factors involved in the pathogenesis of this common disease. Although the cause of RA is still unknown, several factors that contribute to RA have been identified. Among these are the discoveries of: susceptibility genes, disease-causing immune cells, and cytokine and signal transduction networks involved in promoting persistence of inflammation. Various therapeutic strategies, including anti-tumor necrosis factor therapy, have been developed to target one or more of these factors. Although none of these therapeutic strategies can actually cure the disease, some of these novel agents have proven to be more effective than others. This implies that the success of a therapy is very much dependent on the therapeutic targets chosen. Therefore, improved understanding of the cellular and molecular events occurring in the rheumatoid joint during the pathogenesis of the disease is particularly important if we are to better combined therapeutic strategies. In this article we summarize current understanding of the factors that contribute to disease pathogenesis in RA and identify cellular and molecular events that could drive the development of the disease and represent potential new therapeutic targets.
12120906 Hearing loss and middle ear involvement in rheumatoid arthritis. 2002 May In this controlled study, hearing and middle ear functions were investigated in 37 patients with rheumatoid arthritis (RA) and 35 controls in order to study the prevalence and the nature of hearing loss in RA. The prevalence of the hearing impairment was significantly higher in the RA group, and the majority was bilateral (P<0.001). Of the patients, 35.1% had sensorineural (SN), 24.3% had conductive loss, and 10.8% had a mixed type of hearing loss. The hearing loss was positively correlated to the Steinbrocker functional index. The prevalence of abnormal tympanograms was 37.8%, while it was 17.1% in the control group. The probable site of involvement responsible for the SN loss was the cochlea, and discontinuity of the ossicles, rather than stiffness, was responsible for the conductive hearing loss. The presence of a mixed type of hearing loss suggested a multifocal involvement of the audiologic system in RA.
11924648 Kallikreins and kininogens in saliva and plasma of patients presenting with rheumatoid art 2002 We evaluated the activities of salivary kallikrein and tissue/plasma kallikreins, and the plasma levels of high-molecular (HKg) and low-molecular (LKg) weight kininogens in patients with rheumatoid arthritis. The patients exhibited higher levels of the active salivary kallikrein compared to the controls. In contrast, the total salivary kallikrein activity of patients was not different from controls. In plasma from the patients, tissue kallikrein activity or plasma prekallikrein activity was not significantly different from the controls. Plasma HKg levels observed in patients were higher than in controls, whereas plasma LKg levels did not differ significantly from controls. Our results showed that most of the salivary kallikrein seen in patients is in its active form, suggesting the presence of systemic or local factors with the ability to activate salivary pro-kallikrein.
14655006 [Drug therapy of rheumatoid arthritis]. 2003 Dec Nowadays undisputed is the effectiveness of early and long-standing DMARD therapy in the presence of active rheumatoid arthritis on disease progression and avoidance of structural joint changes. "Early" is defined as immediate initiation of drug therapy after diagnosis of rheumatoid arthritis. "Long-term" refers to a mostly life-long therapy, which even in the case of remission should be continued for at least 1 year. Clinical and laboratory routine controls during DMARD therapy are absolutely necessary. "DMARDs" summarize disease-modifying antirheumatic drugs such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, aurum but also the TNF-blockers infliximab and etanercept. In cases of disease remission with combination drug therapy, corticosteroids and NSAID should be discontinued in a timely manner ahead of DMARDs to ensure that the reduction of clinical symptoms is not steroid controlled. DMARD therapy should end at least 6 months prior to conception.
12195256 Comparison of survivorship between standard and long-stem souter-strathclyde total elbow a 2002 Jul This study compared 107 cases of rheumatoid arthritis that had the long-stem humeral component of the Souter-Strathclyde total elbow arthroplasty introduced as a primary procedure with a similar group of 202 cases that had the standard component. Both groups were comparable with regard to age range and sex ratio. Follow-up of the longer-stem component was somewhat shorter, being a mean of 4.4 years as opposed to 9.3 years. Kaplan-Meier survival analyses were undertaken for both revision and radiologic loosening of components as terminal events. There was no significant difference between the cumulative survival of the standard and long-stem humeral implants when revision was the endpoint. Although survival of both implants was similar, the reasons for this were different. More specifically, for the standard humeral component, 25 out of 32 revisions were for humeral loosening. For the long stem, however, 5 out of a total of 7 revisions were due to instability; no long-stem humeral component had been revised for loosening. In addition, linking the components by way of a snap-fit component was associated with a higher rate of loosening; more specifically, 5 out of 16 cases were revised. As a result of this study, we recommend the use of a long-stem Souter-Strathclyde humeral component as a primary implant. Other crucial components for long-stem survival, however, are surgical technique and alignment of the implant.
12612312 Pulmonary granulomas after tumour necrosis factor alpha antagonist therapy. 2003 Mar Tumour necrosis factor alpha (TNFalpha) antagonists are an established therapeutic option in Crohn's disease and rheumatoid arthritis. In recently published studies these agents have been used with great success, but little is known about any side effects or long term consequences. They increase the frequency of infections with mycobacteria, where TNFalpha is thought to be an important host defence factor. We describe one patient who was treated with TNFalpha antagonists and later developed pulmonary granulomas with caseating necrosis without detection of mycobacteria or any other pathogens. Possible mechanisms involved in this newly recognised side effect are discussed.
15142264 Increased AP-1 and NF-kappaB activation and recruitment with the combination of the proinf 2004 To determine the contribution of IL-1beta, tumor necrosis factor alpha (TNF-alpha) and IL-17 to AP-1, NF-kappaB and Egr-1 activation in rheumatoid arthritis, the effect of the cytokines used alone or in combination was measured on TF expression in rheumatoid synoviocytes. Effects on mRNA expression were measured by RT-PCR and effects on nuclear translocation were measured by immunocytochemistry. To assess the functional consequences of cytokine induction, osteoprotegerin levels were measured in synoviocyte supernatants.IL-1beta and TNF-alpha alone at optimal concentration (100 pg/ml) induced the nuclear translocation of NF-kappaB and almost all AP-1 members, except JunB and Egr-1 for IL-1beta and except Fra-2 and Egr-1 for TNF-alpha. IL-17 was clearly less potent since no nuclear translocation was observed, except for a weak activation of Fra-1 and NF-kappaB. More importantly, when these cytokines were used at low concentrations, their combination showed a synergistic effect on almost all the TFs, except for Egr-1, with a particular effect on Fra-1 and NF-kappaB. Increased recruitment of additional factors was induced when the three cytokines were combined. IL-1 and TNF-alpha induced mRNA expression of c-jun while IL-17 had no effect. A synergistic effect was seen with their combination. A similar synergistic effect was observed for osteoprotegerin production when these three cytokines were combined at low concentrations.AP-1 and NF-kappaB pathways were highly sensitive to the combination through synergistic mechanisms. These effects observed in rheumatoid arthritis synoviocytes may reflect the conditions found in the rheumatoid arthritis joint and may contribute to the mode of action of cytokine inhibitors.
15245751 Stress cytokines: pivotal proteins in immune regulatory networks; Opinion. 2004 Aug Stress proteins have three immunological regulatory functions: within the cell, on the cell membrane as signalling receptors, and in the extracellular environment as stress cytokines. They can activate the immune system by providing danger signals or they may downregulate immune and inflammatory responses. In addition, they can modulate immune responses by acting as chaperones for antigenic peptides while they themselves are processed and presented to T cells as self-peptides. We predict that the exploitation of the downregulatory properties of stress cytokines will have therapeutic applications in the treatment of human chronic inflammatory diseases, such as rheumatoid arthritis.
12482523 Monoclonal antibodies in immune and inflammatory diseases. 2002 Dec The era of monoclonal antibody-based therapeutics has arrived. Monoclonal antibodies of high quality targeting almost any antigen can now be engineered and manufactured in large quantities. In the clinic, monoclonal antibodies are proving to be safe and effective for the treatment of a wide range of diseases including rheumatoid arthritis, Crohn's disease, spondyloarthropathies, psoriasis and allograft rejection.