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ID PMID Title PublicationDate abstract
19942450 Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis 2010 Jan The pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) involves an abnormal chemokine regulation. The chemokine receptor CCR4 is necessary for T cell migration to the skin. We, therefore, studied if CCR4 and its ligand macrophage-derived chemokine (MDC/CCL22) could participate in spreading the disease between skin and joints by examining RA, PsA and osteoarthritis (OA) patients. In synovial fluid from RA and PsA patients we observed a significantly higher MDC/CCL22 level compared to OA patients. Additionally, the MDC/CCL22 protein was found to be elevated in RA and PsA plasma compared to OA and healthy volunteers. Flow cytometry revealed that most CD4(+)CCR4(+) lymphocytes also co-expressed CD45RO. Neither the MDC/CCL22 level nor the expression of CCR4 correlated to CRP. Immunohistochemistry of the RA and OA synovial membrane demonstrated CCR4 to be expressed by mononuclear cells and endothelial cells. Our results show that MDC/CCL22 is present within the synovial membrane of RA and OA patients and in high amount in the synovial fluid of patients with RA and PsA. This will enable migration of CCR4 expressing memory cells supporting that MDC/CCR4 could play a role in attracting skin specific memory T cells to the joints.
21109515 IL-17A- versus IL-17F-induced intracellular signal transduction pathways and modulation by 2011 Feb OBJECTIVE: The aim of this study was to compare the effects of interleukin (IL)-17A and IL-17F on gene expression and signalling in human rheumatoid arthritis (RA) synoviocytes. METHODS: IL-17A- and IL-17F-induced mRNA expression was analysed using Affymetrix microarrays. IL-6 and IL-8 secretion was evaluated by ELISA. Inhibition of two receptors (IL-17RA and IL-17RC) was achieved by small interfering RNA (saran). The effects on mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1) and nuclear factor κB (NF-κB) expression and activation were evaluated by western blotting, qRT-PCR and DNA binding assay. RESULTS: IL-17A and IL-17F induced a molecular pattern characterised by 27 inflammation-related genes for IL-17F and 165 for IL-17A. Virtually all IL-17A and IL-17F inducible genes were dependent on NF-κB activation, whereas a small number were modulated by p38. IL-17A induced activation of all three MAPKs (ERK, p38 and JNK) and downstream transcription factors AP-1 and p65 NF-κB. IL-17F was less potent but induced activation of p50 NF-κB. IL-17A was more potent at inducing IL-6 secretion than IL-17F, which was inactive alone. IL-17A and, to a lesser extent, IL-17F induced TRAF6 but not MyD88. Inhibition of either IL-17RA or IL-17RC expression via siRNA led to near complete abrogation of IL-6 expression mediated by IL-17A and the combination of IL-17F and tumour necrosis factor α. CONCLUSION: Like IL-17A, IL-17F regulates proinflammatory gene expression by a very similar but not identical signalling pathway involving IL-17RA and IL-17RC.
19439038 Complex genetic association of 6q23 with autoimmune rheumatic conditions. 2009 In the paper by Dieguez-Gonzalez and colleagues in the present issue of Arthritis Research & Therapy, the results of a detailed genetic investigation of the recently identified rheumatoid arthritis and systemic lupus erythematosus susceptibility region at 6q23 containing the TNFAIP3 gene are reported. Their data confirm the complex nature of the association involving both the TNFAIP3 locus and a region >150 kb upstream that does not encode any known gene. These data are consistent with recent studies of systemic lupus erythematosus susceptibility confirming the presence of several independent genetic contributions to autoimmune rheumatic diseases arising from 6q23.
19916731 Therapeutic agents for patients with rheumatoid arthritis and an inadequate response to tu 2009 Dec BACKGROUND: Rheumatoid arthritis (RA) is a disabling autoimmune disease; unless adequately controlled, patients have a poor long-term prognosis. Tumour necrosis factor (TNF)-alpha antagonists have provided relief for many RA patients; however, despite their efficacy, some patients do not respond or fail to maintain initial response. In the UK, patients with an inadequate response to TNF-alpha antagonists have limited options, as the National Institute of Clinical Excellence (NICE) currently only recommend switching to an alternative TNF-alpha antagonists if discontinuation occurs due to safety during the first 6 months of treatment. The EU has approved three biological agents, rituximab, abatacept, and tocilizumab, for patients with RA with an inadequate response to TNF-alpha antagonists. OBJECTIVE: This review examines the clinical experience with two therapies targeting key immune cells involved in RA -- rituximab (lyses B-cells), and abatacept (T-cell co-stimulation modulator) -- specifically focusing on patients with an inadequate response to TNF-alpha blockade. METHODS: Phase II/III clinical trials and original studies were identified using Medline and Pubmed; articles assessing the efficacy and/or safety of rituximab or abatacept in patients with RA refractory to TNF-alpha blockade were reviewed. CONCLUSIONS: Clinical data for rituximab and abatacept demonstrate that both reduce disease activity in TNF-alpha antagonist inadequate responders, suggesting that agents with alternative mechanisms of action, such as those targeting key immune cells, may be useful in this patient population.
19341203 An evaluation of the efficiency of the use of an anatomical third generation shoulder pros 2009 Jan PURPOSE OF THE STUDY: In this study a series of 102 cases was reviewed in which a so called third generation shoulder prosthesis had been used. There was an interest in evaluating the quality and efficiency of the outcome. MATERIAL AND METHODS: The patient population consisted of 32 men and 70 women. The mean age was 65.8 years. The mean postoperative follow-up time was 44.5 months. Indication for arthroplasty was all common degenerative and traumatic conditions of the shoulder. All patients were evaluated and analysed prospectively by a standardised protocol. The postoperative investigation consisted of a clinical examination and a radiographic analysis. We used the Constant and the Wülker Score. RESULTS: All patients had a significant improvement in shoulder function independent of the specific indication. The mean postoperative shoulder function attained 88% as measured by the Constant score. With regard to the different indications, the significant improvement was confirmed in each of the groups. Osteoarthritis reached the highest (91%) and rheumatoid arthritis the lowest value (71%). The results of total shoulder arthroplasties was better than in hemi-shoulder arthroplasties (93% versus 86%). CONCLUSIONS: In summary, it could be demonstrated that most indications for shoulder arthroplasty can be successfully treated by using a third generation implant. Total shoulders reach better results in a mid-term follow-up.
19409094 Disease modifying and antiangiogenic activity of 2-methoxyestradiol in a murine model of r 2009 May 1 BACKGROUND: A critical component of disease progression in rheumatoid arthritis (RA) involves neovascularization associated with pannus formation. 2-methoxyestradiol (2ME2) is a naturally occurring molecule with no known physiologic function, although at pharmacologic concentrations it has antiproliferative and antiangiogenic activities. We investigated the impact of orally administered 2ME2 on the initiation and development of proliferative synovitis using the anti-collagen monoclonal antibodies (CAIA) model. METHODS: Severe polyarticular arthritis was induced in Balb/c female mice by administration of 2 mg of a monoclonal antibody cocktail intravenously into the tail vein of mice. Twenty-four hours following monoclonal antibody administration, mice were injected with 25 microg of LPS (E. coli strain 0111:B4) via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg, p.o., daily), or vehicle control began 24 hrs following LPS challenge and continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD activity and general histopathology by histomorphometric analysis and immunohistochemistry (vWF staining). In a separate study, different dosing regimens of 2ME2 (100 mg/kg; q.d. vs q.w. vs q.w. x 2) were evaluated. The effect of treatment with 2ME2 on gene expression of inflammatory cytokines and angiogenic growth factors in the joint space was evaluated 5 and 14 days after the induction of arthritis. RESULTS: Mice treated with 2ME2 beginning 24 hours post anti-collagen monoclonal antibody injection, showed a dose-dependent inhibition in mean arthritic scores. At study termination (day 21), blinded histomorphometric assessments of sectioned hind limbs demonstrated decreases in synovial inflammation, articular cartilage degradation, pannus formation, osteoclast activity and bone resorption. At the maximal efficacious dosing regimen (100 mg/kg/day), administration of 2ME2 resulted in total inhibition of the study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1beta, TNF-alpha, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2. CONCLUSION: These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.
20231203 Relationship between arterial stiffness and Stanford Health Assessment Questionnaire disab 2010 May OBJECTIVE: To quantify the relationship between Stanford Health Assessment Questionnaire (HAQ) disability and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: A consecutive series of 114 patients with RA but without overt arterial disease, aged 40-65 years, were recruited from rheumatology clinics. A research nurse measured blood pressure (BP), arterial stiffness (heart rate-adjusted augmentation index), fasting lipids, glucose, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). A self-completed patient questionnaire included HAQ, damaged joint count, EuroQol measure of health outcome, and Godin physical activity score. Multiple linear regression (MLR) adjusted for age, sex, smoking pack-years, cholesterol, mean arterial BP, physical activity, daily fruit and vegetable consumption, arthritis duration, ESR, and RA criteria. RESULTS: Mean age was 54 years (81% women) with a median HAQ of 1.13 (interquartile range 0.50; 1.75). Median RA duration was 10 years, 83% were RF-positive, and median ESR was 16 mm/h. Mean arterial stiffness was 31.5 (SD 7.7), BP 125/82 mm Hg, cholesterol 5.3 mmol/l, and 24% were current smokers. Current therapy included RA disease-modifying agents (90%), prednisolone (11%), and antihypertensive therapy (18%). Arterial stiffness was positively correlated with HAQ (r = 0.42; 95% CI 0.25 to 0.56). On MLR, a 1-point increase in HAQ disability was associated with a 2.8 increase (95% CI 1.1 to 4.4; p = 0.001) in arterial stiffness. Each additional damaged joint was associated with a 0.17 point increase (95% CI 0.04 to 0.29; p = 0.009) in arterial stiffness. The relationship between EuroQol and arterial stiffness was not statistically significant. CONCLUSION: In patients with RA who are free of overt arterial disease, higher RA disability is associated with increased arterial stiffness independently of traditional cardiovascular risk factors and RA characteristics.
20482403 Rituximab treatment for persistent scleritis associated with rheumatoid arthritis. 2010 Jun PURPOSE: To report a clinical case of a patient with severe scleritis associated with rheumatoid arthritis (RA) refractive to conventional treatment that was treated effectively with rituximab. METHODS AND RESULTS: A 55-year-old man with RA, on etanercept and oral methotrexate, was referred with diagnosis of acute stromal keratitis, anterior uveitis, and anterior nodular scleritis in his right eye. Cyclophosphamide induced complete regression of acute stromal keratitis and anterior uveitis, but scleritis was still active and persistent. After two 1000-mg infusions of rituximab, scleritis regressed completely and is still in remission 9 months after the second rituximab infusion, without any concomitant use of oral steroids. CONCLUSION: Rituximab may be a treatment alternative in severe scleritis that is refractive to conventional therapy. Considering its safety profile, further studies are needed to refine its mechanism of action, optimal indications, and dosing in ocular inflammation.
20584722 The impact of HLA-DRB alleles on the subclass titres of antibodies against citrullinated p 2010 Oct OBJECTIVES: The association between HLA-DR haplotypes and RA have been well established. However, the molecular mechanisms of how HLA mediates susceptibility and/or progression of the disease remain elusive. We therefore turned to the RA-specific antibodies directed against citrullinated peptide antigens (ACPAs) and investigated the association between HLA-DRB1 shared epitope (SE) alleles and the IgG subclass titres of cyclic citrullinated peptide (CCP)- and mutated citrullinated vimentin (MCV)-specific antibodies. METHODS: One hundred and twenty-seven RA patients were typed for their HLA-DRB1 haplotypes applying low resolution and alleles potentially carrying the SE were sequenced. All patients' sera were analysed by ELISA for the presence of ACPA and 77 patients positive for CCP-specific antibodies were further analysed for the respective IgG subclasses. Subclass titres were then correlated to the presence of a SE. Finally, all patients were screened for the HLA-DRB4-associated splice variant. RESULTS: We found a gene dosage effect of the HLA-DRB1*04-associated SE on both the MCV- and CCP-specific IgG3 levels. The HLA-DRB4-associated splice variant accumulates in ACPA-negative RA patients. CONCLUSIONS: Both the dose-dependent increase in IgG3 among ACPA and the accumulation of the splice variant in ACPA-negative patients imply differential expression of the HLA alleles as the mechanism contributing to the susceptibility and/or disease progression of RA. The preponderance of IgG3 hints at a skewing towards a Th1 response and is reminiscent of increased signal strengths at the immunological synapse. Likewise, the abrogation of HLA-DRB4 expression due to the splice variant reduces the signal strength and seems to protect from ACPA development.
20061120 Mechanism by which HLA-DR4 regulates sex-bias of arthritis in humanized mice. 2010 Aug HLA class II allele DRB1*0401 is associated with predisposition to Rheumatoid Arthritis in humans as well as collagen-induced arthritis in mice. Predominantly females develop arthritis in humans and DR4 transgenic mice; however the mechanism of sex-bias is still unknown. We have investigated the molecular basis by which DR4 is associated with sex-bias of arthritis. Here we show that differential antigen-specific immune mechanisms in DR4 male and female mice lead to increased susceptibility in female mice. B cells are hyperactive and present DR-restricted peptides robustly in females compared to males. Antigen-specific response showed that females produced B cell modulating cytokines like IL-13 while males produced IFNgamma. Male transgenic mice have higher number of T and B regulatory cells. An exogenous supply of 17beta estradiol in male mice led to enhanced expression of DR4 and antigen-specific response to DR4-restricted peptides. On the other hand, castration increased the incidence of arthritis. We propose that sex-bias in arthritis involves B cells and presentation of antigen by HLA-DR4 leading to activation of autoreactive cells and autoantibodies production in females, while regulatory B cells in males protect them from pathogenesis. The transgenic mice expressing RA susceptible haplotype simulate human RA and may be valuable to study gender differences observed in patients.
20038753 Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflamma 2010 Feb The chronic inflammatory state of rheumatoid arthritis and other inflammatory arthropathies, such as ankylosing spondylitis and psoriatic arthritis, contributes to the accelerated atherosclerosis associated with these conditions. This study evaluates the effect of treatment with tumor necrosis factor (TNF)-alpha antagonists on arterial stiffness in patients with inflammatory arthropathies. A total of 60 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and clinical indication for anti-TNF-alpha therapy were included. Thirty-five patients started with anti-TNF-alpha therapy and were compared with a nontreatment group of 25 patients. Aortic stiffness (aortic pulse wave velocity), augmentation index, and disease activity were assessed at baseline and after 3 months. Aortic pulse wave velocity (mean+/-SD) was reduced in the treatment group but not in the control group (-0.50+/-0.78 m/s versus 0.05+/-0.54 m/s, respectively; P=0.002). Concomitantly, C-reactive protein and the disease activity score were reduced in the treatment group (-9.3+/-20.2 mg/L [P<0.001] and -0.74+/-0.91 [P=0.004]). Augmentation index remained unchanged in both groups (0.1+/-7.1% versus -1.0+/-5.8%, respectively; P=0.53). In a multivariate linear regression model, only treatment with TNF-alpha antagonist and change in mean arterial pressure predicted alterations in aortic pulse wave velocity. In summary, anti-TNF-alpha therapy improved aortic stiffness in patients with inflammatory arthropathies. These findings support the idea that anti-inflammatory treatment has a favorable effect on cardiovascular risk in patients with inflammatory arthropathies.
21110115 Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid art 2011 Aug The aim of this study was to determine whether the vitamin D receptor (VDR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). A meta-analysis was conducted on the associations between the BsmI, TaqI, FokI, and ApaI polymorphisms of VDR and RA or SLE using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of ten studies, six RA and four SLE studies, were considered in the meta-analysis. Meta-analysis of the VDR BsmI and TaqI polymorphisms showed no association between RA in all subjects, or in European or Asian subjects. In contrast, meta-analysis of the F allele, the FF genotype, and the FF vs. the ff genotype of the FokI polymorphism showed significant associations with RA in Europeans. The overall OR of the association between the F allele and RA was 1.502 (95% CI=1.158-1.949, P=0.002). Meta-analysis of the B allele, BB+Bb genotype, and BB genotype (additive model) of the BsmI polymorphism showed significant associations with SLE and LN in Asians. The overall ORs of the associations between the B allele and SLE and LN were 3.584 (95% CI=1.407-9.130, P=0.007) and 3.652 (95% CI=1.347-9.902, P=0.011). This meta-analysis demonstrates that the VDR FokI polymorphism may confer susceptibility to RA in Europeans. Furthermore, associations were found between the VDR BsmI polymorphism and susceptibilities to SLE and LN in Asians.
20080905 Does clinical remission lead to normalization of EQ-5D in patients with rheumatoid arthrit 2010 Feb OBJECTIVE: To compare health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA) to that of the general population and to investigate the association with disease activity, focusing on different clinical remission criteria. METHODS: EQ-5D data from 3156 patients with RA from 11 Danish centers were compared with Danish EQ-5D population norms (n = 16,136). The Disease Activity Score (DAS28) and the Clinical Disease Activity Index score (CDAI) were used as definitions of disease activity and clinical remission. The score difference (DeltaEQ-5D) was calculated in each patient as the difference from the age and sex-matched general population and adjusted for age, marital status, education, body mass index, smoking, exercise habits, disease duration, IgM-rheumatoid factor status, joint surgery, extraarticular features, treatment, and comorbidity in multiple linear regression models. RESULTS: 37% vs 22% fulfilled the DAS28 and CDAI remission criteria, respectively. The DeltaEQ-5D values for women/men in clinical remission were DAS28 0.05/0.06 vs CDAI 0.01/0.02; low disease activity: DAS28 0.12/0.13 vs CDAI 0.11/0.14; moderate disease activity: DAS28 0.18/0.20 vs CDAI 0.20/0.23; and high disease activity: DAS28 0.38/0.28 vs CDAI 0.33/0.26. Adjusting for confounders reduced the DeltaEQ-5D values between 0 and 0.04 units. CONCLUSION: Patients with RA had worse EQ-5D scores than the general population, and the difference was strongly associated with disease activity. The EQ-5D score for patients in clinical remission approached that of the general population, suggesting that strict treatment goals are critical in order to achieve near-normal HRQOL in patients with RA.
20085505 Methotrexate compliance among patients with rheumatoid arthritis: the influence of disease 2010 May OBJECTIVE: To assess methotrexate (MTX) compliance among rheumatoid arthritis (RA) patients. METHODS: Using prescription data, we conducted a 10-year longitudinal study among RA patients who were first-time MTX users. MTX compliance was expressed as the continuous measure of medication gaps (CMG), that is the proportion of treatment gaps compared with the total observation period stratified by age, sex, C-reactive protein (CRP), haemoglobin, co-morbidity, concurrent medication, and disease duration. Multiple linear regression analysis was used to assess the influence of disease activity, disease duration, and co-morbidity on compliance. RESULTS: A total of 941 RA patients redeemed 7501 MTX prescriptions during our study period. Overall, the patients had gaps in 12.3% of the observation period corresponding to a mean period not covered with MTX of 1.5 months/year if all participants were followed for 1 year. Patients with CRP > 32 mg/L had a lower mean CMG than patients with CRP < 8 mg/L [adjusted CMG difference -0.04, 95% confidence interval (CI) -0.07 to - 0.02]. Patients with a disease duration < 1 year had a lower mean CMG than patients with a disease duration between 1 and 5 years (adjusted CMG difference 0.01, 95% CI -0.01 to 0.04). Patients with a diagnosis of ulcer/mild liver disease had a higher mean CMG than patients without this diagnosis (adjusted CMG difference 0.04, 95% CI 0.004-0.084). CONCLUSION: MTX compliance was generally high among RA patients. Compliance decreased with increasing disease duration, low to moderate disease activity, and the presence of a diagnosis of ulcer/mild liver disease.
18708166 A new strategy for the early diagnosis of rheumatoid arthritis: a combined approach. 2009 Jan Rheumatoid arthritis [RA] is one of the most common and severe autoimmune rheumatic diseases, diagnosed primarily according to clinical manifestations and radiological reports. For many years, laboratory diagnosis of rheumatoid arthritis has relied on the detection of rheumatoid factor [RF], as established by the ACR criteria. A recent test to detect antibodies towards citrullinated peptides, called the anti-CCP assay, showed a similar sensitivity but a more elevated specificity than the RF test. Our intention was the recognition of an optimal diagnostic strategy that exhibits the highest sensitivity and specificity for RA detection. To this purpose, we examine the usefulness of autoantibodies in RA testing, evaluating the diagnostic performance of conventional and innovative assays for RF detection, and ELISA anti-CCP test, for anti-CCP antibodies detection, by a prospective study. Multiplex cytofluorimetric test appeared to be more sensitive and specific than nephelometric assay for RF detection. Hence, a novel combined approach, significantly increasing the diagnostic sensitivity for RA, was planned, employing the multiplex RF test in combination with the anti-CCP test.
20694284 Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) sp 2010 Oct Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.
19384550 [Regenerative potential of human adult precursor cells: cell therapy--an option for treati 2009 May Cell-based therapeutical approaches are already in clinical use and are attracting growing interest for the treatment of joint defects. Mesenchymal stem and precursor cells (MSC) cover a wide range of properties that are useful for the regeneration process of bone and cartilage defects. The following article is an overview of the regenerative potential of MSC and discusses how the properties of these cells can be used for the development of new strategies in regenerative medicine.
19829243 Navigated anterior approach to the upper cervical spine after occipitocervical fusion. 2009 Oct 15 STUDY DESIGN: Technical note. OBJECTIVE: To introduce the application of navigation system with software for brain surgery to the upper cervical spine of patients who have previously had occipitocervical (O-C) fusion. SUMMARY OF BACKGROUND DATA: The anterior approach to the spine using a navigation system with software for spine surgery is difficult because the registration tends to be inaccurate. However, after O-C fusion, the upper cervical spine is considered part of the skull, and a navigation system with software for brain surgery in which the registration is performed using the head with several markers attached to it can be applied. METHODS: Three patients with previous O-C fusion-2 with upper cervical chordoma and 1 with a disc herniation at C2/3-were treated using this technique. RESULTS: In the first case, with a huge retropharyngeal C1 chordoma, this technique was very helpful in blindly dissecting the nonvisible parts of the tumor. In the second case, with a C2 chordoma, the vertebral arteries were successfully exposed under the guidance of the navigation system at both primary and revision surgery. In the third case, with disc herniation at C2/3, the herniated disc was removed successfully with the totally fused spine. In this application, computed tomography images can be merged freely with magnetic resonance images, which is helpful to clarify the soft tissues such as tumor, disc herniation, or the dural tube. CONCLUSION: This technique greatly supports surgeons inexperienced in the anterior approach to the upper cervical spine or surgeons at revision surgery who may be lost in and daunted by an unfamiliar operation field surrounded by important structures. Although an anterior approach to the upper cervical spine in the patient with O-C fusion may rarely be required, this application should be considered.
20732646 Embracing novel cytokines in RA - complexity grows as does opportunity! 2010 Aug Current therapeutics for the treatment of rheumatoid arthritis (RA) offer limited efficacy in a restricted number of patients. There is, therefore, an unmet clinical need for the development of more efficacious therapeutics for the treatment of disease. Anti-TNFalpha therapy has provided proof of principle that cytokine blockade is an appropriate strategy by which to inhibit disease progression. In this review, we describe the basic biology of potential novel cytokine targets and the results of recent clinical trials, with particular focus on the cytokines related to Th17 biology, namely interleukin (IL)-12, IL-23 and IL-17, in addition to the TNF superfamily and the adipocytokines.
19281530 Highly arthritis-susceptible DA rats express IL-1beta in articular cartilage. 2009 Mar There are genetically determined differences in susceptibility to arthritis among inbred rat strains. The aim of the present study was to elucidate phenotypical differences, by determining expression of TNF and IL-1beta, two pivotal mediators of arthritis, in the highly arthritis-prone Dark Agouti (DA) rat compared to that of two arthritis-resistant rat strains, the major histocompatibility complex-homologous Piebald-Viral-Glaxo (PVG.1AV1) rat and the Brown Norway (BN) rat, assessed by immunohistochemistry. We demonstrate a distinct difference in articular cartilage, with chondrocytes expressing IL-1beta, not TNF, in the highly arthritis-prone DA rat as opposed to the two arthritis-resistant BN or PVG.1AV1 rat strains, where no cytokine expression was documented. The results were otherwise congruent among the rat strains. We observed TNF- and IL-1beta-expressing cells within the synovial lining layer in all rat strains. Other tissues studied, auricular cartilage as well as muscle, lung, thyroid gland and kidney tissue, were devoid of cytokine expression. Constitutional expression of IL-1beta in chondrocytes might facilitate initiation and perpetuation of inflammation. This may offer one explanation of why erosive arthritides are so easily induced in the DA rat and also support the hypothesis that articular chondrocytes may themselves play a major role in cartilage matrix degradation.