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ID PMID Title PublicationDate abstract
23685257 IL-4 and MTHFR gene polymorphism in rheumatoid arthritis and their effects. 2013 May Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that mainly affects the joints. Polymorphic variations of the cytokine genes and MTHFR gene have received attention as potential markers of susceptibility, severity, and/or protection in RA. The aim of this study was to investigate the MTHFR C677T and IL-4 70bp VNTR variation in Turkish patients with RA and evaluate if there was an association with clinical features, especially ocular involvement, in RA patients. The study included 297 persons (147 patients with RA and 150 healthy controls). Genomic DNA was isolated and genotyped using PCR assay for the MTHFR gene C677T and IL-4 gene 70bp VNTR polymorphisms. Our results show that there was statistically significant difference between the groups with respect to IL-4 genotype (p=0.01) and allele frequencies (p<0.002). There was no statistical significant difference in the genotype frequencies MTHFR gene, but allele frequencies showed statistically significant association (p=0.01). When we examined MTHFR and IL-4 genotype frequencies according to the clinical characteristics, we found that there was a difference between MTHFR genotypes and ocular involvement but it is not to a statistical significant degree (p=0.09). In the combined genotype analysis, MTHFR/IL-4 CCP2P2 combine genotype was estimated to have protective effect against RA, CTP1P2 combine genotype was found to be risk for RA. Our findings suggest that there is an association of IL-4 gene 70bp VNTR polymorphism and MTHFR C677T polymorphism with susceptibility of a person for development of RA.
23883285 Interleukin-4, interleukin-4 receptor, and interleukin-18 polymorphisms and rheumatoid art 2013 OBJECTIVE: The aim of this study was to determine whether the functional interleukin-4 (IL-4) -590 C/T, IL-4 receptor (IL-4R) 1902 G/A, IL-18 -607 C/A, and -137 G/C polymorphisms polymorphisms confer susceptibility to rheumatoid arthritis (RA). METHODS: Meta-analysis was conducted on the associations between these IL-4, IL-4R, and IL-18 polymorphisms and RA. RESULTS: A total of 12 comparative studies were included in this meta-analysis. Meta-analysis of the IL-4 -590 C/T polymorphism showed an association in all study subjects and Europeans (OR for the TT genotype = 2.280, 95% CI = 1.315-3.952, p = 0.003; OR = 2.139, 95% CI = 1.089-4.199, p = 0.027). However, meta-analysis showed no association between RA and the IL-4R 1902 G allele in all study subjects and Europeans. Meta-analysis showed no association between RA and the IL-18 -607 C allele (OR = 1.159, 95% CI = 0.967-1.387, p = 0.110). Meta-analysis of the IL-18 -137 G/C polymorphism revealed no association between RA and the IL-18 -137 G/C polymorphism. CONCLUSIONS: This meta-analysis demonstrates that the IL-4 -590 T/C polymorphism is associated with susceptibility to RA in Europeans, but the IL-4R + 1902 G/A, IL-18 -607 C/A and -137 G/C polymorphisms are not associated with RA.
23784884 A lipidomic study of phospholipid classes and species in human synovial fluid. 2013 Sep OBJECTIVE: Membrane phospholipid species contribute to boundary lubrication that is provided by synovial fluid (SF). Altered levels of lubricants can be associated with increased friction, leading to articular cartilage damage. This study was undertaken to determine whether the composition of phospholipid species is altered in diseases of human knee joints. METHODS: The study was performed using SF from unaffected controls and patients with early osteoarthritis (OA), late OA, or rheumatoid arthritis (RA). Lipids were extracted from cell- and vesicle-free SF from 9 control donors postmortem and from 17 patients with early OA, 13 patients with late OA, and 18 patients with RA. Phospholipid species were quantified by electrospray ionization tandem mass spectrometry. RESULTS: We conducted lipidomic analysis to provide the first detailed overview of phospholipid species in human SF. We identified 130 lipid species belonging to 8 lipid classes (phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, plasmalogens, phosphatidylserine, phosphatidylglycerol, sphingomyelin, and ceramide). Compared to SF from controls, SF from patients with early OA and those with late OA had higher levels of most phospholipid species. Moreover, the concentrations of 64 and 27 phospholipids differed between RA and early OA SF and between RA and late OA SF, respectively. Also, the levels of 66 phospholipid species were altered in early OA versus late OA. CONCLUSION: Our data indicate disease- and stage-dependent differences in the relative composition and levels of phospholipid species in human SF. Such alterations might affect articular joint lubrication. Because certain phospholipids scavenge reactive oxygen species (ROS) and are pro- or antiinflammatory, any altered phospholipid level might influence ROS-scavenging activity of SF and the inflammatory status of joints. Thus, phospholipids may be associated with the pathogenesis of OA.
24960404 Similar blood-borne DNA methylation alterations in cancer and inflammatory diseases determ 2014 Jul 29 BACKGROUND: Although many DNA methylation (DNAm) alterations observed in peripheral whole blood/leukocytes and serum have been considered as potential diagnostic markers for cancer, their origin and their specificity for cancer (e.g., vs inflammatory diseases) remain unclear. METHODS: From publicly available datasets, we identified changes in the methylation of blood-borne DNA for multiple cancers and inflammatory diseases. We compared the identified changes with DNAm difference between myeloid and lymphoid cells extracted from two datasets. RESULTS: At least 94.7% of the differentially methylated DNA loci (DM loci) observed in peripheral whole blood/leukocytes and serum of cancer patients overlapped with DM loci that distinguish between myeloid and lymphoid cells and >99.9% of the overlapped DM loci had consistent alteration states (hyper- or hypomethylation) in cancer samples compared to normal controls with those in myeloid cells compared to lymphoid cells (binomial test, P-value <2.2 × 10(-16)). Similar results were observed for DM loci in peripheral whole blood/leukocytes in patients with rheumatoid arthritis or inflammatory bowel diseases. The direct comparison between DM loci observed in the peripheral whole blood/leukocytes of patients with inflammatory diseases and DM loci observed in the peripheral whole blood of patients with cancer showed that DM loci detected from cancer and inflammatory diseases also had significantly consistent alteration states (binomial test, P-value <2.2 × 10(-16)). CONCLUSIONS: DNAm changes observed in the peripheral whole blood/leukocytes and serum of cancer patients and in the peripheral whole blood/leukocytes of inflammatory disease patients are predominantly determined by the increase of myeloid cells and the decrease of lymphoid cells under the disease conditions, in the sense that their alteration states in disease samples compared to normal controls mainly reflect the DNAm difference between myeloid and lymphoid cells. These analyses highlight the importance of comparing cancer and inflammatory disease directly for the identification of cancer-specific diagnostic biomarkers.
24369241 [High-frequency ultrasound imaging of collagen-induced arthritis in rats]. 2013 Dec OBJECTIVE: To assess the performance of high-frequency ultrasound in evaluating articular lesions in a rat of model collagen-induced arthritis model (CIA). METHODS: Sixty Wistar rats randomized into CIA group (n=50) and the control group (n=10), and in the former group, CIA was induced by immunization with collagen type II. On day 45, the ankle joint was assessed based on the arthritic index (AI) and examined with high-frequency ultrasound in all the rats. Histological evaluations of the joint were performed and the results were compared with ultrasound findings. RESULTS: In CIA group, 62 ankles were confirmed pathologically to have synovitis with typical inflammatory cell infiltration and pannus formation. AI score-based diagnosis was confirmed in 42 ankles with a detection rate of 68% (42/62), significantly lower than the rate of 87% (54/62) with high-frequency ultrasound (P<0.05). CONCLUSION: High-frequency ultrasound is an ideal method for observing CIA in rats in vivo. High-frequency ultrasound can show blood flow in rheumatoid arthritis and is useful in studies of RA synovial angiogenesis.
25742995 [Phaeomycotic cyst caused by Exophiala xenobiotica in a patient with rheumatoid arthritis 2014 In black fungal infections, Exophiala species are frequently encountered as causative agents of human mycosis, particularly in immunocompromised patients. Among them, Exophiala jenselmei was previously reported as the most common etiological agent. Advances in molecular taxonomy proved this taxon to be heterogeneous, and led to newly introduced or redefined species. Exophiala xenobiotica is one of the novel species differentiated from E. jenselmei on the basis of molecular phylogeny.Here, we report a case of pheomycotic cyst caused by E. xenobiotica, which was well controlled via drainage and local thermotherapy. A 70-year-old man developed a cystic nodular lesion on the dorsum of his right thumb over the previous 3 months. He had been treated with prednisolone and methotrexate for 4 years for rheumatoid arthritis. The patient also had lung cancer with vertebral bone metastasis. Direct microscopic examination of the greenish pus aspirated from the cyst revealed mycelial elements. Culture of the pus on blood and Sabouraud dextrose agar yielded numerous black colonies multiple times. Histopathological examination of a biopsy specimen showed subcutaneous abscess formation surrounded by granulomatous tissues. Faintly pigmented pseudohyphae were seen within the abscess. The presence of melanin in the fungal cells was determined by Fontana-Masson staining. Initial microscopic examination of the isolate revealed annellidic conidiogenous cells, suggestive of E. jenselmei. This strain was further identified as E. xenobiotica by sequence analysis of the internal transcribed spacer (ITS) region of ribosomal RNA, showing a 100% sequence homology with the strain type.Pheomycotic cysts should be considered on identifying a slowly developing chronic subcutaneous abscess in immunocompromised patients. Sequencing is recommended for accurate species identification of causative pathogens.
24609758 Indispensable or intolerable? Methotrexate in patients with rheumatoid and psoriatic arthr 2014 May Methotrexate (MTX) has become the first-line treatment for rheumatoid (RA) and psoriatic arthritis (PsA); however, few studies have focused on its tolerability. The objective of our analyses was to study RA and PsA patients in whom MTX was discontinued, the reasons for this and the duration of MTX treatment prior to withdrawal. A retrospective electronic database review was undertaken to identify all patients who had received MTX for RA or PsA. Patients who had discontinued MTX were then identified, and the reasons for this were categorised. The duration of MTX treatment was assessed in those who had stopped treatment due to intolerability. A total of 1,257 patients who had received MTX were identified [762 (61 %) RA and 193 (15 %) PsA]. MTX had been stopped in 260 (34 %) patients with RA and 71 (36 %) patients with PsA most commonly due to gastrointestinal intolerability. The median duration of MTX treatment was 10 months in both groups, mean duration 21 and 18.6 months in RA and PsA groups, respectively. Overall, one third of patients with RA and PsA stop MTX most commonly due to poor tolerability. In the context of chronic disease, the median duration of treatment is short (10 months). Our analysis did not include patients who suffer from side effects but continue therapy; thus, the magnitude of the problem may be substantially greater therefore as poor tolerability impacts treatment adherence.
23471745 Visfatin and adiponectin as novel markers for evaluation of metabolic disturbance in recen 2013 Sep The aim is to assess metabolic disturbance in early rheumatoid arthritis patients and its relation to the clinical characteristics of patients. Forty recently diagnosed untreated rheumatoid arthritis (RA) patients with disease duration less than 1 year (group I) along with age- and sex-matched forty healthy volunteers who served as controls (group II) were studied. Disease activity score was used to assess disease activity. Blood pressure, BMI, glucose, insulin and complete lipid profile, visfatin, and adiponectin were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment for insulin resistance (HOMA-IR). Beta-cell function was estimated by the homeostasis model assessment (HOMA-B). Also, rheumatoid factor, anticyclic citrullinated peptide antibodies were measured. Group I had significantly higher fasting insulin, HOMA-(IR, B), visfatin, lipid profile (except HDL), and lower adiponectin versus group II (p = 0.000). There were significant positive correlations between visfatin and the following biochemical parameters: insulin, HOMA-IR, HOMA-B, cholesterol, triglycerides, LDL-C (p = 0.05, 0.029, 0.005, 0.001, 0.002, 0.045, respectively). Also, the disease activity score was positively correlated with visfatin (p = 0.003). Meanwhile, there were significant negative correlations between adiponectin and the following biochemical parameters: insulin, HOMA-IR, HOMA-B, cholesterol, triglycerides, LDL-C, visfatin (p = 0.031, 0.023, 0.001, 0.000, 0.000, 0.016, 0.000, respectively). Also, the disease activity score was negatively correlated with adiponectin (p = 0.001). The findings of the present study showed that recently diagnosed untreated RA patients are characterized by a severe metabolic disturbance state that is driven primarily by disease activity.
24504437 Development of myeloid sarcoma after long-term methotrexate use for rheumatoid arthritis. 2014 Apr Myeloid sarcoma (MS) in the complete absence of bone marrow disease is an extremely rare phenomenon. We report the case of a 78-year-old woman with multiple subcutaneous lung and liver nodules, including mediastinal and peritoneal lymph node swelling, who had been receiving methotrexate (MTX) for 10 years for rheumatoid arthritis (RA). She was initially diagnosed with ALK-negative anaplastic large cell lymphoma. After one course of an anthracycline-containing regimen, pathologic cells were identified as CD68 (Kp-1)-positive with myeloid-lineage tumor cells and abnormal karyotypes with 8q21 and 21q22. Subsequent treatment was changed to acute myelogenous leukemia (AML) induction chemotherapy. Although the lesions were partially reduced in size following treatment for lymphoma, complete response (CR) was obtained only after AML chemotherapy. The patient remained in CR over 3 years after the last chemotherapy. This case may indicate an association between long-term MTX use and MS. An early diagnosis and adequate therapy may be important for improving survival outcomes in MS. This report demonstrates that CD68 staining is important for the differential diagnosis of MS and lymphoma. Careful follow-up is necessary for this patient, who may be the first case of MS after methotrexate use for RA.
22257601 An incidental finding? Pneumatosis intestinalis after minor trauma. 2013 Feb BACKGROUND: Pneumatosis intestinalis (PI) refers to the identification of air within the wall of the gastrointestinal tract. This finding often marks serious underlying pathology, which can be potentially surgical in nature. However, this process may also occur within a benign context, for example, in patients who are chronically immunosuppressed. The prevalence of benign PI may be greater than previously anticipated, because its discovery is facilitated by the increasingly widespread use of computed tomography (CT) scanning. OBJECTIVES: We will illustrate how widespread use of CT scanning after trauma leads to incidental findings, some of which are difficult to distinguish from acute pathologic findings. We will also discuss the differential diagnosis for PI and the associated clinical significance. CASE REPORT: A female patient with two autoimmune disorders requiring immunosuppression presented after minor trauma. Her clinical stability and benign examination led us to refrain from ordering a full radiographic evaluation, including an abdominal CT scan. She was safely discharged; however, per CT several days later, the incidental finding was made of PI with free intraperitoneal air. These findings after trauma commonly prompt an exploratory laparotomy. However, given her persistent stability, we attributed this to immunosuppression rather than to recent trauma. CONCLUSION: The indications for ordering CT scans after minor trauma must be carefully considered, and incidental findings must be interpreted in the context of the overall clinical scenario.
25344777 The descriptive epidemiology of rheumatoid arthritis in Catalonia: a retrospective study u 2016 Mar Information on the epidemiology of rheumatoid arthritis (RA) in Southern Europe is scarce. We estimated the age- and gender-adjusted incidence and prevalence of RA in Catalonia using routinely collected primary care records. We identified incident (2009-2012) and prevalent (on 31 December 2012) cases of RA in the SIDIAP database using ICD-10 codes. SIDIAP contains anonymized data from computerized primary care records for about five million adults (>80 % of the population). We estimated age- (5-year groups) and gender-specific, and directly standardized incidence and prevalence of RA and confidence intervals (95% CIs) assuming a Poisson distribution. A total of 20,091 prevalent (among whom 5,796 incident) cases of RA were identified among 4,796,498 study participants observed for up to 4 years. Rates of RA increased with age in both genders, peaking at the age of 65-70 years. Age- and gender-standardized incidence and prevalence rates were 0.20/1,000 person-years (95% CI 0.19-0.20) and 4.17/1,000 (4.11-4.23) respectively. Rheumatoid factor was positive (≥10 IU/mL) in 1,833 (73.9 %) of 2,482 cases tested in primary care. The incidence and prevalence of RA in Catalonia are similar to those of other Southern European regions, and lower than those of northern areas. This data will inform health care planning and resource allocation.
25524318 Cemented metal-on-metal total hip replacement with 28-mm head: prospective, long-term, cli 2015 May PURPOSE: The aim of this study was to evaluate the long-term clinical, radiological and metal ion blood concentration results following 28-mm metal-on-metal cemented total hip replacement using Metasul(®) acetabular component and polished, cannulated Allopro CF-30 (Sulzer-Medica, subsequently Centerpulse-Zimmer, Winterthur, Switzerland) femoral component. METHODS: Prospective follow-up of patients operated between 1997 and 2000 at a district general hospital. RESULTS: Seventy-nine patients (89 implants) with female predominance and median age of 66 years (IQR 45-87 years) were prospectively followed up for mean 13 years (11-14 years). There was significant improvement in Harris hip score (paired Student's t test p = 0.0001). The mean plasma cobalt and chromium levels were 1.3 µg/L (IQR 0.5-23.9) and 3.6 µg/L (IQR 1.0-22), respectively. Elevated plasma metal ions >7 µg/L were noted in four asymptomatic patients with negative ultrasound examination. Radiolucent lines were present in various zones but majority were stable. One femoral component was revised due to aseptic femoral loosening. Three acetabular and one femoral component have radiologically failed but not revised yet. The Kaplan-Meier survival at 14 years was 92 % for failure as endpoint. CONCLUSION: The long-term survival of Metasul(®) cemented total hip replacements using 28-mm metal-on-metal head is comparable with metal on polyethylene bearing devices.
23264338 Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis 2014 Jan BACKGROUND: There are conflicting reports in the literature of the mortality risk among patients with psoriatic arthritis (PsA). The objective of this study was to examine the risk of mortality in patients with PsA compared with matched controls, patients with psoriasis and those with rheumatoid arthritis (RA). METHODS: A longitudinal cohort study was performed in a large UK medical record database, The Health Improvement Network, among patients with PsA, rheumatoid arthritis (RA) or psoriasis with data from 1994 to 2010. Unexposed controls were matched on practice and start date within the practice for each patient with PsA. Cox proportional hazards models were used to calculate the relative hazards for death. RESULTS: Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=82 258) were identified; 1 442 357 person-years were observed during which 21 825 deaths occurred. Compared with population controls, patients with PsA did not have an increased risk of mortality after adjusting for age and sex (disease-modifying antirheumatic drug (DMARD) users: HR 0.94, 95% CI 0.80 to 1.10; DMARD non-users: HR 1.06, 95% CI 0.94 to 1.19) whereas patients with RA had increased mortality (DMARD users: HR 1.59, 95% CI 1.52 to 1.66; DMARD non-users: HR 1.54, 95% CI 1.47 to 1.60). Patients with psoriasis who had not been prescribed a DMARD had a small increased risk of mortality (HR 1.08, 95% CI 1.04 to 1.12) while those who had been prescribed a DMARD, indicating severe psoriasis, were at increased risk (HR 1.75, 95% CI 1.56 to 1.95). CONCLUSIONS: Patients with RA and psoriasis have increased mortality compared with the general population but patients with PsA do not have a significantly increased risk of mortality.
24490499 [The role of T helper 17 cells of synovial fluid in rheumatoid arthritis]. 2013 Nov OBJECTIVE: To investigate the role of Th17 cells of synovial fluid (SF)in the pathogenesis of rheumatoid arthritis (RA). METHODS: RA patients with knee synovial fluid (n = 15) and healthy volunteers (n = 15) were enrolled. The amounts of Th17 cells in peripheral blood and SF were measured by flow cytometry. Since there was no SF in healthy control, only the amounts of Th17 cells in peripheral blood were measured. The correlation between the amounts of SF Th17 cells and clinical inflammatory parameters was evaluated. Retinoic acid-related orphan receptor gammat (RORgammat), interleukin-17 (IL-17) gene expression in lymphocytes were assessed by real-time PCR. RESULTS: The percentages of Th17 cells in SF from RA patients (1.89 +/- 0.88)% were significantly higher than that in paired PB from RA patients (1.03 +/- 0.57)% and that in PB from healthy controls (0.35 +/- 0.18)%; (2) The frequency of Th17 cells in SF from RA patients correlated positively with serum CRP (r = 0.519, P = 0.047); (3) The mRNA levels of RORgammat and IL-17 were increased in SF lymphocyte population from RA patients compared to paired PB from RA patients and healthy controls (P < 0.01). CONCLUSION: Increases of Th17 cells in synovial fluid of patients with RA patients might attribute to the difference between local joint inflammation and systemic inflammation, and participates in joint damage.
23001847 PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal t 2013 Jan Migration and invasion of fibroblast-like synoviocytes (FLSs) are critical in the pathogenesis of rheumatoid arthritis (RA). Hypoxic conditions are present in RA joints, and hypoxia has been extensively studied in angiogenesis and inflammation. However, its effect on the migration and invasion of RA-FLSs remains unknown. In this study, we observed that RA-FLSs exposed to hypoxic conditions experienced epithelial-mesenchymal transition (EMT), with increased cell migration and invasion. We demonstrated that hypoxia-induced EMT was accompanied by increased hypoxia-inducible factor (HIF)-1α expression and activation of Akt. After knockdown or inhibition of HIF-1α in hypoxia by small interfering RNA or genistein (Gen) treatment, the EMT transformation and invasion ability of FLSs were regained. HIF-1α could be blocked by phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, indicating that HIF-1α activation was regulated by the PI3K/Akt pathway. Administration of LY294002 (20 mg/kg, intra-peritoneally) twice weekly and Gen (25 mg/kg, by gavage) daily for 3 weeks from day 20 after primary immunization in a collagen-induced arthritis rat model, markedly alleviated the clinical signs, radiology progression, synovial hyperplasia, and inflammatory cells infiltration of joints. Thus, results of this study suggest that activation of the PI3K/Akt/HIF-1α pathway plays a pivotal role in mediating hypoxia-induced EMT transformation and invasion of RA-FLSs under hypoxia.
23448385 Overexpression and secretion of the soluble CTLA-4 splice variant in various autoimmune di 2013 Apr AIM: To explore the potential genetic association of CTLA-4 Exon1 +49A/G and 3'UTR (AT)(n) to susceptibility to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and overlapping (OP) autoimmunity; affected with more than one autoimmune disease. Expression of two major CTLA-4 isoforms; full length (mCTLA-4) and soluble (sCTLA-4) were explored in all subjects. A total of 680-age/gender/ethnically matched Kuwaitis were recruited and polymerase chain reaction (PCR)-fragment analysis was employed for genotyping both markers. mCTLA-4 and sCTLA-4 mRNA expression were analyzed using quantitative real time-PCR. The enzyme-linked immunosorbent assay (ELISA) was used to screen sCTLA-4 in all subjects' sera. RESULTS: Only two CTLA-4 3'UTR (AT)(n) allelotypes; (AT)(15) and (AT)(6) were detected. The heterozygous (AT)(15/6) genotype confers protectivity rather than susceptibility to SLE (p=0.01, odds ratio=0.43, and confidence interval=0.21-0.86). No significant association was observed between Exon 1 +49A/G and any of the tested diseases. A consistently high serum sCTLA-4 level was observed in RA (6.8 ng/mL, p=0.005), SLE (6.34 ng/mL, p=0.007), and OP (8.75 ng/mL, p=0.012) compared to healthy control. A significant increase in the expression of sCTLA-4 mRNA was observed in OP (p=0.05) and SLE (p=0.047), while a significant increase in the expression of mCTLA-4 (p=0.01) was observed only in OP. CONCLUSION: The present study is the first to report a statistically significant association between OP and serum sCTLA-4. The novelty of our study is the significance of CTLA-4 in the pathogenesis of OP besides SLE and RA.
23448899 Factors influencing on retro-odontoid soft-tissue thickness: analysis by magnetic resonanc 2013 Mar 1 STUDY DESIGN: A retrospective, consecutive case series. OBJECTIVE: To analyze the relationship between retro-odontoid soft-tissue thickness and patients' age, sex, and degenerative changes of cervical spine and to investigate the effect these factors have on retro-odontoid soft-tissue thickness. SUMMARY OF BACKGROUND DATA: Thickening of the soft tissue posterior to the odontoid process can form a retro-odontoid pseudotumor causing symptoms of spinal cord compression. Rheumatoid arthritis and long-term dialysis have been reported as possible causes for this. However, there have been reports of retro-odontoid pseudotumors without coexisting diseases. METHODS: Findings from a total of 503 cases of cervical spine magnetic resonance images were reviewed, and retro-odontoid soft-tissue thickness was measured. The values were matched for age, sex, presence of degenerative changes, rheumatoid arthritis, and dialysis and were analyzed for significance. RESULTS: Retro-odontoid soft tissue thickened with age, and this was also seen in male patients and patients with degenerative changes. Significant increase in thickness was also observed in patients undergoing dialysis and further increased with prolonged dialysis. There was no significant association with presence of rheumatoid arthritis. CONCLUSION: There is association between age, sex, degenerative cervical spine changes, and dialysis with retro-odontoid soft-tissue thickness. With dialysis, retro-odontoid soft-tissue thickness increases with increasing duration. Thus, reviewing magnetic resonance image from daily practice indicates that cervical spine degeneration is associated with the development of retro-odontoid pseudotumors.
24249811 B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by re 2015 Jan OBJECTIVE: To investigate whether regulatory T cells (Treg) can control B cell function in rheumatoid arthritis (RA) and if not to explore the basis for this defect. METHODS: Suppression of B cell responses by Treg was analysed in vitro by flow cytometry and ELISA using peripheral blood mononuclear cells from 65 patients with RA and 41 sex-matched and aged-matched healthy volunteers. Blocking and agonistic antibodies were used to define the role of Fas-mediated apoptosis in B cell regulation. RESULTS: Treg failed to restrain B cell activation, proinflammatory cytokine and antibody production in the presence of responder T cells in RA patients. This lack of suppression was not only caused by impaired Treg function but was also due to B cell resistance to regulation. In healthy donors, control by Treg was associated with increased B cell death and relied upon Fas-mediated apoptosis. In contrast, RA B cells had reduced Fas expression compared with their healthy counterparts and were resistant to Fas-mediated apoptosis. CONCLUSIONS: These studies demonstrate that Treg are unable to limit B cell responses in RA. This appears to be primarily due to B cell resistance to suppression, but Treg defects also contribute to this failure of regulation. Our data identify the Fas pathway as a novel target for Treg-mediated suppression of B cells and highlight a potential therapeutic approach to restore control of B cells by Treg in RA patients.
23044076 Successful treatment of pemphigus with biweekly 1-g infusions of rituximab: a retrospectiv 2013 Mar BACKGROUND: Rituximab is increasingly being appreciated as a remarkably effective treatment for pemphigus, mostly concomitantly with other immunosuppressive medications. The majority of studies have used a single cycle of rituximab with the same dosage as approved for the treatment of lymphomas, ie, 375 mg/m(2) weekly × 4 weeks. Rituximab is also approved for the treatment of rheumatoid arthritis, with a different dosing regimen: 1000 mg × 2, days 1 and 15. OBJECTIVE: We aimed to assess the clinical response of patients with pemphigus to a single cycle of rituximab at the dosage used in rheumatoid arthritis. We also evaluated the response to repeated cycles of rituximab. METHODS: A total of 47 patients with pemphigus who were treated with rituximab at a dosage of 1000 mg × 2, days 1 and 15, most with concurrent immunosuppressive medications, were retrospectively studied. RESULTS: Remission rates after the first treatment cycle reached 76%. Repeating the treatment further increased the remission rates to 91%. There was a 22% relapse rate at a median time of 8 months, but 75% of relapsing patients achieved remission again with additional cycles. The side-effect profile was similar to previous reports, except for an immediate postinfusion pemphigus exacerbation in 4 patients. LIMITATIONS: This was a retrospective study with a limited follow-up period. CONCLUSION: The rheumatoid arthritis dosage of rituximab was efficacious and well tolerated in patients with pemphigus. Patients who fail to achieve remission after 1 cycle or patients who relapse seem to benefit from repeated rituximab cycles.
24528544 Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, 2015 Feb OBJECTIVE: Temporal summation (TS) of pain, conditioned pain modulation (CPM), and exercise-induced analgesia (EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia (CFS/FM), and patients with rheumatoid arthritis (RA), both under placebo and paracetamol condition. METHODS: Fifty-three female volunteers - of which 19 patients with CFS/FM, 16 patients with RA, and 18 healthy controls - underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS and CPM. RESULTS: Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo (P < 0.05). In patients with CFS/FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen. CONCLUSION: This study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/FM, these positive effects were only observed after paracetamol and results were inconsistent.