Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18590107 [Diagnosis of wrist joint lesions by arthrosonography in early rheumatoid arthritis]. 2008 AIM: To assess joint and extraarticular wrist lesions in RA patients with arthrosonography in the disease duration up to 6 months. MATERIAL AND METHODS: 38 RA patients aged 40 +/- 10.5 years (25 females and 13 males) entered the study. These patients and 20 controls without musculoskeletal pathology matched by age and sex have undergone sonographic examination of the wrists and extrajoint structures. RESULTS: The following ultrasonographic signs of intra- and extra-articular inflammation were determined: joint cavity expansion, the presence of anechoic/hypoechoic synovial fluid, effusions, synovial thickening, digital flexor and extensor tenosynovitis, incongruous articular surfaces, bone erosions. CONCLUSION: Wrist arthrosonography is an informative diagnostic method in early RA as it detects bone erosions, alterations in the cartilages, muscles, tendons and ligaments.
18669112 [Underfoot pressure distribution of a patient with unilateral ankylosis of talonavicular j 2008 The aim of our study was to estimate underfoot pressure distribution of a patient with unilateral ankylosis of talonavicular joint during rheumatoid arthritis. The pedobarographic examination during bipedal standing revealed localisation of maximal pressure at the H region on the side opposite of ankylosis and increased underfoot pressure on the T region and decreased on GT, MT1-MT3 and H foot regions on the pathology side. After the end of orthopaedic treatment underfoot, pressure distribution changes persist in spite of pain regression.
18516965 [Paradigm shift in the treatment of rheumatoid arthritis by biologics]. 2008 Apr Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes significant morbidity and mortality. TNF-alpha plays a pivotal role in the pathological processes of RA by accumulation of inflammatory cells and the self-perpetuation of inflammation, leading to cartilage and bone destruction. Two TNF inhibitors, infliximab, an anti-TNF-alpha chimeric monoclonal antibody, and etanercept, a fusion protein of soluble TNF receptor and Fc portion of immunoglobulin, were marketed in 2003 and 2005, respectively, in Japan. The combinational use of biologics targeting TNF-alpha and methotrexate (MTX) have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. Namely, biologics targeting TNF have brought about a paradigm shift in the treatment outcome of RA; i) remission induction and maintenance, ii) suppression of progress of joint destruction, iii) improvement of mortality. Furthermore, recent controlled trials have shown that biologics targeting cell surface molecules on B cells and T cells are effective in RA patients with active disease despite TNF inhibitors. Thus, targeting cytokines and lymphocytes not only expands the array of treatments for RA but also provides important insights into the pathogenesis of this disease. In this review, how to use TNF inhibitors for the treatment of RA will also be discussed from domestic as well as global evidence.
17255320 The Toll-like receptor adaptor proteins MyD88 and Mal/TIRAP contribute to the inflammatory 2007 Feb The widespread distribution of Toll-like receptors (TLRs) and their ligands raises the question whether they contribute to the production of inflammatory and tissue destructive molecules in rheumatoid arthritis (RA). We examined the expression and function of TLR2 and TLR4 and their downstream signaling adaptors MyD88 and Mal/TIRAP in synovial membrane cultures from RA tissue. Both TLR2 and TLR4 were detected by flow cytometry, and stimulation with TLR2 and TLR4 ligands augmented the spontaneous production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, indicating that TLR2 and TLR4 are functional in these cultures. In addition, overexpression of dominant-negative forms of MyD88 and Mal/TIRAP significantly down-regulated the spontaneous production of cytokines tumor necrosis factor-alpha, IL-6, and vascular endothelial growth factor, and enzymes MMP-1, MMP-2, MMP-3, and MMP-13 in RA synovial membrane cell cultures. Because TLR2 and TLR4 require both MyD88 and Mal/TIRAP for signaling, this study suggests that TLR function may regulate the expression of these factors in the RA synovium. Conditioned media from synovial membrane cell cultures stimulated human macrophages in a MyD88- and Mal-dependent manner, suggesting the release of a TLR ligand(s) from these cells. Thus, TLRs not only protect against infection but may also promote the inflammatory and destructive process in RA.
17330303 The Disease Activity Score in 28 joints in rheumatoid arthritis and psoriatic arthritis pa 2007 Mar 15 OBJECTIVE: To assess the factorial structure of the Disease Activity Score including a 28-joint count (DAS28) if applied in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: DAS28 values from 85 consecutive PsA outpatients and 2 RA patient cohorts comprising 85 patients each were compared. The first RA cohort (RA1) consisted of age- and sex-matched patients seen during the same period as the patients with PsA. The first 85 RA outpatients from September 2003 were included in the second cohort (RA2). Item weighting, factor loading, and internal consistency were assessed by factor analysis, principal component analysis, and calculation of Cronbach's alpha. RESULTS: The mean +/- SD DAS28 scores of patients in the PsA, RA1, and RA2 cohorts were 3.2 +/- 1.31, 3.21 +/- 1.45, and 3.79 +/- 1.44, respectively. A significant difference between the PsA and RA2 cohorts was found for DAS28 (P = 0.0063), swollen joint count (P = 0.007), and patient's global assessment (P < 0.001), but not for erythrocyte sedimentation rate. Internal consistency of the DAS28 in patients with PsA was considerably lower, item weighting showed remarkable differences, and factor analysis revealed that the DAS28 constitutes a bidimensional instrument in patients with PsA, whereas in both RA cohorts it appeared to be monodimensional. CONCLUSION: With respect to its statistical properties, the DAS28 proved to be considerably different in PsA compared with RA. Therefore its application for disease activity assessment in patients with PsA cannot be recommended without a formal validation procedure.
18512773 Patients with pulmonary tuberculosis are frequently positive for anti-cyclic citrullinated 2008 Jun OBJECTIVE: The anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) has high sensitivity and specificity for rheumatoid arthritis (RA). However, detection of anti-CCP in patients with active pulmonary tuberculosis (TB) has recently been reported. To determine whether this activity was specific for the citrullinated residue, the specificity of anti-CCP-positive sera for CCP versus that for unmodified arginine-containing peptide (CAP) was examined in patients with TB and compared with that in patients with RA. METHODS: Anti-CCP and anti-CAP in sera from patients with pulmonary TB (n = 49), RA patients (n = 36), and controls (n = 18) were tested by ELISA. Sera were available at diagnosis from most TB patients. All TB patients were treated with a combination of 2-4 antibiotics for at least 6 months, and sera were collected over time. RESULTS: Anti-CCP was found in 37% of TB patients and in 43% of RA patients. CAP reactivity was more common in TB than in RA. High anti-CCP:anti-CAP ratios (>2.0) were seen far more commonly in anti-CCP-positive RA patients than in anti-CCP-positive TB patients (94% versus 22%). Anti-CCP was inhibited by CCP peptide in sera from RA patients, but not in sera from TB patients. A slight increase in anti-CCP was common after initiating treatment for TB, although the anti-CCP level decreased after 1-2 months. CONCLUSION: Anti-CCP is frequently present in patients with active TB. However, many anti-CCP-positive TB sera also reacted with CAP, and anti-CCP:anti-CAP ratios in TB sera were low. Anti-CCP:anti-CAP ratios should be useful clinically for distinguishing CCP-specific reactivity seen in RA from reactivity with both CCP and CAP frequently seen in pulmonary TB.
16916651 Soluble HLA-G in rheumatoid arthritis. 2006 Aug We investigated potential correlations between soluble HLA-G (sHLA-G) and soluble HLA class I (sHLA-I) levels, respectively, and parameters of disease activity or genetic factors determined by HLA-DRB1 and HLA-DQB1 in patients with rheumatoid arthritis (RA). SHLA-G plasma concentrations from 106 RA patients (mean age 59.8 years, 80 women) were assessed by a sensitive enzyme-linked immunosorbent assay format. The mean sHLA-G levels were lower and sHLA-I levels higher in the RA patients than in healthy controls. Correlation coefficients of 0.248 to 0.344 (p < 0.01) between sHLA-G and rheumatoid factor, CRP, and EULAR joint swelling score were found. Patients with disease-associated HLA epitopes had higher sHLA-G levels than those without. Significantly lower sHLA-G was observed in groups of patients having HLA-DRB1*03 or HLA-DQB1*02 compared to groups without these genotypes. In contrast, HLA-DQB1*03 or disease-associated epitopes combined with HLA-DQB1*03 were associated with higher sHLA-G levels, whereas the inverse was observed in the combined presence of HLA-DRB1*03 and HLA-DQB1*02. SHLA-G as a percentage of sHLA-I was lower in patients positive for HLA-DQB1*02 and higher in patients positive for HLA-DQB1*03 and in its combined presence with disease-associated epitopes or with HLA-DRB1*07. As especially sHLA-G strongly inhibits T and natural killer (NK) cell functions, low sHLA-G suggests that T and NK cell activities are not efficiently restricted by sHLA-G molecules in rheumatoid arthritis. The sHLA-G levels, however, increase in correlation with parameters of disease activity and appear to be affected by the presence of disease-predisposing epitopes and other HLA-DRB1, DQB1 genotypes.
16631408 Glycogen synthase kinase-3beta inhibition attenuates the degree of arthritis caused by typ 2006 Jul Recently, glycogen synthase kinase-3 (GSK-3) has being identified as an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3beta inhibition on the degree of arthritis caused by type II collagen (CII) in the mouse (collagen-induced arthritis; CIA). Mice developed erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund's adjuvant (CFA). The incidence of CIA was 100% by day 28 in the CII-challenged mice and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of mice with the GSK-3beta inhibitor TDZD-8 (1 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly(ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) revealed a positive staining in inflamed joints from mice subjected to CIA. The degree of staining for nitrotyrosine, PAR, iNOS, and COX-2 was significantly reduced in CII-challenged mice treated with the GSK-3beta inhibitor. Plasma levels of tumor necrosis factor (TNF)-alpha and the joint tissue levels of macrophage inflammatory protein (MIP)-1alpha and MIP-2 were also significantly reduced by GSK-3beta inhibition. These data demonstrate that GSK-3beta inhibition exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.
16934155 Presence of antibodies against cyclic citrullinated peptides in patients with 'rhupus': a 2006 'Rhupus' is a rare condition sharing features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). If rhupus is a distinctive entity, an overlap between RA and SLE or a subset of SLE is currently debated. This study was performed to explore the prevalence of antibodies against cyclic citrullinated peptides (anti-CCP antibodies) in rhupus. Patients meeting American College of Rheumatology criteria for RA, SLE, or both were included. Clinical and radiographic features were recorded and sera were searched for anti-CCP antibodies, rheumatoid factor, antinuclear antibodies, anti-extractable nuclear antigens, and antibodies against double-stranded DNA (anti-dsDNA antibodies). Seven patients for each group were included. Clinical and serological features for RA or SLE were similar between rhupus and RA patients, and between rhupus and SLE patients, respectively. Values for anti-CCP antibodies obtained were significantly (p < 0.05) higher in RA (6/7) and rhupus (4/7) than in SLE patients (0/7) and healthy subjects (0/7). Our data support the possibility that rhupus is an overlap between RA and SLE, because highly specific autoantibodies for RA (anti-CCP) and for SLE (anti-dsDNA and anti-Sm) are detected in coexistence.
17934098 Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility. 2007 Nov OBJECTIVE: To evaluate the available evidence on the efficacy and feasibility of the new concept of tight control in randomised trials in patients with rheumatoid arthritis (RA). Tight control is a treatment strategy tailored to the individual patient with RA, which aims to achieve a predefined level of low disease activity or remission within a certain period of time. METHODS: The literature database PubMed was searched and yielded four trials: the FIN-RACo trial, the TICORA study, the BeSt study and the CAMERA study. RESULTS: Tight control resulted in greater improvement and a higher percentage of patients meeting the preset aim of low disease activity or remission when compared to the control intervention. In the FIN-RACo trial, analysing the subset of patients completing the study, 68% in the tight control group achieved remission (DAS28<2.6) verus 41% in the contrast group [corrected] In the TICORA study, 65% of patients in the tight control group versus 16% of the contrast group achieved remission, based on DAS<1.6 (p<0.0001). In the CAMERA study, 50% of patients in the tight control group using a computer decision model achieved remission, versus 37% in the contrast group (p = 0.029). The BeSt study consisted of only tight control groups aimed at a DAS<1.6; remission was achieved in 38-46% of patients. This is higher than the range of remission in earlier trials of 13-36%. CONCLUSION: Tight control aiming for low disease activity or even better still, remission, seems a promising option in treating patients with RA in clinical trials and probably also in daily practice.
17893995 The immunology of rheumatoid arthritis. 2007 Jun Rheumatoid arthritis (RA) is represents the most common chronic inflammatory joint disease and is still a major medical challenge because of unsolved issues related to the etiologic and pathogenetic questions. Intensive research has been conducted over the last years that focused on the inappropriate activation of the immune system: although T cells have long been deemed to play a central role in the origin and propagation of joint inflammation, data accumulated so far have widened this perspective recognizing the contribution of other cells, as well as the major histocompatibility complex class II proteins and a composite set of costimulatory signals responsible for the production of proinflammatory cytokines and other soluble mediators implicated in tissue destruction typical of the disease. This paper will provide an insight into the immune system in RA, dissecting cellular and humoral aspects both in serum and in synovium of patients.
18565246 Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: association w 2008 Mar OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG isotype are specific diagnostic markers of rheumatoid arthritis (RA). Recent evidence also points to their direct involvement in the pathophysiology. Little information is available, however, regarding the isotype distribution of anti-CCP antibodies and the characteristics of IgA and IgM anti-CCP. METHODS: IgG, IgA and IgM anti-CCP2 and rheumatoid factor (RF) levels were measured in the sera of 119 RA patients and 118 controls, including patients with other rheumatic diseases and healthy subjects. We analyzed the diagnostic performance of IgA and IgM anti-CCP2 antibodies and their relationship with IgG anti-CCP2, RFs, disease duration and the presence of HLA-DRB1 shared epitope (SE) alleles. RESULTS: Patients with RA had significantly higher serum IgA and IgM anti-CCP2 antibody levels than healthy subjects and patients with other rheumatic diseases (p<0.0001). IgG, IgA and IgM anti-CCP2 antibodies were present in 74.8%, 52.9% and 44.5% of RA patients, and their diagnostic specificity was 95.8%, 95.8% and 91.6%, respectively. The presence of anti-CCP2 antibodies was significantly associated with SE alleles (p=0.03). The frequency of IgM anti-CCP2 positivity was lower in longstanding disease compared to early RA (p=0.03). CONCLUSION: IgA and IgM anti-CCP2 antibodies are present in RA patients, and they are similarly specific for RA as IgG anti-CCP2. The higher frequency of IgM anti-CCP2 antibodies in early RA suggests that they are mostly generated during the first phase of immune response; nonetheless, their production seems to be sustained in some patients. Further analysis of IgM and IgA anti-CCP2 antibodies may provide insights into the pathogenesis of RA.
16817042 [Posterior capsule opacification after phacoemulsification in patients with rheumatoid art 2006 PURPOSE: To assess the posterior capsule opacification (PCO) rate after phacoemulsification with polyacrylic intraocular lens (IOL) implantation in patients with rheumatoid arthritis (RA) compared with the controls, and to assess whether preoperative activity of RA is associated with a higher incidence of PCO. METHODS: 24 eyes of 20 RA patients operated in a period of 4 years were included in our study. A control group of 20 eyes from 20 health subjects were also included in our study. All procedures were performed by a single surgeon with the same surgical technique and postoperative medication. RESULTS: One year postoperatively in two eyes (8.3%) of RA-patients lens epithelial cells (LEC) migration of grade 1 was observed, in controls also in two eyes (10%). No correlation was observed between age, duration of RA or preoperative activity of RA and the PCO rate. CONCLUSION: Following acrylic IOL implantation, the PCO rate one year after surgery was 8.3% in RA patients and 10% in controls. RA patients present no higher risk for PCO development than controls.
18524808 Concordant and discordant associations between rheumatoid arthritis, systemic lupus erythe 2008 Aug OBJECTIVES: To quantify the sibling risk of RA, SLE and AS. To analyse the concordant and discordant associations between RA, SLE and AS. METHODS: Follow-up study of all individuals and their siblings born in or after 1932 and hospitalized for RA, SLE or AS between 1973 and 2004 (32 yrs). Data were retrieved from a comprehensive dataconstructed by using several national Swedish data registers, including the Total Population Register, the Swedish Hospital Discharge Register and the Multigeneration Register. Standardized incidence ratios (SIRs) were used to estimate sibling risks. RESULTS: For males, the overall significant SIRs were 4.72, 4.35 and 4.14 for RA, SLE and AS, respectively, if a sibling was affected by any inflammatory disease. The corresponding significant SIRs for females were 4.12, 3.73 and 4.73. The concordant significant SIRs in siblings were 5.12, 17.02 and 17.14 for RA, SLE and AS, respectively. There were also discordant associations between RA and SLE, whereas AS was only associated with AS. CONCLUSIONS: This study was able objectively to quantify the sibling risk of RA, SLE and AS, which represents useful knowledge for clinicians and geneticists. The analysis of concordant and discordant associations may be useful in future studies aimed at finding specific genes associated with these diseases.
17364178 Ten-year survival analysis of the PFC total knee arthroplasty--a surgeon's first 99 replac 2008 Aug Ninety-seven patients with 99 total knee arthroplasties were operated on by a surgeon in the first 3 years of his surgical career. Complete survival data were available for all 99 knees. The cases were reviewed at a minimum of 10 years after their initial operation, but as 37 patients had died before reaching 10 years, the average follow-up was 8 years 8 months with a maximum of 12 years 4 months. Ninety-one patients had osteoarthritis, five had rheumatoid arthritis, and three had juvenile chronic arthritis. No patients were lost to follow-up. Four required revision. The 10-year survival rate, using revision for all causes as an end-point, was 94.96%. The survival rate for aseptic loosening was 97.04%. The survival rate for loose joints that had not been revised was 94.13%. Three of the four revisions occurred in the first 6 patients operated upon, suggesting there may be a learning curve for surgeons at this stage in their career.
18084695 Update on the Japanese guidelines for the use of infliximab and etanercept in rheumatoid a 2007 Application of biological agents targeting tumor necrosis factor-alpha (TNF-alpha) caused a paradigm shift in the treatment of rheumatoid arthritis (RA). The introduction of infliximab in 2003 and etanercept in 2005 in Japan had a significant impact on both Japanese rheumatologists and RA patients, although serious adverse effects such as bacterial pneumonia, tuberculosis and Pneumocystis jiroveci pneumonia are significant concerns. Based on the data from post-marketing surveillance in Japan and accumulating evidence worldwide, the Internal Medicine Rheumatology Study Group of the Ministry of Health, Labor and Welfare (MHLW), Japan, has updated the guidelines for the use of anti-TNF-alpha agents for RA, which were subsequently approved by the Board of Japan College of Rheumatology (JCR). In the present revised guidelines, we combined the guidelines for use of each of infliximab and etanercept together with some modifications and precautions, paying special attention to serious adverse reactions. Although it is still controversial whether the use of TNF-alpha blocking agents per se increases the risk of infection or not, bacterial pneumonia, regardless of the pathogens, is the most frequent complications in RA. The risk factors associated with pneumonia identified in the post-marketing surveillance of infliximab in Japan are presented in this guideline. The diagnostic algorithm is also designed for early diagnosis and treatment of pulmonary lesions seen during the treatment of biological agents. Preventive measures and precautions against tuberculosis, another frequent and significant complication in Japan, are also described. Furthermore, risk factors for developing Pneumocystis pneumonia, which uniquely occurs at 30- to 50-fold frequency under TNF-alpha blockade therapy in Japan, are described here and its preventive measures are discussed. It is stressed that secondary-care rheumatologists should be better familiarized with the proper use of TNF-alpha blocking agents and be alert to any adverse events for a better management of RA patients.
17717913 [Clinical study on effect of total panax notoginseng saponins on immune related inner envi 2007 Jul OBJECTIVE: To study the therapeutic effect and possible mechanism of total panax notoginseng saponins (PNS) for treatment of rheumatoid arthritis (RA), and to observe its safety and influence on RA immune related inner environment. METHODS: Eighty-four patients were randomly assigned to two groups. All were treated with the routine therapy with diclofenac sodium, Leflunomide and prednisone, but for the 43 patients in the treatment group PNS was given additionally. The therapeutic course was 28 days for both groups. Clinical efficacy and change of indexes including platelet counts, immnuoglobulins (IgG, IgA, IgM), complement (C)3, rheumatoid factor (RF), C-reactive protein (CRP), ceruloplasmin (CER), haptoglobin (HPT), and alpha1-acid glycoprotein (AAG) were observed. RESULTS: Significant improvement of clinical symptoms, including the joint swelling index, joint tenderness index, joint pain index, time of morning stiffness and VAS revealed in both groups after treatment, and the effect in the treatment group was better (P<0.05 or P<0.01). PLT, CER, AAG, HPT, CRP, IgG, IgA, IgM, C3 and RF were lowered in both groups (P<0.01), but the lowering in PLT, CER, AAG and CRP in the treatment group was more significant than that in the control group respectively (P < 0.05 or P < 0.01). CONCLUSION: PNS can significantly improve the condition of patients, enhance the therapeutic effect in treating RA, through regulating the disordered immunity and improving the effect of anti-inflammatory and analgesia.
16709864 Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential 2006 Jun 1 Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen recognition as well as recognition of endogenous ligands, which are released during inflammation and cell stress. The recognition of exogenous and endogenous ligands depends on TLRs, which are abundantly expressed in synovial tissue from rheumatoid arthritis (RA) patients. Furthermore TLR ligands are found to be present in RA serum and synovial fluid and are significantly increased, compared with serum and synovial fluid from healthy volunteers and patients with systemic sclerosis and systemic lupus erythematosus. Identification of novel endogenous TLR ligands might contribute to the elucidation of the role of TLRs in RA and other autoimmune diseases. In this study, we investigated whether five members of the small heat shock protein (HSP) family were involved in TLR4-mediated DC activation and whether these small HSPs were present in RA synovial tissue. In vitro, monocyte-derived DCs were stimulated with recombinant alphaA crystallin, alphaB crystallin, HSP20, HSPB8, and HSP27. Using flow cytometry and multiplex cytokine assays, we showed that both alphaA crystallin and HSPB8 were able to activate DCs and that this activation was TLR4 dependent. Furthermore, Western blot and immunohistochemistry showed that HSPB8 was abundantly expressed in synovial tissue from patients with RA. With these experiments, we identified sHSP alphaA crystallin and HSPB8 as two new endogenous TLR4 ligands from which HSPB8 is abundantly expressed in RA synovial tissue. These findings suggest a role for HSPB8 during the inflammatory process in autoimmune diseases such as RA.
17845202 Elevated Th1/Th2 cell ratios in a pregnant woman with a history of RSA, secondary Sjögren 2007 Oct PROBLEM: Elevated Th1/Th2 cytokine producing CD3(+)/CD4(+) cell ratios were reported in women with a history of recurrent spontaneous abortion (RSA) and multiple implantation failures. We report, significantly elevated Th1/Th2 cell ratios were noticed in a pregnant woman with twin pregnancies complicated with one fetal demise, who had a history of RSA, secondary Sjögren's syndrome (SS), and rheumatoid arthritis. METHOD OF STUDY: Case report. RESULTS: Peripheral blood Th1/Th2 cell ratios were significantly elevated 3 weeks prior to a fetal demise of twin pregnancies at 20 week gestation. Two weeks after fetal demise, the ratio of intracellular tumor necrosis factor-alpha/interleukin-10 producing CD3(+)/CD4(+) cells in peripheral blood was further increased to three times higher than prior ratio. Elevated Th1/Th2 ratio was down regulated after increasing dose of IVIg treatment. The patient gave birth to a male baby weighing 2650 g at 36 weeks gestation. No serious complications were found in the patient or the baby. CONCLUSION: Systemic inflammatory immune response pre-exists prior to a fetal demise and the degree of inflammatory immune response got worse with a presence of fetal demise in utero. We infer that the placenta is not an immunological barrier to maternal Th1/Th2 immune responses.
18367613 Glucocorticoid therapy-induced memory deficits: acute versus chronic effects. 2008 Mar 26 Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 +/- 1.0 years, mean +/- SE) with low to moderate doses of prednisone (7.5 +/- 0.8 mg, mean +/- SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.