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ID PMID Title PublicationDate abstract
19116717 Adrenomedullin inhibits MAPK pathway-dependent rheumatoid synovial fibroblast-mediated ost 2009 Aug The objective of this study is to determine the effects of adrenomedullin (AM) on IL-1- and TNF-alpha-induced rheumatoid synovial fibroblasts (RASFs)-mediated osteoclastogenesis. The formation of osteoclasts in co-cultures of RASFs and peripheral blood mononuclear cells was evaluated by tartrate-resistant acid phosphatase and resorption pit formation assay. The expression of RANKL, OPG, p-ERK, p-p38, and p-JNK was examined by immunoblotting and quantitative reverse transcription-polymerase chain reaction. AM (1-52) inhibits IL-1- and TNF-alpha-induced RASFs-mediated osteoclastogenesis. AM affected IL-1-, TNF-alpha-induced RANKL and OPG expression in RASFs. AM also inhibits IL-1 and TNF-alpha-induced phosphorylation of ERK-1/2, p38 MAPK, and JNK. Inhibitor of AM (AM 22-52) inhibits the effects of AM on the osteoclastogenesis. These results suggest that AM might be involved in the inflammatory cytokines-mediated osteoclastogenesis and thus bone damage, and indicate that it can be a new therapeutic strategy against joint destruction in RA.
19862560 How to connect a pedicle screw construct to a Ransford Loop: technical note. 2010 Jan This technical note describes how a standard pedicle screw system can be connected to the 4 mm rod of a Ransford Loop. This report may be of interest for spinal surgeons who need to perform similar add-on stabilizations.
19007749 Inhibition of IL-1beta-mediated inflammatory responses by the IkappaB alpha super-represso 2009 Jan 2 The IL-1beta-NF-kappaB axis is a key pathway in the pathogenesis of rheumatoid arthritis (RA) and is central in the production of proinflammatory mediators in the inflamed synovium. Therefore, we examined whether fibroblast-like synoviocytes (FLS) could be spared from IL-1beta-induced toxicity by an overexpressing IkappaB super-repressor. Infection of FLS with Ad-IkappaB alpha (S32A, S36A), an adenovirus-containing mutant IkappaB alpha, inhibited IL-1beta-induced nuclear translocation and DNA binding of NF-kappaB. In addition, Ad-IkappaB alpha (S32A, S36A) prevented IL-1beta-induced inflammatory responses; namely, the production of chemokines, such as ENA-78 and RANTES, and activation of MMP-1 and MMP-3. Finally, increased cellular proliferation of FLS after IL-1beta treatment was significantly reduced by Ad-IkappaB alpha (S32A, S36A). However, Ad-IkappaB beta (S19A, S23A), the IkappaB beta mutant, was not effective in preventing IL-1beta toxicity. These results suggest that inhibition of IkappaB alpha degradation is a potential target for the prevention of joint destruction in patients with RA.
18848426 Three-dimensional analysis of computed tomography-based navigation system for total knee a 2009 Oct We evaluated the postoperative alignment of 37 primary total knee arthroplasties performed using a computed tomography-based navigation system (Vector Vision Knee 1.5; Brain Lab, Germany) with a new 3-dimensional analysis. The mean coronal femoral angle was 89.0 degrees +/- 1.4 degrees (85.5 degrees -92.8 degrees ), and the coronal tibial component was 89.2 degrees +/- 1.0 degrees (87.4 degrees -91.6 degrees ). The hip-knee-ankle angle was observed to be 178.2 degrees +/- 1.5 degrees (173.9 degrees -181.8 degrees ). The external rotational alignment of the femoral component relative to the surgical epicondylar axis was -0.5 degrees +/- 1.7 degrees (-3.2 degrees to 3.4 degrees ). The results demonstrated that a computed tomography-based navigation system provided a reasonably satisfactory component alignment. The discrepancy between the 2-dimensional and 3-dimensional evaluations was 1.0 degrees +/- 0.9 degrees (0.1 degrees -3.4 degrees ). Three-dimensional analysis is necessary to evaluate the accuracy of the navigation system.
19758153 Autoimmune thyroid disease and autoimmune rheumatic disorders: a two-sided analysis. 2009 Sep Chronic autoimmune thyroiditis (ATD) frequently overlaps with autoimmune rheumatic diseases. The aim of this study was to evaluate the prevalence of various non-organ-specific autoantibodies in patients with ATD, as well as the presence of ATD in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). SUBJECTS AND METHODS: Group 1 comprised 80 patients with ATD, and group 2 contained 80 patients with SLE or RA. A control group consisted of 34 healthy subjects. Group 1 was examined for the presence of non-organ-specific autoantibodies. Serum fT3, fT4, TSH, and antibodies against thyroglobulin, thyroperoxidase, as well as ultrasound of thyroid gland, were determined in group 2. RESULTS: Patients with ATD had a significantly higher prevalence of antinuclear antibodies (ANA) than control subjects (45% vs. 14.7%, P < 0.001). There were no significant differences in the prevalence of other antibodies between the groups. ANA-positive patients were younger than ANA-negative ones and had significantly higher anti-TG values (P < 0.05). The prevalence of ATD in group 2 was significantly higher than in the control subjects (24% vs. 8%, P < 0.05). No significant differences in the prevalence of ATD were detected between SLE and RA. CONCLUSION: The authors conclude that ANA is the most frequent non-organ-specific antibody associated with ATD, while the other antibodies occur rarely. The prevalence of ATD in SLE and RA patients was 24%. These results indicate that it is clinically important to screen patients with SLE and RA for the coexistence of thyroid autoimmune disease.
20300752 Screening and evaluating the mimic peptides as a useful serum biomarker of ankylosing spon 2011 Aug To screen specific serum biomarker for ankylosing spondylitis (AS) using a phage random peptide library. A phage random peptide library of random peptide 12-mers was immunoscreened with purified immunoglobulin (Ig) G from sera of AS patients. Positive clones obtained after three rounds of biopanning were detected with ELISA and sequenced. Reaction of the screened positive clones with sera from AS patients, systemic lupus erythematosus (SLE) patients, rheumatoid arthritis (RA) patients, osteoarthritis (OA) patients and healthy controls was detected using phage ELISA. Correlation among erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and the absorbance value of the positive clone in phage ELISA was examined in AS patients. Seventeen out of twenty randomly selected phage clones exhibited specific reaction with purified sera IgG from AS patients, among them seven coming from the same clone whose inserted peptide sequence was LALPPLAPNHHH (named "AS1"). Phage ELISA results showed that the positive reaction rate of the AS1 clone was 92.0% with AS patients, significantly different (P < 0.01) from those with SLE patients (56.7%), RA patients (50.0%), OA patients (13.3%), and healthy controls (14.0%). Absorbance value of the AS1 clone in phage ELISA was significantly higher than those in the other groups (P < 0.05). In addition, the absorbance value of the AS1 clone showed no statistically significant correlation with ESR and CRP in AS patients, suggesting that AS1 detects AS patients through a unique mechanism other than inflammation. The short peptide AS1 obtained through screening of a phage random peptide library with purified serum IgG from AS patients can specifically react with the sera of AS patients, and thereby may be a candidate of AS-specific serum biomarkers.
19337758 Subaxial subluxation after atlantoaxial transarticular screw fixation in rheumatoid patien 2009 Jun The most common cervical abnormality associated with rheumatoid arthritis (RA) is atlantoaxial subluxation, and atlantoaxial transarticular screw fixation has proved to be one of the most reliable, stable fixation techniques for treating atlantoaxial subluxation. Following C1-C2 fixation, however, subaxial subluxation reportedly can bring about neurological deterioration and require secondary operative interventions. Rheumatoid patients appear to have a higher risk, but there has been no systematic comparison between rheumatoid and non-rheumatoid patients. Contributing radiological factors to the subluxation have also not been evaluated. The objective of this study was to evaluate subaxial subluxation after atlantoaxial transarticular screw fixation in patients with and without RA and to find contributing factors. Forty-three patients who submitted to atlantoaxial transarticular screw fixation without any concomitant operation were followed up for more than 1 year. Subaxial subluxation and related radiological factors were evaluated by functional X-ray measurements. Statistical analyses showed that aggravations of subluxation of 2.5 mm or greater were more likely to occur in RA patients than in non-RA patients over an average of 4.2 years of follow-up, and postoperative subluxation occurred in the anterior direction in the upper cervical spine. X-ray evaluations revealed that such patients had a significantly smaller postoperative C2-C7 angle, and that the postoperative AA angle correlated negatively with this. Furthermore, anterior subluxation aggravation was significantly correlated with the perioperative atlantoaxial and C2-C7 angle changes, and these two changes were strongly correlated to each other. In conclusion, after atlantoaxial transarticular screw fixation, rheumatoid patients have a greater risk of developing subaxial subluxations. The increase of the atlantoaxial angel at the operation can lead to a decrease in the C2-C7 angle, followed by anterior subluxation of the upper cervical spine and possibly neurological deterioration.
20718894 Dental implants in patients with rheumatoid arthritis: clinical outcome and peri-implant f 2010 Oct PURPOSE: Implant prosthodontic treatment outcomes for patients suffering from autoimmune rheumatoid arthritis (RA) with or without concomitant connective tissue diseases (CTD) were evaluated. MATERIAL AND METHODS: Thirty-four female patients' (25 isolated RA; nine RA+CTD) implant survival/success rate, peri-implant conditions (marginal bone loss, pocket depth, plaque index, gingiva index and bleeding index) and incidence of prosthodontic maintenance were retrospectively evaluated. RESULTS: Implants evaluated presented a high implant survival (100%) and a 3.5-year success (93.8%) rate during the follow-up programme (mean 47.6 month) without difference between isolated RA (94.6%) and RA and concomitant CTD (92.3%), respectively. In isolated RA, acceptable marginal bone resorption (mean: 2.1 mm; SD: 0.5 mm), pocket depth (mean: 2.8 mm; SD:3.2 mm) and healthy soft-tissue conditions (plaque/bleeding/gingiva index Grade 0 in 80%) were noticed. However, patients with RA+CTD presented increased bone resorption (mean: 3.1 mm; SD: 0.7 mm) and more vulnerable soft-tissue conditions (higher bleeding index) differing significantly to patients with isolated RA (p<0.01). Peri-implant parameters were significantly influenced by the patients' underlying disease (RA, RA+CTD; Kruskal-Wallis test, Jonckheere-Terpstra test). CONCLUSIONS: In contrast to isolated RA, in RA patients with concomitant CTD, differences in the peri-implant parameters such as pronounced marginal bone resorption and bleeding may be anticipated and appear to be significantly influenced by the patients' underlying disease.
18930338 [Mesenchymal stem cells and immunomodulation: toward new immunosuppressive strategies for 2009 Mar Mesenchymal stem cells (MSC) represent a population of the bone marrow microenvironment, which participates in the regulation of haematopoietic stem cells (HSC) self-renewal and differentiation. MSC are multipotent non-haematopoietic progenitors, which have been explored as a promising treatment in tissue regeneration. Both in vitro and in vivo, the MSC inhibit the T, B, NK and dendritic cell functions. Although MSC immunomodulating properties are not yet completely understood, their low immunogenic potential can be used as a therapeutic tool not only for regenerative medicine, but also for the treatment of graft-versus-host disease (GVHD) after bone marrow transplantation as well as for specific cases of severe refractory autoimmune diseases. Experimental and clinical data gave encouraging results, showing that MSC injection allowed controlling refractory GVHD, restoring bone development in children with osteogenesis imperfecta or improving heart function after myocardial infarction. Phase I-II studies are in progress in various countries to investigate the potential benefit from MSC due to their immunosuppressive properties, as an adjunctive therapy for severe refractory autoimmune disease.
20549515 Genome-wide searching of rare genetic variants in WTCCC data. 2010 Sep Although they have demonstrated success in searching for common variants for complex diseases, genome-wide association (GWA) studies are less successful in detecting rare genetic variants because of the poor statistical power of most of current methods. We developed a two-stage method that can apply to GWA studies for detecting rare variants. Here we report the results of applying this two-stage method to the Wellcome Trust Case Control Consortium (WTCCC) dataset that include seven complex diseases: bipolar disorder, cardiovascular disease, hypertension (HT), rheumatoid arthritis, Crohn's disease, type 1 diabetes and type 2 diabetes (T2D). We identified 24 genes or regions that reach genome wide significance. Eight of them are novel and were not reported in the WTCCC study. The cumulative risk (or protective) haplotype frequency for each of the 8 genes or regions is small, being at most 11%. For each of the novel genes, the risk (or protective) haplotype set cannot be tagged by the common SNPs available in chips (r (2) < 0.32). The gene identified in HT was further replicated in the Framingham Heart Study, and is also significantly associated with T2D. Our analysis suggests that searching for rare genetic variants is feasible in current GWA studies and candidate gene studies, and the results can severe as guides to future resequencing studies to identify the underlying rare functional variants.
21029771 Extracts of Arisaema rhizomatum C.E.C. Fischer attenuate inflammatory response on collagen 2011 Jan 27 AIM OF THE STUDY: Arisaema rhizomatum C.E.C. Fischer (ARCF), called as "Xuelijian", a local herb just growing in China, has been used as a traditional ethnic Chinese medicine for long because of its remarkable activity to alleviate pain and inflammation for patients suffering from rheumatism among the people with weak side-effect. However, rare study on the anti-arthritic activity of ARCF has been reported in vivo. The aim of this study is to investigate the protective effect of the herb on collagen-induced arthritis in mice and explore the potential immunological mechanisms. MATERIALS AND METHODS: CIA was induced in male BALB/c mice by been subcutaneously injected type II bovine collagen (CII) for twice. The combined MeOH extract (ME) of ARCF rhizome was successively partitioned into four fractions with petroleum ether (PE), ethyl acetate (EE), n-butyl alcohol (n-BE) and water (WE). After the second collagen immunization, mice were administered orally with different doses of ME, EE and n-BE (ME 130, 261, 522 mg kg(-1); EE 10.2, 20.4, 40.8 mg kg(-1); n-BE 52, 104, 208 mg kg(-1)) every other day for 3 weeks. The progression of edema of paws and knee joints was inspected by using a vernier calliper every 3 days from the 10th day after the first injection to the end of the experiment. The spleen index was measured and the knee joint destruction was observed by pathological sections. Levels of inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-33 (IL-33 or IL-1F11) and rheumatoid factor (RF) in serum were measured by ELISA. RESULTS: Administration of ME, EE and n-BE significantly suppressed paws and joints swelling and reduced the spleen indexes. Pathological examination demonstrated that ARCF effectively protected anklebone and cartilage from being eroded versus vehicle-treated mice. Moreover, the serum levels of inflammatory cytokines TNF-α, IL-1β, IL-6, IL-33 and RF were markedly lowered in ARCF treated groups compared with the control group (p<0.05). CONCLUSION: Our studies demonstrate that administration of ARCF is obviously suppressed the progression of CIA. The anti-arthritic effectiveness of ARCF will make the herb a strong candidate for further clinical trials on RA patients.
19720992 A broad screen for targets of immune complexes decorating arthritic joints highlights depo 2009 Sep 15 Deposits of Ig and complement are abundant in affected joints of patients with rheumatoid arthritis (RA) and in animal models of RA in which antibodies are demonstrably pathogenic. To identify molecular targets of the Igs deposited in arthritic joints, which may activate local inflammation, we used a combination of mass spectrometry (MS) and protein microarrays. Immune complexes were affinity-purified from surgically removed joint tissues of 26 RA and osteoarthritis (OA) patients. Proteins complexed with IgG were identified by proteomic analysis using tandem MS. A striking diversity of components of the extracellular matrix, and some intracellular components, copurified specifically with IgG from RA and OA tissues. A smaller set of autoantigens was observed only in RA eluates. In complementary experiments, IgG fractions purified from joint immune complexes were tested on protein microarrays against a range of candidate autoantigens. These Igs bound a diverse subset of proteins and peptides from synovium and cartilage, different from that bound by normal serum Ig. One type of intracellular protein detected specifically in RA joints (histones H2A/B) was validated by immunohistology and found to be deposited on the cartilage surface of RA but not OA joints. Thus, autoantibodies to many determinants (whether deposited as "neoantigens" or normal constituents of the extracellular matrix) have the potential to contribute to arthritic inflammation.
19115057 Silicone-induced foreign-body reaction after first metatarsophalangeal joint arthroplasty 2009 Sep We report a case of Jaccoud's arthropathy with forefoot plantar callosity. The lesser toe metatarsal heads were resected and Swanson's double-stemmed flexible-hinge implant arthroplasty of the first metatarsophalangeal joint was performed. An osteolytic defect had formed around the implant after 2 years. Surgical revision comprised implant removal and synovectomy. Histology revealed a foreign-body reaction with birefringent material in multinucleated giant cells. Because the capsuloligamentous system is fragile in Jaccoud's arthropathy, we recommend resection arthroplasty or arthrodesis of the first MP joint as an initial operative approach.
20403460 Myricetin inhibits IL-1beta-induced inflammatory mediators in SW982 human synovial sarcoma 2010 Jul Rheumatoid arthritis (RA) synovial fibroblasts produce inflammatory mediators, which destruct cartilage and bone in RA joint. The aim of this study is to investigate the effect of myricetin on inflammatory cytokine/matrix metalloproteinase (MMP) production and mitogen-activated protein kinases (MAPKs) in IL-1beta-stimulated SW982 synovial cells. Myricetin significantly decreased IL-1beta-induced production of IL-6 and MMP-1 in synovial cells. Moreover, myricetin diminished the phosphorylation of Jun NH2-terminal kinase (JNK) and p38 MAPK. These results suggest that myricetin reduces the production of MMP and IL-6 in SW982 cells by inhibiting MAPKs (JNK and p38).
20191470 Adherence to disease-modifying antirheumatic drugs and the effects of exposure misclassifi 2010 May OBJECTIVE: To describe the effect of different exposure classification strategies for disease-modifying antirheumatic drugs (DMARDs) on drug-outcome associations. METHODS: We studied the association between DMARD initiation and all-cause hospitalizations in patients with rheumatoid arthritis (RA), 1995-2005. Initiators of DMARDs and oral glucocorticoids were followed for < or =180 days. We compared 2 strategies for exposure classification: a persistent exposure required (PER) approach, in which followup stopped when the regimen changed; and a persistent exposure ignored (PEI) approach, in which followup continued despite regimen changes. For PEI, adherence was assessed using the medication possession ratio. All-cause hospitalization risk was compared among RA regimen initiators using Cox models and methotrexate as the reference. RESULTS: We identified 28,906 episodes of medication initiation. In PER analyses, tumor necrosis factor alpha antagonists did not increase hospitalization risk compared with methotrexate, whereas leflunomide did (hazard ratio [HR] 1.36, 95% confidence interval [95% CI] 1.1-1.67). Glucocorticoids increased hospitalization risk (HR 1.29, 1.54, and 2.03 for low, medium, and high doses, respectively). PEI results were similar to PER except that infliximab initiation increased the risk of hospitalization compared with methotrexate (HR 1.46, 95% CI 1.19-1.8), and most other effects were closer to the null. In PEI, adherence ranged from 73% for etanercept to 6% for glucocorticoids and adherence to methotrexate was 59%. CONCLUSION: Compared with methotrexate initiation, leflunomide or glucocorticoid initiation consistently increased all-cause hospitalizations in the first 180 days of use. Most PER and PEI estimates were similar; observed differences in risk between these methods were likely due to differences in adherence.
19651883 Factors associated with fatal outcome of leflunomide-induced lung injury in Japanese patie 2009 Oct OBJECTIVE: To elucidate the factors associated with poor prognosis of LEF-induced lung injury in patients with RA. METHODS: The background and clinical and laboratory features of LEF-induced lung injury were examined and compared between patients who died of and who recovered from it. RESULTS: Among 22 patients who developed LEF-induced lung injury, 9 died of and 13 recovered from it. The patients who died tended to have pre-existing interstitial pneumonia (8/9 vs 6/13, P = 0.07). The loading and maintenance doses, serum concentration of the LEF metabolite A771726 and administration period did not differ between the groups. Patients who died had more frequently hypoxaemia of <60 Torr and mechanical ventilation, and had a high serum CRP level (19.3 +/- 9.4 vs 10.1 +/- 8.1 mg/dl, P = 0.03) and a low albumin level (2.7 +/- 0.6 vs 3.3 +/- 0.5 g/dl, P = 0.03) at the lung injury onset. The peripheral blood lymphocyte count decreased in both groups at the lung injury onset, and it remained low until fatal outcome, in contrast to a re-increase upon recovery (406 +/- 394 vs 1203 +/- 399/microl, P = 0.006). The main histopathological finding in two autopsied patients was diffuse alveolar damage, in contrast to the alveolitis observed in a biopsied patient who recovered. CONCLUSIONS: Pre-existing interstitial pneumonia, extremely high serum CRP and low albumin levels, severe hypoxaemia and mechanical ventilation indicated poor prognosis. Peripheral blood lymphocytopenia developed in association with lung injury, and a sustained low lymphocyte count indicated a fatal outcome.
20610800 gp130 at the nexus of inflammation, autoimmunity, and cancer. 2010 Dec Glycoprotein 130 (gp130) is a shared receptor utilized by several related cytokines, including IL-6, IL-11, IL-27, Leukemia Inhibitory Factor (LIF), Oncostatin M (OSM), Ciliary Neurotrophic Factor (CNTF), Cardiotrophin 1 (CT-1) and Cardiotrophin-like Cytokine (CLC). Gp130 plays critical roles during development and gp130-deficient mice are embryonically lethal. However, the best characterized facet of this receptor and its associated cytokines is the ability to promote or suppress inflammation. The aim of this review is to discuss the role of gp130 in promoting or preventing the development of autoimmunity and cancer, two processes that are associated with aberrant inflammatory responses.
20039412 Involvement of MAPKs and NF-kappaB in tumor necrosis factor alpha-induced vascular cell ad 2010 Jan OBJECTIVE: To investigate the roles of MAPKs and NF-kappaB in tumor necrosis factor alpha (TNFalpha)-induced expression of vascular cell adhesion molecule 1 (VCAM-1) in human rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Human RASFs were isolated from synovial tissue obtained from patients with RA who underwent knee or hip surgery. The involvement of MAPKs and NF-kappaB in TNFalpha-induced VCAM-1 expression was investigated using pharmacologic inhibitors and transfection with short hairpin RNA (shRNA) and measured using Western blot, reverse transcriptase-polymerase chain reaction, and gene promoter assay. NF-kappaB translocation was determined by Western blot and immunofluorescence staining. The functional activity of VCAM-1 was evaluated by lymphocyte adhesion assay. RESULTS: TNFalpha-induced VCAM-1 expression, phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK, and translocation of NF-kappaB were attenuated by the inhibitors of MEK-1/2 (U0126), p38 (SB202190), JNK (SP600125), and NF-kappaB (helenalin) or by transfection with their respective shRNA. TNFalpha-stimulated translocation of NF-kappaB into the nucleus and NF-kappaB promoter activity were blocked by Bay11-7082, but not by U0126, SB202190, or SP600125. VCAM-1 promoter activity was enhanced by TNFalpha in RASFs transfected with VCAM-1-Luc, and this promoter activity was inhibited by Bay11-7082, U0126, SB202190, and SP600125. Moreover, up-regulation of VCAM-1 increased the adhesion of lymphocytes to the RASF monolayer, and this adhesion was attenuated by pretreatment with helenalin, U0126, SP600125, or SB202190 prior to exposure to TNFalpha or by anti-VCAM-1 antibody before the addition of lymphocytes. CONCLUSION: In RASFs, TNFalpha-induced VCAM-1 expression is mediated through activation of the p42/p44 MAPK, p38 MAPK, JNK, and NF-kappaB pathways. These results provide new insights into the mechanisms underlying cytokine-initiated joint inflammation in RA and may inspire new targeted therapeutic approaches.
20864374 Decrement of serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis (RA) 2010 Oct OBJECTIVE: The aim of this study was to evaluate whether serum COMP can estimate the therapeutic response of RA after 6 months of treatment with etanercept. METHODS: Forty-five RA patients receiving 25 mg of etanercept twice a week for 6 months were registered in this prospective observational study. Clinical response to the therapy was evaluated by DAS 28. Laboratory variables- COMP, CRP, ESR, IgM-RF, MMP-3, and anti-CCP Ab -were assessed at baseline and after 6 months of treatment. We assessed the correlations between serum COMP and other variables and whether serum COMP is associated with DAS28 remission. RESULTS: Serum COMP correlated with DAS28-ESR (p < 0.05, r = 0.40) at baseline. At 6 months of etanercept treatment, 10 patients entered remission (DAS28-ESR < 2.6) whereas the other 35 patients did not (DAS28-ESR > 2.6). The decrement of serum COMP at 6 months was significant in the remission group (N = 10) but not in the non-remission group (N = 35). On the other hand, CRP, ESR and MMP-3 decreased at 6 months regardless of remission status. IgM-RF titer as well as anti-CCP Ab titer did not differ at 6 months. CONCLUSIONS: Serum COMP at baseline reflects clinical disease activity of RA. Serum COMP is a valuable serologic marker to identify the subset of RA patients achieving remission during treatment with etanercept.
18842349 Vulvar apocrine adenocarcinoma: a case with nodal metastasis and intranodal mucinous diffe 2009 Primary vulvar adenocarcinomas are rare tumors, and their histogenesis is not fully understood. They are classified into extramammary Paget's disease, sweat gland carcinomas, and "breast-like" adenocarcinomas of the vulva. The latter resemble adenocarcinomas arising in the breast morphologically and immunophenotypically. Rare cases of adenocarcinoma with apocrine features have been reported, and whether these neoplasms originate from the "native apocrine" sweat glands or from "anogenital mammary-like" glands are still debatable. The presence of normal mammary-like glands in the vicinity of the tumor, the transitional malignant morphological features from normal mammary-like glands and the tumor, the breast-like histological features of the tumor, and the expression of estrogen and progesterone receptors generally suggest an origin from anogenital mammary-like glands. Absence of these features points toward native apocrine sweat glands as the source of these neoplasms. In this report, we present a patient who was initially diagnosed with Paget's disease of the right vulva, which was treated by hemi-vulvectomy, and who later presented with primary vulvar apocrine adenocarcinoma with metastasis to the inguinal lymph nodes and intranodal mucinous/colloidal differentiation: a feature, to the best of our knowledge, not reported before. We also reviewed the histogenesis of the vulvar adenocarcinomas, with emphasis on the morphological features that separate the tumors arising from the anogenital mammary-like glands in the vulva from those arising from the native vulvar sweat glands.