For over 10 years there have been no clinical studies about adult-onset Still's disease (AOSD) in Japan. We aimed to investigate recent clinical features and treatment of AOSD and to evaluate the efficacy of cyclosporin A (CyA) in the treatment of AOSD. The data from 34 patients with AOSD who were admitted to our hospital between 1994 and 2007 were analyzed retrospectively. Of several immunosuppressive agents, the efficacy of CyA given to seven patients was precisely evaluated. Clinical features observed in this study did not differ from those in our previous study, and serum ferritin levels were elevated in all the patients. Among immunosuppressive agents CyA, used concomitantly with corticosteroids (CS) for seven patients with severe AOSD, proved to be very effective. The disease was led to remission promptly by CyA in six patients, and all the patients except one experienced no recurrence. These results suggest that CyA can be one of the potent candidates to be used next to CS for patients with AOSD that is resistant to CS.
Background and Study Aims: We have previously reported the success of a method of virtual histology using laser-scanning confocal microscopy (LCM) in vitro on untreated fresh specimens obtained from the gastrointestinal mucosa. In the present study, we aimed to apply LCM to both fresh and formalin-fixed specimens, without additional treatment, in order to validate and compare the quality of the images obtained. Methods: We obtained 18 specimens from 11 patients, either by endoscopic biopsy or following surgical resection. First, we observed the fresh, saline-immersed specimen with LCM using the Fluroview microscope (Olympus Co. Ltd., Tokyo, Japan). We then fixed the specimen with formalin and obtained further LCM images 1 hour, 3 hours, and 24 hours after fixation. Three independent observers observed the images and were asked to assess the origin of the samples, the treatment of the samples, the time after formalin fixation, and whether they showed benign or malignant lesions. We used kappa statistics to compare the agreement among the three observers in each of these four areas of interest. Results: Between January and March 2003, we obtained 191 LCM images from 18 specimens. Thirty images were randomly selected for observation. The overall accuracy for differentiating between esophagus and stomach specimens was 96.6 %. The accuracy of differentiating normal from cancerous lesions was 92.2 %. The differentiation between saline-immersed and formalin-fixed specimens was 59.7 % accurate and the assessment of the time interval after formalin fixation was only 37.3 % accurate. The kappa statistics showed that there was strong interobserver agreement on the differentiation of specimen origin and of cancerous from benign lesions. However, there was no agreement among the observers on the method of specimen preparation or on the estimated time interval after formalin fixation. Conclusions: We concluded that images obtained from fresh specimens using LCM were of a quality good enough to make an accurate diagnosis of upper gastrointestinal carcinoma.
We report the case of a 38-year-old female patient with systemic lupus erythematosus (SLE) who developed acquired hemophilia caused by factor VIII (FVIII) inhibitors. She manifested spontaneous bleeding symptoms such as ecchymoses and hematuria. Laboratory findings showed an isolated prolongation of the activated partial thromboplastin time, reduced FVIII activity, and a high titer of FVIII inhibitors. She was successfully treated with oral predonisolone and cyclosporine in combination with steroid and cyclophosphamide pulse therapy.
To assess the effects of disease activity of systemic lupus erythematosus (SLE) and high-dose corticosteroids on endothelial injuries, the significance of soluble endothelial cell protein C receptor (sEPCR) and soluble thrombomodulin (sTM) was analyzed. Serum levels of sEPCR and sTM were measured by enzyme-linked immunosorbent assay (ELISA) cross-sectionally in 97 SLE patients, 49 patients with other rheumatic diseases and 22 normal subjects. The changes in these levels upon corticosteroid treatment were also analyzed in 41 patients. The levels of sEPCR and sTM were both higher in SLE and other rheumatic disease patients than in normal subjects. When low-dose corticosteroids were used, both the level of sEPCR and the ratio of positive tests for sEPCR were significantly higher in active SLE patients than in inactive patients [median 2.30 ng/ml (range 0.00–147.10 ng/ml) vs 0.00 ng/ml (0.00–58.90 ng/ml) and 53.5 vs 13.0%, respectively] (P < 0.005). Moreover, the ratio of positive tests for sEPCR was higher after corticosteroid treatment in 9 of 19 (47.3%) SLE patients compared to other rheumatic diseases (3/22; 13.6%). Although the mean level of sTM was significantly higher in active SLE patients than in inactive patients, the ratio of positive tests for sTM was not affected by disease activity or corticosteroids. In conclusion, the positive test for sEPCR is a more sensitive biomarker than that for sTM in reflecting endothelial injuries caused by active disease and often by corticosteroids in SLE.
Objective. B cells lacking RP105 produce autoantibodies in patients with SLE. Expression of B-cell activating factor (BAFF) binding receptors (BBRs) and survival of RP105− B cells from SLE patients were examined. Methods. Detection of difference of gene expression between RP105− and RP105+ B cells was done by DNA microarrays. Surface expression was confirmed by flow cytometry. The contribution of BAFF, a proliferation-inducing ligand (APRIL) and monomers/trimers of sCD40L to survival of RP105− and RP105+ B cells was examined. Results. Gene expression of B-cell maturation antigen (BCMA) was different among BBRs in RP105− and RP105+ B cells in SLE. Preferential expression of BCMA on RP105− B cells was confirmed compared with RP105+ B cells by flow cytometry, although BAFF receptor (BAFF-R) expression on RP105− B cells was significantly lower. Additionally, relative ratios of BCMA/BAFF-R expression on RP105− B cells were increased significantly in SLE patients compared with normal subjects. Stimulation by sCD40L decreased the number of surviving RP105− and RP105+ B cells in vitro. RP105+ B cells were not rescued from sCD40L-induced cell death by BAFF and/or APRIL. In contrast, either BAFF or APRIL maintained the survival of RP105− B cells due to avoidance of cell death. Activated RP105− B cells reduced BAFF-R and increased BCMA levels. Conclusions. RP105− B cells from SLE patients showed more preferential expression of BCMA compared with BAFF-R than normal subjects, and were possibly regulated by BAFF/APRIL. Our results provide a new insight of BCMA and their ligands in B cells from SLE patients.
There have been several reports indicating the association between recent stress experiences and the onset or the exacerbation of rheumatic diseases, although few such reports exist in patients with scleroderma (SSc). The present study was performed to elucidate whether there were any functional disturbances in the neuro-endocrine-immune system as a homeostatic system upon stress in SSc patients. Various serum levels of stress-related hormones and cytokines were examined before and after a mental calculation stress test, and a basal questionnaire study of sense of coherence (SOC, which is related to the ability to cope with stress), recent stress experiences, and quality of life (QOL) was performed in 17 SSc patients and in 38 healthy volunteers. Physical QOL state was impaired in patients, but there were no differences in recent stress experiences and SOC scores between patients and controls. Basal serum cortisol levels were similar in patients and controls, but increased levels of proinflammatory cytokine and noradrenalin were seen in SSc patients. Characteristically, contrary to the control group, whose cortisol levels increased significantly following the mental calculation stress test, no significant increase was observed in the patients when post-test cortisol levels were compared to pre-test levels, suggesting a defect in the normal cortisol response upon stress in SSc patients. The present results suggest that there may be impaired function of the neuro-endocrine-immune system upon stress in SSc patients.
We investigated the association of airway comorbidities with the clinical phenotypes and outcomes of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-positive ANCA-associated vasculitis (AAV).An AAV patient multicenter cohort trial was established in 13 hospitals in western Japan between 2012 and 2018. We examined 143 of the new-onset MPO-ANCA-positive AAV patients. Their clinical characteristics and comorbidities at disease onset were compared based on clinical phenotypes. Multivariate analysis was performed to identify factors predictive of remission and death.Twenty-seven cases with granulomatosis with polyangiitis (GPA), 10 with eosinophilic GPA (EGPA), 81 with microscopic polyangiitis (MPA), and 25 with unclassified AAV were identified. The average age of MPO-ANCA-positive patients was 71.4 years. Comorbidity (87.4%) and airway comorbidity (70.6%) were frequently observed in these patients. Examination of the clinical phenotypes revealed that the cases of GPA were frequently accompanied by infectious airway comorbidity (upper airway disease, bronchiectasis, pulmonary infections), and most of the cases of MPA and unclassified AAV were accompanied by fibrotic interstitial lung disease (fILD) or emphysema. Among MPO-ANCA-positive patients, infectious airway comorbidity was predictive of both remission (HR 1.58, P = 0.03) and mortality (HR 2.64, P = 0.04), and fILD was predictive of mortality (HR 7.55, P = 0.008). The combination of infectious airway comorbidities and fILD caused the worst survival outcomes in patients.MPO-ANCA-positive AAV was frequently accompanied by airway comorbidities. In addition to fILD, infectious airway comorbidities were closely associated with those clinical phenotypes and outcomes.
A woman in her late 50s visited our department because an abnormal shadow of her right lung was seen on her chest radiographs. She was diagnosed with Stage ⅠA primary lung adenocarcinoma with EGFR exon 19 deletion mutation by performing thoracoscopic middle lobe resection and lymph node dissection. After 1 and a half years, the lung metastasis recurred and she received gefitinib(GEF)monotherapy for 9 months and withdrew because of the sustained complete response(CR). Three years and 7 months after the first visit, she was diagnosed as having complication of revised international staging system(R-ISS)Ⅱ multiple myeloma with anemia, retinal vein occlusion, and M proteinemia. It was decided that treatment for myeloma should be given priority and hence, Bd, high dose chemotherapy with auto-peripheral blood stem cell transplantation(aPBSCT), Ld, ELd and Pd therapy were performed sequentially until progressive disease(PD)and survival benefit were evident. As lung metastasis of adenocarcinoma also progressed, myeloma treatment was terminated, GEF was administered intermittently and consequently, shrinkage of the lung metastasis was confirmed. Depending on sequential alternating chemotherapy for both malignancies, a relatively long survival time of 5.4 years from the initiation of treatment for myeloma and 7.5 years from the recurrence of lung adenocarcinoma was achieved.
A two dimensional (2-D) Scanner-on-scanner (SOS) has been developed for commercial confocal laser scanning microscope (LSM) "LEXT' series. The SOS consists of a newly developed electromagnetic MEMS scanner mounted on a commercially available galvanometric scanner, being inclined at 45deg. The SOS realizes much smaller distortion in the 2-D scanning pattern than that obtained by gimbaled type MEMS 2-D scanner. Key issue is miniaturizing the MEMS scanner so that it can be mounted onto the galvanometric scanner. It was realized by using a coil for both driving and sensing so that sensing output was increased, and thus size reduction of permanent magnets have become possible, leading to the scanner volume of approximately 9.3 % of the one previously developed for a LSM, Olympus OLS1200
