yoshida shunji

Anti-endothelial cell antibodies (AECA) are frequently detected in patients with systemic lupus erythematosus (SLE), but their pathological role remains unclear. We recently developed a solubilized cell surface protein capture enzyme-linked immunosorbent assay (CSPELISA) to detect antibodies against membrane proteins involved in autoimmune reactions. In this study, sera from 51 patients with biopsy-proven lupus nephritis (LN), 25 with SLE without renal involvement (non-LN SLE), 42 disease control (DC) subjects, and 80 healthy control (HC) subjects were tested for IgG-and IgA-AECA for human umbilical vein endothelial cells (HUVEC) and human glomerular EC (HGEC) by using CSP-ELISA. IgG-and IgA-AECA titers were significantly higher in LN and non-LN SLE patients than in the DC or HC (P < 0.001) groups. IgG-and IgA-AECA titers for HUVEC corresponded well with those for HGEC. The IgA-AECA level correlated with the SLE disease activity index and with histological evidence of active lesions (cellular proliferations, hyaline thrombi and wire loops, leukocytic infiltration, and fibrinoid necrosis) in LN patients (P < 0.001). The sensitivity of IgA-AECA as a diagnostic test for histological evidence of active lesions in LN patients was 0.92, with a specificity of 0.70. The significant correlation of IgA-AECA with glomerular hypercellularity indicates that IgA-AECA are associated with endothelial damage in LN.

Infection by bacteria carrying New Delhi metallo-beta-lactamase 1 (NDM-1) is becoming a global health problem. We report a case of meningitis caused by NDM-1-producing Klebsiella pneumoniae, for which intrathecal administration of colistin was curative. A previously healthy 38-year-old Japanese man, who lived in Hyderabad, India, suddenly collapsed and was brought to a local hospital. He was diagnosed with subarachnoid hemorrhage and underwent emergency surgery which included partial skull removal. Approximately 1 month after surgery, he was repatriated to Japan and was admitted to our institution with information that he had been treated for multi-drug resistant Acinetobacter infection with colistin. A week after admission, he developed aspiration pneumonia due to NDM-1-producing K. pneumoniae, which was successfully treated by intravenous (IV) administration of colistin. Subsequently, he underwent a surgical procedure to repair his skull defect. He developed high-grade fever and altered mental status on postoperative day 2. NDM-1-producing K. pneumoniae was identified in the cerebrospinal fluid, establishing the diagnosis of meningitis. Although IV colistin was only partially effective, intrathecal colistin (10 mg daily by lumbar puncture for 14 days) successfully eradicated the meningitis. Because of economic globalization, NDM-1-producing bacteria may be brought to Japan by those who are repatriated after sustaining critical illnesses and being treated in foreign countries. This report may provide useful information on the treatment of central nervous system infection by NDM-1-producing bacteria. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Patients with polymyositis (PM) or dermatomyositis (DM) frequently show interstitial pneumonia (IP), which is sometimes rapidly progressive or resistant to treatment, thereby significantly affecting the prognosis. The diagnosis and response evaluation of IP are commonly performed qualitatively based on imaging findings, which may cause disagreement among rheumatologists in the evaluation of early lesions and atypical interstitial changes. To determine whether IP could be diagnosed in a quantitative manner during the early stage of PM/DM using a workstation that allows quantitative image processing. Thoracic computed tomography (CT) images of 20 PM/DM patients were reconstructed into a three-dimensional (3D) image using an image processing workstation. The CT values of the constituent voxels were arranged in a histogram of -1000 to +1000 Hounsfield units (HU). The most frequent lung field density was -900 to -801 HU, and relative size was as follows: IP (+) group 0.45 and IP (-) group 0.53. Between -1000 and -701 HU, relative size was not significantly different between the IP (+) group and IP (-) group. Between -700 and -1 HU, the relative size of the lung field was significantly larger in the IP (+) than in the IP (-) group, demonstrating its IP-diagnosing ability. Particularly, within the range from -700 to -301 HU, the macroscopically-assessed ground glass opacity was consistent with the CT value, which, in turn, was closely correlated with KL-6, the pre-existing marker for IP diagnosis. The results of this study may lead to the establishment of quantitative methods of evaluating IP and possible elucidation of the pathogenesis of IP.

The significance of evaluations of stressors in rheumatoid arthritis (RA) patients was investigated from the perspective of holistic medicine. The subjects were RA patients treated in the rheumatology outpatient clinic. They included 30 patients from 1987, 30 from 2002, and 137 from 2009. To investigate the specific causes of stress, the patients were asked the question, "What do you feel is your strongest stressor?" The same patients also underwent psychological testing and was examined the disease activity. Pain was the strongest stressor in RA patients in 1987, 2002, and 2009. However, the percentage of patients citing pain as their major stressor was decreasing with each year. CRP was significantly lower in 2009 than in 2002. CRP was also significantly lower in patients who used biologics than in patients who did not. In 2009, DAS28-CRP was significantly higher in patients whose largest stressor was pain than in patients whose largest stressor was another factor. In 2009, the values for both state anxiety and trait anxiety were significantly higher in patients who said that they had stressors than in those who said they did not. The strongest stressor in RA patients was pain. However, the percentage decreased over the years with lower disease activity from advances in therapeutic agents such as biologics. Meanwhile, stressors other than pain were the same or somewhat increased, and they were related to anxiety or depression. Understanding stressors in RA is thus important in treating RA patients.

Objective: To investigate the safety and efficacy of long-term administration of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH). Research design and methods: In this open-label extension of a preceding multicenter dose-escalation study, 21 Japanese patients with PAH received treatment with 5 or 10 mg of ambrisentan once daily and were comprehensively evaluated every 12 weeks. The primary endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events. The secondary (efficacy) endpoints were change in exercise capacity (as indicated by 6-minute walk distance), World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, cardiopulmonary hemodynamics, and time to clinical worsening of PAH. Clinical trial registration: NCT00554619. Results: The mean total duration of treatment (i.e., including the preceding dose-escalation study) was approximately 139 weeks. There were fewer adverse events related to ambrisentan in this study than in the preceding study, and we identified no new safety signals that might preclude the long-term use of ambrisentan among Japanese adults with PAH. Improvements observed in efficacy endpoints in the preceding study were maintained in the present study. Limitations: This study did not include a control group and lacked the statistical power to reach definite conclusions regarding the efficacy of ambrisentan. Conclusion: Our results suggest that long-term administration of ambrisentan is well tolerated and efficacious for Japanese adults with PAH.

Objective: To investigate the efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH). Research design and methods: In this open-label, uncontrolled, dose-escalation study, 25 Japanese patients with PAH were scheduled to receive 5 mg of ambrisentan once daily for the first 12 weeks, and 10 mg once daily for an additional 12 weeks. The primary endpoint was improvement in exercise capacity from baseline which was indicated by 6-minute walk distance; the secondary endpoints included World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, and cardiopulmonary hemodynamics. Clinical trial registration: NCT00540436. Results: At week 24, improvements were noted in all endpoints, with no clinically significant elevation of serum aminotransferase level. Pharmacokinetics in these Japanese patients was similar to that of non-Japanese populations, suggesting that once-daily dosing is appropriate in Japanese patients. Ambrisentan was generally well tolerated. No new safety signals were identified. Limitation: This study lacked a control group and was insufficiently powered to reach definitive conclusions on the efficacy of ambrisentan. Conclusion: Ambrisentan is considered as safe and effective for Japanese adults with PAH.

Serum (1 -> 3)-beta-d-glucan levels and clinical findings were evaluated in 229 inpatients with connective tissue diseases (CTDs) during the period between June and October 2004. The mean serum (1 -> 3)-beta-d-glucan level was 129.7 +/- A 207.6 pg/mL in patients with a definitive diagnosis of fungal infections and 10.5 +/- A 8.6 pg/mL in patients without fungal infections. Analysis of the diagnostic sensitivity/specificity for various (1 -> 3)-beta-d-glucan cutoff levels gave the best results for a cutoff level of 15 pg/mL, with a sensitivity of 92.3% and specificity of 81.3%. This level was therefore determined to be the optimal cutoff in patients with CTDs.