Yasuhito Nerome

Clinical features of Japanese children and adolescents with systemic lupus erythematosus: results of 1980-1994 survey.

Marked advances have been made in the past decade in the management of adults with systemic lupus erythematosus (SLE). Therefore, a nationwide retrospective survey was conducted between 1980 and 1994 to investigate the clinical manifestations of SLE in Japanese children and adolescents. Questionnaires were sent to 340 hospitals. Of 405 patients reported by 176 hospitals, 373 patients, diagnosed by the criteria established by the Pediatric Study Group of the Japanese Ministry of Health and Welfare in 1985, were enrolled in the study. Forty‐nine of the 354 patients (13.8%) had relatives with a connective tissue disease within the third degree of consanguinity. The frequent manifestations in 373 patients were the presence of antinuclear antibody (98.9%), immunologic disorders (93.0%), hypocomplementemia (87.1%), malar rash (79.6%) and fever (74.0%). Lupus nephritis was present in 148 of the 309 patients (47.9%) at their first visit to a clinic, and 261 of the 373 patients (70.0%) developed renal involvement during the observation period. Of 370 patients, 92 patients (24.9%) exhibited central nervous system lupus. Of 368 patients, 192 patients (52.2%) were treated by methylprednisolone pulse therapy and 148 patients (40.2%) received immunosuppressants in combination with steroid therapy at some stage during the observation period. Survival rate at 5 years from onset was 95.9%. Management of infection, coagulopathies, and central nervous system involvement is essential to improve the prognosis of SLE in Japanese children and adolescents.

Frequent methylprednisone pulse therapy is a risk factor for steroid cataracts in children

Background: Pediatricians use corticosteroids for prolonged periods of time for the treatment of many diseases, including rheumatic disease. The side‐effects of corticosteroids, especially cataracts, are widely recognized, but the predictive risk factors for steroid‐induced cataracts have not yet been fully characterized.

Prediction of long-term remission of oligo/polyarticular juvenile idiopathic arthritis with S100A12 and vascular endothelial growth factor.

Abstract Objectives: This study aimed to evaluate the usefulness of S100A12 and vascular endothelial growth factor (VEGF) for predicting the stability of remission for discontinuing methotrexate (MTX) and/or biological agents in Japanese patients with oligo/polyarticular juvenile idiopathic arthritis (JIA). Methods: Forty-four patients with oligo/polyarticular JIA who received MTX with or without biological agents were enrolled. Serum concentration of both S100A12 and VEGF were simultaneously evaluated by ELISA in active and in remission phase determined by activity markers including DAS-28. Results: S100A12 and VEGF were correlated with DAS-28. Of the 22 patients with oligo/polyarticular JIA in clinical remission, 13 patients with low S100A12 and VEGF concentrations could discontinue treatment without relapse over 2 years. However, nine patients without low S100A12 and VEGF concentrations relapsed afterwards, even though they had been in clinical remission. The cut-off levels of S100A12 and VEGF for division into two groups of the maintenance remission and relapse groups were 177 ng/ml and 158 pg/ml, respectively. Conclusions: S100A12 and VEGF are useful markers for assessing disease activity of oligo/polyarticular JIA in remission phase. These markers should be kept low when clinicians consider tapering or discontinuing treatments in oligo/polyarticular JIA patients.

The translational aspect of complementary and alternative medicine for cancer with particular emphasis on Kampo

Complementary and alternative medicine (CAM) including Japanese Kampo is known to have anticancer potential. An increasing number of cancer survivors are using CAM for disease prevention, immune system enhancement, and symptom control. Although there have been abundant previous clinical reports regarding CAM, scientific investigations aimed at acquiring quantifiable results in clinical trials, as well as basic research regarding CAM, have only recently been undertaken. Recent studies suggest that CAM enhancement of immune function is related to cytokines. This review provides a translational aspect of CAM, particularly Hozai in Kampo from both scientific and clinical points of view for further development of CAM for cancer treatment.

Current human T‐cell lymphotropic virus type 1 mother‐to‐child transmission prevention status in Kagoshima

The aim of this study was to assess the current human T‐cell lymphotropic virus type 1 (HTLV‐I) mother‐to‐child transmission (MTCT) prevention system in Kagoshima Prefecture. We investigated the rate of carrier pregnant women from obstetrics facilities in Kagoshima by mail in 2012 and compared our results with previous study results. We interviewed carrier pregnant women about their choices for infant nutrition, and we interviewed midwives about the follow‐up system. In 2012, 8719 screening tests were performed, covering 58.1% of all pregnant women in Kagoshima; the rate of carrier pregnant women was 1.3%. Of 59 carriers, 39 chose short‐term breast‐feeding. The HTLV‐I carrier rate among pregnant women in Kagoshima has declined. The current HTLV‐I MTCT prevention system in Kagoshima is effective, but not sufficient. To bring the nutrition methods to completion, various types of support are needed. Further studies will elucidate many unsolved problems concerning MTCT.

The Role of Ghrelin and Ghrelin Signaling in Aging

With our aging society, more people hope for a long and healthy life. In recent years, researchers have focused on healthy longevity factors. In particular, calorie restriction delays aging, reduces mortality, and extends life. Ghrelin, which is secreted during fasting, is well known as an orexigenic peptide. Because ghrelin is increased by caloric restriction, ghrelin may play an important role in the mechanism of longevity mediated by calorie restriction. In this review, we will discuss the role of orexigenic peptides with a particular focus on ghrelin. We conclude that the ghrelin-growth hormone secretagogue-R signaling pathway may play an important role in the anti-aging mechanism.

Large intracardiac thrombus in a child with refractory nephrotic syndrome

Patients in a hypercoagulative state with nephrotic syndrome have a risk of various complications, such as salt water retention, thromboembolism, hyperlipidemia, metabolic bone diseases and infections. The hypercoagulative state in nephrotic syndrome is induced by elevated platelets counts, high levels of cholesterol and low levels of albumin and protein C, high plasma levels of fibrinogen and low plasma levels of anti-thrombin III. We describe here the case of an 11-year-old boy with refractory nephrotic syndrome, complicated by a large isolated thrombus in the right ventricle. The patient urgently underwent thoracotomy with resection. In order to detect asymptomatic intracardiac thrombus, it is important to be aware of the possibility of this complication in patients with refractory nephrotic syndrome.

Tumor Necrosis Factor Inhibitors Provide Longterm Clinical Benefits in Pediatric and Young Adult Patients with Blau Syndrome

To the Editor: Blau syndrome is an autoinflammatory disease caused by mutations in the NOD2 gene1. The initial symptoms of Blau syndrome usually include polyarthritis and rash followed by uveitis. In addition, various clinical manifestations beyond the classic clinical triad have been reported in patients with Blau syndrome2,3,4. Although controlling ocular and articular involvements are critical to improve prognosis, no specific therapy for Blau syndrome has yet been established. The use of thalidomide, immunosuppressives [methotrexate (MTX) or azathioprine], and biologic therapy [tumor necrosis factor-α (TNF-α) or interleukin (IL)-1β inhibitor] has been reported in corticosteroid-refractory cases1,4,5,6; however, the small number of patients with Blau syndrome in these studies and case reports makes drawing a definite conclusion difficult. To address these issues, we report a series of 6 patients (3 men and 3 women) with Blau syndrome who received biologic therapy between 2005 and 2013 at the Kagoshima University Hospital, Kagoshima, Japan. Clinical findings and laboratory data were collected from their medical records. No patient had achieved clinical remission with prior treatments, including nonsteroidal antiinflammatory drugs, MTX, and systemic … Address correspondence to Dr. H. Wakiguchi, Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. E-mail: hiroyuki{at}yamaguchi-u.ac.jp

Disease activity score in 28 joints at 3 months after the initiation of biologic agent can be a predictive target for switching to the second biologic agent in patients with polyarticular juvenile idiopathic arthritis.

Abstract Objective: To clarify polyarticular juvenile idiopathic arthritis (pJIA) patients who failed to maintain prolonged remission with the first biologic agent. Methods: Fourteen pJIA patients were observed for 47.5 months (median) after initiating the first biologic agent. Results: Eight maintained sustained clinical remission (median 47 months) with the first biologic agents, while the six switched to the second one due to lack of efficacy, thereafter. Receiver operating characteristic (ROC) analysis revealed that disease activity score in 28 joints (DAS28) of 2.37 at 3 months could distinguish between the two patient groups (p = 0.001). Conclusion: pJIA patients with DAS28 >2.37 at 3 months of the initial biologic therapy may be considered to switch to the second biologics.

Positive Association of Plasma Homocysteine Levels with Cardio-Ankle Vascular Index in a Prospective Study of Japanese Men from the General Population

AIM Observational studies have reported that elevated homocysteine (Hcy) levels are associated with the risk of cardiovascular disease (CVD). However, interventions that lower Hcy do not provide a corresponding risk reduction. Therefore, the causal role of Hcy in CVD remains unclear. This 5-year prospective study investigated the associations of Hcy levels, folate intake, and host factors with arterial stiffness among the general Japanese population. METHODS We prospectively recruited 658 participants (40-69 years old) from the general population during regular health checkup examinations. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) at baseline and the 5-year follow-up. Folate intake was estimated using a structured questionnaire. Genotyping was used to evaluate the MTHFR C677T and MS A2756G gene polymorphisms. Ultrafast liquid chromatography was used to measure total plasma Hcy levels. Association between these variables and CAVI values was evaluated using general linear regression and logistic regression models that were adjusted for atherosclerosis-related factors. RESULTS Men had higher Hcy levels and CAVI values and lower folate intake than women (all, p＜0.001). At baseline, Hcy, folate intake, and the two genotypes were not associated with CAVI values for both sexes. Among men, Hcy levels were positively associated with CAVI values at the 5-year follow-up (p=0.033). Folate intake and the two genotypes were not associated with the 5-year CAVI values. CONCLUSION Plasma Hcy may be involved in arterial stiffness progression, as monitored using CAVI, among men.