IL-6 and tumor necrosis factor (TNF)-alpha have been proven to play an important role in the development of rheumatoid arthritis (RA). It is well known that TNF-alpha induces IL-6 production from synovial cells as well as their proliferation. The effect of IL-6 on synovial cells, however, is not clear. An in vitrostudy was performed to determine the effect of IL-6 on the proliferation of synovial cells. Fibroblastic synovial cells isolated from the synovial tissues of eight RA patients were employed after the third to sixth passages. IL-6 in the presence of soluble IL-6 receptor (sIL-6R) inhibited the proliferation of synovial cells in a dose-dependent manner in seven cases without increasing the number of necrotic or apoptotic cells, while TNF-alpha increased synovial cell proliferation in all cases. The inhibitory effect of IL-6 was observed only in the presence of sIL-6R although small amounts of IL-6R were detected in these cells by RT-PCR analysis. However, anti-IL-6R or anti-gp130 mAb treatment increased spontaneous growth of synovial cells in all eight cases, suggesting that endogenous IL-6 and a small amount of IL-6R expressed in synovial cells suppressed their growth without exogenous IL-6 or sIL-6R. In addition, the IL-6-sIL-6R complex reduced the TNF-alpha-induced proliferation of synovial cells while TNF-alpha induced their IL-6 production. These data suggest that IL-6 may act as a negative feedback factor for TNF-alpha-induced synovial cell growth.

PurposeGait independence is one of the most important factors related to returning home from the hospital for patients treated in the intensive care unit (ICU), but the factors affecting gait independence have not been clarified. This study aimed to determine the factors affecting gait independence at hospital discharge using a standardized early mobilization protocol that was shared by participating hospitals.Materials and methodsPatients who entered the ICU from January 2017 to March 2018 were screened. The exclusion criteria were mechanical ventilation < 48 hours, age < 18, loss of gait independence before hospitalization, being treated for neurological issues, unrecoverable disease, unavailability of continuous data, and death during ICU stay. Basic attributes, such as age, ICU length of stay, information on early mobilization while in the ICU, Medical Research Council (MRC) sum-score at ICU discharge, incidence of ICU-acquired weakness (ICU-AW) and delirium, and the degree of gait independence at hospital discharge, were collected. Gait independence was determined using a mobility scale of the Barthel Index, and the factors that impaired gait independence at hospital discharge were investigated using a Cox proportional hazard regression analysis.ResultsOne hundred thirty-two patients were analyzed. In the univariate analysis, age, APACHE II score, duration of mechanical ventilation, ICU length of stay, incidence of delirium, and MRC sum-score at ICU discharge were extracted as significant. In the multivariate analysis, age (p = 0.014), MRC sum-score < 48 (p = 0.021), and delirium at discharge from ICU (p < 0.0001) were extracted as significant variables.ConclusionsWe found that age and incidence of ICU-AW and delirium were significantly related to impaired gait independence at hospital discharge.

We present a neonatal case with intractable atrial flutter that did not respond to digitalization and electrical cardioversion. Intravenous flecainide administration completely resolved the atrial flutter. Proarrhythmic effects were not induced by flecainide administration. Although the efficacy of flecainide for atrial flutter during the infantile or childhood period is low, intravenous flecainide is worth consideration as a treatment for atrial flutter, even in intractable cases as described here, during the neonatal period.

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H(1)-blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.

International and Japanese guidelines classify childhood asthma as mild, moderate, or severe, and recommend treatment with "as needed" bronchodilators, inhaled sodium cromoglycate, and inhaled corticosteroids, respectively. Alternatively, some investigators proposed inhaled corticosteroids as first-line therapy to prevent airway inflammatory obstruction. This article describes a clinical study assessing the effect of early intervention with inhaled sodium cromoglycate in childhood asthma. This was a retrospective study of 189 asthmatic children treated with inhaled sodium cromoglycate for five years and whose age of onset of asthma was six year of age or younger. An end-of-study questionnaire completed the examination. Children administered oral or inhaled corticosteroids simultaneously with sodium cromoglycate, were excluded. Asthma scores as defined by the Japanese Pediatric Allergic Committee, were reduced continuously during the five years after the start of sodium cromoglycate treatment. The frequency of emergency department visits and hospitalizations also decreased. Significant between-period intervention differences showed improvement of clinical outcomes for children with severe asthma during the five years of sodium cromoglycate inhalation. The early intervention regime of starting sodium cromoglycate inhalation within two years of the onset of asthma shows a large improvement in the long-term prognosis of childhood asthma, especially for children with severe asthma. It is possible that starting inhaled sodium cromoglycate earlier than the present recommendation of corticosteroids could further improve clinical outcomes, but a prospective study should be performed to verify our results.