Search

Asthma exacerbation is a significant clinical problem that causes resistance to corticosteroid therapy and elevated hospitalization risk. Src family kinases (SFKs) contribute to various steps of the immune response, such as airway inflammation in viral or bacterial infections and allergic asthma. Therefore, we determined the effects of dasatinib (DAS), a typical Src inhibitor, on a murine asthma exacerbation model induced by house dust mites (HDM) and synthetic analog of double-stranded RNA, poly(I:C). A/J mice were sensitized to intrapreneurial HDM twice every seven days and challenged with intranasal HDM once every second day for a total of six exposures, and/or exposed to poly(I:C) twice daily for three consecutive days. Drug treatments were performed twice daily for three days, starting one day after the last HDM challenge or 2 h before each poly(I:C) exposure. DAS improved poly(I:C)-induced acute inflammation dose-dependently. Both DAS and fluticasone propionate (FP) attenuated HDM-induced allergic airway inflammation. However, in HDM and poly(I:C) induced-asthma exacerbated mice, DAS significantly improved inflammatory cells in bronchoalveolar lavage fluid and histological changes in the lungs, whereas FP did not. Therefore, SFKs are important targets for controlling severe asthma refractory to conventional therapies.

Background and objectives It is important to examine the roles of specific health check-up and specific health guidance in individuals at high risk of common lifestyle diseases, but evaluation based on a stratified analysis of people undergoing a health check-up has not been adequately performed. In this study, we examined the effects of providing specific health guidance to individuals considered at high risk for a lifestyle disease after specific health check-ups. Method Subjects who underwent a specific health check-up in 2012 were assigned to either a group that received health guidance from public health nurses over three years (n = 393) or a control group (n = 109). Clinical findings of both groups were analysed to evaluate the correlation between their changes and health guidance. Results A significant decrease was observed in blood pressure, and lipid and glucose levels only in the health guidance group. Multiple regression analysis revealed that health guidance was the explanatory variable of serum lipid improvement. Discussion Continued support by Japanese public health nurses through health guidance closely related to the subject's lifestyle over three years may lead to a comprehensive reduction in the risk of lifestyle diseases.

Tachycardia is common in intensive care units (ICUs). It is unknown whether tachycardia or prolonged tachycardia affects patient outcomes. We investigated the association between tachycardia and mortality in critically ill patients. This retrospective cohort study’s primary outcome was patient mortality in the ICU and the hospital. We stratified the patients (n=476) by heart rate (HR) as LowHR, MediumHR, and HighHR groups. We also stratified them by their durations of HR >100 (prolonged HR; tachycardia): MildT, ModerateT, and SevereT groups. We determined the six groups’ mortality. The ICU mortality rates of the LowHR, MediumHR, and HighHR groups were 1.0%, 1.5%, and 7.9%, respectively; significantly higher in the HighHR vs. LowHR group. The in-hospital mortality rates of these groups were 1%, 4.5%, and 14.6%, respectively; significantly higher in the HighHR vs. LowHR group. The ICU mortality rates of the MildT, ModerateT, and SevereT groups were 0.9%, 5.6%, and 57.1%, respectively. The mortality of the HRT=0 (i.e., all HR ≤ 100) patients was 0%. The in-hospital mortality rates of the MildT, ModerateT, and SevereT groups were 1.8%, 16.7%, and 85.7%, respectively; that of the HRT=0 patients was 0.5%. Both higher HR and prolonged tachycardia were associated with poor outcomes.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) causes central nervous system dysfunction including intractable epilepsy caused by impaired glucose transport to the brain. To prevent convulsions and maintain an energy source for the brain in patients with GLUT1DS, the maintenance of adequate ketone body concentrations, compensation of metabolic acidosis, and reduction of surgical stress are essential. We here report the perioperative management of a child with GLUT1DS.

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.

A 60-year-old man was admitted to our hospital with bilateral post auricular masses, first noticed 1 year earlier. Blood tests showed eosinophilia and high immunoglobulin E (IgE) levels, and cervical computed tomography showed 10-mm soft tissue masses with scattered lymphadenopathy. The tumors showed intermediate and high signal intensity on T1- and T2-weighted cervical magnetic resonance imaging, respectively. After mass resection, the tumors were diagnosed as Kimura’s disease (KD). Generally, KD affects young men; however, even in older patients, KD should be included as a differential diagnosis for head and neck tumors in patients with eosinophilia and high IgE.

Objectives: This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods: A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. Results: The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) 3.5 g/dL (HR =0.55), alpha-fetoprotein Conclusions: A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib.

Background & Aims The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers. Methods We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibers were evaluated pixel by pixel (0.46 μm/pixel) using an automated computational method. Consequently, fiber amount and cumulative incidences of HCC within 3 years were analyzed. Results There was a significant correlation between collagen and elastin fibers, whereas variation in elastin fiber was greater than in collagen fiber. Both collagen fiber (p = 0.008) and elastin fiber (p < 0.001) were significantly correlated with F stage. In total, 30 patients developed HCC during follow-up. Patients who have higher elastin fiber (p = 0.002) in addition to higher collagen fiber (p = 0.05) showed significantly higher incidences of HCC. With regard to elastin fiber, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fiber amount, higher elastin was a significant predictor for HCC development (p = 0.02). Conclusions Computational analysis is a novel technique for quantification of fibers with the added value of conventional staging. Elastin fiber is a predictor for the development of HCC independently of collagen fiber and F stage.

The water channel aquaporin 2 (AQP2) at the apical membrane of renal collecting duct cells mediates water reabsorption. The expression of AQP2 at the apical membrane is tightly regulated by vasopressin and was quantitated by measurement of the urinary form by a recently developed ELISA. Tolvaptan, an antagonist of vasopressin type 2 receptor, inhibits water reabsorption in cirrhosis. The aim of this study was to determine the correlation between the pharmacological effect of tolvaptan and the dynamics of urinary AQP2 levels. Tolvaptan was administered to 41 cirrhotic patients with ascites unresponsive to standard diuretic therapy. Urinary excretion of AQP2 and urinary osmolarity were measured at the baseline and at 4, 8, and 24 h after administration of tolvaptan. At the baseline, urinary AQP2/creatinine ratios were significantly higher in cirrhotic patients with ascites than in healthy controls (P

The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers.We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibers were evaluated pixel by pixel (0.46 μm/pixel) using an automated computational method. Consequently, fiber amount and cumulative incidences of HCC within 3 years were analyzed.There was a significant correlation between collagen and elastin fibers, whereas variation in elastin fiber was greater than in collagen fiber. Both collagen fiber (p = 0.008) and elastin fiber (p0.001) were significantly correlated with F stage. In total, 30 patients developed HCC during follow-up. Patients who have higher elastin fiber (p = 0.002) in addition to higher collagen fiber (p = 0.05) showed significantly higher incidences of HCC. With regard to elastin fiber, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fiber amount, higher elastin was a significant predictor for HCC development (p = 0.02).Computational analysis is a novel technique for quantification of fibers with the added value of conventional staging. Elastin fiber is a predictor for the development of HCC independently of collagen fiber and F stage.

We propose a framework to aid a visually impaired user to recognize objects in an image by sonifying image edge features and distance-to-edge maps. Visually impaired people usually touch objects to recognize their shape. However, it is difficult to recognize objects printed on flat surfaces or objects that can only be viewed from a distance, solely with our haptic senses. Our ultimate goal is to aid a visually impaired user to recognize basic object shapes, by transposing them to aural information. Our proposed method provides two types of image sonification: (1) local edge gradient sonification and (2) sonification of the distance to the closest image edge. Our method was implemented on a touch-panel mobile device, which allows the user to aurally explore image context by sliding his finger across the image on the touch screen. Preliminary experiments show that the combination of local edge gradient sonification and distance-to-edge sonification are effective for understanding basic line drawings. Furthermore, our tests show a significant improvement in image understanding with the introduction of proper user training.