Refractory non-small-cell lung cancer responding to combination chemotherapy with gemcitabine and cisplatin

The patient was a 60-year-old female with adenocarcinoma of the lung. An effective radiation therapy was performed for cervical lymph node metastases found 19 months after the operation. A right adrenal metastasis and abdominal paraaortic lymph node metastases were detected 11 months later, and chemotherapy with cisplatin (CDDP) was administered. Although a temporary partial response was obtained, the metastatic lesion was refractory to CDDP. The patient was treated with gemcitabine (GEM) and CDDP, which resulted in near complete response continued for 3 months. The combination therapy of GEM and CDDP may be effective for recurrent non-small-cell lung cancer refractory to other regimens.     

Add‐on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C

Despite the use of pegylated‐interferon (peg‐IFN) plus ribavirin combination therapy, many patients infected with hepatitis C virus (HCV)‐1b remain HCV‐positive. To determine whether addition of pitavastatin and eicosapentaenoic acid (EPA) is beneficial, the “add‐on” therapy option (add‐on group) was compared retrospectively with unmodified peg‐IFN/ribavirin therapy (standard group). Association of host‐ or virus‐related factors with sustained virological response was assessed. In HCV replicon cells, the effects of pitavastatin and/or EPA on HCV replication and expression of innate‐immunity‐ and lipid‐metabolism‐associated genes were investigated. In patients infected with HCV‐1b, sustained virological response rates were significantly higher in the add‐on than standard group. In both groups, sustained virological response rates were significantly higher in patients with genotype TT of IL‐28B (rs8099917) than in those with non‐TT genotype. Among the patients with non‐TT genotype, sustained virological response rates were markedly higher in the add‐on than standard group. By multivariate analysis, genome variation of IL28B but not add‐on therapy remained as a predictive factor of sustained virological response. In replicon cells, pitavastatin and EPA suppressed HCV replication. Activation of innate immunity was obvious in pitavastatin‐treated cells and EPA suppressed the expression of sterol regulatory element binding protein‐1c and low‐density lipoprotein receptor. Addition of pitavastatin and EPA to peg‐IFN/ribavirin treatment improved sustained virological response in patients infected with HCV‐1b. Genotype variation of IL‐28B is a strong predictive factor in add‐on therapy. J. Med. Virol. 85:250–260, 2013. © 2012 Wiley Periodicals, Inc.     

Successful control of life-threatening polymorphic ventricular tachycardia by radiofrequency catheter ablation in an infant

We present a case of a 9-month-old girl in whom malignant polymorphic ventricular tachycardia (VT) was successfully controlled by radiofrequency catheter ablation under guidance with a three-dimensional mapping system. The VTs originated from the left ventricular lateral wall, left ventricular anterior wall, and left ventricular apex. At least six types of VTs were documented during the electrophysiology study. All VTs were successfully controlled after two sessions of radiofrequency catheter ablation, and she was discharged from our hospital on propranolol, mexiletine, flecainide, and aprindine.     

Urinary sulfated bile acid analysis for the early detection of biliary atresia in infants

Background: Measurement of urinary sulfated bile acid (USBA) is a non‐invasive method to detect bile congestion. Our aim was to evaluate the feasibility of USBA analysis for the early detection of biliary atresia (BA). Methods: We determined the USBA‐to‐creatinine ratio (USBA/cr) in 1148 infants at 10–40 days after birth. All infants were followed until the 3‐ to 4‐month postnatal routine health check. The cutoff value for USBA/cr was 55.0 µmol/g creatinine. Results: Among the infants tested, 47 (4.10%) had USBA/cr ratios that exceeded the cutoff value. Two of these 47 infants had liver disease; one was diagnosed with neonatal hepatitis syndrome, and the other was diagnosed with BA. The BA patient underwent USBA analysis for the first time on day 18 after birth and hepatoportoenterostomy on day 49. No other infants were diagnosed with hepatobiliary disease during the follow‐up period. Conclusion: This USBA analysis provided the correct assessment without fail and identified a case of BA. This approach could be used for the screening and early detection of BA when the false‐positive rate is decreased by improving the methods for sample collection and urine storage.     

Effects of agar and pectin on gastric emptying and post-prandial glycaemic profiles in healthy human volunteers

1. Dietary fibre, such as pectin, delays gastric emptying and may enhance post-prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long-term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post-prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2. Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre-free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [(13)C]-acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [(13)CO(2)] excretion time (t((1/2)b)) and the time for maximal [(13)CO(2)] excretion rate (t(lag)) were determined. The post-prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated-measures analysis of variance (anova), followed by a post hoc paired Student's t-test with Bonferroni adjustment. 3. The time-course for respiratory [(13)CO(2)] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [(13)CO(2)] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post-prandially; P < 0.025, Student's t-test) and the pectin meal (between 40 and 180 min post-prandially; P < 0.025, Student's t-test). Among the three meals, significant differences were found in t((1/2)b) (P = 0.002, anova) and t(lag) (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged t((1/2)b) (P = 0.007 and P < 0.0001, respectively, Student's t-test) and t(lag) (P = 0.006 and P = 0.002, respectively, Student's t-test). Neither the agar nor pectin meal affected the post-prandial glucose profile. 4. In healthy adults, agar and pectin delay gastric emptying but have no impact on the post-prandial glucose response.     

Psychological impact of the pandemic (H1N1) 2009 on general hospital workers in Kobe

Aims: In order for hospitals to work efficiently in a pandemic, it is important to know how a pandemic affects the hospital staff. The aim of the present study was to investigate the psychological impact of the pandemic (H1N1) 2009 on hospital workers and how it was affected by the characteristics of the hospital, gender, age, job and work environment. Methods: In late June 2009, soon after the pandemic had ended in Kobe city, Japan, a questionnaire was distributed consisting of questions on sociodemographic characteristics, 19 stress‐related questions and the Impact of Event Scale (IES) to all 3635 employees at three core general hospitals in Kobe. Exploratory factor analysis was applied to the 19 stress‐related questions, and this produced four factors for evaluation (anxiety about infection, exhaustion, workload, and feeling of being protected). Multiple regression models were used to evaluate the association of personal characteristics with each score of the four factors and the IES. Results: Valid answers were received from 1625 employees. Workers at a hospital with intense liaison psychiatric services felt less psychological impact. Workers at a hospital that provided staff with information about the pandemic less frequently, felt unprotected. Workers in work environments that had a high risk of infection felt more anxious and more exhausted. The total IES score was higher in workers in high‐risk work environments. Conclusions: It is important for hospitals to protect hospital workers during a pandemic and to rapidly share information about the pandemic. Liaison psychiatric services can help to reduce the impact of the pandemic on hospital workers.     

Caveolin-1 in extracellular matrix vesicles secreted from osteoblasts

Caveolin-1 is an essential and signature protein of caveolae, which are small invaginations of the plasma membrane enriched in cholesterol and sphingolipids. Although high levels of expression of caveolin-1 have been demonstrated in osteoblasts as well as endothelial cells, fibroblasts, and muscular cells, the role of caveolin-1 in osteoblasts has not been clarified. Here, we show that caveolin-1 is secreted from osteoblasts in the form of matrix vesicles; extracellular vesicles released from the plasma membrane of osteoblasts. In this study, caveolae and matrix vesicles were similarly enriched in cholesterol and sphingomyelin in fractions isolated from mineralizing MC3T3-E1 cells. Interestingly, in the MC3T3-E1 cells caveolin-1 was enriched in the matrix vesicle fraction as well as the caveolar membrane fraction, and the amount of caveolin-1 in the matrix vesicle fraction increased as differentiation progressed. Localization of caveolin-1 in matrix vesicles was also confirmed in murine tibia. Furthermore, overexpression of caveolin-1 enhanced matrix calcification in MC3T3-E1 cells, whereas knockdown of caveolin-1 diminished it. These results suggest that secreted caveolin-1 as a component of matrix vesicles may play an important role in osteoblast calcification.