Background:Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC.Methods:From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day−1). End points were overall survival (OS) and quality of life.Results:An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92–1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting.Conclusion:Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

Adenine nucleotide translocases (ANTs) transport ADP and ATP through mitochondrial inner membrane, thus playing an essential role for energy metabolism of eukaryotic cells. Mice have three ANT paralogs, Ant1 (Slc25a4), Ant2 (Slc25a5) and Ant4 (Slc25a31), which are expressed in a tissue-dependent manner. While knockout mice have been characterized with Ant1 and Ant4 genes, which resulted in exercise intolerance and male infertility, respectively, the role of the ubiquitously expressed Ant2 gene in animal development has not been fully demonstrated. Here, we generated Ant2 hypomorphic mice by targeted disruption of the gene, in which Ant2 expression is largely depleted. The mice showed apparently normal embryonic development except pale phenotype along with a reduced birth rate. However, postnatal growth was severely retarded with macrocytic anemia, B lymphocytopenia, lactic acidosis and bloated stomach, and died within 4 weeks. Ant2 depletion caused anemia in a cell-autonomous manner by maturation arrest of erythroid precursors with increased reactive oxygen species and premature deaths. B-lymphocyte development was similarly affected by Ant2 depletion, and splenocytes showed a reduction in maximal respiration capacity and cellular ATP levels as well as an increase in cell death accompanying mitochondrial permeability transition pore opening. In contrast, myeloid, megakaryocyte and T-lymphocyte lineages remained apparently intact. Erythroid and B-cell development may be particularly vulnerable to Ant2 depletion-mediated mitochondrial dysfunction and oxidative stress.

The prevalence of gastroesophageal reflux disease (GERD) has increased recently in Asia-Pacific countries. However, little is known about its prevalence and clinical characteristics in GERD patients with atypical symptoms in Asia. The aim of this study was to investigate the clinical characteristics of GERD in patients who had laryngeal symptoms in Korea. Data were gathered retrospectively from patients who presented with atypical symptoms, such as throat discomfort, globus pharyngeus, hoarseness, and chronic cough. They underwent a 24-hour ambulatory intraesophageal pH monitoring and filled in a validated reflux questionnaire. Overall, 128 patients (36 men and 92 women) with laryngeal symptoms were included. Of these 128, 43 patients (34%) had erosive esophagitis or pathological reflux from 24-hour ambulatory pH monitoring, and 24 (19%) had a positive Bernstein test or positive symptom index from 24-hour pH monitoring. Sixty-one patients (48%) had no evidence of reflux esophagitis on upper endoscopy and pathological acid reflux on 24-hour pH monitoring. Fifty-six patients (44%) had weekly heartburn or regurgitation. Typical symptoms and dyspepsia were significantly more common in patients with GERD who had laryngeal symptoms than non-GERD. Fifty-two percent of patients had laryngeal symptoms that were associated with GERD. The presence of typical reflux symptoms and dyspepsia are risk factors for GERD in patients who present with laryngeal symptoms.

Laryngoscopyand endobronchial intubation usually cause transient hypertension and tachycardia. We investigated whether thoracic epidurally injected 3 µg/kg clonidine attenuates cardiovascular responses to intubation compared with 2 µg/kg fentanyl and 1 mg/kg lidocaine. Epidural catheterization was performed at the T6 -T7 or T7 -T8 intervertebral space, and saline or clonidine in saline was injected 20 min before anaesthetic induction. Anaesthesia was induced using 5 mg/kg thiopental sodium and 0.1 mg/kg vecuronium. Laryngoscopy and endobronchial intubation were performed 2 min later. Mean blood pressure and heart rate were measured throughout anaesthetic induction. In the control group and the fentanyl group, mean blood pressure and heart rate 3 min after endobronchial intubation were elevated significantly compared with baseline. In the clonidine group, however, mean blood pressure and heart rate did not increase compared with baseline. The control group had higher mean blood pressure and heart rate than the clonidine group 3 min after endobronchial intubation. Thoracic epidural clonidine may attenuate the haemodynamic response to endobronchial intubation.

cis- and trans-4-Aminochroman-3-ols have been prepared and their configurations have been established by stereospecific reactions. The configurations of the cis and trans isomers of both 4-amino-chroman-3-ols and 3-aminochroman-4-ols were confirmed by analysis and iterative refinement of the 270-MHz proton N.M.R. spectra.

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Malaysia and Indonesia are the largest palm oil producers worldwide. In palm oil production, approximately one tonne of empty fruit bunch (EFB) will be generated as waste for every one tonne of palm oil produced. Currently, these fresh EFB are still underutilised and generally disposed under open environment. The fresh EFB are more susceptible to microbial attack under natural environment when exposed even for short period and become degraded empty fruit bunch (DEFB) which have lower quality. Consequently, disposal of DEFB becomes an enormous challenge as well as its following environmental problems including soil pollution and emission of greenhouse gases such as methane. However, DEFB remain as a promising lignocellulosic biomass feedstock with huge potential for production of high value added products entailing biofuels, bio-polymer and membrane with appropriate pretreatment. Therefore, DEFB was subjected to organosolv pretreatment in this research to recover its cellulose content. DEFB was discovered to possess higher cellulose content, lignin content and lower hemicellulose content as compared to fresh EFB. Organosolv pretreatment successfully fractionated DEFB to recover the cellulose portion by removing the lignin and hemicellulose content. Pretreatment with 50 v/v% ethylene glycol in the presence of 3 v/v% NaOH removed 75.1 wt.% lignin and 81.5 wt.% hemicellulose with 90.4 wt.% cellulose recovery. Furthermore, the cellulose purity of treated DEFB was improved drastically from 55.9% to 84.5%. For pretreatment liquor, the recoverable lignin was amounted to 74.6 % at pH 2.0. This study proved that organosolv pretreated DEFB exhibited the desirable properties for subsequent processes such as hydrolysis to synthesise the biomass waste into other high value added bio-products.

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