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Aims: Alcoholic ketosis and ketoacidosis are metabolic abnormalities often diagnosed in alcoholics in emergency departments. We attempted to identify determinants or factors associated with alcoholic ketosis. Methods: The subjects of this cross-sectional survey were 1588 Japanese alcoholic men (≥40 years) who came to an addiction center within 14 days of their last drink. Results: The results of the dipstick urinalyses revealed a prevalence of ketosis of 34.0% (±, 21.5%; +, 8.9%; and 2+/3+; 3.6%) in the alcoholics. Higher urine ketone levels were associated with higher serum total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyl transpeptidase levels. A multivariate analysis by the proportional odds model showed that the odds ratio (95% confidence interval) for an increase in ketosis by one category was 0.94 (0.84–1.06) per 10-year increase in age, 0.93 (0.89–0.97) per 1-day increase in interval since the last drink, 1.78 (1.41–2.26) in the presence of slow-metabolizing alcohol dehydrogenase-1B ( ADH1B\*1/\*1 ), 1.61 (1.10–2.36) and 1.30 (1.03–1.65) when the beverage of choice was whiskey and shochu, respectively (distilled no-carbohydrate beverages vs. the other beverages), 2.05 (1.27–3.32) in the presence of hypoglycemia

Local fronts, such as sea-breeze and land-breeze fronts, play an important role not only from a meteorological aspect but also for pollutant transport and mixing, in urban areas in particular. Due to the difficulty of measuring three-dimensional (3-D) wind fields, there are few studies focusing on short-term fine-scale spatial and temporal variations in aerosol and gas compositions associated with local front passage. At the end of November 2016, a 3-D coherent Doppler lidar was installed in Fukuoka city (33.55°N, 130.37°E), an urban area in Japan, and 3D-wind fields have been continuously measured since then. Two local fronts with typical density current structure were observed on 3 May and 29 June 2017. On 3 May 2017, there was a stepwise increase in concentrations of aerosol (particularly smaller size aerosol), black carbon (BC) and carbon monoxide (CO), supposedly of surface origin, at the passage of the local front. However, O3 content, which can be higher at higher altitudes, decreased. In another case on 29 June 2017, there was light rain in the early morning and all gas and aerosol contents were low before the passage of the front. At the front passage, there was a stepwise increase in aerosol, BC and CO contents as on 3 May, although O3 content gradually increased after sunrise and no clear change was observed in O3. Vertical aerosol observations by the Doppler lidar indicate that the depth of the front system on 29 June was much thinner (up to 300–400 m) than that on 3 May (up to ∼700 m), and the temperature decrease was larger than on 3 May. These facts suggest that the mixing of air masses within the system with those above or ahead of the system on 29 June was no stronger than on 3 May, and thus the aerosol and gas contents at the ground may be strongly affected by the vertical mixing/dilution of the system as well as by local emission.

Ursodeoxycholic acid (UDCA) partly exerts choleretic effects by modifying the function of the bile salt export pump (Bsep, ABCB11). UDCA induces insertion of Bsep into the canalicular membrane of hepatocytes; however, underlying mechanisms remain unknown. We aimed to elucidate molecular mechanisms behind UDCA-induced Bsep activation.We established MDCK II cells stably expressing both Bsep and Na(+)-taurocholate cotransporting polypeptide, and investigated the effect of UDCA on activity and protein expression of Bsep using these cells. We performed inhibitor study to know the molecules involved in UDCA-induced Bsep activation, and also tested the influence of UDCA on Bsep having a disease-associated mutation.UDCA activated Bsep in a dose-dependent manner. UDCA did not affect Bsep protein expression in whole cell lysates but increased its apical surface expression by extending the half-life from 2.4 to 5.0 h. This effect was specific to Bsep because UDCA did not affect other apical and basolateral proteins, and was independent of protein kinase A, adenylate cyclase, p38(MAPK), phosphatidylinositide 3-kinase, Ca(2+), and microtubules. NorUDCA activated Bsep similar to UDCA; however, cholic acid, taurocholic acid, and tauroUDCA had no effect. UDCA significantly increased the activity of Bsep with a benign recurrent intrahepatic cholestasis 2 mutation (A570T) but did not affect Bsep with a progressive familial intrahepatic cholestasis 2 mutation (G982R or D482G).We demonstrated that UDCA stabilizes Bsep protein in the apical membrane and increases its activity in MDCK II cells, presumably by retarding the endocytotic process.

Aim In this multicenter, randomized trial, we evaluated the effectiveness of meloxicam – a non-steroidal anti-inflammatory drug – as an adjuvant for enhancing antiviral efficacy and preventing neutropenia during the treatment of patients with genotype 1 chronic hepatitis C using peginterferon and ribavirin. Methods A total of 60 patients were randomly assigned, in a 1:1 ratio, to either the meloxicam or the control group after stratification by neutrophil count. Both groups received weekly peginterferon-α-2a (180 μg) and a weight-based dose of ribavirin for 48 weeks. The meloxicam group received meloxicam (10 mg/day) for the first 8 weeks after initiation of treatment. Results Through intent-to-treat analysis, we found that the sustained virological response rate in the meloxicam group (19/30, 63.3%) was significantly higher than in the control group (11/30, 36.7%, P

The case of a patient with asymptomatic double common bile duct that was identified by chance is presented. A 41-year-old man underwent esophagogastroduodenoscopy(EGD) as part of a regular health checkup, during which he was found to have an elevated lesion in the lesser curvature of the upper gastric corpus with bile draining from its tip. Further examination led to a diagnosis of double common bile duct from the left intrahepatic bile duct to the opening into the stomach. Morphological abnormalities of the biliary tree are commonly encountered in everyday gastroenterological practice, but a double common bile duct with an ectopic opening into the stomach is comparatively rare. It is also associated with an increased risk of developing cancer of the stomach or bile duct, and as such is a biliary abnormality that must be treated with caution. This case is reported together with a discussion of the literature.

A 74-year-old woman undergoing outpatient follow-up for reflux esophagitis and atrophic gastritis tested positive for Helicobacter pylori and underwent primary eradication therapy with lansoprazole (LPZ) 30 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200 mg twice daily for 1 week in August 2012. A urea breath test (UBT) after this treatment revealed that eradication had failed. Secondary eradication therapy was carried out with esomeprazole (EPZ) 20 mg, AMPC 750 mg, and metronidazole (MNZ) 250 mg twice daily for 1 week, but this also failed. The third attempt at eradication consisted of EPZ 20 mg, AMPC 750 mg, and sitafloxacin (STFX) 100 mg twice daily for 1 week, but this also ended in failure. A fourth attempt using rabeprazole (RPZ) 20 mg (4 times daily) with MNZ 250 mg and STFX 100 mg twice daily for 2 weeks also failed, as did a fifth attempt in April 2015 using vonoprazan (VPZ) 20 mg, AMPC 750 mg, and MNZ 250 mg twice daily for 1 week. Eradication was finally successful after the sixth attempt, in which the patient was treated with vonoprazan 20 mg, MNZ 250 mg, and STFX 100 mg twice daily for 2 weeks.

A 60-year-old man received interferon/ribavirin combination therapy for chronic hepatitis C in 2002 and achieved sustained virological response. In 2008, a hepatocellular carcinoma (HCC) with a diameter of 60 mm appeared and surgical resection was performed. In March 2011, the patient was referred to our hospital because of portal lymph node swelling. Abdominal ultrasonography, dynamic CT and dynamic MRI did not show any tumors in the liver, but revealed portal lymph node swelling (18 × 11 mm). Taking the elevation of serum des-γ-carboxy prothrombin and alpha-fetoprotein levels, including the lectin-bound type, into consideration, we made the diagnosis of HCC metastasis to the portal lymph node. We started sorafenib therapy at a dose of 800 mg/day, but discontinued it after 11 days due to grade 3 hand-foot skin reaction and rash. In spite of treatment termination, portal lymph node swelling disappeared and the serum des-γ-carboxy prothrombin and alpha-fetoprotein levels normalized. We considered that our patient achieved complete response to sorafenib according to the Response Evaluation Criteria in Solid Tumors (RECIST). The patient maintains remission up to June 2012, more than 1 year after the discontinuation of sorafenib therapy. Sorafenib could be a good option for unresectable or recurrent HCC.

Fatty liver and male gonadal dysfunction are potential late effects of therapy in adult survivors treated with stem cell transplantation (SCT) in childhood. Obesity and metabolic syndrome also are associated with low serum testosterone levels in the general population. However, the relationship between the degree of fatty liver and changes in serum testosterone levels in adult survivors has not been fully studied. We reviewed the clinical records of 34 male patients who received allogeneic SCT in childhood or adolescence. The median age at SCT was 10.0 years, and the median follow-up after SCT was 15.9 years. All but one patient showed no tendency toward overweight/obesity during the follow-up period. Fatty liver was diagnosed by ultrasound in 15 patients at 4 to 20 years after SCT. Patients who received cranial radiation therapy before SCT were more likely to develop fatty liver and insulin resistance. Moreover, fatty liver was statistically associated with decreased serum testosterone levels, whereas nonfatty liver was not (median, 527 ng/dL [range, 168-944 ng/dL] versus 302 ng/dL [165-698 ng/dL]; P < .0001). Changes in testosterone levels after SCT are affected not only by primary gonadal dysfunction but also by subsequent development or exacerbation of fatty liver.

A 47-year-old female patient with type C liver cirrhosis underwent endoscopic injection sclerotherapy for esophageal varices 13 years ago. The patient had no past history of hysterectomy or any other gynecological disorders. She was admitted to our hospital because of persistent vaginal bleeding and exacerbation of anemia. A contrast-enhanced computed tomography scan revealed marked dilation of not only the inferior mesenteric vein, but also the left ovarian vein, the uterine vein and the internal iliac vein. A celiac arteriography showed that the blood in the splenic vein was flowing almost totally hepatofugally into the dilated inferior mesenteric vein. An ovarian venography demonstrated knob-shaped dilation of the left ovarian vein draining into the left internal iliac vein. A proximally wedged left ovarian venography visualized the right ovarian vein and the right internal iliac vein with contrast medium via a palisade venous plexus from the dilated uterine and ovarian veins. Partial splenic embolization (PSE) was performed to increase platelet count and to reduce splenic venous blood flow into the ovarian vein. Following the PSE, the platelet count increased, and the blood flow in the dilated ovarian vein and uterine vein diminished. In addition, the portal blood flow became hepatopetal, and remarkably increased. There has as yet been no case report in which vaginal bleeding developed in women with liver cirrhosis without any past history of hysterectomy or other gynecological disorders. The present case report may be warranted in view of the rarity of the condition.

Aim: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. Methods: We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600–1000 mg) and lower dose (400–800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. Results: A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6–89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5–78.2) patients in the lower-dose group (difference, −12.7%; 90% CI, −25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs

A 67-year-old male patient presenting with chronic hepatitis C (CHC) achieved a sustained virological response (SVR) following 6 months of treatment with 6 million units of beta-interferon (IFN). The SVR state continued for 6 years. Hepatocellular carcinoma (HCC) developed in liver segments 4 and 5, and was treated with transcatheter arterial chemoembolization, followed by radiofrequency ablation of the tumors. A recurrence of HCC occurred in segment 4 one and a half years after the initial treatment for HCC and a new tumor also developed in segment 8. These tumors were diagnosed to be recurrent HCC, and the three hepatic segments were resected. The pathological examination and immunostaining of the tumors revealed the tumor in segment 4 to be a well to moderately differentiated typical HCC. On the other hand, the tumor in segment 8 was a moderately to poorly differentiated adenocarcinoma and was diagnosed as an intrahepatic cholangiocellular carcinoma (ICC). HCC developed from CHC in a patient who achieved a 6-year SVR after IFN therapy, followed one and a half years later by the development of a heterochronous ICC at a different site, thus indicating the presence of HCC-ICC double cancer. This was an exceedingly rare and clinically important case in terms of the carcinogenic mechanism of HCC and ICC from a post-SVR CHC patient. We have to be aware of the possible development not only of HCC but of ICC after SVR in CHC patients.

エアロゾルゾンデとライダーを用いた成層圏エアロゾルの粒径分布,空間分布の観測を2002 03年と2007 08年の冬季に行った.2002 03年冬季は,ライダーにより10-15 kmの高度域で高い偏光解消度をもつエアロゾル層を検出した.その高度域で,エアロゾルゾンデ観測から導出したエアロゾルの有効半径は比較的大きい値(0.17-0.24 μm)を示した.気温は極成層圏雲が存在可能な温度よりも非常に高く,有効半径も大きいことから,エル・レベンタドール火山起源のエアロゾルの可能性が強いと思われた.2008年1月9日にライダーで観測した極成層圏雲の固体粒子と液滴粒子の温度履歴は,ほとんど同じ温度変化を示し,両者の違いは見られなかった.極成層圏雲の時間変化(空間分布),トラジェクトリー解析の結果から,グリーランドのような標高の高い地形効果による重力波等の影響により,小さい温度擾乱を受けた可能性を示唆していた., Balloon borne aerosol sonde observation and lidar observations were preformed at Ny-Alesund, Norway in the winters of 2002 03 and 2007 08. In the winter of 2002 03, the aerosol layers with the increment of depolarization ratio were observed at the lower stratosphere below 15 km height by lidar. The effective radius of stratospheric aerosol estimated from aerosol sonde observations showed high values of 0.17-0.24 μm in radius in the height range. The temperature in the height range was remarkably higher than the formation temperature of polar stratospheric cloud (PSC). The depolarized aerosol layer might be volcanic aerosol by the eruption of Mt. El Reventador. The average value of effective radius of stratospheric aerosol in the height range of 10-25 km was estimated to be 0.12 μm. In the winter of 2007 08, PSC events were frequently detected. Both solid and liquid PSC detected by lidar on January 9, 2008 showed that they experienced almost the same temperature history. They might be affected by meso-scale temperature perturbations such as gravity waves.

Contra - Rotating Hybrid Type Rudder Propeller is of the new development-type hybrid device ZP-41RP. It was installed in one of the overseas research purse seiners“Nippon-Maru”. The device consisted of one electromotive motor drive rudder propeller device belonging to in a conventional main engine drive variable-pitch propeller; and to the rear for a contra-propelling effect. We therefore here introduce the summary of the Contra - Rotating Hybrid Type Rudder Propeller.

Objective A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)–enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus–positive liver cirrhosis. Methods In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study. Results Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group. Conclusion Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.

A survey of 21,493 patients who visited our Health Check-up Center during the 6-year period from 2005 to 2010 was conducted for the endpoints of drinking situation and various lifestyle-related diseases. Males accounted for 57.2% (mean age: 53.2 ± 11.4) and females accounted for 42.8% (mean age: 52.5 ± 11.4) of patients surveyed. Patients with no drinking habit accounted for 24.8% and 62.9% of males and females, respectively, and a large gender difference was seen in drinking frequency. When examined by age group, drinking frequency was found to increase with age in males, but gradually decreased with age in females. An examination of alcohol consumption in males revealed that 23.5% had an ethanol conversion rate of 10 g/day, 19.1% had a rate of20 g/day, and 18.2% had a rate of40 g/day. Meanwhile, in females, 22.7% had a rate of ≤ 10 g/day, 7.6% had a rate of ≤ 20 g/day and 4.6% had a rate of ≤ 40 g/day. The association between lifestyle-related disease endpoints and alcohol consumption was next examined by multivariate logistic analysis. The association between drinking and body mass index (BMI) revealed an odds ratio of around 0.8 in patients who consumed ≤ 40 g/day and a significantly reduced frequency of obesity. The odds ratio of hypertension increased in a dose-dependent manner from 1.3 to 1.6 in patients who consumed ≥ 40 g/day. The frequency of high low-density lipoprotein cholesterol (LDL-C) was reduced in light drinkers and the odds ratio decreased from 0.77 to about 0.6 as alcohol consumption increased: The frequency of low high-density lipoprotein cholesterol (HDL-C) was similarly reduced in light drinkers, and the odds ratio decreased remarkably in a dose-dependent manner from 0.73 to 0.22 as alcohol consumption increased. The risk of triglycerides was reduced in light drinkers and was conversely significantly enhanced in heavy drinkers. In patients who consumed ≥ 20 g/day, the risk of impaired glucose tolerance increased significantly in a dose-dependent manner. Increased risk of hyperuricemia was seen even in light drinkers. and the odds ratio increased from 1.2 to 1.8 as alcohol consumption increased. The results of this cross-sectional study suggested that light drinking has a positive effect on BMI, LDL-C, HDL-C and triglycerides. On the other hand, heavy drinking was found to have a positive effect on LDL-C and HDL-C, but a negative effect on systolic blood pressure, triglycerides, fasting blood glucose and uric acid.

Alcohol intake leads to the distribution of alcohol and its metabolite, acetaldehyde throughout the blood and organs. Hepatic cirrhosis is associated with abnormal red blood cell morphology and function, particularly impaired red blood cell deformability. To investigate the effect of drinking on red blood cells in patients with hepatic cirrhosis, erythrocyte deformability was evaluated in response to alcohol and acetaldehyde tolerance. Erythrocyte deformability in 10 healthy and 15 cirrhotic subjects was examined by filterability of the red blood cells. Erythrocyte deformability decreased markedly in the cirrhosis group compared with the healthy group (p0.05). No significant change in erythrocyte deformability was observed in healthy or cirrhotic subjects due to ethanol 100 mM tolerance. Acetaldehyde tolerance elicited a significant decrease in erythrocyte deformability at 2 mM in the cirrhosis group (p0.05). Alcohol consumption in cirrhotic patients was suggested to worsen erythrocyte deformability and red blood cell function. Decreased erythrocyte deformability worsens microcirculation in the liver, resulting in more severe hepatic dysfunction.

A 71-year-old man was referred to us from another hospital for endoscopic treatment of a IIc lesion at the anterior wall of the lower body of the stomach. In November 2008, he underwent resection of this lesion with endoscopic submucosal dissection (ESD). Follow-up endoscopy revealed a IIc lesion in the posterior wall of the lower body of the stomach, and ESD was again performed in February 2009. At the same time, Helicobacter pylori was detected, and successful first-line eradication therapy was verified in May 2009. Subsequent follow-up endoscopy detected multiple ectopic and metachronous gastric cancers at three sites, all of which were endoscopically resected (quintuple gastric cancer). Although ectopic and metachronous recurrence of gastric cancer was detected immediately after H. pylori eradication, recurrence of gastric cancer has not been detected in the 5 years since eradication. Future directions include determining the time point at which the preventative effects of H. pylori eradication therapy appear against gastric cancer recurrence. We report our findings herein, along with a review of the related literature.

European studies have revealed that the ABCB11 c.1331T>C (V444A) polymorphism (rs2287622) C-allele frequency is higher among patients with drug-induced cholestasis. Given the low incidence of this disease, however, this association has not been sufficiently elucidated. We aimed to investigate the significance of this polymorphism in Japanese patients. We determined ABCB11 V444A polymorphism frequencies and HLA genotypes in two independent drug-induced cholestasis cohorts. Expression and taurocholate transport activity of proteins from 444A variants were analyzed using Madin-Darby canine kidney II cells. In cohort 1 (n = 40), the V444A polymorphism C-allele frequency (66%) was lower than that in controls (n = 190, 78%), but this difference was not significant (P = 0.09). In cohort 2 (n = 119), comprising patients with cholestatic (n = 19), hepatocellular (n = 74), and mixed (n = 26) liver injuries, the C-allele frequency was lower among patients with cholestatic liver injury (68%) than among those with hepatocellular (75%) or mixed liver injury (83%), although this difference was not significant. In cohort 1, HLA-A*0201 was observed more frequently in patients (22%) than in controls [11%; P = 0.003; odds ratio, 2.4 (95% confidence interval, 1.4-4.0)]. Taurocholate transport activity of 444A-encoded protein was significantly lower than that of 444V-encoded protein (81% of 444V, P < 0.05) because of the reduced protein stability. In conclusion, ABCB11 444A had slightly reduced transport activity, but it did not contribute to the occurrence of drug-induced cholestasis in Japanese patients. Therefore, genetic susceptibility to acquired cholestasis may differ considerably by ethnicity.

BackgroundThe incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive MethodsWe conducted a cross-sectional study in multi-institutions in Japan. Fasting plasma samples from PC patients (n = 360), chronic pancreatitis (CP) patients (n = 28), and healthy control (HC) subjects (n = 8372) without apparent cancers who were undergoing comprehensive medical examinations were collected. Concentrations of 19 PFAAs were measured by liquid chromatography-mass spectrometry. We generated an index consisting of the following six PFAAs: serine, asparagine, isoleucine, alanine, histidine, and tryptophan as variables for discrimination in a training set (120 PC and matching 600 HC) and evaluation in a validation set (240 PC, 28 CP, and 7772 HC).ResultsSeveral amino acid concentrations in plasma were significantly altered in PC. Plasma tryptophan and histidine concentrations in PC were particularly low, while serine was particularly higher than that of HC. The area under curve (AUC) based on receiver operating characteristic (ROC) curve analysis of the resulting index to discriminate PC from HC were 0.89 [95% confidence interval (CI), 0.86-0.93] in the training set. In the validation set, AUCs based on ROC curve analysis of the PFAA index were 0.86 (95% CI, 0.84-0.89) for all PC patients versus HC subjects, 0.81 (95% CI, 0.75-0.86) for PC patients from stage IIA to IIB versus HC subjects, and 0.87 (95% CI, 0.80-0.93) for all PC patients versus CP patients.ConclusionsThese findings suggest that the PFAA profile of PC was significantly different from that of HC. The PFAA index is a promising biomarker for screening and diagnosis of PC.

To study the relationship between adverse events (AEs), efficacy, and nursing intervention for sorafenib therapy in patients with hepatocellular carcinoma (HCC).We enrolled 37 consecutive patients with advanced HCC who received sorafenib therapy. Relationships among baseline characteristics as well as AE occurrence and tumor response, overall survival (OS), and treatment duration were analyzed. The nursing intervention program consisted of education regarding self-monitoring and AEs management, and telephone follow-up was provided once in 1-2 wk.A total of 37 patients were enrolled in the study, comprising 30 males (81%) with a median age of 71 years. The disease control rate at 3 mo was 41%, and the median OS and treatment duration were 259 and 108 d, respectively. Nursing intervention was given to 24 patients (65%). Every patient exhibited some kinds of AEs, but no patients experienced G4 AEs. Frequently observed AEsG2 included anorexia (57%), skin toxicity (57%), and fatigue (54%). Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years, presence ofG2 skin toxicity, and absence ofG2 hypoalbuminemia. The disease control rate in patients withG2 skin toxicity was 13/20 (65%), which was significantly higher compared with that in patients with no or G1 skin toxicity. Multivariate analysis revealed that nursing intervention andG2 skin toxicity were independent significant predictors for longer treatment duration.Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC. Nursing intervention contributed to better adherence, which may improve the efficacy of sorafenib.

Background: We previously reported that morphological abnormalities and the altered deformability of erythrocytes play important roles in disturbances of hepatic microcirculation associated with alcoholic liver disease. Methods: The subjects of this study were five patients with alcoholic liver cirrhosis, two patients with alcoholic fatty liver, and two healthy volunteers. Concentrating on erythrocyte morphology in the presence of alcoholic liver disease, we observed erythrocytes under a scanning electron microscope and examined their morphological changes in relation to the disease. Results: Among the five patients with alcoholic liver cirrhosis, stomatocytes accounted for about 14% and acanthocytes for about 10% of all erythrocytes. In the fatty liver group (n = 2), acanthocytes were absent, and stomatocytes accounted for 23% in one subject and 56% in the other, of the total. When the two patients with liver cirrhosis were examined over time, one of them was found to have 12% stomatocytes, 21% acanthocytes, and a filtration time of 14.7 sec at admission. Following 1 month of abstinence, this patient had 1% stomatocytes, 6% acanthocytes, and a filtration time of 10.4 sec, which were accompanied by improvements in peripheral blood parameters and liver function. In another patient with liver cirrhosis, there were no acanthocytes, 8% stomatocytes, and a filtration time of 5 sec at admission; this patient had 1% stomatocytes and a filtration time of 7.7 sec after 1 month of abstinence. In one patient with fatty liver who was examined over time, the percentage of stomatocytes was 56%, and the filtration time was 7.7 sec at admission; these parameters were 1% and 5.1 sec, respectively, after 1 month of abstinence. Conclusions: The present study revealed that stomatocytes and acanthocytes are morphologically abnormal erythrocytes observed in the presence of alcoholic liver disease. These abnormal forms of erythrocytes tended to normalize as peripheral blood parameters and liver function were improved by abstinence, which suggests that erythrocyte morphology is related to the pathophysiology of alcoholic liver disease.

Background: The effects of chronic alcohol intake on skeletal muscle are clinically observed as muscle cramps with decrease in the amount of muscle. It was clarified by expired gas analysis that acute alcohol load affects disturbed energy metabolism of skeletal muscle. We studied abnormal energy metabolism of skeletal muscles in alcoholic liver diseases using expired gas analysis. Methods: Subjects of the study were five inpatients with alcoholic liver disease (fatty liver: one case, hepatic fibrosis: one case, liver cirrhosis: three case). Expired gas analysis during exercise was performed using AEROMONITOR. Minute ventilation, oxygen consumption and carbon dioxide output were monitored, and anaerobic threshold (AT) and respiratory compensation point (RCP) were calculated. Results: The anaerobic threshold, which is the limit of the aerobic exercise, was significantly reduced in patients with alcoholic disease (p < 0.01). The respiratory compensation point, which is the limit of the metabolic compensation of intracellular lactic acidosis, was decreased (p < 0.01). Conclusions: The results of expired gas analysis during exercise indicate that the aerobic energy metabolism of skeletal muscle had been disturbed in alcoholic liver disease. The reduced RCP suggests that the lactate metabolism in skeletal muscle is also disturbed in alcoholic liver disease. Expired gas analysis during exercise allows determination of the amount of exercise required to treat liver diseases through analysis of AT.

Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but several other causes might play an important role in PVT pathogenesis. We present a case of alcoholic chronic pancreatitis complicated by acute extensive PVT. The patient was managed conservatively with danaparoid sodium at first, but the thrombosis gradually extended. We then tried radiological intervention using the direct transhepatic and transjugular intrahepatic postsystemic shunt approaches. Although we were able to successfully catheterize the percutaneous transhepatic portal vein (PTP), we could not achieve recanalization of the portal vein. Therefore, PTP catheterization and systemic intravenous infusion of urokinase and heparin was performed to prevent further progression of the thrombosis and cavernous transformation was finally achieved. Computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a pancreatic stone which had possibly induced dilatation of the tail duct and formation of a pancreatic pseudocyst and caused intractable pancreatitis. We performed endoscopic retrograde cholangiopancreatography and placed a stent in the pancreatic duct, which completely cured the pancreatitis. Retrospectively, the previous CT with curved multi-planar reconstruction was reviewed and a fistula was detected between the pancreatic pseudocyst and splenic vein. We concluded that the etiology of the PVT was not only inflammatory extension from pancreatitis but also a fistula between the pancreatic duct and the splenic vein.

Lidar measurements at Fairbanks, Alaska (64°49′N, 147°52′E) and Ny-Ålesund, Svalbard (78°54′N, 11°53′E) in December 1991 and January 1994,respectively, were made to monitor the distribution of stratospheric aerosols. The location of the Fairbanks lidar site is advantageous to observe the effect of the polar vortex margin to stratospheric aerosol density distributions, since the lidar was sometimes located inside and sometimes outside of the polar vortex due to its meandering motion. The lidar site at Ny-Ålesund is usually inside the polar vortex in winter. The comparison of measurements at Fairbanks and Ny-Ålesund has shown that polar vortex dynamics controls profiles of stratospheric aerosol content. Above about 20km there was little aerosol content when the lidar station was inside the polar vortex. The aerosol load on the local tropopause showed large changes, which would be associated with aerosols descending from the stratosphere to the troposphere near the margin of the polar vortex. At the end of February 1994,the aerosol content of layer peak at Fairbanks was apparently smaller than that at Ny-Ålesund even though both lidar stations were inside the polar vortex.

Polar stratospheric clouds (PSCs) were observed with lidar at Ny-Ålesund, Svalbard in the winter of 1994/1995. Compared with the temperature record over several years, the stratospheric temperature over Ny-Ålesund was very low in December and January in this winter. In the period when the PSCs were first observed in mid-December, a slight increase of stratospheric aerosols at the top side of the background aerosol layer was found. This increase can be understood as the first stage of PSC formation in the winter. The lidar-observed PSCs in this period are characterized by high variability in space and/or time. As a typical example of these features, an event on December 12,13 and 14 is presented. In this case two layers of scattering ratio and depolarization were observed within about one km of the vertical separation. The life time of the layers was only a few hours. The characteristics of the PSCs in this period cannot be simply explained by the NAT formation theory which has been widely accepted.

During maturation of hamster oocytes, the distribution of the endoplasmic reticulum (ER) and inositol 1,4,5-trisphosphate receptors (InsP3Rs) was found to change dramatically, as observed using confocal microscopy with DiI and electron microscopy for the ER and immunohistochemistry for InsP3Rs. In immature oocytes at the germinal vesicle (GV) stage, ER and InsP3Rs were located predominantly in several large masses near the surface and also in the perinuclear region near the surface. In contrast, fine ER networks and low-density InsP3Rs were present in the inner cytoplasm. The ER appeared to be formed as vesicles from annulate lamellae (AL) in the subcortical area. Rises in Ca2+ concentration occurred in the cytoplasm and the GV when immature oocytes were inseminated, but clear Ca2+ waves did not occur. Ca2+ rises began preferentially from the perinuclear region in response to low doses of serotonin or to uniform stimulation of InsP3Rs with photocleavage of caged InsP3. Serum also induced inhomogeneous Ca2+ release, shown by nonpropagating Ca2+ rises at multiple surface sites. Between the GV stage and prometaphase I the number and size of the surface ER masses increased, and the AL disappeared. This quantitative ER maturation was followed by a second step, spatial maturation. After prometaphase I, surface ER masses gradually dispersed to a number of much smaller ER clusters near the surface and, together with the perinuclear mass, were incorporated into thicker ER networks, resulting in a reticular pattern of the ER with small patches of InsP3Rs throughout the mature egg. The ER shifted to the peripheral surface with apposition to cortical granules. These developmental changes in ER Ca2+ stores may account, at least partly, for the acquisition of the ability of an egg to undergo normal fertilization.

The concentration of stratospheric aerosols observed with a lidar in Alaska increased from December 1991 to March 1992. The measurements suggested that particulate matter injectedinto the stratosphere through the eruption of Pinatubo (Philippines, June 1991) was transportedto high latitudes and descended there. The speed of descending motion of the aerosollayer in Alaska was about 50 m/day, which is larger than the value in mid-latitudes. Decaytrend of aerosol load disturbed by Pinatubo volcanic eruption was approximately insimillarwith the trend observed in Japan suggesting that global distribution of volcanic aerosols isaffected by dispersion of particles from low and high latitudes and particle descending in highlatitudes.

Stratospheric aerosols originating from the June 1991 explosive eruptions of Mt. Pinatubo has been observed at Fukuoka with a Nd:YAG lidar. Sudden increase of the aerosols in the vicinity just above the tropopause in July 1991 was followed by the appearance of extraordinary strong scattering layer around 21-22 km height. The volcanic aerosols stratified in two distinct layers merged into a broad layer when the background wind field changed from the easterlies to the westerlies and the bulk of the aerosols arrived. After having taken its maximum in the first winter the aerosol burden decreased monotonously. Superposed on the decrease we can read the seasonal variations associated with the seasonal variation in the wind field and the tropopause height also after the second year. Height of the center of gravity of the aerosols relative to the height of tropopause have been approaching gradually to a constant value.

A long-lasting series of transient rises in intracellular Ca2+ concentration ([Ca2+]i) were recorded with Ca2+ imaging during fertilization of bovine eggs matured in vivo or in vitro. The first Ca2+ response could be recorded in zona pellucida-free eggs within 1 min after sperm-egg contact, when a preceding slow [Ca2+]i rise reached 150-170 nM. The response had the peak of 565 ±32 nM (n=15; maximum 780 nM) and the duration of 4-6 min, being significantly larger and longer than any succeeding response (359 ± 12 nM, n=68; 2 min). The series of Ca2+ transients occurred at constant intervals of 19-20 min without attenuation in the magnitude for more than 9 h. Ca2+ transients became smaller progressively during pronuclear migration and nuclear envelope breakdown, and no response occurred in 2-cell embryo. In unfertilized eggs, injection of inositol 1, 4, 5-trisphophate (InsP3) induced a Ca2+ transient and the sulfhydryl reagent thimerosal caused repetitive Ca2+ transients. These responses were markedly inhibited or blocked by preinjection of a monoclonal antibody to the mouse InsP3 receptor. However, sperm-induced responses were not blocked in 2/3 of eggs examined. Another mechanism may be involved in addition to InsP3-induced Ca2+ release from intracelluar stores.

In this multicenter, randomized trial, we evaluated the effectiveness of meloxicam - a non-steroidal anti-inflammatory drug - as an adjuvant for enhancing antiviral efficacy and preventing neutropenia during the treatment of patients with genotype 1 chronic hepatitis C using peginterferon and ribavirin.A total of 60 patients were randomly assigned, in a 1:1 ratio, to either the meloxicam or the control group after stratification by neutrophil count. Both groups received weekly peginterferon-α-2a (180 μg) and a weight-based dose of ribavirin for 48 weeks. The meloxicam group received meloxicam (10 mg/day) for the first 8 weeks after initiation of treatment.Through intent-to-treat analysis, we found that the sustained virological response rate in the meloxicam group (19/30, 63.3%) was significantly higher than in the control group (11/30, 36.7%, P 0.05). The relapse rate was more than twice as high (45%) in the control group than in the meloxicam group (19.0%); however, this difference was not statistically significant. The rate of neutrophil decrease, calculated by dividing the lowest value observed during the first 8 weeks by pretreatment count, was significantly smaller in the meloxicam group (55.1 ± 14.3%) than in the control group (62.3 ± 9.6%, P 0.05).Meloxicam enhanced antiviral efficacy and reduced the decline in neutrophil counts for the peginterferon and ribavirin treatment of genotype 1 chronic hepatitis C. This drug could be a reasonable adjuvant for the treatment of patients with chronic hepatitis C. The present study including a small number of patients warrants larger clinical trials.

The patient, a 69-year-old man, had a chief complaint of hepatomegaly. The liver was palpated four fingerbreadths below the costal margin, and the spleen was three fingerbreadths below the costal margin. There were no other abnormal findings. Laparoscopy showed that the liver resembled an orange-yellow crayon in appearance and was nodular. The pathological findings of the liver biopsy tissue were consistent with liver cirrhosis. Inside the fibrous septum was an apparent aggregation of enlarged macrophages that phagocytosed lipid components, as well as enlarged Kupffer cells that phagocytosed lipid droplets. Electron microscopy showed the lipid droplets to have a moth-eaten appearance. Using monocytes extracted from the peripheral blood, acid lipase activity was measured by fluorescence spectrometry using 4-methylumbelliferone palmitate as a substrate. This patient's human lysosomal acid lipase activity was 0.020 nM/min per 10(6) cells, corresponding to 5.9% of that in healthy subjects (0.332 ± 0.066 nM/min per 10(6) cells). Cholesterol ester storage disease was therefore diagnosed. The acid lipase A base sequence obtained from leukocytes by direct sequencing was compared with a library. This patient had a point mutation of N250H/N250H in exon 7, a novel gene abnormality that has not previously been reported.

The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600-1000 mg) and lower dose (400-800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6-89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5-78.2) patients in the lower-dose group (difference, -12.7%; 90% CI, -25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41-7.92; P = 0.006). Twenty-one (36.2%) in the higher-dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower-dose group (P 0.01). Three of the higher-dose group and two of the lower-dose group required premature termination of therapy. Weight-based lower-dose ribavirin regimen was not equivalent to the higher-dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low-dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight-based higher dose (600-1000 mg) remains the standard-of-care treatment for this genotype.

The effect of an endothelin (ET) A receptor antagonist on hepatic hemodynamics in cirrhotic rats was examined.Portal pressure and hepatic tissue blood flow in cirrhotic rats were measured. Plasma ET-1 levels were determined by radioimmunoassay. BQ-123 was infused to these rats at a rate of 10 nmol/min. The sinusoids were observed by scanning electron microscopy. The localization of ET-1 and ETA receptors was examined using the indirect immunoperoxidase method.In cirrhotic rats, the portal pressure significantly increased to 16.6 ± 1.5 cm H2O, and the hepatic tissue blood flow markedly decreased. Plasma ET-1 levels in cirrhotic rats were higher than those in normal rats. When BQ-123 was infused, the portal pressure was significantly reduced by more than 2 cm H2O, compared with the control group (p0.05). Hepatic tissue blood flow was maintained at the level before infusion. In liver cirrhosis, the sinusoids were covered with continuous endothelial cells, and the number of sinusoidal endothelial fenestrae extremely decreased. ET-1 was remarkably enhanced in sinusoidal endothelial cells within the regenerating nodules, and the reaction products of ETA receptors were mainly recognized in hepatic stellate cells.The augmented action of ET-1 via the ETA receptor may be involved in the mechanism of portal hypertension in liver cirrhosis.

To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%–80%, and

We report on a case of multiple stress fractures in a high school Ekiden runner, caused by overuse. We concluded that the prevention and cure of multiple stress fractures requires early detection, the diffusion of knowledge and education of relevant participants about stress fractures and maintaining communication with managers and trainers.

Histological and clinical features of syncytial giant cell hepatitis (GCH) are rarely observed in adults, and the disease has been associated with several autoimmune disorders and drug reactions. We describe here the case of a 62-year-old woman who presented with evidence of severe acute hepatocellular injury and cholestasis. Serum work-up demonstrated antimitochondrial antibodies specific for primary biliary cirrhosis (PBC) autoantigens, whereas markers of viral infection including hepatitis viruses, paramyxovirus and measles virus were negative. Liver histology revealed the presence of multinucleated hepatocellular giant cells in the parenchymal areas surrounding bridging necrosis. Importantly, damaged interlobular bile ducts were also observed within the lymphocyte-infiltrated portal tracts. Further study using transmission electron microscopy demonstrated the presence of filamentous strands and particles resembling paramyxovirus nucleocapsids in the cytoplasm of syncytial giant cells. To our knowledge, this is the first case of PBC with histological and clinical evidence of syncytial GCH in an adult, and we submit that it might provide novel clues in the enigma of PBC pathogenesis.

We have attempted to determine serum levels of type IV collagen (IV-C), laminin (LM), prolylhydroxylase (PH), metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in chronic liver disease to elucidate the clinical significance of MMPs and TIMPs in the process of hepatic fibrosis.Serum samples were collected from 60 patients with chronic liver disease caused by hepatitis B or C. Serum levels of IV-C, LM, PH, MMP-1, 2 and 3, and TIMP-1 and 2 were measured by a one-step sandwich enzyme immunoassay using monoclonal antibodies. The values were correlated with Histology Activity Index (HAI) scores of liver biopsy specimens.LM and IV-C levels markedly increased in parallel with the progression of the chronic liver disease. The MMP-2 and MMP-3 levels tended to increase in chronic active hepatitis (CAH), and significantly elevated in liver cirrhosis (LC). There was a positive correlation between the IV-C and MMP-2 levels, and the ratio of IV-C to MMP-2 levels was significantly elevated in LC. Both TIMP-1 and TIMP-2 levels were markedly increased in LC. The HAI scores were positively correlated with the serum IV-C and MMP-2 levels.Serum IV-C and MMP-2 levels may be useful diagnostic markers for hepatic fibrosis, since they increased in parallel with the progression of chronic liver disease. In addition, the imbalances between IV-C, LM, and TIMP-1 and 2 as fibrogenic factors and MMP-2 and 3 as fibrolytic factors may lead to fibrosis in chronic viral liver disease, especially in cirrhosis.

[1] The Improved Limb Atmospheric Spectrometer (ILAS)-II on board the Advanced Earth Observing Satellite (ADEOS)-II observed stratospheric aerosol in visible/near-infrared/infrared spectra over high latitudes in the Northern and Southern hemispheres, intermittently from January to March and continuously from April through October 2003. This study assesses the data quality of ILAS-II version 1.4 (V1.4) aerosol extinction coefficient at 780 nm. In the Northern Hemisphere (NH), aerosol extinction coefficient (AEC) from ILAS-II agreed with extinctions from SAGE II and SAGE III within ±10% and with extinction from POAM III within ±15% at heights below 20 km. From 20 to 26 km, ILAS-II AEC was smaller than extinctions from the other three sensors; differences between ILAS-II and SAGE II ranged from 10% at 20 km to 34% at 26 km in the NH. Over the Southern Hemisphere (SH), ILAS-II AEC from 20 to 25 km in February was 12–66% below SAGE II extinction. The difference increased with increasing altitude. Comparisons between ILAS-II and POAM III from January to May in the SH (“non-PSC season”) yielded qualitatively similar results. From June to October (“PSC season”), ILAS-II extinction was also smaller than POAM III extinction above 17 km; however, ILAS-II extinction agreed with POAM III extinction to within ±15% from 12 to 17 km during the PSC season. The comparisons indicate that in both hemispheres the ILAS-II V1.4 AEC is comparable to extinctions from other measurements below approximately 20 km and systematically low above approximately 20 km although the mean difference is as small as ∼2 × 10−5 km−1 during the non-PSC season.

Actual condition of alcohol intake was investigated in forty four thousand one hundred and twenty six individuals who visited the Tokai University Hospital Health Checkup Center from 1989 to 2003. Effects of alcohol intake were also examined in relation to several risk factors for lifestyle-related diseases. The male drinkers who took more than 1 gou of sake per a day were recognized in 53.0% from 1989 to 1991, and decreased to 46.3% from 2001 to 2003. The female drinkers were found in approximately 10%, and remained unchanged during the 15-year survey period. When examined by age, the frequency of habitual drinking among males was 34.4% in the age of 20 years, and then increased to 45% in the 30 years, leading to the peak (54.1%) in the 40 years. In females, the frequency was 27.5% in the age of 20 years, but decreased to 10.9% in the 30 years. The prevalence of systolic hypertension, diastolic hypertension, hyperuricemia, high levels of HbAlc, and hypertriglyceridemia was significantly (P0.0001) increased with an increase in alcohol intake. The prevalence of obesity, fatty liver and hyperglycemia at fasting was markedly (P0.0001) increased in the drinkers whose intake was more than 2 gou per a day. These findings indicate that habitual drinking may be associated with risk factors for lifestyle-related diseases, such as obesity, fatty liver, hypertension, hypertriglyceridemia and hyperuricemia.

To elucidate the mechanisms of thrombocytopenia in alcoholic liver diseases, we investigated activation status of platelets in patients with alcoholic fatty liver (Al-FL), alcoholic liver cirrhosis (Al-LC) or hepatitis-C liver cirrhosis C (C-LC).Platelet activation was evaluated by flow cytometry using monoclonal antibodies against P-selectin (CD62P) and the fibrinogen receptor (PAC-1), both specific for platelet activation, and anti-CD61 antibody for the presence of microparticles (PMP) in seven patients with Al-FL, thirteen patients with Al-LC and, as a non-alcoholic liver disease control, nine patients with C-LC. As a normal control, seventeen healthy subjects without liver dysfunction were also evaluated.Compared with the healthy controls, the platelet count was significantly decreased in patients with alcoholic liver diseases or C-LC. Ten days after discontinuation of alcohol intake, the platelet count was significantly higher in both the Al-FL and Al-LC groups than that measured on admission. There was an inverse correlation between the platelet count and PMP, a marker of platelet activation. The Al-FL, Al-LC and C-LC groups showed significantly higher percentages of platelets positive for CD62P than the healthy controls. The PAC-1 positivity was increased only in the C-LC group. PMP were significantly increased in the Al-FL, Al-LC and C-LC groups compared to that in the healthy group. In the Al-LC group, PMP were significantly decreased 10 days after discontinuation of alcohol intake from that measured on admission.Patients with alcoholic liver diseases have increased platelet activation, which may contribute to the occurrence of thrombocytopenia. The formation of PMP might be one of the important factors of thrombocytopenia in alcoholic liver diseases.

We assessed changes in skeletal muscle energy metabolism by 31P-magnetic resonance spectroscopy (31P-MRS) and oxygen supply by near-infrared spectroscopy (NIR), after exercise and after administration of glucose and a branched-chain amino acids (BCAA), in healthy volunteers and patients with liver cirrhosis. As for the patients with liver cirrhosis, 4 were classified in Child-Pugh Grade A and the other 4 in Grade B. In patients with liver cirrhosis, the intramuscular pH and PCr index (PCr/PCr + Pi) were lower than in healthy subjects after exercise in the fasting state; the deltapH and deltaPCr index were statistically siginificant (p0.05), indicating a disorder of aerobic metabolism. NIR revealed normality with oxygen supply and suggested a decreased oxygen utilization efficiency; that is, failure of the TCA cycle. The deltapH improved slightly after the administration of glucose alone, while it was definitely low (p0.05) after co-administration of glucose and BCAA, which acts directly on the TCA cycle, indicating improvement of skeletal muscle energy metabolism.

Background: The chronic intake of alcohol affects the function of skeletal muscles. To elucidate the influence of acute alcoholic load on muscular metabolism during exercise, we analyzed expired gases to measure the volume of consumed oxygen and the volume of exhaled CO 2 . Methods: Healthy volunteers were enrolled for the study. For the exercise test, they were asked to rest for 5 min, warm up on an aerohike at 20 W for 2 min, and then gradually increase the load by 2 W every 6 sec. On another day, they were asked to drink 0.5 to 0.6 g/kg ethanol in 30 min, rest for 30 min, and then do the test. The expired gas analysis was used to measure changes in the anaerobic threshold and the respiratory compensation point. The blood concentrations of lactate, ethanol, and acetate also were measured. Results: The anaerobic threshold showed no significant change in the case of exercise without alcoholic load. The respiratory compensation point decreased significantly in the case of alcoholic load (p < 0.001). and the interval from the anaerobic threshold to the respiratory compensation point decreased (p < 0.02). The blood concentration of lactate increased, after alcoholic load, to a level significantly higher than the level measured before the alcoholic load (p < 0.001). It showed a marked increase immediately after exercise stress (p < 0.001). The blood concentration of acetate tended to decrease after exercise load, but no significant change was noted. Conclusions: The anaerobic threshold, which is the limit of the aerobic glycolytic system (i.e., the so-called aerobic exercise limit) was not influenced by exercise under an acute alcoholic load. However, after the production of lactate started, the respiratory compensation point, which is the limit of the metabolic compensatory action, appeared earlier. This suggested that the intake of alcohol would influence the energy metabolism of skeletal muscles by a mechanism in which the disturbed metabolism of lactate in skeletal muscles was mainly involved.

We have speculated that the degree of liver dysfunction in alcoholic liver disease with ALDH2*1/2*2 may be less pronounced than that with ALDH2*1/2*1. In the present study, outpatients with alcoholic liver injury were examined for ALDH2 genotype and biochemical data. The number of patients was 29 cases of nonspecific changes, 16 cases of fatty liver, 5 cases of liver fibrosis, and 44 cases of liver cirrhosis. Biochemical data were evaluated with ALDH2 heterozygotes data obtained by PCR-SSCP. The ALDH2*1/2*1 and ALDH2*1/2*2 genotypes accounted for 90% and 10%, respectively. As for ALDH2*1/2*2, there were three patients with nonspecific changes, three with fatty liver, one with liver fibrosis, and two with liver cirrhosis. In alcoholic liver disease patients, when the ALDH2*1/2*2 genotype was compared with the ALDH2*1/2*1 genotype with biochemical data, the γ-GTP value in patients with ALDH2*1/2*2 was significantly higher than with ALDH2*1/2*1 (p < 0.005). When the frequency of ALDH2 genotype was determined in patients with alcoholic liver injury, ALDH2 heterozygotes accounted for 15% for the non-cirrhosis group, and 5% for the cirrhotic group. When a relationship between the amount of ethanol intake and biochemical data were determined in patients with alcoholic liver injury who have ALDH2 heterozygotes, the glutamic oxaloacetic transaminase (GOT) and γ-GTP values were significantly higher at an ethanol intake amount of ethanol more than 100 g per day than intake less than 100 g per day (p < 0.05). The alcoholic patients with ALDH2*1/2*2 drink a slight amount of ethanol, the liver injury is found to be stronger than those with Al DH2*1/2*1 when they drink more than 100 g ethanol per day.

Background & Aims Although a low plasma level of branched-chain amino acids (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect disease progression. We performed a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and survival in patients with cirrhosis. Methods We enrolled 299 patients from 14 medical institutions in Japan in a prospective, multicenter study in 2009; 267 patients were followed through 2011. Patients were given BCAA supplements (5.5–12.0 g/day) for more than 2 years (n = 85) or no BCAAs (controls, n = 182). The primary end points were onset of hepatocellular carcinoma (HCC) and death. Factors associated with these events were analyzed by competing risk analysis. Results During the study period, 41 of 182 controls and 11 of 85 patients given BCAAs developed HCC. On the basis of the Cox and the Fine and Gray models of regression analyses, level of α-fetoprotein, ratio of BCAA:tyrosine, and BCAA supplementation were associated with development of HCC (relative risk for BCAAs, 0.45; 95% confidence interval, 0.24–0.88; P = .019). Sixteen controls and 2 patients given BCAAs died. Factors significantly associated with death were Child–Pugh score, blood level of urea nitrogen, platelet count, male sex, and BCAA supplementation (relative risk of death for BCAAs, 0.009; 95% confidence interval, 0.0002–0.365; P = .015) in both regression models. Conclusions On the basis of a prospective study, amino acid imbalance is a significant risk factor for the onset of HCC in patients with cirrhosis. BCAA supplementation reduces the risk for HCC and prolongs survival of patients with cirrhosis.

A rare case of chondroma of the diaphragm is reported. The patient was a 23-year-old female who had had recurrent upper abdominal pain for 4 years. Her symptoms and physical findings on admission suggested an intra-abdominal tumor. Roentgenological study disclosed a mass with a thick calcified wall in the upper abdomen. Laparoscopy revealed a multinodular white mass protruding from the left hemidiaphragm. The mass was surgically enucleated from the diaphragm. The resected tumor had a thick, calcified wall and a narrow lumen containing colorless fluid. Microscopic examination disclosed a hyaline chondroid matrix with mature chondrocytes, as well as extensive ossification. Primary tumor of the diaphragm is an uncommon disease. Only one case of chondroma of the diaphragm has been reported in the literature. Laparoscopy was useful in confirming the tumor's location and in speculating on its nature.