[A case of hepatic portal venous gas and upper gastrointestinal mucosal injury due to accidental ingestion of hydrogen peroxide].

A 40-year-old woman was admitted to our hospital by ambulance due to accidental ingestion of 100ml of 35% hydrogen peroxide. Although the patient suffered from frequent vomiting, abdominal distension, and abdominal pain, signs of peritonitis were not observed. An abdominal computed tomography examination demonstrated obvious gas images in the gastric wall and intrahepatic portal veins. Upper gastrointestinal endoscopy revealed mucosal redness, swelling, and erosion from the lower part of the esophagus to the duodenum. Portal venous gas and upper gastrointestinal mucosal injury due to accidental hydrogen peroxide ingestion were suspected. As the vital signs were stable and there were no signs peritoneal irritation or neurological symptoms, she was treated medically with vonoprazan, rebamipide, and sodium alginate. The next day, abdominal symptoms immediately improved and 3 days later, hepatic portal venous gas had disappeared on ultrasonography. She was discharged on the 5th day after admission. Two months later, upper gastrointestinal endoscopy showed improvement in inflammatory findings. We report a remarkable case of hepatic portal venous gas and upper gastrointestinal mucosal injury and elucidate the endoscopic findings associated with hydrogen peroxide ingestion.

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy.

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.

Ipragliflozin Ameliorates Liver Damage in Non-alcoholic Fatty Liver Disease.

BACKGROUND: There are few effective medications for non-alcoholic steatohepatitis (NASH). We investigated the efficacy of ipragliflozin (selective sodium-glucose cotransporter-2 inhibitor [SGLT2I]) for the treatment of patients with type 2 diabetes mellitus (T2DM) complicated by non-alcoholic fatty liver disease (NAFLD). METHODS: We prospectively enrolled patients with T2DM complicated by NAFLD treated at our institutions from January 2015 to December 2016. Patients received oral ipragliflozin (50 mg/day) once daily for 24 weeks. Body composition was evaluated using an InBody720 analyzer. We used transient elastography to measure liver stiffness and the controlled attenuation parameter for the quantification of liver steatosis in patients with NASH. RESULTS: Forty-three patients with T2DM and NAFLD were enrolled (12 with biopsy-proven NASH and 31 with NAFLD diagnosed by ultrasonography). After 24 weeks, body weight, hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase, body fat mass, and steatosis were significantly decreased compared to baseline measurements in patients with NASH. However, muscle mass was not reduced, and liver stiffness showed a statistically insignificant tendency to decrease. NAFLD patients also showed a significant reduction in body weight, HbA1c, AST, and ALT compared to baseline measurements. CONCLUSION: Ipragliflozin may be effective in patients with T2DM complicated by NAFLD.

Cigarette smoking is a risk factor for the onset of fatty liver disease in nondrinkers: A longitudinal cohort study.

BACKGROUND: The effect of cigarette smoking on the onset of nonalcoholic fatty liver disease (NAFLD) is unclear, especially that associated with drinking small amounts of alcohol. We conducted a longitudinal study to investigate the relationship between cigarette smoking and NAFLD onset, which was stratified according to the amount of alcohol consumed. METHODS: We enrolled 7,905 Japanese subjects who had received annual health checkups more than twice between April 2003 and August 2013, 4,045 of whom met at least one of the following exclusion criteria and were excluded: (a) fatty liver at baseline; (b) hepatitis B or hepatitis C; (c) alcohol consumption (men: ≥210 g/wk; women: ≥140 g/wk); (d) change in alcohol drinking status between baseline and the study's endpoint; (e) change in cigarette smoking habits between baseline and the study's endpoint; or (f) current treatment with antidiabetic agents, antihypertensive agents, and/or lipid-lowering agents. The remaining 3,860 subjects (1,512 men, 2,348 women) were divided into two groups based on average alcohol consumption. RESULTS: After adjusting for the variables associated with metabolic disease, smoking was associated with fatty liver disease onset compared with nonsmokers in nondrinkers (adjusted hazard ratio = 1.988, 95% confidence interval 1.057-3.595; p = 0.034). No association was found between smoking and fatty liver disease onset in the low alcohol consumption group (men: <210 g alcohol/week; women: <140 g alcohol/week). The fatty liver disease incidence increased significantly among the nondrinkers as the number of cigarettes smoked increased (p = 0.001). CONCLUSIONS: Cigarette smoking may be a significant risk factor associated with NAFLD onset in nondrinkers. These results may help clinicians to identify patients who are at a high risk of developing NAFLD and to prevent the progression of NAFLD by promoting earlier interventions that help people discontinue unhealthy lifestyle habits.

Dietary intake habits and the prevalence of nocturia in Japanese patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: No reports have been published on the association between dietary intake habits and nocturia in the diabetes population. We therefore evaluated this issue among Japanese patients with diabetes mellitus. MATERIALS AND METHODS: Study participants in the present study were 785 Japanese patients with type 2 diabetes mellitus. Self-administered questionnaires were used to assess each type of dietary intake habit. Vegetable intake habit was assessed by the following question: "Do you have vegetables or seaweed every day?" We used the following two outcomes: (i) nocturia: ≥2 voids per night; and (ii) severe nocturia: ≥3 voids per night. Adjustment was made for age, sex, body mass index, glycated hemoglobin, hypertension, dyslipidemia, smoking, drinking, exercise habit, stroke, ischemic artery disease, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy. RESULTS: The prevalence of nocturia, severe nocturia, and vegetable intake habit was 39.9%, 14.4% and 67.3%, respectively. After adjusting for confounding factors, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted odds ratios were 0.67 (95% confidence interval [CI] 0.48-0.94) and 0.46 (95% CI 0.30-0.71), respectively. Among male patients, vegetable intake habit was independently inversely associated with severe nocturia, but not nocturia: the adjusted OR was 0.51 (95% CI 0.29-0.88). Among female patients, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted ORs were 0.44 (95% CI 0.24-0.79) and 0.34 (95% CI 0.15-0.78), respectively. CONCLUSIONS: We found an inverse association between vegetable intake habit and nocturia in Japanese patients with type 2 diabetes mellitus.

Primary Type3 (Non-ABC, Non-GCB) Subtype of Extranodal Diffuse Large B-Cell Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization.

Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of mostly neoplastic transformation of germinal center-like B cells (GCB) or memory B cells. Other B-cell-type malignancies arising primarily in the thyroid have rarely been described. Immunohistochemical examination of autopsied primary malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL) without the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B-cell (ABC) subtype, and the detection of an extremely aggressive yet local clinical phenotype demonstrated that the present case was an exceptional entity of the type3 (non-GCB and non-ABC) subtype.

Macrovascular Complications and Prevalence of Urgency Incontinence in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

Objective Macrovascular diseases and urgency incontinence are common among Japanese patients with type 2 diabetes mellitus. However, little evidence exists regarding the association between stroke and urgency incontinence among patients with type 2 diabetes mellitus. We examined the associations between macrovascular complications and urgency incontinence among Japanese patients with type 2 diabetes mellitus. Methods The study subjects were 818 Japanese patients with type 2 diabetes mellitus. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate?" We adjusted our analyses for sex, age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, glycated hemoglobin, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy. Results The prevalence of urgency incontinence was 9.2%. Stroke was independently positively associated with urgency incontinence, with an adjusted odds ratio of 2.34 (95% confidence interval: 1.03-4.95). The associations between ischemic heart disease or peripheral artery disease and the prevalence of urgency incontinence were not significant. Conclusion In Japanese patients with type 2 diabetes mellitus, stroke, but not ischemic heart diseases or peripheral artery disease, was independently positively associated with urgency incontinence.

Self-reported sitting time and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

AIMS: No evidence exists regarding the association between sitting time and erectile dysfunction (ED) among patients with type 2 diabetes mellitus. The aim of this study was to evaluate the association between self-reported sitting time and ED among patients with type 2 diabetes mellitus. METHODS: Study subjects were 430 male Japanese patients with type 2 diabetes mellitus (mean age, 60.5years). A self-administered questionnaire was used to collect information on the variables under study. The study subjects were asked about time spent sitting during typical 24-hour periods over the past 12months. Subjects were divided into four groups according to self-reported sitting time: 1) <5hours, 2) 5-7hours, 3) 7-9hours, and 4) ≥9hours. ED was defined as present when a subject had a Sexual Health Inventory for Men score <8. Adjustment was made for age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, coronary artery disease, stroke, glycated hemoglobin, walking habit, and diabetic neuropathy. RESULTS: The prevalence values of moderate to severe ED and severe ED were 36.1% and 49.8%. At least 9hours sitting was independently positively associated with severe ED but not moderate to severe ED; the adjusted OR was 1.84 (95% CI: 1.06-3.33). In the multivariate model, there was a statistically significant inverse exposure-response relationship between the self-reported sitting time and severe ED (p for trend=0.029). CONCLUSIONS: Self-reported sitting time may be positively associated with ED in Japanese patients with type 2 diabetes mellitus.

Smoking and prevalence of nocturia in Japanese patients with type 2 diabetes mellitus: a post-hoc analysis of The Dogo Study.

AIMS: No evidence exists regarding the association between smoking status and nocturia among patients with type 2 diabetes mellitus. We evaluated this association among Japanese patients with type 2 diabetes mellitus by post-hoc analysis. METHODS: Study subjects were 817 Japanese patients with type 2 diabetes mellitus. Study subjects were considered to have nocturia if they answered "once or more" to the question: "Within one week, how many times do you typically wake up to urinate from sleeping at night until waking in the morning?" We used the following three outcomes: (1) nocturia was ≥1 voids per night; (2) moderate nocturia was ≥2 voids per night; and (3) severe nocturia was ≥3 voids per night. Adjustments were made for age, sex, body mass index, hypertension, dyslipidemia, stroke, glycated hemoglobin, current drinking, use of anti-hypertensive agent, use of insulin, use of oral anti-hyperglycemic agent, and diabetic retinopathy. RESULTS: The prevalence values of one void per night, two voids per night, and three or more voids per night were 39.5%, 27.1%, and 14.8%, respectively. Current smoking was independently inversely associated with severe nocturia compared with never or former smoking; the adjusted PR was 0.47 (95%CI: 0.25-0.89). Among the 443 patients who had ever smoked, compared with former smoking, current smoking was independently inversely related to severe nocturia; the adjusted PR was 0.44 (95%CI: 0.24-0.82). CONCLUSIONS: In Japanese patients with type 2 diabetes mellitus, current smoking may be independently inversely associated with severe nocturia.

Alcohol consumption and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: Baseline data from the Dogo Study.

Diabetes mellitus and heavy alcohol consumption are both associated with vascular disease, a category that includes erectile dysfunction (ED). However, the association between alcohol consumption and ED among patients with type 2 diabetes mellitus remains unclear. The aim of the present multicenter cross-sectional study was to investigate the relationship between drinking frequency, weekly alcohol consumption, daily alcohol consumption, and ED among Japanese patients with type 2 diabetes mellitus. Study subjects were 340 male Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. ED was defined as present when a subject had a Sexual Health Inventory for Men score <8. Adjustment was made for age, body mass index, duration of type 2 diabetes mellitus, current smoking, hypertension, dyslipidemia, glycated hemoglobin, stroke, coronary artery disease, diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. The prevalence of ED was 43.2% (147/340). The frequency of alcohol consumption and weekly alcohol consumption were independently inversely associated with ED (p for trend p = 0.001 and 0.004, respectively). The relationship between daily alcohol consumption and ED was an inverted J-shaped curve: alcohol consumption of less than 60 g, but not 60 g or more, per day was independently related to a lower prevalence of ED (p for quadratic trend = 0.003). In Japanese men with type 2 diabetes mellitus, an inverted J-shaped relationship between daily alcohol consumption and ED was observed, while frequency of alcohol consumption and weekly alcohol consumption were significantly inversely associated with ED.

Microvascular Complications and Prevalence of Nocturia in Japanese Patients With Type 2 Diabetes Mellitus: The Dogo Study.

OBJECTIVE: To evaluate the association between microvascular complications and nocturia among Japanese patients with type 2 diabetes mellitus. METHODS: Study subjects were 731 Japanese patients with type 2 diabetes mellitus. A self-administered questionnaire was used to collect information on the variables under study. Study subjects were considered to have nocturia if they answered "once or more" to the question: "How many times do you typically wake up to urinate from sleeping at night until waking in the morning?" Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, the absence of the Achilles reflex, or abnormal vibration perception. Diabetic nephropathy was defined as positive when the estimated glomerular filtration rate was <30 mL/min/1.73 m(2) and/or the urine albumin-to-creatinine ratio was ≥34 mg/mmol creatinine. Several ophthalmology specialists were responsible for evaluating diabetic retinopathy. Adjustment was made for sex, age, body mass index, duration of diabetes mellitus, current smoking, current drinking, hypertension, stroke, ischemic heart disease, and glycated hemoglobin. RESULTS: The prevalence of nocturia was 80.4%. Diabetic retinopathy was independently positively associated with nocturia (adjusted odds ratio 2.39 [95% confidence interval: 1.08-6.11]). In contrast, diabetic nephropathy or diabetic neuropathy was not associated with nocturia. CONCLUSION: In Japanese patients with type 2 diabetes mellitus, only diabetic retinopathy was independently positively associated with nocturia.

Serum lipoprotein(a) levels and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus.

AIMS: We aimed to evaluate the association between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. METHODS: This study included 581 patients with type 2 diabetes mellitus. Serum Lp(a) levels were divided into four groups; the cut-off points were at the 30th, 60th, and 90th percentile values on the basis of the distribution for all subjects. Diabetic nephropathy was defined as present when the urinary albumin-creatinine ratio was ≥33.9mg/mmol creatinine and/or the estimated glomerular filtration rate was <30ml/min/1.72m(2). Adjustment was made for age, sex, body mass index, hemoglobin A1c, duration of diabetes mellitus, current drinking, current smoking, hypertension, dyslipidemia, coronary heart disease, and stroke. RESULTS: Higher serum Lp(a) levels were significantly associated with a higher prevalence of diabetic nephropathy: the adjusted odds ratios (95% confidence intervals) for diabetic nephropathy in relation to serum Lp(a) levels of ≤6, 7-15, 16-38, and ≥39mg/dl were 1.00 (reference), 2.74 (1.08-7.00), 3.31 (1.28-8.54), and 4.80 (1.57-14.60), respectively (P for trend=0.004). CONCLUSIONS: The results suggest that serum Lp(a) levels may be positively associated with diabetic nephropathy among Japanese patients with type 2 diabetes mellitus.

Microvascular complications and prevalence of urgency incontinence in Japanese patients with type 2 diabetes mellitus: The dogo study.

AIMS: Diabetes was significantly positively associated with urgency incontinence in several epidemiological studies. We examine the association between diabetic neuropathy, which we defined based on neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception, and urgency incontinence among Japanese patients with type 2 diabetes mellitus. METHODS: Study subjects were 742 Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate ?". Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception. Adjustment was made for sex, age, body mass index, duration of type 2 diabetes mellitus, current smoking, hypertension, dyslipidemia, glycated hemoglobin, stroke, coronary artery disease, insulin therapy, diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. RESULTS: The prevalence of urgency incontinence was 8.6%. Diabetic neuropathy was independently positively associated with urgency incontinence: the adjusted OR was 2.20 (95%CI: 1.16-4.36). Associations between diabetic retinopathy or nephropathy and the prevalence of urgency incontinence were not significant. CONCLUSIONS: In Japanese patients with type 2 diabetes mellitus, only diabetic neuropathy was independently positively associated with urgency incontinence. Neurourol. Urodynam. 35:1024-1027, 2016. © 2015 Wiley Periodicals, Inc.

Association between subclinical hypothyroidism and diabetic nephropathy in patients with type 2 diabetes mellitus.

Subclinical hypothyroidism (SCH) has been associated with type 2 diabetes mellitus. However, it is unknown whether common complications of type 2 diabetes, such as diabetic nephropathy, are also present with SCH. Here, we investigated the association between SCH and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. In this multicenter cross-sectional study, we recruited 414 such patients who had no previous history of thyroid disease. Serum thyroid hormone levels and the urinary albumin:creatinine ratio were measured. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (>4.0 mIU/L), and diabetic nephropathy was defined as urinary albumin/creatinine ratio ≥300 mg/g. The prevalence of SCH was 8.7% (n = 36) among patients with type 2 diabetes mellitus. The SCH group had a higher prevalence of dyslipidemia (p = 0.008) and diabetic nephropathy (p = 0.014) than the euthyroid group. Multivariate analysis identified significant positive associations between diabetic nephropathy and SCH (odds ratio [OR], 3.51; 95% confidence interval [CI], 1.10-10.0; p = 0.034), hypertension (OR, 4.56; 95% CI, 1.69-14.7; p = 0.001), and smoking (OR, 3.02; 95% CI, 1.14-7.91; p = 0.026). SCH may be independently associated with diabetic nephropathy in Japanese patients with type 2 diabetes mellitus.

Nocturnal intermittent hypoxia as an associated risk factor for microalbuminuria in Japanese patients with type 2 diabetes mellitus.

OBJECTIVE: We estimated the prevalence of nocturnal intermittent hypoxia, a surrogate marker of obstructive sleep apnoea, among type 2 diabetes mellitus (T2DM) patients and examined the association between nocturnal intermittent hypoxia and microvascular diseases. DESIGN AND METHODS: We recruited 513 Japanese patients (292 men and 221 women) with T2DM. Nocturnal intermittent hypoxia was diagnosed using the 3% oxygen desaturation index, with less than five events per hour corresponding to normal and five events or more per hour corresponding to nocturnal intermittent hypoxia. RESULTS: The prevalence of nocturnal intermittent hypoxia was 45.4% among T2DM patients. The nocturnal intermittent hypoxia group was older and had a higher BMI, greater weight change since the age of 20 years, higher smoking rate and increased prevalence of hypertension, hyperlipidaemia, microalbuminuria and macroalbuminuria. Microalbuminuria (model 1: odds ratio (OR), 3.41; 95% CI, 1.85-6.40; model 2: OR, 3.69; 95% CI, 1.85-7.59 and model 3: OR, 3.12; 95% CI, 1.45-6.95) and nephropathy (model 1: OR, 4.51; 95% CI, 1.58-15.1; model 2: OR, 7.31; 95% CI, 2.11-31.6 and model 3: OR, 5.23; 95% CI, 1.45-23.8) were derived as factors from all the three statistical models and constantly associated with nocturnal intermittent hypoxia only in women. CONCLUSIONS: Nocturnal intermittent hypoxia was highly prevalent among T2DM patients and may be an independent associated risk factor for microalbuminuria in Japanese women with T2DM.

Clinical course of tuberculous peritonitis determined by laparoscopy.

We describe laparoscopic findings of tuberculous peritonitis in a 68-year-old man and those at follow-up 8 months later. The initial laparoscopic findings revealed typical yellowish-white nodules on the liver surface, and histological findings showed granulomas with caseous necrosis. Laparoscopy 8 months later showed that anti-tubercular drugs had diminished the nodules and adhesions with a fibrin net appearance were evident. Laparoscopy and biopsy are useful for a rapid diagnosis of tuberculous peritonitis.

Practical synthesis of a key intermediate for lactacystin from (R)-4-hydroxymethyl-2-phenyl-4,5-dihydrooxazol-4-ylmethyl acetate.

A practical synthesis of a key intermediate for the proteasome inhibitor lactacystin from (R)-4-hydroxymethyl-2-phenyl-4,5-dihydrooxazol-4-ylmethyl acetate was established. (R)-4-Hydroxymethyl-2-phenyl-4,5-dihydrooxazol-4-ylmethyl acetate is a useful chiral building block for the synthesis of biologically active compounds containing alpha-substituted alpha-amino acid moieties.

Budd-Chiari syndrome associated with hypereosinophilic syndrome; a case report.

A 27-year-old man was admitted due to abdominal fullness. He had ascites and subcutaneous nodules on his head, with liver dysfunction and eosinophilia. Abdominal imaging revealed obstruction of the hepatic veins and stenosis of the inferior vena cava. Histological diagnosis of a subcutaneous nodule revealed obstructive thrombophlebitis with eosinophils. Tyrosine kinase created by fusion of the FIP1L1 and PDGFRA genes, which is characteristic of hypereosinophilic syndrome (HES), was detected. He was diagnosed with Budd-Chiari syndrome associated with HES. Liver function tests improved after interventional therapy followed by steroid therapy. It is important to diagnose the cause of Budd-Chiari syndrome.

Efficacy of lamivudine therapy for decompensated liver cirrhosis due to hepatitis B virus with or without hepatocellular carcinoma.

The prognosis for patients with decompensated hepatitis B virus (HBV) related liver cirrhosis (LC-B), especially for those with LC-B complicated with hepatocellular carcinoma (HCC), is poor. We investigated the effects of lamivudine in patients with decompensated LC-B, with and without HCC. Decompensated LC-B patients (n=55) with Child-Pugh classification scores (CPS) >7 points were enrolled. All were admitted to the hospitals of the authors between January 1997 and December 2004. Decompensated cases due to a severe exacerbation of hepatitis with CH-B and patients with HCC showing an extra hepatic metastasis or portal vein tumor thrombus were excluded. Some 19 cases (including 5 cases complicated with HCC at the start of therapy) were treated with lamivudine at 100 mg/day (L group), and 36 (including 7 cases with HCC at time of admittance) were treated without lamivudine (non-L group). The median of CPS points in the L group was higher than that of non-L group (11 points versus 9 points, p<0.02). Prothrombin time (%), albumin, ascites, CPS, and HBV-DNA quantity were each significantly improved after 6 months in the L group (p<0.05). A mutation in the YMDD motif was observed in 5 patients in the L group, however liver function did not deteriorate. Further, the survival rate was significantly higher in the L group (p<0.05). HCC was found in 3 L group and 4 non-L group patients during the study. In the L group, all patients complicated with HCC were treated repeatedly or until cured, whereas 91% of those in the non-L group could not be treated (p<0.01). Our results suggest that lamivudine is a useful and important therapy for patients with decompensated LC-B with and without HCC, as well as those who are restricted from having liver transplantation.

Terpene isocyanides, isocyanates, and isothiocyanates from the Okinawan marine sponge Stylissa sp.

Seven new nitrogenous terpenoids, (1R,6R,7S,10S)-10-isothiocyanatocadin-4-ene (1), (1S,2S,5S,6S,7R,8S)-13-isothiocyanatocubebane (2), (1R,3S,4R,7S,8S,12S,13S)-7-isocyanoamphilecta-10,14-diene (3), (1S,3S,4R,7S,8S,12S,13S)-8-isocyanoamphilecta-11(20),14-diene (4), (3S,4R,7S,8S,11S,13S)-8-isocyanoamphilecta-1(12),14-diene (5), 8-isocyanatocycloamphilect-10-ene (6), and 8-isothiocyanatocycloamphilect-10-ene (7), were isolated from the Okinawan sponge Stylissasp., along with 12 known related compounds. Structural determinations of these compounds were made by spectroscopic analysis, and assessment was made of their cytotoxicity toward HeLa cells.