Clinical features and treatment of nonalcoholic fatty liver disease across the Asia Pacific region-the GO ASIA initiative.

BACKGROUND: The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the relationships between obesity and gastrointestinal diseases in the Asia Pacific region. AIM: To study factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Retrospective study of biopsy-proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort. RESULTS: We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%-83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count <150 × 109 /L, constituting the Asia-Pacific NAFLD advanced fibrosis risk score. A low score has a negative predictive value of 95%-96% for advanced fibrosis. Only 1.7% of patients were referred for structured lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone. CONCLUSIONS: More severe liver disease can be suspected or ruled out based on factors identified in this study. Utilisation of structured lifestyle program, vitamin E and pioglitazone was limited despite this being a cohort of biopsy-proven NAFLD patients with majority of patients having NASH.

[Aortic and mitral valve replacement for calcified valvular annulus in a dialysis patient; report of a case].

A 77-year-old man on hemodialysis was admitted to our hospital due to heart failure. Echocardiography showed aortic valve stenosis and regurgitation, mitral valve stenosis and regurgitaion, and tricuspid valve regurgitation. Catheter examination revealed severe calcification at aortic valve and mitral valve including their annulus. At the operation, the calcifications of the aortic and mitral valvular annulus was removed using a cavitron ultrasonic surgical aspirator (CUSA). Reconstructions of the defect of the posterior part of the mitral annulus and of the aortic annulus at the site of the left coronary cusp were achieved by patch technique using autologous pericardium. Aortic and mitral valve replacement and tricuspid valve annuloplasty were performed. The postoperative course was uneventful. Operative technique to remove calcification from valvular annulus using CUSA and reconstruct of the defect of the annulus with autologous pericardium is a very useful technique to prevent left ventricular rupture, perivalvular leakage and any other complications.

Results of a national survey on laparoscopic bariatric surgery in Japan, 2000-2009.

INTRODUCTION: In Japan, laparoscopic bariatric surgery has not been popular until recently because morbidly obese patients were infrequently encountered previous and Japanese health insurance does not cover this type of surgery. In 2010, the Japan Research Society for Endoscopic and Laparoscopic Treatments of Obesity undertook the first nationwide survey on laparoscopic bariatric surgery to evaluate its current status and outcomes. METHODS: A mail survey was sent to the society's 64 member institutions, which included almost all institutions in Japan actively performing laparoscopic gastrointestinal surgery. RESULTS: From 2000 to 2009, 340 laparoscopic bariatric procedures, in total, were performed in nine of the 64 institutions (14%). The most popular procedure was laparoscopic Roux-en-Y gastric bypass (LRYGB, n=147), second was laparoscopic sleeve gastrectomy (LSG, n=102), and third was laparoscopic adjustable gastric banding (LAGB, n=55). However, the number of LRYGB procedures has decreased while the number of LSG procedures has rapidly increased. Total morbidity rates were 12.2% for LRYGB, 10.9% for LAGB, and 7.8% for LSG. Percent excess weight loss was 78% at 5 years after LRYGB, 52% at 4 years after LAGB, and 68% at 2 years after LSG. Although the bariatric procedures frequently resolved or improved obesity-related comorbidities, LRYGB appears to be superior to LAGB, as was previously reported. CONCLUSION: The first nationwide survey of laparoscopic bariatric surgery in Japan clearly showed the current status and outcomes of this group of procedures. The Japanese results appear to be comparable to similarly undertaken surveys in Europe and the USA.

A groundbreaking new suturing device: the Excalibur.

BACKGROUND: Laparoscopic knot tying can be stressful. We reported two simple techniques, known as the Thumbs up! knot and the Tornado knot. We have further refined these procedures with the development of a new needle holder, called the Excalibur suturing needle holder. MATERIALS: This forceps differ from most conventional forceps in that the hinge is designed to stick out. The large hinge is stored out of the way when the forceps are closed, to prevent the thread accidentally catching. RESULTS: The thread is hooked on the projected hinge, which resembles the heel of a high-heel shoe. By using this forceps, the laparoscopic knot tying becomes easier for not only well experienced but also less experienced surgeons. CONCLUSIONS: The Excalibur, with its high heel, can complete knots with simple straight-line motion, making knot tying easier. This forceps will help reduce the stresses associated with intra-corporeal knot tying.

Persistent fifth aortic arch and fourth arch interruption in a 28-year-old woman.

A 28-year-old woman having persistent fifth aortic arch and aortic coarctation associated with the fourth arch interruption, without other cardiac malformation, underwent graft interposition, 20 mm in diameter, between the fourth arch including the left subclavian artery and the descending aorta.

Laparoscopic resection of the pancreas and review of the literature.

BACKGROUND: Laparoscopic pancreatic surgery still is not a common procedure worldwide. Postoperative complications such as a pancreatic leakage cause a serious condition. We report our consecutive laparoscopic pancreatic resections of islet cell tumors or benign diseases and their outcomes. METHOD: Laparoscopic pancreatic resections were attempted in three patients. Preoperative diagnoses were insulinoma in two patients and cystadenoma in one patient. The lesions were located in the pancreas body in two patients and the pancreas tail in one patient. Their sizes ranged from 1 to 6 cm in diameter (mean, 3 cm). RESULTS: We performed distal pancreatectomy using an endoscopic linear stapler with conservation of the spleen in two patients and enucleation in one patient. Of the distal pancreatectomies, the splenic artery and vein were preserved in one patient, whereas in the other they were divided. There were no perioperative complications in any of the cases. The mean postoperative hospital stay was 10 days (range, 7-14 days). There were no episodes of hypoglycemia or recurrence during the mean follow-up period of 25 months (range, 11-36 months). CONCLUSIONS: Although laparoscopic pancreatic resection of selected patients is a feasible and safe procedure in the hands of experienced laparoscopic surgeons, patients must be carefully observed after surgery to avoid serious conditions by pancreatic fistula.

Video-assisted bullectomy using needlescopic instruments for spontaneous pneumothorax.

Patients with spontaneous pneumothorax require immediate insertion of a chest drain to evacuate the intrathoracic air. During video-assisted bullectomy, we made use of an existing chest drain hole to insert a thoracoscope or an endoscopic linear stapler. Video-assisted bullectomy was performed through three ports-two 2-mm ports and the existing chest drain hole. Therefore, no new skin incisions were required for the insertion of the 2-mm ports. A chest drain was again inserted via the existing chest drain hole after bullectomy. This procedure was used on 8 of 10 patients with spontaneous pneumothorax. There were no postoperative complications or recurrences. Thoracoscopic bullectomy using needlescopic instruments is technically feasible, safe, and effective. Currently, the procedure is indicated only for simple cases and not for the lysis of adhesions.

[MALT lymphoma of the larynx].

We describe a 25-year-old Japanese woman with a MALT-type lymphoma of the larynx. She presented with a one-year history of hoarseness and increasing pain in the larynx. A small tumor was found on the left side of the false cord, and was biopsied under laryngoscopy in the department of laryngology. Histological examination showed the presence of centrocyte-like cells infiltrating the submucosa and forming lymphoepithelial lesions. The neoplastic cells were CD20+, CD79a+, and CD5-. Staining for keratin with CAM 5.2 highlighted the infiltrated epithelium. Analysis of DNA extracted from the biopsy specimen showed a clonal immunoglobulin heavy chain gene rearrangement, confirming the histological diagnosis of extranodal marginal zone B-cell lymphoma of the MALT type. To our knowledge, only 6 cases of MALT lymphoma of the larynx have been reported previously. The presence of MALT lymphomas arising at rare sites emphasizes the importance of accurate diagnosis and appropriate clinical management. Patients require careful periodic evaluation in order to time the therapy appropriately, and to avoid overtreatment and complications of therapy, including secondary malignancies.

Thirteen-week dietary intake of rapeseed oil or soybean oil as the only dietary fat in Wistar Kyoto rats-change in blood pressure.

Wistar Kyoto (WKY) rats were fed a diet containing 10% rapeseed (canola) oil or soybean oil as the only dietary fat for 13 weeks. From week 5 of feeding, systolic blood pressure of the canola oil group became higher than that of the soybean oil group. The 13-week canola oil intake increased plasma levels of Na(+) and lipids, and decreased the level of K(+) compared to those in the soybean oil group. The canola oil group also showed a high density of neutrophils and a low density of platelets compared to the soybean oil group. Moreover, the activities of catalase and superoxide dismutase in the hepatic cytosol were depressed in the canola oil group. The mechanisms for the higher blood pressure are unclear. However, an increase in body fluid via activation of Na(+) pump or Na(+), K(+)-ATPase and/or a blunt endothelium-dependent vasodilation by increased superoxide might have relevance to the elevated blood pressure. The increased plasma lipids and the changes in the densities of platelets and neutrophils appear not to be critical in WKY rats. However, these would tend to promote peripheral vascular lesions in the strains, such as spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats, which are prone to present atheroscrelotic vascular injury.

[The role of daunorubicin in induction therapy for adult acute myeloid leukemia].

The relationship between the total dose of daunorubicin (DNR) in induction therapy and the treatment outcome were evaluated based upon individualized doses of DNR during induction therapy for patients with acute myeloid leukemia(AML). Ninety-two previously untreated adult AML patients admitted to our hospital were analyzed for the dose of DNR required for complete remission (CR), the CR rate, disease-free survival (DFS) and overall survival (OS). The induction therapy consisted of DNR (40 mg/m2/d, i.v., from D 1 until the marrow was hypoplastic), Ara-C, prednisolone, and/or 6-thioguanine. Eighty-three out of 92 patients were assessable. Sixty-three patients entered CR (76%), of whom 52 attained CR with the first course of induction therapy. The 10-year DFS and OS rates were 31.2% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120-480 mg/m2), which was not influenced by initial WBC count, or FAB type. These results indicate that when the dose is linked to the observed tumor response, the optimal dose of DNR in the induction therapy is around 280 mg/m2 (40 mg/m2 x 7 times), which is higher than the conventional dose of 40-60 mg/m2 for 3 days. The higher dose of DNR in the induction therapy for adult AML should be selected when the feasibility of a new drug is evaluated in a randomized trial.

Effect of food restriction on hepatotoxicity of carbon tetrachloride in rats.

Five-week-old Sprague-Dawley rats of both sexes were assigned to two types of feeding condition. One was fed ad libitum (AL) on commercial chow and another was fed a restricted amount of the chow (FR), approximately 75% of that fed in the AL condition. In each feeding condition, animals were orally administered carbon tetrachloride (CCl4) at levels of 0 (control), 0.1 or 0.2 ml/kg 6 days a week for 8 weeks. Lesions of the liver (hepatic cellular degeneration and fibrosis) and of the kidney (proximal tubular vacuolation and glomerular sclerosis) induced by CCl4 were aggravated in the FR group. The FR-control showed a higher metabolic activity of aniline in the liver than the AL-control group. Plasma lipid-peroxide (LPO) level was higher in the AL-control group than in the FR-control group. With CCl4 0.2 ml/kg treatment, however, the plasma LPO level was reversed between the AL and the FR groups. Taking together these somewhat unexpected results, it was concluded that (1) 25% food restriction increases toxicity of repeatedly administered CCl4 in rats, and (2) aggravation of CCl4 toxicity may be partly due to enhanced metabolic activation of CCl4 resulting from food restriction.

Severe aplastic anemia associated with chronic natural killer cell lymphocytosis.

Chronic natural killer (NK) lymphocytosis involves a persistent increase in CD56+ large granular lymphocytes (LGLs) that is sometimes associated with immune-mediated complications, such as anemia and neutropenia. However, aplastic anemia (AA) is a rare complication. Here we describe 2 patients with severe AA who presented with persistent increases in NK cells. Their LGLs were positive for CD56, CD16, and intracellular interferon (IFN)-gamma but negative for CD3, Fas-ligand, and T-cell receptor rearrangement, findings that are compatible with NK cells. Not only the number of NK cells, but NK activity as well, was increased in both patients. The number of NK cells changed according to hematologic recovery and relapse in 1 case. Thus, there seemed to be a close relationship between NK cells and the progression of AA, at least in this instance. Further investigation of the clinical course of similar cases and the characteristics of NK cells is necessary.

Suppression of late asthmatic response by low-dose oral administration of interferon-beta in the guinea pig model of asthma.

We investigated the anti-asthmatic effects of low-dose oral and subcutaneous administration of interferon-beta (IFN-beta) on an ovalbumin (OVA)-sensitized and challenged guinea pig model of asthma. Subcutaneous administration of IFN-beta suppressed the eosinophil infiltration by 14.2% of the control and the respiratory resistance (Rrs) by 58.2% at 2.0 MIU/kg. Oral administration of IFN-beta inhibited the late asthmatic response (LAR) by suppressing the increase of Rrs by 29% of the control at 1 IU/ml and the eosinophil infiltration into the trachea and lung by 34.6% at the optimum dosage of 10 IU/ml. Both subcutaneous and oral administration could not inhibit the early asthmatic response (EAR). Additionally we found 2',5'-oligoadenylate synthetase (2',5'-OAS) induction by low-dose oral administration (LDOA) of IFN-beta to the same extent as by subcutaneous administration in whole blood in vivo. These data suggest that LDOA of IFN-beta would have some clinical benefit for patients with asthma.

Selective reduction in alpha-hydroxypalmitic acid-containing sphingomyelin and concurrent increase in hydroxylated ceramides in murine skin tumors induced by an initiation-promotion regimen.

The sphingomyelin cycle is activated to accumulate ceramides in the process of epidermal differentiation. We found that sphingomyelin in the epidermis of 4 different murine strains gave three bands on TLC, the lower band containing alpha-hydroxypalmitic acid (C16h:0(alpha)). However, in the papillomas induced in the skin of SENCAR and SSIN mice by initiation with 7,12-dimethylbenz[a]anthracene followed by promotion with 12-O-tetradecanoylphorbol acetate, the concentration of C16h:0(alpha)-containing sphingomyelin was selectively diminished with a concomitant increase in the concentrations of the ceramides containing alpha-hydroxy fatty acids. These findings indicate a possible involvement of the selective hydrolysis of alpha-hydroxy fatty acid-containing sphingomyelin in the process of tumorigenesis in mouse skin.

Pharmacokinetics and biologic activities of human native and asialointerferon-beta s.

Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in vivo. They are desialylated and taken up by the liver via an asialoglycoprotein receptor. Fibroblast-derived natural human interferon-beta is a glycoprotein having a single asparagine-linked sugar chain. Although natural human interferon-beta may also be metabolized through this pathway, there is very little information about the biologic features of human asialointerferon-beta. We evaluated the pharmacokinetics and biologic activities of human native and asialointerferon-beta s. After intravenous administration to rabbits, human asialointerferon-beta was cleared from the blood circulation faster than the human native interferon-beta. More asialoprotein was distributed to the liver than the native type, but it induced less 2'5'-oligoadenylate synthetase. The human asialointerferon-beta had less activity than the human native interferon-beta on cell growth inhibition and 2'5'-oligoadenylate synthetase induction in Hep-G2 and HuH6 human hepatoblastoma cells. Southern blotting using a hepatitis B virus-transfected HuH6 cell line, HB611, revealed that the inhibition of hepatitis B virus DNA replication by the asialoprotein was weaker than that by the native protein. The results showed that the different effects exerted by the human native and asialointerferon-beta s may be a result of recognition of the sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results also suggested that the terminal sialic acid of the sugar chains in natural human interferon-beta significantly affects its pharmacokinetics and biologic activities.

Carbohydrate-dependent biological activities of glycosylated human interferon-beta on human hepatoblastoma cells in vitro.

To evaluate the relationship between the sugar chain structure and biological activity, fibroblast-derived glycosylated human interferon-beta, Chinese hamster ovary cell-derived glycosylated recombinant human interferon-beta and Escherichia coli-derived unglycosylated recombinant human interferon-beta were evaluated using human hepatoblastoma cells in vitro. Native fibroblast interferon-beta expressed more cell-growth inhibitory action, 2'5'-oligoadenylate synthetase induction, and the inhibition of hepatitis B virus DNA replication than its asialoform and two recombinant interferon-betas. These results showed that the sugar chain structure of human interferon-beta affects its biological activity on human hepatoblastoma cells.

Cryostat sectioning of formalin-fixed brain: further attempt to improve section quality by previous infiltration with O.C.T. compound.

We previously reported that in non-brain and formalin-fixed specimens, one can obtain frozen sections of markedly improved quality not only by supporting specimens with O.C.T. compound as usually done, but by infiltrating them with the medium prior to embedding. In the present paper we show that this technic also proved to be quite effective in the cryosectioning of brain tissues, which so far has been difficult because of the liability of sections to shattering, particularly when one attempts to obtain a thick section. The present paper also discusses about the reason why sectioning is improved by the procedure, and aims to establish the optimal temperature for cryostat sectioning in relation to section thickness.

[Case report of toxic shock-like syndrome due to group A streptococcal infection].

A case of streptococcal toxic shock like syndrome occurring in a 44-year-old previously healthy Japanese male is reported. He initially had a sore throat, low grade fever, diarrhea and mild pains in a lower extremities. Shortly thereafter, he rapidly developed a high fever, profound hypotension, multifocal epidermal necrosis, and sever purulent fasciitis and myositis in both lower extremities, which required above knee amputation of both legs. He later developed disseminated intravascular coagulopathy, adult respiratory distress syndrome, acute renal failure, coma and necrotizing inflammation of both arms and external genitalia despite treatment. He died on the 13th hospital day. Streptococcus pyogenes was isolated from the necrotic muscles and right knee joint. The organism was typed as M3, T3, was sensitive to penicillins, and was found to be producing streptococcal pyogenic exotoxin A in vitro. This is the first case report of streptococcal toxic shock like syndrome in Japan.

Pharmacokinetic properties of recombinant feline interferon and its stimulatory effect on 2',5'-oligoadenylate synthetase activity in the cat.

The pharmacokinetic behavior of recombinant feline interferon produced in silkworm infected with recombinant baculovirus harboring cDNA coding for feline interferon was studied in vivo in cats. The decreasing profile of the serum interferon level after intravenous administration was fitted to a two-compartment model. The half-times of the first phase (distribution phase) and second phase (metabolic phase) were 5.0 +/- 0.5 min and 31 +/- 5 min, respectively. In the whole body autoradiogram, at 15 min after the administration, the highest radioactivity was observed in urine in the bladder, and predominant radioactivity in the kidneys, liver, thyroid gland and spleen. Almost no radioactivity was detected in the brain or fat. Three hr after administration, the highest radioactivity was recorded in the thyroid gland, urine in the bladder, intestinal contents, and gastric mucous membrane. The data obtained in this study suggest that recombinant feline interferon has similar pharmacokinetic properties to human interferons and that it is distributed primarily in the liver and kidneys, is catabolized rapidly mainly in the kidneys, and is excreted in the urine without residual accumulation in the body. It was confirmed that 2',5'-oligoadenylate synthetase activity was increased by the interferon in vivo for 3 days after an intravenous bolus injection in cats.

Procedure for evaluating changes in respiratory symptoms of experimentally asthma-induced guinea pigs by a personal computer.

An automated system was developed for evaluating changes in respiratory symptoms in guinea pigs over a long period with a personal computer. The data on breathing curves obtained with a body plethysmograph were analyzed to determine respiratory rate, expiration/inspiration ratio, ventilation ratio, and other parameters. With this system, respiratory changes in guinea pigs, such as increase or decrease of respiratory rate, expiration/inspiration ratio, and ventilation ratio, and death of animals could be easily observed. Investigation of delayed respiratory response to Candida albicans in sensitized guinea pigs and of the effects of SO2 or NO2 exposures on its response was carried out using this system. Respiratory changes in delayed respiratory response were mostly increased respiration rate and succeeding expiratory prolongation being noted just before death. In the influences of SO2 or NO2 exposure on delayed respiratory response, increase of respiratory rate in NO2 and expiratory and inspiratory prolongation in SO2 were found. This system should prove useful for evaluating changes in respiratory symptoms due to toxic agents, medicines, and air pollutants in small animals.