Diets with no or low amounts of dietary fiber can reduce small intestinal ulcers induced by non-steroidal anti-inflammatory drugs in dogs.

Recent progress in endoscopic techniques has revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but effective therapy is not available at present. In the present study, we investigated the effects of feeding condition and the amount of dietary fiber (DF) in the diet on the formation of gastrointestinal ulcers induced by NSAIDs in dogs. Several types of diets containing various percentages of DF were given to dogs. Indomethacin (1 or 3 mg/kg, p.o.), ketoprofen (2 mg/kg, s.c.), or fulnixin (1 mg/kg, s.c.) was administered once daily at 10 a.m. after a morning meal or without a morning meal (fasted condition) for 3 - 7 days. Gastrointestinal lesions were examined 24 h after the final dose of the drugs. When indomethacin (3 mg/kg) was administered after a morning meal (fed condition) for 7 days, it produced many lesions in the small intestine. However, when it was given in the fasted condition without the morning meal, the lesions were markedly decreased. All the NSAIDs given after feeding of regular dry food containing 6% DF once a day for 3 days produced many lesions in the small intestine. The lesions were decreased or increased in dogs given prescription diets containing low DF (1.1%) and high DF (15.4%), respectively. Furthermore, lesions were not observed in dogs given canned diet containing very low DF (< 0.1%), whereas lesions appeared again in dogs given canned diet supplemented with cellulose (3 or 10%) but not with pectin (10%). These results suggested that both feeding condition and insoluble DF, such as cellulose in the diet, play an important role in the formation of NSAID-induced small intestinal lesions, and that a diet with no or low amounts of DF may decrease gastrointestinal side-effects associated with the use of NSAIDs.

Reduction en masse of inguinal hernia: MDCT findings of two cases.

Reduction en masse of inguinal hernia is an extremely rare complication arising from manual reduction of a hernia. The hernial content remaining in the hernia sac returns above the inguinal canal but remains in the abdominal wall. Accurate preoperative diagnosis of reduction en masse of inguinal hernia is challenging because the hernia appears to be reduced upon physical examination. We experienced two cases of reduction en masse. In both cases, multidetector row computed tomography revealed a closed loop obstruction near the inguinal fossa. In addition, we observed a continuous tract of the hernia sac to the inguinal canal and prominent peritoneal thickening suggestive of the hernia sac.

Role of dietary fibres, intestinal hypermotility and leukotrienes in the pathogenesis of NSAID-induced small intestinal ulcers in cats.

BACKGROUND: Recent advances in endoscopy have revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the human small intestine. However, the mechanism of intestinal ulcer formation is still unclear. AIMS: The role of dietary fibre (DF), intestinal motility and leukotrienes (LTs) in the formation of small intestinal ulcers induced by indomethacin (IND) was investigated in cats. METHODS: Several types of diets containing DF at various percentages were given to animals twice daily during the experiment. IND was administered orally once daily after the morning meal for 3 days, and the area of mucosal lesions in the intestine was measured. Gastrointestinal motility was measured using a telemetry system in conscious cats implanted with force transducers. RESULTS: In cats fed regular dry food containing 2.8% DF, IND (3 mg/kg, p.o.) significantly increased the motility of the lower half of the small intestine and produced many severe lesions; the total lesion area was 7.7 (SEM 2.0) cm(2) (n = 5). The lesions were markedly decreased with the low-DF diet (0.4%) and increased with the high-DF diet (7.2%). The lesion area was 0.1 (SEM 0.1) cm(2) (p<0.05) and 18.2 (SEM 4.1) cm(2) (p<0.05), respectively. Supplementation with insoluble DF (6% cellulose), but not soluble DF (pectin), in the low-DF diet increased the lesion area significantly. The hypermotility and lesion formation in the small intestine induced by IND were significantly (p<0.05) inhibited by AA-861 (a 5-lipoxygenase inhibitor), pranlukast (a LT receptor antagonist) or atropine. CONCLUSIONS: Insoluble DF, intestinal hypermotility, leukotrienes and cholinergic pathways are implicated in the pathogenesis of small intestinal ulcers induced by NSAIDs.

Rho-kinase as a novel gene therapeutic target in treatment of cold ischemia/reperfusion-induced acute lethal liver injury: effect on hepatocellular NADPH oxidase system.

In the transplant surgery, reactive oxygen species (ROS) from the reperfused tissue cause ischemia-reperfusion injury, resulting in the primary graft failure. We have recently reported that Rho-kinase, an effecter of the small GTPase Rho, plays an important role in the ROS production in the hyperacute phase of reperfusion; however, the sources and mechanisms of the ROS production remain to be elucidated. The aim of this study was to investigate the source of ROS production with a special reference to Rho-kinase to develop a new strategy against ischemia-reperfusion injury. In an in vivo rat model of liver transplantation, Kupffer cells in the graft were depleted using liposome-encapsulated dichloromethylene diphosphonate to examine the source of ROS production. The effect of adenoviral-mediated overexpression of a dominant-negative Rho-kinase (AdDNRhoK) in hepatocytes in the graft was also examined. Kupffer cells were not involved in the ROS production, whereas the AdDNRhoK transfection to hepatocytes significantly suppressed the ROS production. Furthermore, the ROS production was dose-dependently inhibited by apocynin, an NADPH oxidase inhibitor. Expression of DNRhoK also suppressed the release of pro-inflammatory cytokines, and ameliorated the lethal liver injury with a significant prolongation of the survival. These results suggest that the Rho-kinase-mediated pathway plays a crucial role in the ROS production through NADPH oxidase in hepatocytes during the hyperacute phase of reperfusion in vivo. Thus, Rho-kinase in hepatocytes may be a new therapeutic target for the prevention of primary graft failure in liver transplantation.

Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. METHODS: Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. RESULTS: The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. CONCLUSIONS: A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.

S100 beta protein: the preoperative new clinical indicator of brain damage in patients with fulminant hepatic failure.

The aim of this study was to clarify the role of serum S100 beta on the accurate assessment of reversibility of brain damage after fulminant hepatic failure (FHF). Among the 13 patients with FHF enrolled in this study, 12 underwent living donor liver transplantation; one patient could not the procedure because of volvulus of the sigmoid colon. Serum S100 beta was serially measured using a chemiluminescent immunoassay. Preoperative serum S100 beta in patients with diffuse brain edema was significantly higher than that in patients with localized brain edema (P < 0.05). Patients with preoperative brain death showed serum S100 beta levels over 7.0 microg/L. Serum S100 beta levels correlated with the degree of brain edema of FHF. It has the potential to be a new clinical, noninvasive indicator of brain damage due to FHF.

Is graft size a major risk factor in living-donor adult liver transplantation?

Graft size is known to be a major risk factor in living donor adult liver transplantation (LDALT). The aim of this study is to reassess whether graft size is a critical factor in LDALT or not. A series of 75 LDALTs excluding auxiliary transplantation and ABO blood-type incompatible transplantation were analyzed. The patients were divided into two groups, according to graft volume (GV) and standard liver volume (SLV): group 1 (small-size group) (GV/SLV: <40%), and group 2 (non-small-size group) (> or =40%). Perioperative clinical data were compared between the two groups, including graft survival and postoperative complications. These parameters were also compared under the conditions of cirrhotic recipients. No difference in graft survival was found between the two groups. No difference was found in incidence of postoperative complications, such as intractable ascites and persistent hyperbilirubinemia. Even in cirrhotic patients with Child-Pugh's class C, there was no difference in graft survival between the two groups. Risk factors related to graft loss were a preoperative urgent status due to chronic liver disease, pre-operative hyperbilirubinemia of over 10 mg/dl, and ABO blood type of not identical but compatible combination between donor and recipient. Graft size is not always considered to be a major risk factor in LDALT, although the number of patients was small in this study. Therefore, a left-lobe graft, even a "small-for-size" graft for adult recipients, remains a feasible option in LDALT.

External radiotherapy for decompression of cholangiocellular carcinoma with obstructive jaundice: report of a case.

Percutaneous transhepatic catheter drainage (PTCD) is generally performed for the treatment of obstructive jaundice. However, in some cases it is difficult to perform insertion because of lack of dilatation of the intrahepatic bile duct. We report a patient who had been suffering from jaundice as a result of recurrent cholangiocarcinoma near the hilum and whose symptoms were relieved by external radiotherapy. We consider radiotherapy for cholangiocarcinoma effective palliative treatment for decompression of obstructive jaundice.

Pharmacokinetic study of human natural beta-interferon in patients with end-stage renal failure.

AIMS: Although human natural beta-interferon (beta-IFN) is currently used in the treatment of a number diseases, there have been no published studies of the pharmacokinetics and pharmacodynamics of beta-IFN in patients with end-stage renal failure. MATERIALS: Five maintenance hemodialysis patients with chronic hepatitis C (4 men and 1 woman) were enrolled in this study. METHODS: For the pharmacokinetic study, blood samples were obtained from a forearm vein at intervals, before infusion and 0, 3, 5, 10, 20, 30, and 40 minutes after a 15-minute intravenous infusion of human natural beta-IFN (Feron, Toray Industries, Inc., Tokyo) at a dose of 600 MIU. RESULTS: Intravenous beta-IFN was administrated safely to all five patients. The plasma half-life of beta-IFN was found to be 6.91 +/- 2.80 (mean +/- SD) minutes. The initial volume of distribution was found to be 0.49 +/- 0.02 l/kg. CONCLUSION: A 15-minute intravenous infusion of human natural beta-IFN was safely administered to the hemodialysis patients. This pharmacokinetic study showed that it is not necessary to reduce the dosage in patients with end-stage renal failure.

Diagnosis of chest wall invasion by lung cancer: useful criteria for exclusion of the possibility of chest wall invasion with MR imaging.

PURPOSE: To compare the accuracy of thin-section CT, conventional static MR imaging (conventional MRI), and breathing dynamic echo planar magnetic resonance imaging (BDEPI) in evaluating lung cancer invasion to the chest wall. MATERIALS AND METHODS: Thin-section CT, conventional MRI, and BDEPI were performed preoperatively in 20 patients suspected of having primary lung cancers adjacent to the chest wall on conventional CT. The results of imaging findings were compared with those of surgical and histopathological findings. RESULTS: All patients were confirmed to have no chest wall invasion after surgery. By thin-section CT, 10 of 20 patients were correctly diagnosed as having no chest wall invasion (50% specificity). Two of the 20 patients were incorrectly diagnosed as having chest wall invasion by conventional MRI and BDEPI (90% specificity). CONCLUSION: When chest wall invasion is suspected on CT scans, static and breathing dynamic MRI are recommended to avoid false positive interpretations.

[Living donor liver transplantation in Kyushu University].

We performed living donor liver transplantation (LDLT) for 40 patients at Kyushu University Hospital, Fukuoka Japan during the period from October 1996 to April 2000. The patients consisted of 32 adults and 8 children with a mean age of 35.8 years (range: 1 year and 10 months to 65 years old). The underlying liver diseases of the 40 patients included the fulminant hepatic failure (n = 14), biliary atresia (n = 7), liver cirrhosis (HCV) (n = 6), primary biliary cirrhosis (n = 5), primary sclerosing cholangitis (n = 2), familiar amyloidotic polyneuropathy (n = 2), Alagille syndrome (n = 1), glycogen storage disease (n = 1), huge hepatic hemangiomas (n = 1), and Wilson's disease (n = 1). All liver grafts were obtained from each patient's family members except for one domino transplant donor's case, comprised of 13 parents, 13 sons and daughters, 11 brothers and sisters, and 3 wives. The donors are presently all doing well. The patient survival rate is presently 92.5%.

Detection of minute pleural fluid in the pleural retracted space associated with peripheral lung cancer: evaluation with MR imaging.

PURPOSE: To evaluate the efficacy of magnetic resonance imaging (MRI) in detecting minute pleural fluid in the pleural retracted space (PRS) associated with peripheral lung cancer. MATERIALS AND METHODS: Our subjects were 20 patients with peripheral lung cancer in whom thin-section CT in the lung window setting demonstrated lesions adjacent to the pleural surface, and who were referred for MR imaging. The imaging findings were retrospectively evaluated and correlated with the histopathologic specimens. Pleural fluid was aspirated for cytology under ultrasound (US) guidance in six patients. RESULTS: STIR MR images revealed water SI areas beneath the chest wall associated with the lung cancer, whereas, on CT images, lung cancer and minute pleural fluid in the PRS showed similar soft-tissue density without enabling easy differentiation. Two of the six patients who underwent aspiration cytology showed malignancy. All histopathologic specimens obtained from 18 patients who underwent surgery showed pleural retraction corresponding to the water SI areas on STIR images. Histopathological study revealed that the fibrotic focus of the tumor tended to occur more intensively when the shape of pleural retraction was thinner and deeper. CONCLUSION: Water SI areas on STIR images were thought to suggest pleural fluid retention in the PRS. MRI was sensitive in detecting minute pleural fluid in the PRS and may help to avoid overdiagnosis of chest wall invasion induced from peripheral lung cancers.

Producing a full-scale model from computed tomographic data with the rapid prototyping technique using the binder jet method: a comparison with the laser lithography method using a dry skull.

Rapid prototyping using the binder jet method has recently been established and has already produced excellent results in industrial applications. The authors recently developed a technique for producing a full-scale model from computed tomographic (CT) data with the binder jet method as an approach to overcome the shortcomings of the laser lithography method, which is already widely used in medicine. They conducted a comparative investigation of full-scale models made with both techniques using a dry skull to determine the accuracy of the models. It was clearly demonstrated that the accuracy of the binder jet method was high enough to be used in craniomaxillofacial surgery because it was the same as the laser lithography method. This study employed data from the latest helical volume scan computed tomography device using a multidetector. The study showed that the new rapid prototyping technique was satisfactory in terms of speed, cost, installation environment, and accuracy of models, and that detailed shapes and structures can be reproduced well. Because this technique has many advantages over the laser lithography method, it should play a major role in craniomaxillofacial surgery and in other medical fields in combination with advances in CT devices. Although plaster is a more suitable fixation material when the emphasis is on the reproducibility of detailed structures, the binder jet method using starch is extremely useful for simulating operations and determining implant shapes because it allows for the prompt production of models.

[T1-weighted vs. short-TE-long-TR images: usefulness for knee MR examinations of ligament and meniscal lesions].

The purpose of this study was to compare short-TE-long-TR images with T1-weighted images in knee MR examinations. Sagittal MR images of the knee were obtained in 31 patients with knee pain. T1-weighted images were obtained by the spin-echo technique (TR/TE = 350/15), and short-TE-long-TR images by fast spin-echo (TR/TE = 1300/15) with an echo-train length of 5. Contrast-to-noise-ratios (CNRs) of the anterior cruciate ligament and synovial space, meniscus and articular cartilage, and meniscal lesion and normal meniscus were compared between short-TE-long-TR images and T1-weighted images. On each of the three examinations, short-TE-long-TR images provided significantly higher CNRs than T1-weighted images. It was concluded that short-TE-long-TR images can be a useful alternative to T1-weighted images in evaluating the anterior cruciate ligament and meniscal lesions.

Evaluation of small internal mammary lymph node metastases in breast cancer by MRI.

PURPOSE: In breast cancer, diagnosis of a small internal mammary lymph node (IMLN) metastasis of less than 10 mm in size has been difficult. Our purpose was to retrospectively evaluate MRI findings of small IMLN metastases in comparison with dissected IMLNs. METHODS: We studied 43 dissected IMLNs (range 2-12 mm, mean 4.512+/-2.763 mm) in 16 women with breast cancer (15 primary, and 1 recurrent). MRI examinations were performed using a 1.5 Tesla scanner (200FX; Toshiba, Tokyo, Japan) to obtain noncontrast T1-weighted SE images (TR/TE; 500/15 or 400/15ms), with a slice thickness of 5 mm on coronal images, 10 mm or 7 mm on sagittal images, FOV 15x15 cm, matrix 256x256, using a surface coil with patients in the supine position. MR images were evaluated regarding the major diameter and shape and margin of each node. RESULTS: Regarding the presence of IMLN metastases, there was a significant difference between nodes with a major diameter of 5 mm or more and those of less than 5 mm (p<0.05). Using the size-based criterion (defining< or =5 mm as positive), MRI had 90.7% accuracy, 93.3% sensitivity, and 89.3% specificity. There were no significant differences in the shape-or margin-based criterion. CONCLUSIONS: MRI was useful in diagnosing small IMLN metastases, using a size-based criterion.

MRI in predicting the response of ovarian endometriomas to hormone therapy.

OBJECTIVE: Our goal was to investigate the usefulness of MRI in predicting the response of endometriomas to hormone therapy. MATERIALS AND METHODS: MRI and laparoscopy at the onset of treatment and follow-up MRI after 6 months of hormone therapy were performed in 21 patients with 49 endometriomas. T1- and T2-weighted images were obtained with a 1.5 T apparatus using a body coil. The lesions were divided into a responder group and a nonresponder group according to whether the lesion size decreased by > or = 50% or not. RESULTS: With MRI, shading was seen in 25 of 27 lesions (93%) from the nonresponder group, but in only 6 of 22 (27%) from the responder group. Low SI rim was seen in 59% of the responders and 89% of the nonresponders. Multiplicity in 68% of the responders and in 85% of the nonresponders and irregularity in 41% of the responders and in 78% of the nonresponders were shown. Multiple logistic analysis revealed shading was the most important factor in prediction of the response to hormone therapy. CONCLUSION: Shading was an important sign in evaluating the response of endometriomas to hormone therapy. MRI may assist in selecting the appropriate therapy for endometriomas.

Pharmacological actions of the racemic and the enantiomeric 1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benz azo nines (C-homobenzomorphans).

The racemate and optical isomers of the C-homobenzomorphans, 1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzaz onine, were evaluated in a number of assays sensitive to narcotics of different types. All three C-homobenzomorphans were active in vitro in guinea pig ileum, mouse vas deferens, and rat brain membrane binding assays, but were of low potency. These C-homobenzomorphans showed different profiles of in vivo activity. The (+)-isomer and racemate were active as agonists in the tail-flick assay, whereas the (-)-isomer was inactive. At higher doses, the (-)-isomer and the racemate behaved as antagonists of morphine in the tail-flick assay. All three compounds were active in the phenylquinone test, but naloxone did not block this effect. In addition, all three were potent in the hot-plate test. Neither of the isomers substituted for morphine in dependent rats or monkeys. However, the (+)-isomer precipitated withdrawal in these monkeys. The (-)-isomer produced opioid-like physical dependence in both rats and monkeys. Some of the implications regarding the results with these remarkable homobenzomorphans are discussed.

Optical resolution of some homobenzomorphan derivatives and their pharmacological properties.

Racemic 1,4-dimethyl- (1), 1,4,12 alpha-trimethyl- (2), and 1,4,12 beta-trimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine (3) have been optically resolved. The analgesic potency and physical-dependence capacity of the optical isomers and their racemic parents were determined. The levo isomers of compounds 2 and 3 were analgesically much more potent than the dextro isomers and were equipotent with morphine. Optical resolution gave no effect on the activity of compound 1. None of the optical isomers and the racemates suppressed the morphine-withdrawal syndrome in the monkey.