Immobilization of amphiphilic dendron on silica particles toward the application to ultrahigh pressure liquid chromatography.

Amphiphilic poly(amido amine) (PAMAM) dendrons were immobilized on the surface of silica particles, following the solid phase strategy. PAMAM dendrons were constructed by the repetitive feeding of methyl acrylate and ethylenediamine as the monomers. The peripheral functionalization of amine to long alkyl ends generated the amphiphilic PAMAM dendron on the silica surface. These amphiphilic dendron-modified silica particles were applicable as new packing materials for ultrahigh pressure liquid chromatography.

Evaluation of hepatocellular carcinoma with portal vein tumor thrombosis by CEUS before and after hepatic arterial infusion chemotherapy.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Portal vein tumor thrombosis (PVTT) is a common complication of advanced HCC, and the prognosis of advanced HCC with PVTT is extremely poor. We report a case of HCC with PVTT evaluated by contrast-enhanced ultrasonography (CEUS) before and after hepatic arterial infusion chemotherapy (HAIC). A 59-year-old man with chronic hepatitis C was admitted to our hospital. CEUS clearly showed the thread and streaks sign in a solid lesion that occupied the right main branch of the portal vein. HAIC was performed, and CEUS after HAIC clearly showed disappearance of the thread and streaks sign. CEUS was very useful in diagnosing PVTT and in evaluating the effectiveness of HAIC in this case.

Outcomes and factors influencing survival in cirrhotic cases with spontaneous rupture of hepatocellular carcinoma: a multicenter study.

BACKGROUND: Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE). METHODS: A retrospective multicenter study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC. Conservative treatment was employed in 32 patients (ConT group) and TAE was performed in 16 patients (TAE group). RESULTS: The median survival time (MST) in the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4% at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at 3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of univariate analyses, factors associated with poor hepatic function and poor suitability for TAE was important determinants of short-term death (less than 3 weeks) among the patients (p < 0.05). On the other hand, among the patients in whom initial TAE was successfully performed (n = 15), a multivariate analysis showed that a maximum tumor size not exceeding 7 cm was the only independent factor determining long-term survival (p = 0.0130). CONCLUSION: Despite the inherent limitations of this retrospective study, TAE appears to be a useful treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it yielded a longer survival period compared with conservative treatment in patients with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was successfully performed, the maximum tumor size was an important factor influencing survival.

Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment. METHODS: The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses. RESULTS: The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group. CONCLUSIONS: The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.

Levovist ultrasonography imaging in intracystic hemorrhage of simple liver cyst.

The differential diagnosis between intracystic hemorrhage and cystadenocarcinoma of the liver is often difficult even with the use of various imaging modalities. A 73-year-old woman was admitted to our hospital with the complaint of right upper quadrant pain. Ultrasonography (US) demonstrated a heterogeneous echogenic cyst measuring 11 cm multiply 8 cm in size in S2 of the liver, indicated intracystic hemorrhage of simple liver cyst or cystadenocarcinoma, but the differential diagnosis was considerably difficult. Levovist (Schering, Berlin, Germany) US revealed no enhancement of the intracystic structures, suggesting a clot in the case of intracystic hemorrhage. An operation was performed and the resected lesion showed a solitary benign liver cyst, measuring 5.5 cm multiply 4.7 cm multiply 8.5 cm containing a large blood clot. The patient had an uneventful recovery after the surgery. Levovist US may play an important role in discrimination between intracystic hemorrhage of simple hepatic cysts and cystadenocarcinoma of the liver.

Early effects of peppermint oil on gastric emptying: a crossover study using a continuous real-time 13C breath test (BreathID system).

BACKGROUND: The aim of this study was to determine whether there was a correlation between peppermint oil and gastric emptying by using a novel noninvasive technique for measuring gastric emptying with a continuous real-time (13)C breath test (BreathID system, Oridion, Israel). METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects were randomly assigned to receive a test meal (200 kcal per 200 ml) containing 0.64 ml of peppermint oil or the test meal alone, after fasting overnight. A (13)C-acetic acid breath test was continuously performed with the BreathID system, which monitors gastric emptying, for 4 h after the administration of the test meal. Using Oridion Research Software (beta version), the time for emptying of 50% of the labeled meals (T 1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (T lag), the gastric emptying coefficient (GEC), and the regression-estimated constants (beta and kappa) were calculated. The parameters between two occasions were compared using the Wilcoxon signed-rank test. RESULTS: After peppermint oil intake, the T lag and beta constant were significantly decreased. No significant differences in T 1/2, GEC, or kappa were observed between the two occasions. CONCLUSIONS: The decrease in the T lag and beta constant suggests acceleration of gastric emptying during the early phase. This study showed that peppermint oil enhances gastric emptying, suggesting the potential use of peppermint oil in clinical settings for patients with functional gastrointestinal disorders.

mRNA expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and vascular endothelial growth factor in esophageal mucosa biopsy specimens from patients with reflux esophagitis.

BACKGROUND/AIMS: Nitric oxide (NO) production is elevated in the intestine and may contribute to intestinal injury during inflammation. However, how the expression of inducible NO synthase (iNOS) mRNA and endothelial NO synthase (eNOS) mRNA in the esophageal mucosa contribute to mucosal damage caused by reflux esophagitis remains unknown. Since vascular endothelial growth factor (VEGF) exerts its action on microcirculation, contributing to angiogenesis and inflammation, we examined the role of VEGF together with iNOS and eNOS on development of reflux esophagitis. METHODOLOGY: The mRNA expression levels of iNOS, eNOS and VEGF were measured in biopsy specimens from 25 patients with reflux esophagitis, using TaqMan PCR and reverse transcription PCR. RESULTS: The expression of iNOS mRNA in the esophageal mucosa increased parallel to the severity of the esophagitis. There were no significant differences between both eNOS and VEGF mRNA expression levels and the severity of the esophagitis. The existence of gastric mucosal atrophy, hiatus hernia, therapy and Helicobacter pylori infection did not affect the levels of mRNA expression. CONCLUSIONS: The accumulation of NO, produced by iNOS, was considered to be related to the exacerbation of reflux esophagitis. Therapeutic intervention that reduces NO production may thus be of use in preventing development of esophageal mucosal injury in patients with reflux esophagitis.

Pleural effusions following endoscopic injection sclerotherapy for cirrhotic patients with esophageal varices.

BACKGROUND/AIMS: Endoscopic injection sclerotherapy is in widespread use for patients with esophageal varices. It is well known that pleural effusions are among complications following endoscopic sclerotherapy. However, there are few studies regarding the proportion of patients developing pleural effusions after sclerotherapy. METHODOLOGY: Between August 1991 and September 1998, 575 endoscopic injection sclerotherapies were carried out in 128 patients. Chest radiographs were obtained prior to and 24 hours after all procedures. We also obtained other clinical data from all patients. RESULTS: In total, 17.7% of post-sclerotherapy patients were diagnosed as having small amounts of pleural effusions. Logistic regression revealed pleural effusions after sclerotherapy to be associated with ascites, chest pain for 24 hours, total volume of sclerosant and submucosal injection of more than 4mL of sclerosant. In parallel with injection of an increasing amount of submucosal sclerosant, the proportion of patients with pleural effusion increased. CONCLUSIONS: Pleural effusions were related to ascites, chest pain for 24 hours, total sclerosant volume and submucosal injection of sclerosant.

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

BACKGROUND: Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects. METHODS: A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10 mg lafutidine or 20 mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364 kcal; protein, 10.1 g; fat, 16 g; carbohydrates, 44.9 g; NaCl, 1.1 g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6 h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored. RESULTS: In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6 h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6 h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. CONCLUSIONS: Lafutidine 10 mg produces a prompter rise in intragastric pH than rabeprazole 20 mg in fasting and postprandial Helicobacter pylori-negative male subjects.

Efficacy of a triple therapy with rabeprazole, amoxicillin, and faropenem as second-line treatment after failure of initial Helicobacter pylori eradication therapy.

BACKGROUND/AIMS: Triple therapy consisting of lansoprazole, amoxicillin, and clarithromycin (LAC regimen) is widely used to eradicate Helicobacter pylori in Japan. However, the need for appropriate treatment after failure of initial therapy to eradicate H. pylori has been increasing. We therefore assessed the efficacy of a combination of rabeprazole, amoxicillin, and faropenem for second-line eradication therapy. METHODOLOGY: The subjects were 116 patients positive for H. pylori infection. Patients initially received lansoprazole 60 mg/day, amoxicillin 1500 mg/day and clarithromycin 400 mg/day in two divided doses for 7 days. Patients in whom eradication treatment failed were given rabeprazole 20 mg/day and amoxicillin 1500 mg/day in two divided doses, and faropenem 600 mg/day in three divided doses (RAF regimen) for 7 consecutive days. H. pylori status was assessed by the 13C-urea breath test combined with rapid urease test or H. pylori culture method 8 weeks after completion of therapy. Susceptibility to clarithromycin was determined by the agar dilution method, and genetic polymorphism of CYP2C19 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The initial H. pylori eradication rate with the LAC regimen was 76.4% (84/110). Assessment of the CYP2C19 genotypes of the patients in whom eradication therapy failed revealed that homozygous extensive metabolizers accounted for 70.0% (16/23) and heterozygous extensive metabolizers for 30.0% (7/23), with no poor metabolizers. The acquired resistance rate for clarithromycin was 52.0% (12/23). The success rate of re-eradication with the RAF regimen was 91.3% (21/23) with no serious adverse effects. CONCLUSIONS: Triple therapy comprising rabeprazole, amoxicillin, and faropenem is effective for second-line eradication treatment of H. pylori infection, regardless of the genetic polymorphism of CYP2C19 or the presence of resistance to clarithromycin.

Pancreatoscopy assisted by endoscopic sphincter dilation.

To investigate tumor extension to the main pancreatic duct in patients with intraductal papillary mucinous tumors, we conducted pancreatoscopy assisted by endoscopic sphincter dilation (ESD). Two patients with intraductal papillary mucinous tumors were included in this study. The endoscopic sphincter dilation was performed using an Olbert balloon-tipped catheter. A mother-baby scope system was used for endoscopic examination. After dilation of the orifice, the babyscope was inserted smoothly. Tumorous lesions (especially the typical salmon-roe appearance of the tumors) were clearly observed in the main pancreatic duct in one patient, while no tumorous lesions were identified in the other patient. The ESD procedure may be applicable for assisting insertion of the endoscope through the papilla of Vater into the pancreatic duct. ESD is useful both for treating and for diagnosing pancreatic lesions.

Gene expression profile after peroxisome proliferator activator receptor-gamma ligand administration in dextran sodium sulfate mice.

BACKGROUND: Peroxisome proliferator activator receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily. Ligands of PPARgamma, thiazolidione derivatives, have been reported to be the one of the candidates for the treatment of inflammatory bowel disease (IBD). Given the fact that PPARgamma is a transcription regulator, expression pharmacogenomics, including differential gene expression profiling of drug responses in a colitis model, is thought to be a useful approach for finding relevant genes that can serve as the target for new drug treatment of IBD. METHODS: We performed a global analysis for differential gene expression of the intestine in a dextran sodium sulfate (DSS) colitis mouse model following PPARgamma ligand administration. By applying a high-density oligonucleotide array method, the expression patterns of approximately 12000 genes were analyzed, and selected genes were confirmed by a real-time quantitative PCR method. RESULTS: The analysis of downregulated genes in the DSS mice following PPARgamma administration revealed several functional gene clusters with altered expression: (1) oncogene families such as GRO1 oncogenes, (2) inflammatory mediator-related genes such as the interferon-gamma gene, (3) water electrolyte-associated genes, and (4) others. CONCLUSIONS: This is the first demonstration of global gene expression analysis using the DSS colitis mouse model with a PPARgamma ligand, and these results provide new insight for finding novel target genes for treating IBD.

The comparative effects of single intravenous doses of omeprazole and famotidine on intragastric pH.

BACKGROUND: The ideal medication for the treatment of acid-related diseases, for example, hemorrhagic ulcers and stress-related gastric bleeding, should have a rapid onset of action to promote hemostasis and alleviate symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of omeprazole 20mg and famotidine 20 mg. METHODS: Ten healthy Helicobacter pylori-negative male subjects participated in this randomized, double-masked, two-way crossover study. Intragastric pH was monitored continuously for 4 h after a single intravenous administration of omeprazole 20 mg and after a single intravenous administration of famotidine 20 mg. The administration of the two agents was separated by a 7-day washout period. RESULTS: In all ten subjects, the length of time that intragastric pH remained over 3, during the 0- to 3- and 0- to 4-h study periods, was greater after famotidine treatment than after treatment with omeprazole, and famotidine increased the average pH during the 0 to 3- and 0 to 4-h study periods significantly more than omeprazole did. During the 4-h study period, famotidine provided a longer duration of pH of more than 2, 3, 3.5, 4, 5, 6, and 7, compared to omeprazole. CONCLUSIONS: In Helicobacter pylori-negative healthy male subjects, an intravenous dose of 20 mg famotidine increased intragastric pH more rapidly than intravenous omeprazole 20 mg.

Chemoprevention of precursors to colon cancer by dehydroepiandrosterone (DHEA).

Although dehydroepiandrosterone (DHEA) is recognized as one of the major adrenal androgens, its precise physiological role in the human endocrine system remains to be elucidated. In particular, the effect of DHEA on carcinogenesis has not been fully characterized. We undertook this study to determine whether DHEA has a chemopreventative effect on the precursors of colon cancer in a murine model of azoxymethane (AOM)-induced aberrant crypt foci (ACF). The number of ACF was significantly decreased in mice treated with 0.4% (p < 0.001) and 0.8% DHEA (p < 0.001), but there were no significant differences between DHEA-treated and control mice in terms of the ACF size, 3-catenin expression or level of dysplasia. This is the first study of colon cancer carcinogenesis demonstrating that DHEA treatment can decrease the number of ACF without apparently modifying their malignant potential. These data strongly suggest that DHEA might be a potential chemopreventative agent against human colon cancer.

Endoscopic Diagnosis of Biliary Tract Lesions Using Hydrostatic Balloon Sphincter Dilation: A Preliminary Experience.

We report some encouraging results of endoscopic balloon sphincter dilation (EBSD) and discuss its clinical relevance in the diagnosis of bile duct lesions by endoscopically accessing the biliary tree. Endoscopic approach to the bile duct was performed in seven patients with various biliary tract diseases (bile duct cancer in 2 cases, pancreatic cancer in 1, Caroli disease with bile duct stones in 1, gallbladder cancer in 1, and hepatocellular carcinoma in 2) after passing a baby scope through the papilla of Vater using EBSD. The instrument used was a Maxforce 5 French balloon-tipped biliary catheter for EBSD, an Olympus CHF-BP30 or Pentax FCP-9P baby fiberscope, and an Olympus TJF-M20 mother fiberscope for endoscopic examination. Using EBSD, it was possible to advance a baby fiberscope through the papilla of Vater in all cases. In 6 patients, endoscopic observation was successfully achieved. Apart from minimal self-limiting venous oozing seen following balloon deflation, there was no papillary hemorrhage or perforation observed. Pancreatitis developed in one patient and was resolved within 24 hours. Although our series is limited and several technical issues remain to be solved, this new procedure has potential for endoscopic diagnosis of biliary tract lesions. One of the major advantages may lie in the possibility of preserving sphincter function. We favor the use of EBSD for diagnostic evaluation of bile duct diseases.