Clinical trial: extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late responders.

BACKGROUND: The benefits of prolonging peginterferon and ribavirin after 48 weeks of treatment to maximize sustained virological responses (SVR) in hepatitis C virus (HCV) genotype 1-infected patients remain to be understood. AIM: To investigate whether extended treatment longer than 72 weeks may be superior to 72-week treatment. METHODS: A total of 120 treatment-naïve or retreated patients with HCV genotype 1 were treated with peginterferon-alpha-2b (1.5 microg/kg/week) plus weight-based ribavirin. We had 34 late responders, in whom HCV RNA first became undetectable at week 12-48, and randomized them into three groups receiving standard-dose peginterferon-alpha-2b plus low-dose ribavirin (200 mg/day) for extended 24 weeks (group A), receiving low-dose peginterferon-alpha-2b (0.75 microg/kg/week) plus low-dose ribavirin for extended 48 weeks (group B) or no extended treatment (group C), and evaluated the outcome according to their virological response. RESULTS: Multivariate analysis showed that the treatment for 96 weeks was identified as a significant, independent factor associated with SVR in HCV genotype 1-infected late responders in comparison with group A [odds ratio (OR), 10.002; P = 0.080] and group C (OR, 17.748; P = 0.025). CONCLUSION: Extending the treatment duration from 48 weeks to 96 weeks improves SVR rates in genotype 1-infected patients with late virological response to peginterferon-alpha-2b and ribavirin.

[Complete disruption of cervical trachea, whose distal airways were migrated into the mediastinum].

The first case was a 55-year-old man, who suffered by a rope while driving his motor bicycle. On 7th day after injury, tracheotomy was scheduled due to progressive dyspnea. Following intubation of a endotracheal tube, his trachea was ruptured. The second case was a 16-year-old man, who was stabbed his trachea with a sword by his mother. His trachea completely separated following coughing during the examination of bronchoscopy. For 2 cases, we immediately excised their necks for tracheotomy but couldn't find their distal portion of trachea, because they were migrated into the mediastinum. We inserted our finger into the mediastinum for exploration and could draw it back. Both case's postoperative course was uneventful. Whenever cervical trachea is completely separated, tracheal distal end may be pulled down into the mediastinum. We invited new technique of exploration for migrated trachea using our finger.

A case of undifferentiated carcinoma of the gallbladder with anomalous arrangement of the pancreaticobiliary ductal system.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is a congenital anomaly associated with gallbladder carcinoma. Especially patients with noncystic dilatation and without dilatation of the biliary tract are at risk of gallbladder carcinoma. A 56-year-old woman with advanced gallbladder cancer associated with AJPBD but without dilatation of the biliary tract was treated at our hospital. Although histologically cancer cells remained in the layer of the proprial mucosa, extensive metastases to lymph nodes including the paraaorta and peripancreas were detected. According to the TNM classification this case was of Stage IVB. The cancer consisted of medullary round cells, and was diagnosed as undifferentiated carcinoma. After surgery poor prognosis was expected, but three years have elapsed with no recurrence. The case is of interest because of two points of discrepancy: the primary cancer did not show deep invasion but demonstrated extensive lymph node metastases; the cancer was histologically malignant but prognosis was relatively good.

Therapeutic effect of balloon-occluded retrograde transvenous obliteration on portal-systemic encephalopathy in patients with liver cirrhosis.

OBJECTIVE: Balloon-occluded retrograde transvenous obliteration (B-RTO) has recently been introduced as a new interventional modality to prevent fatal bleeding from solitary gastric varices. A large portal-systemic shunt including gastric varices also causes severe encephalopathy in some cirrhotic patients. In this study, we evaluated the effect of B-RTO as a candidate therapeutic method to treat chronic recurrent hepatic encephalopathy due mainly to a portal-systemic shunt. PATIENTS AND METHODS: Since July 1995, we experienced 43 cirrhotic patients with chronic reccurent hepatic encephalopathy. Among them, six patients had anigographically proven large (>1 cm in diameter) portal-systemic shunt, and received B-RTO. B-RTO was carried out only once using 5% ethanolamine oleate with iopamidole to obliterate the portal-systemic shunt for 30 minutes. The median observation period after B-RTO was 29 months (range 23-46 months). RESULTS: In all 6 patients, encephalopathy had disappeared after B-RTO, and the patients were free of encephalopathy during the following 6 months. B-RTO significantly reduced blood ammonia levels at one month, 3 months, and 6 months later, without affecting serum aspartate aminotransferase activity, total bilirubin and albumin concentrations, and plasma prothrombin time. Encephalopathy relapsed in 4 patients between 6 and 30 months. Additional B-RTO was required and effective in 2 of them. CONCLUSION: B-RTO is an effective treatment for chronic recurrent hepatic encephalopathy with an angiographically proven portal-systemic shunt.

Inflammatory pseudotumor of the liver with primary sclerosing cholangitis.

Inflammatory pseudotumor (IPT) of the liver is a rare benign variant of hepatic masses, and its exact etiology has not been elucidated. We report a case of IPT associated with primary sclerosing cholangitis (PSC). The patient was a 50-year-old man admitted to our hospital because of jaundice. Abdominal ultrasonography (US) and computed tomography showed multiple dilations of the intrahepatic bile ducts and multiple masses in the liver. On magnetic resonance imaging, the masses were slightly hypointense on T1-weighted images and slightly hyperintense on T2-weighted images. On T1-weighted images after the bolus infusion of Gd chelate, the masses had no contrast enhancement, and they were hypointense in the arterial phase and portal venous phase. However, they were slightly enhanced and became almost isointense relative to the surrounding normal liver parenchyma in the delayed phase. Endoscopic retrograde cholangiography demonstrated multiple irregular strictures and dilations of the intrahepatic bile ducts. Angiography demonstrated no abnormal findings, but, interestingly, subsequent dynamic CO2-enhanced US showed a strongly hyperechoic string, indicating that an artery had penetrated through the hypoechoic mass. A US-guided percutaneous needle biopsy revealed that the lesions were morphologically comparable to IPT. After cholangiography and microscopic analysis of the tumor, the final diagnosis was determined to be IPT of the liver with PSC. A number of previous reports have suggested a possible relationship between IPT and PSC, based on pathological findings. This report confirmed, based on clinical findings, that PSC is one of the causes of hepatic IPT.

Benign schwannoma of the esophagus removed by enucleation: report of a case.

A submucosal tumor of the esophagus was enucleated by a thoracotomy. A microscopic examination showed the tumor to be composed of spindle-shaped cells showing mild nuclear atypia with vague nuclear palisading and scarce mitotic figures. The tumor was surrounded by peripheral lymphoid cuffs. An immunohistochemical study demonstrated diffuse positive staining for S-100 protein in the tumor cells. The lesion was diagnosed to be an esophageal schwannoma based on these pathological features. Benign schwannoma of the esophagus has been described in five cases in four reports in the English literature. This is the sixth case diagnosed by immunohistochemical studies.

Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure.

OBJECTIVES: To compare the circulating concentrations of endotoxin and cytokines in patients with fulminant hepatitis and patients with the severe form of acute hepatitis, and to assess the effects of plasma exchange on the circulating concentrations of these inflammatory mediators in patients with acute hepatic failure. DESIGN: Prospective, consecutive entry study of patients meeting fulminant hepatitis criteria and the severe form of acute hepatitis criteria. SETTING: University hospital, intensive care unit. PATIENTS: Five patients with fulminant hepatitis, eight patients with the severe form of acute hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. INTERVENTIONS: Plasma endotoxin, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined on admission in five patients with fulminant hepatitis and eight patients with the severe form of acute hepatitis. Circulating concentrations of the inflammatory mediators were measured before and after a single course of plasma exchange in eight patients with acute liver failure, including five patients with fulminant hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-6 in patients with fulminant hepatitis were significantly higher than in patients with the severe form of acute hepatitis, whereas endotoxin concentrations did not differ between patients with fulminant hepatitis or the severe form of acute hepatitis. IL-1beta was not detectable in patients with either fulminant hepatitis or the severe form of acute hepatitis. Plasma endotoxin concentrations decreased immediately after plasma exchange. Serum concentrations of TNF-alpha and IL-6 were significantly lower after plasma exchange than before plasma exchange. CONCLUSION: TNF-alpha and IL-6 may be important in the pathogenesis of the clinical symptoms that differentiate fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange removes these inflammatory mediators from the circulation of patients with severe liver disease.

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/thymidine phosphorylase/platelet-derived endothelial cell growth factor and histological prognostic factor, and influence of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase activities and serum immunosuppressive acidic protein levels. A study group of oral anti-cancer drugs in Seiban/Tajima area].

PURPOSE: Among the pyrimidine nucleoside phosphorylases (PyNPase), thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, and is an enzyme which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor which was an antiogenetic factor, therefore. We think dThdPase may be a prognostic factor. METHODS: We investigated the possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, and examined influences of preoperative oral 5'-DFUR administration at a dose of 1,200 mg/body for 7 days on PyNPase activities and serum immunosuppressive acidic protein levels in patients with gastric cancer. RESULTS: Higher levels of PyNPase activities were especially observed in patients with v+ (p = 0.0161). PyNPase activities (p = 0.1668) and IAP (p = 0.0830) levels showed a decrease by 5'-DFUR administration. CONCLUSION: This study suggests that we must investigate in detail the possibility of PyNPase being prognostic factor, and 5'-DFUR administration may improve the prognosis of patients with gastric cancer.

Endoscopic papillary balloon dilatation for common bile duct stones: efficacy of combination with extracorporeal shockwave lithotripsy for large stones.

BACKGROUND: Endoscopic papillary balloon dilatation (EPBD) is generally considered a safe and effective technique for removal of common bile duct (CBD) stones. However, some reports have prompted concern about the risk of pancreatitis following the procedure, and it seems to be more difficult and to require adjunctive procedures more frequently in patients with large stones. AIMS: To analyse the factors influencing pancreatitis after the procedure, and to examine which is the more suitable adjunct for treating large stones, mechanical lithotripsy (ML) or extracorporeal shockwave lithotripsy (ESWL). PATIENTS AND METHODS: EPBD was performed in 92 patients, including 40 with large stones (> or = 12 mm). These 40 patients were randomly assigned to two groups receiving ML or ESWL to fragment stones (20 patients each). RESULTS: Complete ductal clearance was obtained in all 92 patients. Significant elevation of the serum amylase level compared with the prior value (> 300 IU/l) was observed in 26 (28%), and eight (8.7%) developed clinical pancreatitis. To assess the influence of various factors on the amylase level, multivariate analysis was used. The number of stones and the time required for treatment had a significant influence on the incidence of increased amylase level (P < 0.05), and ML also significantly increased it (P < 0.05). On the other hand, the amylase level remained low in the ESWL group. ML caused elevation of amylase level in 11 patients (55%), while three (15%) had elevation after ESWL. CONCLUSIONS: In patients with multiple stones, elevation of the amylase level is more frequent. This seems to be because repeated cannulation and much time is required for treatment. In patients with large stones, the rate was also high if ML was used, but was low when ESWL was used. ESWL may reduce the incidence of pancreatitis.

Chronic anti-ataxic actions of the novel thyrotropin-releasing hormone (TRH) analog, TA-0910, during and after repeated administration in Rolling mouse Nagoya: behavioral and pharmacokinetic studies.

Anti-ataxic effects of TA-0910, a novel thyrotropin-releasing hormone analog, in mice of the ataxic mutant mouse strain Rolling mouse Nagoya (RMN) are sustained beyond its 2-week oral administration period (Kinoshita et al., Eur. J. Pharmacol., 274, 65-72, 1995). We examined the concentration of TA-0910 in the central nervous system (CNS) of RMN after repeated administration in an attempt to clarify the mechanism of the sustained effect of the drug. Repeated administration of TA-0910 (3 mg/kg/d, i.p.) for 2 weeks produced a long-lasting ameliorating effect on ataxia in RMN, and this effect was maintained until 3 weeks after drug withdrawal. The concentrations of TA-0910 in the cerebrum and brain stem 24 h after the final administration were twice the concentration observed 24h after single administration. The cerebellum cencentration of TA-0910 was more than 4 times that observed 24 h after final administration. After repeated administrations, the drug concentrations in the brain tissues gradually decreased, but the drug was still detectable in the cerebrum and brain stem 3 weeks after withdrawal. However, these concentrations of TA-0910 3 weeks after withdrawal were as low those observed 24 h after single administration when there were no anti-ataxic effects. These observations suggest that the long-lasting ameliorating effect on the ataxia during and after repeated administration of TA-0910 is not ascribable to the drug remaining in the CNS of RMN.

Distribution of thyrotropin-releasing hormone (TRH) receptors in the brain of the ataxic mutant mouse, rolling mouse Nagoya.

Thyrotropin-releasing hormone (TRH) and its analog, TA-0910, ameliorate the ataxia of the mutant mouse, rolling mouse Nagoya, by metabolic normalization in the ventral tegmental field (VTF). We here investigated the distribution of cerebral TRH receptors in the rolling mouse to clarify the sites of action of these drugs. TRH receptors were widely distributed in multiple brain areas, including in the VTF and the cuneiform nucleus (CnF) which terminates in the VTF. These results suggest that TRH and TA-0910 directly activate the VTF by acting on TRH receptors in the VTF and indirectly activate it through the receptors in the CnF.

First case report of spontaneous pulmonary hemorrhage following heparin therapy in acute myocardial infarction.

Since its discovery in 1916, heparin has been used extensively for treatment of thromboembolic disorders. Bleeding is its most well-known and frequent complication. We are describing the first case report of overt pulmonary hemorrhage in a patient who received heparin after emergent angioplasty for prevention of coronary artery rethrombosis.

[Follow-up study of obese pupils and their life styles in the lower grades of primary schools].

Physical examinations and a questionnaire survey of life style were carried out on all pupils (105 boys and 110 girls) at the first grade of primary school in Saigo town, Fuse village, Goka village, and Tsuma village of Shimane prefecture in 1992. In 1994, physical examinations and a questionnaire survey were again performed along with a newly-added blood examination on the same cohort. Parents of the pupils answered the questionnaire. The pupils who were included in both the first (in 1992) and the second (in 1994) examinations and surveys (89 boys and 101 girls, but 71 boys and 77 girls for blood examination) were subjects in this study to analyse the relationship between obesity and life style. The results showed (a) the proportional rates of obese boys and girls increased during the two years; (b) the obesity index of boys and girls in the third grades correlated with the obesity index of their mothers; (c) obese boys ate snacks frequently, had a higher speed in eating, and disliked physical exercise; and (d) the obesity index of boys and girls correlated with serum total cholesterol. These findings indicate that obesity occurs as early as the lower grades of primary schools and that it continues for at least two years.

Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure.

Branched-chain amino acids (BCAA) are known to improve hepatic encephalopathy as well as protein malnutrition in cirrhosis. However, such effects in acute hepatic failure (AHF) remain to be elucidated. The current study was conducted to investigate whether BCAA improves protein metabolism in AHF. AHF was induced in male Donryu rats weighing approximately 230 g by giving 60 mg/kg lipopolysaccaride intravenously and 800 mg/kg D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF rats and control rats were given one of the following five solutions intravenously for 6 hours: 1) saline, 2) 10% glucose, 3) standard 10% amino acid formula with total nitrogen content of 12.2 g/L and BCAA/aromatic amino acid molar ratio of 37.05, 4) BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 148.2, or 5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 37.05. In parallel, each group was given a continuous infusion of 14C-leucine. After the plasma radioactivity of 14C-leucine and the expired 14CO2 level reached a plateau, protein turnover was analyzed according to the kinetic model proposed previously by Waterlow. When compared with the control, rates of total protein turnover (total flux), oxidation, and breakdown all increased significantly in AHF. Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution.(ABSTRACT TRUNCATED AT 250 WORDS)