bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of the Behavioral and Electrophysiological Abnormalities of An Animal Model of Hepatic Encephalopathy by Benzodiazepine Receptor Ligands
Authors: Gammal Sergio H. , Basile Anthony S. , Geller David , Skolnick Phil , Jones Anthony E. 
Published: March 2007

Behavioral and electrophysiological evidence implicating the GABA–benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy was obtained using an improved rat model of hepatic encephalopathy caused by thioacetamide–induced fulminant hepatic failure. After the administration of thioacetamide together with supportive therapy, acute hepatocellular failure developed in rats as a result of massive hepatocellular necrosis without evidence of renal failure or hypoglycemia. The evolution of hepatic encephalopthy in this model was sufficiently slow to readily permit the staging of the syndrome. Prominent features of the encephalopathy include a marked reduction in open field activity and an abnormal visual evoked response.
Both the deficits in spontaneous motor function and visual evoked response abnormalities of rats in stages III to IV hepatic encephalopathy were significantly improved after the administration of the benzodiazepine receptor ligands flumazenil or Ro 15–4513. Doses of flumazenil or Ro 15–4513 that produced these effects in rats with hepatic encephalopathy had no detectable action on either the behavior or the visual evoked responses of normal rats.
The ability of benzodiazepine receptor ligands to ameliorate both the behavioral depression and the visual evoked response abnormalities associated with hepatic encephalopathy in the thioacetamide–induced rat model suggest an involvement of the GABA/benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy. In addition, the similarity of these observations to those in rabbits with hepatic encephalopathy caused by galactosamine–induced fulminant hepatic failure is compatible with the hypothesis that the mechanisms of hepatic encephalopathy in these two distinct models share a common final pathway, the allosteric enhancement of GABAergic tone through the benzodiazepine receptor. These observations suggest that increased concentrations or availability of a ligand with agonist properties at the benzodiazepine receptor may be involved in the pathogenesis of hepatic encephalopathy and that administration of benzodiazepine receptor antagonists may be of value in the management of hepatic encephalopathy in man. (Hepatology 1990; 11: 371-378.)
Early Involvement of Hepatic Parenchymal Cells in Erythrohepatic Protoporphyria? An Ultrastructural Study of Patients With and Without Overt Liver Disease and the Effect of Chenodeoxycholic Acid Treatement
Authors: Raedemakers Louk H.P.M. , Cleton Maud I. , Kooliman Carole , de La Fajlle Harold Baart , van Hattum Jan 
Published: March 2007

Liver biopsy specimens obtained from two groups of erythrohepatic protoporphyria patients were studied histopathologically and ultrastructurally. Group 1 comprised seven erythrohepatic protoporphyria patients with a normal liver histology; from two patients liver biopsy specimens were available before and after 1 yr of chenodeoxycholic acid treatment. Group 2 consisted of four patients with a history of liver disease and liver histopathology; three patients were observed before and after 1 yr of chenodeoxycholic acid treatment. Liver specimens of nine kidney transplant donors served as controls.
Unlike the morphology at the light microscopic level, the ultrastructure of hepatic parenchymal cells was affected in both groups of erythrohepatic protoporphyria patients. In both groups the nuclei, endoplasmic reticulum, lateral plasma membranes and bile canaliculi were altered. Collagen fibers were frequently present. In addition, in group 2 bile thrombi and intracytoplasmic protoporphyrin crystals were observed. After chenodeoxycholic acid administration, the latter feature had diminished.
It is concluded that (a) in erythrohepatic protoporphyria ultrastructural changes are present in the hepatic parenchymal cells even in early stages of the discase. Changes in bile canalicular ultrstructure suggest a defective hepatic excretory function, probably caused by the toxic effect of protoporphyrin. (b) Chenodeoxycholic acid administration causes no distinct improvement of the ultrastructure of organelles in the hepatic parenchymal cell or the bile canalicular system but may decrease crystalline protoporphyrin deposition in the liver.(Hepatology 1990;11:449-457.)
The Effects of Ethanol Administration on Portal Pressure and Gastroesophageal Collateral Blood Flow in Patients With Alcoholic Cirrhosis
Authors: Ready Joanna B. , Hossack Kenneth F. , Rector William G. 
Published: March 2007

The pathogenesis of variceal hemorrhage is not well understood. Portal pressure and gastroesophageal collateral (azygous) blood flow are similar in patients with cirrhosis with or without a history of variceal bleeding. However, acute increases in these parameters in individual patients might predispose them to variceal rupture.
Fifteen patients with alcoholic cirrhosis and portal hypertension were evaluated to test the hypothesis that ethanol intake acutely increases portal pressure or gastroesophageal blood flow and is a possible risk factor in variceal hemorrhage. A 10% solution of ethanol in 5% dextrose in water was infused intravenously at a rate sufficient to raise the blood–alcohol level to 100 mg/dl over 30 min. Eight patients received ethanol 5% dextrose in water; seven patients received a placebo (5% dextrose in water alone). Ethanol did not produce a significant change in wedged hepatic–vein pressure, free hepatic–vein pressure, azygous blood flow, mean arterial pressure or heart rate compared with the effects of 5% dextrose in water alone.
Acute administration of ethanol does not increase portal pressure or gastroesophageal blood flow. It is unlikely that acute ethanol ingestion is a risk factor for variceal hemorrhage.(HEPATOLOGY 1990; 11:674–677.)
Methanethiol Metabolism and Its Role in the Pathogenesis of Hepatic Encephalopathy in Rats and Dogs
Authors: Blom Henk J. , Chamuleau Robert A.F.M. , Rothuizen Jan , Deutz Nicolaas E.P. , Tangerman Albert 
Published: March 2007

The metabolism of methanethiol was studied in rats. Administration of a noncomatogenic dose of methanethiol through inspired air or injection into the upper colon resulted in an elevation of the concentrations of methanethiol mixed disulfides in serum (protein-S-S-CH3 and X-S-S-CH3, × yet unknown) and in urine (X-S-S-CH3. The concentrations of methanethiol mixed disulfides proved to be a relative measure of exposure to methanethiol. The levels of volatile sulfur compounds methanethiol, dimethylsulfide and dimethyldisulfide in the air expired by rats exposed to a noncomatogenic dose of methanethiol through the colon were also elevated. Rats with acute hepatic encephalopathy caused by liver ischemia also showed elevation of methanethiol mixed disulfide levels on challenge of methanethiol through the colon or inspired air, but to a significantly smaller extent than did the corresponding sham–operated rats. This suggests that the liver is at least partly responsible for formation of methanethiol mixed disulfides. No additional toxic effects were observed in the rats with ischemic livers on methanethiol exposition when compared with normal rats, suggesting that the liver does not play an essential role in methanethiol detoxification. Metabolism of methanethiol by blood to sulfate, for example, might be more important.
In rats with acute hepatic encephalopathy caused by liver ischemia and in dogs suffering from hepatic encephalopathy resulting from chronic liver disease, large and significant increases in ammonia levels were measured. However, the mean levels of methanethiol mixed disulfides in rats and dogs with hepatic encephalopathy were not different from the mean normal levels in these animals. It is concluded that in these animal models of liver failure the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor or insignificant.(HEPATOLOGY 1990; 11:682–689.)
Blunt Hepatic and Splenic Trauma: Where Have All the Surgeons Gone?
Authors: Baker Christopher C. 
Published: March 2007

To further define the computed tomographic (CT) criteria on which to guide the nonsurgical treatment of adult patients with blunt hepatic injury, the authors retrospectively reviewed abdominal CT scans obtained before surgery during a 35–month period. Blunt hepatic injury was diagnosed in 187 patients, and review revealed 37 patients in whom the liver was the site of sole or principal intraabdominal injury detected with the help of CT before surgery. A CT–based hepatic injury classification system partly derived from similar systems established with surgical assessment was devised to grade the severity of hepatic injury. CT–based injury scores ranging from grade 1 to 5 were compared with the clinical outcome in patients treated surgically and nonsurgically. Thirty–one patients (83.7%) were successfully treated without surgery, and four patients (10.8%) had findings at celiotomy that did not require further surgery. No patient who was initially treated without surgery required delayed celiotomy due to hepatic injury. The results indicate that even major hepatic injury up to and including grade 4 severity assessed with preoperative CT can usually be managed without surgery in hemodynamically stable patients.
Nonsurgical management of blunt splenic injury in children is a well–established method to salvage splenic function; however, nonsurgical management of adult blunt splenic trauma remains controversial. To assess the value of preoperative abdominal CT in predicting the outcome of blunt splenic injury in adults, a CT based injury–severity score consisting of four grades was devised and applied in 39 adult patients with blunt splenic injury as the sole or predominant intraperitoneal injury detected with preoperative CT. While patients with high grades of splenic injury generally required early surgery, eight (35%) of 23 patients with initial grade 3 or 4 injury were treated successfully without surgery, and four (29%) of 15 patients with grade 1 or 2 injury initially treated nonsurgically required delayed celiotomy (n = 3) or emergency rehospitalization. Results show that while CT remains an accurate method of identifying and quantifying initial splenic injury, as well as documenting progression or healing of critical injury, CT cannot reliably help predict the outcome of blunt splenic injury in adults. Treatment choices should therefore be based on the hemodynamic status of the patient and results of serial laboratory and bedside assessments.
Propranolol–Induced Reduction in Recurrent Variceal Hemorrhage in Schistosomiasis
Authors: Conn Harold O. 
Published: March 2007

Fifty patients with non–cirrhotic portal fibrosis who were admitted to hospital because of upper gastrointestinal bleeding were randomly assigned to treatment with either oral propranolol given in does that reduced the resting pulse rate by 25% (25 patients) or with a placebo (25 patients). One year after the start of the study 20 patients in the propranolol group and five patients in the placebo group were free from recurrent gastrointestinal bleeding (p < 0.0001).
Giving continuous oral propranolol treatment is therefore effective in preventing recurrent upper gastriontestinal bledding in patients with noncirrhotic portal fibrosis.
Computerized Measurement of Iron in Liver Biopsies: A Comparison With Biochemical Iron Measurement
Authors: Olynyk John , Hall Pauline , Sallie Richard , Reed William , Shilkin Keith , Mackinnon Malcolm 
Published: March 2007

The measurement of stainable hepatic iron using a microcomputer image analysis system was compared with standard biochemical measurements of liver iron content in 103 liver biopsy specimens-29 of idiopathic hemochromatosis, 51 of alcoholic liver disease and 23 of various nonalcoholic liver diseases. Sections were stained using Perls' method for iron; the mean area staining positively for iron was measured and expressed as a percentage of the area of biopsy measured. Biochemical (biochemical hepatic iron [μmol/gm dry wt]/age) and morphometrical (morphometrical hepatic iron [%]/age × 100) hepatic iron indices were calculated. Patients in the idiopathic hemochromatosis group had significantly higher biochemical hepatic iron concentrations (p < 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 284 (range = 119 to 631), 21 (range = 2 to 65) and 15 (range = 3 to 31) μmol/gm dry wt, respectively. The biochemical hepatic iron index was also significantly higher (p < 0.001) in the hemochromatosis group compared with the alcoholic liver disease and nonalcoholic liver disease groups: 5.8 (range = 2.1 to 13.7), 0.4 (range = 0 to 1.6) and 0.4 (range = 0 to 1.1), respectively. Computerized measurements were significantly higher in the hemochromatosis group (p < 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 9.72% (range = 1.50% to 29.26%), 0.13% (range = 0% to 1.20%) and 0.03% (range = 0% to 0.40%), respectively. The morphometrical hepatic iron index was also significantly higher (p < 0.001) in the hemochromatosis group compared with the alcoholic liver disease and nonalcoholic liver disease groups: 19.32 (range = 2.60 to 75.10), 0.21 (range = 0 to 1.90) and 0.09 (range = 0 to 1.10), respectively. There was no overlap between the hemochromatosis and the alcoholic liver disease and nonalcoholic liver disease groups. Significant linear relationships were demonstrated between morphometrical and biochemical measurements of hepatic iron (p < 0.001) and morphometrical and biochemical hepatic iron indices (p < 0.001).
We conclude that computerized measurements of stainable hepatic iron show a significant linear relationship with biochemical iron measurements. Also, the morphometrical hepatic iron index, like the biochemical hepatic iron index, may help differentiate idiopathic hemochromatosis from other disorders with increased hepatic iron levles. (Hepatology 1990;12:26-30).
Immunoelectron Microscopic Observation of Intrahepatic Hbeag in Patients With Chronic Hepatitis B
Authors: Yamada Gotaro , Takaguchi Kouichi , Matsueda Kazuhiro , Nishimoto Hiroshi , Takahashi Michiko , Fujiki Shigeatsu , Mizuno Motowo , Kinoyama Shingo , Tsuji Takao 
Published: March 2007

Immune light and electron microscopic studies using monoclonal antibodies have been applied to localize HBeAg in liver biopsy specimens of 19 patients with chronic hepatitis B. Under the light microscope, HBeAg was demonstrated in nuclei, cytoplasm and on the cell surface of hepatocytes. The number of HBeAg–positive hepatocytes correlated well with the serum levels of HBeAg (enzyme immunoassay) and DNA–polymerase. Of 11 patients in whom high numbers of HBeAg–positive hepatocytes were found at the light microscopic level, HBeAg was also studied in hepatocytes at the electron microscopic level. The HBeAg in nuclei was either found as aggregates or dispersed diffusely. In the aggregates of HBeAg, the 27–nm core particles were frequently found. In addition, the antigen was found in the cytosol of some hepatocytes as amorphous mass and in some hepatocytes in the cisternae of perinuclear space, endoplasmic reticulum and Golgi saccules. Occasionally the antigen was found on the membranes of the cell organelles and on the plasma membranes that faced the intercellular and the Disse spaces.
These findings suggest that cytoplasmic HBeAg in hepatocytes may be ultrastructurally classified into two different patterns by its distribution, mainly in endoplasmic reticulum or in cytosol. The ratio varied between hepatocytes with these two types of patterns. The titer of serum HBeAg tended to be higher when the corresponding liver biopsy specimens contained more hepatocytes with HBeAg in endoplasmic reticulum than those with HBeAg in the cytosol. (Hepatology 1990;12:133-140).
Changes in Brain Metabolism During Hyperammonemia and Acute Liver Failure: Results of A Comparative 1H–Nmr Spectroscopy and Biochemical Investigation
Authors: Bosman Diederik K. , Deutz Nicolaas E.P. , De Graaf Albert A. , Vd Hulst Rene W.N. , Van Eijk Hans M.H. , Bovée Wim M.M.J. , Maas Martinus A.W. , Jörning George G.A. , Chamuleau Robert A.F.M. 
Published: March 2007

The effects of hyperammonemia on brain function have been studied in three different experimental models in the rat: acute liver ischemia, urease–treated animals and methionine sulfoximine-treated animals. To quantify the development of encephalopathy, clinical grading and electroencephalographic spectral analysis were used as indicators.
In all three experimental models brain ammonia concentrations increased remarkably associated with comparable increases in severity of encephalopathy. Furthermore, in vivo
1H–nuclear magnetic resonance spectroscopy of a localized cerebral cortex region showed a decrease in glutamate concentration in each of the aforementioned experimental models. This decreased cerebral cortex glutamate concentration was confirmed by biochemical analysis of cerebral cortex tissue post mortem. Furthermore, an increase in cerebral cortex glutamine and lactate concentration was observed in urease–treated rats and acute liver ischemia rats. As expected, no increase in cerebral cortex glutamine was observed in methionine sulfoximine-treated rats.
These data support the hypothesis that ammonia is of key importance in the pathogenesis of acute hepatic encephalopathy. Decreased availability of cerebral cortex glutamate for neurotransmission might be a contributing factor to the pathogenesis of hyperammonemic encephalopathy. A surprising new finding revealed by 1H–nuclear magnetic resonance spectroscopy was a decrease of cerebral cortex phosphocholine compounds in all three experimental models. The significance of this finding, however, remains speculative. (Hepatology 1990;12:281-290).
Demonstration of “Naturally Occurring Mitochondrial Antibodies” in Family Members of Patients With Primary Biliary Cirrhosis
Authors: Klein Reinhild , Berg Peter A. 
Published: March 2007

Sera from 81 healthy family members (including husbands) of 13 patients with primary biliary cirrhosis were tested by Western blotting against the antigen fractions M9 and M2 derived respectively from rat liver and beef heart mitochondria. Fifty–eight (70%) were positive and recognized four major (molecular weights 98 kD, 65 kD, 61 kD, 58 kD) and eight minor determinants (85 kD, 81 kD, 78 kD, 54 kD, 48 kD, 45 kD, 40 kD, 30 kD) labeled α–my. Each of the 58 sera recognized at least one of the four major polypeptides. In contrast, only 6% of 80 primary biliary cirrhosis patients had antibodies against one of these epitopes. Sera from 25 patients with different infectious disorders previously shown to react with submitochondrial particles by enzyme–linked immunosorbent assay also recognized at least one of the four major determinants.
From these findings it was concluded that these antibodies may belong to the family of natural autoantibodies. Since they reacted with submitochondrial fractions, they were defined as “naturally occurring mitochondrial antibodies.”
The high incidence of “naturally occurring mitochondrial antibodies” in primary biliary cirrhosis contact persons may be taken as indirect evidence for a contagious immunogenic agent circulating in the blood of primary biliary cirrhosis-patients. In contrast, the absence of “naturally occurring mitochondrial antibodies” in primary biliary cirrhosis-patients themselves implies that an underlying B–cell defect is responsible for this lack of antibody production. Considering the protective role of naturally occurring antibodies in general, this postulated B–cell defect could be a major factor in the etiopathogenesis of primary biliary cirrhosis. (Hepatology 1990; 12:335-341).
Hepatitis B virus replication in chinese patients with hepatocellular carcinoma
Authors: Lok Anna S. F. , Ma Oliver C. K. 
Published: March 2007

We studied the frequency of hepatitis B virus replication in Chinese patients with hepatocellular carcinoma. Hepatitis B e antigen and hepatitis B virus DNA could be detected in the sera of 28% and 47% of 116 HBsAg-positive patients, but not in the sera of 15 HBsAg-negative patients. Replicative forms of hepatitis B virus DNA were detected in the neoplastic and nonneoplastic liver tissues from 34% and 62% of 29 HBsAg-positive patients and 0% and 20% of five HBsAg-negative patients by Southern blot hybridization analysis.
Of the 10 patients with chronic hepatitis B virus infection in whom hepatocellular carcinoma developed during follow-up, hepatitis B e antigen and hepatitis B virus DNA were detected in the sera of seven and eight patients, respectively, at presentation, 13 to 43 mo before the diagnosis of hepatocellular carcinoma. In nine patients, hepatitis B virus DNA was persistently or intermittently detected in the serum during follow-up. Five patients remained hepatitis B e antigen-positive and seven were detectable for hepatitis B virus DNA in serum when hepatocellular carcinoma was diagnosed. Four patients had one or more episodes of exacerbations before the diagnosis of hepatocellular carcinoma; in three, the exacerbations were associated with changes in level of hepatitis B virus replication.
Our study demonstrated that despite the long interval between the onset of hepatitis B virus infection and the development of hepatocellular carcinoma, hepatitis B virus replication persisted in most patients with hepatocellular carcinoma, albeit at a low level. (Hepatology 1990;12:582-588).
Histological features and clinical course of large regenerative nodules: Evaluation of their precancerous potentiality
Authors: Kondo Fukuo , Ebara Masaaki , Sugiura Nobuyuki , Wada Katsunori , Kita Kazuhiko , Hirooka Noboru , Nagato Yoshinobu , Kondo Yoichiro , Ohto Masao , Okuda Kunio 
Published: March 2007

Seventeen patients with cirrhosis and histologically defined, ultrasonically detected, large regenerative nodules of the liver were followed without treatment for more than 1 yr (range = 13 to 51 mo). During the follow-up period, none of the nodules were demonstrated sonographically to have enlarged. Computed tomography and/or hepatic angiography were also performed in 14 patients, but there was no evidence of malignant transformation in these lesions. None of the 17 patients showed acute elevation of serum α-fetoprotein levels. Furthermore, four nodules became undetectable by these imaging procedures. Follow-up biopsy performed in seven patients revealed no significant histological changes from the first biopsy sample. However, HCCs developed apart from these large regenerative nodules in four patients. These HCCs suddenly appeared and did not seem to have been derived from preexisting large regenerative nodules.
From these observations, it was not possible to regard a large regenerative nodule having no cytological atypia as a high-potential premalignant lesion. Their precancerous potentiality needs to be compared with that of ordinary pseudolobules. (Hepatology 1990;12:592-598).