bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced acetaminophen toxicity in rats with bilirubin glucuronyl transferase deficiency
Authors: de Morais Sonia M. F. , Wells Peter G. 
Published: March 2007

Glucuronidation is the major pathway for elimination of acetaminophen, diverting it from the toxifying pathway catalyzed by cytochromes P-450. A genetic deficiency in bilirubin UDP-glucuronyl transferase may predispose humans and animals to the toxicity of drugs that are extensively glucuronidated, if other glucuronyl transferase isoenzymes are concurrently deficient. Homozygous and heterozygous Gunn rats are, respectively, severely and moderately deficient in glucuronyl transferase. Acetaminophen (500 mg per kg) was administered intraperitoneally to homozygous and heterozygous Gunn rats and to Wistar controls. Hepatic and renal cellular damage was assessed by peak plasma concentrations of ALT and blood urea nitrogen, respectively. Homozygous and heterozygous Gunn rats showed, respectively, 115-fold and 9-fold higher ALT concentrations compared to Wistar controls. Blood urea nitrogen was elevated only in the homozygous Gunn rats (3-fold). Biotransformation of acetaminophen was measured by high-performance liquid chromatography. Acetaminophen glucuronidation was decreased by 72 and 35% (p < 0.05), respectively, in the homozygous and heterozygous Gunn rats compared with Wistar controls. Production of acetaminophen glucuronide correlated negatively with ALT concentration (r = −0.89, p < 0.001). Production of glutathione-derived metabolites, reflecting acetaminophen bioactivation, was 2 to 3-fold higher in the Gunn rats (p < 0.05) and correlated with ALT concentrations (r = 0.90, p < 0.001).
The results indicate that heterozygous and homozygous deficiencies in glucuronyl transferase are, respectively, intermediate and major determinants of acetaminophen bioactivation and toxicity. Also, a genetic deficiency in bilirubin glucuronyl transferase in Gunn rats is associated with a deficiency in the glucuronidation of drug substrates.
Balloon tamponade vs. endoscopic sclerotherapy in the management of active variceal hemorrhage
Authors: Terés Josep 
Published: March 2007

Sengstaken-Blakemore tamponade is used for the initial control of bleeding esophageal varices (BEV), although it is known to be potentially dangerous. Sclerotherapy has been shown to be effective in the treatment of BEV. This trial has been designed to evaluate comparatively the effectiveness of both procedures in the initial control of the hemorrhage.
Forty-three patients with BEV were included in the trial. Twenty patients (group SB) were treated by tamponade. Twenty-three patients (group ST) were treated by sclerotherapy by means of a simple technique.
During the first 24 hours, hemostasis was obtained in 16 of the SB patients and in all 23 of the ST patients (p < 0.05). At seven days, nine SB patients and 19 ST patients were free of hemorrhagic relapse (p < 0.05). By stratifying in relation to hepatic failure, the difference was greater (p < 0.005) if patients with Child’s A classification were excluded. It is concluded that sclerotherapy should be undertaken in almost every instance at the same moment that diagnosis is made, bypassing the intermediate step of tamponade.
Bile acids inhibit endotoxin-induced release of tumor necrosis factor by monocytes: An in Vitro study
Authors: Greve Jan Willem , Gouma Dirk J. , Buurman Wim A. 
Published: March 2007

Endotoxins play an important role in the pathogenesis of complications of surgery in obstructive jaundice. Preoperative treatment with orally administered deoxycholic acid prevented endotoxin-related complications, such as renal malfunction. Other bile acids, however, were less effective, and the mechanism of action is not known.
Endotoxin toxicity is considered to be largely mediated by tumor necrosis factor/cachectin, a cytokine release by mononucler phagocytes. Therefore, we studied the influence of different bile acids on endotoxin-induced tumor necrosis factor production by monocytes in vitro.
Bile acids inhibit tumor necrosis factor production through a direct inhibitory effect on the monocytes. Deoxycholic acid was the most effective, chenodeoxy-cholic acid was less effective and ursodeoxycholic acid was ineffective in the concentrations used. Bile acids did not inactivate endotoxin as measured in a chromogenic Limulus amebocyte lysate assay.
The therapeutic effect of bile acids in obstructive jaundice can be explained by an inhibition of endotoxin-induced tumor necrosis factor release by mononuclear phagocytes.
Reduced–Size Orthotopic Liver Transplantation: Use in the Management of Children With Chronic Liver Disease
Authors: Emond Jean C. , Whitington Peter F. , Thistlethwaite Richard J. , Alonso Estella M. , Broelsch Christoph E. 
Published: March 2007

Reducing the size of a liver for use in a recipient smaller than the donor is one way to reduce mortality before orthotopic liver transplantation in children because of the scarcity of pediatric organ donors. In this report, we review the results of this approach over the past 2 years, during which we have used reduced–size orthotopic liver transplantation routinely in small children.
Forty–nine children underwent orthotopic liver transplantation between September, 1986, and October, 1988; orthotopic liver transplantation with a whole organ (full–size orthotopic liver transplantation) was performed in 36 children, whereas 13 patients received reduced–size orthotopic liver transplantation. In two pairs of patients, the reduced grafts were obtained from single donors, using a “split–liver” procedure. All grafts were implanted in the orthotopic position following total recipient hepatectomy.
The preoperative diagnostic categories were not significantly different between groups. Patients receiving reduced–size orthotopic liver transplantation were younger (1.6 ± 1.5 vs. 4.4 ± 4.6 years), and a higher percentage were in the intensive care unit prior to transplant (31 vs. 9%). Thirty of 36 (82%) patients receiving full–size orthotopic liver transplantation and 10 of 13 (77%) patients receiving reduced–size orthotopic liver transplantation are alive 3 to 27 months after transplantation. The rates of retransplantation were 24% for full–size orthotopic liver transplantation and 15% for reduced–size orthotopic liver transplantation.
Despite the greater complexity of reduced–size ortho–topic liver transplantation and the higher frequency of critically ill recipients selected for the procedure, the results of reduced–size orthotopic liver transplantation are comparable with full–size orthotopic liver transplantation. These results justify the continued use of reduced–size orthotopic liver transplantation in children with end–stage liver disease.
Angiographically Undetected Small Hepatocellular Carcinoma: Clinicopathological Characteristics, Follow–Up and Treatment
Authors: Sonoda Takashi , Shirabe Ken , Takenaka Kenji , Kanematsu Takashi , Yasumori Kotaro , Sugimachi Keizo 
Published: March 2007

We studied 36 cases (38 nodules) of small hepatocellular carcinoma with special attention directed to detectability using angiography and histology. Among the 38 nodules, 31 nodules (81.6%) were evident. The remaining seven (18.4%) were not evident angiographically but were detected using ultrasonography and/or computed tomography, prior to angiography. An elevated level of serum α–fetoprotein also suggested a diagnosis of hepatocellular carcinoma. When comparisons were made between angiographically detected and undetected nodules, there was no statistically significant difference in parameters, including sex of the patient, tumor size, location of the tumor, positive rate for hepatitis B surface antigen, history of liver disease and values of α–fetoprotein.
The small hepatocellular carcinomas not detected angiographically and evidenced only histologically had the following characteristics: (i) no fibrous capsule surrounding the nodules; (ii) well–differentiated tumors; (iii) replacing growth pattern of cancer cells, and (iv) remains of portal tracts within the tumor. The replacing growth pattern and the presence of portal tracts may correlate with the low detectability in angiography.
When a definite diagnosis of angiographically undetectable tumors cannot be made using close surveillance with ultrasonography or α–fetoprotein and/or needle biopsy under ultrasonic guide, surgical intervention should be considered, particularly for patients at high risk for hepatocellular carcinoma.
Prospective Study of Bacterial Infection in Acute Liver Failure: An Analysis of Fifty Patients
Authors: Rolando Nancy , Harvey Felicity , Brahm Javier , Philpott-Howard John , Alexander Graeme , Gimson Alexander , Casewell Mark , Fagan Elizabeth , Williams Roger 
Published: March 2007

Fifty consecutive patients admitted with acute liver failure, minimal grade II encephalopathy, were studied prospectively to determine to incidence, timing and cause of bacterial infection, the relationship to clinical criterial for infection; and the influence of early microbiological diagnosis on clinical outcome. There were 53 proven bacterial infections in 40 patients, whereas in 5 of the remaining 10 patients infection was suspected on clinical grounds in the absence of significant cultures. Seven patients (14%) had more than one bacterial infection, and four patients had simultaneous infections caused by different organism at each site. Fourteen infections (26.4%) were associated with backteremia, and in six of these no source was found. Twenty–five infections (47.1%) arose from the respiratoory tract, 12 (22.6%) from the urinary tract and 2 (3.7%) from central venous due to gram–positive bacteria; Staphylococcus aureus accounted for 19 (35.8%) of all the infections.
Thirty patients died (60%), 28 of whom had bacterial infection at some time; in 24 of these the infection was diagnosed less than 24 hr before death. All nine deaths that occurred more than 7 days after admission were directly attributable to microbial infection.
Clinical features such as elevated temperature and elevated peripheral white blood cell count were poor indicators of bacterial infection because these were absent in 30.2% of cases.
These data show that there is a high incidence of bacterial infection early in the course of acute liver failure and suggest that porphylactic antimicrobial therapy, although unproven, might be justified. (HEPATOLOGY 1990; 11: 49-53.
Hemodynamic Mechanisms of Emerging Portal Hypertension Caused by Schistosomiasis in the Hamster
Authors: Morgan James S. , Groszmann Roberto J. , Rojkind Marcos , Enriquez Rosa 
Published: March 2007

A hamster model of schistosomiasis has provided the first opportunity to sequentially examine the early phases of the development of portal hypertension in a natural model of chronic liver disease.
Groups of hamsters were infected with 50 cercariae of Schistosoma mansoni and underwent hemodynamic evaluation at intervals of 5, 8, 12 and 20 wk after infection. A progressive rise in intrahepatic resistance (from 4.0 ± 0.4 to 8.4 ± 1.0 mm Hg min. ml-1. gm liver weight [p <0.01]) appeared to play a major role in the initial stages of evolving portal hypertension. A gradual decline in portal blood flow (from 2.1 ± 0.3 to 1.3 ± 0.1 ml. min-1gm-1liver weight [p <0.01]) was only partially compensated for by an increase in hepatic arterial flow. Accordingly, by week 20, total hepatic blood flow decreased 23%. Liver weight that increased markedly between 5 and 12 wk after infection, as a result of the acute accumulation of obstructing granulomas, stabilized between wk 12 and 20, while a gradual but progressive rise in hepatic collagen content was seen. Portal pressure increased 75% during the study period.
Chronic examination of this natural model should help define the pathogenesis of the complications of portal hypertension and contribute to the basis for effective intervention in this disease process.
Molecular Characterization of A New Variant of Hepatitis B Virus in A Persistently Infected Homosexual Man
Authors: Bhat Ramesh A. , Ulrich Paul P. , Vyas Girish N. 
Published: March 2007

Based on the diversity of nucleotide sequences of cloned hepatitis B virus DNA genomes, we have predicted possible replication of genetic variants of human hepatitis B virus. This prediction is exemplified by studies of a chronic carrier of HBsAg/adw2, who lacked anti–HBc but carried exceedingly high levels of hepatitis B virus DNA in serum. Molecular characterization of a number of clones revealed a restriction map that deviated significantly from the typical pattern of the adw2 subtype, especially around the EcoRI site commonly used as a reference point. Mutations appearing consistently in the precore and core regions included (a) mutation in the precore region resulting in a termination codon after the initiation codon, (b) mutation of the core initiation codon and (c) an inframe insert of 36 nucleotides in the precore region with a new initiation site for the core protein.
The 36–nucleotide insertion resulted in a new core protein with 12 extra amino acids at its amino–terminal end. A few scattered point mutations were clustered in the amino–terminal half of the core gene. Although the core protein of this hepatitis B virus variant carried immunologically detectable HBcAg, the absence of a humoral immune response to HBcAg could have been caused by previous infection with human immunodeficiency virus. This naturally occurring human hepatitis B virus variant replicated efficiently without expressing the precore region, confirming previous observations made of the artificial mutants of duck hepatitis B virus.
Hepatis C Virus: A Giant Leap Forward
Authors: Zuckerman Arie J. 
Published: March 2007

A random–primed complementary DNA library was constructed from plasma containing the uncharacterized non–A, non–B hepatitis (NANBH) agent and screened with serum from a patient diagnosed with NANBH. A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections. This clone is not derived from host DNA but from an RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and that is positive–stranded with respect to the encoded NANBH antigen. These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae. This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents.
A specific assay has been developed for a blood–borne non–A, non–B hepatitis (NANBH) virus in which a polypeptide synthesized in recombinant yeast clones of the hepatitis C virus (HCV) is used to capture circulating viral antibodies. HCV antibodies were detected in six of seven human sera that were shown previously to transmit NANBH to chimpanzees. Assays of ten blood transfusions in the United States that resulted in chronic NANBH revealed that there was at least one positive blood donor in nine of these cases and that all ten recipients seroconverted during their illnesses. About 80 percent of chronic, post–transfusion NANBH (PT–NANBH) patients from Italy and Japan had circulating HCV antibody; a much lower frequency (15 percent) was observed in acute, resolving infections. In addition, 58 percent of NANBH patients from the United States with no identifiable source of parenteral exposure to the virus were also positive for HCV antibody. These data indicate that HCV is a major cause of NANBH throughout the world.
Energy Metabolism in Patients With Acute and Chronic Liver Disease
Authors: Schneeweiss Bruno , Graninger Wolfgang , Ferenci Peter , Eichinger Sabine , Grimm Georg , Schneider Barbara , Laggner Anton N. , Lenz Kurt , Kleinberger Gunter 
Published: March 2007

Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsyproven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 ± 4.0 (mean ± S. E. M.), 216.4 ± 4.7 and 228.8 ± 7.1 (p < 0.05 vs. controls), respectively. When related to body surface area (Kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 ± 0.02), patients with acute hepatitis (1.03 ± 0.02) and cirrhotic patients (1.06 ± 0.03). However, when related to 24–hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was in creased in cirrhosis (p < 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% ± 5%), carbohydrate (2% ± 4%) and protein (12% ± 1%) were different from those of normal controls who metabolized 45% ± 4%, 38% ± 4%, 17% ± 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate.
In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrbosis resembles that in starvation. Data on resting energy expenditure depend on the calculations used. Resting energy expenditure was not increased in either group when related to body surface area. An inverse association between the severity of liver disease and energy expenditure was found in cirrhosis. (Hepatology 1990;11:387-393.)
The Relevance of the Order of Revascularization in Liver Grafting
Authors: Hickman Rosemary , Innes Cath Rose 
Published: March 2007

A study was conducted comparing the effects of initial arterialization vs. initial portal revascularization in unstored warm ischemic (for 30 min) livers, livers stored for 4 hr at 0° C in Collins solution and livers rendered warm ischemic for 1 hr before removal and replacement as autografts. All livers that received initial arterialization showed uniform diffuse perfusion, whereas those with initial portal perfusion were patchy and well perfused only in the right lobe. In the experimental animal, initial arterialization using an end–to–end method was much casier and required less retraction.
The energy charge and ATP levels dropped sharply during brief warm ischemia but returned rapidly to normal on revascularization. Although the decline in energy charge was less in stored livers, the return to normal was slower and incomplete. Plasma levels of AST indicated much greater damage in the stored livers and were lowest in recipients in unstored livers that were arterialized first. After longer warm ischemia, energy charge values declined and only completely returned to 60% of preoperative values within 2 hr of grafting. Despite this, the survival rate of these animals was very poor and only one survived overnight. Seven of the 12 survived the procedure, but in five death occurred within 30 min of full revascularization. In this group, AST levels rose sharply after revascularization to a mean level of 1,000 U. The resutls suggest that while initial arterizlization is beneficial if brief warm ischemia has occurred, it has no advantages other than improved subjective appearance of the liver and ease of performance after a 4–hr period of cold storage. Neither order of revascularization reversed the damage caused by 1 hr definitive warm ischemia. Although the advantages were limited, there were no appearent detrimental effects of primary arterialization and thus this order could be undertaken if so desired.(Hepatology 1990;11:471-476.)
Effects of Streptozotocin Diabetes in the Rat on Blood Levels of Ten Specific Plasma Proteins and on Their Net Biosynthesis by the Isolated Perfused Liver
Authors: Miller Leon L. , Treat Donna Eddy , Fridd Bruce , Wemett Drusilla 
Published: March 2007

Adult male Sprague–Dawley rats with streptozotocin–induced diabetes (6 to 8 wk duration), treated or untreated with insulin, were studied with two aims: (a) to ascertain whether protracted diabetes in the rat is associated with changes in circulating plasma protein levels analogous to those reported in human diabetic patients with clinical evidence of complications; (b) to evaluate the effects of experimental diabetes on the net cumulative biosynthesis of 10 specific plasma proteins by the isolated liver, perfused for 24 hr.
Samples of liver donor plasma and samples of perfusate were analyzed by single radial immunodiffusion or by rocket immunoelectrophoresis for albumin, α1–macroglobulin and the acute phase glycoproteins: fibrinogen, α1–acid glycoprotein (Darcy), α1, acid glycoprotein (Kawasaki), haptoglobin, α2–(acute phase) globulin, hemopexin, C3–complement and ceruloplasmin.
Diabetes (6 to 8 wk), untreated with insulin, resulted in significantly increased liver donor plasma levels of α1–acid glycoprotein (Darcy) and α1–acid glycoprotein (Kawasaki); plasma levels of hemopexin and of C3 decreased to 75% and 30% of normal, respectively. Insulin treatment of diabetic liver donors for 6 to 8 wk prevented the increase in α1–acid glycoprotein (Darcy) and α1–acid glycoprotein (Kawasaki) and minimized the decrease in C3 to 75% of normal.
Perfused livers from untreated diabetic rats (6 to 8 wk) showed slightly decreased cumulative synthesis and secretion of α1–acid glycoprotein (Darcy); however, synthesis of albumin was reduced to 35% of normal and that of eight glycoproteins ranged from 25% of normal and that of eight glycoproteins renged from 25% of normal (fibrinogen) to 12% of normal (C3). The striking in vitro induction of increased synthesis of acute–phase proteins by cortisol plus insulin in the isolated perfused normalliver was in contrast to the severely attenuated induction in perfused livers of untreated diabetic rats, which ranges from 50% of normal for α1–acid glycoprotein (Darcy) to 5% of normal (C3).
Severely negative perfusate nitrogen balance and impaired glucose utilization by perfused untreated diabetic livers contrasted with positive nitrogen balance and good glucose utilization of normal livers in response to insulin plus cortisol. The plasma protein synthetic capacity and the in vitro response to insulin plus cortisol of perfused livers from insulin–treated diabetic rats were normal for seven of the proteins but moderately decreased for albumin, haptoglobin and C3.(HEPATOLOGY 1990; 11:635–645.)