bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitronectin in Liver Disorders: Biochemical and Immunohistochemical Studies
Authors: Inuzuka Sadataka , Ueno Takato , Torimura Takuji , Tamaki Seishu , Sakata Ryuichiro , Sata Michio , Yoshida Hiroshi , Tanikawa Kyuichi 
Published: March 2007

The concentration of plasma vitronectin was determined and compared with various parameters of liver function including the blood coagulation system in patients with liver diseases. The severity of cirrhosis was graded according to Child's criteria and compared with the plasma vitronectin level. Furthermore, the distribution of vitronectin in the liver of patients with liver diseases was studied by light and electron microscopy using the indirect immunoperoxidase method.
The plasma vitronectin level was low in all liver disease groups as compared with the healthy controls. The difference from the controls was significant in patients with hepatocellular carcinoma and decompensated cirrhosis. Moreover, the plasma vitronectin level was positively correlated with the levels of serum cholinesterase, albumin, plasma α2 plasmin inhibitor–plasmin complex and the prothrombin time and results of the hepatoplastin test. Plasma vitronectin decreased with increasing severity of cirrhosis according to Child's criteria. These results suggest that the plasma vitronectin level is a useful parameter of hepatic synthetic function in patients with liver diseases; it may also reflect the severity of cirrhosis.
Light microscopy revealed vitronectin in the area of focal necrosis and the portal tracts in the liver of patients with acute viral hepatitis, in the area of piecemeal necrosis in the liver of patients with chronic hepatitis and along the area of fiber deposition in the liver of patients with cirrhosis. Immunoelectron microscopy showed vitronectin in the rough endoplasmic reticulum of hepatocytes. Moreover, vitronectin was seen around inflammatory cells, endothelial cells, Ito cells and hepatocytes in the perisinusoidal area near focal necrosis and piecemeal necrosis and on collagen fibers.
These results suggest that vitronectin may be produced by hepatocytes and that they play an important role as an extracellular matrix component in the injured liver. (Hepatology 1992;15:629-636).
Hyperfibrinolysis Increases the Risk of Gastrointestinal Hemorrhage in Patients With Advanced Cirrhosis
Authors: Violi Francesco , Ferro Domenico , Basili Stefania , Quintarelli Claudio , Saliola Mirella , Alessandri Cesare , Cordova Corrado , Balsano Francesco 
Published: March 2007

Sixty–one patients with different degrees of liver failure, 23 with Child–Pugh class B and 38 with Child–Pugh class C, were studied and observed for 3 yr. Coagulation index analysis showed significantly lower values of prothrombin activity, more prolonged activated partial thromboplastin time, higher bilirubin and fibrinogen degradation products values in class C patients. Among all patients, 28 had fibrinogen degradation products values greater than 10 μg/ml, and in these patients a hyperfibrinolytic state was confirmed by higher values of circulating plasminogen activator antigen (17.3 ± 8.7 ng/ml vs. 5.41 ± 1.9 ng/ml; p < 0.0001) and activity (6.6 ± 2.1 IU/ml vs. 1.92 ± 1.12 IU/mi; p < 0.0001) and significantly lower plasminogen activator inhibitor antigen (6.4 ± 3.5 ng/ml vs. 15.8 ± 5.6 ng/ml; p < 0.0001) and activity (3.6 ± 2.2 IU/ml vs. 8.5 ± 3.9 IU/ml; p < 0.0001). Patients with positive fibrinogen degradation products had higher serum bilirubin (6 ± 4 mg/dl vs. 2 ± 2 mg/dl; p < 0.0001) and lower fibrinogen (156 ± 52 mg/dl vs. 194 ± 62 mg/dl; p < 0.02) than patients without hyperfibrinolysis. During the follow–up period, 41 patients died, 22 from fatal gastrointestinal hemorrhage and 19 from liver failure. Thirty patients experienced fatal (22 patients) and nonfatal (8 patients) gastrointestinal hemorrhage. Patients with positive fibrinogen degradation products or class C had a higher risk of gastrointestinal bleeding than patients with negative fibrinogen degradation products (odds ratio = 8) or class B (odds ratio = 3.5), respectively. Cox's multiple regression model showed that positive fibrinogen degradation products was the best bleeding predictor (β coefficient = 3.9 ± 0.7 S.E.M., p < 0.001).
This study indicates that in cirrhosis the presence of hyperfibrinolysis should be regarded as an important warning sign of gastrointestinal bleeding. (Hepatology 1992;15:672-676).
Predicting Postprocedure Bleeding in Liver Disease
Authors: Davenport Robertson D. 
Published: March 2007

Prophylactic transfusions of fresh frozen plasma and platelets are sometimes given to patients with mild elevations in prothrombin time (PT) and partial thromboplastin time (PTF) and mild thrombocytopenia before percutaneous liver biopsy. To determine whether PTs and PTFs 1.1-1.5 times midrange normal levels and platelet counts 50-99 × 109/L are associated with increased bleeding complications, hospital records of all patients who underwent percutaneous liver biopsy during 56 consecutive months (n = 291) were reviewed. Complete information was available for 177 inpatient procedures (155 standard, 22 fine needle). Overall, the frequency of bleeding complications in patients with platelet counts ± 50 × 109/L was 3.4% (6 of 175), with no significant difference between patients with mild hemostatic abnormalities and patients with normal parameters. These data suggest that prophylactic transfusions may not be necessary. One factor was highly associated with bleeding complications: a patient diagnosis of malignancy, 14% (7 of 50) compared with 0.8% (1 of 127) among other patients (P < 0.001). These patients should be monitored closely after biopsy.
To determine whether untreated mild coagulopathy in patients with no evidence of clinical bleeding is associated with an increased risk of hemorrhage after paracentesis or thoracentesis, retrospective examination was conducted of 608 consecutive procedures for which prothrombin time (PT), partial thromboplastin time (PTT), platelet (Plt) counts, and preprocedure and postprocedure hemoglobin concentrations were available. There was no increased bleeding in patients with mild to moderate coagulopathy (defined as PT or PTT up to twice the midpoint normal range or plt count of 50 to 99 × 103 per μL [50-99 × 109 L]). However, patients with markedly elevated serum creatinine levels (6.0 to 14.0 mg/dL [530-1240 μmol/L]) had a significantly greater average hemoglobin loss (–0.82 ± 1.3 g/dL [–8 ± 13 g/L], n = 11) than patients with normal serum creatinine levels (–0.12 ± 088 g/dL [–1 ± 9 g/L], n = 450) (p = 0.011). Overall, the frequency of bleeding complications requiring red cell transfusions was very low: 0.2 percent of events. The most common diagnosis for patients who had paracentesis was alcoholic liver disease (72%); for those having thoracentesis, it was infection (37%). It can be concluded that, for these patients, prophylactic plasma or platelet transfusions are not necessary. Patients with markedly elevated serum creatinine deserve close postprocedure observation.
Genetic Structure and Heterogeneity of Hepatitis C Virus: A Vaccine Impediment?
Authors: Daugherty Daryl 
Published: March 2007

The nucleotide sequence of the RNA genome of the human hepatitis C virus (HCV) has been determined from overlapping cDNA clones. The sequence (9379 nucleotides) has a single large open reading frame that could encode a viral polyprotein precursor of 3011 amino acids. While there is little overall amino acid and nucleotide sequence homology with other viruses, the 5′ HCV nucleotide sequence upstream of this large open reading frame has substantial similarity to the 5′ termini of pestiviral genomes. The polyprotein also has significant sequence similarity to helicases encoded by animal pestiviruses, plant potyviruses, and human flaviviruses, and it contains sequence motifs widely conserved among viral replicases and trypsin–like proteases. A basic, presumed nucleocapsid domain is located at the N terminus upstream of a region containing numerous potential N–linked glycosylation sites. These HCV domains are located in the same relative position as observed in the pestiviruses and flaviviruses and the hydrophobic profiles of all three viral polyproteins are similar. These combined data indicate that HCV is an unusual virus that is most related to the pestiviruses. Significant genome diversity is apparent within the putative 5′ structural gene region of different HCV isolates, suggesting the presence of closely related but distinct viral genotypes.
The nucleotide sequences of cDNAs (275 base–pairs) in the non–structural protein 5 regions of Japanese isolates of hepatitis C virus (HCV–J) from the plasma of 11 patients with non–A, non–B hepatitis and the livers of five patients with hepatocellular carcinoma were analyzed. Approximately 14 to 17% of nucleotide sequences of the HCV–Js examined differed from that of the original isolate in the United States (HCV–US). Furthermore, 2.5 to 11% sequence diversity was found among the HCV–Js. The nucleotide sequences of the HCV–Js showed characteristic common differences from that of HCV–US, although they also showed some random substitutions. Plural HCV–J genomes were found in two of the cDNAs derived from liver specimens, and a deletion of 102 nucleotides was found in the eDNA derived from one plasma specimen. These results suggest that HCV–J is a strain different from the HCV–US and that mutation of the viral genome occurs at as high a frequency as in that of the human immunodeficiency virus.
Mirex–Induced Adaptive Liver Growth in Rats Subjected to Thyroidectomy
Authors: Yarbrough James D. , Grimley Jo M. , Thottassery Jaideep V. 
Published: March 2007

ABSTRPlCT

The organochlorine compound mirex (dodecachlorooctahydro–1,3,4–metheno–2H–cyclobuta–CD–pentalene) induces an adaptive liver growth dependent on the hormonal status of the experimental animal. In the intact laboratory rat, mirex induces liver growth that is an expression of both cellular hyperplasia and hypertrophy. However, in rats subjected to adrenalectomy, mirex induces liver growth that is essentially hyperplastic. Corticosterone supplements given to rats subjected to adrenalectomy and treated with mirex restore the hypertrophic component of liver growth. Therefore it appears that the expression of the hypertrophic component of mirex–induced liver growth is corticosterone dependent.
To further explore the hormonal modulation of the expression of mirex–induced adaptive liver growth, rats subjected to thyroidectomy were studied. In male rats subjected to thyroidectomy, a single oral dose of mirex (100 mg/kg body wt) increased relative liver weight (liver wt/body wt × 100) by 62% within 72–hr after mirex administration. Liver growth occurred in the absence of [H]thymidine incorporation into liver DNA. Thus the observed liver growth was totally hypertrophic. However, in mirex–dosed rats subjected to thyroidectomy given twice–daily subcutaneous injections of thyroxine (5 mg/kg body wt), relative liver weight was increased by 204% of the control value within 72–hr after mirex administration, and there was a peak of [H]thymidine incorporation into liver DNA 54 hr after mirex administration. These studies suggest that the expression of hyperplasia in mirex–induced adaptive liver growth is thyroxine dependent. (Hepatology 1992;15:923-927).
Opposite Responses of Nuclear Spermidine N 8–Acetyltransferase and Histone Acetyltransferase Activities to Regenerative Stimuli in Rat Liver
Authors: Desiderio Maria Alfonsina 
Published: March 2007

ABSTRPlCT

Experiments performed in different models of hepatic regeneration at the time of maximal DNA synthesis, determined by thymidine kinase activity assay, demonstrated that spermidine N
8–acetyltransferase activity increased 48 hr after CCl4 administration (2–fold), 72 hr after CCl4 plus phenobarbital (3–fold) and 24 hr after partial hepatectomy (4.5–fold). On the contrary, at these times histone acetyltransferase activity diminished (approximately twofold) and was unchanged compared with control values in the liver of hepatotoxin–treated and hepatectomized rats, respectively. Histone acetylation was, however, enhanced 1.5–fold before the onset of DNA replication (14 hr), and 3.4–fold after the peak of DNA synthesis (32 hr) in the liver of hepatectomized rats.
α–Difluoromethylornithine, a specific and irreversible inhibitor of ornithine decarboxylase that was administered to hepatectomized rats, blocked polyamine synthesis, thymidine kinase activity and consequently liver regeneration 24 hr after the surgery. In those conditions, spermidine N
8–acetyltransferase activity was decreased approximately twofold, whereas histone acetyltransferase activity was elevated approximately twofold. All these effects were reversed by putrescine coadministration.
Altogether, these findings showed that nuclear spermidine N
8–acetyltransferase and histone acetyltransferase activities were regulated in opposite ways during the processes associated with liver regeneration. Moreover, they suggested that the polyamines themselves might have a direct or indirect role in this regulation. (Hepatology 1992;15:928-933).
Is Continued Enthusiasm for Ursodeoxycholic Acid Therapy for the Treatment of Primary Biliary Cirrhosis Warranted?
Authors: Wiesner Russell H. 
Published: March 2007

ABSTRPlCT

Background.
In primary biliary cirrhosis the hepatic lesions may result, at least in part, from the intracellular accumulation of potentially toxic endogenous bile acids. Preliminary work suggests that the administration of ursodiol (also called ursodeoxycholic acid), a hydrophilic bile acid without hepatotoxicity, leads to improvement in the condition of patients with primary biliary cirrhosis.

Methods.
We conducted a two–year, multicenter, double–blind trial to compare the efficacy of ursodiol with that of placebo. Patients with biopsy–proved primary biliary cirrhosis were randomly assigned to receive either ursodiol (13 to 15 mg per kilogram of body weight per day) (n = 73) or placebo (n = 73). Treatment failure was defined as a doubling of bilirubin levels to more than 70 μmol per liter or the occurrence of a severe complication (ascites or variceal bleeding) or an adverse reaction.

Results.
Treatment failed in 6 patients in the ursodiol group, as compared with 13 in the placebo group (P < 0.01 by Cox regression model). A single patient in each group withdrew because of minor adverse effects. After two years of treatment, the proportion of patients with clinically overt disease decreased only in the ursodiol group (P < 0.02). The patients treated with ursodiol had significant improvements in serum levels of bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, γ–glutamyltransferase, cholesterol, and IgM (all P < 0.001); the antimitochondrial–antibody titer (P < 0.01); and the Mayo risk score (P < 0.001). Follow–up analysis of 95 liver–biopsy specimens showed a significant improvement in the mean histologic score (P < 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol.

Conclusions.
Ursodiol is a safe and effective treatment for primary biliary cirrhosis.
Terlipressin Vs. Somatostatin in Bleeding Esophageal Varices: A Controlled, Double–Blind Study
Authors: Walker Siegfried , Kreichgauer Heinz-Peter , Bode Christian J. 
Published: March 2007

Fifty episodes of bleeding from esophageal or gastric varices in 33 patients with cirrhosis were randomized to treatment with either intravenous terlipressin (2 mg initially and 1 mg every 4 hr for 24 hr together with bolus injection and continuous infusion of placebo) or with somatostatin (250 μg as a bolus and continuous infusion of 250 μg/hr somatostatin for 24 hr and placebo injections). Standard therapy with transfusions, fluid and electrolyte correction and lactulose was administered in both groups.
In the terlipressin group, 22 of 25 bleeding episodes (88%) were initially stopped by the vasoactive drugs, and in the somatostatin group 19 of 25 bleeding episodes (76%) were initially stopped by the vasoactive drugs. Two of the three bleeding episodes not arrested by terlipressin and five of the six bleeding episodes not arrested by somatostatin were controlled by balloon tamponade. In one patient in each group variceal bleeding initially could not be stopped, and the patients died. The failure rate of the vasoactive treatment alone, including rebleeding episodes within the study period, was 20% in the terlipressin group and 32% in the somatostatin group. The control rate, including balloon tamponade, was 96% in both groups. The hospital mortality rate was 16% (4 of 25) in the terlipressin group and 24% (6 of 25) in the somatostatin group. Blood transfusions, use of balloon tamponade and duration of bleeding did not differ significantly.
This interim analysis of the ongoing study indicates that a large proportion of bleeding episodes from esophageal and fundic varices can be stopped initially (82%) and definitively controlled (74%) by vasoactive drugs alone. Differences in the effectiveness of terlipressin and somatostatin were not observed. (Hepatology 1992;15:1023–1030).
Bleeding From Staple Line Erosion After Esophageal Transection: Effect of Omeprazole
Authors: Kaye Graham L. , McCormick Aiden P. , Siringo Sebastiano , Hobbs Kenneth E.F. , McIntyre Neil , Burroughs Andrew K. 
Published: March 2007

Esophageal staple transection effectively controls acute variceal bleeding, but up to 50% of these patients will have recurrent upper gastrointestinal bleeding. In our experience, most of these bleeding episodes are caused by total or partial circumferential ulceration at the level of the staple transection: staple line erosion. It caused rebleeding in 29 (40%) of our patients. Whereas the pathogenesis of this lesion is unknown, acid reflux is a consequence of transection surgery. Assuming that staple line erosion could be healed by acid suppression therapy, thereby preventing recurrent bleeding, an acid suppression regimen was evaluated prospectively in 24 patients. Only six (25%) healed with daily standard (300 mg) or high–dose (1,200 mg) ranitidine combined with sucralfate (4 gm). The remaining 18 (75%) healed after omeprazole administration (40 mg/day) for 1 mo. Maintenance ranitidine alone (300 mg/day) was introduced, but 11 (48%) had relapse of erosions. All 11 healed with omeprazole (40 mg/day) for 2 mo, but again on maintenance ranitidine, 10 relapsed. All healed with further omeprazole and healing persisted with long–term administration (20 mg/day). Fifteen rebleeding episodes occurred in eight patients on maintenance ranitidine. Whereas relapse of staple line erosions did occur in the absence of rebleeding, all rebleeding episodes were associated with the relapse of staple line erosion.
Omeprazole is more effective than ranitidine alone and combined with sucralfate in healing staple line erosion. Omeprazole prevents rebleeding, which may enhance the long–term benefits of staple transection for acute variceal bleeding. (Hepatology 1992;15:1031-1035).
Effects of Vasopressor Agents and Epoprostenol on Systemic Hemodynamics and Oxygen Transport in Fulminant Hepatic Failure
Authors: Wendon Julia A. , Harrison Phillip M. , Keays Richard , Gimsson Alexander E. , Alexander Graeme J.M. , Williams Roger 
Published: March 2007

Hypotension is a serious complication in patients with fulminant hepatic failure, because it is associated with tissue hypoxia and a further compromise to end–organ function. In this study we investigated the effects of epinephrine and norepinephrine on hemodynamics and oxygen transport variables in 30 patients with fulminant hepatic failure. All had a mean arterial pressure of less than 60 mm Hg, despite adequate intravascular filling pressures.
Both epinephrine (n = 15) and norepinephrine (n = 15) improved mean arterial pressure (p < 0.001 epinephrine and norepinephrine), although this was not associated with a rise in oxygen delivery. Oxygen consumption fell (p<0.05 epinephrine, p<0.001 norepinephrine) because of a lower oxygen extraction ratio (p<0.01 epinephrine and norepinephrine). The addition of epoprostenol, a microcirculatory vasodilator, in 10 patients from each group led to an increase in oxygen consumption (p<0.001 epinephrine and norepinephrine) because of a rise in oxygen delivery (p<0.05 epinephrine, p<0.01 norepinephrine) and oxygen extraction ratio (p<0.01 epinephrine, p<0.001 norepinephrine), without a fall in mean arterial pressure.
The fall in oxygen consumption after the institution of vasopressor therapy could exacerbate tissue hypoxia and thus contribute to further organ damage in an already susceptible patient. In patients with fulminant hepatic failure who are given vasopressor support, the addition of epoprostenol may prevent the development of tissue hypoxia. (Hepatology 1992;15:1067–1071).
Cytokines Tumor Necrosis Factor and Interleukin–6 in Experimental Biliary Obstruction in Mice
Authors: Bemelmans M. H.A. , Gouma D. J. , Greve J. W. , Buurman W. A. 
Published: March 2007

The putative role of the cytokines interleukin–6 and tumor necrosis factor in the pathophysiology of the complications and mortality after surgery in jaundiced patients was studied in a murine model. Cytokine serum levels were determined in mice with experimental biliary obstruction. As an indicator of the activation status of macrophages, cytokine release by mononuclear phagocytes obtained from such mice was assessed.
Following surgery, interleukin–6 levels increased to 2 to 3 ng/ml after 3 to 4 hr, but declined rapidly afterward to levels of 60 pg/ml after 10 days, After 12 days, substantial interleukin–6 levels were observed in jaundiced mice (100 pg/ml), whereas levels in sham mice further decreased (p<0.001). The cytokine tumor necrosis factor was frequently present in the serum of jaundiced mice. After 22 days, when killed, all jaundiced mice showed significant tumor necrosis factor levels (p<0.001). This was in contrast to sham mice in which tumor necrosis factor was never detected.
The presence of an activated state of macrophages in jaundiced mice was concluded from the observed high spontaneous cytokine release and significantly higher release after stimulation (p<0.05). The presence of circulating cytokines was discussed in the context of the postoperative complications observed in jaundiced patients. (Hepatology 1992;15:1132-1136).