bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients
Authors: Gatta Angelo , Angeli Paolo , Caregaro Lorenza , Menon Francesca , Sacerdoti David , Merkel Carlo 
Published: March 2007

It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% ± 0.28% vs. 0.80% ± 0.50%; p < 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% ± 5.8% vs. 23.4% ± 7.2%; p < 0.025) than responders. Moreover, nonresponders showed lower distal sodium reabsorption, both in absolute terms (2,360 ± 723 μEq/min vs. 3,221 ± 960 μEq/min; p < 0.01) and as a percentage of filtered sodium load (17.5% ± 5.7% vs. 23.1% ± 7.6%; p < 0.01) despite higher values of plasma aldosterone (524 ± 542 pg/ml vs. 136 ± 213 pg/ml; p < 0.025).
We conclude that unresponsiveness to adequate doses of spironolactone in nonazotemic ascitic cirrhotic patients is related to a pathophysiological condition in which the role of aldosterone in renal sodium retention is limited by markedly enhanced proximal sodium reabsorption. (HEPATOLOGY 1991;14:231-236.)
Antithrombin III supplementation reduces heparin requirement and platelet loss during hemodialysis of patients with fulminant hepatic failure
Authors: Langley Peter G. , Keays Rick , Hughes Robin D. , Forbes Alastair , Delvos Ullrich , Williams Roger 
Published: March 2007

Previous studies have shown that antithrombin III levels are low in fulminant hepatic failure, and heparin kinetics are abnormal, making control of heparinization difficult during hemodialysis of these patients who are at risk of bleeding. In this study, we have performed a controlled, randomized trial of antithrombin III supplementation on heparin activity, occurrence of bleeding and the platelet count and activation during hemodialysis in 24 patients with fulminant hepatic failure. The treated group of 12 patients was given 3,000 units of antithrombin III before hemodialysis. Antithrombin III supplementation was shown to normalize antithrombin III levels during hemodialysis (prelevels: 0.22 ± 0.03 U/ml S.E.; at 1 hr 0.99 ± 0.06 U/ml; p <0.001; control prelevels: 0.24 ± 0.03 U/ml; at 1 hr 0.23 ± 0.04 U/ml). Total heparin usage was significantly decreased by antithrombin III supplementation (median 5,200 U; range = 2,005 to 13,000) as compared with the control group (median 10,200 U; range = 5,000 to 16,500; p <0.005). Blood heparin level (antifactor Xa activity) after the initial bolus was significantly greater in the antithrombin III—supplemented subjects (0.40 ± 0.07 U/ml compared with 0.22 ± 0.05 U/ml in the control group; p < 0.05). The significant reduction in platelet count observed in the control patients (18% ± 6% at 1 hr; p < 0.05) did not occur in antithrombin III patients (6% ± 4% at 1 hr), which was reflected by a lower release of the platelet-specific protein β-thromboglobulin. Two of 12 patients in both groups showed minor bleeding around vascular access sites during the first hemodialysis. Over the course of the study, no significant difference was seen in the frequency of bleeding from vascular access sites, gastrointestinal tract or other locations.
Thus in a controlled study, supplementation of antithrombin III markedly reduced the amount of heparin required during hemodialysis of patients with fulminant hepatic failure and also reduced platelet losses. Antithrombin III supplementation may be of benefit in hemodialysis, continuous arteriovenous hemofiltration or other invasive techniques requiring anticoagulation in these patients at particular risk of bleeding. (HEPATOLOGY 1991;14:251-256.)
Immunohistochemical detection of transforming growth factor-β1 in fibrotic liver diseases
Authors: Nagy Peter , Schaff Zsuzsa , Lapis Károly 
Published: March 2007

Transforming growth factor-β1 was localized by means of immunohistochemical reaction in liver biopsy specimens taken from patients having different chronic liver diseases with extending fibrosis. Two polyclonal antibodies that were produced in rabbits were directed against the amino terminal of transforming growth factor-β1.
Staining by anti-CC(1-30) was primarily extracellular and located in the portal and periportal fibrotic areas of all seven cases with chronic active hepatitis. No staining was noted in the four chronic persistent cases studied. A strong reaction was seen with the antibody in nine of the ten cirrhotic samples, whereas it was negative in one inactive cirrhosis case and in all five cases with normal liver histological findings. No positive staining could be detected by the anti-LC(1-30) in any of the liver tissues.
Detection of transforming growth factor-β1 in active liver diseases at the site of fibrosis suggests that transforming growth factor-β1 might have a role in the process and progression of fibrosis during the development of the disease. (HEPATOLOGY 1991;14:269-273.)
Export of intracellular HBsAg in chronic hepatitis B virus infection is related to viral replication†
Authors: Lau Johnson Y. N. , Bain Vincent G. , Davies Susan E. , Alexander Graeme J. M. , Williams Roger 
Published: March 2007

Serum and liver HBsAg bear an inverse relation to each other during the evolution of chronic hepatitis B virus infection and the quantity of HBsAg in tissue rises gradually with time. In this study, intracellular and extracellular levels of HBsAg were measured by radioimmunoassay in primary culture of hepatocytes from 30 patients with chronic hepatitis B virus infection to determine a possible relationship with hepatitis B virus replication.
Serum levels of HBsAg correlated with markers of active viral replication (serum hepatitis B virus DNA, p < 0.005, and tissue HBcAg, p < 0.02) but inversely with tissue HBsAg (p < 0.05). In similar fashion, in vitro export of HBsAg was also related to the presence of active viral replication markers (serum hepatitis B virus DNA, p < 0.02, and tissue HBcAg, p < 0.05) and negatively with tissue HBsAg (p < 0.001). Export of HBeAg also correlated positively with markers of active viral replication (serum hepatitis B virus DNA, p < 0.05 and tissue HBcAg, p < 0.05). Further experiments indicated that intrahepatic pre-S1 and pre-S2 correlated closely with intrahepatic HBsAg, indicating that a failure to export HBsAg was unlikely to be attributable to deficient intracellular expression of pre-S1 or pre-S2.
These data indicate that in vitro primary hepatocyte culture of hepatitis B virus—infected cells provides an accurate reflection of in vivo export of HBsAg and that this is closely related to the presence of active viral replication.
Are patients with primary biliary cirrhosis hypermetabolic? a comparison between patients before and after liver transplantation and controls
Authors: Green Hilary J. , Bramley Peter N. , Losowsky Monty S. 
Published: March 2007

Wasting is common in end-stage primary biliary cirrhosis and causes concern in patients facing liver transplantation. We have quantified resting metabolic rate and diet-induced thermogenesis in seven patients with primary biliary cirrhosis, in seven patients after liver transplantation who had previously been diagnosed as having primary biliary cirrhosis and in seven controls.
Resting metabolic rate was elevated in the primary biliary cirrhosis group (4.44 ± 0.81 kJ/hr/kg body wt; mean ± S.D.) compared with the post-liver-transplantation group (3.39 ± 0.40 kJ/hr/kg body wt) (p < 0.005) and compared with control subjects (3.65 ± 0.23 kJ/hr/kg body wt) (p < 0.01). A highly significant relationship was found between the severity of liver disease in the primary biliary cirrhosis group, as assessed by Child-Pugh score, and the resting metabolic rate group (r = 0.93; p < 0.005).
After a liquid meal (41 kJ/kg body wt), the metabolic rate increased, with similar peak changes from baseline occurring in all three groups. However, the rise persisted significantly longer in the primary biliar cirrhosis patients, and thus the integrated mean postprandial energy expenditure over the 4-hr postprandial observation period was greater in the primary biliary cirrhosis group than in the other two groups (p < 0.001).
Fasting glucose and protein oxidation rates were similar between groups, but fasting fat oxidation rate was higher in the primary biliary cirrhosis group (3.90 ± 0.83 kJ/hr/kg body wt) than in the post-liver-transplantation group (2.11 ± 0.90 kJ/hr/kg body wt) (p < 0.025) and than in the control group (2.49 ± 1.19 kJ/hr/kg body wt) (p < 0.05). Postprandial glucose oxidation rates were similar in all groups, but the protein oxidation rate was lower in the primary biliary cirrhosis group than in the other two groups (p < 0.01). The fat oxidation rate remained higher after food intake in the primary biliary cirrhosis group than in the post-liver-transplantation group (p < 0.05), but no significant differences were found between the primary biliary cirrhosis and control groups or between the post-liver-transplantation and control groups. No differences in total fasting plasma free fatty acids were seen between groups, but the level of stearic acid was higher in the control group (41.3 ± 10.3 μmol/L) than in the primary biliary cirrhosis group (27.5 ± 9.2 μmol/L) (p < 0.05) or than the post-liver-transplantation group (26.9 ± 6.6 μmol/L) (p < 0.05).
These data suggest that, as liver disease progresses, resting. metabolic rate increases. This, together with the greater overall diet-induced thermogenesis in these patients, could make a significant contribution to increased energy expenditure and thereby exacerbate malnutrition.
Movement of IgM antibody from blood to bile in rats
Authors: Hansen Peter G. C. , Jackson Graham D. F. 
Published: March 2007

The movement from blood to bile of passively injected autologous IgM antibody against horse erythrocytes was studied in rats. Both native and neuraminidase-treated antibody entered bile intact, with the peak titers for both measured between 60 and 90 min after injection. A small part (0.38%) of the injected dose of native antibody and 1.05% of the asialo-IgM antibody appeared in bile over 24 hr. These recoveries represented only a small fraction of the activity, which apparently disappeared from serum over the period. The pathways used by IgM antibody to enter bile were partially assessed. Prior injection of fetuin was found to abrogate the biliary secretion of native antibody and to significantly reduce the recovery of asialoantibody in bile.
In contrast, the presence of asialofetuin reduced (but not significantly) the secretion of native antibody and markedly changed the kinetics of appearance of asialo-IgM activity in bile. Some candidate routes to bile can be excluded as unlikely. The parahepatocellular pathway to bile canaliculi appears uninvolved because the secretion of antibody is slow and the inhibitory effects of fetuin argue against secretory component-mediated transport. Instead, two secretory pathways appear to be present. The first appears to be available to both native and asialo-IgM antibody, and may involve the peribiliary capillary plexus. The second route to bile is available to asialo-IgM antibody alone and is probably initiated by binding to the hepatic asialoglycoprotein receptor.
Bone loss after liver transplantation
Authors: McDonald Jennifer A. , Dunstan Colin R. , Dilworth Pamela , Sherbon Kenneth , Sheil Ross A.G. , Evans Richard A. , McCaughan Geoffrey W. 
Published: March 2007

We studied 35 adult patients (mean age = 43 yr) referred for orthotopic liver transplantation. Spinal bone mineral density was measured by quantitative computed tomography scanning before transplantation (n = 35) and at 3 mo (n = 21) and 12 mo (n = 11) after orthotopic liver transplantation. The readings were corrected to age 50 yr, using the regression equations derived from normal control subjects. Quantitative bone histological studies were performed in 17 patients before orthotopic liver transplantation and 3 mo after orthotopic liver transplantation. Before orthotopic liver transplantation, the corrected spinal bone mineral density in men was 108 ± 20 mg/cm3, less than in male control subjects (129 ± 22 mg/cm3, p < 0.005). In women patients the value was 117 ± 27 mg/cm3, and in female control subjects 126 ± 19 mg/cm3 (NS). However, women patients with primary biliary cirrhosis had lower spinal bone mineral density (106.5 ± 14.8) than female control subjects (p < 0.005). Histologically, the resorbing surface was near the normal mean, whereas the osteoblast surface, tetracycline surface and bone formation rate was lower in men (p < 0.05) but not women. Spinal bone mineral density decreased by 24% in the first 3 mo after orthotopic liver transplantation with no further decrease at 12 mo. Five patients had vertebral fractures within 6 mo of orthotopic liver transplantation. One patient fractured a wrist and three had osteonecrosis of the hip or knee. Bone histological studies 3 mo after orthotopic liver transplantation showed no change in resorbing surface but an increase in osteoblast surface from 2.1% ± 3.0% to 6.0% ± 7.0% (p < 0.05), increased bone formation in men (21 ± 31 to 80 ± 96 μm2/mm2 p < 0.05) and serum osteocalcin increased from 2.3 ± 0.3 pg/ml before transplantation to 5.9 ± 1.8 pg/ml (p <0.05). Bone loss was related to the number of hospital days after orthotopic liver transplantation (r = 0.79, p < 0.001) but not to any other factor, including prednisone and cyclosporin dose.
The study shows that bone mass is reduced in men with end-stage liver failure and that considerable bone loss occurs in the first 3 mo after orthotopic liver transplantation, frequently resulting in vertebral fractures. The exact cause of the bone loss is not clear, although immobilization appears to be important, probably in combination with corticosteroid therapy. The cellular changes causing this bone loss must occur very early after orthotopic liver transplantation because by 3 mo after transplantation, increased bone formation had begun to occur. (Hepatology 1991;14:613-619.)
Hepatic activity and mRNA expression of aspartate aminotransferase isoenzymes in alcoholic and nonalcoholic liver disease
Authors: Pol Stanislas , Nalpas Bertrand , Vassault Anne , Bousquet-Lemercier Bernadette , Franco Dominique , Lacour Bernard , Berthelot Pierre , Hanoune Jacques , Barouki Robert 
Published: March 2007

In liver and serum, AST activity is dependent on two isoenzymes, which are mitochondrial and cytosolic in nature. In an attempt to explain the well-known increase of serum mitochondrial AST-to-total AST ratio in chronic alcoholism (which is due to a specific increase of the mitochondrial isoenzyme), we analyzed: (a) liver and serum AST, ALT and glutamate dehydrogenase activities in 23 active drinkers with minimal liver changes, 11 alcoholic patients with cirrhosis who had stopped drinking, 18 nonalcoholic patients with viral chronic hepatitis and 11 subjects with normal livers; and (b) the expression of messenger RNAs for AST isoenzymes in the corresponding liver samples.
Enzymatic activities were decreased in the liver irrespective of the origin of the liver disease. In patients with viral chronic hepatitis (or in those with alcoholic cirrhosis when abstinent), variations in liver proteins and messenger RNAs paralleled significant decreases in mitochondrial AST, ALT and glutamate dehydrogenase and a nonsignificant decrease of cytosolic AST. In alcoholic patients with minimal liver changes, the significant decrease of hepatic cytosolic AST, ALT and glutamate dehydrogenase activities contrasted with a close-to-normal liver mitochondrial AST activity; the increased amounts of mitochondrial AST messenger RNA give evidence for a pretranslational mechanism of regulation, indicating a possible increase in the total production of mitochondrial AST in the liver. The decrease of hepatic cytosolic AST activity was statistically significant only in alcoholic patients without cirrhosis who had a normal cytosolic AST mRNA level, thus suggesting a contributory role of translational or posttranslational regulation. In conclusion, regulation of AST isozymes during liver disease is complex, including differential, pretranslational and translational or posttranslational mechanisms. (Hepatology 1991;14:620-625.)
Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage
Authors: Day Christopher P. , Bashir Rumaisa , James Oliver F. W. , Bassendine Margaret F. , Crabb David W. , Thomasson Holly R. , Li Ting-Kai , Edenberg Howard J. 
Published: March 2007

Little is known about factors determining individual susceptibility to the physical complications of alcohol abuse but genetically determined differences in ethanol metabolism may be important. The oxidative metabolism of alcohol is catalyzed by alcohol and aldehyde dehydrogenase. Polymorphisms have been observed at two of the five loci encoding alcohol dehydrogenase subunits: ADH2 (producing three β subunits) and ADH3 (producing two subunits) and also at the locus encoding the metabolically important form of aldehyde dehydrogenase, ALDH2. We have compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol-related cirrhosis (n = 59) and chronic pancreatitis (n = 13) with 79 local healthy control subjects. The different alleles were detected with allele-specific oligonucleotide probes after amplification of leukocyte DNA by the polymerase chain reaction.
All patients and all but one control subject were homozygous ADH2★1, encoding the β1 subunit. No ADH2★3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2★1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3★1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p < 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency.
Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: Univariate and multivariate analyses
Authors: Shirabe Ken , Kanematsu Takashi , Matsumata Takashi , Adachi Eisuke , Akazawa Kohhei , Sugimachi Keizo 
Published: March 2007

The purpose of this study was to clarify the factors linked to recurrence of small hepatocellular carcinomas, up to 3cm in diameter, after hepatectomy. Fifty patients with small hepatocellular carcinomas who underwent hepatectomy between 1976 and 1988 were observed for possible recurrence for at least 2 yr. These patients were divided into two groups: 20 patients who had recurrence within 2 yr and 30 patients who had no recurrence within 2 yr. The recurrence pattern was analyzed by hepatic angiography. Statistical analysis by the X2 test and stepwise logistic regression showed that the risk factors linked to recurrence were (a) tumor diameter greater than 2.2 cm, (b) intracapsular infiltration of tumor cells, (c) tumor location deep in the liver, (d) macroscopical and microscopical tumor invasion into the portal vein and (e) tumor invasion into the portal vein or intrahepatic metastasis.
When patients diagnosed with small hepatocellular carcinomas have any of these risk factors, postoperative adjuvant therapy and follow-up should be particularly carefully considered, since these patients are at high risk for early recurrence. (Hepatology 1991;14:802-805).
Histochemical demonstration of sinusoidal γ-glutamyltransferase activity by substrate protection fixation: Comparative studies in rat and guinea pig liver
Authors: Lanca António José , Israel Yedy 
Published: March 2007

Most histochemical methods for the detection of an enzymatic activity are preceded by tissue fixation with chemical agents that partially inactivate the enzymes. It is well known that substrates exert a marked protection against fixative-induced inactivation. The conventional histochemical methods for the demonstration of hepatic γ-glutamyltransferase activity have not been successful in detecting the activity of the enzyme on the sinusoidal side of the hepatocytes despite mounting biochemical evidence for its presence on that pole of the hepatocyte. Under conventional fixation the enzymatic activity in hepatocytes is only seen on the bile canalicular side. This may be the result of a preferential protective effect of γ-glutamyltransferase by its normal substrate, glutathione, present in the bile canaliculus at concentrations 500 times higher than in the sinusoidal lumen (8 mmol/L vs. 10 to 20 mmol/L). To test this hypothesis and to reduce the degree of fixative-induced inhibition of the enzyme activity, glutathione was either incorporated in the fixative solution or the livers were perfused with high concentrations of glutathione (10 mmol/L) before fixation.
Our results histochemically demonstrate, in the normal adult rat liver, the existence of γ-glutamyl-transferase activity not only on the bile canalicular pole but also on the sinusoidal pole of the hepatocytes. Visualization of the enzyme activity on the sinusoidal pole is dependent on glutathione protection. Guinea pig livers, which present a 10-fold higher γ-glutamyltransferase activity than rat livers (similar to that in human beings), showed marked sinusoidal γ-glutamyltransferase activity even in the absence of glutathione protection. Glutathione protection further increased this sinusoidal activity. Histochemical data in the guinea pig paralleled the biochemical findings indicating that in a single pass guinea pig liver can remove considerably higher amounts (more than two thirds) of circulating glutathione than rat liver. The histochemical demonstration of γ-glutamyl-transferase activity in the sinusoidal pole of the hepatocyte in normal adult rat and guinea pig liver adds further evidence to the biochemical data supporting the existence of a sinusoidal γ-glutamyltransferase ectoactivity capable of removing glutathione from the circulation. (Hepatology 1991;14:857-863).