摘要:

AbstractNitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 ± 6.5 mm Hg (mean ± S.D.) to 15.1 ± 5.1 mm Hg (p<0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 ± 10 mm Hg to a peak decrease of 76 ± 18 mm Hg (p<0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p<0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 ± 15 to 83 ± 15 beats per min, p<0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal‐pressure‐reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal‐collateral va

ISSN:0270-9139    

DOI:10.1002/hep.1840070502

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractEndoscopic injection sclerotherapy was given to 155 patients with esophageal varices mainly related to non‐alcoholic liver cirrhosis. The formation of a superficial ulcer in the lower esophagus was achieved in 141 (91.0%) of the 155 patients, with an average of 4.1 sessions of endoscopic injection sclerotherapy during an average time of 4.9 weeks. The average volume of 5% ethanolamine oleate sclerosant used was 24.8, 19.2, 12.3 and 6.5 ml for the initial to fourth sessions of endoscopic injection sclerotherapy, respectively.For 14 patients, a sufficient number of sessions of endoscopic injection sclerotherapy could not be given: 10 early deaths (5 hepatoma, 4 liver failure and 1 gastric bleeding), and 4 refused further sessions.When the esophageal mucosa had been eliminated and a superficial ulcer had formed, episodes of recurrent bleeding or recurrence of esophageal varices were nil over a median follow‐up of 14.6 months, with a range of 1 to 27 months. In seven patients, bleeding recurred before elimination of the mucosa could be achieved, but these bleeding episodes were well controlled with an additional session of endoscopic injection sclerotherapy.At the time of analysis, there were 36 deaths (20 hepatoma, 14 liver failure and 2 gastric bleeding) among these 155 patients. Thus, the mean follow‐up was 16.3 months (range: 7 to 27 months) in the 119 survivors, with no recurrence of the varices.We propose that removal of the esophageal mucosa may well be the endpoint of repeated endoscopic injection sclerotherapy in the management of patients on injection scleroth

ISSN:0270-9139    

DOI:10.1002/hep.1840070503

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe aim of the study was to verify the role of γ‐aminobutyric acid in the pathogenesis of hepatic encephalopathy occurring in cirrhotic patients by attempting to correlate plasma and cerebrospinal fluid content of authentic γ‐aminobutyric acid with the neurological manifestations of hepatic encephalopathy. For this purpose, plasma and cerebrospinal fluid γ‐aminobutyric acid levels were measured by means of mass fragmentography in 17 cirrhotic patients with hepatic encephalopathy and in 6 cirrhotics without neurological symtoms. Moreover, in all patients, a second sample was obtained during the clinical course of hepatic encephalopathy.The mean plasma and cerebrospinal fluid γ‐aminobutyric acid levels were not different in patients with or without hepatic encephalopathy and did not change during the evolution of the neurological symptoms. The lack of changes in the γ‐aminobutyric acid content in plasma and cerebrospinal fluid during hepatic encephalopathy is in contrast with the hypothesized importance of increased entry into the brain of γ‐aminobutyric acid in the pathogenesis of hepat

ISSN:0270-9139    

DOI:10.1002/hep.1840070504

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractHyperammonemia is a well‐recognized metabolic abnormality which occurs in cirrhotic patients with advanced liver dysfunction. We recently documented that hyperglucagonemia that occurs as a result of hepatic glycogen depletion may be responsible for this hyperammonemia by promoting gluconeogenesis to provide glucose as a fuel for functioning of several organ systems. Thus, hepatic glycogen depletion may be the initial process responsible for hyperammonemia. Since the glucose rise following intravenous glucagon administration is a reflection of hepatic glycogen breakdown, we studied the effect of glucagon (1 mg) injection on plasma glucose, insulin and ammonia levels after an overnight fast in cirrhotic patients and normal subjects. Glucose rise was significantly stunted, and ammonia rise was significantly greater in patients with advanced liver dysfunction as compared to normal subjects. Furthermore, the smaller the glucose increment, the earlier the ammonia rise. The smallest glucose responses were seen in the patients with the highest basal plasma ammonia levels. Finally, significant negative relationships were noted between the glucose response to glucagon administration (δglucose) and the degree of liver dysfunction as reflected by Composite Clinical Laboratory Index, as well as basal ammonia and ammonia responses (Δam‐monia) on the other. Therefore, this study suggests that hepatic glycogen depletion may be the initial event leading to elevated plasma ammonia concentrations in hepatic cirr

ISSN:0270-9139    

DOI:10.1002/hep.1840070505

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractEvidence for increased plasma levels of complexes containing Gc (vitamin D‐binding protein) and cellular actin has been previously reported during fulminant hepatic necrosis in man. In order to study this process in more detail, we produced liver injury in hamsters using increasing doses of acetaminophen, with serial collection of sera for up to 168 hr after acetaminophen injection. Hamster Gc was purified using a three‐step procedure and was shown to resemble closely human Gc. Polyclonal antihamster Gc was prepared and used in rocket immunoelectrophoresis and radial immunodif‐fusion studies for quantitation of total serum Gc and the percentage of Gc complexed with actin. Serum Gc levels were depressed in animals having liver damage, and the extent of depression 42 hr after acetaminophen correlated with the extent of elevation of AST. The proportion of the total Gc that was present in the complexed form increased in relation to the severity of the liver disease. In serial studies, diminution in Gc level preceded the rise in AST and increase in the percent complexed. These changes closely resemble observations in man and suggest that the hamster‐acetaminophen hep‐atotoxicity model may be of value in further study of interactions of Gc with intracellular actin components and its role in actin homeostasis in conditions of massive tissue

ISSN:0270-9139    

DOI:10.1002/hep.1840070506

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe major part of hepatocellular iron is derived from uptake of transferrin‐bound iron by means of nonspecific fluid‐phase endocytosis and specific, saturable binding on high‐affinity transferrin receptors. We investigated the expression of transferrin receptors on hepatocytes in liver biopsies of 22 cases of hemochromatosis (21 primary hemochromatosis and 1 secondary hemochromatosis), using immunohistochemical demonstration of the human transferrin receptor with the specific monoclonal antibody OKT9. Fifty liver biopsies (normal and pathological) without demonstrable iron storage (Perls' stain negative) served as controls. In the controls, membranous and/or cytoplasmic transferrin receptor expression was always present on hepatocytes, albeit in variable numbers and patterns without obvious relation to the underlying liver disease. In 19 of 22 hemochromatosis cases with severe iron overload, OKT9 immunoreactivity on hepatocytes was completely absent. Three hemochromatosis cases showed few hepatocytes positive for OKT9. One showed mild iron overload, while the second, a successfully treated case, was free of iron. The remaining hemochromatosis case was a known alcoholic with severe iron overload. Since OKT9 binding to the transferrin receptor is not blocked by previous binding of transferrin, the findings show that in advanced hemochromatosis hepatocytes do not express transferrin receptors. This finding is in keeping with the inverse relation between transferrin receptor expression and exogenous iron supply in various cell cultures.These results indicate that in hemochromatosis, apparently as a result of progressive iron overload, transferrin receptor expression on hepatocytes disappears. This leaves the hepatocytes with a nonsaturable mechanism for uptake of transferrin‐bound iron (fluid‐phase pinocytosis) and with uptake of potentially more toxic forms of nontransferrin‐bound iron, which may represent up to 30% of serum iron in fully established hemo

ISSN:0270-9139    

DOI:10.1002/hep.1840070507

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe pattern of copper distribution in human newborn liver was investigated by histochemical methods (rhodamine, orcein and rubeanic acid) and by atomic absorption spectroscopy. A significant correlation (p<0.005) was found between the degree of histochemical positivity and the copper concentration found by atomic absorption spectroscopy. In the majority of the 30 livers examined (first group), the copper concentration was much higher than that of normal adult liver, although exhibiting striking individual differences. No correlation between the copper content and sex, body weight or gestational age was found. From a second group of five livers, longitudinal tissue slices 0.5 cm thick were partitioned into regular blocks of about 0.5 gm, which were individually analyzed by atomic absorption spectroscopy. Copper appeared unevenly distributed within each liver, with marked differences even between adjacent blocks. However, a consistent tendency of copper to accumulate in the left lobe more than in the right one was evident. Five additional blocks, one for each liver, were further partitioned into 10 small specimens of a final size (0.05 gm), comparable to that of a needle biopsy. Even at this sampling level, consisting of tissue fragments taken from a small tissue area, the copper concentration appeared quite irregularly distributed. These findings may be considered for two different aspects: (a) the biological implications of the pattern of copper accumulation in different lobar and lobular liver compartments and (b) the statistical inference, for diagnostic purposes, of the mean liver copper content from measurements of single percutaneous biopsy specimens.

ISSN:0270-9139    

DOI:10.1002/hep.1840070508

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractInhibition of a major hepatic form of human cationic glutathioneS‐transferase by bilirubin, biliverdin, indocyanine green and chenodeoxycholic acid was investigated as a function of pH (range = 6.5 to 9.1). Changes in pH had little effect on the extent of inhibition by indocyanine green. However, inhibition by bilirubin, biliverdin and chenodeoxycholic acid was found to be pH‐dependent, with markedly less inhibition at the high values of pH. The reduced inhibition at the high values of pH could not be ascribed to a failure of the enzyme to bind the nonsubstrate ligand. Instead, the complete inhibition observed at pH 6.5 became partial (hyperbolic) inhibition at pH 9.1. This behavior can be ascribed to the binding of the nonsubstrate ligands at a site other than the active site, i.e., at high values of pH there is formation of an enzyme‐substrate‐inhibitor complex which still retains considerable catalytic activity. At physiologic values of pH (7.0), the human transferase was completely inhibited by saturating concentrations of the tested nonsubstrate ligands. This is in contrast to our previous studies performed with the rat transferases where, although inhibition also was affected by buffer pH, some forms of the enzyme retained significant catalytic activity at pH 7.0 despite high concentrations of nonsubstrate ligands. We conclude that the ability of the human cationic glutathioneS‐transferases to serve as enzymes of detoxification in the presence of high intracellular concentrations of nonsubstrate ligands may be significantly reduced, and this may render the cholestatic liver unusually susceptible to injury by toxic elec

ISSN:0270-9139    

DOI:10.1002/hep.1840070509

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractWe studied a possible acinar heterogeneity in the transport of organic cations, using rhodamine B as model compound. Employing perfusions of isolated rat livers in the ante‐ and retrograde mode and quantitative fluorescence microscopy, Zones 1 and 3 were shown to be equally efficient in taking up rhodamine B. Ten minutes after injection in an antegrade perfusion, 95% of the dose was localized in the portal half of the acinus. Fifty minutes later, however, the amount of rhodamine B in Zone 1 had been reduced to 23%; 30 and 31% were in Zones 2 and 3, respectively, and the medium concentration was doubled. Thus, unchanged rhodamine B appeared to be transported downstream within the liver, either via the medium or directly from cell to cell, finally resulting in a relatively higher rhodamine B concentration in Zone 3. To obtain additional data, we designed a perfusion setup in which the zones could be studied separately. In both zones, the amount excreted into the medium was about 30 times the amount excreted into bile. Intracellular sequestration of rhodamine B and the rate constant for sinusoidal secretion were higher in Zone 3, while the sinusoidal uptake rates were equal; biliary excretion was higher in Zone 1.Acinar distribution changed with time because rhodamine B, primarily accumulated in Zone 1, was secreted into the sinusoids and taken up again by downstream cells. The finally higher rhodamine B concentration in Zone 3 was caused by a zonal heterogeneity in intracellular sequestration and sinusoidal secretion of rhodamine

ISSN:0270-9139    

DOI:10.1002/hep.1840070510

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractEndothelial liver cells were obtained from guinea pig by enzymatic digestion and centrifugal elutriation. Cells were cultured on gelatin and fibronectin pretreated culture vessels. Endothelial cells were characterized by phase‐contrast microscopy, electron microscopy and the presence of Factor VIII‐related antigen. Fibronectin secretion was determined in cell‐free supernatants by a sensitive and specific ELISA and localized on fixed cultured cells by immunofluorescence. [35S]Methionine endogeneously labeled fibronectin was immunoprecipitated from supernatants and cellular lysates and displayed on sodium dodecyl sulfate polyacrylamide slab gel electrophoresis.After attachment to the culture vessel, one day after plating, endothelial cells start to produce fibronectin as measured by ELISA and demonstrated by immunoprecipitation and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Secretion of fibronectin increases as cells proliferate to form a confluent monolayer. By immunofluorescence, fibronectin is visualized inside permeabilized cells and as a fibrillar network on the cell surface. Underneath the cell bodies, fibronectin‐positive material is present as short strands. From supernatants and cellular lysates, fibronectin is immunoprecipitated with an apparent Mrof about 235,000 obviously larger than plasma fibronectin with an Mrof 220,000, which behaves electrophoretically like fibronectin isolated from early hepatocyte cultures. As endothelial cells incorporate [3H]fucose in fibronectin, whereas hepatocytes do not, we conclude that endothelial cells in contrast to hepatocytes produce cellular fibronectin. Endothelial cells, therefore, are probably the cellular source of the fibronectin present in the space of Disse. The significance of this finding with respect to fibrotic liver disease is

ISSN:0270-9139    

DOI:10.1002/hep.1840070511

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY