摘要:

AbstractIn patients with portal hypertension and tense ascites, large‐volume paracentesis improves patient comfort and may improve systemic hemodynamics. However, it has been avoided in nonedematous patients because of concern for complications, including intravascular volume depletion. In this study, 12 nonedematous patients with chronic liver disease, portal hypertension and tense ascites underwent 14 large‐volume (5‐liter) paracenteses for the relief of discomfort and/or respiratory distress. Plasma volume was measured directly by a dilution method with125I‐labeled human serum albumin prior to and at 24 or 48 hr after 13 of the paracenteses. All patients felt better postparacentesis. No dizziness, hypotension, tachycardia, encephalopathy or change in mean serum sodium, creatinine or blood urea nitrogen occurred. Two patients experienced a decrease in hematocrit, which was not explained by blood loss or increase in plasma volume. Mean plasma volume was 3,713 ± 129 ml (55.1 ± 1.5 ml per kg ideal body weight) preparacentesis and 3,684 ± 136 ml postparacentesis, the difference being −0.78% (p = 0.48, NS). Our results suggest that 5‐liter paracentesis in nonedematous patients with tense portal hypertension‐related ascites improves patient comfort and is not associated with a decrease in measur

ISSN:0270-9139    

DOI:10.1002/hep.1840080202

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractPrevious studies have established the reliability of percutaneous portal venous pressure measurement using a Chiba needle, a procedure requiring fluoroscopic guidance. Intrahepatic pressure has been advocated by some as a simple and safe index of portal venous pressure. The aim of this study was to examine the reliability of intrahepatic pressure measurement and its relationship to portal venous pressure. Fifty patients requiring liver biopsy were included: 29 with cirrhosis (n = 20 micronodular, n = 9 macronodular) and 21 with various hepatic disorders but no cirrhosis. The procedure was performed under fluoroscopic guidance, using a Chiba needle connected to a manometer by a saline‐filled catheter. Immediately prior to biopsy, each patient underwent measurement of: (i)3 to 5 separate intrahepatic pressures, the intraparenchymal site being inferred by the lack of blood or bile return; and (ii)portal and hepatic venous pressures, the intravascular position of the needle being ascertained by the reflux of blood and the vessel identified with injection of contrast. Intrahepatic pressure measurements showed great intraindividual variability (variation coefficient up to 115%). Mean intrahepatic pressure (13.19 ± 8.32 mm Hg) was similar to portal venous pressure (14.43 ± 6.10 mm Hg) in the noncirrhotics but significantly lower in the cirrhotics (intrahepatic pressure = 18.34 ± 8.82 mm Hg, portal venous pressure = 22.52 ± 9.47 mm Hg; p<0.01). The difference between these two parameters exceeded 3 mm Hg in 50% of patients (mean = 9 mm Hg, range = 4 to 19 mm Hg), both in cirrhotics and noncirrhotics. We conclude that intrahepatic pressure measurements are not reproducible and do not represent a reliable index of portal venous pre

ISSN:0270-9139    

DOI:10.1002/hep.1840080203

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractDuring the development of liver fibrosis in rats by an individual dose‐titrated CCl4administration, hepatic proton spin‐lattice relaxation time (T1) has been measuredin vivoevery 2 weeks for 8 weeks. Liver content of collagen, triglycerides and water has been measured biochemically in biopsy material.After 4 weeks of CCl4treatment, T1increased signifcantly and remained at the same level, whereas liver collagen reached its maximum at 8 weeks. It is concluded that, under our experimental conditions, increased hepatic T1represents drug‐induced edema and that hepatic T1is not a reliable noninvasive parameter for developing liver fibrosisin

ISSN:0270-9139    

DOI:10.1002/hep.1840080204

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractThe relationships between portal pressure, liver function and clinical variables on one hand and development of variceal hemorrhage and death on the other were investigated in 58 men with newly diagnosed alcoholic cirrhosis. Portal pressure was determined during hepatic vein catheterization as wedged minus free hepatic vein pressure, and median pressure was 14 mm Hg (range = 3 to 26 mm Hg). Fourteen of 31 patients (45%) had esophageal varices at upper gastrointestinal endoscopy (the size being considered large in nine patients).During follow‐up (median = 31 months; range = 2 to 51 months), 12 patients (21%) developed variceal hemorrhage. Applying Cox's regression analysis, information about previous variceal bleeding (p = 0.0046), large varices at endoscopy (p = 0.012), hepatic vein pressure gradient (p = 0.0056) and indocyanine green clearance (p = 0.038) all contained significant prognostic information regarding development of variceal hemorrhage, even when easily obtained variables with known prognostic information were included [modified Child‐Turcotte's criteria and incapacitation index (a weighted sum of days without normal health)].During follow‐up, 17 patients (29%) died. Applying Cox's regression analysis, large varices at endoscopy (p = 0.012) and hepatic vein pressure gradient (p = 0.019) contained significant prognostic information regarding death, in addition to the information contained in the modified Child‐Turcotte's criteria and incapacitation index. In conclusion, prediction of prognosis in alcoholic cirrhotic men may be significantly improved by information about size of esophageal varices and level of portal p

ISSN:0270-9139    

DOI:10.1002/hep.1840080205

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractWe studied the effects of a series of 16 vasodilators on the intrahepatic vasoconstriction induced by norepinephrine in the isolated perfused rat liver. The vasodilators were nonselective α‐adrenergic antagonists (phentolamine, ifenprofil, isoxsuprine and buflomedil), a nonselective β‐adrenergic antagonist (propranolol) and an agonist (isoproterenol), an α2‐adrenergic agonist (clonidine), calcium channel blockers (verapamil and diltiazem), nitrovasodilators (nitroglycerin, sodium nitroprusside), papaverine and other unclassified vasodilators, some of them with rheological properties (diazoxide, vincamine, cinepazide, naftidofuryl and pentoxifylline). The most potent drugs were ifenprofil, phentolamine, isoxsuprine, clonidine, sodium nitroprusside and buflomedil. Diazoxide, papaverine, pentoxifylline and trinitrine were less powerful. Verapamil, diltiazem, propranolol, isoproterenol, vincamine, cinepazide and naftidofuryl were ineffective. We conclude that different classes of pharmacological agents have significant vasodilatory properties on the hepatic microvasculature. This offers interesting perspectives in the treatment of cirrhosis and stressful states where high levels of circulating norepinephrine may contribute to the altered liver p

ISSN:0270-9139    

DOI:10.1002/hep.1840080206

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractEndotoxin concentrations were measured in the portal, hepatic and peripheral venous blood of two groups of patients with cirrhosis using a limulus‐based chromogenic assay. The high sensitivity of chromogenic detection allowed measurement of endotoxin as low as 10 to 15 pg per ml, an order of magnitude greater than previously possible by gelation studies. Group 1 consisted of 56 patients with cirrhosis undergoing angiographic evaluation. In this group, there was wide variability in hepatic venous concentration [ 73 ± 110 pg per ml (mean ± S.D.)] and peripheral venous concentration [31 ± 58 pg per ml]. However, paired t test showed peripheral venous concentration was significantly (p<0.001) lower than hepatic venous concentration. Neither hepatic or peripheral venous endotoxin levels correlated significantly with a variety of clinical, biochemical or radiological parameters. Group 2 consisted of 21 patients with cirrhosis undergoing shunt surgery. Endotoxin levels again showed a wide range, with portal venous concentration (142 ± 167 pg per ml) and simultaneous peripheral venous concentration (82 ± 150 pg per ml). Paired t test in this group showed a significant (p<0.001) portal to peripheral venous gradient.This study showed the feasibility of measuring endotoxin in plasma to low concentrations by a chromogenic assay technique. It supports the concept of relatively high levels of endotoxin in the portal circulation. In the presence of liver disease, systemic endotoxemia occurs, which is augmented by stressful situ

ISSN:0270-9139    

DOI:10.1002/hep.1840080207

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractThe effects of ethanol on liver regeneration are poorly understood. Acute and chronic exposure to ethanol have been found to exert opposite effects on the induction of ornithine decarboxylase, the rate‐limiting enzyme for polyamine biosynthesis. Polyamines are necessary for DNA synthesis and liver regeneration after chemical or surgical liver injury. Short‐term exposure to ethanol, which inhibits ornithine decarboxylase has been shown to inhibit DNA synthesis and liver regeneration, whereas more chronic exposure to ethanol increases ornithine decarboxylase activity and therefore could conceivably stimulate DNA synthesis and regeneration. To explore this later possibility, the effects of chronic ethanol consumption on ornithine decarboxylase activity, DNA synthesis and liver regeneration were studied in rats after sham laparotomy and partial hepatectomy. Chronic ethanol feeding failed to inhibit the induction of ornithine decarboxylase that occurred after partial hepatectomy and yet significantly inhibited posthepatectomy DNA synthesis and restitution of liver mass. These data suggest that the induction of hepatic polyamine biosynthesis is dissociated from DNA synthesis and liver regeneration after chronic consumption of etha

ISSN:0270-9139    

DOI:10.1002/hep.1840080208

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractThe hepatic lobular localization of alcohol dehydrogenase was determined in male, female and castrated male rats. Alcohol dehydrogenase immunoreactive protein and activity were increased in female and castrated rats as compared to normal male rats. By immunohistochemistry, alcohol dehydrogenase protein was found localized principally in the perivenous area of the hepatic lobule in all of the animals. Alcohol dehydrogenase activity eluted from the male rat liver, during bidirectional digitonin perfusion, exhibited a pattern characteristic of cytosolic enzymes predominantly localized to the perivenous area. The elution of the enzyme was more rapid during cava‐porta than porta‐cava perfusion occurring in close association with the elution of glucokinase, an enzyme localized principally in the perivenous area. By contrast, elution of lactate dehydrogenase, which is located predominantly in the periportal area, preceded elution of alcohol dehydrogenase during porta‐cava perfusion, but followed it during cava‐porta perfusion. These differences were less apparent in the cava‐porta than in the porta‐cava direction. The predominant localization of alcohol dehydrogenase immunoreactive protein and activity to the perivenous area of hepatic lobule was not affected by sexual difference or increase in the enzyme following

ISSN:0270-9139    

DOI:10.1002/hep.1840080209

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractThe effect of prostacyclin on acetaminophen‐induced liver injury has been investigated in the mouse. Two structurally unrelated thromboxane synthetase inhibitors, OKY 1581 and benzyl imidazole, were also examined in order to investigate the role of the prostacyclin‐thromboxane balance in the development of hepatic lesions.Whereas prostacyclin or OKY 1581 given shortly after acetaminophen prevented mortality and reduced liver necrosis, as assessed by serum ALT activity and histology, benzyl imidazole was only effective if given prior to acetaminophen.Acetaminophen overdose resulted in an enhanced prostaglandin and thromboxane generation by liver homogenates. While OKY 1581 inhibited thromboxane production by the liver homogenates, prostacylcin synthesis was increased. Pretreatment with the cyclooxygenase inhibitor indomethacin blocked both the increase in prostacyclin generation and the protective effect of OKY 1581. Benzyl imidazole inhibited the synthesis of thromboxane but did not enhance prostacyclin production. In addition, the protective effect of benzyl imidazole was unaltered by indomethacin pretreatment. Furthermore, whereas benzyl imidazole interfered with hepatic drug metabolism, as assessed by prolongation of the pentobarbitone sleeping time, prostacylcin and OKY 1581 were without activity.Prostacyclin treatment can prevent acetaminophen‐induced liver necrosis in mice. Enhanced prostacyclin synthesis by the selective thromboxane synthetase inhibitor OKY 1581 also exerts a protective role in this

ISSN:0270-9139    

DOI:10.1002/hep.1840080210

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractHuman polymorphonuclear neutrophils, when exposed to soluble or particulate stimuli, can destroy various types of cells. The aim of this study was to investigate their toxicity against hepatocytes. Human polymorphonuclear neutrophils were incubated in basal conditions and after stimulation with 5 mg per ml opsonized zymosan in the presence of rat hepatocytes isolated by collagenase digestion. Cytotoxicity was quantified by the percentage of ALT activity released by hepatocytes in culture medium. Whereas unstimulated neutrophils exhibited only minor effects, opsonized zymosan‐stimulated neutrophils induced, after 16 hr incubation, a 24.0 ± 4.1% (mean ± 1 S.E.) ALT activity release at a neutrophil/hepatocyte ratio of 5, and a 51.7 ± 6.8% ALT activity release at a ratio of 20. At this ratio of 20, the ALT activity release was 9.0% at 1 hr and 24.0% at 4 hr. Three proteinase inhibitors (i.e., soybean trypsin inhibitor, α1‐proteinase inhibitor and fetal calf serum) decrease cytotoxicity by 78, 76 and 78%, respectively. The protective effect of proteinase inhibitors was not due to a nonspecific effect of proteins, since bovine serum albumin did not decrease the toxicity of stimulated polymorphonuclear cells. The supernatant of stimulated neutrophils was also found to be toxic against hepatocytes, and again, this effect was inhibited by soybean trypsin inhibitor, α1‐proteinase inhibitor and fetal calf serum. Finally, the role of proteinases was supported by the demonstration of a cytotoxic effect of two purified proteinases: porcine pancreatic elastase and human neutrophil cathepsin G. The toxicity of these proteinases was also markedly reduced by the specific inhibitors used in the study. These results show that human polymorphonuclear neutrophils stimulated with opsonized zymosan may destroy hepatocytes through the release of proteinases. This might have important path‐ophysiological implications, especially in alcoholic hepatitis in which polymorphonuclear neutrophils regularly infiltrate the liver and could therefore participate in the hepatocel

ISSN:0270-9139    

DOI:10.1002/hep.1840080211

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY