摘要:

AbstractTo assess if propranolol prevents the first bleeding in cirrhosis, we randomly assigned 174 patients with large varices to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (oral vitamin K, 89 patients). Sixty‐nine patients had alcoholic cirrhosis, 24 posthepatitic cirrhosis and 81 cryp‐togenic cirrhosis. At the time of inclusion, 75 patients (43%) had ascites and according to the Child‐Pugh classification, 103 (59%) had Class A disease, 60 (34%) Class B and 11 (7%) Class C. We report here an interim analysis of the study when all patients had been followed for at least 1 year (mean follow‐up = 22 months). At this time, the cumulative proportion of patients free of bleeding was 74% in the propranolol group and 63% in the placebo group; corresponding survival figures were 59 and 74% (both differences not significant), respectively. A retrospective analysis showed that the cumulative percentage of patients free of bleeding was significantly higher in the propranolol‐ than in the control‐group in the subsets of patients without ascites or in Child‐Pugh Class A: respectively, 87 vs. 64% (p = 0.023) and 88 vs. 64% (p = 0.01). No differences in bleeding incidence were found in patients with ascites or in Child‐Pugh Class B or C. Propranolol treatment did not affect survival in any subgroup. Twenty‐five patients had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 2). If confirmed on a longer follow‐up, these results suggest that propranolol could prevent the first bleeding in patients with well‐

ISSN:0270-9139    

DOI:10.1002/hep.1840080102

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractPropranolol has been reported to prevent the risk of hemorrhage in patients who survived episodes of variceal rupture. Since the first bleeding episode can be lethal, we did a prospective, randomized trial to see whether β‐blockers could also prevent the first hemorrhage. Seventy‐nine consecutive cirrhotics with large esophageal varices by endoscopy and who had never bled were randomly allocated to one of the following treatments: placebo; ranitidine (300 mg per day), or nadolol (40 to 120 mg per day)—which is not cardioselective, reduces portal hypertension and does not interfere with renal flow. Since no significant differences between ranitidine and placebo treatment were observed, the two groups were combined as the control group and compared with the nadolol group.After a mean follow‐up of 24 months, only 1 of the 30 patients in the nadolol group had bled, while 11 of the 49 patients in the control group had bled. The percentages of patients who had not bled 1 and 2 years after the inclusion‐were 100 and 94.4% for the nadolol group and 81.2 and 70.2% for the control group (p<0.02), respectively. There were no differences in the mortality rate.In conclusion, nadolol significantly protects against the first gastrointestinal bleeding episode in

ISSN:0270-9139    

DOI:10.1002/hep.1840080103

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractDue to the marked effects of hemorrhage on cardiac output and splanchnic hemodynamics, the circulatory actions of vasopressin may differ during bleeding as opposed to stable conditions. We evaluated this hypothesis in conscious rats with portal hypertension due to chronic portal vein stenosis, by comparing the effects of a vasopressin infusion (0.02 IU per kg per min) to those of a control saline infusion, during and after a hypoten‐sive hemorrhage (25 ml per kg). We also studied unbled portal hypertensive rats receiving an identical infusion of vasopressin or saline. During and after hemorrhage, vasopressin induced significant changes in systemic hemodynamics but had no effect on portal pressure, portal tributary blood flow and nonhepatic splanchnic arteriolar resistance. In unbled animals, by contrast, vasopressin decreased portal pressure and portal tributary blood flow and increased nonhepatic splanchnic arteriolar resistance. Our data further indicate that hemorrhage alone caused an early vasoconstriction in the portal tributaries and a delayed vasoconstriction in the nonsplanchnic vascular bed while vasopressin during hemorrhage induced an early and sustained vasoconstriction in the nonsplanchnic vascular bed as well as in the portal tributaries. The results show that, during and after severe bleeding, vasopressin exerts little influence on portal hemodynamics. Although these data do not allow firm conclusions concerning the therapeutic efficacy of vasopressin in bleeding esophageal varices, they demonstrate that the splanchnic actions of vasoac‐tive substances cannot be readily extrapolated from stable conditions to hemorrh

ISSN:0270-9139    

DOI:10.1002/hep.1840080104

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractSix of 85 patients (7%) with alcoholic liver disease undergoing transhepatic portal pressure measurement had either stagnant (3 patients) or reversed (3 patients) portal blood flow documented by gentle hand injection of 1 to 2 ml of angiographic contrast. Portal blood flow was uniformly hepatopetal in 24 patients with nonalcoholic liver disease. Recurrent spontaneous hepatic encephalopathy and sodium retention occurred in 4 of 6 patients with stagnant or reversed portal flow; gastrointestinal bleeding was not seen. Standard laboratory tests of liver function were widely variable. Net portal pressure was lower in this group than in patients with alcoholic liver disease and forward portal flow (9.2 ± 2.6 vs. 15.6 ± 4.1 mm Hg, p<0.001). Wedged hepatic vein pressure was 1 to 7 mm Hg higher than portal vein pressure in patients with reversed portal flow. The arterioportal extraction of bile acid was calculated from the difference in concentration between artery and portal vein, and total functional hepatic blood flow was calculated from the hepatic extraction and systemic clearance of indocyanine green. Extraction was 0%, and hepatic blood flow was 0.469 liter per min in a patient with hepatofugal portal flow and recurrent encephalopathy. Extraction was 20%, and hepatic blood flow was 4.014 liters per min in a patient who had never had encephalopathy. These data indicate that arterioportal communications may be sinusoidal or presinusoidal in patients who lose forward portal flow and that the amount of flow in the arterioportal circuit, together with its efficiency, largely determine the clinical outcom

ISSN:0270-9139    

DOI:10.1002/hep.1840080105

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractSodium retention in liver cirrhosis is thought to be due to, among other things, lack of a natriuretic factor or failure to respond to one. α‐Human‐atrial natriuretic peptide is a peptide that accounts partly or entirely for the circulating natriuretic activity in man.In the present study, we have evaluated the effects of the bolus administration of synthetic α‐human‐atrial natriuretic peptide (1 μg per kg) to patients with liver cirrhosis and variable degrees of sodium retention, α‐Human‐atrial natriuretic peptide induced rapid and marked increases of diuresis and natriuresis in patients without sodium retention or with moderate retention. The results were comparable to those obtained in six healthy control subjects. Conversely, the diuretic and natriuretic effects of α‐human‐atrial natriuretic peptide were attenuated or completely blunted in patients with avid sodium retention. The two groups of patients differed not only in basal sodium excretion, but also in plasma renin activity and in plasma aldosterone levels, suggesting that the reduced responsiveness to atrial natriuretic peptide might be due to excessive antagonism by antinatriuretic factors. The direct relationship between baseline sodium excretion rate and that stimulated by human‐atrial natriuretic peptide administration was consistent with this interpretation. In none of the subjects did plasma renin activity peptide and cortisol levels change after human‐atrial natriuretic peptide, while plasma aldosterone slightly declined in cirrhotics. Blood pressure fell after the administration of the peptide, with the drop greater in cirrhotic than in normal subjects. These data show that the hormonal and the vascular effects of human‐atrial natriuretic peptide are not blunted in cirrhotics. Since angiotensin II plays a central role in sustaining blood pressure in patients with advanced liver cirrhosis, the marked drop in blood pressure has been tentatively ascribed to the specific ability of atrial natriuretic peptide to antagonize angiotensin, but other mechanisms cannot be excluded.In conclusion, these data suggest that renal unrespon‐siveness to atrial natriuretic peptide develops in patients with liver cirrhosis during the course of the disease and is strictly related to the

ISSN:0270-9139    

DOI:10.1002/hep.1840080106

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractWe investigated whether spontaneous bacterial peritonitis in cirrhosis is a recurrent process and attempted to identify possible predictors of recurrence in 75 consecutive cirrhotics who had recovered from a first episode of spontaneous bacterial peritonitis between January, 1981 and December, 1984 and who were followed closely throughout their illness (follow‐up period 10 ± 13 months; mean ± S.D.). Thirty‐eight patients (51%) developed one or more episodes of spontaneous bacterial peritonitis during follow‐up, the probability of recurrence (Kaplan‐Meier's method) being 43% at 6 months, 69% at 1 year and 74% at 2 years. Twenty‐three variables (age, sex, etiology of cirrhosis, standard liver and renal function tests and characteristics of the first spontaneous bacterial peritonitis) were analyzed as possible predictors of recurrence of spontaneous bacterial peritonitis. In univariate analysis (curves of Kaplan‐Meier compared with Mantel‐Cox's method), serum bilirubin>4 mg per dl, prothrombin ⩽45% and protein concentration in ascitic fluid ⩽1 gm per dl were significantly (p<0.05) associated with a high risk or recurrence of spontaneous bacterial peritonitis. In multivariate analysis (Cox multiple regression model), only ascitic fluid protein concentration (p = 0.005) and prothrombin activity (p = 0.009) were found to be independent predictors of recurrence of spontaneous bacterial peritonitis. Fifty‐nine patients (79%) died during follow‐up, 18 of them (31%) secondary to spontaneous bacterial peritonitis. The 1‐year survival probability in the whole series of patients was 38%. We conclude that spontaneous bacterial peritonitis frequently recurs in cirrhosis, particularly in patients with severe liver failure or low protein concentration in ascitic fluid, and that the survival of cirrhotics who recover from a first episode of spontaneous bacterial peritonitis is very short, the cause of death being the recurrence of spontaneous bacterial

ISSN:0270-9139    

DOI:10.1002/hep.1840080107

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractLike the peritoneal macrophage, the isolated Kupffer cell is capable of processing and releasing iron acquired by phagocytosis of immunosensitized homologous red blood cells. When erythrophagocytosis is restrained to levels which do not affect cell viability, or less than 1.5 red cells/macrophage (phagocytic index of 150%), over 40% of iron acquired from red cells is released within 24 hr. More active erythrophagocytosis results in greater release of iron but progressive deterioration in cell viability. Iron release is temperature‐dependent, the rate at 37° C being nearly 5‐fold greater than at 4° C. Inclusion of either desferrioxaminine or apotransferrin in the culture medium augments iron release by 25 to 30%, with both agents together having an almost additive effect. Despite its effect on iron release, apotransferrin is not found in sonicates of Kupffer cells, while desferrioxamine appears to chelate iron within the cells. Ascorbate also enhances iron release, but at the expense of cell viability. Neither chloroquine nor colchicine at concentrations which do not affect cell viability influence iron release. The inflammatory state, characterized by hypoferremia due to impaired processing or release of iron by the reticuloendothelial system, may be modeledin vitrowhen serum from rats bearing turpentine‐induced abscesses is included in the culture medium. Attempts to delineate the humoral agent responsible for this effect have not been successful, iron release being insensitive to the presence of interleukin‐1, γ‐interferon and tumor nec

ISSN:0270-9139    

DOI:10.1002/hep.1840080108

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

Abstract(i) Hepatocytes isolated from adult rats were cultured for 2 to 3 weeks on collagen in a modified, serum‐free Waymouth medium containing fatty acids and varying concentrations of glucocorticoid, insulin and glucagon. (ii) In the presence of all three hormones, it was possible to maintain the content of DNA, the activity of glucokinase, pyruvate kinase, hexokinase and lactate dehydrogenase at initial levels for 2 to 3 weeks. The activity of glucokinase and pyruvate kinase was affected by the concentration of insulin. (iii) The activity of alcohol dehydrogenase was stable for 3 days and declined to about 25% of the initial level after 2 weeks of culture, irrespective of the presence of hormones. (iv) Maintenance of albumin secretion was dependent on the presence of glucocorticoid, and glucocorticoid and insulin showed an additive or, at some time points, a synergistic effect on its secretion. (v) The content of cytochrome P‐450 could be kept at 65% of the initial level, provided that a relatively high concentration of dexamethasone was present (10−6M). (vi) In the absence of hormones, urea synthesis was 70% of initial levels throughout the experimental period. With insulin and glucocorticoid present, a high concentration of glucagon (10−8M) was required to maintain the synthesis of urea at this level. (vii) It is concluded that hepatocyte cultures as described in the present study may be a useful, well‐defined system for long‐term metabolic, pharmacologic and toxicolo

ISSN:0270-9139    

DOI:10.1002/hep.1840080109

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractThe numbers of Kupffer cells (macrophages) and pit cells (large granular lymphocytes) were counted by light and electron microscopy in perfusion‐fixed liver sinusoids. After a single intravenous injection of the biological response modifiers zymosan,Propionibacterium acnesand OK‐432, a 4‐ to 6‐fold increase in the number of pit cells and a 2‐ to 4‐fold increase in the number of Kupffer cells were observed within a period of 4 to 7 days. The mechanisms of the pit cell accumulation were further studied by the metaphase arrest method and by selective irradiation of the liver, or of the rest of the body, with a dose of 8.5 Gy. Stimulated pit cells showed mitotic activity in the liver and to a lesser extent in peripheral blood. The zymosan‐induced increase in pit cell number was inhibited by irradiation of the liver but not by irradiation of the rest of the body (with shielded liver). It is concluded that the hepatic pit cell population, which has been shown to have natural tumoricidal activity, can be induced to expand by biological response modifiers, and local division of preexisting cells contributes significantly to t

ISSN:0270-9139    

DOI:10.1002/hep.1840080110

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractRats fed a diet high in fat and low in protein continuously infused by intragastric cannula were given ethanol for 2 to 6 months in order to examine the response of liver adenine nucleotides to changes in systemic PO2. Hepatic adenine nucleotides were measuredin vivomonthly using liver obtained by biopsy from rats while a high blood alcohol level was maintained. Ethanol decreased hepatic ATP and the total adenylate pool, but did not change the levels of ADP and AMP. Adenylate energy charge showed only a tendency to be decreased. Carotid arterial PO2was mildly but significantly lower in ethanol‐fed rats compared to the pair‐fed controls. Pure O2inhalation for 3 min increased the PO2four times in the ethanol and control‐fed rats, and tended to increase ATP and decrease ADP in ethanol‐fed rats as well as pair‐fed controls. It restored the energy charge to a normal level in the ethanol‐fed rats. Ten per cent O2+ 90% N2inhalation for 3 min decreased the PO2to 40 mm Hg in both the ethanol‐fed and control rats, and this rapidly decreased ATP. This effect was significantly greater in the ethanol‐fed rats compared to the controls. The total adenylate pool and the energy charge were decreased only in ethanol‐fed rats. The results show that the reduced energy stores in the rat liver induced by ethanol are rapidly responsive to changes in PO2. Thus, the livers of ethanol‐fed rats were more vulnerable to transient hypoxia

ISSN:0270-9139    

DOI:10.1002/hep.1840080111

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY