摘要:

AbstractThe interobserver variation in diagnosis and grading of esophageal varices may be ascribed by characteristics of the observers as well as to the patients. Assessment of this variation therefore requires the contributions of multiple observers and patients. Twenty‐eight patients with cirrhosis without previous bleeding or known presence of varices were subjected to upper gastrointestinal endoscopy. Each endoscopy was videotaped and shown to 22 endoscopists. The varices were graded on a scale of 0 to 3 according to size. Each endoscopist diagnosed varices in 8 to 20 patients (mean = 15.9). Overall agreement on the presence (grades 1 to 3) or absence (grade 0) of varices was 70%. The average κ value was 0.38 (standard deviation = 0.16). Discrimination between varices graded 0 to 1 and varices graded 2 to 3 gave a higher κ value (p<0.01) of 0.52 (standard deviation = 0.17). There was a large variation in κ values (range = −0.025 to 0.975). No significant correlation was observed between κ values for the two dichotomies (range = 0.16). The κ values were not related to the experience of the endoscopist. Considerable variation in the agreement on diagnosis and grading of esophageal varices was found. These results must be taken into account in the assessment of trials of prophylaxis of first‐time variceal bleeding. (HEPATOLOGY1990;1

ISSN:0270-9139    

DOI:10.1002/hep.1840110302

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractHigh recurrence and rebleding rates have been reported when endocopic sclerotherapy has been performed on patients with esophageal varices. We studied the relationship between embolization range and recurrence rate in 26 patients in whom percutaneous transhepatic portography was carried out before and after sclerotherapy. Patients were divided into complete and incomplete embolization groups. The complete and incomplete embolization groups. The complete embolization group consisted of 16 patients whose esophageal varices had disappeared and in whom embolization of the feeders to the varices had occurred. The incomplete embolization group consisted of 10 patients whose esophageal varices had disappeared, but no embolization had occurred. Recurrence rates within 2 yr after the treatment were compared between complete and incomplete embolization groups. The recurence rates in the respective groups were 6.7% (1 of 15) and 70.0% (7 of 10), indicating a significant difference between the two groups (p<0.05) and indicating that embolization of both esophageal varices and their feeders is essential to lower the recurrence rate after sclerotherapy. (HEPATOLOGY1990;11:348–352

ISSN:0270-9139    

DOI:10.1002/hep.1840110303

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractThis trial was carried out to assess the value of propranolo for the prevtion of recurrent variceal bleeding in patinets with well‐compensated cirrhosis. We also compared porpranolol therapy to long‐term injection sclerotherapy. One hundred and eight patients, in whom the orginal variceal hemorrhage stopped spontaneousley (before diagnostic endocopy) and without sclerotherpay or surgical intervention were included. All were pugh grade A or B; 55% had alcoholic cirrohosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long‐term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long‐term sclerothrapy. Follow ‐up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long‐term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (P<0.20). On an intetion‐to‐treat basis, the risk of bleedings expressed per patient‐month of follow‐up was similar for the two groups, at 0.05 and 0.037, respectitively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p<0.40). Stepwise regression analysis of possible factors prediciting further bleeding in patients taking propranolo selected only two variables — the pretreatment pulse rate and the extent of pulse‐rate reduction in response to propranolol.These data support propranolol as an alternative first‐line measure to long‐term injection for the management of variceal bleeding. The pretreatment pulse rate and subsequent response to propranolo may provide means of selecting those most likely to benefit.

ISSN:0270-9139    

DOI:10.1002/hep.1840110304

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractSpontaneous bacterial peritonitis in cirrhosis is a serious complication that demands urgent attention. We report here a prospective study of the treatment of 27 episodes of spontaneous bacterial peritonitis in 22 cirrhotic patients with amoxicillin and clavulanic acid. The infection of ascitic fluid was diagnosed by a positive culture plus an ascitic neutrophil count exceeding 75/μl, or by an ascitic neutrophil count exceeding 500/μl. The infection was treated with 1 gm amoxicillin and 0.2 gm clavulanic acid every 6 hr for 14 days. In 17 cases (63%), bacteria were isolated from the ascitic fluid. All the bacteria isolated were sensitive to amoxicillin and clavulanic acid, whereas in five cases they were resistant to amoxicillin alon (Escherichia coliin two cases,Klebsiella pneumoniaein two cases and Bacteroides fragilis in one case). Cure of the infection was achieved in 23 episodes (85%) after 14 days' treatment; 17 patients (63%) were able to leave the hospital. Fourteen of 20 patients (70%) treated for the first episode of infection died within 1 yr: eight from infection, two from gastrointestinal hemorrhage, one from infection and hemorrhage and three from tumors. One patient who had repeated infections underwent liver transplantation and has not had any infectious complications 1.5 yr after surgery. Amoxicillin and clavulanic acid may be an effective first‐line therapy for ascitic fluid infection in cirrhosis. Nevertheless, the 1‐yr prognosis continues to be grave and the severity of the underlying liver disease remains the most important determinant for survival. (HEPATOLOGY1990;11:360

ISSN:0270-9139    

DOI:10.1002/hep.1840110305

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractEleven episodes of spontaneous bacterial empyema were identified in eight cirrhotic patients with ascites. Criteria for spontaneous bacterial empyema included positive pleural fluid culture or polymorphonuclear cell concentration>500 cells/mm3, evidence of pleural effusion before an infectious episode and transudate characteristics during infection. In five cases, spontaneous bacterial empyema was culture‐negative and was associated with spontaneous bacterial peritonitis. Ascitic fluid was culture‐negative in two of these cases and culture‐positive in three. Blood cultures were negative in all five of these cases. In six cases spontaneous bacterial empyema was culture‐positive (Escherichia coliin four,Klebsiella pneumoniaein one andClostridium perfringensin one). Four of these patients had the same organism in ascites; one had culture‐negative spontaneous bacterial peritonitis and one had no infection of ascites. Blood cultures were positive in four of these patients; three died. Death was more frequent in patients with positive cultures than in those with negative ones (p<0.05).Patients with hydrothorax are prone to spontaneous bacterial empyema. This infection probably occurs through hematogenous seeding, but transfer of infected ascites from the abdominal cavity through the diaphragm cannot be excluded. Patients with spontaneous bacterial empyema may be asymptomatic or may be seen with fever, chills and dyspnea. Spontaneous bacterial empyema must be differentiated from parapneumonic empyemas. The presence of pleural effusion before the infectious episode, fluid characteristics and the organisms isolted are the clues for differential diagnosis. Treatment includes antibiotics; chest tube insertion probably is not necessary. (HEPATOLOGY1990;11

ISSN:0270-9139    

DOI:10.1002/hep.1840110306

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractBehavioral and electrophysiological evidence implicating the GABA‐benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy was obtained using an improved rat model of hepatic encephalopathy caused by thioacetamide‐induced fulminant hepatic failure. After the administration of thioacetamide together with supportive therapy, acute hepatocellular failure developed in rats as a result of massive hepatocellular necrosis without evidence of renal failure or hypoglycemia. The evolution of hepatic encephalopthy in this model was sufficiently slow to readily permit the staging of the syndrome. Prominent features of the encephalopathy include a marked reduction in open field activity and an abnormal visual evoked response.Both the deficits in spontaneous motor function and visual evoked response abnormalities of rats in stages III to IV hepatic encephalopathy were significantly improved after the administration of the benzodiazepine receptor ligands flumazenil or Ro 15‐4513. Doses of flumazenil or Ro 15‐4513 that produced these effects in rats with hepatic encephalopathy had no detectable action on either the behavior or the visual evoked responses of normal rats.The ability of benzodiazepine receptor ligands to ameliorate both the behavioral depression and the visual evoked response abnormalities associated with hepatic encephalopathy in the thioacetamide‐induced rat model suggest an involvement of the GABA/benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy. In addition, the similarity of these observations to those in rabbits with hepatic encephalopathy caused by galactosamine‐induced fulminant hepatic failure is compatible with the hypothesis that the mechanisms of hepatic encephalopathy in these two distinct models share a common final pathway, the allosteric enhancement of GABAergic tone through the benzodiazepine receptor. These observations suggest that increased concentrations or availability of a ligand with agonist properties at the benzodiazepine receptor may be involved in the pathogenesis of hepatic encephalopathy and that administration of benzodiazepine receptor antagonists may be of value in the management of hepatic encephalopathy in man. (HEPATOLOGY1990; 1

ISSN:0270-9139    

DOI:10.1002/hep.1840110307

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractAcute intravenous amino acid infusion or a highprotein diet increases renal plasma flow and the glomerular filtration rate in healthy subjects. Conversely, a low‐protein diet reduces renal plasma flow and glomerular filtration rate. The aim of this study was to investigate the effect of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis. Protocol 1: renal plasma flow and glomerular filtration rate were measured before and during intravenous administration of a 10% amino acid solution (0.043 ml/kg/min) to eight compensated cirrhotic patients (group 1), nine nonazotemic cirrhotic patients with ascites (group 2) and seven cirrhotic patients with ascites and functional renal failure (group 3). Amino acid administration induced a significant increase in renal plasma flow and glomerular filtration rate in all groups studied. Renal plasma flow and glomerular filtration rate increased by 16% and 14%, and 21% in group 3. Protocol 2: Renal plasma flow and glomerular filtration rate were measured in nine cirrhotic patients with ascites after 11 days on a low‐protein diet (0.5 gm/kg body weight/day) and also after the patients followed for 11 days a moderately high‐protein diet (1.5 gm/kg body weight/day). The moderately high‐protein diet was associated with a significant increase in renal plasma flow (12%) and glomerular filtration rate (13%) compared with values obtained while the patients followed the low‐protein diet. Plasma glucagon levels increased markedly during the intravenous administration of amino acid and the intake of the moderately highprotein diet. However, no correlation existed between changes in renal plasma flow and glomerular filtration rate induced by intravenous amino acid or dietary proteins and changes in plasma glucagon levels. The renal effects of intravenous amino acid or dietary proteins were not associated with significant changes in plasma renin and norepinephrine levels and urinary excretion of 6‐keto‐prostaglandin‐F1α. In conclusion, a moderately high‐protein diet or intravenous amino acid administration increases renal plasma flow and glomerular filtration rate in cirrhosis. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840110308

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractEnergy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsyproven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 ± 4.0 (mean ± S. E. M.), 216.4 ± 4.7 and 228.8 ± 7.1 (p<0.05 vs. controls), respectively. When related to body surface area (Kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 ± 0.02), patients with acute hepatitis (1.03 ± 0.02) and cirrhotic patients (1.06 ± 0.03). However, when related to 24‐hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was in creased in cirrhosis (p<0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% ± 5%), carbohydrate (2% ± 4%) and protein (12% ± 1%) were different from those of normal controls who metabolized 45% ± 4%, 38% ± 4%, 17% ± 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate.In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrbosis resembles that in starvation. Data on resting energy expenditure depend on the calculations used. Resting energy expenditure was not increased in either group when related to body surface area. An inverse association between the severity of liver disease and energy expenditure was found in cirrhosis. (HEPATOLOGY19

ISSN:0270-9139    

DOI:10.1002/hep.1840110309

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractIsolated hepatocyte cultures have become a frequently used model system for investigating drug metabolism. Although rat and hamster hepatocytes are frequently used for this purpose, metabolism in these species differs in many respects from human metabolism. A species with a metabolism more closely resembling that of humans might be more useful. Ourin vivoexperiments demonstrated that the metabolism of propranolol in the rabbit is more similar to that in humans than in rats or hamsters. We therefore examined the usefulness of rabbit parenchymal liver cells for studies of propranolol metabolism. A detailed method is presented for their preparation and culture, along with data on their viability, structure and protein synthesizing capability. One‐ or two‐day‐old hepatocyte cultures were exposed to 10 μmol/L3H‐propranolol from 30 min to hr; metabolites were identified by gas chromatography‐mass spectrometry and quantitated by high‐performance liquid chromatography. Propranolol metabolism was linear over 1 hr, with 15% of the substrate metabolized during this time. The cytochrome P‐450 pathways, which result in ring oxidation and sidechain oxidation, were expressed in a reproducible fashion similar to that foundin vivoin humans. The arylhydrocarbon hydroxylase inhibitor α‐naphthoflavone (100 μmol/L) inhibited side‐chain oxidation of propranolol by 90% without affecting ring oxidation. In contrast, cholorpromazine (100 μmol/L) was shown to inhibit ring oxidation of propranolol by 85% without affecting sidechain oxidation. Cimetidine (250 μmol/L) inhibited both pathways by about 50%. These observations suggest that rabbit hepatocyte metabolic pathways more closely resemble human cell metabolism and thus may be a more useful adjunct that rat or hamster hepatocytes in the study of drug‐drug interactions when combined within vivostudies in humans. (HE

ISSN:0270-9139    

DOI:10.1002/hep.1840110310

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractWe have previously reported that a 37‐kD liver protein formed an adduct with acetaldehydein vivowhen rats were fed alcohol chronically. To understand the mechanism of the formation of this proteinacta ldehyde adduct, rat hepatocytes in primary culture were treated with ethanolin vitrofor several days. When cultured in hormone‐enriched and trac metalenriched Waymouth's medium, alcohol dehydrogenase activities in hepatocytes decreased only about 30% during 6 days of culture. At the end of the specified time, protein extracts of hepatocytes were immunotransbloted with rabbit immunoglobulin G that recognized acetaldehyde adduct as an epitope. The 37‐kD protein, acetaldehyde adduct band could be detected within 3 days in cells that had been treated with alcohol at a steady‐state concentration as low as 5 mmol/L. Although the maximal intensity was obtained at approximately 10 to 40 mmol/L ethanol, addition of cyanamide (an inhibitor of aldehyde dehydrogenase) further increased the intensity of this protein‐acetaldehyde adduct band by more than twofold. A good correlation existed between acetaldehyde concentration in the medium and the intensity of the 37‐kD protein acetaldehyde adduct band. Formation of the 37‐kD liver protein‐acetaldehyde adduct is thus dependent on acetaldehyde, and the 37‐kD protein is apparently unusually susceptible to chemical modification by acetaldehyde.(HEPATOLOG

ISSN:0270-9139    

DOI:10.1002/hep.1840110311

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY