摘要:

AbstractHepatic extraction of solutes depends on microvascular angioarchitecture, hemodynamics and solute concentrations. These factors may contribute to the heterogeneity observed in solute transport and uptake in the hepatic lobules. However, predictions of liver extraction based on black‐box models require assumptions about these factors and the microvascular transport mechanisms involved. Consequently, the purpose of this study was to investigate solute transport and uptake by hepatocytes. Livers from male Sprague‐Dawley rats were perfused at physiological flowrates and portal pressures on the stage of anin vivomicroscope using a low‐hematocrit Ringer solution. A bolus of fluorescein isothiocyanate‐dextrans (17,900, 39,000, 65,600 or 156,900 MW), which are considered inert fluid‐phase markers, was injected into the portal vein. Fluorescein isothiocyanate fluorescence, as a measure of solute concentration, was video recorded in periportal or centrivenular regions of the lobules. Spatial and temporal fluorescence data, measured in sinusoids and hepato‐cytes, were fit to one‐dimensional transport models to determine estimates for an intracellular effective diffusion coefficient and for hepatocyte permeability. The calculated effective diffusion coefficients were 2.5 times larger for dextrans less than 66,000 MW, but were not different between the periportal and centrivenular regions. Also, the values did not show the inverse log‐log molecular weight dependency for dextrans seen in other microvascular tissues. Values of permeability were much larger than values for nonfenestrated capillaries and also did not exhibit any regional differences. Finally, comparison of the magnitudes of effective diffusion coefficients and permeability suggested that the controlling resistance to dextran uptake occurs

ISSN:0270-9139    

DOI:10.1002/hep.1840090112

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractDrugs reported to reduce portal pressure through different mechanisms were combined in the hope of either additive portal hypotensive effects in “responders,” or inducing a portal hypotensive effect in “nonresponders” to the initial drug. Seven patients with alcoholic cirrhosis received verapamil, 10 mg i.v., and, 60 min later, ketanserin, 5 mg i.v. Verapamil decreased heart rate and increased free hepatic venous pressure but had no effect on hepatic venous pressure gradient or azygos blood flow. When combined with verapamil, ketanserin significantly diminished wedged hepatic venous pressure and hepatic venous pressure gradient. Ten other patients with alcoholic cirrhosis received propranolol, 15 mg i.v., and 45 min later, ketanserin, 5 mg i.v. In all patients, heart rate, cardiac index and azygos blood flow significantly decreased after propranolol. After propranolol alone, however, wedged hepatic venous pressure decreased in only five patients, responders. In five other patients, defined as nonresponders, propranolol did not decrease this pressure. The addition of ketanserin to propranolol induced further significant reduction in wedged hepatic venous pressure, hepatic venous pressure gradient and azygos blood flow. Among the five nonresponders, three had a reduced wedged hepatic venous pressure after ketanserin was combined. We conclude that verapamil does not reduce portal pressure or collateral blood flow in patients with alcoholic cirrhosis. The splanchnic hemodynamic effects of propranolol and ketanserin appear to be independent and additive, without significant systemic alt

ISSN:0270-9139    

DOI:10.1002/hep.1840090113

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractKetanserin, a 5‐hydroxytryptamine‐2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 ± 2.7 mmHg. It decreased significantly to 13.3 ± 2.0 mmHg (p<0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 ± 4.0 to 20.1 ± 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function.This study confirms evidence in favor of a role for 5‐hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.Although the long‐term oral administration of ketanserin reduces the mean portal pressure in patients with alcoholic cirrhosis and portal hypertension, the high incidence of side effects may limit its value, especially in patients who have a poor liv

ISSN:0270-9139    

DOI:10.1002/hep.1840090114

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractThe interferon responsiveness of two cell lines transfected with the hepatitis B virus genome was investigated. A cosmid vector containing multiple copies of the hepatitis B virus genome was transfected into FL5‐1 cells; it reduced their sensitivity to interferons as measured by inhibition of the cytopathic effect of Sindbis virus challenge. Similar vectors transfected into HeLa cells reduced their sensitivity to interferon as measured by production of β2‐microglobulin.This resistance to interferon in hepatitis B virus‐transfected cells may be a trans‐acting phenomenon related to nucleotide homology between hepatitis B virus DNA and sequences regulating the interferon‐induced antiviral system. Alternatively, other mechanisms involving transcription or translation products of hepatitis B virus may be responsible.Hepatitis B virus‐induced cellular resistance to the action of interferon may be important in maintaining the chronic c

ISSN:0270-9139    

DOI:10.1002/hep.1840090115

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractWe analyzed the demographic, clinical, laboratory and histologic features of 13 patients who were diagnosed as having polyarteritis nodosa associated with hepatitis B virus infection over a 12‐year period, 1974 to 1985. All 13 patients were Yupik Eskimos and resided in southwest Alaska, an area hyperendemic for hepatitis B virus infection. The annual incidence of hepatitis B virus‐associated polyarteritis nodosa for this population is 7.7 cases per 100,000 population. All patients presented with multisystem disease, and all had biopsy or angiographic findings consistent with polyarteritis nodosa. All 13 were positive for hepatitis B surface antigen and hepatitis B e antigen at diagnosis. Two untreated patients and two of five patients who received corticosteroids died, vs. none of six who received corticosteroids plus cyclophosphamide. None of the patients who survived the initial bout of polyarteritis nodosa has relapsed after a mean follow‐up of 55 months, but all have become chronic HBsAg carriers. In eight patients, clinical or serologic evidence indicated that polyarteritis nodosa followed recent hepatitis B virus infection. We concluded that hepatitis B virus‐associated polyarteritis nodosa is a serious, life‐threatening complication that occurs early in the course of hepatitis B virus infection, is ameliorated by immunosuppressive therapy and can be prevented by hepatitis

ISSN:0270-9139    

DOI:10.1002/hep.1840090116

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractA total of 128 HBsAg carrier infants born to HBeAg‐positive HBsAg carrier mothers were tested for serum HBsAg, HBeAg, hepatitis B virus DNA and anti‐HBc. Ninety‐three of them had received hepatitis B vaccination. Anti‐HBc had been found to be negative in sera of 12 infants who were HBsAg, HBeAg and hepatitis B virus DNA positive during the follow‐up period of 3 to 5 years. Liver damage, as measured by serum ALT levels, was found to be normal among the 12 HBsAg carrier infants with serum anti‐HBc negativity, whereas 39.7% of the 116 anti‐HBc‐positive HBsAg carrier infants had abnormal ALT levels during the follow‐up period. Anti‐HBe and anti‐HBs also were not detected in sera of these anti‐HBc‐negative HBsAg carrier infants. Thus, HBsAg carrier infants with anti‐HBc negativity probably result from immune incompetency of the

ISSN:0270-9139    

DOI:10.1002/hep.1840090117

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractBasal levels of the interferon‐associated enzyme 2′,5′‐oligoadenylate synthetase were studied in lymphocytes of 46 patients with acute viral hepatitis and in 46 patients with chronic hepatitis B. Measurement ofin vitroproduction of 2′,5′‐oligoadenylate synthetase following overnight incubation of lymphocytes with exogenous interferon was used to assess functional capacity of the lymphocyte interferon system. In acute hepatitis patients, an early but transient elevation of 2′,5′‐oligoadenylate synthetase was observed; the mean level at 1 week was significantly greater than the mean level at 4 weeks after the onset of their illness (p<0.01). Serial 2′,5′‐oligoadenylate synthetase levels did not identify those patients who were to progress to chronic hepatitis. Patients with chronic hepatitis B infection, regardless of background liver histology, generally had normal basal lymphocyte 2′,5′‐oligoadenylate synthetase levels. In both acute viral hepatitis and chronic hepatitis B, there was an inverse correlation between basal 2′,5′‐oligoadenylate synthetase level and 2′,5′‐oligoadenylate synthetase response to overnight incubation with interferon, a finding that suggested a transient down regulation of interferon responsiveness. These findings provided no support for the hypothesis that there is an inherent or persistently induced deficiency in the interf

ISSN:0270-9139    

DOI:10.1002/hep.1840090118

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractTwo hundred ninety patients (203 men, 87 women), age 7 to 74 years (mean: 39.1 years), with chronic hepatitis B virus infection, were prospectively followed for a period of 1 to 4 years to determine the value of α‐fetoprotein monitoring in the early detection of hepatocellular carcinoma. At presentation, 66% of the patients were asymptomatic, 19% had chronic hepatitis and 15% had established cirrhosis.Forty‐four (15%) patients had elevated α‐fetoprotein levels on one or more occasions during the study period. Twenty patients with normal α‐fetoprotein levels at presentation developed elevated α‐fetoprotein levels during the course of follow‐up, whereas 24 patients had elevated α‐fetoprotein levels at presentation. Six (14%) of these 44 patients (five men and one woman), age 23 to 66 years, had persistent or progressive increase in α‐fetoprotein levels and were confirmed to have hepatocellular carcinoma. In four patients, the α‐fetoprotein levels were below 500 ng per ml at the time of tumor localization. Only three patients had resectable tumors. All six patients would have been missed if α‐fetoprotein screening was restricted to men above the age of 40 with cirrhosis and anti‐HBe. Of the remaining 38 patients, elevation in α‐fetoprotein levels in 18 patients was associated with exacerbations of the underlying liver disease and/or significant changes in level of hepatitis B virus replication, but in 20 patients, no apparent cause could be identified. The elevation in AFP levels exceeded 200 ng per ml in 26% and persisted beyond 6 months in 15% of these patients.We observed that elevation in α‐fetoprotein levels occurred quite frequently in patients with chronic hepatitis B virus infection. The differentiation between benign and malignant causes of α‐fetoprotein elevation was at times difficult. Thus, α‐fetoprotein monitoring alone is not a satisfactory tool in the ea

ISSN:0270-9139    

DOI:10.1002/hep.1840090119

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to investigate the use of a radiolabeled mouse monoclonal antibody (and its F(ab′)2fragment) against α‐fetoprotein in the scinti‐graphic diagnosis of hepatocellular carcinoma. Twenty‐six southern African Blacks and one Caucasian with hepatocellular carcinoma and four patients with other malignant tumors of the liver were studied. Although six hepatocellular carcinomas appeared to selectively concentrate α‐fetoprotein antibody, one of these tumors was not producing α‐fetoprotein. Moreover, in another 18 patients with α‐fetoprotein‐producing hepatocellular carcinomas, uptake of α‐fetoprotein antibody was at best only equal to that in nontumorous hepatic tissue, and three hepatocellular carcinomas that were not producing α‐fetoprotein concentrated the antibody to the same extent as did the α‐fetoprotein‐producing tumors and hepatic tissue. All four tumors other than hepatocellular carcinoma concentrated α‐fetoprotein antibody as well as did hepatic tissue. These findings suggest that the penetration of hepatocellular carcinomas by α‐fetoprotein antibody is a passive and nonselective process. This conclusion is supported by anin vitrostudy in which a non‐α‐fetoprotein‐producing hepatic metastasis took up as much radiolabeled α‐fetoprotein antibody as did three of four α‐fetoprotein‐producing hepatocellular carcinomas. A likely explanation for the failure of α‐fetoprotein monoclonal antibody to be selectively concentrated by hepatocellular carcinomas is that α‐fetoprotein is an export protein and is not

ISSN:0270-9139    

DOI:10.1002/hep.1840090120

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractMembranous obstruction of the inferior vena cava has been incriminated as a risk factor for hepatocellular carcinoma in South African Blacks and in Japanese. However, the frequency with which this anomaly is found in patients with hepatocellular carcinoma, and hence its numerical importance as an etiological association of the tumor, has not been ascertained. Using radionuclide and contrast venography as well as necropsy and laparotomy examination, we investigated 162 unselected southern African Blacks with hepatocellular carcinoma together with appropriate controls for the presence of membranous obstruction of the inferior vena cava. Membranous obstruction of the inferior vena cava was detected in six of 162 (3.7%) hepatocellular carcinoma patients, compared with one of 279 subjects (0.36% p = 0.011) dying a violent death, none of 55 patients (p = 0.169) with malignant disease other than hepatocellular carcinoma and eight of 150 patients (5.3%; p = 0.336) being investigated for conditions which might have been associated with membranous obstruction of the inferior vena cava. Six of the 15 individuals (40%) found to have membranous obstruction of the inferior vena cava had concomitant hepatocellular carcinoma, confirming that membranous obstruction of the inferior vena cava constitutes a risk factor for the development of the tumor. However, only a very small proportion of hepatocellular carcinoma patients have this abnormality, so that it is a minor causal association of the tumor only. All of the patients found to have membranous obstruction of the inferior vena cava and hepatocellular carcinoma, but only a minority of those with membranous obstruction of the inferior vena cava alone, were born and had grown up in the Transvaal province. This suggests that membranous obstruction of the inferior vena cavaper sedoes not cause hepatocellular carcinoma, but rather that its presence renders the individual susceptible to one or more environmental hepatocarcinogens. The nature of these putative carcinogens is not known, but there is no evidence that chronic hepatitis B virus infection, alcohol ingestion or cigarette smoking is implicated.

ISSN:0270-9139    

DOI:10.1002/hep.1840090121

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY