bluuebunny/crossref_metadata_2025 huggingface dataset:
Fulminant Hepatic Failure Caused by Acute Fatty Liver of Pregnancy Treated by Orthotopic Liver Transplantation
Authors: Ockner Samuel A. , Brunt Elizabeth M. , Cohn Steven M. , Krul Elaine S. , Hanto Douglas W. , Peters Marion G.
Published: March 2007

A previously healthy 35–year–old woman was seen at 37 weeks' gestation with a 10–day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein–Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.
Incorporation of Iododeoxyuridine Into Neoplastic Dna: A Fraudulent Magic Bullet?
Authors: Calabresi Paul , Curt Gregory
Published: March 2007

Fourteen patients received 5–iodo–2 –deoxyuridine (IdUrd) before surgery for placement of a hepatic arterial catheter. Biopsy specimens were obtained at the time of surgery and the incorporation of IdUrd into DNA in tumor and normal hepatic tissue was measured by high–performance liquid chromatography and used as an index of drug selectivity. Over a 3–day intravenous infusion of IdUrd at 1,000 mg/m2/day, substitution for thymidine in tumor DNA averaged 3.1%. Normal hepatic DNA contained <1% substitution by IdUrd. Arterial delivery of IdUrd increased levels in DNA, whereas modulation with fluorodeoxyuridine produced mixed results. In six patients, flow cytometric analysis showed that the tumor contained a median of 32% tumor cells that had incorporated IdUrd in 3 days, corresponding to a potential doubling time of only 10 days. Thymidylate synthetase activity in tumors was 20–fold greater than in normal liver tissue, whereas thymidine kinase activity was two–fold greater in tumors. These pharmacological studies encourage further clinical trials of IdUrd as a cytotoxic agent or radiosensitizer.
Endoscopic Markers of Impending Varceal Hemorrhage: Correlation With the Pressure in the Varices
Authors: Beppu Kazushige , Hashizume Makoto
Published: March 2007

In 40 patients with cirrhosis and esophageal varices, transmural variceal pressure was assessed endoscopically by fine needle puncture and related to endoscopicsigns as well as to the severity of liver disease. Transmural pressure was significantly (p < 0.01) higher in the presence of a red color sign (26.7[7.8] cm H2O) than in its absence (19.1 [6.6] cm H2). Transmural pressure, however, was not significantly related to diameter or number of varices (diameter >5mm: 23.7 [8.4], diameter ≤5 mm: 22.2 [7.9] cm H20; number > 3: 23.2 [8.0], number ≤3: 22.2 [7.8] cm H2O. The Child status (Child A: 23.9 [8.0], Child B/C: 21.3 [8.1] cm H2O) and individual Child–Pugh parameters including ascites (ascites present: 23.2 [8.3] cm H2O, ascites absent: 22.8 [8.1] cm H2O) were not significantly related to transmural variceal pressure. We conclude that the endoscopic visibility of a red color sign on the varices is associated with a high transmural esophageal variceal pressure. Our results favor the hypothesis that variceal pressure may be of major importance for the development of the red color sign.
S –Adenosyl–L–Methionine Attenuates Alcohol–Induced Liver Injury in the Baboon
Authors: Lieber Charles S. , Casini Alessandro , Decarli Leonore M. , Kim Cho-Il , Lowe Nancy , Sasaki Rika , Leo Maria A.
Published: March 2007

Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S–adenosyl–L–methionine concentration: 74.6 ± 2.4 nmol/gm vs. 108.9 ± 8.2 nmol/gm liver in controls (p < 0.005). The depletion was corrected with S–adenosyl–L–methionine (0.4 mg/kcal) administration (102.1 ± 15.4 nmol/gm after S–adenosyl–L–methionine-ethanol, with 121.4 ± 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 ± 0.13 μmol/gm after ethanol vs. 4.87 ± 0.36 μmol/gm in controls) that was attenuated by S–adenosyl–L–methionine (3.89 ± 0.51 μmol/gm in S–adenosyl–L–methionine–methanol vs. 5.22 ± 0.53 μmol/gm in S–adenosyl–L–methionine controls). There was a significant correlation between hepatic S–adenosyl–L–methionine and glutathione level (r = 0.497; p < 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 ± 21.4 IU/L vs. 13.4 ± 1.8 IU/L; p < 0.001, whereas in a corresponding group of animals given S–adenosyl–L–methionine with ethanol, the values were only 30.3 ± 7.1 IU/L (vs. 9.6 ± 0.7 IU/L in the S–adenosyl–L–methionine controls). This attenuation by S–adenosyl–L–methionine of the ethanol–induced increase in plasma glutamic dehydrogenase (p < 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme. Succinate dehydrogenase activity was increased in liver homogenates of animals fed ethanol (81.4 ± 4.0 mU/mg protein vs. 55.4 ± 2.1 mU/mg in controls; p < 0.001), probably reflecting the increased mitochondrial mass. S–adenosyl–L–methionine decreased succinate dehydrogenase levels (66.7 ± 3.6 mU/mg protein in S–adenosyl–L–methionine–ethanol group vs. 45.5 ± 2.2 mU/mg in S–adenosyl–L–methionine controls; p < 0.001). S–adenosyl–L–methionine supplementation also significantly lessened the ethanol–induced increase of plasma AST. Thus long–term ethanol intake is associated with hepatic S–adenosyl–L–methionine depletion, which can be corrected at least in part by S–adenosyl–L–methionine administration, resulting in an attenuation of some alcohol–induced liver injury.
N –Acetylglucosamine–6–Phosphate Deacetylase in Hepatocytes, Kupffer Cells and Sinusoidal Endothelial Cells From Rat Liver
Authors: Campbell Patrick , Thompson Jerry N. , Fraser Robert J.E. , Laurent Torvard C. , Pertoft HåKan , Rodén Lennart
Published: March 2007

The activity of N–acetylglucosamine–6–phosphate deacetylase, a key enzyme in the pathway of N–acetylglucosamine catabolism, was measured in hepatocytes, Kupffer cells and sinusoidal endothelial cells from rat liver and cultured human skin fibroblasts. Kupffer cells and endothelial cells had similar high levels of deacetylase activity that were more than twice the level observed in fibroblasts. In contrast, hepatocytes had extremely low activity (several hundredfold less than Kupffer cells and endothelial cells). A major implication of deacetylase deficiency in hepatocytes is that N–acetylglucosamine generated as a result of the catabolism of complex carbohydrates in these cells cannot enter glycolysis and must be largely reused for the synthesis of plasma glycoproteins and other N–acetylglucosamine–containing macromolecules.
Effect of Colchicine on Lymphocyte and Monocyte Function and Its Relation to Fibroblast Proliferation in Primary Biliary Cirrhosis
Authors: Kershenobich David , Rojkind Marcos , Quiroga Alfonso , Alcocer-Varela Jorge
Published: March 2007

Lymphocyte and monocyte function was investigated in eight patients with primary biliary cirrhosis and in age–matched and sex–matched controls. In three of the eight cirrhotic patients, two were in the late stage of the disease (stage III) and concanavalin A–induced suppressor cell function was markedly decreased; it returned to normal levels after 1 mo of treatment consisting of 5 mg per week of orally administered colchicine. The relative percentage of T cell subsets (CD3, CD4 and CD8) and the mean percentage of the helper and the suppressor phenotype were similar in cirrhotic patients and in controls. Basal production of interleukin–1 activity by a monocyte–enriched fraction of peripheral blood mononuclear cells of cirrhotic patients was three–fold above control values: after stimulation with endotoxin, interleukin–1 values increased tenfold above basal levels in monocyte–enriched fraction of peripheral blood mononuclear cells of both normal and cirrhotic patients. Colchicine normalized the basal production of interleukin–1 and inhibited its stimulation by endotoxin by 50%. Culture supernatants of endotoxin–stimulated monocyte–enriched fraction of peripheral blood mononuclear cells increased the proliferation of cultured human skin fibroblasts by 50%. In contrast, supernatants from stimulated monocyte–enriched fraction of peripheral blood mononuclear cells obtained from colchicine–treated patients significantly inhibited fibroblast proliferation. These findings suggest that stimulated chronic inflammatory cells may play an important role in liver fibrosis. Some of the actions of colchicine could be related to its effects on lymphocyte and monocyte function.
Inactivation and Dissociation Of S –Adenosylmethionine Synthetase by Modification of Sulfhydryl Groups and Its Possile Occurrence in Cirrhosis
Authors: Corrales Fernando , Cabrero Carmen , Pajares Maria A. , Ortiz Pablo , Martin-Duce Antonio , Mato Jose M.
Published: March 2007

Catalytically active human and rat liver S–adenosylmethionine synthetase exists mainly in tetramer and dimer form. In liver biopsy samples from cirrhotic patients a marked reduction in total S–adenosylmethionine synthetase activity and a specific loss of the tetrameric form of the enzyme exist. We have investigated the possible role of sulfhydryl groups in maintaining the structure and activity of S–adenosylmethionine synthetase. Both forms of S–adenosylmethionine synthetase are rapidly inactivated by N–ethylmaleimide, and the loss of enzyme activity correlates with the incorporation of approximately 2 moles N–ethylmaleimide per mole of subunit. In addition, reaction with N–ethylmaleimide resulted in displacement of the tetramer–dimer equilibrium of the enzyme toward the dimer, but no monomer was detected under these conditions. A catalytically active monomeric S–adenosylmethionine synthetase was detected in the cytosolic extract from a liver biopsy sample from a cirrhotic patient, supporting our model for the structure of S–adenosylmethionine synthetase. Because treatment of S–adenosylmethionine synthetase with N–ethylmaleimide resembles the situation of this enzyme in cirrhotic patients, it is proposed that impaired protection of the enzyme from oxidizing agents caused by a decreased synthesis of glutathione can explain the diminished synthesis of S–adenosylmethionine in liver cirrhosis.
Hemodynamic Evaluation of Molsidomine: A Vasodilator With Antianginal Properties in Patients With Alcoholic Cirrhosis
Authors: Vinel Jean Pierre , Monnin Jean-Luc , Combis Jean-Marc , Cales Paul , Desmorat Herve , Pascal Jean-Pierre
Published: March 2007

Organic nitrates were reported to reduce portohepatic venous pressure gradient in patients with cirrhosis. However, these drugs lower arterial pressure and are well known to induce tolerace. The aim of the present study was to assess the hemodynamic effects of molsidomine, an antianginal agent, which does not induce tolerance and has little effect on arterial pressure in patients with normal liver, in 13 patients with alcoholic cirrhosis. Wedged hepatic vein pressure (-11%, p < 0.01), portohepatic venous pressure gradient (-15%, p < 0.005), hepatic blood flow (-17.4%, p < 0.005), mean arterial pressure (-13.5%, p < 0.01) and cardiac output (-17%, p < 0.001) were significantly reduced by molsidomine. Free hepatic vein pressure, intrinsic hepatic clearance indocyanin green, heart rate and systemic vascular resistances were not significantly modified. There was no correlation between the decrease in portohepatic venous pressure gradient and the reduction in mean arterial pressure on one hand and the decrease in cardiac output on the other hand. We therefore conclude that in patients with cirrhosis, molsidomine has effects similar to nitrates on systemic and splanchnic hemodynamics.
Immunocytochemical and Electron Microscopic Study of Hepatitis B Virus Antigen and Complete Particle Production in Hepatitis B Virus Dna Transfected Hepg2 Cells
Authors: Roingeard Philippe , Lu Shilun , Sureau Camille , Freschlin Marianne , Arbeille Brigitte , Essex Max , Romet-Lemonne Jean-Loup
Published: March 2007

The relationship between the presence of hepatitis B virus antigens, their localization and hepatitis B virus replication was studied in different clones of cultured HepG2 hepatoblastoma cells transfected with cloned hepatitis B virus DNA. Intracellular hepatitis B virus antigens were detected by immunofluorescence. The production of these antigens was evaluated in the culture media by enzyme–linked immunoassay. Hepatitis B virus DNA was detected using dot–blot hybridization. Three types of HBeAg staining were observed in transfected HepG2 cells: (a) cells with nuclear HBcAg, (b) cells with cytoplasmic HBcAg and (c) cells with both nuclear and cytoplasmic HBcAg. Cell types b and c also expressed hepatitis B virus DNA in their culture media. Our results suggest that cytoplasmic HBcAg may be more involved than nuclear HBcAg in hepatitis B virus replication. The site of hepatitis B virus formation in hepatocytes was studied by electron microscopic examination of a specific hepatitis B virus producer clone, thereby allowing detection of intracellular Dane particles more easily than liver biopsy samples from infected patients. Dane particles and HBsAg filaments were found in large, dilated structures probably related to the endoplasmic reticulum. Budding of core particles into cisternae of endoplasmic reticulum–related structures appears to be a possible mechanism for hepatitis B virus formation; our results suggest that the exocytosis of cisternae to extracellular spaces may be a mechanism for release of hepatitis B virus particles.
Increase in Hepatocyte and Nuclear Volume and Decrease in the Population of Binucleated Cells in Preneoplastic Foci of Rat Liver: A Stereological Study Using the Nucleator Method
Authors: Jack Elspeth M. , Bentley Philip , Bieri Francoise , Muakkassah-Kelly Samar F. , Stäubli Willy , Suter Joseph , Waechter Felix , Cruz-Orive Luis M.
Published: March 2007

Gamma–glutamyltranspeptidase–positive hepatocyte foci were produced in female rats given a single dose of diethylnitrosamine neonatally after birth and, after weaning, a diet containing phenobarbitone for 30 wk. The nucleator method, a new stereological approach, provided an efficient, unbiased estimate of mean cell volume in focal lesions and extrafocal areas. It also provided an unbiased sample of cells to estimate hepatocyte nuclear volume and the percentage of binucleated cells. The results showed an increase in the mean volume of mononucleated cells-from 4,700 μm3 in extrafocal areas to 12,700 μm3 in foci-and of binucleated cells-from 6,900 μm3 to 25,000 μm3. This demonstrated the hypertrophic effect of the carcinogenic treatment in focal lesions. A striking reduction in the proportion of binucleated cells was also observed in the preneoplastic lesions. Nuclear volume measurements from mononucleated and binucleated hepatocytes were used to assess ploidy. An apparent increase in nuclear ploidy, with no change in cellular ploidy, was noted in focal tissue when compared with nonfocal tissue. This appeared to be caused by an increase in mononucleated tetraploid cells and a reduction in binucleated cells with two diploid nuclei, indicating an altered mitotic mechanism in focal lesions. The significance of these changes in cell volume, apparent ploidy levels and binuclearity in preneoplastic foci is discussed in relation to the hepatocarcinogenic process.
Contraceptive Steroids As A Risk Factor for Hepatocellular Carcinoma: A Case/Control Study in South African Black Women
Authors: Kew Michael C. , Song Ernest , Mohammed Abdullah , Hodkinson John
Published: March 2007

The role of contraceptive steroids in the etiology or pathogenesis of hepatocellular carcinoma in urban South African black women was investigated in a hospital–based case and control study. Participating were 46 women, 19 to 54 yr old, with carcinoma, and 92 matched controls. South African blacks have a high incidence of hepatocellular carcinoma, and urban black women have used contraceptive steroids fairly widely for a number of years. Use of contraceptive steroids for longer than 6 mo (mean duration 46.7 mo) was not found to pose a risk for development of hepatocellular carcinoma in this population-relative risk 0.8 (95% confidence interval [C. I.] 0.4 to 1.7). This was also true of use for longer than 8 yr-relative risk 0.6 (95% C. I. 0.2 to 2.5), and if a combination of an estrogen and a progestogen or a progestogen alone was used (relative risk 1.7 [95% C. I. 0.7 to 4.2] and 0.4 [95% C. I. 0.1 to 1.2], respectively). Chronic hepatitis B virus infection was confirmed to have an etiological association with hepatocellular carcinoma, but there was no evidence that contraceptive steroids acted as a co–carcinogen with the virus or, conversely, that they played a causal role in patients negative for hepatitis B surface antigenemia. We cannot, however, exclude the possibility that contraceptive steroids may play a causal role in hepatocellular carcinoma in black women who have never been infected with the hepatitis B virus. Nor was there evidence that contraceptive steroids acted in concert with either cigarette smoking or chronic alcohol abuse in hepatocarcinogenesis. We conclude that contraceptive steroids cannot at present be incriminated as a risk factor for the development of hepatocellular carcinoma in South African black women.
An Additional Argument for A Toxic Mechanism of Peliosis Hepatis in Man
Authors: Zafrani Elie Serge
Published: March 2007

A patient with acute myeloblastic leukaemia developed jaundice revealing peliosis hepatis after receiving 6–thioguanine for two months. Peliosis hepatis was severe and was associated with mild lesions of centrilobular veins. Withdrawal of 6–thioguanine was followed by a progressive improvement of liver dysfunction. This report shows that 6–thioguanine, a thiopurine already reported to be responsible for veno–occlusive disease of the liver, can induce peliosis hepatis. This suggests that some liver vascular disorders caused by thiopurines (6–thioguanine, azathioprine and 6–mercaptopurine), particularly peliosis hepatis, veno–occlusive disease, sinusoidal dilatation and perisinusoidal fibrosis, might be related syndromes caused by similar lesions at different sites.
Sclerotherapy With Alcohol-A Two–Edged Sword!
Authors: Sarin S. K.
Published: March 2007

Absolute alcohol is a potentially optimal agent for sclerotherapy of esophageal varices. It is cheap and readily available. We compared the efficacy and safety of alcohol with those of a commonly used sclerosing agent, polidocanol. The study was planned to include patients with previous bleeding from esophageal varices randomly assigned to one of the two treatments. After the inclusion of the first 11 patients (6 in the polidocanol group and 5 in the alcohol group), however, the trial was interrupted because of serious complications in patients treated with alcohol (four major bleeding episodes and one esophageal stenosis). The two agents were of comparable efficacy in the small sample of patients studied. The complications were related to the presence of iatrogenic esophageal ulcers which were more frequent (100% vs 30%) and significantly larger (mean, 1.4 cm vs 0.7 cm, p < 0.05) in patients treated with alcohol.
Changing Trends of Inborn Errors in Reye's Syndrome: Rarity Is Relative
Authors: Hsia Edward Y.
Published: March 2007

Genetic disorders were identified infrequently among children presenting with Reye's syndrome in the past. During a two–year period, we evaluated four consecutive patients referred for intensive care of Reye's syndrome. A standard investigation for inborn errors of metabolism revealed that two patients had enzymatic defects of fatty acid oxidation, and the other two had partial deficiencies of ornithine transcarbamoylase. None had experienced a previous episode of Reye's syndrome, and three of the four had been entirely healthy in the past. Our experience suggests that as the incidence of Reye's syndrome has decreased, patients with its clinical features are now more likely to have manageable inborn errors of metabolism (e. g. disorders of ureagenesis, ketogenesis, and branched–chain amino acids).
Agreement Among Multiple Observers on Endoscopic Diagnosis of Esophageal Varices Before Bleeding
Authors: Bendtsen Flemming , Skovgaard Lene Theil , Sørensen Thorkild I.A. , Matzen Peter
Published: March 2007

The 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. (Hepatology 1990;11:341-347.)
Amoxicillin–Clavulanic Acid Therapy of Spontaneous Bacterial Peritonitis: A Prospective Study of Twenty–Seven Cases in Cirrhotic Patients
Authors: Grange Jean D. , Amiot Xavier , Grange Veronique , Gutmann Laurent , Biour Michel , Bodin François , Poupon Raoul
Published: March 2007

Spontaneous 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 coli in two cases, Klebsiella pneumoniae in 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. (Hepatology 1990;11:360-364.)
Spontaneous Bacterial Empyema in Cirrhotic Patients: Analysis of Eleven Cases
Authors: Xiol Xavier , Castellote Jose , Baliellas Carme , Ariza Javier , Roca Ana Gimenez , Guardiola Jordi , Casais Luis
Published: March 2007

Eleven 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 coli in four, Klebsiella pneumoniae in one and Clostridium perfringens in 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. (Hepatology 1990;11:365-370.)
Antibodies Against the Hepatic Asialoglycoprotein Receptor Perfused In Situ Preferentially Attach to Periportal Liver Cells in the Rat
Authors: McFarlane Barbara M. , Sipos Jozsef , Gove Christopher D. , McFarlane Ian G. , Williams Roger
Published: March 2007

Autoantibodies reacting with the galactose–specific hepatic asialoglycoprotein receptor—a liver–specific component expressed on the surfaces of hepatocytes—are often found in patients with chronic active hepatitis of presumed autoimmune origin. As part of an investigation into whether these anti–asialoglycoprotein receptor antibodies might be involved in the development of periportal liver damage in chronic active hepatitis, livers of ether–anesthetized rats were perfused in situ with polyclonal guinea pig anti–rabbit asialoglycoprotein receptor or murine monoclonal antihuman galactose–specific hepatic asialoglycoprotein receptor antibodies in excess at <8° C or, as a control, with guinea pig anti–human plasma protein antibodies or normal guinea pig serum. Rapid (1 min) antegrade (by way of portal vein) or retrograde (through hepatic veins by way of vena cava) perfusions were performed in a nonrecirculating (once–through) mode in Ca++–free medium. Blocks of liver tissue were immediately snapfrozen and the distribution of the antibody examined in cryostat sections by using an avidin–biotin immunohistochemical technique. In all of the perfusions with anti–asialoglycoprotein receptor (six antegrade, seven retrograde), the antibodies were found to be prominently and almost exclusively deposited on liver cells in the periportal areas. No deposition of immunoglobulins was detected in livers perfused with the control guinea pig sera. The findings suggest that the asialoglycoprotein receptor is expressed at high density mainly on cells in zone 1 of the hepatic lobule, and this may have implications for the development of periportal liver damage in chronic active hepatitis.(Hepatology 1990;11:408-415.)
Plasma Des–γ–Carboxyprothrombin in the Early Stage of Hepatocellular Carcinoma
Authors: Tsai Sun-Lung , Huang Guan-Tarn , Yang Pei-Ming , Sheu Jin-Chuan , Sung Juei-Low , Chen Ding-Shinn
Published: March 2007

To evaluate the role of plasma des–γ–carboxyprothrombin in the early diagnosis of hepatocellular carcinoma, we simultaneously studied both des–γ–carboxyprothrombin activities by staphylocoagulase method and des–γ–carboxyprothrombin antigen levels by enzyme immunoassay in 39 patients with early stage hepatocellular carcinoma (tumor size <3 cm in 21 patients, 3 to 5 cm in 18 patients); 68 patients had large hepatocellular carcinoma and 54 patients had chronic hepatitis or cirrhosis. Des–γ–carboxyprothrombin levels by staphylocoagulase method (X) and enzyme immunoassay method (Y) on the same plasma specimens of hepatocellular carcinoma patients showed a linear correlation (Y = 0.15X – 10.5, r = 0.533, n = 67, p < 0.001). Elevated des–γ–carboxyprothrombin activities were present in 10 of 21 patients (47.6%) with hepatocellular carcinoma <3 cm, 66.7% of 18 with hepatocellular carcinoma 3 to 5 cm, 67.6% of 68 with hepatocellular carcinomas >5 cm and 27.8% of 54 with chronic hepatitis or cirrhosis. The plasma des–γ–carboxyprothrombin levels did not correlate with the tumor size or serum α–fetoprotein levels. Plasma des–γ–carboxyprothrombin and serum α–fetoprotein measurements were comparable in the diagnosis of hepatocellular carcinoma because 22 (56.4%) and 21 (53.8%) of 39 patients with hepatocellular carcinoma <5 cm had increased des–γ–carboxyprothrombin and α–fetoprotein levels, respectively. Up to 77% had an abnormal elevation in either marker. The des–γ–carboxyprothrombin antigen levels by enzyme immunoassay method are more specific to hepatocellular carcinoma than des–γ–carboxyprothrombin activities by the staphylocoagulase method: the positive rates of elevated des–γ–carboxyprothrombin antigen levels in the patients with hepatocellular carcinoma <3 cm, 3 to 5 cm, >5 cm and chronic hepatitis or cirrhosis were 19.0%, 55.6%, 66.2% and 14.8%, respectively. We conclude that des–γ–carboxyprothrombin assay may serve as a complementary tool in the diagnosis and follow–up of hepatocellular carcinoma and is particularly useful in patients with normal or low α–fetoprotein levels. Because of higher specificity to hepatocellular carcinoma and less tedious assay procedures, the enzyme immunoassay method is more practical than the staphylocoagulase method in the measurement of des–γ–carboxyprothrombin. For early detection of hepatocellular carcinoma, measurement of plasma des–γ–carboxyprothrombin levels only is not sensitive enough. (Hepatology 1990;11:481-488.)
Hepatocirculatory Failure: Diverse Pathogeneses Deserve Diverse Therapies
Authors: Cohn Jay N.
Published: March 2007

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8–ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p < 0.01), urine volume (108 (29)%; p < 0.05) and sodium excretion (168 (30)% p < 0.05). The hyperdynamic circulation of hepatic failure, as characterised by in creased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p < 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and reninangiotensin–axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).
Mechanism of γ–Glutamyl Transpeptidase Release in Serum During Intrahepatic and Extrahepatic Cholestasis in the Rat: A Histochemical, Biochemical and Molecular Approach
Authors: Bulle Frederique , Mavier Philippe , Zafrani Elie Serge , Preaux Anne-Marie , Lescs Marie-Claude , Siegrist Sylvie , Dhumeaux Daniel , Guellaën Georges
Published: March 2007

The mechanism of the elevation of serum γ–glutamyl transpeptidase activity in cholestasis is not clear. We therefore analyzed rat γ–glutamyl transpeptidase activities in liver, bile and serum during intrahepatic cholestasis induced by a single dose of α–naphthyl isothiocyanate (20 mg/100 gm body weight) and during extrahepatic cholestasis after bile duct ligation. At days 1 and 2 after α–naphthyl isothiocyanate ingestion, we saw a fivefold and a 60–fold increase in serum and bile γ–glutamyl transpeptidase activities, respectively. These increases were associated with a decrease in hepatic γ–glutamyl transpeptidase activity and of corresponding mRNA. Simultaneously, necrosis of the biliary epithelium appeared in portal tracts. From day 2 to day 14, γ–glutamyl transpeptidase activity in bile and serum progressively returned to basal levels; in the liver, cholangiolar proliferation was mild and was associated with moderate elevation of the γ–glutamyl transpeptidase activity and of its corresponding mRNA. In extrahepatic cholestasis, a 10–fold increase in serum γ–glutamyl transpeptidase activity was detected between day 0 and day 14. This increase was associated with major cholangiolar proliferation and with a progressive rise in hepatic γ–glutamyl transpeptidase activity and in specific mRNA; in bile, γ–glutamyl transpeptidase activity was slightly elevated. In these two models of cholestasis, histochemically detected γ–glutamyl transpeptidase activity was largely predominant in biliary cells. We found no significant induction of γ–glutamyl transpeptidase activity in hepatocytes. These results suggest that in these two models of cholestasis, the increase in serum γ–glutamyl transpeptidase activity is of biliary cell origin and does not originate from hepatocytes. This mechanism is quite different from the hepatocyte inductionhypothesized for alkaline phosphatase.(HEPATOLOGY 1990; 11:545:550.)
Effect of Iron and Desferoxamine on Cell Growth And In Vitro Ferritin Synthesis in Human Hepatoma Cell Lines
Authors: Hann Hie-Won L. , Stahlhut Mark W. , Hann Christine L.
Published: March 2007

To investigate the effects of iron supplementation on hepatoma cell growth, cells from a human hepatoma cell line, PLC/PRF/5, were grown in RPMI 1640 supplemented with 0, 10 and 20 μg/ml of FeSO4 and harvested weekly. At the end of 6 wk culture, cell mass measured 9.6, 14.7 and 13.2 gm, respectively. Amounts of ferritin from these cell masses were 0 (undetectable), 0.89 and 2.27 μg/gm of cells.

To study the effects of iron deprivation of hepatoma cells, three human hepatoma cell lines (PLC/PRF/5, Hep G2 and Hep 3B) were incubated in tissue culture medium mixed with graded amounts of an ironchelating agent, desferoxamine, for 48 to 96 hr at 37°C with 5% CO2. Over 50% cell death in PLC/PRF/5 cells and 30% to 50% cell death in Hep G2 and Hep 3B cells were observed 48 to 72 hr after exposure to desferoxamine. Addition of ferric citrate partially reversed the cytotoxic effect of desferoxamine. On the other hand, viability of control cells, human diploid cell line (WI 38), was not affected by desferoxamine. Even after 96 hr exposure to desferoxamine, cell death was only 2% to 4%.

These results suggest that (a) iron enhances tumor cell growth, (b) iron induces increased ferritin synthesis by tumor cells in vitro and (c) iron depletion causes tumor cell death but has little effect on normal human diploid cells.

These findings should be considered when designing treatment of patients with hepatoma. Iron oversupply in patients with cancer might enhance tumor growth and adversely affect cancer therapy. Iron chelation with desferoxamine might have a place in the treatment of patients with hepatoma in conjunction with other anticancer agents.(HEPATOLOGY 1990; 11:566:569.)
Long–Term Maintenance of the Adult Pattern of Liver–Specific Expression for P–450B, P–450E, Albumin and α–Fetoprotein Genes in Intrasplenically Transplanted Hepatocytes
Authors: Maganto Paloma , Traber Peter G. , Rusnell Christopher , Dobbins William O. , Keren David , Gumucio Jorge J.
Published: March 2007

Hepatocytes isolated from livers of Fischer 344 rats and transplanted into the spleens of rats from the same strain survived for at least 15 mo in the absence of immunosuppressive drugs. Hepatocytes attached themselves only in the red pulp of the spleen, most commonly in clumps without a discernible structure. Throughout the 15–mo period, intrasplenically transplanted hepatocytes expressed cytochrome P–450b, P–450e and albumin messenger RNAs, whereas alphafetoprotein messenger RNA was not expressed. In addition, the relative expression of albumin and P–450 genes was similar to that in liver. For example, albumin messenger RNA was expressed to higher levels than P–450b or e messenger RNAs. Northern blots hybridized with oligonucleotides specific for P–450b or P–450e showed that, as in liver, both P–450b and P–450e genes were induced in response to phenobarbital. Quantitative slot–blot hybridizations performed at 15 days and 1, 6, and 15 mo after hepatocyte transplantation revealed that cytochrome P–450b and P–450e messenger RNAs were induced about 20– to 30–fold by a single dose of phenobarbital. This level of induction was also similar to that observed in liver. Hence, intrasplenically transplanted hepatocytes represent a unique system in which hepatocytes, cultured in an extrahepatic in vivo environment, maintain for at least 15 mo a pattern of expression for these four liver genes similar to that in the adult liver. Moreover, these studies suggest that neither the organization of liver into acini nor a specific zonal sinusoidal microenvironment is necessary for adult hepatocytes to respond to phenobarbital with induction of P–450b and P–450e genes.(HEPATOLOGY 1990; 11:585:593.)
Response of Fibronectin to Liver Regeneration After Hepatectomy
Authors: Kwon A-Hon , Inada Yoshiaki , Uetsuji Shoji , Yamamura Manabu , Hioki Koshiro , Yamamoto Masakatsu
Published: March 2007

The relationship between plasma fibronectin concentration and the regenerative process in liver remnants after hepatectomy was studied in 12 patients and in male Sprague–Dawley rats with and without cirrhosis. Plasma fibronectin levels were reduced immediately after hepatectomy in humans and rats. Patients and rats without cirrhosis displayed preoperative fibronectin levels within 1 mo and 1 wk, respectively, but low fibronectin levels persisted longer in those with cirrhosis. Plasma fibronectin levels correlated well with the degree of hepatic regeneration in the patients with cirrhosis (r = 0.4227; p < 0.05) and without cirrhosis (r = 0.8148; p < 0.001), and also with the percentage of change in liver weight during regeneration in the rat with thioacetamide–induced cirrhosis (r = 0.4905; p < 0.01) or in the rat without cirrhosis (r = 0.6422; p < 0.001). These results suggest that plasma fibronectin is a useful marker for the detection of regenerating liver.(HEPATOLOGY 1990; 11:593:598.)
Stimulation of Hepatic Lipocyte Collagen Production by Kupffer Cell–Derived Transforming Growth Factor β: Implication for A Pathogenetic Role in Alcoholic Liver Fibrogenesis
Authors: Matsuoka Masaki , Tsukamoto Hidekazu
Published: March 2007

Transforming growth factor β has a specific stimulatory effect on collagen formation by hepatic lipocytes, a cell type believed to be a major source of extracellular matrices in the liver. Because monocytes and macrophages are the known sources of transforming growth factor β, Kupffer cells–resident macrophages in the liver–may also play an important role in liver fibrogenesis by releasing this cytokine and stimulating lipocyte collagen production. The present study tested this hypothesis using Kupffer cells and hepatic lipocytes isolated from a rat model of alcoholic liver fibrosis. Kupffer–cell–conditioned medium derived from the rat liver with alcoholic fibrosis, but not that from pair–fed control animals, significantly stimulated the net collagen formation of lipocytes isolated from the alcohol–fed, pair–fed control and chow–fed animals. Acidification of the Kupffer–cell–conditionied medium potentiated this effect threefold to fourfold, indicating the presence of a latent form. Fractionation of the Kupffer–cell–conditioned medium by high–performance liquid chromatography gel filtration revealed the major peak of the stimulatory activity corresponding to the molecular weight between 20 kD and 30 kD. It was completely inhibited by anittransforming growth factor β IgG. Furthermore, Northern blotting and hybridization of Kupffer–cell messenger RNA from alcohol–fed rats with 32P–labeled transforming growth factor β complementary DNA demonstrated the presence of 2.5 kb messenger RNA for this cytokine. We conclude that: (a) Kupffer cells isolated from the rat liver with alcoholic fibrosis express and release transforming growth factor β; (b) that this cytokine is largely responsible for the Kupffer–cell–conditioned medium–induced stimulation of collagen formation by hepatic lipocytes; and (c) that this may represent a possible molecular mechanism of lipocyte stimulation during alcoholic liver fibrogenesis.(HEPATOLOGY 1990; 11:599:605.)
Immunolpathology of Acute Galactosamine Hepatitis in Rats
Authors: Jonker Meike A. , Dijkhuis Freke W.J. , Kroese Frans G.M. , Hardonk Machiel J. , Grond Joris
Published: March 2007

Galactosamine hydrochloride induces liver disease in tats that morphologically resembles drug–induced hepatitis in man. In this study we analyzed the character of the inflammatory reaction following the toxic damage resulting from the administration of galactosamine hydrochloride using a broad panel of mono clonal antibodies to lymphocyte subsets and macrophages. Fat–storing cells were identified with a polyclonal anti–desmin antibody. Cellular proliferation was assessed by labeling S–phase cells with the thymidine analog bronmodeoxyuridine. Injection of galactosamine hydrochloride was associated with conspicuous hepatocyte necrosis and parenchymal granulocyte influx in the first 24 hr. thereafter, mononuclear inflammatory cells predominated, mainly T lymphocytes and macorphages, with maximal numbers at 48 hr. The majority of T lymphocytes were CD8–positive cells and were located in the portal tracts and parenchyma. CD4 positive T cells were scarce and confined to the portal tracts. Proliferation of fat–storing cells paralleled hepatocyte regeneration with maximal values after 48 to 72 hr.

The temporal relationship between infiltrating mononuclear cells, mainly T lymphocytes of CD8 phenotype and macrophages, fat–storing cell proliferation and hepatic gegeneration suggests pathophysiological interactions between these cell types in liver injury in the rat after galactosamine hydrochloride administration.(HEPATOLOGY 1990; 11:622:627.)
Excessive In Vitro Bacterial Lipopolysaccharide–Induced Production of Monokines in Cirrhosis
Authors: Devière Jacques , Content Jean , Denys Chantal , Vandenbussche Paul , Schandene Liliane , Wybran Joseph , Dupont Etienne
Published: March 2007

The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor α, interleukin 1β, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor α, interleukin 6 and interleukin 1β was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (<2 U/ml vs. 9.5 ± 3 U/ml) and tumor necrosis factor α (3.1 ± 1.2 pg/ml vs. 12.0 ± 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor α, interleukin 1β and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor α and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1β secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis. This might lead–possibly through the recognized cytopathic and cytotoxic effects of excessive production of monokines–to the decompensation of the underlying liver disease. Monokine oversecretion may also play a role in the pathogenesis and perpetuation of the disease and may be associated with clinical and biological features of cirrhosis such as cachexia, muscle wasting and hypergammaglobulinemia.(HEPATOLOGY 1990; 11:628:634.)
Fate of Mallory Body–Containing Hepatocytes: Disappearance of Mallory Bodies and Restoration of the Hepatocytic Intermediate Filament Cytoskeleton After Drug Withdrawal in the Griseofulvin–Treated Mouse
Authors: Zatloukal Kurt , Spurej Gerlinde , Rainer Ingrid , Lackinger Elisabeth , Denk Helmut
Published: March 2007

Mallory bodies are characteristic morphological features of alcoholic hepatitis in man and can be produced in the mouse by chronic griseofulvin intoxication. The appearance of Mallory bodies in hepatocytes is associated with derangement of the cytokeratin intermediate filament cytoskeleton, at least as revealed by immunofluorescence and suggested by immunoelectron microscopy. Immunohistochemical studies were performed to answer the question whether Mallory body formation and cytoskeleton alterations finally lead to cell death or are reversible phenomena. Chronically griseofulvin–intoxicated mice killed at different stages of recovery on a normal diet served as experimental animals. It could be shown that (a) Mallory bodies are very durable structures and are found for up to 6 mo after griseofulvin withdrawal as a result of persistence and neoformation; (b) new Mallory bodies can appear even several months after cessation of griseofulvin feeding; (c) Mallory body formation and cytoskeletal changes by themselves do not lead to irreversible cell damage; (d) the cytoskeletal changes are reversible within 7 mo after griseofulvin withdrawal; (e) a dissociation between disappearance of Mallory bodies and restoration of a regularly immunostained cytoplasmic cytokeratin meshwork is observed.(HEPATOLOGY 1990; 11:652–661.)