bluuebunny/crossref_metadata_2025 huggingface dataset:
The acute vanishing bile duct syndrome (acute irreversible rejection) after orthotopic liver transplantation
Authors: Ludwig Jurgen , Wiesner Russell H. , Batts Kenneth P. , Perkins James D. , Krom Ruud A. F.
Published: March 2007

The acute vanishing bile duct syndrome can be defined as an irreversible, rejection-related condition that affects hepatic allografts within 100 days after orthotopic liver transplantation and whose presence requires retransplantation. We have observed the acute vanishing bile duct syndrome in 5 of 48 consecutive patients (approximately 10%) who underwent orthotopic liver transplantation. In 4 cases, the condition progressed relentlessly within approximately 7 to 11 weeks after orthotopic liver transplantation from mild rejection to severe rejection to acute vanishing bile duct syndrome. A fifth patient had severe rejection in the first week and required retransplantation after 17 days because of thrombotic venoocclusive disease complicating the acute vanishing bile duct syndrome. Clinically, signs of impending acute vanishing bile duct syndrome included abrupt onset of fever and jaundice and marked elevation of serum bilirubin and alkaline phosphatase levels which persisted despite antirejection treatment. Biopsy specimens revealed destructive cholangitis (rejection cholangitis), ductopenia, and, if retransplantation was delayed, presence of noninflammatory, “burnt-out” portal tracts without bile ducts. We recommend to base the diagnosis of acute vanishing bile duct syndrome on documentation of severe ductopenia in at least 20 portal tracts which may require several consecutive needle biopsies. Rejection arteriopathy which was found in 3 of our 5 cases might have been another important diagnostic clue but could not be recognized prior to retransplantation. The pathogenesis of acute vanishing bile duct syndrome is not clear; until the condition had manifested itself, we found no qualitative differences between acute reversible and irreversible rejection. After retransplantation, severe rejection has recurred in the four patients who could be evaluated in this regard; one of these patients already needed a second retransplantation for vanishing bile duct syndrome.
Effects of ethanol feeding and withdrawal on plasma glutathione elimination in the rat
Authors: Callans David J. , Wacker Laura S. , Mitchell Mack C.
Published: March 2007

Chronic ethanol feeding increases hepatic turnover and sinusoidal efflux of glutathione in rats. The present study was performed to determine whether the observed increase in glutathione efflux was due to increased extrahepatic requirements for glutathione. The concentration and disposition of plasma glutathione were determined in rats fed liquid diets containing 36% of calories as ethanol or pair-fed an isocaloric mixture with carbohydrate replacing ethanol calories for 5 to 8 weeks. The half-life and plasma clearance of [35
S]glutathione were found to be similar in ethanol-fed and control rats and in rats withdrawn 24 hr from ethanol. Uptakes of the sulfur moiety of [35
S]glutathione by kidney, jejunal mucosa, liver, lung, spleen, muscle and heart were also unchanged by ethanol feeding. The plasma glutathione concentration was significantly higher in ethanol-withdrawn rats 22.30 ± 3.06 nmoles per ml (p < 0.05) compared to pair-fed controls (13.51 ± 2.04), while rats continuing to drink ethanol had intermediate levels (16.96 ± 2.22). Plasma cysteine levels were slightly, but not significantly, higher in ethanol-fed rats. These findings suggest that increased sinusoidal efflux of glutathione in ethanol-fed rats is due to a direct effect of ethanol on hepatic glutathione transport and not due to an alteration in extrahepatic disposition of glutathione. In order to characterize further the effects of ethanol feeding on glutathione-dependent detoxification, activities of glutathione S-transferase, glutathione reductase and γ-glu-tamyltransferase were determined. Both glutathione S-transferase and glutathione reductase activities were significantly increased by ethanol feeding whereas γ-glutamyltransferase was increased only slightly. Thus, chronic ethanol feeding in rats results in altered hepatic glutathione metabolism, both through nondetoxification pathways and potentially by glutathione-dependent detoxification enzymes.
Secretory component-dependent binding of immunoglobuin A in the rat, monkey and human: A comparison of intestine and liver
Authors: Daniels Christopher K. , Schmucker Douglas L.
Published: March 2007

The source and significance of immunoglobulin A in bile remains controversial. In the rat, and several other species, immunoglobulin A is transported through hep-atocytes by a specific receptor, secretory component. In humans, immunohistochemical methods have indicated a distinct lack of receptors for immunoglobulin A on hepatocytes. Binding assays with 125I-immunoglobulin A and membranes from hepatocytes and intestinal cells of the rat display secretory component-dependent binding. Primate intestinal cells also show secretory component-specific binding of immunoglobulin A. Primate liver, on the other hand, does not show immunoglobulin A binding mediated by the polymeric immunoglobulin receptor.
Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens
Authors: Hill Gretchen M. , Brewer George J. , Prasad Ananda S. , Hydrick Connie R. , Hartmann Deborah E.
Published: March 2007

The standard therapy for preventing copper accumulation in Wilson's disease, D-penicillamine, has been a life-saving drug, but it has many side effects and some patients are completely intolerant. We have been using oral zinc as another approach to the therapy for Wilson's disease, with copper balance studies as the key initial assessment of the adequacy of a given dose or regimen of zinc therapy. We earlier reported that an intensive regimen of zinc (zinc taken every 4 hr) was effective in controlling copper balance. We have now shown with balance studies that a simplified zinc therapy regimen of 50 mg zinc taken 3 times per day is effective in controlling copper balance. Preliminary work presented here with other simplified regimens also indicate their effectiveness. These studies increase the data base, in terms of copper balance, for zinc therapy of Wilson's disease, and expand the dose range and regimens of zinc which have been shown to control copper balance.
Effect of complete sulfation of bile acids on bile formation in rats
Authors: Yousef Ibrahim M. , Barnwell Stephen G. , Tuchweber Beatriz , Weber Andrée , Roy Claude C.
Published: March 2007

The effect of sulfation of common bile acids on the formation of bile was investigated in male rats by infusing them with the sulfate esters of cholic, chenodeoxycholic, deoxycholic, lithocholic or dehydrocholic acid in four step-wise, increasing doses. Each dose was infused for 30 min and bile collected every 10 min. Control studies were performed by using either albumin solution (the bile acid carrier) or corresponding nonsulfated bile acids at concentrations similar to those of the sulfated products. The secretion of sulfated bile acids was slower and less than that of nonsulfated bile acids, demonstrating transport maximum kinetics rather than the secretory rate maximum characteristic of nonsulfated bile acids. Sulfation significantly increased bile salt-independent bile flow and the choleretic potency of the bile acids tested. With the exception of deoxycholic acid, which had a slight stimulatory effect, bile acid sulfation generally prevented a rise in bile acid-dependent phospholipid and cholesterol secretion. In fact, it reduced biliary phospholipid and cholesterol secretion associated with the secretion of endogenous bile acids. These data are in agreement with the physicochemical properties of sulfated bile acids. They indicate that sulfation prevents the cholestatic action of nonsulfated bile acids, perhaps by increasing bile flow via a high choleretic potential and/or by stimulating bile acid-independent bile flow. The effect of sulfated bile acids on the secretion of biliary phospholipids may protect the canalicular membrane from the detergent properties of bile acids and may thus block the cholestasis which results from high, nonsulfated bile acid concentrations.
Human hepatocellular carcinoma: Cross-reactive and idiotypic antigens associated with malignant transformation of epithelial cells
Authors: Wiedmann Karl H. , Trejdosiewicz Ludwik K. , Southgate Jennifer , Thomas Howard C.
Published: March 2007

Monoclonal antibodies were isolated following immunization with the HBsAg and α-fetoprotein-secreting human hepatoma PLC/PRF/5 (“Alexander”) cell line. Three antibodies (K-PLC1, K-PLC2 and K-PLC3) showed evidence of carcinoma-associated reactivity by indirect immunofluorescence. Antibodies K-PLC2 and K-PLC3 reacted only with PLC/PRF/5 cells, but not with any other normal or malignant cell type tested, including the Hep/G2 hepatoma cell line. The reactivity of these antibodies was not removed by absorption with homogenates of either normal liver or a primary hepatocellular carcinoma. These results suggest that K-PLC2 and K-PLC3 identify PLC/PRF/5 idiospecific determinants. Following surface iodination of PLC/PRF/5 cells, immunoprecipitation and analysis on polyacrylamide gels, these specific determinants were found to be of 200,000 and 76,000 daltons, respectively. On the other hand, antibody K-PLC1, although unreactive by immunofluorescence on the majority of normal cell types, including those of lymphoid organs and bone marrow liver cells and most epithelia, was weakly positive on some normal ductal secretory epithelia and was positive on vascular endothelium. However, K-PLC1 reacted strongly with all carcinoma specimens tested, and with most carcinoma-derived cell lines, indicating a large increase in K-PLC1 antigen expression by epithelial cells after malignant transformation. Absorption of K-PLC1 with normal liver homogenate had no affect, but absorption with a hepatocarcinoma homogenate abolished its activity. The K-PLC1 antigen could not be immunoblotted or immunoprecipitated and resolved on polyacrylamide gels; yet it showed the properties of a phospholipid, namely resistance to proteases, extractability with organic solvents and sensitivity to phospholipase C.
Hepatitis b virus replication in acute hepatitis B, acute hepatitis B virus-hepatitis delta virus coinfection and acute hepatitis delta superinfection
Authors: Genesca J. , Jardi R. , Buti M. , Vives L. , Prat S. , Esteban J. I. , Esteban R. , Guardia J.
Published: March 2007

To evaluate the effect of hepatitis delta virus on the level of replication of hepatitis B virus and to assess the clinical significance that such an effect might have on the final outcome of the infection, the serological profile of hepatitis B virus DNA was investigated in 153 patients with acute or chronic hepatitis B virus infection with or without associated delta infection. Serum hepatitis B virus DNA was detected in 57% of patients with acute hepatitis B, 67% of those with acute hepatitis B virus-hepatitis delta virus coinfection and 25% of HBsAg carriers with hepatitis delta virus superinfection during the first week after the onset of symptoms. Patients with acute hepatitis B and those with acute hepatitis B virus-hepatitis delta virus coinfection did not differ significantly with respect to the serological profile of hepatitis B virus DNA and final clinical outcome. Within the group of HBsAg carriers with hepatitis delta virus superinfection, all patients who were initially negative for hepatitis B virus DNA developed chronic hepatitis delta virus infection, whereas 3 of the 4 patients with active hepatitis B virus infection at the time of superinfection showed transient inhibition of hepatitis B virus replication followed by termination of hepatitis delta virus infection in two patients. Therefore, although delta virus may inhibit the replication of hepatitis B virus among chronic HBsAg carriers, this effect is not readily apparent among patients with hepatitis B virus-hepatitis delta virus coinfection.
Levamisole in chronic hepatitis: A favorable trend is not enough
Authors: Hoofnagle Jay H.
Published: March 2007

A double-blind, randomized, controlled trial has been undertaken to evaluate treatment of chronic hepatitis type B with levamisole. Ten patients received levamisole (150 mg/day, 3 days/wk) and 10 received placebo until seroconversion to antibody to hepatitis B e antigen eventually occurred, or for a maximum of 18 mo. Final evaluation at 24 mo after starting treatment revealed that 60% of the patients in the levamisole group had become hepatitis B e antigen negative, 90% were hepatitis B virus-deoxyribonucleic acid negative in serum, and 8 of 9 (89%) patients had cleared hepatitis B core antigen from the liver. On the other hand, in the placebo group only 4 of the 10 subjects (40%) were hepatitis B e antigen and hepatitis B virus-deoxyribonucleic acid negative in serum and 3 of 8 (37.5%) of them became hepatitis B core antigen free in the liver. Moreover, in 8 patients of the treated group and in 4 of the control cases amino-transferase activities fell into the normal range. A liver biopsy specimen was obtained after treatment in 17 patients and 7 of 9 levamisole recipients showed marked improvement in hepatic histology, compared with 3 of 8 placebo recipients. These data show that patients treated with long-term levamisole therapy have a tendency toward normalization of aminotransferase activities and suppression of hepatitis B virus replication, suggesting that the drug may be of benefit in chronic hepatitis B e antigen-positive hepatitis.
Is weekly sclerotherapy really better than every three weeks?
Authors: Terblanche John , Hobbs Kenneth E. F.
Published: March 2007

To compare the efficacy and safety of one week versus three weeks interval treatment schedules of endoscopic sclerotherapy, injections were carried out in a prospective manner in 96 patients with variceal bleeding; 47 on a one week and 49 on a three week treatment schedule. Weekly endoscopic sclerotherapy eradicated oesophageal varices significantly (p < 0.01) earlier (mean ± SD 7.1 ± 2.43 weeks) as compared with the three week regimen (mean ± SD 14.86 ± 4.86 weeks). The rebleeding rate was also significantly less (p < 0.05) with weekly endoscopic sclerotherapy (8.5%) as compared with three week endoscopic sclerotherapy treatment (26.5%). The amount of alcohol and the number of endoscopic sclerotherapy courses required for complete variceal eradication did not differ significantly between the two groups. Patients undergoing weekly injections were seen to have significantly more oesophageal ulcers (p < 0.01) as compared with the three week group, necessitating at times (23%) postponement of the procedure. There was, however, no difference between the two groups in the frequency of oesophageal structure formation, dysphagia, retrosternal pain, and fever. Mortality was also similar in the two groups. It can be concluded that a weekly schedule of endoscopic sclerotherapy appears superior to a three week schedule.
mechanism of the excessive sedative response of cirrhotics to benzodiazepines: Model experiments with triazolam
Authors: Bakti GÜL , Fisch Hans U. , Karlaganis Georg , Minder Christoph , Bircher Johannes
Published: March 2007

Mechanisms responsible for disproportional sedation resulting from triazolam administration to patients with cirrhosis were investigated. Ordinary sedative doses (0.25 mg) were given p.o. to 8 cirrhotics and 18 controls. Plasma concentrations of unbound drug were assessed by capillary gas chromatography and equilibrium dialysis. Median apparent oral clearances of unbound triazolam were 14.8 ml per min per kg in cirrhotics and 23.9 ml per min per kg in controls (p < 0.01). Clearances were significantly correlated with severity of liver disease as assessed by the aminopyrine breath test (Rs = 0.77, n = 17, p < 0.001). At a time when plasma concentrations of unbound triazolam were the same in both groups, i.e., 2.25 hr after dosing, flicker sensitivity at 5 Hz which was used as an index of CNS performance was impaired by a factor of 3.2 in cirrhotics and 1.4 in controls (p < 0.01 for group difference). Performance was also significantly lower in cirrhotics with the digit symbol substitution test (p < 0.05). It is concluded that, in patients with cirrhosis, disproportional sedation after benzodiazepine administration may be due not only to impaired drug elimination, but also to hypersensitivity of the brain.
Beneficial hemodynamic effects of ketanserin in patients with cirrhosis: Possible role of serotonergic mechanisms in portal hypertension
Authors: Hadengue Antoine , Lee Samuel S. , Moreau Richard , Braillon Alain , Lebrec Didier
Published: March 2007

We studied the acute effects of ketanserin, a serotonin S2 antagonist, on systemic and splanchnic hemodynamics in 11 patients with cirrhosis. Mean arterial pressure decreased moderately but significantly after ketanserin. This effect was maximal at 5 min and correlated to the severity of cirrhosis. Cardiac index and systemic vascular resistance were not significantly changed. The hepatic venous pressure gradient, used as an index of portal pressure, significantly decreased after ketanserin (-23%). Azygos blood flow, a reflection of superior portosystemic collateral blood flow, also significantly decreased (-26%), but this effect was delayed, progressive and not correlated to the arterial pressure decrease. Hepatic blood flow was unchanged. These findings suggest that the systemic and splanchnic circulations may be hypersensitive to ketanserin in cirrhotic patients, and that serotonergic mechanisms may contribute to maintain portal hypertension. New specific antiserotonergic drugs deserve further evaluation for potential therapeutic implications in portal hypertension.
Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients
Authors: Vorobioff Julio , Picabea Eduardo , Villavicencio Roberto , Puccini Viviana , Rossi Oscar , Bordato Juan , Audano Marcelo
Published: March 2007

Different and contradictory results concerning the use of propranolol in the treatment of portal hypertension have been reported. This study was designed to investigate the hemodynamic effects of short- and long-term administration of propranolol in portal hypertensive patients. Portal pressure, cardiac index, heart rate and blood pressure were obtained in 18 unselected alcoholic cirrhotic patients with esophageal varices before and 60 min after the oral administration of 40 mg propranolol and again after 106 ± 35 days of continuous oral administration (mean dose = 158 ± 63 mg per day). Baseline portal pressure was 21.7 ± 7.2 mm Hg. It decreased after 60 min to 17.2 ± 5.5 mm Hg (p < 0.01) and after long-term administration of propranolol to 16.1 ± 5.7 mm Hg (p < 0.01). No decrease in portal pressure was noted in 9 of 18 (50%) patients after acute administration and 5 of 17 (30%) patients after long-term administration. Baseline cardiac index was 5.1 ± 1.2 liters. min-1 m-2. It decreased after 60 min to 3.9 ± 1.4 liters. min-1 m-2 (p < 0.01) and to 3.6 ± 1.0 liters. min-1 m-2 after long-term administration (p < 0.001). Baseline heart rate was 85 ± 11 beats per min. It decreased after 60 min to 75 ± 9 (p < 0.001) and after long-term administration to 62 ± 6 (p < 0.001) beats per min. Baseline mean arterial pressure was 108 ± 11 mm Hg. It decreased after 60 min to 97 ± 14 mm Hg (p < 0.01) and after long-term administration to 103 ± 14 mm Hg (not statistically significant). No significant correlations were found between the decrease in portal pressure and cardiac index nor between portal pressure and heart rate reductions

This study shows that, in unselected cirrhotic patients, propranolol administration fails to decrease portal pressure in a significant proportion of them. This parameter should be measured in every patient under pharmacologic treatment of portal hypertension, and its reduction should not be inferred through other hemodynamic measurements.
Clinical and statistical validity of conventional prognostic factors in predicting short-term survival among cirrhotics
Authors: Infante-Rivard Claire , Esnaola Santiago , Villeneuve Jean-Pierre
Published: March 2007

The objective of this study was to assess the prognostic validity of Child-Turcotte classification with regard to short-term (1-year) survival. The Child-Turcotte classification, as modified by Pugh et al., was recorded on admission in 177 cirrhotic patients. The variables that comprise the Pugh modification are ascites, encephalopathy, serum albumin, serum bilirubin and prothrombin time. Using multiple logistic regression, we evaluated the contribution of different models to the likelihood of survival, defining different ways to use the Pugh score. The Pugh score categorized in three strata (5 to 6, 7 to 9 and 10 to 15) captured less variance in the survival than the Pugh score counted from 5 to 15. This, in turn, captured less variance than a model in which the parameters of the Pugh score were analyzed according to their original units. The prediction rule based on the last model was tested in another sample of cirrhotics. The “original unit” model was studied in both training and testing samples, using receiver-operating characteristic curves to evaluate its clinical validity (sensitivity and specificity). The prediction rule based on the “original units” Pugh score allowed for a good discrimination of patients who lived and those who died. (At the point of maximum discrimination, sensitivity and specificity reached a mean of 80%.) Validity of the prediction rule was confirmed by the testing sample. The qualities of simplicity, availability, low cost and good discriminating power for a life or death outcome make the Pugh score a very useful method to estimate prognosis in patients with cirrhosis.
Lactosylation of albumin reduces uptake rate of dibromosulfophthalein in perfused rat liver and dissociation rate from albumin In Vitro
Authors: Van Der Sluijs Peter , Postema Bart , Meijer Dirk K. F.
Published: March 2007

Two types of models have recently been proposed to describe hepatic uptake kinetics of protein bound drugs: a model in which dissociation from plasma protein is rate limiting the process, and a model in which an interaction between protein and hepatocyte surface is thought to promote dissociation and uptake of the drug. This study was designed to investigate several aspects of both models, using lactosylated albumin as a binding protein that can interact with the Ashwell receptor abundantly present on the hepatocyte. Dibromosulfophthalein clearance was studied in rat liver in the presence of 150 μM (1%) albumin or 150 μM lactosylated albumin. Initial disappearance rate from perfusate in the presence of lactosylated albumin indicated a 2-fold decrease in hepatic uptake rate compared with native albumin. This was confirmed by compartmental analysis, showing a similar decrease in hepatic uptake rate constant. Protein binding of dibromosulfophthalein to lactosylated albumin was only marginally different from normal albumin. Consequently, modification of the protein retarded uptake of the organic anion at an essentially unchanged unbound concentration. Fluorescence spectroscopy of lactosylated albumin showed a blue-shifted tryptophan emission spectrum compared with albumin, indicating increased hydrophobicity of the neoglycoprotein. We therefore considered a change in off-and-on rate for binding of dibromosulfophthalein to lactosylated albumin. Rapid filtration experiments indicated that the dissociation rate constant of dibromosulfophthalein from lactosylated albumin was half that of controls. We conclude that the decreased off-rate from lactosylated albumin can explain the retarding influence on hepatic uptake rate of dibromosulfophthalein. This observation argues for the concept of dissociation-limited uptake in the hepatic clearance of the organic anion.
Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant α-interferon
Authors: McDonald J. A. , Caruso L. , Karayiannis P. , Scully L. J. , Harris J. R. W. , Forster G. E. , Thomas H. C.
Published: March 2007

In a randomized controlled trial, 41 chronic hepatitis B virus carriers were allocated, by opening numbered computerized randomization envelopes, to receive recombinant interferon-α2A at three different doses: 2.5; 5.0, and 10.0 mU per m2. Thirty-two patients received treatment (6 for 3 months, 26 for 6 months), and 9 patients were controls (received no treatment). Ninety-three per cent of our patients were homosexual, and 41% had anti-HTLV-III in their serum

None of the control patients lost HBeAg. In contrast, six of the anti-HTLV-III-negative patients (33%) responded to treatment (p < 0.02): five of these responders were homosexual (p < 0.05). The response rate was greatest (44%) in the anti-HTLV-III-negative patients who received 10 mU per m2 of recombinant interferon-α2A. None of the anti-HTLV-III-positive patients responded to treatment. The percentage reduction of hepatitis B virus DNA was significantly less in the anti-HTLV-III-positive group in comparison to the anti-HTLV-III-negative group at 1 and 4 months of treatment and at 3 months after the end of treatment (p < 0.05). These patients were younger (33 vs. 42 years, p < 0.02), had lower mean baseline AST values (42 vs. 80 IU per liter, p < 0.02) and tended to have milder histo-logical disease

Homosexual men with HBeAg-positive chronic liver disease who are anti-HTLV-III-positive appear to be less responsive to the direct antiviral and immunomodulatory effects of recombinant interferon-α2A. This may be due to the subclinical immunosuppressive effects of co-infection with HTLV-III.
Effect of estradiol upon serum enzymes in primary biliary cirrhosis
Authors: Guattery Joseph M. , Faloon William W.
Published: March 2007

The repeated observation of a fall in serum enzymes at midmenstrual cycle in an untreated patient with primary biliary cirrhosis stimulated a study of estrogen administration in five patients with primary biliary cirrhosis. One patient was premenopausal, one patient was postmenopausal and three had had oophorectomy. After 2 weeks of ethinyl estradiol, AST was under 100 IU per dl in all and had decreased by 50% or more in 4 of 5 patients. γ-glutamyltransferase and alkaline phosphatase fell by 50 and 30% or more, respectively, in all patients. The decreases in serum enzymes were statistically significant in all patients for γ-glutamyltransferase, in 4 of 5 for AST and in 3 of 5 for alkaline phosphatase. One patient developed increased icterus leading to withdrawal of estradiol. Withdrawal of estradiol was followed by return toward control values over variable periods, usually 1 to 4 weeks. Repeated courses of estradiol reproduced these enzyme changes. These observations indicate that estradiol in the doses used (0.05 mg per day) reversibly lowers serum enzyme values in biliary cirrhosis. The mechanism of the effect is unexplained, but an immune system alteration may be responsible.
Auricular pressure in the treatment of gallstones: A randomized, clinical trial of traditional chinese medicine
Authors: Wu Xiening
Published: March 2007

Gallstones, which were diagnosed in 365 patients on the basis of symptoms, signs, ultrasound scanning and cholecystography were treated by compression of specific auricular points. The patients were predominantly women (76%) from 19 to 78 years of age. The stones were in the gallbladder in 326, in intrahepatic ducts in 20, in the common bile duct in 6 and at multiple sites in 14. An adhesive plaster with a seed of Semen vaccariae (an oblate spheroid 2 mm in diameter) fixed at its center was placed over the main auricular points which include the liver, gallbladder, bile duct and duodenum. The liver and gallbladder have corresponding points over the posterior surface of the ears, and compression of both the anterior and posterior points at the same time enhances the effect. Correct positioning over these points is of primary importance. If the individual ear varies in shape, then corresponding points can be taken. These seeds are chosen because of their hardness. Pressure was applied for 20 min thrice a day postprandially by the patients themselves, as shown by the doctor at the start, to one ear every other day and to the other ear on alternate days for 30 days. The seeds were changed by the physician every 3 days. All stools were collected by the patients and examined for expelled stones by the doctors. One hundred forty-four stone specimens were assayed for their cholesterol and bilirubin content, and 16 were examined by infra-red spectrophotography and scanning electron microscopy. After treatment, gallstones were demonstrated in the stool of 299 treated patients (82%) but in only 7 of the 47 controls cholagogue-treated patients (9%). These differences from the treated patients are highly significant statistically (p < 0.01). Reexamination with ultrasonography (except for 25 who were lost to follow-up)revealed the stones to be absent in 16 patients (5%), reduced in number to about half in 72 (20%). In 127, the number rermained the same (35%) and in 69, the number of gallstone increased (19%).

Stones were expelled more frequently from the common duct than from the gallbadder (p < 0.05). Multiple stones were expelled from the gallblader more frequently than single stones, and small stones (<0.5 cm) were expeleld more frequently than those > 1.0 cm. The explusion rate could be improved by prologing the treatment beyond 30 days.
Asymptomatic, isolated elevations of serum aminotransferase activity: The disorders and their diagnosis
Authors: Murray-Lyon I. M.
Published: March 2007

The accidental finding of raised levels of serum aminotransferase levels may lead to extensive investigations of the liver in apparently healthy people. To identify diagnostic groups and their need for investigations, we have evaluated the results of all investigative procedures carried out in 149 asymptomatic patients with persistently raised serum levels of aminotransferases. Fatty liver was found in 64%. These patients often had a high body weight. A high alcohol intake and diabetes mellitus were also noted. Chronic active or persistent hepatitis was found in 20% of the patients. Six per cent had cirrhosis, 4% had alpha1-antitrypsin deficiency, and 3.5% had hemochromatosis. Apart from ferritin, alpha1-antitrypsin, and markers for hepatitis B, blood tests were of little value for distinguishing among different diagnostic groups. This was the case also for the imaging procedures, and neither liver scintigraphy nor ultrasonography was a reliable source of diagnostic information. The results of our study indicate that diagnosis in this group of patients cannot be made without liver biopsy.
Antibodies to acetaldehyde-protein adducts: Epiphenomenon or pathogenic mechanism?
Authors: Jennett Richard B. , Tuma Dean J. , Sorrell Michael F.
Published: March 2007

Immunization of mice with acetaldehyde conjugated to human plasma proteins resulted in the production of polyclonal antibodies that reacted with erythrocyte protein-acetaldehyde conjugates, but not with control erythrocyte proteins. Such antibodies recognized erythrocyte protein-acetaldehyde conjugates prepared with 20-100 μM acetaldehyde, concentrations that exist in the blood of alcoholics. The antibodies also recognized acetaldehyde condensation products with synthetic poly-(L-lysine). Immunization with keyhole limpet hemocyanin-acetaldehyde conjugates resulted in antibodies against both plasma protein-acetaldehyde and erythrocyte protein-acetaldehyde conjugates, which did not cross-react with the respective unmodified carrier proteins. Immunization with human erythrocyte protein-acetaldehyde condensates led to the production of antibodies against both the protein moiety as well as the condensate. Monoclonal antibodies with affinities 50 times greater for the condensate than for the carrier protein were produced by hybridization of spleen cells from the immunized mice. Chronic alcohol administration to mice for 45-50 days led to the generation of antibodies that reacted against protein-acetaldehyde conjugates, suggesting that such adducts are formed in vivo and can act as neoantigens. Antibodies against acetaldehyde adducts should be of value in the identification of alcohol consumption and in the study of the biology of the adducts in relation to organ pathology.
Dietary sodium restriction during diuresis of ascites
Authors: Sherlock Sheila
Published: March 2007

To compare the effect of diet, cirrhotic patients with ascites were randomised into two treatment groups: (1) a low sodium diet (21 mmol) per day or (2) an unrestricted sodium intake. Both groups received effective doses of diuretics (spironolactone or, if necessary, spironolactone and furosemide. One hundred and forty patients from 12 liver units were included according to well defined criteria (group 1: 76; group 2: 64). After an initial four to seven day period of bed rest and salt restriction (21 mmol sodium pd), randomisation was done in each centre. We saw no significant difference between the two groups with respect to (1) clinical and biochemical data; (2) mortality or withdrawal (definitive or temporary) because of biochemical disturbances (group 1: 34%; group 2: 22%); (3) the time for complete disappearance of ascites was significantly shorter (p = 0.014) for salt restricted patients; (4) actual survival (curves plotted up to the 120th day) was not statistically different (p = 0.18), but division into subgroups using various prognostic factors showed that survival was significantly better for salt restricted patients without previous gastrointestinal bleeding (p = 0.02); (5) hospitalisation time and costs were identical in both groups. We conclude that the advantage of a normal salt diet was not shown in this study.
Treatment of hepatocellular carcinoma by simultaneous embolization of the hepatic artery and the portal veins
Authors: Lightdale Charles J.
Published: March 2007

Transcatheter arterial embolization (TAE) is an effective means of treatment in primary hepatocellular carcinoma (HCC). However, in many cases of HCC the tumor recurs after treatment. In an attempt to obtain complete tumor necrosis, the authors studied the clinical and histologic effect of simultaneous embolization of both the hepatic artery and portal vein in ten patients with HCC. In those cases in which combined embolization caused infarction, tumor cells in the main tumor, tumor cells that had invaded the tumor capsule, and small intrahepatic metastases had become totally necrotic following treatment. No visible tumor cells were detected in four patients who subsequently underwent operations; nor were viable tumor cells present in one other patient who later died as a result of a perforated duodenal ulcer. Five patients who did not subsequently undergo operations were still free of the disease 2-17 months after combined arterial and portal embolization. The impact of combined embolization on liver function was nearly the same as that produced when TAE was performed alone. Combined embolization may be a viable alternative to hepatectomy for the treatment of HCC.
Partial portal decompression--partially proven
Authors: Langer Bernard
Published: March 2007

In a serial analysis of splanchnic hemodynamics, we compared partial with total portal decompression in 16 alcoholic cirrhotic patients who underwent portacaval shunts for variceal hemorrhage. Partial decompression was achieved with 8 or 10 mm polytetrafluoroethylene portacaval H grafts and aggressive collateral ligation. Total decompression was achieved with larger diameter H grafts (12 or 14 mm). Early and follow-up (mean interval, 18 months) postoperative studies of portal hemodynamics included: (1) direct measurement of shunt gradients, (2) scintigraphic quantitation of portal and mesenteric flow distribution to the liver, and (3) a portal and splenic collateral scoring system developed from standardized splenic venography. Partial portal decompression reduced portal pressure by 43% ± 8% compared with 81% ± 5% after total decompression (p < 0.01). Scintigraphy demonstrated that partial decompression provided a greater fraction of portal flow to the liver than did total decompression (57% ± 9% versus 2% ± 1% intrahepatic radioactivity) and mesenteric flow distribution (14.5% ± 5.4% versus 1.2% ± 0.7%). Only one patient with partial decompression had a significant loss of portal perfusion during the interval studies. Significantly more residual collaterals were visualized in patients with partial decompression than in those with total decompression, and interval studies showed no significant changes from early studies. We conclude that partial decompression maintains higher portal pressures, more residual collaterals, and a greater fraction of portal and mesenteric flow to the liver than does total decompression. A modest but uniform reduction of portal pressure minimizes stimulus for new collateral formation and further shunting of portal flow.
The association of hepatic glycogen depletion with hyperammonemia in cirrhosis
Authors: Kabadi Udaya M.
Published: March 2007

Hyperammonemia is a well-recognized metabolic abnormality which occurs in cirrhotic patients with advanced liver dysfunction. We recently documented that hyperglucagonemia that occurs as a result of hepatic glycogen depletion may be responsible for this hyperammonemia by promoting gluconeogenesis to provide glucose as a fuel for functioning of several organ systems. Thus, hepatic glycogen depletion may be the initial process responsible for hyperammonemia. Since the glucose rise following intravenous glucagon administration is a reflection of hepatic glycogen breakdown, we studied the effect of glucagon (1 mg) injection on plasma glucose, insulin and ammonia levels after an overnight fast in cirrhotic patients and normal subjects. Glucose rise was significantly stunted, and ammonia rise was significantly greater in patients with advanced liver dysfunction as compared to normal subjects. Furthermore, the smaller the glucose increment, the earlier the ammonia rise. The smallest glucose responses were seen in the patients with the highest basal plasma ammonia levels. Finally, significant negative relationships were noted between the glucose response to glucagon administration (δglucose) and the degree of liver dysfunction as reflected by Composite Clinical Laboratory Index, as well as basal ammonia and ammonia responses (Δam-monia) on the other. Therefore, this study suggests that hepatic glycogen depletion may be the initial event leading to elevated plasma ammonia concentrations in hepatic cirrhosis.
Diminished serum Gc (vitamin D-binding protein) levels and increased Gc:G-actin complexes in a hamster model of fulminant hepatic necrosis
Authors: Lee William M. , Emerson David L. , Young William O. , Goldschmidt-Clermont Pascal J. , Jollow David J. , Galbraith Robert M.
Published: March 2007

Evidence for increased plasma levels of complexes containing Gc (vitamin D-binding protein) and cellular actin has been previously reported during fulminant hepatic necrosis in man. In order to study this process in more detail, we produced liver injury in hamsters using increasing doses of acetaminophen, with serial collection of sera for up to 168 hr after acetaminophen injection. Hamster Gc was purified using a three-step procedure and was shown to resemble closely human Gc. Polyclonal antihamster Gc was prepared and used in rocket immunoelectrophoresis and radial immunodif-fusion studies for quantitation of total serum Gc and the percentage of Gc complexed with actin. Serum Gc levels were depressed in animals having liver damage, and the extent of depression 42 hr after acetaminophen correlated with the extent of elevation of AST. The proportion of the total Gc that was present in the complexed form increased in relation to the severity of the liver disease. In serial studies, diminution in Gc level preceded the rise in AST and increase in the percent complexed. These changes closely resemble observations in man and suggest that the hamster-acetaminophen hep-atotoxicity model may be of value in further study of interactions of Gc with intracellular actin components and its role in actin homeostasis in conditions of massive tissue necrosis.
Uneven copper distribution in the human newborn liver
Authors: Faa Gavino , Liguori Carla , Columbano Amedeo , Diaz Giacomo
Published: March 2007

The pattern of copper distribution in human newborn liver was investigated by histochemical methods (rhodamine, orcein and rubeanic acid) and by atomic absorption spectroscopy. A significant correlation (p < 0.005) was found between the degree of histochemical positivity and the copper concentration found by atomic absorption spectroscopy. In the majority of the 30 livers examined (first group), the copper concentration was much higher than that of normal adult liver, although exhibiting striking individual differences. No correlation between the copper content and sex, body weight or gestational age was found. From a second group of five livers, longitudinal tissue slices 0.5 cm thick were partitioned into regular blocks of about 0.5 gm, which were individually analyzed by atomic absorption spectroscopy. Copper appeared unevenly distributed within each liver, with marked differences even between adjacent blocks. However, a consistent tendency of copper to accumulate in the left lobe more than in the right one was evident. Five additional blocks, one for each liver, were further partitioned into 10 small specimens of a final size (0.05 gm), comparable to that of a needle biopsy. Even at this sampling level, consisting of tissue fragments taken from a small tissue area, the copper concentration appeared quite irregularly distributed. These findings may be considered for two different aspects: (a) the biological implications of the pattern of copper accumulation in different lobar and lobular liver compartments and (b) the statistical inference, for diagnostic purposes, of the mean liver copper content from measurements of single percutaneous biopsy specimens.
Inhibition of human cationic glutathione S -transferase by nonsubstrate ligands
Authors: Boyer Thomas D. , Vessey Donald A.
Published: March 2007

Inhibition of a major hepatic form of human cationic glutathione S-transferase by bilirubin, biliverdin, indocyanine green and chenodeoxycholic acid was investigated as a function of pH (range = 6.5 to 9.1). Changes in pH had little effect on the extent of inhibition by indocyanine green. However, inhibition by bilirubin, biliverdin and chenodeoxycholic acid was found to be pH-dependent, with markedly less inhibition at the high values of pH. The reduced inhibition at the high values of pH could not be ascribed to a failure of the enzyme to bind the nonsubstrate ligand. Instead, the complete inhibition observed at pH 6.5 became partial (hyperbolic) inhibition at pH 9.1. This behavior can be ascribed to the binding of the nonsubstrate ligands at a site other than the active site, i.e., at high values of pH there is formation of an enzyme-substrate-inhibitor complex which still retains considerable catalytic activity. At physiologic values of pH (7.0), the human transferase was completely inhibited by saturating concentrations of the tested nonsubstrate ligands. This is in contrast to our previous studies performed with the rat transferases where, although inhibition also was affected by buffer pH, some forms of the enzyme retained significant catalytic activity at pH 7.0 despite high concentrations of nonsubstrate ligands. We conclude that the ability of the human cationic glutathione S-transferases to serve as enzymes of detoxification in the presence of high intracellular concentrations of nonsubstrate ligands may be significantly reduced, and this may render the cholestatic liver unusually susceptible to injury by toxic electrophiles.
Acinar redistribution and heterogeneity in transport of the organic cation rhodamine B in rat liver
Authors: Braakman Ineke , Groothuis Geny Martha Maria , Meijer Dirk Klaas Fokke
Published: March 2007

We studied a possible acinar heterogeneity in the transport of organic cations, using rhodamine B as model compound. Employing perfusions of isolated rat livers in the ante- and retrograde mode and quantitative fluorescence microscopy, Zones 1 and 3 were shown to be equally efficient in taking up rhodamine B. Ten minutes after injection in an antegrade perfusion, 95% of the dose was localized in the portal half of the acinus. Fifty minutes later, however, the amount of rhodamine B in Zone 1 had been reduced to 23%; 30 and 31% were in Zones 2 and 3, respectively, and the medium concentration was doubled. Thus, unchanged rhodamine B appeared to be transported downstream within the liver, either via the medium or directly from cell to cell, finally resulting in a relatively higher rhodamine B concentration in Zone 3. To obtain additional data, we designed a perfusion setup in which the zones could be studied separately. In both zones, the amount excreted into the medium was about 30 times the amount excreted into bile. Intracellular sequestration of rhodamine B and the rate constant for sinusoidal secretion were higher in Zone 3, while the sinusoidal uptake rates were equal; biliary excretion was higher in Zone 1.

Acinar distribution changed with time because rhodamine B, primarily accumulated in Zone 1, was secreted into the sinusoids and taken up again by downstream cells. The finally higher rhodamine B concentration in Zone 3 was caused by a zonal heterogeneity in intracellular sequestration and sinusoidal secretion of rhodamine B.
Sinusoidal endothelial cells from guinea pig liver synthesize and secrete cellular fibronectin in vitro
Authors: Rieder Hartmut , Ramadori Giuliano , Dienes Hans-Peter , Büschenfelde Karl-Hermann Meyer Zum
Published: March 2007

Endothelial liver cells were obtained from guinea pig by enzymatic digestion and centrifugal elutriation. Cells were cultured on gelatin and fibronectin pretreated culture vessels. Endothelial cells were characterized by phase-contrast microscopy, electron microscopy and the presence of Factor VIII-related antigen. Fibronectin secretion was determined in cell-free supernatants by a sensitive and specific ELISA and localized on fixed cultured cells by immunofluorescence. [35
S]Methionine endogeneously labeled fibronectin was immunoprecipitated from supernatants and cellular lysates and displayed on sodium dodecyl sulfate polyacrylamide slab gel electrophoresis.

After attachment to the culture vessel, one day after plating, endothelial cells start to produce fibronectin as measured by ELISA and demonstrated by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Secretion of fibronectin increases as cells proliferate to form a confluent monolayer. By immunofluorescence, fibronectin is visualized inside permeabilized cells and as a fibrillar network on the cell surface. Underneath the cell bodies, fibronectin-positive material is present as short strands. From supernatants and cellular lysates, fibronectin is immunoprecipitated with an apparent Mr of about 235,000 obviously larger than plasma fibronectin with an Mr of 220,000, which behaves electrophoretically like fibronectin isolated from early hepatocyte cultures. As endothelial cells incorporate [3H]fucose in fibronectin, whereas hepatocytes do not, we conclude that endothelial cells in contrast to hepatocytes produce cellular fibronectin. Endothelial cells, therefore, are probably the cellular source of the fibronectin present in the space of Disse. The significance of this finding with respect to fibrotic liver disease is discussed.