bluuebunny/crossref_metadata_2025_split huggingface dataset:
A coded histologic study of hepatic graft-versus-host disease after human bone marrow transplantation
Authors: Shulman Howard M. , Sharma Pankaj , Amos Deborah , Fenster Frederick L. , McDonald George B. 
Published: March 2007

We tested the hypothesis that liver histology from patients with graft-versus-host disease could be distinguished from other common liver diseases. Liver biopsies from 33 allogeneic marrow transplant recipients with acute and chronic graft-versus-host disease and 37 nontransplant liver disease patients without graft-versus-host disease were recut, restained and coded for blind review.
Analysis of individual histologic features showed significantly more cytologic aberration of bile duct epithelium and more cholestasis among biopsies with graft-versus-host disease when compared to biopsies without graft-versus-host disease (p ≤ 0.05). The duration of graft-versus-host preceding the biopsy influenced the histologic features. Biopsies before Day 35 showed frequent acidophilic bodies but infrequent bile duct changes. Biopsies from Days 35 to 90 posttransplant had more frequent bile duct exocytosis and disruption, and biopsies from patients with chronic graft-versus-host disease (beyond Day 90) showed more frequent portal fibrosis and bile duct dropout.
Pattern assessment of coded biopsies showed that a histologic diagnosis of graft-versus-host disease had a positive predictive value of 86%, a sensitivity of 66% and a specificity of 91%. False-negative diagnoses occurred most frequently in biopsies obtained less than 4 weeks posttransplant, usually because bile duct abnormalities were not present. False-positive diagnoses of graft-versus-host disease occurred in nongraft-versus-host disease biopsies with periportal inflammation and proliferated bile ducts. However, biopsies of chronic graft-versus-host disease had more frequent dropout and disruption of bile duct epithelium than did biopsies of acute or chronic hepatitis.
We conclude that a histologic diagnosis of hepatic graft-versus-host disease is likely to be correct if histology shows abnormal bile duct epithelium and cholestasis. While distinction between chronic graft-versus-host disease and non-A, non-B viral hepatitis is imprecise, cytologically atypical and destructive bile duct features favor chronic graft-versus-host disease.
The histologic appearance of graft-versus-host disease is similar to that of primary biliary cirrhosis.
Lymphoblastoid interferon in controlled trials of chronic hepatitis B virus infection
Authors: Hadziyannis Stephanos J. 
Published: March 2007

A controlled trial of lymphoblastoid interferon versus no therapy in patients positive for HBsAg, HBeAg and DNA polymerase activity with separate randomisation for sexual preference and histology is underway. Thirty-two patients have been followed for a minimum period of 6 months of whom 15 have been randomised to receive interferon thrice weekly for 6 months after a 5-day induction phase.
Five treated patients developed an hepatitis-like illness during the 3rd month of therapy concurrent with an abrupt and complete loss of DNA polymerase activity from serum. In 3 this was permanent and anti-HBe subsequently developed; 2 of these have also lost HBsAg. In the other 2 patients inhibition of viral replication was transient. In 5 further treated patients DNA polymerase activity was completely inhibited throughout treatment only to return as soon as interferon was withdrawn. In this group serum aminotransferase became normal during treatment. In the remaining 5 treated patients, inhibition of DNA polymerase activity was never complete and serum amino-transferases were unaffected. All the control patients remain seropositive for HBsAg, HBeAg and DNA polymerase activity. The low seroconversion rate in treated patients and the absence of seroconversion in the control group are probably a reflection of the exclusion of patients with marked elevation of serum aminotransferases.
The occurrence of an hepatitis-like illness in the 3rd month of therapy in a third of the patients and the loss of HBsAg in 2 of 3 who eventually sero-converted are likely to be a consequence of therapy rather than spontaneous events. If these data prove representative of the completed trial, the results will indicate a small but real benefit from interferon therapy in patients with stable disease.
Thirty male patients (27 homosexual) with biopsy proven chronic active hepatitis B were randomised to receive lymphoblastoid interferon (Wellferon) or no treatment. All patients were HBeAg positive and had continuing viral replication. Patients receiving treatment were given a single daily intramuscular injection of interferon for 28 days at a starting dose of 2.5 MU/m2 increasing to a maximum of 7.5 MU/m2/day. Transient side effects of malaise and influenza like symptoms occurred in all patients and resolved rapidly after treatment. Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy. After one year there was not appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly, three month regimes recently reported from other centres.
Phospholipids and bile acids as diffusional carriers of Na+ across nonpolar media
Authors: Accatino Luigi , Gavilan Patricia 
Published: March 2007

Phospholipids and bile acids, by virtue of their amphiphilic properties, can interact in nonpolar media forming “inverted” structures (micelles) which presumably have an hydrophilic core and might act as diffusional carriers (ionophores) of electrolytes across low dielectric constant media or lipid membranes.
The Na+ ionophoretic capability of various purified phospholipids and the modulating effects of bile acids and phospatidylcholine was examined by: (a) measurement of 22Na+ partition into the organic phase (chloroform) of a two-phase system and (b) direct measurement of the translocation of 22Na+ across a bulk chloroform phase separating two aqueous phases in a Pressman cell. All phospholipids tested, except for phosphatidylcholine, showed ionophoretic capability for Na+ at micromolar concentrations. Cardiolipin and phosphatidylserine were the most efficient Na+ carriers, comparable with monensin, an established Na+ ionophore. In contrast, cholic acid as well as other bile acids demonstrated only marginal or no Na+ ionophoretic capability. However, hydroxylated bile acids (particularly cholic acid), sodium dodecyl sulfate and Triton X-100, which can induce and stabilize inverted structures in lipid membranes, were able to increase 5- to 8-fold the phospholipid-mediated Na+ transport. Interaction of cardiolipin with Na+ in the chloroform phase followed a rectangular hyperbolic function with an apparent Kd within the physiological Na+ concentration range (16.9 ± 5.1 mM). Addition of cholic acid to the cardiolipin-containing organic phase resulted in a 10-fold increase of maximal Na+ uptake and no change in apparent Kd. The effect of cholic acid on both cardiolipin-mediated Na+ partition and Na+ translocation across the chloroform phase showed a marked dependence on pH, being greater at pH 7.4. On the other hand, phosphatidylcholine, which is reported to stabilize phospholipid bilayers and to inhibit formation of inverted structures, inhibited Na+ cardiolipin interactions. Cholic acid addition completely prevented the inhibitory effect of phosphatidylcholine.
This study permits us to establish that the acidic phospholipids cardiolipin and phosphatidylserine can act as efficient Na+ ionophores in this in vitro system, at physiological Na+ concentrations and with kinetics comparable to those of systems involved in Na+ transport (e.g. Na+/H+ antiports) in liver surface membrane and other biomembranes. Modulation by bile acids (stimulation) and phosphatidylcholine (inhibition) of cardiolipin-mediated Na+ transport suggests that the underlying mechanism probably involves inverted-mixed micelle formation in the organic phase. The possibility exists that the Na+ ionophoretic properties of acidic phospholipids are relevant to the bile secretory process.
Fragmentation of gallstones using extracorporeal shock waves: An in Vitro study
Authors: Schachler Roland , Sauerbruch Tilman , Wosiewitz Ulrich , Holl Joseph , Hahn Dietbert , Denk Roland , Neubrand Michael , Paumgartner Gustav 
Published: March 2007

Eighty in vitro experiments were performed with single (n = 51) or multiple (n = 29) gallstones in order to find out which parameters are of prime importance for their disintegration by extracorporeal shock waves. A Dornier lithotripter and an upper limit of 1,500 discharges were employed.
Although computed tomography density was significantly lower in cholesterol stones than in the noncholesterol stones (p < 0.0001) and although the latter were significantly more often radiopaque (p < 0.0001), we found no clear-cut correlation between the cholesterol content or computed tomography density and the degree of fragmentation of the stones. The most important variable which limited successful disintegration was the total stone volume. In stones with a mean total volume of 0.83 ml ± 0.25 S.E. (diameter for single stones = 11.5 ± 0.9 mm), none of the fragments exceeded 2 mm, whereas in stones with a mean volume of 3.6 ml ± 0.64 (diameter = 17.2 ± 1.5 mm) at least one fragment larger than 2 mm remained (p < 0.002). Under the in vitro conditions, fragmentation was similar in multiple and solitary stones, provided the volume of the stones was comparable.
These data show that, in general, the number and size of the stones, i.e. their total volume, and much less significantly their chemical composition are the major determinants of fragmentation by extracorporeal shock waves.
Hepatic cytoprotection by prostaglandins: Theories unlimited
Authors: Levine Robert A. 
Published: March 2007

16,16 Dimethyl prostaglandin E2 (dmPGE2), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulminant viral hepatitis, murine hepatitis virus type 3 (MHV-3). Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 ± 619 IU/liter). In contrast, animals treated with dmPGE2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total CO2, and ALT determinations (mean ALT, 63 ± 40 IU/liter). Treatment of infected mice with PGF2 demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE2-treated and -untreated animals throughout the course of infection.
In a parallel in vitro study, dmPGE2 (10−4-10−8 M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0. In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10 ± 5 mU/106 splenic macrophages to a maximum of 615 ± 102 mU/106 splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE2. These results suggest that dmPGE2, without detectably altering viral replication or infectivity in vivo, confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro, and prevents the induction of macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.
Is primary sclerosing cholangitis a progressive disease or not?
Authors: Wiesner Russell H. , Grambsch Patricia , Larusso Nicholas F. , Dickson Rolland E. 
Published: March 2007

The clinicopathologic features and natural history of primary sclerosing cholangitis were reviewed in 53 patients followed at the Yale Liver Center during the past 30 yr. At presentation, the mean age of patients was 46 yr, and the male to female ratio was 1.4:1. Biliary sclerosis was limited to the intrahepatic ductal system in 21% of the patients. Fifty-three percent of the patients had mild disease without portal hypertension at presentation, and 25% had no symptoms attributable to their liver disease. Long-term follow-up was available for 42 patients and averaged 56 mo. Over this period, 16 patients remained mildly symptomatic, and 11 were asymptomatic. Survival was calculated by a Kaplan-Meier life-table analysis and demonstrated that 75% of the patients were alive 9 yr after the diagnosis of primary sclerosing cholangitis. A multivariate analysis of clinical features revealed that hepatomegaly and a serum bilirubin level > 1.5 mg/dl at the onset of disease were independent discriminators of a poor prognosis. Patients referred to this university medical center displayed different clinical characteristics than previously reported in primary sclerosing cholangitis. A higher percentage were older, female, and asymptomatic, and more had disease limited to the intrahepatic ductal system. Survival was also considerably improved in this group of patients and suggests that long-term prognosis for patients with primary sclerosing cholangitis may be considerably better than previously believed.
The natural history and prognostic factors of primary sclerosing cholangitis (PSC) are poorly defined. We reviewed our experience with PSC to determine its natural history and whether any factors on presentation or during follow-up were indicative of a favorable or unfavorable prognosis. Thirty-eight patients were followed up for 75.1 ± 58.7 months; 17 (45%) had a poor outcome, defined as the occurrence of death (11 patients [29%]), variceal hemorrhage, hepatic encephalopathy, or hepatic transplantation. We found the following: (1) the rate of progression of PSC is highly variable; (2) an asymptomatic presentation may not indicate a more favorable outcome or prolonged survival; (3) a serum bilirubin value of four times or more the upper limit of normal, particularly if sustained so as to exclude a reversible cause, is indicative of late-stage disease with a likelihood of subsequent poor outcome and death; and (4) variceal hemorrhage may occur before the terminal stage of the disease.
Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats
Authors: Olsen Peter Skov , Boesby Steen , Kirkegaard Preben , Therkelsen Kim , Almdal Thomas , Poulsen Steen Seier , Nexø Ebba 
Published: March 2007

The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner’s glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner’s glands decreased liver regeneration, whereas removal of the submandibular glands had no effect on liver regeneration. Epidermal growth factor antiserum reduced liver regeneration significantly. Oral or s.c. administration of epidermal growth factor had no effect on liver regeneration, whereas epidermal growth factor enhanced the effect of insulin and glucagon on liver regeneration.
The results suggest that endogenous epidermal growth factor participates in stimulation of liver regeneration after partial hepatectomy in rats. Epidermal growth factor given together with insulin and glucagon had a synergistic effect on liver regeneration which suggests that liver regeneration in the rat is controlled by multiple regulatory peptides.
Galactose elimination capacity and liver volume in aging man
Authors: Marchesini Giulio , Bua Vincenzo , Brunori Alessandra , Bianchi Giampaolo , Pisi Paolo , Fabbri Andrea , Zoli Marco , Pisi Emilio 
Published: March 2007

The galactose elimination capacity, a measure of the functional liver cell mass, and liver volume were measured in 50 normal subjects of five different age groups (<50, 51 to 60, 61 to 70, 71 to 80 and >81 years). The volume of the liver was evaluated by ultrasonography. All subjects had normal routine liver function tests and no history of liver disease. Galactose elimination progressively decreased from 3.05 ± 0.58 (S.D.) mmoles per min in younger subjects to 1.83 ± 0.24 mmoles per min in subjects over 81 (p < 0.00003), without any change in the apparent volume of distribution of the sugar. Similarly, the estimated volume of the liver decreased from 110 ± 14 units to 75 ± 13 units with increasing age (p < 0.0002). Both galactose elimination capacity and the estimated liver volume inversely correlated with age (r = 0.728 and r = −0.579, respectively) whereas a positive correlation was observed between galactose elimination and the estimated liver volume (r = 0.520). Part correlation analysis confirmed that age, when entered in a multiple regression already containing body weight and estimated liver volume as independent variables, had a significant effect on liver function, whereas no significant independent effect of liver volume was present. Both age and body weight had a significant independent effect on the estimated liver volume.
The maximum functional capacity of the liver, measured by galactose elimination, is reduced in the elderly. Although several factors may play a role, our data suggest that aging is associated with a slight decline in the intrinsic metabolic activity of the hepatic parenchyma.
A prospective evaluation of bacteremic patients with chronic liver disease
Authors: Barnes Peter F. , Arevalo Cecilia , Chan Linda S. , Wong Sandra F. , Reynolds Telfer B. 
Published: March 2007

We prospectively studied 51 consecutive bacteremic patients with chronic liver disease in order to evaluate their clinical presentation and to assess the relationship of various clinical parameters to mortality. Forty-two patients had alcoholic liver disease and 40 were in Class C, by the Pugh modification of Child’s criteria.
Soft tissue infections were the most common source of bacteremia, followed by pneumonia, spontaneous bacterial peritonitis and urinary tract infection. Gram positive organisms were isolated in 69% of cases, and Gram negative ones in 31%. In nine patients, no source of bacteremia was detected. Leukocytosis occurred in 59% of patients and bandemia in only 41%.
Although appropriate antibiotic therapy was begun in all cases on admission, 17 patients (33%) died in the hospital. Of 38 clinical parameters evaluated, multivariate analysis revealed that the three variables contributing the most independent information toward predicting in-hospital mortality were the absence of a history of fever, an elevated serum creatinine and marked leukocytosis. Improved understanding of the pathophysiologic relationship between these parameters and patient outcome may enable us to improve the therapy of bacteremic patients with chronic liver disease.
Prophylactic sclerotherapy of high-risk esophageal varices: Results of a multicentric prospective controlled trial
Authors: Piai Guido , Cipolletta Livio , Claar Max , Marone Giampiero , Bianco Maria Antonietta , Forte Giovanni , Iodice Giuseppe , Mattera Daniele , Minieri Mauro , Rocco Pietro , Santoro Lorenzo Michele , Mazzacca Gabriele 
Published: March 2007

In this prospective, multicenter trial, 140 cirrhotic patients with no previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage were randomized to receive either sclerotherapy or conservative treatment for the prevention of first variceal bleeding. The end-points of the study were bleeding and death. Life table curves showed that prophylactic sclerotherapy significantly diminished the incidence of variceal hemorrhage (p < 0.001) and overall mortality (p < 0.01). Two-year cumulative bleeding rate was 18% in the sclerosis group (95% confidence interval = 10 and 31) and 57% (95% confidence interval = 40 and 72) in the control group. Two-year cumulative mortality rate was 30% (95% confidence interval = 19 and 45) in the sclerotherapy group and 56% (95% confidence interval = 39 and 72) in the controls. One patient died after hemorrhage from an ulcer secondary to sclerotherapy. Analysis by the Cox model of the factors potentially confounding or interacting with the effect of sclerotherapy suggested that sclerotherapy was more efficient in preventing first bleeding in patients with decompensated disease (Child B and C) than in those in good condition (Child A). However, the 2-year cumulative bleeding rate of untreated Child A patients was only 19%, showing how in this group the endoscopic findings were unreliable in selecting high-risk varices and explaining why after a 2-year follow-up prophylactic sclerosis did not show any benefit in such patients.
We conclude that sclerotherapy can decrease the incidence of first variceal bleeding and death for a period of 2 years in cirrhotic patients with high-risk varices.
S-Phase cells in diseased human liver determined by an in Vitro BrdU-anti-BrdU method
Authors: Shimizu Akio , Tarao Kazuo , Takemiya Shouji , Harada Masaoki , Inoue Tohru , Ono Tetsuo 
Published: March 2007

Using a monoclonal antibody to bromodeoxyuridine, we studied the cell kinetics of human hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis. Specimens were taken either by biopsy or surgery and immediately incubated with 0.1% bromodeoxyuridine solution at 37°C for 45 min. After in vitro labeling, the bromodeoxyuridine taken up by the nuclei of S-phase cells was determined by the avidinbiotin-peroxidase complex method, using an anti-bromodeoxyuridine monoclonal antibody as the first antibody. The number of positive nuclei in 1,000 hepatic cells was counted, and the bromodeoxyuridine labeling index was expressed per thousand.
The mean bromodeoxyuridine labeling index ± S.D. of the cancerous portion of hepatocellular carcinoma, the noncancerous portion of hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis were 64.1 ± 31.3, 33.6 ± 14.4, 23.2 ± 20.8, 9.1 ± 6.1 and 21.6 ± 13.0, respectively. The mean bromodeoxyuridine labeling index of the hepatocellular carcinoma cancerous portion was statistically higher than that of any other group. There was no statistical difference by the t test or the Wilcoxon test between the noncancerous portion of hepatocellular carcinoma and liver cirrhosis, and these two groups were proved interdependent by χ2 test (Fisher’s exact test), whether they were subdivided by bromodeoxyuridine labeling index ±10 or not.
Bromodeoxyuridine labeling index was not significantly correlated with the usual biochemical parameters such as serum AST, ALT, γ-GTP, alkaline phosphatase, lactate dehydrogenase, cholinesterase, albumin, and α-fetoprotein.
These results suggest that the bromodeoxyuridine labeling index of biopsied or resected specimens could give valuable information on cell kinetics when analyzing liver diseases and could be especially useful in distinguishing hepatocarcinogenesis from hepatic cirrhosis.