bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refractory Ascites: Modulation of Atrial Natriuretic Factor Unresponsiveness by Mannitol
Authors: Morali Gilles A. , Tobe Sheldon W. , Skorecki Karl L. , Blendis Laurence M. 
Published: March 2007

We have previously shown that unresponsiveness to atrial natriuretic factor is a marker of the severity of ascites. The tubular mechanisms are unknown, but it seems that increased reabsorption of sodium proximal to the main site of action of atrial natriuretic factor (i.e., the inner medullary collecting duct) plays an important role. We attempted to decrease the proximal reabsorption of sodium with mannitol in patients unresponsive to atrial natriuretic factor. The results of mannitol in such a group of patients has previously been conflicting. We studied 10 patients with massive, resistant ascites who were off diuretics and on a 20–mmol/day sodium diet for 7 days. Atrial natriuretic factor unresponsiveness was confirmed by failure of a 2–hr atrial natriuretic factor infusion to induce a natriuresis. The next day all patients received an infusion of 40 gm of mannitol and subsequently a combined infusion of mannitol and atrial natriuretic factor. Proximal reabsorption of sodium and water were evaluated by lithium clearance, and glomerular filtration rate and renal blood flow were evaluated by inulin clearance and p–aminohippurate clearances, respectively. Six patients responded to mannitol alone with an increased diuresis (from 39 ± 7 to 148 ± 35 ml/hr) and natriuresis (from 0.27 ± 0.05 mmol/hr to 1.65 ± 0.53 mmol/hr; p < 0.05) (responders), whereas four did not (nonresponders). The combination of atrial natriuretic factor and mannitol induced a further significant increase in sodium excretion (3.28 ± 0.68 mmol/hr) but not in urine excretion, compared with mannitol alone. Lithium clearance increased in the responders after mannitol infusion, but it did not increase further with ANF plus mannitol. Inulin and p–aminohippurate clearances were equally low in the two groups and did not change during the infusions. The responders had significantly lower plasma renin activity, aldosterone and norepinephrine levels than the nonresponders (plasma renin activity = 1.9 ± 0.7 vs. 7.3 ± 1.5 ng/L/sec; aldosterone = 2,830 ± 1,273 vs. 9,457 ± 3,873 pmol/L; norepinephrine = 2.6 ± 1.6 vs. 8.4 ± 1.6 nmol/L; p < 0.05).
We conclude the following: (a) atrial natriuretic factor unresponsiveness in cirrhotic patients is due, in part, to increased reabsorption of sodium proximal to the distal site of atrial natriuretic factor action; (b) increased proximal reabsorption of sodium might be mediated in part by increased renin aldosterone and sympathetic nervous system activity; with moderate as opposed to marked elevation, this effect can be overcome by mannitol; and (c) with increased mannitol–induced distal delivery of sodium, atrial natriuretic factor further increases sodium excretion, indicating that receptor or intracellular signaling of atrial natriuretic factor response remains intact. (Hepatology 1992;16:42-48.)
Lack of Association Between Cytomegalovirus Infection, Hla Matching and the Vanishing Bile Duct Syndrome After Liver Transplantation
Authors: Paya Carlos V. , Wiesner Russell H. , Hermans Paul E. , Larson-Keller Jeffrey J. , Ilstrup Duane M. , Krom Ruud A.F. , Moore Breanndon S. , Ludwig Jurgen , Smith Thomas F. 
Published: March 2007

In this study we evaluated the association between cytomegalovirus infection alone or in relation to human leukocyte antigen matching and the development of vanishing bile duct syndrome, a form of chronic hepatic allograft rejection.
A total of 81 consecutive liver transplant recipients were studied. Cytomegalovirus infection developed in 46 recipients (57%), and vanishing bile duct syndrome occurred in 9 recipients (11%). Cytomegalovirus infection developed in only five of the nine patients with vanishing bile duct syndrome. Univariate analysis of pretransplant recipient/donor cytomegalovirus serological tests and human leukocyte antigen typing showed they were not significant risk factors for the development of vanishing bile duct syndrome. Timedependent analysis of cytomegalovirus infection after transplantation as a risk factor for vanishing bile duct syndrome, in a multivariate analysis with human leukocyte antigen match, showed no statistical significance.
In our study, no association was found between cytomegalovirus infection alone or in relation to class I or II human leukocyte antigen match and the subsequent development of vanishing bile duct syndrome. (Hepatology 1992;16:66-70.)
Direct Measurement of Hepatic Blood Flow in Native and Transplanted Organs, With Accompanying Systemic Hemodynamics
Authors: Paulsen William A. , Klintmalm Goran B.G. 
Published: March 2007

The purpose of this study was to investigate intraoperatively a population of patients with end–stage liver disease before and after liver transplantation with respect to (a) the range of hepatic and systemic hemodynamics and their changes associated with transplantation and (b) the ability to identify native hemodynamic correlates with specific diagnostic groups. Hepatic artery and portal vein blood flows were determined with square–wave electromagnetic flowmetry. Significant differences related to the type of preservation solution used-Euro–Collins or University of Wisconsin-were identified in some hepatic and systemic hemodynamic measurements from the graft livers. Specifically, cardiac output, total liver blood flow and liver weight were significantly increased in the Euro–Collins group compared with the native and University of Wisconsin groups. Hepatic artery flow was significantly greater and portal vein pressure was significantly lower in the University of Wisconsin group than in the native or Euro–Collins group. In general, comparing the graft and native livers, hepatic artery and portal vein blood flow increased significantly after transplantation, as did hepatic oxygen consumption. Portal vein pressures were dramatically reduced, but systemic arterial pressure remained remarkably constant. The percentage of cardiac output going to the liver increased, as did the portal vein percentage of the total liver blood flow.
Diagnostic groups could not clearly be associated with characteristic native liver or systemic hemodynamics. Hemodynamics may be associated more with the stage of the disease process than the disease itself. (Hepatology 1992;16:100-111.)
Association Between Heterozygous β1–Antitrypsin Deficiency and Genetic Hemochromatosis
Authors: Rabinovitz Mordechai , Gavaler Judith S. , Kelly Robert H. , Van Thiel David H. 
Published: March 2007

Primary hemochromatosis is a genetically determined autosomal recessive disorder characterized by the excessive accumulation of body iron, most of which is deposited in the parenchymal cells of various organs.
β1–Antitrypsin deficiency is characterized among others by defective secretion of β1–antitrypsin from liver cells. Whereas the risk of cirrhosis is increased in homozygous patients (P1 ZZ) and possible in heterozygous patients (non–PI MM) as well, a greater risk for hepatocellular carcinoma has been suggested only in homozygous patients.
Because these two metabolic disorders are relatively common, it has been difficult to determine whether they are associated with each other. In this study, we tried to determine the relationship between these two disorders using the case material seen at the University of Pittsburgh during a 7–yr period.
We studied 15 patients with genetic hemochromatosis. β1–Antitrypsin quantitation and phenotyping were performed in each case using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds ratio and χs2 tests were used to measure the relative risk and significance of association, respectively.
Eleven patients (73%) were found to be PI M and four (27%) were identified as being heterozygotes: three (20%) were PI MZ, and one (7%) was PI MS. The prevalence of the PI MS phenotype was similar to that in the general population (7% vs. 6.4%; NS). The PI MZ phenotype, however, was statistically more common in patients with hemochromatosis than in the general population (20% vs. 2.2%; p <0.004). The odds of having hemochromatosis among PI MZ patients is increased 11–fold (odds ratio = 11.25; 95% confidence interval: 1.95, 44.23). The mean serum level of β1 antitrypsin and the occurrence of hepatocellular carcinoma was similar in the patients with the PI M and non–PI M phenotypes.
It can be concluded that abnormal β1–antitrypsin alleles are seen more frequently in patients with genetic hemochromatosis than in the general population. Their coexistence may contribute to the earlier development of cirrhosis in some of these patients. However, it does not increase the risk for hepatocellular carcinoma despite the fact that each disorder alone is known to do so. (Hepatology 1992;16:145-148.)
Cytomegalovirus Infection Persists in the Liver Graft in the Vanishing Bile Duct Syndrome
Authors: Arnold Joachim C. , Portmann Bernard C. , O'grady John G. , Naoumov Nikolai V. , Alexander Graeme J.M. , Williams Roger 
Published: March 2007

Cytomegalovirus infection is one factor implicated in the cause of the vanishing bile duct syndrome complicating liver transplantation. To further investigate the role of cytomegalovirus in this syndrome, we studied serial liver biopsy material by in situ hybridization for cytomegalovirus DNA using a highly sensitive technique that allows the localization of viral replication.
Cytomegalovirus DNA was identified in hepatocytes in 10 of 12 patients with the vanishing bile duct syndrome, 1 of whom had no serological evidence of cytomegalovirus infection. It was also present in all 18 patients with uncomplicated cytomegalovirus infection but was not identified in any of 10 subjects with transplants who had neither complication. Nine of the patients in this series underwent a diagnostic liver biopsy at 1 wk and subsequently had cytomegalovirus infection develop; cytomegalovirus DNA was identified in liver tissue of all nine patients, indicating that cytomegalovirus replication commences at an early stage.
In those with uncomplicated cytomegalovirus, infection occurred earlier (p < 0.05) but was eliminated more quickly (p < 0.0005), and the number of infected hepatocytes was greater (p < 0.05) when compared with those with the vanishing bile duct syndrome; in these, cytomegalovirus DNA was detectable until death or retransplantation. Cytomegalovirus DNA was never identified in either biliary or endothelial tissue. These data indicate that the vanishing bile duct syndrome is associated with persistent cytomegalovirus replication within hepatocytes. (Hepatology 1992;16:285-292.)
Postinfantile Giant–Cell Transformation in Hepatitis
Authors: Devaney Kenneth , Goodman Zachary D. , Ishak Kamal G. 
Published: March 2007

Giant–cell hepatitis is a frequent pattern of liver injury in the neonate, but it is rare after infancy. Such cases have been attributed to autoimmune disease, to non–A, non–B hepatitis and, most recently, to paramyxovirus infection. To better define the entity of postinfantile (syncytial) giant–cell hepatitis, we reviewed 24 biopsy specimens from 20 patients with this finding, either alone or in combination with other diagnoses. The number of multinucleated giant cells varied greatly from one specimen to another. Varying degrees of portal inflammation appeared in all but one of the patients, and all had hepatitislike acinar inflammation associated with hepatocellular injury. Fibrosis was a common finding, varying from mild periportal fibrosis to established cirrhosis (33%). The changes were interpreted as acute giant–cell hepatitis in 25%, as CAH in 42% and as active cirrhosis in the remainder.
The patients ranged in age from 2 to 80 yr, with a mean of 35 yr and a male/female ratio of approximately 1:1. The signs and symptoms of liver disease were present for more than 1 mo in most patients. A positive antinuclear antibody titer was found in seven of the patients. Three patients had a direct Coombs reaction and anemia. Overall, evidence of autoimmune disease was found in 40% of the patients. One patient had non–Hodgkin's lymphoma involving the liver. Only one patient had a history of blood transfusion or risk factors for hepatitis C. No patient underwent serological study for paramyxovirus antibodies. Liver tissue from one patient was examined ultrastructurally, but no viral particles could be identified. Follow–up information was available in 17 of the patients. Four had died (one of causes unrelated to liver disease); one of the surviving patients underwent successful orthotopic liver transplantation. It would appear that postinfantile giant–cell hepatitis is best regarded as an unusual reaction pattern that can occur in both acute and chronic hepatitis. The most frequently identified underlying cause in our series was autoimmune disease, which may have significant implications for treatment of many of these patients. (Hepatology 1992;16:327-333.)
Tumor Size Determines the Efficacy of Percutaneous Ethanol Injection for the Treatment of Small Hepatocellular Carcinoma
Authors: Vilana Ramón , Bruix Jordi , Bru Concepció , Ayuso Carmen , Solé Manel , Rodés Joan 
Published: March 2007

This study was aimed at defining the therapeutic value of percutaneous ethanol injection in patients with solitary hepatocellular carcinoma less than 4 cm. Ultrasound–guided ethanol injection was performed in 24 cirrhotic patients (9 Child A, 10 Child B and 5 Child C), with hepatocellular carcinoma not suitable for surgical treatment. Its efficacy was assessed by repeated ultrasound, computed tomography and tumor biopsy during a follow–up ranging between 4 and 41 mo. Ethanol injection did not achieve a complete tumor necrosis in five cases after a minimum of 12 injections. Seven of the remaining 19 cases, with initial success, have shown recurrence during follow–up, thus resulting in 50% success rate, which was significantly related to baseline tumor size. The six patients with nodules less than 2 cm achieved a complete response, whereas this was recorded in 2 of the 7 with tumor size between 2 and 3 cm, and in only 1 of the 11 cases between 3 and 4 cm. The 1– and 2–yr survival of Child's A and B patients was 87% and 70%, respectively.
These results indicate that percutaneous ethanol injection is a useful treatment for hepatocellular carcinoma, especially in tumors less than 3 cm. The high survival rate among patients with nonadvanced liver disease suggests that this therapeutic approach can be considered an alternative approach to surgical resection for tumors smaller than 3 cm. (Hepatology 1992;16:353-357.)
Bile–Duct Destruction and Collagen Deposition: A Prominent Ultrastructural Feature of the Liver in Cystic Fibrosis
Authors: Lindblad Anders , Hultcrantz Rolf , Strandvik Birgitta 
Published: March 2007

To study the liver disease of patients with cystic fibrosis, percutaneous liver biopsies were performed in 10 patients with cystic fibrosis aged 6 to 22 yr.
Nine of 10 patients had high Shwachman scores, eight had normal serum levels of transaminases. Lightmicroscopical examination showed steatosis in seven cases and in five slight or moderate inflammatory infiltration. Eight patients showed varying degrees of fibrosis and even cirrhosis. Six patients had bile–duct proliferation and, in one case a bile plug was found. Other signs of cholestasis were not seen.
Electron–microscopical investigation showed no specific signs of cholestasis such as ductal plugs or intracellular bile pigments. The canaliculi were not dilated, except in one case. Most patients had bile–duct cells with irregular shapes, protruding into the lumen, and some cases even had necrotic cells. Around the bile ducts and ductules, collagen was deposited and fatstoring cells were a common finding.
Our findings do not support the view that cholestasis is the pathogenetic factor in liver disease in cystic fibrosis. A cytotoxic influence on the biliary cells, stimulating collagen deposition, seems more likely. (Hepatology 1992;16:372-381.)
Spontaneously Diabetic Biobreeding Rats and Impairment of Bile Acid-Independent Bile Flow and Increased Biliary Bilirubin, Calcium and Lipid Secretion
Authors: González Javier , Fevery Johan 
Published: March 2007

Chemically induced diabetes has been reported to induce profound changes in bile formation, but possible toxic effects of the streptozotocin or alloxan used cannot be excluded totally. This study was undertaken to evaluate biliary function in spontaneously diabetic female biobreeding rats with a diabetes duration of 2 wk and compare them with nondiabetic littermates. Diabetic animals evidenced glycosuria, hyperglycemia and hypoinsulinemia. Biliary concentration and secretion of bile acids, cholesterol and phospholipids were significantly increased, with no enhancement in the lithogenic index of bile. Bile flow and the biliary secretion of sodium, potassium, chloride and bicarbonate were significantly reduced despite the increased bile acid secretion. The cholestatic condition was confirmed by an increased serum concentration of bile acids and a higher activity in serum of the alkaline phosphatase liver isoenzyme. Biliary calcium concentration increased without any change in its serum concentration. A linear relationship was observed between biliary calcium and bile acid secretion. Serum concentration of unconjugated and of conjugated bilirubin was increased 1.6–fold and 8–fold, respectively, with a 1.5–fold enhanced biliary secretion of bilirubins despite the cholestasis; this points to an enhanced bilirubin production. An increased proportion of conjugated bilirubin was found in serum together with an enhanced bilirubin diconjugate/monoconjugate ratio in bile. A higher UDP–glucuronyltransferase activity and a delayed transit of bilirubin could account for these effects. Administration of insulin to diabetic animals tended to reverse the above reported changes.
The spontaneously diabetic biobreeding rat thus represents a model of bile acid-independent cholestasis with enhanced biliary bile acid and calcium secretion and with presumably an enhanced bilirubin production. (Hepatology 1992;16:426-432.)
Identification and Partial Characterization of A Somatostatin–14 Binding Protein on Rat Liver Plasma Membranes
Authors: Raper Steven E. , Kothary Piyush C. , Valle John Del 
Published: March 2007

Binding of somatostatin–14 to rat liver plasma membranes was characterized with 125–labeled[tyr11] somatostatin–14. Binding at 24° C reached a plateau at 50 min and was reversible by synthetic somatostatin–14. Scatchard analysis revealed a single class of binding sites (affinity constant = 2.4 ± 0.2 nmol/L, binding capacity = 148 ± 0.02 fmol/mg protein). Specificity for somatostatin–14 was demonstrated by the inhibition of 125I–[tyr11]somatostatin–14 binding by biologically active somatostatin analogs but not by a biologically inactive somatostatin analog or unrelated peptides. The radioiodinated binding site complex could be cross–linked with disuccinimidyl suberate. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel autoradiography revealed a 70,000–Da band. Dithiothreitol, a reducing reagent, did not alter the mobility of the band, and the band could be abolished in the presence of 10 μmol/L synthetic somatostatin–14. Covalently crosslinked, iodinated binding protein complexes could be solubilized by the nonreducing detergents Zwittergent 3-12 and 3–([3–cholamidopropyl] diethylammonio)–1–propanesulfonic acid (CHAPS). Solubilized complex bound to wheat–germ agglutinin-agarose columns and was eluted by N, N′, N”–triacetylchitotriose. Binding to wheat–germ agglutinin agarose columns was lost after pretreatment with endo–β–N–acetylglucosaminidase F. Binding studies with liver plasma membranes, 125I–labeled[tyrosine11]somatostatin–14 and guanine nucleotides showed inhibition of binding in the presence of guanine nucleotides.
These results indicate that the purified rat liver plasma membranes contain a specific binding protein for somatostatin–14, the binding protein appears to be glycosylated and somatostatin–14 binding to rat liver plasma membranes may be regulated by G proteins. (Hepatology 1992;16:433-439.)
High Concentrations of Soluble Tumor Necrosis Factor Receptors in Ascites
Authors: Andus Tilo , Gross Volker , Holstege Axel , Ott Margit , Weber Marlies , David Martina , Gallati Harald , Gerok Wolfgang , Schölmerich Jürgen 
Published: March 2007

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy–related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor–α concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy–related (p55: 26.0 ± 8.6 ng/ml; p75: 20.5 ± 17.4 ng/ml; mean S.D.) and infected ascites (p55: 25.1 ± 10.9 ng/ml, p75: 22.6 ± 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 ± 4.4 ng/ml; p75: 6.0 ± 2.6 ng/ml). Patients with infected or malignancy–related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 ± 15.2 ng/ml to 10.7 ± 1.9 ng/ml and from 20.2 ± 14.4 ng/ml to 7.5 ± 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients. Levels of soluble tumor necrosis factor receptor p75 were also higher in ascites than in plasma in patients with malignant and infected ascites, but soluble tumor necrosis factor receptor p75 levels were usually higher in plasma than in ascites in patients with uncomplicated hepatic ascites. The concentrations of both tumor necrosis factor receptors correlated well in ascites (r = 0.83, p < 0.001) and plasma (r = 0.85, p < 0.001) but only weakly with tumor necrosis factor–α levels in ascites (p55: r = 0.32, p = 0.03; p75: r = 0.29, p = 0.047) and not with tumor necrosis factor–α in plasma.
The high soluble tumor necrosis factor receptor concentrations found in ascites may influence the local bioavailability of tumor necrosis factor and might have an impact on the treatment of peritoneal carcinomatosis with recombinant tumor necrosis factor. Furthermore, the determination of soluble tumor necrosis factor receptors could be of value for the differential diagnosis of ascites. (Hepatology 1992;16:749-755.)