bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific histologic features of Santa Marta hepatitis: A severe form of hepatitis δ-virus infection in Northern South America
Authors: Buitrago Bernardo , Popper Hans , Hadler Stephen C. , Thung Swan N. , Gerber Michael A. , Purcell Robert H. , Maynard James E.
Published: March 2007

Stimulated by observations in an outbreak of hepatitis δ-virus infection among Yucpa Indians in Venezuela, in which unusual histologic features were found, we studied 100 cases of fatal hepatitis from Colombia, South America, which had been obtained by autopsy or viscerotomy. These cases were considered to be “Santa Marta hepatitis,” or “hepatitis of the Sierra Nevada de Santa Marta,” which has been observed in this region for more than 40 years. Of the 100 cases, 19 had a variety of histologic lesions or were normal, and hepatitis δ-virus antigen was not demonstrated immunocytochemically in any of them. By contrast, 81 cases had a characteristic histologic picture with intense microvesicular steatosis associated with conspicuous eosinophilic necrosis of the hepatocytes, which apparently were sluggishly removed by cytolysis. Hepatitis δ-virus antigen was detected in 70% of the 81 cases, and the absence of detection of this antigen was often associated with poor tissue preservation and more extensive hepatocyte necrosis. A smaller percentage of patients had hepatitis B virus antigens detectable in liver tissue. The characteristic lesion in these 81 cases could be distinguished from other causes of microvesicular steatosis by the extensive eosinophilic necrosis. Other variable accompanying features included intraacinar, mainly macrophagic, scavenger cell inflammation, intense portal inflammation, parenchymal regeneration, and ductular and arteriolar proliferation. Santa Marta hepatitis as a severe form of hepatitis δ-virus infection differs markedly from fulminant δ-hepatitis in Europe and the United States in which the microsteatosis with marked eosinophilic degeneration is not found. The causes for these differences are unknown but may relate to nutritional factors or environmental toxins. Hepatitis δ-viral infection appears to be endemic in the indigent, rural populations of Northern South America where hepatitis B virus is also endemic. The severity of Santa Marta hepatitis stresses the importance of preventive measures against hepatitis B virus in these populations.
Further studies by immunofluorescence of the monoclonal antibodies associated with experimental non-A, non-B hepatitis in chimpanzees and their relation to D hepatitis
Authors: Shimizu Yohko K. , Purcell Robert H. , Gerin John L. , Feinstone Stephen M. , Ono Yasushi , Shikata Toshio
Published: March 2007

To further investigate the specificity of the monoclonal antibodies (48-1 and S-1) associated with non-A, non-B hepatitis, extensive immunofluorescence studies were performed on liver biopsy specimens from chimpanzees with experimental hepatitis A, B, non-A, non-B or δ, or from normal chimpanzees. Both 48-1 and S-1 antibodies reacted in the same manner with liver biopsy specimens from 47 of 50 (94%) chimpanzees with acute or chronic non-A, non-B hepatitis and 15 of 18 (83%) chimpanzees with type D hepatitis.

Examinations of serial liver biopsy specimens revealed that the duration of expression of the antigen reacting with the antibodies in hepatocytes of chimpanzees infected with non-A, non-B viruses appeared to be longer than that of chimpanzees infected with the hepatitis δ-virus.

By thin-section electron microscopy, the presence of the microtubular aggregates, identical to those previously described for chimpanzees with non-A, non-B hepatitis and shown by immunoelectron microscopy to react with the antibodies, was noted in hepatocytes during the acute phase of hepatitis δ-virus.

The antibodies did not react with liver biopsy specimens from chimpanzees acutely or chronically infected with hepatitis B virus or hepatitis A virus, or from normal chimpanzees. The present results confirm our previous observations with the 48-1 and S-1 antibodies. Furthermore, the finding that these two antibodies were also associated with hepatitis D would support the possibility that non-A, non-B agents and the hepatitis δ-virus may have a similar nature or may elicit a similar host response.
Protective effects of fibronectin in galactosamine-induced liver failure in rats
Authors: Moriyama Takashi , Aoyama Hiromu , Ohnishi Shin , Imawari Michio
Published: March 2007

The effects of supplementation with fibronectin on liver damage and survival in rats with galactosamine-induced liver failure were studied. In rats with acute liver failure induced by a low dose of galactosamine, supplementation with purified plasma fibronectin at 3 hr after the administration of galactosamine provided significant increase of plasma fibronectin levels and augmentation of reticuloendothelial system function at 4 hr, significantly higher plasma fibronectin levels and significant protection of liver damage with shorter prothrombin times, lower AST and less histological damage at 48 hr as compared to control animals. Plasma fibronectin levels were inversely correlated with both plasma prothrombin times and AST. Fibronectin supplementation at 6 hr also resulted in the significant decrease of liver damage at 48 hr as evaluated histologically. When rats with liver failure, induced by a high dose of galactosamine, were supplemented with fibronectin at 3 hr, the survival rate was significantly higher than that of control rats. The results indicate that fibronectin supplementation in the early stages of acute liver failure could reduce liver damage and improve the survival of rats with galactosamine-induced liver failure.
The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D-galactosamine
Authors: Francavilla Antonio , Dileo Alfredo , Polimeno Lorenzo , Gavaler Judith , Pellicci Riccardo , Todo Satoro , Kam Igal , Prelich John , Makowka Leonard , Starzl Thomas E.
Published: March 2007

Galactosamine induces a dose-dependent hepatic injury in rats and many other animals. The toxicity of D-galactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of D-galactosamine-induced hepatic necrosis in rats. D-Galactosamine (2.6 gm per kg of body weight) was administered intraperitoneally to 438 male Lewis strain rats. The animals were divided into six groups according to the type of treatment: Group 1 (n = 131) saline; Group 2 (n = 40) cytosol (75 mg total protein); Group 3 (n = 75) hepatic stimulatory substance (20 mg total protein); Group 4 (n = 42) 300,000 subfraction (4 mg total protein); Group 5 (n = 68) 300,000 subfraction (2 mg total protein), and Group 6 (n = 82) 50,000 subfraction (0.6 mg total protein). All rats received 4 ml of the test solution intraperitoneally at 48 hr after D-galactosamine administration. The percentage of rats surviving in each group was determined daily for 20 days. Although hepatic stimulatory substance and 50,000 subfraction tended to improve survival in intoxicated rats, only those rats treated with the 300,000 subfraction attained statistical significance with respect to the saline control.
Brainstem auditory evoked potentials in hepatic encephalopathy
Authors: Yang Sien-Sing , Chu Nai-Shin , Liaw Yun-Fan
Published: March 2007

Brainstem auditory evoked potentials were obtained from 30 patients primarily with viral hepatitis to determine the functional status of the brainstem in hepatic encephalopathy. The patients were divided into four groups: Group 1 with compensated hepatic diseases; Group 2 with hepatic failure but no hepatic encephalopathy; Group 3 with Grade 1 or 2 hepatic encephalopathy, and Group 4 with Grade 3 or 4 hepatic encephalopathy. The brainstem auditory evoked potential central conduction times (I-V interval) of four patient groups were not significantly different from that of the age-matched control group. The present data suggest that the brainstem auditory pathways remain undisturbed in hepatic encephalopathy.
The effects of ethanol and hyperosmotic perfusates on albumin synthesis and release
Authors: Rothschild Marcus A. , Oratz Murray , Schreiber Sidney S. , Mongelli Joseph
Published: March 2007

Sucrose and ethanol inhibit albumin synthesis; sucrose via an osmotic mechanism and ethanol during its metabolism. The present study was undertaken to compare the effects of both of these agents on albumin synthesis and secretion, and to see if ethanol inhibition could be related to an osmotic effect.

Male, fed rabbits served as liver donors in all studies. There were a total of 35 studies: 13 control; 10 ethanol (39 to 52 mM); 4 cycloheximide (0.5 mM), and 8 sucrose (1%). Plasma volume was measured with 125I-albumin (human) and extracellular volume measured with either 99mTc diethylenetriamine pentaacetic acid or [14C]sucrose. During perfusion, rabbit albumin content in the perfusate was measured immunologically every 15 to 30 min for 225 min. Interstitial albumin efflux was measured by the rate of appearance in the perfusate of 125I-albumin given to 10 other rabbits 3 days prior to hepatic removal and perfusion.

During the initial 75 min of perfusion, 74% of the in vivo equilibrated exchangeable 125I-albumin appeared in the perfusate, and during this period the rabbit albumin that entered the perfusate was taken to represent efflux from the interstitial volume plus synthesis. Rabbit albumin appearing in the perfusate during the later period of 150 min was taken to represent mainly synthesis and was used to calculate the amount of albumin that would be synthesized in 75 min. The difference between these two values would be hepatic interstitial albumin appearing in the perfusate. Acute ethanol exposure reduced hepatic extracellular volume from 18.4 ± 0.3 to 14.1 ± 0.2 ml per 100 gm wet liver weight, did not significantly alter hepatic plasma volume (8.4 ± 0.3 vs. 7.5 ± 0.2 ml in alcohol studies) and reduced hepatic interstitial volume from 10.0 ± 0.4 to 6.6 ± 0.3 ml. Sucrose infusions in eight rabbits did not alter hepatic extracellular volume, averaging 17.2 ± 0.8 ml, nor were plasma volume (mean = 8.7 ± 0.5 ml) and calculated hepatic interstitial volume (mean = 8.5 ± 0.4 ml) significantly altered. The amount of albumin (mg per 100 gm wet liver weight per hr) released from control livers during the first 75 min averaged 48 ± 3 mg, decreased to 36 and 38 mg with ethanol and cycloheximide, respectively, but was not effected by sucrose, even though all of these test substances reduced synthesis during the later time periods (T-75 to T-225). The synthetic rates for this time period were 27 mg per 100 gm wet liver weight per hr in controls, 9.5 mg in ethanol studies, 6.4 mg in the cycloheximide studies and 12.3 mg in the sucrose studies. Ethanol and cycloheximide, thus, must have lowered albumin synthesis nearly immediately, but sucrose required a longer exposure.
Ground-glass hepatocytes: A spectrum of inclusions
Authors: Gerber Michael A. , Grases Pedro J.
Published: March 2007

A new type of ground-glass hepatocyte is described. The appearance is due to pale, homogeneous, weakly eosinophilic inclusions filling a portion of or the entire hepatocytic cytoplasm. On haematoxylin and eosin stained sections, these cells closely resemble ground-glass hepatocytes described in other conditions. However, they are negative on special stains for HBsAg and on PAS staining. Immunohistochemically, they reveal a selective and exclusive positivity for fibrinogen. On electron microscopy, the immunoreactive fibrinogen appears as amorphous, fluffy or granular material within dilated cisternae of the rough endoplasmic reticulum. This finding suggests intracellular storage possibly reflecting a defective intracellular transport of fibrinogen.
Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis
Authors: Liaw Yun-Fan , Pao Chia C. , Chu Chia-Ming , Sheen I-Shyan , Huang Miau-Ju
Published: March 2007

Two types of clinical events, acute exacerbation and uneventful course, precede spontaneous HBeAg serocon-version to its antibody (anti-HBe) in chronic type B hepatitis. To examine the possible mechanism responsible for these two types of clinical events, serial serum specimens from 75 patients who underwent spontaneous HBeAg seroconversion were assayed for hepatitis B virus DNA by slot blot hybridization with 32P-labeled cloned hepatitis B virus DNA as probe. Of these 75 patients, 47 (62.7%) had episodes of acute exacerbation (ALT >300 IU per liter) within 3 months prior to HBeAg seroconversion. All of these 47 patients had high hepatitis B virus DNA levels (> 1,000 pg per ml) at the onset of acute exacerbation. Their serum hepatitis B virus DNA disappears shortly before or simultaneously with the HBeAg clearance in 27 patients (57.4%) and persisted but with decreasing levels for 2 to 40 months in 20 patients. Most of these patients had high α-feto-protein levels or evidence of bridging hepatic necrosis. In contrast, the serum hepatitis B virus DNA was undetectable for a minimum of 3 (3-17) months in the 28 patients who had an uneventful course before HBeAg seroconversion. Twenty of these 28 patients had well-documented episodes of acute exacerbation with high hepatitis B virus DNA levels, but with normal α-feto-protein and little evidence of extensive necrosis as far back as 6 to 27 months before HBeAg seroconversion. The data might suggest that all spontaneous HBeAg seroconversion in chronic type B hepatitis was preceded by acute exacerbation as a result of immune clearance of hepatitis B virus, and the clinical events occurred within 3 months before HBeAg seroconversion were related to the serum hepatitis B virus DNA levels.
Antibody to liver membrane antigens in chronic active hepatitis. IV. Exclusion of specific reactivity to polypeptides and glycolipids by immunoblotting
Authors: Frazer Ian H. , Jordan William T. , Collins Elizabeth C. , Andrews Paul , Mackay Ian R.
Published: March 2007

The reactivity of sera was examined in patients with autoimmune chronic active hepatitis and other liver diseases by immunoblotting. Polypeptides and glycolipids of liver plasma membrane, liver-specific lipoprotein and kidney membrane were separated and probed with sera from patients and from a rabbit immunized with mouse liver plasma membrane. Chronic active hepatitis sera reacted with a number of polypeptides in the liver plasma membrane preparations; similar but weaker reactivity was observed with sera from patients with other diseases and in some healthy subjects. Chronic active hepatitis sera did not react with glycolipids from liver plasma membrane. The immune rabbit serum reacted with two polypeptides of 180 kd present in liver plasma membrane but absent from kidney membrane, with two polypeptides of 50 kd which were nonliver-specific but species-specific, and with three major glycolipid components of liver plasma membrane: this reactivity thus differed markedly from that of the chronic active hepatitis sera. In studies using dot-blotting, it was found that solubilization of liver plasma membrane in detergents resulted in a marked reduction of the reactivity to liver plasma membrane of chronic active hepatitis sera, but little change in the reactivity of the immune rabbit antiserum. Analysis of the reactivity of chronic active hepatitis and other sera with liver-specific lipoprotein by immunoblotting indicated that liver-specific lipoprotein consisted of constituents of liver plasma membrane together with intracellular proteins. While conditions utilized for electrophoretic separation of components of liver plasma membrane prior to immunoblotting do allow identification of some polypeptide-directed reactivities in chronic active hepatitis sera, these were not disease-specific.
The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers
Authors: Krogsgaard Kim , Lindhardt Bjarne ÖRskov , Nielsen Jens Ole , Andersson Poul , Kryger Peter , Aldershvile Jan , Gerstoft Jan , Pedersen Court
Published: March 2007

The presence of antibodies to HTLV-III and markers of active hepatitis B virus replication was examined in a longitudinal study of 33 consecutive male homosexual HBsAg carriers. The mean follow-up time was 37 months (range = 4 to 109 months). All patients were initially hepatitis B virus DNA-positive and HBeAg positive. Antibodies to HTLV-III were detectable in eight patients while they were positive for both of these markers. One of them cleared hepatitis B virus DNA and seroconverted from HBeAg to anti-HBe. This corresponds to an annual clearance/seroconversion rate of 4% (95% confidence limits = 0 to 15%). In two patients, antibodies to HTLV-III appeared after clearance of hepatitis B virus DNA and HBeAg, and in one of them, hepatitis B virus DNA reappeared. Among the 25 patients negative for HTLV-III antibodies, the annual hepatitis B virus DNA clearance rate was 20% and HBeAg to anti-HBe seroconversion rate was 11% (95% confidence limits = 11 to 31% and 4 to 20 % respectively). The observed hepatitis B virus DNA clearance rates in the two groups were significantly different (p < 0.05). Disease activity, as determined by transaminase levels, was significantly lower in HTLV-III infected individuals as compared to individuals without HTLV-III infection (p < 0.05). Infection with HTLV-III may extend the period of active viral replication or even reactivate hepatitis B virus replication and seems to diminish inflammatory disease activity in chronic HBsAg carriers.
Serum type III procollagen peptide concentrations in severe chronic active hepatitis: Relationship to cirrhosis and disease activity
Authors: McCullough Arthur J. , Stassen William N. , Wiesner Russell H. , Czaja Albert J.
Published: March 2007

To analyze the correlations between the presence of cirrhosis and hepatocellular inflammation and the serum concentrations of the amino-terminal peptide of procollagen type III in chronic liver disease, we measured procollagen type III concentrations in paired serum samples from 46 patients (17 had cirrhosis) with severe chronic active hepatitis during a therapeutic treatment trial. Coded sera were analyzed for procollagen type III concentrations using both a standard and a recently described Fab radioimmunoassay to compare their relative diagnostic accuracy.

Mean procollagen type III levels were elevated to the same extent in the cirrhotic and noncirrhotic groups at entry into the study. In response to immunosuppressive therapy, the initially elevated procollagen type III levels improved to normal values at remission in both groups. Qualitatively, the results were similar using either assay, but the standard assay was more sensitive for identifying the clinical stage of disease (i.e., active disease vs. disease in remission) than the Fab assay. Since both procollagen type III levels and standard liver function tests correlated well individually with the presence or absence of active disease, they also correlated with each other when both entry and remission values were considered. However, procollagen type III levels correlated poorly with indicators of inflammation (histologic grade and serum transaminase levels) during active disease.

It is concluded that procollagen type III levels change in concert with standard liver function tests but do not quantitatively reflect inflammation or static measurements of hepatic fibrosis in severe chronic active hepatitis. However, these preliminary results suggest that procollagen type III can distinguish active disease from chronic active hepatitis in remission. Consequently, this test may be useful for monitoring disease activity and therapeutic response in severe chronic active hepatitis. For this purpose, the standard procollagen type III radioimmunoassay has greater diagnostic accuracy than the Fab radioimmunoassay.
Ethanol-induced increase in portal hepatic blood flow: Interference by anesthetic agents
Authors: Carmichael Frederick J. , Saldivia Victor , Israel Yedy , McKaigney John P. , Orrego Hector
Published: March 2007

While a number of studies show that acute oral administration of ethanol results in increases in liver blood flow, a large body of evidence has also been presented in which such an effect is not observed. To shed light on this discrepancy, we have studied in rats, a number of variables that might modulate or inhibit the effect of ethanol. These included the use of three anesthetic agents studied at two different times after anesthetic administration and the effect of animal age, gender, batches and seasonal variation.

Portal blood flows were determined by the radiolabeled microsphere method in 12 separate experiments in awake rats. Ethanol given at doses ranging from 0.5 to 4.0 gm per kg consistently increased portal vein blood flow by approximately 50% (42.2 ± 3.5 to 63.4 ± 6.5 ml per min per kg). The interexperiment variation was 2.4 to 3.0%, showing remarkable consistency, typical of an all-or-none effect at the doses employed. On the other hand, the ethanol-induced increase in portal blood flow was completely suppressed by ketamine (75 mg per kg), thiopental (50 mg per kg) and fentanyl (15 μg per kg) when given 15 min prior to blood flow determinations. This suppression was dependent on the dose and duration of anesthesia. These anesthetic agents had no effect on basal hepatic arterial or portal blood flows. Ethanol or the anesthetics were without effects on hepatic artery blood flow. Neither gender, weight (150 to 350 gm) nor animal batch had effect on the response to ethanol. Similarly, there was no effect of seasonal variation. The increase in portal vein blood flow following a dose of 2 gm per kg of ethanol disappeared only after 6 hr when blood levels of ethanol had decreased to concentrations below 3 mM.

The consistency, under nonpathological conditions, of an increase in portal blood flow by ethanol is of interest because, as ethanol also increases liver oxygen consumption, an increment in oxygen delivery induced by ethanol could play a compensatory role preventing the occurrence of hypoxic liver damage.
Purification and physical-chemical characterization of hepatic stimulator substance†
Authors: Labrecque Douglas R. , Steele Gregory , Fogerty Steven , Wilson Michelle , Barton James
Published: March 2007

Hepatic stimulator substance is a liver growth stimulator derived from the hepatocyte cytosol of weanling or regenerating adult rat livers. The present paper reports the almost 9,000-fold purification of hepatic stimulator substance with an approximately 100,000-fold increase in specific growth stimulator activity. Purification steps included heating at 95°C for 15 min, 40% cold ethanol precipitation, passage over Procion Red HE3B, DEAE cellulose and Sephadex G75 columns and gel filtration and reverse-phase fast protein liquid chromatography techniques. As little as 27 ng per ml of the purest material produced a 2-fold stimulation in the standard HTC cell activity assay. Further studies indicate that hepatic stimulator substance is a highly negatively charged protein and that disulfide bonds or a complex tertiary structure are not essential to its activity. Hepatic stimulator substance is stable over a wide range of pH's and temperatures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver stain revealed 1 major band at 12,400 daltons and 1 minor band at 17,500 daltons.
Compensated cirrhosis: Natural history and prognostic factors
Authors: Ginés Pere , Quintero Enrique , Arroyo Vicente , Terés Josep , Bruguera Miguel , Rimola Antoni , Caballería Joan , Rodés Joan , Rozman Ciril
Published: March 2007

To investigate the natural history of compensated cirrhosis, 293 consecutive patients without previous major complications (ascites, jaundice, encephalopathy or gastrointestinal hemorrhage) were studied in terms of morbidity (probability of developing decompensated cirrhosis during follow-up) and survival. Patients were diagnosed by liver histology between 1968 and 1980. Median follow-up was 63 months. Decompensation of cirrhosis was considered when a patient first developed one of the major complications of the disease. Ten years after diagnosis, the probability of developing decompensated cirrhosis and the survival probability rate were 58 and 47%, respectively. A multivariate survival analysis (Cox's regression model) using clinical, biochemical and histological data obtained at diagnosis disclosed seven factors that predicted prognosis: serum bilirubin; serum γ-globulin concentration; hepatic stigmata; prothrombin time; sex; age, and alkaline phosphatase. According to the contribution of each one of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. The predicting value of this index was validated by a split sample testing technique.
The effect of peritoneovenous shunting on catecholamine metabolism in patients with hepatic ascites
Authors: Blendis Laurence M. , Sole Michael J. , Campbell Peter , Lossing Alan G. , Greig Paul D. , Taylor Bryce R. , Langer Bernard
Published: March 2007

The elevated catecholamine levels in cirrhotic patients with ascites have been proposed to be due to sympathetic overactivity secondary either to reduced intravascular volume or to an underlying cardiovascular abnormality such as reduced pressor responsiveness. Furthermore, these elevated catecholamine levels have been proposed to be involved in the pathogenesis of salt and water retention. Therefore, the effect of peritoneovenous shunting on the circulating levels and renal excretion of catecholamines were studied in six patients with massive refractive ascites preoperative within the first 8 hr postoperative and by 2 weeks postoperative under metabolic conditions. The recirculation of ascites into the intravascular compartment resulted perioperatively in significant rises in cardiac output (p = 0.001), para-amino-hippurate clearance (p = 0.08), creatinine clearance, diuresis (p = 0.05) and natriuresis (p = 0.06). Systemic blood pressure remained unchanged while systemic vascular resistance decreased (p < 0.05).

Preoperative circulating levels of free catecholamine were highly elevated, and renal vein concentrations were about 25% higher than renal arterial levels. Peri-operatively, there was little change in circulating catecholamine levels or distribution of renal blood flow although renal artery and vein concentrations tended to equalize.

In contrast by 2 weeks postoperatively, free catecholamine levels had fallen to within the normal ranges: mean norepinephrine from 1,477.6 ± 194.6 to 395 ± 62.9 pg per ml (p < 0.05); epinephrine from 276 ± 74.2 to 65.7 ± 15.0 pg per ml (p < 0.02), and dopamine from 325.6 ± 175.2 to 47.9 ± 5.3 pg per ml. There was little change in circulating conjugated catecholamine levels, either urinary excretion or clearance of catecholamines, except epinephrine clearance which rose significantly (p < 0.05). Despite the normalization of circulating free catecholamine levels, the patients tended to remain hypotensive with a low peripheral vascular resistance. The return of circulating free catecholamine levels to normal following reexpansion of the intravascular volume by peritoneovenous shunting are in favor of their being elevated in response to vascular underfilling.
Hemodynamic effects of a clonidine-induced decrease in sympathetic tone in patients with cirrhosis
Authors: Moreau Richard , Lee Samuel S. , Hadengue Antoine , Braillon Alain , Lebrec Didier
Published: March 2007

A decrease in plasma noradrenaline—a reflection of sympathetic nervous system activity—by clonidine, a centrally acting α2-agonist, could reduce the hyperdynamic circulation observed in cirrhosis and may thereby decrease portal hypertension. Plasma noradrenaline concentration and plasma renin activity as well as systemic and splanchnic hemodynamics were measured in 12 patients with cirrhosis and ascites before and after administration of either 150 μg of clonidine or placebo. Plasma noradrenaline concentration significantly decreased in all patients after clonidine administration, whereas plasma renin activity did not change significantly. There were statistically significant reductions of cardiac output (−17.4%), mean arterial pressure (−12.2%), hepatic venous pressure gradient (−19.7%) and azygos blood flow (−26.6%) after administration of clonidine. No significant correlation was found between the reduction of plasma noradrenaline concentration and changes in systemic or splanchnic hemodynamics. Hepatic blood flow was not changed by clonidine. Placebo administration had no effect on any laboratory or hemodynamic measurement. We conclude that the reduction in sympathetic nervous system activity by clonidine and the subsequent decrease in the hyperdynamic circulation suggests that sympathetic overactivity contributes to the circulatory derangements in patients with cirrhosis.
Biliary stenosis: Balloons in the bile duct
Authors: Kozarek Richard A. , Conn Harold O.
Published: March 2007

Five patients with benign strictures of the biliary tract were treated by Gruntzig balloon dilation during endoscopic retrograde cholangiopancreatography. All of the strictures were effectively dilated. One patient with a retained stone in the proximal biliary tree underwent surgery 3 weeks after the dilation because of cholangitis. The other four patients were well at a mean follow-up of 6 months. There were no complications related to the procedure. We conclude that Gruntzig balloon dilation of benign bile duct strictures is safe and effective. Further experience is needed to determine its efficacy.
Cholestasis and vitamin E deficiency: Neurologic disorders
Authors: Alvarez Fernando , Alagille Daniel
Published: March 2007

To determine the frequency of biochemical vitamin E deficiency and of the clinical signs of the vitamin E deficiency neurologic syndrome in children with prolonged neonatal cholestatic disorders, we studied 46 children (aged 1 month to 17.0 years) with chronic forms of intrahepatic neonatal cholestasis and 47 children (aged 4 months to 8.0 years) with extrahepatic biliary atresia. Based on serum vitamin E concentrations and the ratios of serum vitamin E concentration to total serum lipid concentration, 64% of the intrahepatic and 77% of the extrahepatic cholestasis groups were vitamin E deficient. Prior to age 1 year, neurologic function was normal in all children. Between ages 1 and 3 years, neurologic abnormalities were present in approximately 50% of the vitamin E-deficient children; after age 3 years, neurologic abnormalities were present in all vitamin E-deficient children. Areflexia was the first abnormality to develop between ages 1 and 4 years; truncal and limb ataxia, peripheral neuropathy, and ophthal-moplegia developed between ages 3 and 6 years. Neurologic dysfunction progressed to a disabling combination of findings by ages 8 to 10 years in the majority of vitamin E-deficient children. Neurologic function was normal in the vitamin E-sufficient children. We conclude that vitamin E status should be evaluated in infants in whom cholestasis is diagnosed, and effective therapy should be initiated to prevent or treat vitamin E deficiency at an early age.
Mono-octanoin in the dissolution of gallstones in bile ducts: Limitations and precautions
Authors: Thistle Johnson L.
Published: March 2007

The efficacy and safety of mono-octanoin, a cholesterol solvent for the direct dissolution of stones in the biliary tract, was assessed by collating case reports on 343 patients provided by 222 physicians who used the material between 1977 and 1983. Most patients had previously undergone cholecystectomy, with common duct exploration, the majority within the preceding six weeks. In most, sphincterotomy was impossible or if carried out, had not induced stone passage. Stone dissolution was considered preferable to surgery, especially in patients who were frail, elderly, or had multiple medical problems. Treatment was unquivocally successful in 88 patients (26%) and was a valuable adjunct to interventional treatment in another 29 subjects (8%). In 70 patients (20%), calculi became smaller, but remained within the biliary tree. Thus, mono-octanoin was judged to have been useful in 54%) of patients. Treatment was ineffective in 124 cases (36%). In the remaining 32 patients (9%), treatment was aborted because of side effects. Such sie effects were common, occurring in 67% of cases, and in 41% of patients they were multiple. Abdominal pain was the most common complication. Other side effects reported were nausea, vomiting, and diarrhoea. Side effects were usually dose related and responded to reduction in infusion rate. Side effects were life-threatening in 12 patients (5%), but there were no permanent sequelae and no deaths occurred. These data indicate that mono-octanoin is modedrately effective, generally second line, but sometimes first line, treatment for retained biliary duct calculi.
Understanding and limiting observer variability: Lessons from liver scans
Authors: Horwitz Ralph I. , Bordley Donald R.
Published: March 2007

Two specialists in nuclear medicine and two trainees independently read 106 liver scans for abnormalities suggestive of metastases. The four observers made a positive diagnosis with a significantly different frequency. The overall agreement between pairs of observers was 0.83-0.87. After adjusting for the expected chance agreement, K-values between 0.66 and 0.74 were obtained. No difference was found in the level of agreement between the two specialists or between the two trainees. After a consensus conference where the observers tried to unify their diagnostic interpretation, another 106 scans were read for abnormalities suggestive of metastases. The conference did not increase the level of agreement. Scintigraphic lesions that especially imply a risk of disagreement are pointed out.
The dietary prevention of hepatic coma in eck fistula dogs: Ammonia and the carbohydrate to protein ratio
Authors: Zieve L. , Zieve F. J.
Published: March 2007

The conventional animal model of human portal systemic encephalopathy is the dog with Eck fistula. Dogs fed standard dog chow after Eck fistula manifest anorexia, weight loss, hepatic atrophy and encephalopathy. This study was done to determine the natural history of dogs undergoing Eck fistulas when adequate nutrition is maintained with a palatable diet. Twenty-four mongrel dogs were divided into four groups—Eck fistula fed standard dry dog chow (EF-SC) (n equals nine); sham-operated fed standard chow (SO-SC) (n equals five); Eck fistula fed a liquid (Isocal) diet (EF-LD), and sham-operated fed a liquid diet (SO-LD) (n equals five). Dogs were sacrificed when they had clinical signs of encephalopathy or up to 120 days after operation. EF-SC dogs had a daily caloric intake approximately 40 per cent of that of the other groups. Two EF-SC dogs died of sepsis within two weeks of the operation, the other seven became encephalopathic between 46 and 91 days (a mean of 63.6 ± 15.6). On other dogs had signs of neurologic deterioration. EF-SC dogs lost 19 ± 9 per cent body weight and the serum albumin level decreased 14.5 per cent while the other groups maintained body weight and serum albumin levels. Both EF-SC and EF-LD groups had decreased liver weight to body weight ratios (LW × 100/BW) compared with sham-operated upon dogs reflecting hepatic atrophy (1.97 ± 0.7 and 2.2 ± 0.23 versus 3.04 ± 0.85 and 3.48 ± 0.44). Results of histologic examination of the liver revealed hepatocyte atrophy, deglycogenation and lipid accumulation in EF dogs. We conclude from these data that providing dogs with Eck fistula a palatable diet prevents weight loss and malnutrition, but not hepatic atrophy. The lack of neurologic signs in well nourished dogs suggests to us that data concerning hepatic coma from the standard Eck fistula model should be interpreted with extreme caution.
Accumulation of 7α-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in patients with cerebrotendinous xanthomatosis: Effect of treatment with chenodeoxycholic acid
Authors: Björkhem Ingemar , Skrede Sverre , Buchmann Marie S. , East Cara , Grundy Scott
Published: March 2007

Evidence was recently presented that an essential part of the accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is due to acceleration of a novel pathway, involving 7α-hydroxylated intermediates in bile acid biosynthesis as precursors (J. Clin. Invest. 1985; 75:448-456). Such intermediates accumulate in patients with cerebrotendinous xanthomatosis due to lack of the mitochondrial 26-hydroxylase involved in the major pathway for bile acid biosynthesis. The new pathway may involve the following steps: 7α-hydroxycholesterol→7α-hydroxy-4-cholesten-3-one→cholesta-4,6-dien-3-one→4-cholesten-3-one→choles-tanol.

Accurate methods have been developed for assay of 7α-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in serum, based on isotope dilution-mass spectrom-etry. The serum levels of 7α-hydroxy-4-cholesten-3-one as well as those of cholesta-4,6-dien-3-one were found to be markedly elevated in the three patients with cerebrotendinous xanthomatosis. Treatment of two of the patients with chenodeoxycholic acid reduced the serum levels of the two steroids by more than 80%. The concentration of cholestanol was reduced by 72% in one patient and by 48% in the other.

The possibility is discussed that accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is secondary to accumulation of 7α-hydroxy-4-cho-lesten-3-one and cholesta-4,6-dien-3-one.
The disposition of 6-deoxyacyclovir, a xanthine oxidase-activated prodrug of acyclovir, in the isolated perfused rat liver
Authors: Jones Brian D. , Rustgi Vinod K. , Kornhauser David M. , Woods Amina , Quinn Richard , Hoofnagle Jay H. , Jones Anthony E.
Published: March 2007

The antiviral drug, acyclovir, has been used in the treatment of chronic type B hepatitis. High serum concentrations of acyclovir are required to achieve inhibition of hepatitis B viral replication. Because only 15 to 20% of an oral dose is absorbed, it is necessary to administer acyclovir by intravenous infusion. 6-Deoxyacyclovir, an analog of acyclovir, is well absorbed when given orally, and is converted to acyclovir by xanthine oxidase which is present in the gut and liver. This study has examined the hepatic disposition of 6-deoxyacyclovir in a 100 ml recirculating (12 ml per min) perfused rat liver system. Following administration of a bolus dose of 5 μmoles 6-deoxyacyclovir to the reservoir, perfusate concentrations of 6-deoxyacyclovir declined monoexponentially, as the metabolite acyclovir appeared in the perfusate. Addition of the xanthine oxidase inhibitor allopurinol (5 mg) to the perfusate reservoir prior to the administration of 6-deoxyacyclovir resulted in impaired hepatic metabolism of 6-deoxyacyclovir, as demonstrated by a 47% reduction in systemic clearance rate (4.5 ± 0.4 to 2.4 ± 0.9 ml per min; p < 0.05) (mean ± S.E., n = 6) and a 1.8-fold increase in terminal elimination half-life of 6-deoxyacyclovir (23.5 ± 2.7 to 42.7 ± 4.1 min; p < 0.05), accompanied by a 30% reduction in appearance of acyclovir. The efficient hepatic conversion of 6-deoxyacyclovir to the active antiviral drug, acyclovir, provides a rationale for trials of oral 6-deoxyacyclovir in the treatment of chronic type B hepatitis.
Evidence that host size determines liver size: Studies in dogs receiving orthotopic liver transplants
Authors: Kam Igal , Lynch Steven , Svanas Gregory , Todo Satori , Polimeno Lorenzo , Francavilla Antonio , Penkrot Ronald J. , Takaya Sunichi , Ericzon Bo G. , Starzl Thomas E. , Van Thiel David H.
Published: March 2007

Orthotopic liver transplantation was performed in two groups of dogs; Group I animals consisted of large dogs that served as recipients of livers obtained from smaller dogs while Group II animals consisted of dogs that received liver from donor dogs of nearly the same size. The small-for-size livers transplanted into the Group I dogs rapidly increased in size over the course of 2 weeks until they achieved a size equal to that originally present in the larger recipient dogs. In contrast, the livers transplanted into dogs of the same size as the donors underwent some degree of atrophy. In both groups of animals, plasma levels of insulin and glucagon and hepatic (graft) activities of thymidine kinase and ornithine decarboxylase were followed serially. The only difference between the two groups of animals for these measures was that the ornithine decarboxylase activity rose to a greater degree in the liver that underwent graft enlargement. These data suggest that recipient size determines, at least in part, liver graft size once it is transplanted. These data also suggest that of the parameters followed, only ornithine decarboxylase activity parallels the finding of growth of the transplanted liver.
Focal Infiltrations of Polymorphonuclear Leukocytes in Liver Biopsies: Traumatic Lesions?
Authors: Fenster Frederick L. , Conn Harold O.
Published: March 2007

A young man with chronic active hepatitis was heavily sedated during an attempted transjugular liver biopsy. The procedure was abandoned after 3 h and an immediate percutaneous liver biopsy was performed. This showed features of chronic active hepatitis but, in addition, groups of poly-morphonuclear leukocytes in the parenchyma. These were similar to the operation associated neutrophils encountered in liver biopsies taken during the course of abdominal surgery. In a review of 78 liver biopsies from patients with chronic active hepatitis, this type of infiltrate was seen in four of eight surgically resected specimens but not in 70 percutaneous biopsies. The neutrophilic infiltrate in the present case appears to be an unique occurrence in a percutaneous liver biopsy. It was probably related to hypoperfusion during the preceding prolonged sedation and illustrates the ease with which an already diseased liver can be further damaged.
β2-Adrenergic receptors in propranolol therapy: Does down-regulation do it?
Authors: Burroughs Andrew K.
Published: March 2007

The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers.
Dating gallstones
Authors: Ransohoff David F.
Published: March 2007

We investigated the natural history of cholelithiasis in 59 samples of stones from the gallbladder or common bile duct in 15 patients, using as a tracer for the timing of stone formation the 14C released into the environment during nuclear weapons testing. The ages of the stones were correlated with the dates of onset of symptoms and with other clinical data.

None of 11 symptomatic patients had symptoms or complications until at least two years (mean ± SD, 8.0 ± 5.1 years) after stone formation began. There was a lag time of 11.7 ± 4.6 years between initial stone formation and cholecystectomy. The growth rates of stones from 11 symptomatic patients and 4 asymptomatic patients were similar (2.6 ± 1.4 and 2.6 ± 1.1 mm per year). Studies of two stones retrieved from the common bile duct showed that one had the same age as a cholecystic stone; the other, removed two years after cholecystectomy, apparently grew in the common bile duct.

The long latency period between the formation of gallstones and the onset of symptoms indicates that interruption of the natural progression of gallstone disease is potentially possible with medical therapy.
Inflammatory pseudotumor of the liver: An enigmatic lesion with polyclonal plasma cell proliferation
Authors: Larson Eric B.
Published: March 2007

Five cases of inflammatory pseudotumour of the liver are reported and compared with seven individual previously published case reports. Clinical presentation was variable but often comprised low grade intermittent fever, vague abdominal symptoms, and a history of weight loss. Leucocytosis, raised erythrocyte sedimentation rate, and polyclonal hyperglobulinaemia were also sometimes detected. All five cases in the present series were considered to be clinically malignant; and in two the histological diagnosis was also that of malignancy.

The lesion is clearly inflammatory and reactive, but the aetiology remains unknown.
Sclerotherapy vs. Distal splenorenal shunt in the elective treatment of variceal hemorrhage: A randomized controlled trial
Authors: Terés Josep , Bordas Josep M. , Bravo Dolores , Visa Josep , Grande Luis , Garcia-Valdecasas Juan Carlos , Pera Cristóbal , Rodés Joan
Published: March 2007

One hundred and twelve consecutive Child Class A and B cirrhotic patients were included in a prospective controlled trial aimed at investigating the efficacy and safety of endoscopic sclerotherapy vs. distal splenorenal shunt in the elective treatment of hemorrhage from esophagogastric varices. Fifty-seven patients were randomly allocated to splenorenal shunt and 55 to endoscopic sclerotherapy. Since only 4 of the 55 patients assigned to endoscopic sclerotherapy had to be excluded after randomization and before treatment as compared to 14 of the 57 patients assigned to splenorenal shunt, it is suggested that the applicability of endoscopic sclerotherapy is greater than that of splenorenal shunt. One patient in each group died within 30 days of the procedure and two in the endoscopic sclerotherapy group were lost to follow-up just after discharge. Variceal rebleeding during follow-up occurred in 37.5% (18/48) of patients in the endoscopic sclerotherapy group and in 14.3% of those in the splenorenal shunt group (6/42) (p <0.02), whereas hepatic encephalopathy was more frequent in patients submitted to splenorenal shunt (10/42, 24%) than in those treated by endoscopic sclerotherapy (4/48, 8%) (p <0.05). The therapeutic modality was the only variable with independent predictive value for rebleeding during follow-up, whereas for hepatic encephalopathy, the therapeutic modality, and the presence of encephalopathy related to the bleeding episode each showed independent predictive value. Early and long-term mortality, did not differ between the two therapeutic groups, being the 2-year survival was 71% for splenorenal shunt and 68% for endoscopic sclerotherapy. It is concluded that endoscopic sclerotherapy is a good alternative to splenorenal shunt in the elective treatment of esophageal variceal bleeding, especially in patients prone to develop hepatic encephalopathy.