bluuebunny/crossref_metadata_2025 huggingface dataset:
Stapling instruments for intestinal anastomosis in colorectal surgery
Authors: Moran B J
Published: March 2007

The circular stapling instrument has had a major impact in the practice of colorectal surgery. Stapling technology was pioneered in the early part of this century and subsequently modified. Russian initiatives led to development of the original circular stapling instrument and further progress has resulted in instruments that are widely available, reliable and totally disposable. Mechanical failure is now rare and malfunction is generally due to operator error. Complications related to the stapling technique are uncommon, although anastomotic stricture may be more frequent than when handsewn anastomosis is performed. A stapling instrument facilitates and may expedite a surgical procedure but it is an adjunct to, and not a substitute for, meticulous surgical technique.
Elimination of fat emulsion particles from plasma during glucose infusion
Authors: Iriyama K , Tsuchibashi T , Urata H , Miki C , Ilunga K , Li H , Carpentier Y A
Published: March 2007

To determine the optimal rate of infusion of a fat emulsion (long-chain triglycerides; LCTs) for parenteral nutrition, the rate of elimination of triglycerides from plasma was measured on two occasions in three healthy subjects, once while receiving LCTs alone (study I) and once while receiving a combined infusion of glucose and LCTs (study 2). In study 1 a hypertriglyceridaemic clamp was set up by raising the concentration of triglycerides to 2 mmol 1−1 (60-min priming infusion at 0·2 g LCTs per kg body-weight per h) and maintaining this value for 300 min. In study 2 a constant infusion of glucose at a rate of 0·32 g per kg body-weight per h was given throughout the 420-min test, and the hypertriglyceridaemic clamp was set up after 70 min. The infusion of glucose induced a progressive increase in the mean(s.d.) concentration of insulin from 4·3(0·4) μU ml−1to a plateau value of 11·0(0·2) μ ml−1 which was sustained during the last 310 min of the study. During the steady state of the hypertriglyceridaemic clamp, the concentration of triglycerides (2·16(0·17) versus 2·12(0·20) mmol l−1, P = 0·26), as well as the mean(s.d.) rates of infusion of LCTs (0·12(0·08) versus 0·12(0·04) per kg body-weight per h, P = 0·38), did not differ between studies 1 and 2. Thus, an infusion of glucose (and the associated physiological increase in the concentration of insulin) at doses commonly used in parenteral nutrition does not influence the rate of elimination of triglycerides from plasma in normal subjects.
Effect of flow on the resistance of modelled femoral artery stenoses
Authors: Dodds S R , Bourne N K , Chant A D B
Published: March 2007

An accurate model of the pressure-flow relationship of a stenosis is necessary for the correct interpretation of haemodynamic measurements. Modelled femoral artery stenoses were tested in vitro and the pressure drop: flow ratio (resistance) was most accurately represented by a fixed component (Rf) combined with a variable component (Rv) that increased linearly with flow (Q) such that Rv = SvQ. For stenoses of 68–94 per cent area, Rfincreased from 3·2 to 77·7 milliperipheral resistance units (mPRU), while Sv increased from 0·009 to 0·578 mPRU ml−1 min and Rv was dominant for physiological flow rates. It was concluded that the approximation of a significant stenosis to a fixed resistance is incorrect.
Anal transitional zone and columnar cuff in restorative proctocolectomy
Authors: Thompson-Fawcett M W , McC. Mortensen N J
Published: March 2007

The popularity of double stapling the ileal pouch-anal anastomosis probably owes more to the technical ease it brings than to histological considerations or functional results. It is preservation of a ‘columnar cuff’ of mucosa, rather than the restricted site of the anal transitional zone, that should be the focus of research with respect to long-term risk of malignancy and inflammatory complications. If cancer is present in colon that has been removed for ulcerative colitis, there is a 25 per cent incidence of dysplasia in the columnar cuff in the short term. In other circumstances, those who are spared from carcinoma by colectomy are likely to have a similar risk of developing dysplastic change in the columnar cuff with longer follow-up. Double stapling the pouch-anal anastomosis and preserving the anal canal mucosa improves function, but long-term surveillance of the columnar cuff is then required, including biopsies.
Wound metastases following laparoscopic and open surgery for abdominal cancer in a rat model
Authors: Mathew G , Watson D I , Rofe A M , Baigrie C F , Ellis T , Jamieson G G
Published: March 2007

The recent application of laparoscopic resection techniques to malignant disease has raised safety concerns due to metastasis to surgical access wounds. The significance and incidence of this problem are controversial. In the present study a rat model, in which an implanted tumour was lacerated, was used to investigate whether application of laparoscopic techniques for malignant abdominal disease leads to an increased risk of tumour dissemination and implantation within the peritoneal cavity, and abdominal wall wounds. Malignant cells were implanted into the abdominal wall of 42 rats, resulting 7 days later in the growth of a tumour measuring 20–25 mm in diameter. There were three control groups: no surgery (n = 6); blunt manipulation of the tumour laparoscopically (n = 6); and blunt manipulation of the tumour at laparotomy (n = 6). Twenty-four rats underwent surgical laceration of the tumour capsule at either laparoscopy (n = 12) or laparotomy (n = 12). All rats were killed 1 week later, and examined for macroscopic evidence of tumour metastasis. The abdominal surgical wounds were excised for independent microscopic examination by a histopathologist. Growth of the primary tumour was greater in rats that had an operation than in unoperated controls, and was greatest after laparotomy. However, wound metastases were five times more likely after laparoscopic tumour laceration than after the same procedure through an open incision (ten of 12 rats versus two of 12, P = 0·0033). Wound metastases following laparoscopic tumour manipulation are an important and real problem, with significant implications for the application of laparoscopic techniques to excise malignant disease in humans.
Vitamin D3 exacerbates intimal hyperplasia in balloon-injured arteries
Authors: Lamawansa M D , Wysocki S J , House A K , Norman P E
Published: March 2007

Although a high dose of vitamin D3 is known to cause arterial calcification and degeneration, its effect on intimal hyperplasia has never been studied. The aim of this study was to examine the influence of a moderate supplement of vitamin D3 on intimal hyperplasia in the balloon-injured rat carotid artery. Forty-four rats had balloon injury to the carotid artery; 22 were given oral vitamin D3 supplementation (0·25 μg kg−1 day−1). Animals were killed at 4 weeks and the carotid arteries were perfusion fixed and assessed morphometrically by means of computerized image analysis of transverse sections. Mean(s.e.m.) intimal area was significantly greater in the vitamin D3-treated animals than in controls: 0·92(0·05) versus 0·71(0·07) mm2 (P = 0·02). The area of the media of both injured and uninjured arteries was not influenced by vitamin D3 administration. A small dose of vitamin D3 resulted in significant exacerbation of intimal hyperplasia in this rat carotid artery model and raises the question of the role of dietary vitamin D3 in restenosis following vascular intervention.
Prognosis after surgery in patients with incurable rectal cancer: A population-based study
Authors: Mahteme H , Påhlman L , Glimelius B , Graf W
Published: March 2007

In a defined population between 1973 and 1992 151 patients with irresectable metastatic or local rectal cancer were identified. Eighty-one patients underwent resection of the primary tumour (group 1) whereas the primary tumour was left in situ in 70 patients (group 2). During the same time period, 444 patients underwent curative resection. The median survival was 7·5 months in group 1, and 3·5 and 1·9 months for surgically and non-surgically treated patients respectively in group 2. A colostomy for intestinal obstruction became necessary in 12 per cent of the patients with a retained primary tumour. Bilateral hepatic involvement, abnormal liver function test results, peritoneal growth or abdominal lymph node metastases correlated with a short survival (P < 0·01). These results support a selective approach to patients with incurable rectal cancer.
Coagulation and fibrinolytic responses of human peritoneal fluid and plasma to bacterial peritonitis
Authors: van Goor H , Bom V J J , van der Meer J , Sluiter W J , Bleichrodt R P
Published: March 2007

Significantly higher (P < 0·05) thrombin-antithrombin III complex levels were found in the abdominal exudate of patients with peritonitis (median 5500 ng/ml) than in that of controls (median 89 ng/ml). In patients, peritoneal fluid concentrations of tissue and urokinase-type plasminogen activator were increased by factors of 65 and 10 respectively (P < 0·05). The concentration of plasminogen activator inhibitor (PAI) 1 was increased by a factor of about 800 (median 395 versus 0·5 ng/ml, P < 0·05). Despite markedly raised concentrations of PAI, peritoneal fluid displayed fibrinolytic activity as demonstrated by significantly increased (P < 0·05) concentrations of plasmin-α2-antiplasmin complex (median 10 952 versus 57 ng/ml) and fibrin degradation products (median 40 360 versus 126 ng/ml). There was no correlation between plasma and peritoneal fluid concentrations. Intra-abdominal coagulation and fibrinolysis are stimulated in the abdominal cavity of patients with bacterial peritonitis.
Food intake after gastrectomy for gastric carcinoma: The role of a gastric reservoir
Authors: Liedman B , Andersson H , Berglund B , Bosaeus I , Hugosson I , Olbe L , Lundell L
Published: March 2007

Patients with carcinoma of the stomach who underwent curative resection were randomized to total gastrectomy (n = 49), total gastrectomy and an S-shaped gastric substitute (n = 28) or subtotal gastrectomy (n = 12); all had a Roux-en-Y reconstruction. The gastric substitute and gastric remnant allowed a volume of 400–500 ml to be installed without increments in basal pressures. The corresponding volume in the Roux limb was 100 ml. Energy intake was approximately 120 kJ/kg preoperative weight per day 3 months after operation, and then remained constant. Patients who had subtotal gastrectomy ate less (91·7 kJ/kg preoperative weight) 3 months after operation, but thereafter increased their intake. Patients allocated to have a gastric pouch or subtotal gastrectomy complained more frequently of adverse postprandial symptoms (P < 0·03) as a major cause of reduced calorie intake. The construction of a gastric reservoir did not improve nutritional adaptation after surgery for gastric carcinoma.
Protection by antibiotics against experimental focal cholangitis produced in mice by a schistosomicidal isothiocyanate
Authors: Batzinger Robert P. , Bueding Ernest , Popper Hans
Published: March 2007

Oral administration to mice of high doses of 4-isothiocyano-4′nitrodiphenylamine (amoscanate), a potent antischistosomal drug, produced focal necrotizing lesions of the large intrahepatic and extrahepatic bile ducts and the gallbladder. Coadministration of erythromycin and, to a somewhat lesser degree, of paromomycin, markedly reduced the effects of amoscanate on the biliary tract. These results suggest that amoscanate may be converted to a cholangiotoxic product by one or several constituents of the enteric bacterial flora. Since erythromycin does not affect the antischistosomal activity of amoscanate, coadministration of an antibacterial agent can reduce toxic effects of a drug while full chemotherapeutic activity is maintained. The possibility of toxic effects of metabolites of xenobioties produced by intestinal bacteria deserves attention and the experimental production of focal intrahepatic and extrahepatic cholangitis by such drug metabolites suggests a possible mechanism in human bile diseases.
Liver histopathology in chronic common bile duct stenosis due to chronic alcoholic pancreatitis
Authors: Afroudakis Angelos , Kaplowitz Neil
Published: March 2007

The liver histopathology in 40 liver biopsies from 24 patients with verified chronic common bile duct stenosis due to chronic alcoholic pancreatitis has been reviewed code-blinded. This represents an 8% prevalence of this complication in approximately 300 patients with alcoholic pancreatitis screened biochemically for alkaline phosphatase >two-fold for >1 month. The majority were anicteric with no symptoms other than from acute exacerbations of chronic pancreatitis. Biliary obstructive liver histopathology of varying severity was diagnosed in 19 patients (79%), seven of whom (29%) had secondary biliary cirrhosis. In 3 of these 7 cases, progression to biliary cirrhosis was documented with sequential biopsies. The remainder demonstrated this histologic picture when first diagnosed, supporting the insidious nature of this process. Stromal edema of the portal tracts, increased portal connective tissue, and marked proliferation of interlobular bile ducts and ductules were the most striking histologic features. Histologic cholangitis, although frequent, was generally mild or absent, reflecting the incomplete nature of the duct obstruction. Features of alcoholic liver disease were observed in only two cases. The results indicate that (1) chronic alcoholic pancreatitis with incomplete duct obstruction frequently causes secondary biliary cirrhosis, (2) significant alcoholic liver disease very infrequently coexists with persistent common bile duct stricture from alcoholic pancreatitis, and (3) surgical biliary decompression should be considered in any patient with documented persistent common bile duct stenosis from alcoholic pancreatitis.
Modulation of the transport of bilirubin and asialoorosomucoid during liver regeneration
Authors: Gärtner Ulrich , Stockert Richard J. , Morell Anatol G. , Wolkoff Allan W.
Published: March 2007

The normal rat hepatocyte divides approximately once per year but, following two thirds hepatectomy, rapid cellular replication occurs throughout the remaining liver remnant. Using a multiple indicator dilution technique, single-pass transport of 3H-bilirubin and 125I-asialoorosomucoid was studied in isolated perfused liver from 6hr to 6d after two thirds hepatectomy or sham surgery. Influx (k1), efflux (k2), and sequestration (k3) rates were quantitated by computer analysis. k1 for 3H-bilirubin fell by over 50% within 6hr after two thirds hepatectomy and returned to normal 4d later. k2 progressively decreased with a nadir at 2d, and returned to normal by 4d. k3 was transiently depressed, and became normal within 2d. Although hepatic uptake of asialoglycoproteins has been thought to be irreversible, the experimental data required k2 and k3 parameters for best fit. Similar to results for 3H-bilirubin, the k1 of 125I-asialoorosomucoid was 20% of normal at 1d after two thirds hepatectomy, and returned to normal by 6d. Unlike results for 3H-bilirubin, there was a prolonged 50% reduction of k2 and k3 with return to normal by 6d. The transport changes during regeneration are independent of reduced liver mass or changes in hepatic spaces of distribution. The fact that influx of both compounds reaches a nadir at the time of greatest cellular proliferation with subsequent return to normal suggests a „maturation” of liver cell function for restoration of these specific hepatocyte functions. Modulation of the hepatocyte receptor for desialylated glycoproteins may also be required for cellular recognition as a prerequisite for proliferative responses.
Effects of corticosteroids on bilirubin metabolism in patients with Gilbert’s syndrome
Authors: Ohkubo Hideki , Okuda Kunio , Iida Shinji
Published: March 2007

To elucidate the mechanism whereby corticosteroids decrease the serum bilirubin concentration, changes in bilirubin metabolism were studied in patients with Gilbert’s syndrome using a bilirubin load test and/or nicotinic acid test before and after corticosteroid treatment. Steroid administration increased hepatic clearance and uptake of bilirubin; the transfer rate for biliary excretion was unaffected. These results suggest that the main effect was enhancement of hepatic uptake or storage of bilirubin, which may be an important mechanism whereby corticosteroids reduce serum bilirubin concentrations in various liver disorders.
Urinary Coproporphyrin isomers in Rotor’s syndrome: A study in eight families
Authors: Shimizu Yoshitaka , Naruto Hiroshi , Ida Setsuko , Kohakura Masateru
Published: March 2007

Urinary coproporphyrin isomers were measured in 17 patients with Rotor’s syndrome, 65 phenotypically normal relatives of 14 patients from eight families, and 21 normal subjects. Coproporphyrin I was elevated in Rotor’s syndrome (p < 0.001) and, to a lesser degree, in phenotypically normal parents (p < 0.005), children, and siblings (p < 0.025) as compared to normal controls. Coproporphyrin III in patients, parents, and children did not differ from that in normal controls. Genetic analysis was consistent with transmission of Rotor’s syndrome as an autosomal recessive trait with respect to urinary excretion of coproporphyrin I. After i.v. injection of σ-aminolevulinic acid, urinary coproporphyrin I increased to a similar extent in Rotor’s syndrome and in normal subjects; urinary coproporphyrin III excretion was less in Rotor’s syndrome than in normal subjects.
Is there a regeneration stimulator substance in the effluent from perfused partially hepatectomized livers?
Authors: van Hoorn-Hickman Rosemary , Kahn Del , Green Jewel , Macleod Heather A. , Terblanche John
Published: March 2007

An attempt was made to transfer a stimulator substance from the perfusate of partially hepatectomized perfused livers to the portal stump of portacaval-shunted pig recipients. Blood was either cross-circulated with recipients during perfusion or was given by exchange tranfusion after 4 hr perfusion. There was an increase in thymidine kinase activity and mitotic indices in biopsies from portacaval-shunted recipients whether perfusions were performed 2 or 4 days after partial hepatectomy. Blood perfused through intact livers did not enhance the regenerative response of portacaval-shunted pigs; in fact it appeared to suppress the normal small response. Approximately 10% of the portacaval-shunted recipients died acutely when perfusate was infused into the portal stump. This did not occur if saline or unperfused blood was used suggesting that some toxic substance accumulated during liver perfusion. In end-stage fulminant hepatic failure, use of blood perfused through a partially hepatectomized animal liver may provide the regenerative stimulus which often appears to be lacking.
Immune regulation and HLA types in chronic hepatitis
Authors: Krawitt Edward L. , Albertini Richard J. , Webb Duane D. , Chastenay Bette F. , Holdstock Greg , Macpherson Bruce R.
Published: March 2007

Studies were undertaken in 32 patients with hepatitis B-negative or -positive chronic active hepatitis or chronic persistent hepatitis to define the relationship between immunoregulatory activity and the HLA-B8 and B12 phenotypes. Suppressor T-cell activity measured by a concanavalin A-induced suppressor system using allogeneic responder cells was dependent on which individual was selected as a source of responder cells. No differences were noted using isogeneic cells as responders. Suppressor T-cell activity measured by the effect of a noninduced suppressor cell on a mixed leukocyte culture was not different from controls. Increased prostaglandin-producing suppressor cell activity was found in patients with hepatitis B-negative (p < 0.005) and hepatitis B-positive (p < 0.05) chronic active hepatitis. When results of the suppressor activities were compared among patients with chronic hepatitis dependent on the presence of HLA-B8, B12, or neither of these phenotypes, no significant differences were present. These results provide further evidence of altered immunoregulatory function in patients with chronic active hepatitis, which may reflect increased suppression by a population of prostaglandin-producing suppressor cells. The results do not, however, suggest that a gene coding for altered immune regulation is linked to HLA-B8 or B12.
A constitutional unconjugated hyperbilirubinemia combined with indocyanine green intolerance: A new functional disorder?
Authors: Ohkubo Hideki , Okuda Kunio , Iida Shinji
Published: March 2007

The kinetics of plasma clearance of indocyanine green and bromosulfophthalein were studied in 49 consecutive patients with chronic unconjugated hyperbilirubinemia. Forty-four patients had Gilbert’s syndrome whereas five patients had impaired hepatic uptake of indocyanine green and virtually normal hepatic bromosulfophthalein uptake. There was no difference in bilirubin metabolism between the two groups. A family study of the patients with impaired indocyanine green uptake revealed that the defect appears to be transmitted as an autosomal dominant trait associated with inheritance of impaired bilirubin metabolism. These patients manifest a novel disorder of organic anion transport which, like Gilbert’s syndrome, is also characterized by chronic mild unconjugated hyperbilirubinemia.
Choleretic effect of valproic acid in the rat
Authors: Watkins John B. , Klaassen Curtis D.
Published: March 2007

Valproic acid (VPA) is an anticonvulsant agent which produced marked choleresis in the rat. Bile flow rate increased from 50 to 60 μl per min per kg to 120 to 145 μl per min per kg immediately after i.v. injection of VPA (37.5 to 150 mg per kg; 2 ml per kg) in male Sprague-Dawley rats. The duration of maximal bile flow was dose-dependent and increased from 30 min (37.5 mg VPA per kg) to approximately 2 hr (150 mg VPA per kg). Choleresis diluted the biliary concentrations of bile acids, Cl−, cholesterol, and phospholipids. VPA did not change the bile/plasma ratio for erythritol suggesting that the increased bile flow is of canalicular origin. VPA did not influence the excretion of bile acids or their osmotic activity, whereas bile salt-independent flow doubled in rats treated with 150 mg VPA per kg. The bile/plasma, bile/liver, and liver/plasma concentration ratios for VPA were 11.7, 1.6, and 7.3, respectively. Approximately 90% of VPA appearing in bile was biotransformed, primarily as a glucuronide. Bile flow correlated with VPA excretion; 16 μl of bile was produced per μmole VPA which suggests that choleresis is primarily due to the osmotic activity of VPA metabolites in bile. VPA enhanced the excretion of inorganic ions which may also contribute to choleresis. Biliary excretion of phenol-3,6-dibromophthalein disulfonate and ouabain was unaffected. Thus, VPA is an effective choleretic which stimulates bile salt-independent flow of canalicular origin largely as a consequence of the osmotic properties of VPA conjugates in bile.
A controlled clinical trial of the efficacy of the hepatitis B vaccine (heptavax B): A final report
Authors: Szmuness Wolf , Stevens Cladd E. , Zang Edith A. , Harley Edward J. , Kellner Aaron
Published: March 2007

A controlled, randomized, double-blind trial in 1,083 homosexual men from New York confirmed that a highly purified, formalin-inactivated vaccine against hepatitis B prepared from HBsAg positive plasma, is safe immunogenic, and highly efficacious. Over 95% of vaccinated subjects developed antibody against the surface antigen. Vaccine-induced antibody persisted for the entire 24-month follow-up period. The attack rate of all hepatitis B virus infections (excluding conversions of anti-HBc alone) was 3.2% in vaccine recipients compared with 25.6% in placebo recipients (p < 0.0001). In those who received all three doses of vaccine, of 40 μg each, the protective efficacy rate was close to 100%. The vaccine protects against acute hepatitis B, asymptomatic infection, and chronic antigenemia. There is reason to assume that the vaccine is also partially effective when given postexposure.
Electron microscopic studies of Dane particles in hepatocytes with special reference to intracellular development of Dane particles and their relation with HBeAg in serum
Authors: Kamimura Tomoteru , Yoshikawa Akira , Ichida Fumihiro , Sasaki Hiroshi
Published: March 2007

Electron microscopic observations in 30 cases of HBsAg positive liver disease and 12 asymptomatic carriers of HBsAg suggested the following mechanism of intracellular development of Dane particles: core particles migrated from the nucleus into the cytoplasm through the nuclear pores. Intracytoplasmic core particles protruded into the cisternae of endoplasmic reticulum by budding the outer coat of Dane particles being derived from the membrane of endoplasmic reticulum. Release of Dane particles into the blood stream by reversed pinocytosis was suggested by the finding of submembranous localization of endoplasmic reticulum containing these particles. No budding from the cell surface of the hepatocytes was encountered. Dane particles in the hepatocytes were detected in 14 of 15 cases positive for serum HBeAg while no particles were seen in 27 HBeAg negative cases, thus suggesting that serum HBeAg reflected ongoing replication of hepatitis B virus in the hepatocytes.
The risk of hepatitis B transmission from staff to patients in hemodialysis units--an overrated problem?
Authors: LaBrecque Douglas R. , Dhand Arun K.
Published: March 2007

The staff and patients in hemodialysis units have the greatest hospital risk of acquiring hepatitis B (HB) infection. We followed the patients of two dialysis nurses in two different dialysis units. One nurse dialyzed 19 patients a total of 50 times during the prodrome of acute HB. The second nurse was a known, asymptomatic carrier of HBsAg who was also HBeAg(+) and anti-HBc(+). Over a 2-year period, she dialyzed 30 patients a total of 742 times. Neither group of patients showed evidence of having acquired HB, suggesting that the risk of HB transmission from staff to patient is low even in the high-risk setting of a dialysis unit and a presumably highly infectious HBeAg(+) chronic carrier. In our study, the risk in this latter setting was less than 0.0040 (binomial probability p < 00.05). The data do not support restricting care of patients by health workers who are chronic carriers of the virus.
The hepatocellular uptake and biliary excretion of endotoxin in the rat
Authors: Maitra Shyamal K. , Rachmilewitz Daniel , Eberle David , Kaplowitz Neil
Published: March 2007

Endotoxin is known to cause a dose-dependent impairment of hepatic bile secretion, organic anion excretion, and activity of Na+, K+-activated ATPase. Since it is possible that this impaired excretory function is a result of direct interaction of endotoxin with hepatocytes, we examined: (a) the excretion of endotoxin into bile, and (b) its association with an hepatocyte-enriched, Kupffer cell-depleted population of liver cells. Escherichia coli 0127:B8 endotoxin (17 to 54 μg per 100 gm body weight) was given i.v. to male Sprague Dawley rats and bile collected up to 48 hr. The expected significant decrease in bile secretion was seen, confirming the biological effectiveness of the endotoxin. Endotoxin was quantitated by a gas chromatography/mass spectroscopy method which detects the β-hydroxymyristic acid in the lipid A moiety of endotoxin. Approximately 7% of the administered dose of endotoxin was recovered as β-hydroxymyristic acid in bile in the 48 hr following injection. Approximately two thirds of the administered dose of endotoxin was recovered as β-hydroxymyristic acid in the whole liver. Further analysis of the β-hydroxymyristic acid in bile and liver by Folch extraction and thin-layer chromatography was performed. The β-hydroxymyristic acid in bile was associated with polar and nonpolar metabolites of endotoxin. The β-hydroxymyristic acid recovered in the liver distributed similarly in Folch extraction to intact endotoxin added in vitro. Endotoxin quantitated as β-hydroxymyristic acid was measured in whole liver homogenate and hepatocyte-enriched preparations 3 hr following i.v. administration. The mass abundance by gas chromatography/mass spectrometry of β-hydroxymyristic acid per 106 hepatocytes was similar in crude liver homogenate and the hepatocyte-enriched fractions indicating the presence of substantial amounts of β-hydroxymyristic acid in association with parenchymal liver cells. Thus, our studies indicate that the bulk of the β-hydroxymyristic acid of endotoxin given i.v. to rats is found in hepatocytes in a form suggesting minimal degradation of the endotoxin. A small proportion of the β-hydroxymyristic acid associated with the endotoxin in the liver is then released slowly into bile as a complex mixture of polar and nonpolar metabolites of endotoxin.
Acute effects of ethanol on hepatic uptake and distribution of narcotics in the isolated perfused rabbit liver
Authors: Kreek Mary Jeanne , Rothschild Marcus A. , Oratz Murray , Mongelli Joseph , Handley Anne C.
Published: March 2007

This study was performed as an initial step in systematically defining the hepatic interactions between ethanol and opioids using a controlled in vitro system. The acute effects of ethanol on the initial uptake and distribution of long- and short-acting narcotics were studied using isolated rabbit liver perfused with rabbit blood without or with ethanol. A pulse injection of 1.5 mg of 14C-labeled narcotic [methadone, 1-α-acetylmethadol (LAAM), morphine, or meperidine] was made into the portal vein cannula followed by perfusion for 2 min. Radioactivity was determined in liver homogenates and subcellular fractions; methadone and its metabolites were measured by thin-layer chromatography with zonal scanning in each fraction. Ethanol preperfusion and concomitant ethanol perfusion did not effect hepatic uptake of methadone, LAAM, morphine, or meperidine. Although subcellular localization of morphine and meperidine differed from that of methadone and LAAM, perfusion with ethanol did not alter the acute hepatic uptake and distribution of any of the narcotics. These findings suggest that acute exposure to ethanol does not alter the acute hepatic disposition of narcotics.
Hepatocyte and Kupffer cell functions during liver regeneration in streptozotocin-diabetic rats
Authors: Cornell Robert P. , Hinck Brenda K. , Halley Randall E.
Published: March 2007

The insulinoprivic influence of acute severe streptozotocin diabetes on liver regeneration in rats was evaluated by determining liver weights as well as hepatocyte and Kupffer cell functional capacities. Functional capacities were assessed by bromosulfophthalein uptake for hepatocytes and carbon phagocytosis for Kupffer cells. Evaluation immediately after partial hepatectomy revealed a 66% reduction of liver mass, a 63% decrease in hepatocyte bromosulfophthalein removal, and a 65% decline in Kupffer cell carbon phagocytosis. Per cent recovery at 48-hr posthepatectomy was considerably greater for carbon phagocytosis than for bromosulfophthalein removal by regenerating livers. This apparent difference in functional recovery was likely due in part to enhanced non-Kupffer cell carbon phagocytosis. No significant differences of the three regeneration indices were noted for untreated streptozotocin-diabetic rats compared to nondiabetic animals. However, insulin administration to fasted streptozotocin diabetics significantly stimulated liver regeneration above that of untreated fasted rats and almost equivalent to that of pair-fed animals. Fasted rats had in general slower liver regeneration than pair-fed animals as expected. Furthermore, insulin administration to fasted nondiabetic rats after partial hepatectomy caused severe hypoglycemia and resulted in a further depression of liver regeneration.
Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis†
Authors: Knodell Robert G. , Ishak Kamal G. , Black William C. , Chen Thomas S. , Craig Robert , Kaplowitz Neil , Kiernan Thomas W. , Wollman Jerome
Published: March 2007

A Histology Activity Index has been developed which generates a numerical score for liver biopsy specimens obtained from patients with asymptomatic chronic active hepatitis. Biopsies are graded in four categories: periportal necrosis, intralobular necrosis, portal inflammation, and fibrosis. Under code, three pathologists and three hepatologists evaluated 14 liver biopsy specimens obtained from five patients with asymptomatic chronic active hepatitis. Good correlation was seen between severity of liver biopsy lesions as judged by conventional histological descriptions and Histology Activity Index scores. Significant differences in Histology Activity Index score occurred in only 2 of 28 duplicate scorings of biopsy specimens by two observers. This system provides definitive endpoints for statistical analysis of serial changes in liver histology and offers an alternative to the use of conventional pathological descriptions in following the natural history and treatment responses of asymptomatic chronic active hepatitis.
Biliary excretion of sulfobromophthalein compounds in normal and mutant corriedale sheep. Evidence for a disproportionate transport defect for conjugated sulfobromophthalein
Authors: Barnhart James L. , Gronwall Ronald R. , Combes Burton
Published: March 2007

Biliary excretion of dye was evaluated in three normal and one mutant Corriedale sheep (characterized by depressed biliary transport of many organic anions) during infusion of unconjugated sulfobromophthalein (BSP) and its preformed glutathione conjugate (BSP-GSH). Maximal dye excretion rates in bile in normal sheep were higher when BSP-GSH rather than BSP was administered. In confirmation of earlier studies, dye excretion in bile was markedly depressed in the mutant animal. However, movement of unconjugated BSP from liver cells into bile remained relatively intact whereas transport of conjugated BSP compounds was virtually absent. Preservation of unconjugated dye entry into bile suggests the presence of a transport mechanism for unconjugated BSP which is preserved in mutant sheep and is distinct from that involved in BSP-GSH excretory transport. Renal clearance of conjugated BSP compounds was greater than of unconjugated BSP and clearance values were comparable in the normal and mutant sheep. Thus, no excretory defect comparable to that present in liver was identifiable in the kidney.
Balloon dilatation of stenotic portacaval anastomosis
Authors: Bredfeldt James E. , Pingoud Erik G. , Groszmann Roberto J. , Tilson David M. , Conn Harold O.
Published: March 2007

Hemorrhage from esophageal varices is an infrequent occurrence after a portacaval anastomosis. A stenotic portacaval anastomosis resulted in persistent portal hypertension and variceal hemorrhage. Treatment by transluminal balloon dilatation of the stenotic shunt resolved the hemodynamic abnormality as demonstrated by angiographic and hemodynamic techniques.
Dane particle DNA polymerase and HBeAg: Impact on clinical, laboratory, and histologic findings in hepatitis B-associated chronic liver disease
Authors: Andres Ljudevit L. , Sawhney Vinod K. , Scullard George H. , Smith Joseph L. , Merigan Thomas C. , Robinson William S. , Gregory Peter B.
Published: March 2007

Fifty patients with chronic HBs antigenemia and Dane particle-associated DNA polymerase and HBeAg in their serum were contrasted to 46 HBsAg positive patients who had neither serum DNA polymerase or HBeAg. The time from acute onset and the duration of antigenemia were longer in patients who were DNA polymerase and HBeAg negative than in those who had both serum markers. Cirrhosis, hypoalbuminemia, and sequelae of chronic liver disease were more common in DNA polymerase, HBeAg negative patients than in those who were positive. These findings are consistent with the hypothesis that active viral replication is an early, albeit prolonged stage in the development of advanced HBsAg-associated liver disease.
Alcoholic liver disease: I. Interrelationships among histologic features and the histologic effects of prednisolone therapy
Authors: Boitnott John K. , Maddrey Willis C.
Published: March 2007

Interrelationships among histologic features of alcoholic liver disease were studied in 24 chronic alcoholics who took part in a double-blind, controlled trial of prednisolone vs. placebo therapy. Each patient underwent liver biopsy at the start and upon completion of the 1-month study. Although all patients had a clinical diagnosis of alcoholic hepatitis and had at least mild alcoholic hepatitis with alcoholic hyalin in their initial liver biopsy specimens, each of the histologic features studied (fat accumulation, bile stasis, alcoholic hyalin, acute inflammation, active intralobular fibrosis, chronic inflammation, bile duct proliferation, established fibrosis, and parenchymal nodularity) covered a wide spectrum of severity.

Relationships of the severities of the individual histologic features were studied within the initial biopsy specimens and between the pre- and posttreatment biopsies. Four major histopathologic categories were evident in the correlation patterns: fat accumulation; cholestasis; alcoholic hepatitis, and cirrhosis. While having common pathogenetic ties and thus often occurring together, the severities of these categories in a given patient at a given time were little related and they are best considered as separate features of alcoholic liver disease. The amount of alcoholic hyalin appeared to be the best single indicator of the severity of alcoholic hepatitis in these patients and was the best predictor in the pretreatment biopsies of the amounts of hepatocellular injury, active fibrosis, acute inflammation, and total inflammation in the posttreatment biopsy specimens. Active fibrosis and hepatocellular injury in turn appeared to be the most immediate precursors of established fibrosis and parenchymal nodularity. Bile duct proliferation was, in part, a reflection of cholestatic disease and, in part, a more nonspecific reflection of chronic alcoholic liver injury, correlating with the amount of established fibrosis. The relationship of chronic inflammation to other histologic features was complex, but probably included an intralobular component related to the severity and stage of alcoholic hepatitis and another, more nonspecific, component related to the amount of established fibrosis or bile duct proliferation.

One month of prednisolone therapy (40 mg per day) significantly decreased the amount of inflammation, but did not have a comparable effect on hepatic fibrosis.

The statistical methods used in this study to investigate the multiple interrelationships among histologic features are useful in evaluating potential pathogenetic relationships and are quite helpful in assessing the effects of treatment.
Morphometric study of the esophageal mucosa in cirrhotic patients with variceal bleeding
Authors: Ponce Julio , Froufe Agustin , de la Morena Eduardo , Mir José , Rayón Miguel , Pina Ramón , Berenguer Joaquin
Published: March 2007

A morphometric study of the distal esophageal mucosa (within 5 cm above the gastroesophageal junction) has been carried out in a group of 11 cirrhotic patients undergoing esophageal transection with SPTU gun for variceal bleeding. The relative thickness of the papillae (62.2 ± 3.9%) and basal zone (11.8 ± 1.9%) were within normal limits. Polymorphonuclear infiltrates were not found either in the lamina propria or in the epithelium. The absence of histopathologic changes in the esophageal mucosa from patients with liver cirrhosis and bleeding esophageal varices confirms the hypothesis that gastroesophageal reflux does not play a pathogenic role in the development of variceal bleeding.
A Retrospective Study of the Role of Delta Agent Infection in Children With Hbsag–Positive Chronic Hepatitis
Authors: Maggiore Giuseppe , Hadchouel Michelle , Sessa Fausto , Vinci Maria , Craxi Antonio , Marzani Maria D. , De Giacomo Constantino , Alagille Daniel
Published: March 2007

The prevalence of intrahepatic delta antigen and/or anti–delta antibody was retrospectively investigated in 102 children with chronic HBsAg–positive hepatitis who were seen consecutively in three medical institutions between 1974 and 1982. Delta infection markers were found in 13 patients (12.7%) who exhibited high serum titers of anti–delta antibody; intrahepatic delta antigen was detected in ten. Eleven of the 13 children had severe progressive liver disease associated in all but one with absence of hepatitis B virus replication as evaluated by analysis of serum hepatitis B virus DNA. The factors which seem to increase the risk of delta infection in children who are hepatitis B virus carriers are geographic origin, a history of exposure to blood derivatives and age. A further 37 of 102 children had chronic active hepatitis (20 patients) or cirrhosis (17 patients) without evidence of delta infection. These results indicate that delta infection occurs in children with chronic hepatitis. This possibility should be considered in investigation of children with HBsAg–positive chronic liver disease. Although the delta agent is an important cause of progressive liver disease in children who are chronic HBsAg carriers, severe liver injury and especially cirrhosis can occur without evidence of delta infection.
Hepatitis B Virus Dna in Serum From Patients With Acute Hepatitis B
Authors: Krogsgaard Kim , Kryger Peter , Aldershvile Jan , Andersson Poul , Brechot Christian
Published: March 2007

Sera from 77 consecutive patients with acute type B hepatitis were examined for hepatitis B virus DNA (HBV DNA) by a spot hybridization method. The median follow–up time was 8 months (range, 1 week to 3 years). HBV DNA was detected in 26 (34%) patients on admission to the hospital. A significant positive correlation was found between short duration of symptoms and the presence of HBV DNA (p < 0.025). Twenty–four (46%) of 52 HBeAg–positive patients were HBV DNA positive compared to 2 HBV DNA–positive patients of 25 HBeAg–negative patients (8%) (p < 0.001). Four HBeAg–negative patients had serum HBV DNA initially or during follow–up; three had anti–HBe. Six of 77 patients with acute type B hepatitis (8%) became chronic HBsAg carriers, and HBV DNA was detectable from 5 months to more than 3 years after onset of symptoms. The presence of serum HBV DNA for more than 8 weeks after initial symptoms may predict development of a chronic HBsAg carrier state. In none of the chronic carriers was serum HBV DNA present after clearing of HBeAg.
Effect of Endotoxin on Fibronectin and Kupffer Cell Activity
Authors: Richards Peter S. , Saba Thomas M.
Published: March 2007

The phagocytic activity of the reticuloendothelial system (RES) in the liver is important in host resistance to shock. Fibronectin is a large molecular weight glycoprotein which influences particulate uptake by phagocytic cells. This study addressed the effect of repeated low–dose endotoxin challenge on immunoreactive fibronectin and reticuloendothelial phagocytic function in rats. Intravenous Escherichia coli endotoxin increased circulating immunoreactive fibronectin by 100% within 24 hr; normalization was within 96 hr. Elevated fibronectin levels at 48 hr were associated with increased plasma opsonic activity as tested by liver slice phagocytic assay and RES stimulation, and in vitro uptake of gelatinized target particles by Kupffer cells in liver slices from endotoxin treated rats was significantly increased. Endotoxin tolerance was produced by repeated low dose challenge with endotoxin for 7 days and was associated with RES stimulation, even though the circulating fibronectin concentrations had returned to normal. By immunofluorescence, insoluble fibronectin was widely distributed in the liver in a pattern analogous to the sinusoidal vascular network. We suggest that increased RES phagocytic activity after low dose endotoxin challenge is due to early elevation of plasma fibronectin and cellular stimulation of phagocytic function followed by a sustained stimulation of Kupffer cells in the presence of normal fibronectin levels. Both cellular and humoral factors may contribute to increased Kupffer cell phagocytic activity during endotoxin tolerance.
A Radioimmunoassay Procedure for Type Iii Procollagen: Its Use in the Detection of Hepatic Fibrosis
Authors: Galambos Michael R. , Collins Delwood C. , Galambos John T.
Published: March 2007

Recent studies suggest that the serum level of Type III procollagen (PC–III) could be a valuable, noninvasive monitor of hepatic fibrogenesis. We have developed a sensitive and specific radioimmunoassay for PC–III procollagen isolated and purified from fetal goat skin which shows high cross–reaction for human PC–III. In a double–blind study, serum samples taken from 8 normal volunteers and 50 patients at the time of liver biopsy were assayed for PC–III. Each biopsy was reviewed without knowledge of the radioimmunoassay results, and old or active fibrosis was graded on a 0 to 3 (none, minimal, moderate, severe) scale. There was a significant difference between serum concentrations of PC–III in normals (mean ± S.D. = 72 ng per ml ± 8) as compared to patients with biopsy evidence of active fibrosis (mean ± S.D. = 153 ng per ml ± 12; p < 0.001). The serum concentration of PC–III showed a good correlation (r = 0.58; p < 0.001) with the histological grade of active lobular fibrosis. Measurement of PC–III is a noninvasive test for detection of active fibrosis in the liver.
Prevalence of Hbeag and Anti–Hbe in Chronic Active Hepatitis, Cirrhosis and Primary Hepatocellular Carcinoma in Korea
Authors: Kim Chung-Yong , Bae Soon-Kee , Hann Hie-Won L. , London Thomas W. , Blumberg Baruch S.
Published: March 2007

The prevalence of HBeAg was studied in Korean patients with chronic active hepatitis, cirrhosis and primary hepatocellular carcinoma. There is an independent association of HBeAg prevalence with age and diagnosis. These findings are discussed in terms of a developmental model for primary hepatocellular carcinoma which could explain the lower frequency of HBeAg in the cancer cases.
Effect of Parenteral Amino Acid Supplementation in Alcoholic Hepatitis
Authors: Diehl Anna Mae , Boitnott John K. , Herlong Franklin H. , Potter James J. , Van Duyn Mary Ann , Chandler Elizabeth , Mezey Esteban
Published: March 2007

A controlled randomized study was performed in 15 patients with biopsy–proven alcoholic hepatitis to determine the effect of the administration of a parenteral amino acid–glucose solution for 1 month on nutritional, clinical, biochemical and histological parameters. All patients were allowed ad libitum consumption of a hospital diet. Five patients received the amino acid–glucose solution, while 10 received the glucose solution without amino acids. There was more improvement in nitrogen balance in the treated group than the control group. However, amino acid therapy was no more beneficial than control therapy in improving creatinine–height index, arm muscle area, arm fat area, and plasma levels of retinol binding proteins, prealbumin and pyridoxal–5′–phosphate. Clinical and biochemical markers of liver disease improved in both groups. This improvement in composite clinical index was more rapid in the treated than in the control group, but this early advantage was no longer apparent at the end of one month. Hepatocellular necrosis, inflammation and fat improved in the entire group. Amino acid treatment resulted in a greater resolution of fatty infiltration, but did not otherwise affect hepatic histology. Hepatocellular necrosis and inflammation in both the initial and final liver biopsies were highly correlated with nitrogen balance on admission. Initial clinical index correlated with the quantity of ethanol consumption prior to admission but not with liver injury on biopsy. However, by the end of the study, clinical index correlated with hepatocellular necrosis and inflammation. It is concluded that the clinical syndrome of alcoholic hepatitis is heavily influenced initially by metabolic consequences of alcohol consumption and that it is the resolution of this alcohol effect that is most influenced by parenteral amino acid supplementation.