Intracerebral Whipple''s disease diagnosed by stereotactic biopsy: a case report and review of the literature

We studied the effects of bile stasis in a guinea pig model of pigment gallstone. The common bile ducts of guinea pigs were partially ligated, and the guinea pigs killed one or two weeks later. Biliary sludge or stones were examined with the Fourier transform infrared spectroscopy and the scanning electromicroscopy. The bile was analyzed for pH, free calcium, bile acids and bilirubin fractions, and the activities of both bacterial and endogenous beta-glucuronidase. After bile duct ligation, calcium bilirubinate precipitates or stones formed in all except one of the animals studied. The bile pH and the proportion of unconjugated bilirubin rose after bile duct ligation, with a concomitant fall of bilirubin monoglucuronide. The activity of bacterial beta-glucuronidase decreased after ligation, while the activity of endogenous beta-glucuronidase rose at week 2. Our results imply that precipitation of calcium bilirubinate in this animal model was induced by an increased bile pH and the nonenzymatic hydrolysis of conjugated bilirubin.     

The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo

BACKGROUND & AIMS: Hydrophobic bile acids have been implicated in the pathogenesis of cholestatic liver injury. The hypothesis that hydrophobic bile acid toxicity is mediated by oxidant stress in an in vivo rat model was tested in this study. METHODS: A dose-response study of bolus intravenous (i.v.) taurochenodeoxycholic acid (TCDC) in rats was conducted. Rats were then pretreated with parenteral alpha-tocopherol, and its effect on i.v. TCDC toxicity was evaluated by liver blood tests and by assessing mitochondrial lipid peroxidation. RESULTS: Four hours after an i.v. bolus of TCDC (10 mumol/100 g weight), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels peaked, hepatic mitochondria showed evidence of increased lipid peroxidation, and serum bile acid analysis was consistent with a cholestatic injury. Liver histology at 4 hours showed hepatocellular necrosis and swelling and mild portal tract inflammation. Treatment with parenteral alpha-tocopherol was associated with a 60%-70% reduction in AST and ALT levels, improved histology, and a 60% reduction in mitochondrial lipid peroxidation in rats receiving TCDC. CONCLUSIONS: These data show that hepatocyte injury and oxidant damage to mitochondria caused by i.v. TCDC can be significantly reduced by pretreatment with the antioxidant vitamin E. These in vivo findings support the role for oxidant stress in the pathogenesis of bile acid hepatic toxicity.     

Radiology of skeletal tuberculosis

The process of hepatic fibrosis, and the changes in contents of hepatic hyproxyproline (HYP) and serum procollagen type III peptide (PIIINP) were examined in two rat models for hepatic fibrosis, i.e. bile duct ligation/scission (BDL/s)- and dimethylnitrosamine (DMN)-induced models. In addition, an expression of type III collagen mRNA in the liver of BDL/s model was also examined. In BDL/s model, hepatic fibrosis started at 2 weeks after operation (WAO) and cirrhosis with prominent bile duct hyperplasia was detected at and after 5 WAO. Serum PIIINP content measured using a modified double armed inhibition enzyme-linked immunosorbent assay (ELISA) method proposed by us started to increase at 1 WAO and continued to increase thereafter. Hepatic HYP content measured colorimetrically started to increase at 3 WAO and it continued to increase until 7 WAO. An expression of type III collagen mRNA in the liver was enhanced at and after 2 WAO, especially at 4 and 5 WAO. In DMN model, marked hepatic fibrosis was detected at 1 week after the last DMN administration (WAA), and the degree of fibrosis was apparently reduced at 4 WAA. Serum PIIINP content prominently increased at 1 WAA and decreased at and after 3 WAA. Hepatic HYP content showed a marked increase at 1 WAA and decreased thereafter. The present results indicated that the sequences of hepatic fibrosis, hepatic HYP content and serum PIIINP content were well correlated with each other in both BDL/s and DMN models. In conclusion, ELISA system for the detection of serum PIINP content is considered to be reliable method for assessment of cirrhotic liver, and the present two rat models for liver fibrosis/cirrhosis seems to be a good tool for researching antifibrotic agents.     

Endothelin A-receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis

BACKGROUND & AIMS: Endothelin 1 is considered to be an important regulator of sinusoidal blood flow and increases during endotoxemia. The purpose of this study was to investigate the role of endothelin 1 in hepatic microcirculation, oxygen transport, and liver injury during endotoxemia. METHODS: Male Sprague-Dawley rats were continuously infused with 2.5 mL/h of saline, 0.8 mg . kg-1 . h-1 of lipopolysaccharide (LPS), 3 mg . kg-1 . h-1 of BQ-485, an endothelin A-receptor antagonist, or LPS plus BQ-485 for 7 hours. RESULTS: BQ-485 infusion had no significant effect on hepatic microcirculation and liver injury. LPS increased the plasma levels of aspartate aminotransferase (AST) and total bilirubin and decreased the hepatic adenosine triphosphate (ATP) level and bile flow rate. LPS + BQ-485 infusion further increased the plasma levels of AST and total bilirubin and decreased the bile flow rate and the hepatic ATP level. Dual-spot microspectroscopy revealed mild decreases in sinusoidal erythrocyte velocity and oxygen transport in the LPS group and profound decreases in these parameters in the LPS + BQ-485 group. Histological examinations revealed massive necrotic changes in the pericentral regions of the LPS + BQ-485 group. CONCLUSIONS: These results suggest that blockade of endothelin A receptors disturbs hepatic microcirculation and oxygen transport and aggravates the necrotic injury induced by endotoxin.     

Treatment of extrahepatic occlusive jaundice with activated charcoal hemoperfusion in dogs

To find the feasibility of treatment for congenital bile duct atresia, we studied the usefullness of extracorporeal hemoperfusion over activated charcoal in canine obstructive jaundice. One, three and five weeks after ligation and disection of common bile duct in 5 dogs we performed the hemoperfusion over activated charcoal extracorporeally (group 3). In this animals we examined hematological and blood coagulation studies, serum electrolyte levels, kidney function tests and liver chemistries. As control in 5 animals we carried out after sham operation the perfusion without common bile duct ligation (group 2) and in 5 animals only common bile duct ligation without perfusion (group 1). In the liver chemistries we found 2 weeks after 2nd and 3rd perfusion (5 and 7 weeks after bile duct ligation) lower levels of serum bilirubin, GOT, GPT and SDH in treated group than in non-treated jaundiced animals. It suggest the effectiveness of hemoperfusion with activated charcoal in the treatment of occlusive jaundice. There were no alteration in the hematological studies, serum electrolyte levels and kidney function tests. PT and PTT was prolonged in the jaundiced animals there were no significant differences with and without hemoperfusion.     

Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and urinary prostaglandin levels in rats with obstructive jaundice

BACKGROUNDS/AIMS: No study has so far been conducted to clarify whether the presence of hyperbilirubinemia is detrimental to liver and renal functions. In the present study, the effects of polyethylene glycol-modified bilirubin oxidase (PEG-BOX) therapy on liver and renal function tests, hepatic energy charge and urinary prostaglandin levels were evaluated in a rat model of obstructive jaundice. METHODS: Sprague-Dawley rats were used in the experimental model of obstructive jaundice. PEG-BOX or an equivalent amount of PEG alone was intravenously injected into the animals and sampling of blood and urine, and liver harvesting were done sequentially after bile duct ligation. RESULTS: Conventional liver function tests showed no difference between PEG-BOX and control groups. However, bilirubin concentrations in the peripheral blood and liver tissue specimens markedly decreased, and the hepatic energy charge significantly increased in the PEG-BOX group as compared to controls. The blood concentration of bile acid was lower, but its urinary excretion was higher in the PEG-BOX group than in the control group. In vitro incubation of PEG-BOX with serum from rats with obstructive jaundice decreased the concentration of bilirubin but not that of bile acid. The urinary levels of prostaglandin E2 and the thromboxane B2/6-keto-prostaglandin Fla ratio were significantly lower in the PEG-BOX group than in the control group. CONCLUSIONS: The systemic reduction of bilirubin concentration may contribute to normalization of the urinary levels of prostaglandins and thromboxane B2, to decrease in serum bile acid levels, and to improvement of the hepatic energy charge in obstructive jaundice. These findings suggest that preoperative improvement of jaundice may be beneficial to patients with obstructive jaundice.     

Operative cholangiography and special technical consideration in the management of severe injury of the liver

The majority of hepatic injuries can be adequately managed by control of bleeding locally at the site, debridement and ample drainage. In some instances, severe blunt trauma and high velocity missile wounds may result in the disruption of intrahepatic structures and significant devitalization of the parenchyma of the liver, necessitating hepatic resection. Operative cholangiography was found to be useful in the evaluation and management of this type of severe injury to the liver. It is simple, practical method to recognize and localize a major disruption of the parenchyma of the liver and bile ducts; to help decide whether or not segmental, sublobar or labor hepatectomy should be performed, and to detect bile leaks from the divided bile ducts after resection of the liver. A modified technique for performing hepatic resection during an emergency situation was suggested to be more suitable than the classic technique. This is based on finger dissection along the line of injury and individual ligation of bile ducts and vessels as they are exposed within the parenchyma of the liver instead of isolation and ligation of the main inflow vessels and of the major ducts at the hilus and retrohepatic ligation of the hepatic veins.     

Safety standards for stab-resistant body armour: a computer tomographic assessment of organ to skin distances

Biliary drainage has long been called the Achilles' heel of liver transplantation, and biliary complications compromise the success of liver transplantation by increasing graft loss and the rates of a required second operation, morbidity, and mortality. One cause of complications is unrecognized anomalous biliary anatomy. We examined 73 intraoperative donor duct cholangiograms (IODDCs) to assess our ability to identify biliary anomalies intraoperatively. Normal anatomy was seen in 42% (31/73); some part of the right-sided biliary system drained into the left bile duct in 22% (16/73); trifurcated systems with a single branch point for the right posterior, right anterior, and left ducts appeared in 16% (12/73); low insertion of a right segmental duct to the hepatic duct was seen in 11% (8/73); and drainage of a right segmental duct into the cystic duct or into the hepatic duct at the cystic duct origin was noted in 8% (6/73). It was believed that the last group represented a condition that dictated extra caution in biliary reconstruction. The incidence of radiographic recognition of these anomalies was more than twice the clinical recognition in our patient population, implying that many such "problem" ducts usually go unrecognized. IODDCs facilitate training of transplant fellows. Costs are low, and morbidity is nil.     

The efficacy of FP 736-04 in experimental liver cirrhosis

PURPOSE: To determine whether the uptake of FP 736-04, a hepatocyte-specific CT contrast agent, is influenced by cirrhotic changes in the liver. MATERIAL AND METHODS: Liver cirrhosis was induced by bile duct ligation (BDL) in Sprague-Dawley rats. Seventy-four animals were divided into three groups comprising: rats with acute BDL; rats with chronic BDL; and normal controls. CT was performed after i.v. infusion of FP 736-04 or saline at a dose of 2 ml/kg b.w., and the mean attenuation in the liver and spleen was measured. The livers from the chronic BDL group were taken for histopathological examination and the extent of the disease was graded according to an arbitrary scale. RESULTS AND CONCLUSION: There was a significant reduction of the native liver attenuation in both chronic and acute BDL groups as compared with the normal controls. FP 736-04 was taken up by the liver parenchyma with a similar degree of enhancement in all three groups.     

Septic cholangitis occurring 11 years after inadvertent ligation of the right hepatic duct during cholecystectomy: a case report

We report a case of acute cholangitis caused by the inadvertent ligation of the right hepatic duct during a cholecystectomy performed 11 years before. When the condition of the right hepatic duct or accessory bile duct ligation persists for more than several years, resulting in atrophy of the relevant part of the liver, bile duct ligation will rarely cause severe clinical problems. However, acute cholangitis may occur, as in our patient, so long-term follow-up of the patient is warranted.     

A microcholangiographic study of liver disease models in rats

RATIONALE AND OBJECTIVES: Rats develop hepatobiliary injury due to small bowel bacterial overgrowth (SBBO) that, at specimen, resembles cholangiography sclerosing cholangitis. To better visualize the smaller bile ducts, we used microcholangiography to determine the spectrum of biliary lesions in this and five other models of liver disease. METHODS: The models studied were as follows: (1) Surgically created jejunal, self-filling blind loops induce SBBO. (2) Intraperitoneal injection of a bacterial cell wall polymer, peptidoglycan-polysaccharide (PG-PS), causes granulomatous hepatitis. (3) Intraperitoneal injection of endotoxin (lipopolysaccharide) causes sinusoidal congestion and shock. (4) Bile duct ligation induces bile duct proliferation. (5) Alpha-naphthyl-isothiocyanate (ANIT) induces bile duct proliferation. (6) Carbon tetrachloride (CCl4) causes fibrosis and cirrhosis. Warmed barium sulfate, gelatin, and saline were injected in the extrahepatic bile duct. Liver slices (2 mm) underwent microradiographic techniques, and images were correlated with histology. RESULTS: Rats with SBBO had irregular and dilated extrahepatic bile ducts with thickened walls. Rats treated with endotoxin and CCl4 had normal microcholangiograms. Bile duct proliferation was identified following ANIT and bile duct ligation. Rats given PG-PS demonstrated irregular intrahepatic bile ducts. Microcholangiograms following SBBO and PG-PS showed similarities including focal ductal dilatation, narrowing, proliferation, and destruction. CONCLUSION: Various models of liver injury induce characteristic cholangiographic appearances. Microcholangiography is useful in examining biliary tract lesions and complements histology.     

Increased neutrophil function induced by bile duct ligation in a rat model

Neutrophil function was studied in rats with common bile duct ligation. Superoxide production stimulated by phorbol myristate acetate, opsonized zymosan or formyl-methionyl-leucyl-phenylalanine; phagocytosis; and chemotaxis were significantly greater in neutrophils from rats with common bile duct ligation than in sham-operated control rats. Enhanced neutrophil activity was observed within 12 hr of bile duct ligation; it remained increased during the 15-day study. Preincubation of neutrophils from control rats with sera of rats with common bile duct ligation did not increase superoxide generation. This suggests that the high superoxide production observed in neutrophils of rats with common bile duct ligation was not an immediate effect of the serum. Neutrophils of rats with portal vein ligation exhibited normal activity, indicating that portal systemic shunting per se is not the underlying mechanism for increased activity. The elevated levels of AST and alkaline phosphatase, indicating liver damage, that appeared within 12 hr of bile duct ligation correlated with the increased superoxide generation.     

Morphometric studies on the rat liver in biliary obstruction

The common bile ducts of the Wistar rats were ligated and severed, and liver biopsies were done weekly for 7 postoperative weeks. Light and electron microscopic specimens were prepared for the morphometric studies. The volume ratio of the hepatic parenchyma decline with the lapse of time after bile duct ligation. However, elevated mean sectional area of the nucleus, increased mitotic index and unchanged estimated weight of the hepatic parenchyma after biliary obstruction suggested that lost hepatocytes were compensated by regeneration. Mitochondrial swelling and curling of the cristae were noted in biliary obstruction in general. Moreover, both the number and volume ratio of the mitochondria were increased corresponding to the duration of biliary obstruction. These changes were interpreted as an adaptation process to mitochondrial dysfunction.     

Jaundice associated with polycystic liver disease. Relief by surgical decompression of the cysts

Jaundice is an unusual feature of polycystic liver disease. In a 46-year-old woman with polycystic liver disease and jaundice, the bilirubin level was 42.0 mg/100 ml. Because of the rapid rise in bilirubin level, relief of supposed obstruction of intrahepatic bile ducts was attempted by unroofing the hepatic cysts. Following operation the bilirubin level returned to normal, and the patient has remained well since.     

Founder effect at PGL1 in hereditary head and neck paraganglioma families from the Netherlands

After repeated exposure to inhaled anesthetics, the hepatic function and metabolism of anesthetics may change. The purpose of this study was to investigate inorganic fluoride (F-) kinetics and renal and hepatic function after repeated exposure to sevoflurane. Ten patients (aged 40-70 yr) who had received sevoflurane anesthesia with a gas flow of 6 L/min for neurosurgery twice in 30-90 days were studied. Serum and urine F- concentrations were measured up to 24 h after anesthesia. Blood urea nitrogen, serum creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-D-glucosaminidase, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin concentrations were measured up to 7 days after anesthesia. The area under the curve (AUC) of serum and urine F- concentration and half-life of serum F concentration were calculated. Urine beta2-microglobulin, AST, and ALT increased to abnormal levels after both anesthesias, with no difference between anesthesias. No measured variables, AUC of serum and urine F- concentration, or half-life of serum F- concentration showed any differences between the first and second anesthesias. In conclusion, the second exposure to sevoflurane with a high gas flow of 6 L/min in 30-90 days did not change the hepatic and renal function or affect the metabolism of sevoflurane. Implications: We studied the changes of metabolism of sevoflurane and hepatic and renal function after repeated sevoflurane anesthesia in 30-90 days. There were changes indicative of mild liver and kidney injury after sevoflurane anesthesia, but repeated exposure to sevoflurane did not enhance these changes.     

The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor

BACKGROUND/AIMS: Models of hepatopulmonary syndrome require both hepatic injury and portal hypertension to develop pulmonary microvascular and gas exchange abnormalities. Recently, increased endothelin-1 levels associated with vasodilatation, have been observed in cirrhosis. We investigated endothelin-1 production in common bile duct ligated animals with hepatopulmonary syndrome in comparison to partial portal vein ligated animals that do not develop hepatopulmonary syndrome. METHODS: Organ and plasma endothelin-1 were measured in sham, bile duct ligated and portal vein ligated rats, and Northern analysis and immunohistochemistry were performed in liver. Plasma endothelin-1 levels were correlated with pulmonary endothelial nitric oxide synthase levels and alveolar-arterial oxygen gradients. RESULTS: Hepatic and plasma endothelin-1 increased only after bile duct ligation, and were accompanied by increased hepatic endothelin-1 mRNA and increased endothelin-1 protein in biliary epithelium. Plasma endothelin-1 levels correlated directly with both pulmonary endothelial nitric oxide synthase levels and alveolar-arterial gradients. CONCLUSIONS: Enhanced hepatic production and increased plasma levels of endothelin-1 occur after bile duct ligation, but not after portal vein ligation, and correlate with associated molecular and gas exchange alterations in the lung. Endothelin-1 may contribute to the pathogenesis of hepatopulmonary syndrome.     

Intrahepatic bile duct injury and nodular regenerative hyperplasia of the liver in a patient with polyarteritis nodosa

Although involvement of the hepatic vasculature in patients with polyarteritis nodosa is not unusual, biliary manifestations are very rare. We describe a patient with polyarteritis nodosa presenting with a febrile cholestatic anicteric syndrome. Histological examination of the liver revealed necrotizing arteritis of small hepatic arteries associated with significant lesions of intrahepatic bile ducts of the sclerosing cholangitis type, i.e. fibrous collar around the ducts, periductal inflammation and ductal proliferation. Concomitant nodular regenerative hyperplasia was found, a condition which has rarely been described in association with polyarteritis nodosa. We think that hepatic arteritis compromising arterial blood flow to the liver was responsible for the most likely ischemic nature of the bile duct injury and the nodular regenerative hyperplasia seen in our patient.     

Treatment of irresectable hepatocellular carcinoma with repeated transient dearterialization]

A joint clinical prospective study between SUMS and Lund university was reported. 40 patients with the irresectable hepatocellular carcinoma (HCC) admitted to the department of HPB surgery in the First Affiliated Hospital of SUMS were randomized into two groups: (20 each) from Feb. 1994 to April, 1995. The patients were treated with hepatic artery ligation (HAL) and repeated transient dearterialization (RTD) respectively. Postoperative response to treatment, liver function change (ALT), AFP, imaging examination of the tumor, patient's survival were evaluated. It has been shown that RTD is superior to HAL in terms of the objective response to the therapy, reduction of tumor size, patient's symptom relief, liver function and AFP changes and patient's survival. In the RTD group, the effective rate was 70%, the mean survival time was 8.2 months, and the 6-month survival rate was 79.7%. In HAL group, the effective rate was only 5%, the mean survival time was 5.1 months, 6 months survival rate was 35.8%. It has been postulated that RTD may prevent the rapid development of collateral circulation and increase the production of oxygen-derived free radicals, which may be the responsible factors for the ischemic treatment of hepatic tumours. We consider that RTD would be a promising polliative method for HCC.     

Should all hepatic arterial branches be reconstructed in living-related liver transplantation?

BACKGROUND: Because graft arteries are smaller and shorter in living-related liver transplantation (LRLT) than in whole or reduced-size liver transplantation from cadavers, arterial reconstruction is thought to be one of the critical points for success. METHODS: Thirty LRLT patients were classified into two groups: those in whom all graft hepatic arteries were reconstructed (group A), and those whom only had some were reconstructed (group B). In group A 17 patients had a single hepatic artery and three had two hepatic arteries. In group B the thickest one of several arteries was reconstructed, but the others were ligated after pulsatile back-bleeding from their cut stumps had been confirmed. The clinical results were compared between the two groups. RESULTS: Neither arterial thrombosis nor liver dysfunction related to the arterial blood supply was observed during the postoperative course. One case of bile leakage and two cases of bile duct stenosis occurred in group A. No significant difference was noted in the postoperative values of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase between the two groups. Overall patient and graft survival was 90%. CONCLUSIONS: Although several hepatic arteries may supply the potential allograft in LRLT, it is not always necessary to reconstruct all of them.     

A non-bile duct origin for intestinal crypt-like ducts with periductular fibrosis induced in livers of F344 rats by chloroform inhalation

To evaluate the toxic effects of prolonged exposure to chloroform vapors, female and male F344 rats were exposed to 0, 2, 10, 30, 90 and 300 p.p.m. chloroform by inhalation for 7 or 5 days/week for up to 13 weeks. The purpose of this study was to characterize a lesion that occurred in the livers of rats in the 300 p.p.m. exposure groups. Atypical glandular structures lined by intestinal-like epithelium and surrounded by dense connective tissue occurred in the livers of rats exposed to strongly hepatotoxic atmospheric concentrations of chloroform. Bile duct bromodeoxyuridine labeling indices as well as observations of the locations of the early lesions at the 3 and 6 week time points indicate that these lesions arose from a population of cells remote from the bile ducts. We refer to these lesions as intestinal crypt-like ducts with periductular fibrosis to distinguish them from true cholangiofibrosis. Here, intestinal crypt-like ducts with periductular fibrosis were seen only in rats exposed to 300 p.p.m. chloroform, and the multiplicity and severity of the lesions were greater in the right liver lobe. The lesion only occurred in association with liver necrosis and dramatic increases in hepatocyte labeling indices, while labeling indices in bile ducts in the same animals were not significantly different from controls. There was a treatment-related increase of transforming growth factor-alpha immunoreactivity in hepatocytes, bile duct epithelium, bile canaliculi and oval cells, and an increase in transforming growth factor-beta immunoreactivity in hepatocytes, bile duct epithelium and intestinal crypt-like ducts. Thus, intestinal crypt-like ducts with periductular fibrosis appeared to develop from a population of cells unrelated to bile ducts. Also, they occurred only in animals exposed to chloroform concentrations that induced significant hepatocyte necrosis and regenerative cell proliferation and were associated with increased growth factor expression or uptake.