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The histochemical enzyme pattern in normal, extra-hepatic bile ducts from rabbits was studied. A difference between the duct epithelium and the crypt epithelium was noted mainly in the activity of gamma-glutamyl-transpeptidase and alkaline phosphatase which only stained positively in the crypts. No difference from the normal enzyme pattern was noted after diversion of the bile flow for up to 30 days.
The time required for precipitation of cholesterol crystals (nucleation time, NT) was determined and related to the cholesterol saturation in gall bladder bile of gall stone free subjects (n = 11), patients with pigment stones (n = 3), and patients with cholesterol gall stones (n = 30) undergoing cholecystectomy. Seven of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and nine with ursodeoxycholic acid (UDCA), 15 mg/kg/day for three weeks before operation. NT was longer in gall stone free subjects (mean, 20 days), patients with pigment stones (14 days) and patients treated with CDCA (24 days) and UDCA (17 days) compared with untreated patients with cholesterol gall stones (1.5 days). In spite of low cholesterol saturation and prolonged NT, and in contrast to those treated with CDCA, four of the nine patients treated with UDCA had cholesterol crystals in their bile. These observations give further support to the concept that the mechanism for inducing gall stone dissolution may be different for CDCA and UDCA.
The biliary and urinary excretion and the choleretic effect of iopanoic acid (Telepaque) were studied in nonanesthetized bile-fistula dogs using a stepwise increase of infusion rates of iopanoic acid and a constant infusion of sodium taurocholate at a rate of either 0.5 or 2.0 mumoles/min./kg. The maximum rate of bile excretion (0.671 mumoles/min./kg) when taurocholate was infused at the lower rate nearly doubled (1.325 mumoles/min./kg) when given at the higher rate. Maximum biliary concentrations of iopanoic acid at both rates of taurocholate infusion (70-77 mumoles/ml) were almost double the maximum concentration previously determined for iodipamide (Cholografin) (42 mumoles/ml).
Ion-replacement studies were carried out in the isolated perfused rat liver to obtain insight into the role played by inorganic electrolytes in bile acid-independent canalicular bile flow (BAICF). The BAICF decreased significantly when Na+ (146 mM) was replaced by 120 mM K+, Rb+, Cs+, or choline and when Cl- (127 mM) was replaced by 120 mM acetate or isethionate; there was no reduction in BAICF when Na+ was replaced by Li+ (146 mM) and Cl- by NO-3. K+, Rb+, and Cs+, however, also caused a simultaneous decline in the perfusion rate. The BAICF decreased by 50% when HCO-3 was replaced by equimolar tricine; under this condition replacement of Cl- by NO-3, but not Na+ by Li+, decreased BAICF by 45%. Thus the hepatic transport of Cl- cannot be explained by simple diffusion only, and a special mechanism, probably Na+-coupled Cl- transport, may contribute about 30% of the BAICF. With Li+ replacing Na+ in the medium, the intracellular concentration of Li+ in isolated rat hepatocytes was less than that calculated for electrochemical equilibrium and was increased by 2 mM KCN, indicating active extrusion of this ion. Li+ was unable to activate Mg2+-ATPase of isolated rat liver plasma membranes, and 1 mM ouabain did not affect the Li+ distribution. These results suggest the potential importance of ion pumps other than Na+-K+-ATPase in BAICF.
In male rats with acute liver dystrophia, caused by carbon tetracloride, effect of sodium slentie (at doses of 1 mg and 10 mg per 100 g of body weight) on the bile secretion was studied. The drug normalized rapidly the functions of liver tissue, synthesis and excretion of bile acids, bilirubin secretion and excetion of cholesterol. Treatment with sodium selenite increased detoxication process in the organism, prevented death of the animals.
In 10 patients who had formed new stones in the common bile duct after cholecystectomy, the lipid composition of the hepatic bile was determined on three different days after relaparotomy and placing of T-tude and the cholesterol content of the stones was investigated. The cholesterol content in 9 out of 10 recurrent gallstones was between 78 and 93%. The lipid content was lithogenic in these 9 cases. In the tenth (a patient with mixed recurring gallstones) solubility for cholesterol was in the critical area. There thus seems to be no normalization of lipid composition in patients with cholesterol stones after cholescystectomy, and the conditions for recurrence of cholesterol stones remain unaltered.
In a 72-year-old male carcinoma of the bile duct was suspected because of an abnormality on laboratory examination. Ultrasound showed the dilatation of extrabiliary duct. Endoscopic ultrasound revealed localized wall thickening of the common bile duct. ERCP demonstrated the dilatation of the CBD. Within the dilated duct a filling defect was present. Histology of the resected specimen disclosed hyperplasia of the epithelium in the CBD.
It is established in the experiment, that in stable obturation of the cystic and common bile ducts, the biliary pressure increases to the level of secretory hepatic pressure, at which it maintains for 9 days. Beginning from the day 10 of obturation, the common bile duct pressure sharply decreases (P less than 0.01) and remains decreased up to the end of investigation (day 27). The author distinguishes the periods of increase and stabilization of the pressure, stable hypertension, stable decrease of the pressure. The first two periods are indicative of compensation of the secretory function, the third one--of its decompensation.
This paper reports a case of bile duct carcinoma associated with an extra-hepatic bile duct anomaly. In the present case, the anomaly induced an uncorrect preoperative diagnosis and obliged to change the surgical procedures during operation. A correct preoperative diagnosis was difficult to make in the present case, when the anomaly in the biliary system was not kept in mind.
In spite of many reports which suggested the efficacy of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) on cholesterol gallstone dissolution, problems still remain to be solved, such as the ideal dosage and duration of treatment to obtain maximal benefit with minimal untoward effects. The author reports in this paper a comparative study on changes of bile acid level and lipid composition in blood and bile during the clinical course after initiation of CDCA and UDCA therapy in effectively and ineffectively responding groups of patients with cholesterol gallstones in the gallbladder.
The ionization and conjugation effect on infrared spectra of bile acids has been studied. The interpretation of spectra of native bile absorption in the infrared range was conducted with allowance for different types of functional groups oscillations.
The electron impact mass spectra of conjugated bile acids, their 5alpha-analogs and methyl esters of glyco conjugates were determined by direct insertion into the ion source and their fragmentation patterns were found to be basically similar to those of methyl esters of the free bile acids. The conjugates are additionally characterized by a significant loss of [NH2CH2CO2H] from the glycine moiety and [CH2 = CHSO3 H] from the taurine group. Several 5 alpha- and 5 beta-isomers can be differentiated, but no general pattern of recognition is discernable. Field desorption mass spectra contain [M + Na]+ and [m + Na]2+ ions.
Biliary epithelial cells (BECs) are distributed along the length of both the extrahepatic and intrahepatic biliary tree, but have distinctly different phenotypes and functions according to their anatomical location. It has been reasoned that the distinct appearance of pathogenic lesions in different biliary diseases may be associated with the expression of distinct proteins. These data prompted us to immunize rats with cultured murine BECs with the objective of determining if there are unique antigens on BECs. Of the 45 monoclonal antibodies (mAbs) produced, 12 mAbs (MBEC 1-12) were selected for detailed study based on their classification into three major groups. These groups included four antibodies (MBEC 1-4) that reacted in a staining pattern typical of mucin. A second group of mAbs, MBECs 5 to 8, reacted strongly along the biliary tract and by immunoblot analysis, reacted with several bands ranging from 44 kd to 64 kd. These antibodies were considered as markers of pan BECs and their staining pattern proved similar to that of a control polyclonal pan-cytokeratin. The final group of mAbs, MBECs 9 to 12, recognized a 36-kd antigen using lysates of murine BECs. These antibodies also predominantly stained small peripheral bile ducts. The reactive antigen was purified by immunoprecipitation and microsequenced; the peptides sequenced showed 100% homology with murine annexin V. The identification of annexin V with predominantly intrahepatic bile ducts, is of significant interest because of the multiple roles of annexin V, including that of membrane cytoskeletal interactions during transport and apoptosis.
A series of covalently binding derivatives of bile acids, fusidic acid and of compounds similar to cholecystographic agents were synthesized. Nearly all of them inhibited the development of protrusions on the surface of isolated hepatocytes regularly seen after treatment with phalloidin. The same compounds inhibited the uptake of demethylphalloin and of cholate in a concentration dependent manner. Two kinds of effects could be distinguished: The irreversible part of the inhibition depended on the incubation period and could not be removed by washing procedures. The reversible one was independent on the duration of the preincubation. Final results indicated that the tested derivatives inhibited either both transports, and the phalloidin response of liver cells to the same degree and in the same manner, or were found to be ineffective in all tests. The above parallelism supports the hypothesis that phallotoxins may be translocated by a carrier system normally responsible for the uptake of bile acids from the portal blood.
A 8-year-old Japanese girl had congenital bile duct dilatation, associated with both choledocholithiasis and acute pancreatitis. Ultrasonography (US) was used to demonstrate a stone within a dilated common bile duct, and US provides the most useful preoperative information to proceed to surgery.
Percutaneous transhepatic biliary drainage procedures are associated with a small but definite incidence of complications. One of the most feared complications, leakage of bile, is commonly presumed to be a catastrophic clinical event. We present an unusual case in which a patient manifested only minimal abdominal symptoms associated with a massive biliary ascites. The bile leakage was first detected by diisopropyl iminodiacetic acid (DISIDA) scanning.
Serum total bile acid levels (STBA), a sensitive indicator of cholestasis, were measured during the long-term postoperative period in patients with congenital bile-duct dilatation (CBDD) (choledochal cyst) and the factors contributing to elevation of STBA were analyzed in 44 patients. Their ages at operation ranged from 1 month to 16 years. A STBA level over 12 nmol/ml on two or more measurements during outpatient follow-up was considered abnormal. Patients were classified into three groups: group 1, STBA, 12-50 nmol/ml; group 2, STBA > or = 50 nmol/ml; group N, STBA normal. In 19 patients (43.2%) STBA was normal. Of the 25 patients (56.8%) with elevated STBA, groups 1 and 2 comprised 12 (27.3%) and 13 patients (29.5%), respectively. The mean age in group N was 5.1 +/- 4.2 years, which was higher than in groups 1 (2.6 +/- 2.3) and 2 (2.3 +/- 2.5 years) ( P< 0.05). Preoperative STBA and total bilirubin were higher in group 2 (79.2 +/- 75.1 nmol/ml resp. 5.2 +/- 4.2 mg/dl) than in groups N (20.1 +/- 32.6, 1.3 +/- 1.4) and 1 (22.8 +/- 37.2, 1.4 +/- 1.0) ( P< 0.05). Preoperative alkaline phosphatase and gamma-glutamyl transpeptidase were higher in group 2 (1,006 +/- 872 IU/l, 452 +/- 326 IU/l) than in group N (573 +/- 371, 205 +/- 238) ( P< 0.05). Histologic findings on liver biopsy showed fibrosis in 38.5% of group 2 patients, which was significantly higher than in groups N (15.8%) and 1 (16.7%) ( P< 0.05). Cholestasis was detected in 41.7% of group 1 and 61.5% of group 2 patients, compared to 10.5% of group N patients ( P< 0.05). Postoperative elevation of STBA may thus persist in more than one-half of patients with CBDD, and is likely to occur in patients of young age who have severe cholestasis or liver fibrosis preoperatively. Further investigations may be required in regard to the development of postoperative complications.
Of the 101 patients with congenital cystic dilatation of the common bile duct, eighty-eight with adult-type cysts are reported on. The association of primary bile duct stone and adult-type cyst of this anomaly is discussed and found to be higher than previously recognized. In the cases without calculi, abnormal arrangement of the pancreaticobiliary ductal system is indicated to play an important role in the manifestation of the symptom. The anatomic and clinical features and the results of treatment for this type of cyst are reviewed.