Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Report of a 10-year-old boy with congenital hypoplasia of the intrahepatic bile ducts, the socalled MacMahon-Thannhauser-Syndrome. The patient had been suffering from a varying degree of jaundice since his 2nd day of life and from pruritus since his 21st month of life. Furthermore, he had hepatomegaly, a systolic cardiac murmur, hypogenitalism, retarded growth, and finally hypertension. Transitory xanthomas existed between 1 3/4 and 2 3/4 years of age. Signs of persistent intrahepatic cholestasis was manifested by increased levels of bilirubin and bile acids in serum as well as raised activities of leucine aminopeptidase, gamma-glutamyl transpeptidase and alkaline phosphatase. Pathological values of serum glutamic dehydrogenase pointed to a persistent destruction of liver cells. Without treatment, the activities of vitamin K dependent clotting factors were decreased. Cholesterol, phosphatides and triglycerides in serum were increased and lipoprotein-X was detectable. Aortography revealed stenosis of both renal arteries. An exploratory laparotomy and 5 liver biopsies led to the diagnosis of hypoplasia of the intrahepatic bile ducts. Therapeutic trials with steroids and the anion exchange resin "cholestyramine" were ineffective. Phenobarbital relieved the pruritus. Parenteral administration of fat soluble vitamins restored the activity of vitamin K dependent clotting factors to normal. The high blood pressure fell significantly due to treatment with adelphan. The etiology of hypoplasia of the intrahepatic bile ducts is unknown. It may be a malformation or an obliteration secondary to inflammation. In our patient, narrowing of the renal arteries, increase of plasma-renin activity and hypertension were probably secondary to hyperlipidemia. It has been suggested that hyperlipemia secondary to cholestasis may be due to a disturbance of lipoprotein metabolism. A review of reports on 118 patients suffering from intrahepatic bile ducts hypoplasia is included.
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PMID:[Hypertension and bilateral stenosis of the renal artery associated with congenital hypoplasia of the intrahepatic bile ducts (author's transl)]. 124 84

The present study correlated the reversibility of bile flow (BF) impairment with biochemical and morphological changes in the liver after injection of a cholestatic dose (12 mumole/100 g body weight) of lithocholic acid (LCA). BF declined maximally at 60 min but recovered totally at 210 min after LCA treatment. During the cholestatic period, there was an increase in tight junction permeability as measured by the bile to plasma (B/P) ratio of inulin and using lanthanum as a tracer. Cholesterol content and the cholesterol/phospholipid ratio in liver plasma membranes (LPM) were augmented while the fluidity of bile canalicular membranes (BCM) was decreased at 30 and 60 min after LCA injection. These changes in cholesterol content and membrane fluidity seemed to be correlated with LCA incorporation in LPM; their reversal at 120 min preceded the recovery of BF (210 min). Some biochemical disorders were evident after LCA injection, but they did not correlate with the variation in BF. These data suggest that increased tight junction permeability and decreased BCM fluidity are important pathogenic steps in LCA-induced cholestasis.
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PMID:Tight junction permeability and liver plasma membrane fluidity in lithocholate-induced cholestasis. 139 92

The prevalence and the pathogenesis of gallstones in patients with chronic pancreatitis have never been studied prospectively. The aim of this study was to evaluate prospectively the prevalence of gallstones with ultrasonography and to look for markers of pigment or cholesterol stone formation in gallbladder bile. Ultrasonography was performed in 39 patients and detected gallstones in 7 patients and sludge in 3. Common bile duct and intrahepatic bile duct dilatation were observed in 16 and 13 patients, respectively. Liver biopsies were obtained in 31 patients and cirrhosis was found in 4. There were calcium bilirubinate granules in 7 of the 27 bile samples examined. Cholesterol crystals were not found in any case. The nucleation time (median: 21 days) was higher in patients with chronic pancreatitis than in patients with cholesterol stones (median: 2 days) (P < 0.001) but was not different from nucleation time in patients either free of stones (median: 21 days) or with pigment stones (median: 21 days). The cholesterol saturation index was similar in patients with chronic pancreatitis and in controls. The 2 patients with chronic pancreatitis who underwent cholecystectomy had pigment stones. Calcium bilirubinate granules were more frequent in patients with intrahepatic bile ducts dilatation (P < 0.02). In conclusion, this study demonstrates a high prevalence of cholelithiasis in chronic pancreatitis patients. Pigment stone formation could be favored by cholestasis.
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PMID:[Pathogenesis of cholelithiasis in chronic pancreatitis]. 148 57

Diabetes is thought to be associated with alterations in biliary function involved in a higher prevalence of gallstones in diabetic patients. However, the presence of supersaturated bile in diabetes is still controversial. To gain information on this point, we studied the effect of insulin deficiency on biliary secretion of bile acid, phospholipid, and cholesterol in anesthetized rats. Diabetes was induced by streptozotocin injection (6 mg/100 gm body weight, intraperitoneally). Experiments were carried out at different times (from 1 to 28 days) after diabetes induction. Some rats received insulin (10.5 U/100 gm body weight; divided into five doses) from the third to the sixth day after administration of streptozotocin. Shortly after streptozotocin injection (1 day), bile acid output was decreased but later markedly increased (from 6 days). However, cholestasis was apparent in all insulin-deficient groups. Biliary lecithin concentrations and secretion rate were enhanced from the first day of diabetes. Moreover, an increase in the biliary percentage of lecithin (from 53% to 71% of total biliary phospholipid), which was counterbalanced mainly by a decrease in the biliary concentration of phosphatidylethanolamine, was observed in rats with diabetes for 6 days. Cholesterol concentrations in bile were also higher in diabetic rats. However, the lithogenic index (i.e., percent of cholesterol saturation) was never higher than in healthy rats (55.7%). Cholesterol output induced by taurocholate infusion was not significantly different in control and in 6-days diabetic rats. Nevertheless, biliary lecithin secretion stimulated by taurocholate infusion was markedly increased (the number of lecithin molecules accompanying every 100 molecules of bile acid into bile was 7 and 18 in control and diabetic rats, respectively, at bile acid rates lower than 150 nmol/min per gram liver). Administration of insulin to diabetic rats reversed the above-reported changes. These results indicate that streptozotocin induces profound changes in the mechanisms responsible for bile acid-induced biliary lipid secretion, which are due to the insulin deficiency rather than to a direct hepatotoxic effect of the diabetogenic drug.
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PMID:Enhancement of bile acid-induced biliary lipid secretion by streptozotocin in rats: role of insulin deficiency. 213 93

Bile samples from patients suffering from cholestasis were tested. Cholesterol, phospholipids, and bile acids (cholic, lithocholic, deoxycholic, chenodeoxycholic) were measured and the methods for the gas-chromatographic determination of cholesterol and major bile acids as well as for the colorimetric determination of phosphorus in phospholipids of human bile are described in extenso. Bile samplings were first carried out on the day the drainage tube was positioned and were repeated every 5 days for four times. Between the first and the last sampling, 1250 mg of phosphatidylcholine was intravenously administered to each patient daily. The aim of the experiment was to evaluate the possible variations in the bile constituents occurring over the specified time.
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PMID:[Chemico-experimental data on the principal bile constituents in patients with obstructive jaundice]. 252 67

Cholesterol and triglyceride plasma levels are usually increased in cholestasis. The excess of cholesterol and that of triglyceride are carried in abnormal low-density lipoproteins (LP) named LP-X and beta 2-LP respectively. It has been assumed that chylomicron metabolism is involved in these alterations. To gain insight into the LP disturbances in this pathology, artificial chylomicrons (AC) were prepared in protein-free aqueous solutions containing lecithin, cholesteryl-oleate, cholesterol and triolein. AC were labelled simultaneously with cholesteryl--14C-oleate (14C-CO) and 3H-triolein (3H-TO) and pulse injected intra-arterially in rats subjected to total obstruction of the bile duct for 48 hours and sham-operated rats. Blood was collected at 2-minute intervals during 10 minutes for radioactivity determination. Fractional clearance rates of 3H-TO and 14C-CO were diminished. Since plasma decay of 3H-TO reflects predominantly the rate of lipolysis (L) whereas chylomicron remnant removal (CRR) by the liver is represented by the 14C-CO decay, our data suggest that in cholestasis both L and CRR are defective.
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PMID:[Chylomicron metabolism in experimental cholestasis]. 263 94

The clinical presentations of 20 patients with four or more choledochal stones were compared with those of 68 patients who had one to three choledochal stones, investigated during the same time period. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy. Patients with multiple choledochal stones usually presented with insidious onset of painless jaundice, simulating malignant bile duct obstruction, in contrast to the abrupt onset of cholangitis or pain experienced by patients with one to three stones. The latter patients had an increased number of duodenal diverticula, higher bilirubins, smaller stones, and fewer positive stones as detected by ultrasound of the bile ducts. Cholesterol crystals were more numerous in duodenal aspirates of patients with multiple choledochal stones. We conclude that multiple choledochal stones have a unique, more smoldering clinical presentation, and that ERCP is the diagnostic procedure of choice. Endoscopic sphincterotomy is an efficient, simple, and safe alternative to surgery when there is no cholecystitis.
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PMID:Choledocholithiasis: a comparison between the clinical presentations of multiple and solitary stones in the common bile duct. 267 89

Lithocholic acid (LCA)-induced intrahepatic cholestasis is associated with increased de novo synthesis of hepatic cholesterol and augmented cholesterol content of the liver cell plasma membrane fraction enriched in bile canalicular complexes (BCM). To determine whether inhibition of cholesterol synthesis could prevent LCA-induced cholestasis, adult male Wistar rats were treated daily with the hypocholesterolemic agents, clofibrate (250 mg/kg) or mevinolin (25 mg/kg), for one, two or four days. After bile duct cannulation and bile collection for one hr, the animals were injected intravenously with 120 mumoles/kg of LCA or its carrier (albumin). Cholesterol synthesis was measured in liver homogenates, and its contribution to the BCM was estimated. LCA reduced bile flow by 51%, 35% and 25% after clofibrate pretreatment for one, two and four days, respectively, and by 51%, 30% and 42% in mevinolin-pretreated animals after one, two and four days. In control animals, cholesterol synthesis and the contribution of newly synthesized cholesterol in the BCM were increased after LCA injection. However, despite that cholesterol synthesis and the contribution of newly synthesized cholesterol in the BCM were reduced in drug-pretreated rats, LCA injection caused a relative increase in these parameters of a magnitude similar to that observed in controls. Thus, the ability of LCA injection to augment de novo cholesterol synthesis and its transport to the BCM may be an important pathogenetic step in the development of cholestasis.
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PMID:Cholesterol synthesis in the pathogenesis of lithocholic acid-induced cholestasis. 337 78

Five patients with primary biliary cirrhosis and prolonged cholestasis underwent intensive plasmapheresis. The indications for plasmapheresis included intractable pruritus or hypercholesterolemia and xanthomatous neuropathy. Patients noted a rapid improvement of pruritus and fatigue which was sustained as long as plasmapheresis was continued. Cholesterol levels were lowered an average of 10.3 mmol/l and xanthomata were reduced in three of four patients. Two patients with painful neuropathy caused by xanthomata experienced relief of this symptom. The liver and spleen size were not affected by plasmapheresis, and activities of aminotransferases, alkaline phosphatase and titres of mitochondrial antibody remained unchanged. We conclude that plasmapheresis has a role in the therapeutic management of patients with advanced primary biliary cirrhosis who are disabled by the complications of pruritus, xanthomatous neuropathy, or hypercholesterolemia with xanthoma formation.
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PMID:Role of plasmapheresis in primary biliary cirrhosis. 397 76

Biliary lipid compositions in infants with cholestasis were analysed. Bile acid and phospholipid values were appreciably lower in infants with idiopathic neonatal hepatitis syndrome or corrected biliary atresia than in control infants. Cholesterol values were not, however, notably lower in infants with cholestasis. When biliary lipid components were determined in terms of molar percent, bile acid values were considerably lower in infants with cholestasis than in controls, and cholesterol and phospholipids were appreciably higher, as was the lithogenic index.
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PMID:Biliary lipid compositions in cholestatic diseases of infancy. 663 32


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