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)

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical and histopathological correlation in liver transplant: the first 180 days. 150 12

The disposition of bromosulfophthalein was studied in chronically bile duct obstructed rats. In this model a catheter was inserted into the common bile duct and the distal tip was sealed. Resumption of bile flow was achieved with great ease. Obstruction of bile duct for 18 days in rats resulted in elevated bilirubin, ALT, AST, and alkaline phosphatase levels. Portal hypertension developed within this period (11.6 +/- 0.5 in obstructed rats vs. 8.6 +/- 0.6 mm Hg in sham-operated group). After the bile duct obstruction was opened, the half-life time for elimination of bromosulfophthalein (42.30 +/- 6.47 min) was longer than in sham-operated rats (21.23 +/- 3.34 min). Plasma clearance was reduced by 70% in bile duct obstructed rats. In spite of increased bile flow rate, biliary excretion of the dye was reduced by 40% in chronically bile duct obstructed rats. Hepatic glutathione levels were significantly reduced by 20% in this model. The specific activity of glutathione S-transferase with chlorodinitrobenzene and styrene oxide, as substrates, was reduced by 50% and 30%, respectively. However, the percent of conjugated bromosulfophthalein in bile was similar to that of sham-operated rats.
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PMID:Bromosulfophthalein disposition in chronically bile duct obstructed rats. 150 59

The purpose of this study was to determine the chronic toxicity of methidathion, an organophosphate insecticide, in dogs. Groups of beagle dogs, four/sex/dose, were fed methidathion at constant dietary concentrations of 0, 0.5, 2, 4, 40, or 140 ppm for 1 year. The equivalent daily dosages were approximately 0, 0.02, 0.07, 0.15, 1.4, and 4.7 mg/kg. There were no deaths or adverse clinical signs associated with the treatment. Weekly body weights and weight gains were not affected. Mean daily food consumption was reduced in male dogs given the 140-ppm diet. Major treatment-related effects were cholestasis, chronic inflammation in the liver, and cholinesterase (ChE) inhibition. The liver effects were indicated by gross and microscopic pathologic findings as well as moderate increases in serum bile acids and enzyme activities (alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, and alkaline phosphatase) in all dogs receiving greater than or equal to 40 ppm. RBC ChE was inhibited in males at greater than or equal to 40 ppm and in females and 140 ppm. Brain ChE was inhibited in both sexes at 140 ppm; the magnitude of inhibition relative to control was slightly greater with the cerebellar fraction than with the cerebral fraction. Serum ChE was not affected at any dose level. In conclusion, liver was the target organ in beagle dogs given greater than or equal to 40 ppm (equivalent to 1.4 mg/kg/day) methidathion in diet for 1 year. The no-observable-effect level was 4 ppm (0.15 mg/kg/day) for both liver cholestasis and ChE inhibition.
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PMID:One-year dietary toxicity study with methidathion in beagle dogs. 151 89

Jaundice is a disorder of bilirubin metabolism and has many causes. History and physical examination help establish the diagnosis in 70 to 80 percent of patients. Elevation of alkaline phosphatase and gamma-glutamyl transpeptidase suggests cholestasis, either intrahepatic (e.g., medication reactions) or extrahepatic (e.g., choledocholithiasis), whereas markedly elevated serum aminotransferases are indicative of hepatocellular damage from infection, toxins or ischemia. Ultrasound examination is a useful initial procedure when extrahepatic obstruction is suspected. Endoscopic retrograde cholangiopancreatography and computed tomography may be better used to diagnose obstruction at the level of the pancreas or distal common bile duct. The treatment is based on the etiology of jaundice and includes removal of offending medications or toxins, therapy for underlying liver disease or surgery for extrahepatic obstruction.
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PMID:Jaundice. 154 99

Administration of trimethoprim-sulfadiazine in a dog was associated with vomiting, inappetence, and icterus, and high values of alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltransferase, and total bilirubin concentration. The clinical signs and biochemical abnormalities resolved after discontinuation of the treatment. Histologic examination of sections from a liver biopsy specimen revealed moderate, predominantly portal hepatitis with cholestasis.
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PMID:Presumptive trimethoprim-sulfadiazine-related hepatotoxicosis in a dog. 154 70

Fifteen cases of hepatitis related to a combination of amoxycillin and clavulanic acid are reported. Most patients were aged 60 years or more and there were more men than women (sex ratio 4:1). The amoxycillin-clavulanic acid had been given at doses ranging from 0.5 to 6 g/day (mean 2 g/day) for seven to 60 days (mean 18 days). In 11 cases, the first symptoms appeared one to four weeks after stopping treatment. Jaundice was observed in all patients and was frequently associated with pruritus. Serum aminotransferase activities were increased in all patients and were generally two to 10 times the upper limit of normal. Serum alkaline phosphatase activity was considerably increased, from two to seven times the upper limit of normal. Histological examination of the liver, performed in seven patients, showed centri- or panlobular cholestasis in all cases, associated with granulomatous hepatitis in one. The prognosis of amoxycillin-clavulanic acid induced hepatitis seemed to be good. None of the patients exhibited biological or clinical features of hepatic failure and the course of the disease was characterised by the resolution of jaundice within one to eight weeks and a complete recovery within four to 16 weeks. Taking into account the number of treated subjects and reported cases, we estimated the risk of developing hepatitis with this drug combination to be very low, probably below 1/100,000. Our data suggest that the risk of hepatotoxicity may be increased in elderly men given lengthy treatment. The association of hepatitis and signs of hypersensitivity may suggest an immunoallergic mechanism of hepatotoxicity in some patients.
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PMID:Hepatitis associated with amoxycillin-clavulanic acid combination report of 15 cases. 145 90

Ursodeoxycholic acid therapy (600 mg/day) was evaluated in twelve patients with non-advanced chronic cholestasis. Within four months, ursodeoxycholic acid replaced more than 50% of total bile acids in 8 patients and the reduction of serum gamma-glutamyltranspeptidase, alkaline phosphatase and transaminases averaged 30% or more. The serum levels of chenodeoxycholic acid depend on those of ursodeoxycholic acid, but are not related to those of biochemical parameters. Drug therapy was continued in three poor responders for 2-3 four-month periods. In one case an increase of the serum proportion of ursodeoxycholic acid was associated with a reduction in biochemical parameters. The other two cases had high serum levels of chenodeoxycholic acid and/or cholic acid throughout the entire course of treatment. While the treatment of chronic cholestasis requires an effectual serum proportion of ursodeoxycholic acid, it is important to distinguish endogenous persistent hyper-bile-acidemia from ursodeoxycholic acid-related acidemia.
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PMID:The effectual level of ursodeoxycholic acid in therapy for non-advanced chronic cholestasis is fifty percent of total serum bile acids. 157 28

The effects of rifampicin treatment (10 mg.kg-1.day-1) on pruritus and cholestasis were evaluated in 16 patients with primary biliary cirrhosis and pruritus followed up for 2-24 months. Assessment of pruritus severity, liver tests, aminopyrine breath test, and bile acids was done at 2 weeks and every 3 months after the beginning of the study. Two patients (12.5%) were withdrawn after 2 months of treatment because they had hepatitis caused by rifampicin. Four patients were withdrawn after 4 months because of liver transplantation (3 cases) and the development of leg edema associated with administration of rifampicin. The remaining 10 patients received therapy for 14.4 +/- 0.7 months and did not experience side effects. Pruritus improved in all patients and disappeared in 11 patients (79%) after 3 months of treatment. Moreover, all patients followed up for more than 1 year were free of pruritus. The alkaline phosphatase level decreased significantly, and the aminopyrine breath test results increased significantly after 2 weeks of treatment (P less than 0.001) and did not change thereafter. In the 9 patients treated for 15 months, alkaline phosphatase levels decreased to 63% of the basal levels and aminopyrine breath test results increased to 153% of baseline values. Transaminases, gamma-glutamyltransferase, and total bile salt levels decreased significantly after 2 weeks of treatment but returned to baseline after 3 months. No changes in bilirubin and cholesterol levels were observed. It is concluded that long-term rifampicin treatment is effective for relieving pruritus in primary biliary cirrhosis, but liver enzymes should be monitored to detect drug-induced hepatitis.
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PMID:Effects of long-term rifampicin administration in primary biliary cirrhosis. 158 27

The use of the drug cyclosporin is limited by toxicity. It would be advantageous to develop therapeutic monitoring of cyclosporin which would predict the development of clinical toxicity. In the present study, alternative methods of measuring cyclosporin levels were evaluated in a heterogenous population of transplant patients, comparing a fluorescent polarization immunoassay using a non-specific polyclonal antibody, which measures both cyclosporin and its main metabolites, and a specific high-performance liquid chromatography assay for unchanged cyclosporin in blood. Neither measured variable alone correlated with laboratory evidence of renal toxicity (serum creatinine) or liver toxicity (serum glutamate transaminase, lactic dehydrogenase, alkaline phosphatase, or serum bilirubin). The relationship between metabolites and parent cyclosporin was quantitated using the ratio of cyclosporin levels determined by fluorescent polarization immunoassay over levels determined by high-performance liquid chromatography. A cohort of patients with markedly elevated ratios of cyclosporin were identified. When patients' data were reviewed collectively and individually there was a correlation between an elevated ratio and the serum bilirubin (r = 0.41, P less than 0.001). This association could be either due to cyclosporin as a cause of cholestasis or to cholestasis from any cause resulting in metabolite accumulation. Further studies are needed to clarify the role of cyclosporin in hepatic dysfunction and develop early, specific markers for this cyclosporin-associated toxicity.
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PMID:Cholestasis in transplant patients--what is the role of cyclosporin? 160 41

The case of a patient with intrahepatic cholestasis, probably induced by an oral contraceptive agent, is reported. Initially, early primary biliary cirrhosis was suspected, but this diagnosis could not be verified either clinically or by immunological tests. Re-examination and re-evaluation of the liver biopsy revealed some eosinophilia and sinusoidal dilatation, changes indicative of drug-induced liver injury. The cholestasis gradually disappeared as indicated both biochemically and histologically, but the elevation of serum alkaline phosphatase levels persisted for some 10 years after termination of drug therapy. Oral contraceptive agent-induced jaundice or cholestasis is generally reported to disappear when the drug is stopped, and we are unaware of similar cases in the literature with a protracted course such as that described here. Still, the circumstances of this patient suggest that a correlation between the oral contraceptive agent and the hepatic reaction is most likely, and we consider it important that colleagues pay attention to this possibility.
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PMID:Protracted cholestasis probably induced by oral contraceptive. 160 95


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