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)

A 27-yr-old Jamaican male presented with a 2-month history of jaundice, pruritus, intermittent diarrhea, and right upper quadrant abdominal pain. Over the next month, his abdominal pain and diarrhea improved, but his jaundice and pruritus worsened. He was afebrile and profoundly jaundice, with a benign abdominal examination. Medical workup included a normal abdominal ultrasound, iron studies, ceruloplasm, and serum electrophoresis. Negative viral (Epstein-Barr virus, cytomegalovirus, mononucleosis, hepatitis A, B, C) studies, ANA, AMA, ASMA, RPR were noted. He denied any alcohol, drug, or toxin exposure. Liver tests revealed total bilirubin of 25.6 mg/dl, direct bilirubin of 13.9 mg/dl, alkaline phosphatase 278 IU/L, AST 45 IU/L, and ALT 71 IU/L. Liver biopsy demonstrated centrilobular zonal necrosis and cholestasis most consistent with a toxic reaction. The patient was again interviewed regarding potential toxins, and he admitted to the ingestion of ackee fruit, a native Jamaican fruit that is illegal in the United States. Shortly after he had ceased intake of the fruit, his symptoms resolved and his liver function tests returned to normal. We present a case of chronic ackee fruit ingestion that led to cholestatic jaundice, vomiting, and abdominal pain.
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PMID:Cholestatic jaundice due to ackee fruit poisoning. 807 44

The effects of acute poisoning by cupric sulfate in a number of species are well known; however, the effects of chronic low-level ingestion of cupric sulfate are less well characterized. Because exposure of humans to cupric sulfate may occur through drinking water, food, soil, or ambient air, subchronic toxicity studies were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week exposure) and dosed feed (2- and 13-week exposure) routes. Animals were evaluated for histopathology, clinical pathology, reproductive toxicity, and tissue metal accumulation, and target organs were examined by a variety of special stains and by electron microscopy to characterize the observed lesions. In drinking water, cupric sulfate concentrations of 300 to 100 ppm produced no ill effects, whereas concentrations of 3000 to 30,000 ppm were lethal to rats and mice within 2 weeks. In feed, cupric sulfate concentrations of 4000 to 16,000 ppm caused significant reductions in body weight gain in both species in the 2- and 13-week studies. Hyperplasia and hyperkeratosis of the limiting ridge of the forestomach were present in both species in the 2- and 13-week studies. Rats in the dosed feed studies had a dose-related increase in inflammation in the liver and changes in clinical chemistry parameters which were indicative of hepatocellular damage and cholestasis. Histologic changes in the kidneys of rats consisted of a dose-related increase in the number and size of eosinophilic protein droplets in the epithelial cytoplasm and the lumina of the proximal convoluted tubules. Droplets were larger and more numerous in males than in females. Urinalysis results were suggestive of renal tubular epithelial damage. Iron staining of spleens from treated animals indicated a marked depletion of iron stores in both male and female rats, but not in mice, while hematologic and clinical chemistry alterations in rats in the 13-week study, along with histologic changes in bone in the 2-week dosed feed study, were indicative of a microcytic anemia. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. These results indicate that cupric sulfate at high exposure levels is a hepatic and renal toxicant, as well as an inducer of anemia in rodents, with rats more sensitive than mice following subchronic exposure.
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PMID:Subchronic toxicity of cupric sulfate administered in drinking water and feed to rats and mice. 825 99

Interleukin-3 treatment of juvenile rhesus monkeys elicits a dose- and time-dependent syndrome that includes urticaria, palpable lymph nodes, splenomegaly, thrombocytopenia, anemia, vomiting, diarrhea, intestinal bleeding, edema, and arthritis, apart from a strong stimulation of hemopoiesis. Arthritis was found to occur significantly more often in animals expressing the major histocompatibility complex alleles B9 and Dr5. Histological analysis revealed an abundance of mast cells in urticaria and, to a lesser extent, in lungs and synovia of arthritic joints. Active osteoclasts were abundant in ribs and arthritic joints. Extramedullary hemopoiesis was encountered in liver, spleen, and kidneys. The spleen showed deposits of hemosiderin, and in the liver, Kupffer cells were loaded with iron, indicating enhanced turnover of hemoglobin. Lymph nodes and bone marrow showed macrophages involved in hemophagocytosis, which probably contributed to the development of anemia and thrombopenia. Biochemical parameters in sera were indicative of parenchymal liver damage, with cholestasis and increased erythrocyte destruction. The side effects were strongly reduced in monkeys subjected to total body irradiation just before interleukin-3 treatment. Histamine antagonists were not significantly effective in preventing side effects, which is explained by the perpetual stimulation of basophilic granulocytes by exogenous interleukin-3. The nature of the side effects indicates that interleukin-3 may be involved in the pathogenesis of acute type hypersensitivity reactions and arthritis.
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PMID:Acute side effects of homologous interleukin-3 in rhesus monkeys. 825 52

The preceding pages have described an organism that is far removed from mammals on the taxonomic scale of vertebrates but one that has proven to have a unique and most useful system for studies of liver function and, in particular, bile product transport and excretion. It is also an organism in which iron loading can be studied in the liver and other organs and tissues. Many of the events that occur in this animal during its life cycle with regard to bile pigment metabolism as normal programmed phenomena are unparalleled among the vertebrates. In the larval (ammocoete) period of lampreys, there is an intrahepatic gallbladder and a biliary tree that is well equipped for the storage, transport, and elimination of bile products into the intestine for ultimate excretion with the feces. The importance of the patency of these bile ducts to bile excretion is illustrated in one species of lampreys in which the bile ducts of young ammocoetes become infested with larval nematodes to a degree that bile pigment regurgitation into the blood results in a green serum that is identified as biliverdin. Despite having serum levels of biliverdin that would be toxic to humans, these individuals live a complete larval life. The larvae of all lamprey species undergo a phase of metamorphosis in which they transform into adults. During this phase the larval gallbladder, the bile canaliculi of the hepatocytes, and all the intrahepatic bile ducts completely regress in a developmental process called lamprey biliary atresia. The epithelium of the extrahepatic common bile duct transforms and expands into a caudal portion of the endocrine pancreas of the adult. Many of the events of lamprey biliary atresia resemble events occurring during experimental and pathological conditions of mammalian cholestasis, including disruption to the bile-blood barrier (intercellular junctions), accumulation of bile components in the cytoplasmic inclusions, and alteration of the distribution of membrane enzymes in hepatocytes. Regression of the bile ducts and ductules is accompanied by a periductular fibrosis that seems to be a product of activity by lipocytes (Ito cells). The regurgitation of bile products into the interstitial tissue of the liver during early biliary atresia may be the stimulus for both inflammatory (granulomatous) and autoimmune responses. There are no bile ducts in adults lampreys, yet they seem to show no immediate consequences of the absence of an exocrine mechanism for the elimination of bile products.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biliary atresia in lampreys. 827 15

Liver samples from four groups of calves were analysed chemically and histologically for copper and iron levels. Milk replacer-fed 'yellow' calves were compared with milk replacer-fed 'white' calves, concentrate and silage-fed 'pink' calves and concentrate and silage-fed young 'red' fattening bulls. In the milk replacer-fed calves high copper and low iron levels were measured in the liver, whereas in the concentrate and silage fed pink calves and fattening bulls lower copper and higher iron levels were found. The yellow calves appeared to be icteric and had chronic hepatitis. Their hepatic histopathology was characterised by fibrosis, cirrhosis, fatty change, increased amounts of stainable copper, necrobiosis and prominent cholestasis; some animals had intranuclear inclusion bodies in the hepatocytes. They had similar or lower hepatic copper levels than the white calves and varying iron levels, indicating that copper toxicity was not the primary cause of the hepatic damage.
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PMID:Yellow discoloration in veal calves: the role of hepatic copper. 845 46

The significance of the biochemical and nutritional roles of trace elements is widely recognized, since metals are found as constituent components of many metalloproteins and metalloenzymes. Some trace elements such as copper act as cofactors against hepatic fibrosis in chronic liver diseases, particularly in the biosynthesis of collagen. As the disease progress from chronic hepatitis to liver cirrhosis, serum calcium, magnesium, phosphorus and zinc concentrations decrease, while the copper concentration increases. In the patients with hepatocellular carcinoma, serum concentrations of trace elements are similar to those of liver cirrhosis. In the patients with acute hepatitis, serum calcium, magnesium and zinc concentrations decrease, while phosphorus, iron and copper concentrations decrease. These trace element abnormalities may reflect such pathological conditions as liver dysfunction, cholestasis, hepatic fibrosis or liver regeneration.
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PMID:[Liver diseases and essential trace elements]. 858 11

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.
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PMID:[Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol]. 873 82

Apart from viruses, hepatotoxins, hereditary metabolic disorders, immunological factors and cholestasis may cause chronic hepatitis both clinically and histologically. As far as the etiology is concerned, a complete history can be very helpful. The clinical examination, however, is rarely diagnostic. Nevertheless, some clinical signs (e.g. ascites, splenomegaly, spider naevi) are suggestive of cirrhosis. The activities of gammaglutamyl transferase and ALT in the serum are augmented in most of the patients with chronic hepatitis independent of its etiology. Electrophoresis reveals disturbance of serum albumin and globulin ratios. "Basic' laboratory tests are supplemented by carefully selected additional investigations (e.g. immunological tests) according to the history and clinical data of the individual patient. Retrograde cholangiography is diagnostic in the majority of patients suffering from primary-sclerosing cholangitis. Liver histology, best obtained during laparoscopy, allows classification (and prognosis) of the underlying liver disease in many patients. Results of iron and copper determination in liver tissue are diagnostic in cases of congenital liver disease (hemochromatosis, M. Wilson).
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PMID:[Current diagnosis of chronic nonviral hepatitis]. 898 77

We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].
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PMID:Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies. 902 Oct 8

Iron(III)-N, N'-ethylenebis[2-(2-hydroxy-5-phenyl)glycine] [Fe-(5-C2H5-EHPG)-] is a paramagnetic complex designed for use as a hepatobiliary agent. Test procedures included synthesis, characterization, toxicity evaluation, biodistribution and experiments for animal MR images. The dose of LD50 in acute toxicity test of Fe-(5-C2H5-EHPG)- in mice was 3.49 mmol/kg. 111In-(5-C2H5-EHPG)- biodistribution studies revealed that the activities were (4.78 +/- 0.97, 5.34 +/- 0.91, 4.53 +/- 0.35)%ID and (0.88 +/- 0.18, 0.99 +/- 0.17, 0.84 +/- 0.06)%ID/gm in the liver at time intervals of 10, 30 and 60 minutes after injection; (5.76 +/- 0.15, 5.75 +/- 0.15, 4.00 +/- 0.04)%ID and (0.49 +/- 0.03, 0.49 +/- 0.05, 0.34 +/- 0.01)%ID/gm in the blood; (1.27 +/- 0.91, 1.46 +/- 1.00, 1.52 +/- 0.46) %ID and (0.89 +/- 0.17, 1.02 +/- 0.18, 1.06 +/- 0.08)%ID/gm in the kidneys, respectively. The results of image enhancement correlated well to the biodistribution. Analysis of the MR images showed degrees of maximal parenchymal % increase of signal to noise ratio (S/N) was 42.09 +/- 3.59% for normal liver at 30 minutes postinjection, which exceeded the value of pathologic liver with bile duct obstruction 16 hours 17.26 +/- 6.6 %, 1 week 19.80 +/- 6.46% and 4 weeks 32.20 +/- 9.01%, respectively, and acute hepatitis 16.50% +/- 4.02%. Persistent enhancement plateau was documented up to 60 minutes after injection and normalized to precontrast value within 22 hours. The common duct was opacified at 10-15 minutes after injection of contrast agent. These results indicated that the Fe-(5-C2H5-EHPG)- could be rapidly extracted from the blood stream by the hepatocytes and excreted into the bile duct. The initial evaluation of Fe-(5-C2H5-EHPG)- demonstrated that Fe-(5-C2H5-EHPG)- was well suited for enhancement of normal liver parenchyma and was compromised with deterioration of liver function. However, the increase of the liver intensities in the animal model of the total biliary obstruction group normalized to precontrast value within 22 hours, which indicated that renal clearance as an effective alternative pathway for biliary excretion. In conclusion, these results indicate that Fe-(5-C2H5-EHPG)- has the potential of becoming a safe and reliable magnetopharmaceutical for the hepatobiliary system.
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PMID:Preclinical evaluation of Fe-(5-C2H5-EHPG)- as a contrast agent in MR imaging of hepatobiliary system. 909 45


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