Hepatobiliary scintigraphy and gamma-GT levels in the differential diagnosis of extrahepatic biliary atresia.
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AIM: The aim of this paper is to identify extrahepatic biliary atresia (EHBA) as the cause of cholestasis in neonates with prolonged jaundice and thus accelerate the decision for surgical intervention, which is critical for prognosis. METHODS: We retrospectively studied 21 infants (13 girls, 8 boys) aged 2-16 weeks who have undergone( 99m)Tc-mebrofenin iminodiacetate ((99m)Tc-BrIDA) scintigraphy. They were referred because of direct hyperbilirubinemia and jaundice persisting beyond the 2nd postnatal week. They had received phenobarbitone premedication prior to scintigraphy. Dynamic images for 30 min and then static images (if required) at 1, 2 and 24 h postinjection were acquired. Images were evaluated visually and semiquantitatively, by calculating the liver-to-heart (L/H) ratio. Age, L/H ratios, and serum gamma glutamyl transpeptidase (gamma-GT) levels were compared (Mann-Whitney U test) between infants with EHBA (Group A) and infants without (Group B). The L/H ratios were correlated with age in each group and with gamma-GT in the entire population. RESULTS: A total of 7/21 infants were classified in Group A and 14/21 in Group B. The L/H ratios were significantly lower in Group A. The correlation between L/H ratio and age was negative in EHBA and positive in non-atretic infants. The gamma-GT levels were inversely correlated with the L/H ratios in the entire population, being significantly higher in Group A. CONCLUSION: In long-standing neonatal direct hyperbilirubinemia, (99m)Tc-BrIDA scintigraphy and the L/H ratio index seem to give useful information in the differential diagnosis of EHBA, especially when associated with markedly elevated serum gamma-GT levels. (+info)
Growth evaluation in infants with neonatal cholestasis.
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BACKGROUND: [corrected] Chronic liver diseases in childhood often cause undernutrition and growth failure. To our knowledge, growth parameters in infants with neonatal cholestasis are not available AIM: To evaluate the nutritional status and growth pattern in infants with intrahepatic cholestasis and extrahepatic cholestasis. PATIENTS AND METHODS: One hundred forty-four patients with neonatal cholestasis were followed up at the Pediatric Gastroenterology Service of the Teaching Hospital, State University of Campinas, Campinas, SP, Brazil, in a 23-year period, from 1980 to 2003. The records of these patients were reviewed and patients were classified into two groups, according to their anatomical diagnosis: patients with intrahepatic cholestasis - group 1, and patients with extrahepatic cholestasis - group 2. Records of weight and height measurements were collected at 4 age stages of growth, in the first year of life: 1) from the time of the first medical visit to the age of 4 months (T1); 2) from the 5th to the 7th month (T2); 3) from the 8th to the 10th month (T3); and 4) from the 11th to the 13th month (T4). The weight-by-age and height-by-age Z-scores were calculated for each patient at each stage. In order for the patient to be included in the study it was necessary to have the weight and/or height measurements at the 4 stages. Analyses of variance and Tukey's tests were used for statistical analysis. Repeated measurement analyses of variance of the weight-by-age Z-score were performed in a 60-patient sample, including 29 patients from group 1 and 31 patients from group 2. The height-by-age data of 33 patients were recorded, 15 from group 1 and 18 from group 2 RESULTS: The mean weight-by-age Z-scores of group 1 patients at the 4 age stages were: T1=-1.54; T2=-1.40; T3=-0.94; T4=-0.78. There was a significant difference between T2 X T3 and T1 X T4. The weight-by-age Z-scores for group 2 patients were :T1=-1.04; T2=-1.67; T3=-1.93 and T4=-1.77, with a significant difference between T1 X T2 and T1 X T4. The mean weight-by-age Z-scores also showed a significant difference between group 1 and group 2 at stages T3 and T4. The mean height-by-age Z-scores at the four stages in group 1 were: T1=-1.27; T2=-1.16; T3=-0.92 and T4=-0.22, with a significant difference between T3XT4 and T1XT4. The scores for group 2 patients were: T1=-0.93; T2=-1.89; T3=-2.26 and T4=-2.03, with a significant difference between T1XT2 and T1XT4. The mean height-by-age Z-scores also showed a significant difference between group 1 and group 2 at T3 and T4 CONCLUSION: The weight and height differences between the groups became significant from the 3rd measurement onward, with the most substantial deficit found in the extrahepatic group. In this group, there is evidence that the onset of weight and height deficit occurs between the first and second evaluation stages. (+info)
Cyclic Arg-Gly-Asp peptide-labeled liposomes for targeting drug therapy of hepatic fibrosis in rats.
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Targeting hepatic stellate cells (HSCs) has been challenging due to the lack of specific receptors or motifs on the cells. The aim of the present study was to develop a HSC-specific system for improving drug delivery to HSCs. The affinity of a cyclic peptide containing Arg-Gly-Asp (cRGD) to collagen type VI receptor on HSCs was examined in both in vitro and in vivo experiments. Sterically stable liposomes (SSLs) were modified with this peptide to yield a new carrier, cRGD-SSL. The targeting efficiency of this carrier in delivering interferon (IFN)-alpha1b was investigated in a rat model of liver fibrosis induced by bile duct ligation (BDL). When incubating HSCs or hepatocytes with cyclic RGD peptide, the peptide was bound preferentially to activated HSCs. Biodistribution study showed that the accumulation of cRGD peptide-labeled liposomes in HSCs isolated from BDL rats was 10-fold more than unlabeled SSLs. BDL rats receiving injections of IFN-alpha1b entrapped in cRGD-SSL exhibited significantly reduced extent of liver fibrosis compared with BDL control rats or BDL rats treated with IFN-alpha1b entrapped in SSLs. Thus, cRGD-SSL is an efficient drug carrier, which selectively targets activated HSCs and improves drug therapy for liver fibrosis to a significant extent. This liposomal formulation represents a new means of targeting drug carrier for the treatment of liver fibrosis, and it may have potential clinical applications. (+info)
Knockout of alpha-calcitonin gene-related peptide reduces cholangiocyte proliferation in bile duct ligated mice.
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The role of sensory innervation in the regulation of liver physiology and the pathogenesis of cholestatic liver disease are undefined. Biliary proliferation has been shown to be coordinately controlled by parasympathetic and sympathetic innervation of the liver. The aim of our study was to address the role of the sensory neuropeptide calcitonin gene-related peptide (alpha-CGRP) in the regulation of cholangiocyte proliferation during cholestasis induced by extrahepatic bile duct obstruction (BDL). Our study utilized a knockout (KO) mouse model, which lacks the sensory neuropeptide alpha-CGRP. Wild-type (WT) and alpha-CGRP KO mice were subjected to sham surgery or BDL for 3 and 7 days. In addition, immediately after BDL, WT and KO mice were administered the CGRP receptor antagonist (CGRP(8-37)) for 3 and 7 days by osmotic minipumps. Liver sections and isolated cholangiocytes were evaluated for proliferation markers. Isolated WT BDL (3 days) cholangiocytes were stimulated with alpha- and beta-CGRP and evaluated for proliferation and cAMP-mediated signaling. Lack of alpha-CGRP inhibits cholangiocyte proliferation induced by BDL at both 3 and 7 days. BDL-induced cholangiocyte proliferation in WT mice was associated with increases of circulating alpha-CGRP levels. In vitro, alpha- and beta-CGRP stimulated proliferation in purified BDL cholangiocytes, induced elevation of cAMP levels, and stimulated the activation of cAMP-dependent protein kinase A and cAMP response element binding protein DNA binding. In conclusion, sensory innervation of the liver and biliary expression of alpha-CGRP play an important role in the regulation of cholangiocyte proliferation during cholestasis. (+info)
Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis.
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Cholestasis is associated with systemic accumulation of bile salts and with deficiency of bile in the intestinal lumen. During the past years bile salts have been identified as signaling molecules that regulate lipid, glucose, and energy metabolism. Bile salts have also been shown to activate signaling routes leading to proliferation, apoptosis, or differentiation. It is unclear, however, whether cholestasis affects the constitution and absorptive capacity of the intestinal epithelium in vivo. We studied small intestinal morphology, proliferation, apoptosis, expression of intestine-specific genes, and carbohydrate absorption in cholestatic (1 wk bile duct ligation), bile-deficient (1 wk bile diversion), and control (sham) rats. Absorptive capacity was assessed by determination of plasma [(2)H]- and [(13)C]glucose concentrations after intraduodenal administration of [(2)H]glucose and naturally enriched [(13)C]sucrose, respectively. Small intestinal morphology, proliferation, apoptosis, and gene expression of intestinal transcription factors (mRNA levels of Cdx-2, Gata-4, and Hnf-1alpha, and Cdx-2 protein levels) were similar in cholestatic, bile-deficient, and control rats. The (unlabeled) blood glucose response after intraduodenal administration was delayed in cholestatic animals, but the absorption over 180 min was quantitatively similar between the groups. Plasma concentrations of [(2)H]glucose and [(13)C]glucose peaked to similar extents in all groups within 7.5 and 30 min, respectively. Absorption of [(2)H]glucose and [(13)C]glucose in plasma was similar in all groups. The present data indicate that neither accumulation of bile salts in the body, nor their intestinal deficiency, two characteristic features of cholestasis, affect rat small intestinal proliferation, differentiation, apoptosis, or its capacity to digest and absorb carbohydrates. (+info)
Coexistence of Mirizzi syndrome with adenomyomatosis in the gallbladder: report of a case.
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BACKGROUND: Mirizzi syndrome is a rare complication of cholelithiasis. Adenomyomatosis is a common tumor-like lesion of the gallbladder. METHODS: A 52-year-old man was admitted to our hospital complaining of right hypochondriac pain and jaundice. Ultrasonography and computed tomography revealed stones in the gallbladder and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography revealed narrowing of the common bile duct caused by compression of the gallbladder. Laparotomy revealed type II Mirizzi syndrome. RESULTS: Partial cholecystectomy with a Roux-en-Y hepaticojejunostomy reconstruction was performed. Histologically, Rokitansky-Aschoff sinus proliferation, hypertrophy of smooth muscles, and fibrosis were seen in the gallbladder. A segmental type of adenomyomatosis of the gallbladder was diagnosed. CONCLUSIONS: The pathogenic link between the two peculiar entities is unclear. A possible explanation is considered that the pathogenesis of Mirizzi syndrome is resulted from chronic inflammation due to adenomyomatosis. (+info)
Intraluminal biliary obstruction.
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Jaundice caused by intraluminal bile duct obstruction in infancy is rare but may occur in association with biliary sludge, inspissated bile plugs, or gall stones. Nine boys (aged 2 weeks-6 months) with obstruction caused by inspissated bile (n = 7) or gall stones (n = 2) are presented. Haemolysis was not a factor in the patients' histories but an abnormal entry of the common bile duct into the third part of the duodenum was demonstrated in two and one had an asymptomatic haemangioma. Ultrasonography was the most useful investigation. Surgical removal of the bile duct obstruction was necessary in eight cases and included biliary tract drainage in six and cholecystectomy for changes of cholecystitis in four. Obstruction resolved spontaneously in one infant after percutaneous cholangiography. There were no postoperative complications. (+info)
Chronic rejection and extrahepatic biliary tract obstruction 8 years after orthotopic liver transplantation using the gallbladder-conduit technique.
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A case of delayed biliary obstruction and cholangitis, occurring in the setting of chronic allograft rejection, 8 years after liver transplantation using the gallbladder-conduit, is presented. Extrahepatic biliary obstruction may be seen in the late follow-up of liver grafting and rejection phenomena may play a significant role in the development of such obstruction. (+info)