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Biomedical subjects

Adolf Stiehl

Publications and source records attributed to Adolf Stiehl.

10 recordsLinked to original sources
PubMed2006

Biliary candida infections in primary sclerosing cholangitis.

BACKGROUND/AIMS: Patients with Primary Sclerosing Cholangitis (PSC) frequently develop dominant stenoses of the bile ducts and bacterial infections represent a major problem in such patients. In the present study, the role of fungal infections of the bile ducts has been evaluated. METHODS: In a prospective non-randomized trial, in 67 consecutive patients with PSC, 148 bile samples, each taken at one endoscopic examination, were microbiologically analysed. RESULTS: Candida species were found in 8/67 patients whereas Aspergillus was not detected. Seven patients with biliary Candida had a dominant stenosis and one had a wide papillotomy with chronic ascending cholangitis. Altogether 7/49 of patients with dominant stenosis and 1/18 of patients without dominant stenosis had Candida in their bile. All patients with biliary Candida intermittently had received antibiotics and had advanced disease with cholestasis. Candida disappeared spontaneously in 2/7 patients, cleared after antifungal treatment in 2, and persisted in 3 patients. Patients with biliary Candida had more severe cholangitis with higher CRP and serum bilirubin compared to those without Candida infection. CONCLUSIONS: This is the first report on the identification of Candida species in the bile of patients with PSC. Apart from bacterial also fungal infection of the bile ducts should be considered in the treatment of such patients.

Adult↗
PubMed2006

Primary sclerosing cholangitis: the role of endoscopic therapy.

Primary sclerosing cholangitis is characterized by progressive fibrosing inflammation of the bile ducts leading to their obliteration, resulting in cholestasis, and finally, cirrhosis of the liver. The majority of patients with advanced disease with time develop dominant stenoses of major bile ducts. Such dominant stenoses may be recognized by magnetic resonance cholangiopancreatography with good specificity and sensitivity, but for definite diagnosis and especially for therapeutic decisions, endoscopic retrograde cholangiography still represents the gold standard. Ursodeoxycholic acid treatment does not prevent the development of such stenoses. Endoscopic measures allow the opening of short- and long-segment stenoses of the common bile duct. Short- but not long-segment stenoses of the hepatic ducts near to the bifurcation also may be treated endoscopically. Repeated balloon dilatations over years appear to be the treatment of choice. In patients treated by early endoscopic dilatation of dominant stenoses, survival may be significantly improved compared with the predicted survival.

Bile Ducts↗
PubMed2006

The role of dominant stenoses in bacterial infections of bile ducts in primary sclerosing cholangitis.

OBJECTIVE: Primary sclerosing cholangitis (PSC) is characterized by progressive fibrotic inflammation and strictures of the biliary system. We studied the role of dominant stenoses in bacterial biliary infections and the effect of routine antibiotic administration with cholangiography. DESIGN: A prospective clinical trial without blinding or randomization. SETTING: The endoscopy unit in a university hospital. PARTICIPANTS: Fifty patients with PSC entered and finished the study. INTERVENTIONS: A total of 103 endoscopic retrograde cholangiographies (ERC) was performed in 37 PSC patients with dominant stenosis and 13 controls with PSC but no dominant stenosis. After selective cannulation of the bile duct, bile samples were obtained during each procedure. All patients received systemic antibiotic treatment with ciprofloxacin for one week after ERC. RESULTS: Enteric bacteria were detected in the bile specimens of 15 out of 37 PSC patients (40.5%) with dominant stenosis but never in the absence of dominant stenosis (P=0.004). Positive cultures for enteric bacteria were associated with elevated serum C-reactive protein, high leukocyte counts in bile (P<0.05) and the deterioration of liver function assessed by increasing bilirubin levels during the follow-up period lasting a median of 7 months (P=0.06). Despite the high rate of susceptibility in vitro, ciprofloxacin treatment eradicated enteric bacteria in only two out of 12 cases. CONCLUSION: Bacterial infection of the bile ducts with dominant stenosis is a frequent finding and may play a role in the progression of PSC. Short-course antibiotic treatment is not very effective in eradicating acteria from the bile ducts.

Antibiotic Prophylaxis↗
PubMed2005

Endoscopic treatment of dominant stenoses in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis is characterized by progressive fibrosing inflammation of the bile ducts, leading to their obliteration, which results in cholestasis and, finally, cirrhosis of the liver. Over time, the majority of patients with advanced disease develop dominant stenoses of major bile ducts. Ursodeoxycholic acid (UDCA) treatment does not prevent the development of such stenoses. Endoscopic measures allow the opening of short- and long-segment stenoses of the common bile duct and also of short segment stenoses of the hepatic ducts. Inpatients treated by early endoscopic dilatation of dominant stenoses, as well as with UDCA,survival may be significantly improved (compared with the predicted survival).

Bile Duct Neoplasms↗
PubMed2004

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis.

Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseases. In primary sclerosing cholangitis (PSC), there is evidence that high doses (+/- 20 mg/kg) of UDCA may be more effective than average doses. Biliary enrichment of UDCA at such high doses may represent the decisive factor for its beneficial effect. Up to now it is not clear how high-dose UDCA correlates with its biliary enrichment and whether bacterial degradation of large amounts of UDCA may lead to an increased bacterial formation of more toxic hydrophobic bile acids. We determined the biliary bile acid composition in 56 patients with PSC including 30 patients with repeat bile samples treated with various doses of UDCA. At a UDCA dose of 10-13 mg/kg/d (n = 18) biliary UDCA represented 43.1% + 0.3% (mean + SD) of total bile acids; at a UDCA dose of 14-17 mg/kg (n = 14), its biliary content increased to 46.9% + 0.3%, at 18-21 mg/kg (n = 34) to 55.9% + 0.2%, at 22-25 mg/kg (n = 12) to 58.6% + 2.3%, and at 26-32 mg/kg (n = 8) to 57.7% + 0.4%. During UDCA treatment, the biliary content of all other bile acids was unchanged or decreased. In conclusion, biliary enrichment of UDCA increases with increasing dose and reaches a plateau at 22-25 mg/kg. There was no increase of toxic hydrophobic bile acids. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, it seems likely that UDCA doses of up to 22-25 mg/kg may be more effective than lower doses.

Adult↗
PubMed2004

Guanylin regulates chloride secretion in the human gallbladder via the bile fluid.

BACKGROUND & AIMS: The biliary epithelium of bile ducts and gallbladder modifies the composition of primary hepatic bile by absorption and secretion of an electrolyte-rich fluid. The underlying transport mechanisms, however, are still incompletely understood. We investigated the expression, the cellular localization, and the functional role of guanylin, a bioactive intestinal peptide involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-regulated electrolyte/water secretion, in the human gallbladder. METHODS: Peptide-specific antibodies were raised to localize guanylin and its affiliated signaling proteins, i.e., the guanylin receptor, guanylate cyclase C (GC-C), cGMP-dependent protein kinase type II (cGKII), and CFTR in the human gallbladder and cholangiocarcinoma cells (Mz-Cha-1) by RT-PCR, Western blot, and immunocytochemistry. A sensitive ELISA was used to assess the range of guanylin concentration in human bile fluid. The functional role of guanylin was investigated in subconfluent Mz-Cha-1 cell monolayers by isotope efflux experiments. RESULTS: Guanylin and its affiliated signaling proteins are highly expressed in the human gallbladder. Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells. Functional studies in Mz-Cha-1 cells identify guanylin as a specific regulator of biliary Cl(-) secretion that very likely is mediated by an intracellular increase of cGMP-concentration. CONCLUSIONS: Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.

Bile↗
PubMed2003

Endoscopic Interventions in the Biliary Tract.

In patients with common bile duct stones, the endoscopic removal of such stones has become the standard therapy. The surgical approach is indicated only for stones that cannot be extracted endoscopically. In biliary obstruction due to pancreaticobiliary malignancy, endoscopic interventions represent the first-line therapy in the palliative situation. If endoscopic access is not possible, the percutanous approach often represents an alternative, followed by palliative surgical options. Biliary strictures or bile leaks after liver transplantation very often may be treated effectively by endoscopic dilatation or temporary stenting. In most cases, endoscopic therapy of such problems represents the first option before the percutaneous or surgical approach is indicated. In primary sclerosing cholangitis, dominant biliary strictures develop frequently and endoscopic treatment allows their opening in most cases. There is no real alternative to endoscopy in this situation. The situation is more complex in postoperative biliary strictures and chronic pancreatitis. In these conditions, advantages and disadvantages of the endoscopic versus the surgical approach have to be evaluated to find the most effective form of treatment in the individual situation. The surgical intervention often represents the better alternative.

Journal Article↗
PubMed2003

Regulation of rat organic anion transporters in bile salt-induced cholestatic hepatitis: effect of ursodeoxycholate.

Hepatic uptake of organic anions, including bile salts, is mediated by members of the organic anion-transporting polypeptide (Oatp) family. In rat liver, Oatp1 (Slc21a1), Oatp2 (Slc21a5), and Oatp4 (Slca10) are expressed at the basolateral membrane of hepatocytes and may be differentially regulated under pathophysiologic conditions such as cholestasis. The aim of this study was to determine the effects of cholic acid (CA) and ursodeoxycholic acid (UDCA) on the expression of Oatp4 compared with Ntcp, Oatp1, and Oatp2. Wistar rats were fed with CA (0.5%) or both CA (0.5%) and UDCA (0.25%) for 3 weeks. Oatp expression was studied by Northern and Western blot analysis as well as immunofluorescence analysis. Transport function was compared measuring biliary secretion of (14)C-CA and (14)C-taurocholic acid (TCA). In CA-fed animals, biliary secretion of (14)C-CA and (14)C-TCA was markedly delayed over 40 minutes compared with controls. Accordingly, Oatp4 protein was significantly down-regulated in CA-fed animals together with Oatp1 and Ntcp. Cofeeding of CA plus UDCA prevented the impairment of (14)C-CA and (14)C-TCA secretion and the down-regulation of Oatp4. Oatp4 messenger RNA (mRNA) levels did not differ significantly between bile salt-fed groups, suggesting a posttranscriptional effect of CA on Oatp4 expression. In contrast to Oatp1 and Oatp4, Oatp2 protein expression was increased by CA feeding, indicating a differential regulation of Oatp transporters. In conclusion, we show that CA feeding may cause cholestasis associated with a posttranscriptional down-regulation of Oatp4. UDCA may prevent impairment of hepatic function by restoring hepatic transporter expression.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2002

Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment.

BACKGROUND/AIMS: Primary sclerosing cholangitis is characterized by progressive fibrotic inflammation and obliteration of intra- and/or extrahepatic bile ducts. METHODS: In a prospective study of 106 patients treated for up to 13 years with ursodeoxycholic acid, the development of major bile duct stenoses and the efficacy of endoscopic measures have been evaluated. RESULTS: Of 106 patients ten had major duct stenoses at entry, and during a median follow-up period of 5.0 years another 43 developed a dominant stenosis. Fifty-two patients with dominant stenoses were treated endoscopically by repeated balloon dilatations and five patients were temporarily stented. Complications of endoscopic procedures were pancreatitis (5.2%), bacterial cholangitis (3.3%) and bile duct perforation (0.5%). Five years after the first dilatation of a dominant stenosis the Kaplan-Meier survival rates free of liver transplantation were 100% in stage 2, 72% in stage 3 and 50% in stage 4 disease. The actuarial survival free of liver transplantation of the whole group at 3, 5 and 7 years were 0.987, 0.935 and 0.891 and the corresponding survival rates predicted with the Mayo multicenter survival model were 0.860, 0.775 and 0.737 (P<0.001). CONCLUSIONS: In advanced disease, occlusion of major bile ducts with time occurs in the majority of patients. Endoscopic opening of dominant stenoses is effective and appears to be a valuable addition to the medical treatment of such patients.

Adolescent↗