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Biomedical subjects

H Bühler

Publications and source records attributed to H Bühler.

At least 19 recordsLinked to original sources
PubMed2004

Impairment of the antiproliferative effect of glucocorticosteroids by 11beta-hydroxysteroid dehydrogenase type 2 overexpression in MCF-7 breast-cancer cells.

To verify the relevance of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in controlling breast-cancer cell growth, we have evaluated the correlation of 11beta-HSD2 expression and antiproliferative effects of glucocorticosteroids (GCs) on breast cancer cell proliferation. We cloned human 11beta-HSD2 cDNA into the expression vector pBK-CMV. The interspersing lac promoter region was deleted, achieving differential translational efficiency. The constructs were stably transfected into wild-type MCF-7 breast-cancer cells possessing almost no oxidative and no reductive 11beta-HSD activity. Low (times 7) and high (times 718) 11beta-HSD2 overexpression was achieved. We compared growth behavior of transfected cells In the presence of GCs to MCF-7 cells transfected with pBK-CMV alone (internal control). The antiproliferative effects of GCs were reversed and total cell growth boosted by overexpression of 11beta-HSD2; about 50 % of the increase in cell proliferation was attained by low 11beta-HSD2 overexpression, while high enzyme overexpression led to an increase in cell growth of about 120 %. Using direct evidence, this study shows 11beta-HSD2 to impair antiproliferative glucocorticosteroid effects, thus acting as an enzymatic shield aggravating breast-cancer cell growth. These results indicate a possible therapeutic role for 11beta-HSD inhibitors in the treatment of breast cancer.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

[Quality of long-term oral anticoagulation: an observation study].

The aim of this observation study was to analyse the quality of the oral anticoagulation in a non-randomised field. Prospectively all patients with an oral anticoagulation were registered when entering the hospital. An assessment was made of the indication for the oral anticoagulation, the co-medication (especially the ones that influence the effect of the anticoagulation), the current International Normalized Ratio (INR), as well as any possible complications. All INR values were taken from the personal anticoagulation card of the patient. 140 patients were identified for the study. 16% of these patients had no obvious indication for an oral anticoagulation. Of the 1278 registered INR values, 582 (46%) were within the recommended range, according to the common guidelines. 359 (28%) INR values were too high and 337 (26%) were too low. 39 (28%) anticoagulation cards had been kept with the prothrombin time instead of INR measurements. The results of this observation survey show that the quality of the oral anticoagulation in a non-randomised field is mostly insufficient.

Administration, Oral↗
PubMed2002

11beta-hydroxysteroid dehydrogenase type 1: a new regulator of fetal lung maturation.

Glucocorticoids (GCs) induce surfactant synthesis in the late fetal lung. Deficient GC action causes respiratory distress syndrome. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. We investigated 11beta-HSD1 in the late fetal lung using the licorice-derived inhibitor, glycyrrhetinic acid (GE), in pregnant rats (day 13 of gestation until term). Control fetal mice and rats showed high 11beta-HSD activity in the late fetal lung; levels of plasma 11-dehydrocorticosterone were also high. Reduction/loss of pulmonary 11beta-HSD1 activity in GE-treated rats substantially impaired fetal lung maturation. Lungs from GE-exposed rats had lower surfactant protein-A (mRNA and protein) levels and reduced amniotic fluid lecithin/sphingomyelin ratios. There was a marked depletion of lung surfactant before and after birth, as detected by both light and electron microscopy. The data emphasize the importance of 11beta-HSD1 in amplifying key GC-dependent maturational processes in the late fetal lung.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Ontogeny of 11beta-hydroxysteroid dehydrogenase: activity in the placenta, kidney, colon of fetal rats and rabbits.

Mechanisms to regulate closely fetal GC exposure are of considerable importance, as certain organs (kidney, brain) are adversely affected by excess GCs. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) reduces transplacental passage of maternal GCs to the fetus. We hypothesized that 11beta-HSD2, if active in fetal kidney and colon, might allow local tissue modulation of GC access during the critical last trimester. We determined the presence, ontogeny and functionality of 11beta-HSD in the placenta and fetal, neonatal and adult kidney and colon in rats and rabbits and the cortisol:cortisone ratio in human amniotic fluid, which represents fetal urine. There was clear a 11beta-HSD2 expression in last trimester fetal colon, kidney and placenta in both rats and rabbits. This appeared of functional importance, since the potency of cortisol on fetal rabbit colonic sodium flux in the Ussing chamber was increased by 11beta-HSD inhibition. In human amniotic fluid, we found a decreasing ratio of cortisol:cortisone across the last trimester, suggesting an analogous onset of renal 11beta-HSD2 activity in the human fetal kidney. Local fetal tissue 11beta-HSD2 may modulate exposure to the deleterious effects of GCs upon target tissue maturation during sensitive periods of late gestation when fetal GC levels rise to prepare other organs (lung) for adaptations at birth.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Current use of HER2 tests.

Reliable detection of HER2 overexpression is important for the success of trastuzumab (Herceptin) therapy. Several methods are available for measuring HER2 expression at the DNA, RNA or protein level. The method most frequently employed is immunohistochemical (IHC) detection of the HER2 receptor in paraffin sections. Advantages include the precise localization of the HER2 protein, the availability of paraffin material and the ease of the procedure. However, IHC can be influenced by the sensitivity/specificity of the antibody, tissue treatment and, in particular, subjective assessment. These disadvantages do not exist in the detection of gene amplification by fluorescence in situ hybridization (FISH) or polymerase chain reaction. However, FISH requires expensive equipment that is not widely available in pathology laboratories. Another approach quantitates shed HER2 antigen in the serum by an enzyme-linked immunosorbent assay. The key advantage of this method is the ease of sampling blood, however, serum HER2 concentrations do not accurately reflect the tumor status. Furthermore, this method does not register single-cell expression, which is important for therapeutic decision making. For routine diagnostics, the combination of IHC and FISH is useful. In addition to improving the accuracy and comparability of HER2 assays, these optimized protocols may further enhance the efficacy of trastuzumab therapy by selecting those patients most likely to respond.

Biomarkers, Tumor↗
PubMed2000

A convenient synthesis of optically active 5,5-disubstituted 4-amino- and 4-hydroxy-2(5H)-furanones from (S)-ketone cyanohydrins.

(S)-Ketone cyanohydrins (S)-2 are accessible by enantioselective HCN addition to ketones 1 by using hydroxynitrile lyase from Manihot esculenta ((S)-MeHNL) as a biocatalyst. Acylation of (S)-2 gave the corresponding (S)-acyloxynitriles (S)-3, which can be cyclized by LHMDS to give 5,5-disubstituted (S)-4-amino-2(5H)-furanones (S)-4 and (S)-5. Different substituents (H. Me, OBn, OH) in the 3-position of the furanones were introduced by selecting the appropriate acylating agent, which in the case of benzyloxyacetyl chloride led to the novel structure type of 4-amino-3-hydroxyfuranones (S)-5. For the synthesis of 5,5-disubstituted (S)-tetronic acids (S)-8, ketone cyanohydrins (S)-2 were first transformed into the corresponding 2-hydroxy esters (S)-6. Acylation of (S)-6 gave 2-acyloxy esters (S)-7, which, by treatment with LHMDS or LDA, afforded tetronic acids (S)-8 in high yields and enantiomeric excesses. By debenzylation of benzyloxy acetoxy derivatives (S)-8e,f, the new vitamin C analogues (S)-9a,b were generated. All the described tetronic acid and aminofuranone derivatives were obtained in good chemical yields and without racemization with respect to the starting cyanohydrins (S)-2. In many cases the enantiomeric purity could be enriched by simple recrystallization (e.g. (S)-4a from 69% ee to > 99% ee).

Acylation↗
PubMed2000

Kinetic studies on rabbit liver glucocorticoid 5alpha-reductase.

The serum concentration of active glucocorticosteroids depends not only on adrenal synthesis but also on enzymatic activation of 11-dehydro-glucocorticoids in the liver by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). In order to define the respective involvement of other regulative enzymes in the metabolism of 11-dehydro-glucocorticoids in the liver, the objective of this study was to evaluate the kinetic behavior of NADPH:delta 4-3-ketosteroid-5alpha-reductase (5alpha-reductase, EC 1.3.99.5). The interrelations to liver 11beta-HSD1 will be discussed. The kinetic properties of 5alpha-reductase of the rabbit liver were measured by a radioenzymatic assay and characterized with respect to protein-, substrate-, cosubstrate-, and pH-dependence. Michaelis-Menten enzyme kinetic parameters (Km and Vmax) were obtained for the formation of 5alpha-reduced 11-dehydrocorticosterone and corticosterone metabolites. We found that both 11-dehydrocorticosterone (Km 4.2 x 10(-6) mol/l, Vmax 2,600 pmol x min(-1) x mg(-1)) and corticosterone (Km 0.5 x 10(-6) mol/l, Vmax 38 pmol x min(-1) x mg(-1)) exhibit a high affinity to 5alpha-reductase. With respect to cosubstrate-, pH-dependence and finasteride inhibition, it is likely that 11-dehydrocorticosterone metabolism is primarily controlled by isoenzyme 5alpha-reductase type 1. This study shows that the deactivation of GCS especially of 11-dehydro-glucocorticoids via 5alpha-reductase is an important metabolic pathway in the liver. The metabolic activation of GCS by 11beta-HSD could possibly lead to an excess of GCS in the hepatocytes. Due to 5alpha-reductase activity this excess can be limited - on the level of CORT as well as of 11-DHC.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

[Ticlopidine-induced cholestasis].

UNLABELLED: We report a case of ticlopidine-induced cholestatic hepatitis. CASE SUMMARY: An 82-year-old man suffered a myocardial infarction in February 1998. Because of persistent angina pectoris a coronary stent was implanted in May 1998. At this time medication with 1 x 250 mg ticlopidine was started in addition to the preexistent medication of aspirin 1 x 100 per day, metoprolol fumarate 1 x 95 mg per day and isosorbide dinitrate 1 x 100 mg per day. Three weeks after starting ticlopidine the patient complained of itching, and on day 28 painless jaundice developed. At this time, the serum activities of alkaline phosphatase (923 U/l), gamma-GT (823 U/l) and total bilirubin concentration (129 mumol/l) were markedly elevated, whereas the activities of the transaminases (AST 131 U/l, ALT 194 U/l) were slightly increased. An extra- or intrahepatic biliary obstruction was ruled out, and there were no signs of a toxic, infectious or immunological cause for the hepatic injury. Liver biopsy showed centro-acinar cholestasis. After drug discontinuation the itching stopped after 4 weeks and jaundice disappeared after 2 weeks. Eight months after the onset of symptoms, the activities of alkaline phosphatase (226 U/l) and gamma-GT (213 U/l) were still elevated but the patient was asymptomatic. CONCLUSIONS: Ticlopidine-induced mild serum liver enzyme elevations have been observed in some studies (incidence 1-2%). The incidence of severe hepatitis has been estimated at 0.0013%. Only a few cases (in approximately 20 patients receiving ticlopidine) of a severe cholestatic pattern of injury have been reported. In all cases the jaundice resolved and serum liver enzyme concentrations normalised over a period of months. Characteristically, liver biopsies demonstrated centro-acinar cholestasis. Monitoring of serum liver enzyme concentrations is not recommended. When itching or jaundice occur in a patient taking ticlopidine, the possibility of toxic liver damage should be taken into account.

Aged↗
PubMed1999

Impact of the endothelin system on water and sodium excretion in patients with liver cirrhosis.

BACKGROUND: Impaired renal function in patients with liver cirrhosis is a serious complication and is characterized by sodium and water retention in the absence of identifiable specific causes of renal dysfunction. The endothelin system has been shown to be activated in liver cirrhosis and might contribute to impaired renal function. However, the mechanisms leading to an activation of the endothelin system in these patients and the effects of an activated endothelin system on renal function in these patients are as yet unknown. METHODS: To determine the correlation between the activity of the endothelin system and the ability to excrete water and sodium in patients with liver cirrhosis, we measured plasma endothelin-1 concentrations by reversed phase-HPLC followed by an endothelin RIA and performed an oral water load tests in 10 healthy control subjects and 43 patients with liver cirrhosis. In addition, we analysed possible mechanisms/factors like plasma endotoxin that might contribute to the activation of the endothelin system in liver cirrhosis. RESULTS: This study showed that the endothelin system is activated in patients with liver cirrhosis in a disease-stage-dependent manner. Patients with Child C liver cirrhosis have a 5.45-fold increased plasma ET-1 concentration compared to healthy controls, whereas plasma ET-1 is only increased 2.74-fold in Child A patients. An oral water load test revealed a highly significant (P < 0.0001) inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water load. Plasma endotoxin, a well-known stimulus of ET-1, is significantly (P < 0.03) correlated with plasma ET-1 in cirrhotic patients. The ET-1 concentrations in the ascites of patients with liver cirrhosis were lower and not related to plasma ET-1. CONCLUSION: The activity of the endothelin system in patients with liver cirrhosis depends on the severity of liver impairment. Plasma endotoxin might be an important stimulus of the endothelin system in liver cirrhosis. We observed a highly significant inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water and sodium load, suggesting that the endothelin system plays a role in the regulation of water excretion in patients with liver cirrhosis.

Case-Control Studies↗
PubMed1997

[Bile duct cysts in adults].

INTRODUCTION: Bile duct cysts are rare, congenital dilations of the intrahepatic and/or extrahepatic biliary tract. Most of them present during childhood. The classical triad right upper quadrant pain, jaundice and abdominal mass is present only in a few instances. We report here the bile duct cysts which were diagnosed at our institution from 1989 to 1996. METHODS: 3245 consecutive endoscopic retrograde cholangiopancreatograms (ERCP) were evaluated retrospectively. Diagnosis was made when localized cystic dilations of the intrahepatic and/or extrahepatic biliary tract were present. Diffuse dilations of the intrahepatic and extrahepatic biliary tract were excluded. RESULTS: Bile duct cysts were found in 20 patients (17 females, 3 males) among 3245 ERCPs. Their mean age was 56 +/- 20 (median 64, range 10 to 83) years. The cyst types (according to the Alonso-Lej classification with the Todani modification) were type I in 11 (55%), type II, III and IV in two instances each (10%), and type V (or Caroli's disease) in 3 patients (15%). Leading symptoms were cholestasis in 14 patients, 10 of whom had abdominal pain, jaundice in 4 patients, and single cases of pancreatitis, cholangitis, and abdominal mass. In 2 patients the diagnosis was made incidentally. 10 patients had bile duct stones. We performed endoscopic sphincterotomy in 15 patients with concretions or persistent symptoms, 3 patients had cyst resection. One of these, with a type I cyst, already had a disseminated cholangiocarcinoma. 10 of 17 patients without cyst resection are currently symptom-free after complete removal of all gallstones. One male patient with cholecystolithiasis, who is not operable due to advanced liver disease, has recurrent cholangitis, 4 patients have died from causes unrelated to the bile duct cysts, and 2 patients are lost to follow up. CONCLUSION: Bile duct cysts in adults are rare. There is a preponderance in the female gender, and the most common type is the extrahepatic (choledochal) cyst. The leading symptoms are cholestasis and right upper quadrant pain. There is an increased risk of cholangiocarcinoma. In young patients the cysts should be entirely removed to prevent malignancy. Older persons are usually symptomless after complete removal of gallstones.

Adolescent↗
PubMed1997

Influence of hepatitis G virus infection on liver disease.

The influence of hepatitis G virus (HGV) infection on disease activity in hepatitis C related and unrelated liver disease was investigated in 254 individuals using an EIA polymerase chain reaction assay for HGV. One hundred patients had chronic hepatitis C, 26 primary biliary cirrhosis, and 30 alcoholic liver cirrhosis. In addition, 51 hepatitis B surface antigen (HBsAg)-positive and 47 anti-hepatitis C virus (HCV)-positive blood donors were screened. Hepatitis G virus was detected in 18% of patients with chronic hepatitis C, 13% of patients with alcoholic liver cirrhosis, 11% of patients with primary biliary cirrhosis, 10% of anti-HCV-positive blood donors, and 2% of HBsAg-positive blood donors. Virus load and alanine aminotransferase (ALT) levels did not differ significantly in patients with HCV alone versus patients coinfected with HCV and HGV. However, mild liver fibrosis correlated with HGV coinfection. Hepatitis G virus did not influence ALT levels or liver damage in liver disease unrelated to viral infection.

Adult↗
PubMed1997

Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.

Adult↗
PubMed1997

Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.

This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

[The absence of autoantibodies does not rule out autoimmune hepatitis].

UNLABELLED: The diagnosis of autoimmune hepatitis is mainly based on the finding of characteristic autoantibodies. Untreated patients have a poor prognosis because of rapid development of cirrhosis. Immunosuppressive treatment most often leads to remission. We report on 2 female patients aged 44 and 53 with autoimmune hepatitis. Initially no significant titers of autoantibodies against nuclear, cytosolic or microsomal components of the hepatocyte could be demonstrated. Seropositivity for autoantibodies was demonstrated 6 and 8 weeks later in the course. Immunosuppressive therapy with steroids resulted in rapid decrease of transaminases with persistent remission of autoimmune hepatitis. CONCLUSION: seropositivity for characteristic autoantibodies is not an absolute criterion for the diagnosis of autoimmune hepatitis. Patients with hepatitis of unknown origin should therefore be given a steroid treatment trial.

Adult↗
PubMed1996

[Clinico-pharmacological case (2). Bradycardia and ventricular tachycardia of the torsades de pointes type as a side effect of vasopressin: 3 case reports].

We present three patients with ornipressin-induced bradycardia, one of which developed also ventricular tachycardia of the torsade de pointes type. All three patients were treated with this vasopressin derivative because of bleeding esophageal varices due to portal hypertension in liver cirrhosis. Bradycardia ceased after discontinuing ornipressin therapy. One patient was treated successfully with atropine, one with isoprenalin and magnesium (he had to be defibrillated); the third patient recovered after cessation of ornipressin administration. Bradycardia is a known but rarely reported side effect of vasopressin and its derivatives. Animal studies suggest that this effect is due to its cardiodepressive action and also to a vagus-mediated reflex following vasopressin-induced increase in blood pressure. When injected directly into the ventricles of the brain, vesopressin leads to a decrease of the heart rate without affecting blood pressure; however, it remains unclear whether this mechanism is responsible for bradycardia after intravenous administration. Careful monitoring is essential during the treatment with vasopressin and its derivatives.

Aged↗
PubMed1996

Fixed versus titrated interferon-alpha 2B in chronic hepatitis C. A randomized controlled multicenter trial. The Swiss Association for the Study of the Liver.

BACKGROUND/AIM: Interferon has become the mainstay of treatment of chronic hepatitis C; however, duration of treatment and dose remain unresolved questions. The present study aimed to compare standard dose interferon with a titrated dose regimen carried out for 1 year. METHODS: This was a randomized, controlled multicenter trial. Patients with chronic hepatitis C were randomly allocated to a control group (n = 30), to a fixed dose group (n = 31) where interferon-alpha 2b 3 MU thrice weekly was given for 1 year or a titrated group (n = 34) where interferon was titrated starting at 5 MU thrice weekly to the lowest dose keeping the patient in remission as assessed by a normal ALT value. Liver biopsies were obtained before and at the end of treatment; in addition, galactose elimination capacity was measured as a measure of cytosolic function. RESULTS: In the control, fixed and titrated groups a complete response was achieved in 2/29, 10/28 and 15/31, respectively (p < 0.001 in favor of treatment, p = n.s. for the two treatments). The corresponding figure for sustained response was 1/29, 5/28 and 6/ 31 (p = n.s). In the titrated group, a complete (sustained) response was achieved with 5 MU in 2 (2), with 4 MU in 1 (0), with 3 MU in 4 (0), with 2 MU in 3 (0) and with 1 MU in 5 (4). Liver biopsy score and galactose elimination capacity improved significantly in responders but not in treatment failures. CONCLUSIONS: Both fixed and titrated dosing of interferon given for 1 year induced virus clearance in only a minority of treated patients. However, in a small number of patients, a complete and sustained response can be achieved with low doses of interferon. Dose titration could be an interesting approach to decreasing the cost and side effects in the treatment of chronic hepatitis C.

Adult↗
PubMed1996

Long-term follow-up after treatment of common bile duct stones by extracorporeal shock-wave lithotripsy.

BACKGROUND AND STUDY AIMS: The efficacy of extracorporeal shock-wave lithotripsy (ESWL) of difficult bile duct stones that were not amenable to routine endoscopic extraction was assessed, with evaluation of the long-term follow-up after successful treatment. PATIENTS AND METHODS: Fifty-four patients (mean age 74 years, range 33-92) were treated with ESWL for difficult bile duct stones. Treatment was performed either with the Dornier HM3 kidney lithotriptor (49 patients) or with the MPL 9000 lithotriptor (five patients). RESULTS: Stone disintegration was achieved in 50 patients (93%), with complete stone clearance in 45 patients (83%) (mean 1.2 session). Patients with successful stone removal after one session had significantly smaller stones than patients with treatment failure (20 +/- 9 versus 27 +/- 8 mm; p < 0.05). An intrahepatic location of stones was significantly associated with treatment failure (p < 0.005). Serve complications occurred in 7% (procedure-related 5%), with a 30-day mortality rate of 0% (in-hospital mortality rate of 2%). Minor side effects such as fever, petechiae, and mild arrhythmias were frequent (37%), and microhematuria (95%) occurred in nearly all of the patients. Symptomatic recurrent bile duct stones were observed in two patients (5%) after three and four years, respectively (mean follow-up 5.3 years). CONCLUSION: Extracorporeal shock wave lithotripsy represents a safe and effective treatment modality for difficult bile duct stones, with a low rate of symptomatic recurrences.

Adult↗