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Biomedical subjects

C von Ritter

Publications and source records attributed to C von Ritter.

At least 19 recordsLinked to original sources

Extracorporeal shock wave lithotripsy for clearance of bile duct stones resistant to endoscopic extraction.

BACKGROUND: Endoscopic extraction of bile duct stones after sphincterotomy has a success rate of up to 95%. Failures occur in patients with extremely large stones, intrahepatic stones, and bile duct strictures. This study examined the efficacy and the safety of extracorporeal shock-wave lithotripsy in a large cohort of patients in whom routine endoscopic measures including mechanical lithotripsy had failed to extract bile duct stones. METHODS: Out of 1587 consecutive patients, endoscopic stone extraction including mechanical lithotripsy was unsuccessful in 313 (20%). These 313 patients (64% women, median age, 73 years) underwent high-energy extracorporeal shock-wave lithotripsy. Stone targeting was performed fluoroscopically (99%) or by ultrasonography (1%). RESULTS: Complete clearance of bile duct calculi was achieved in 281 (90%) patients. In 80% of the patients, the fragments were extracted endoscopically after shock-wave therapy; spontaneous passage was observed in 10%. For patients with complete clearance compared with those without there were no differences with regard to size or number of the stones, intrahepatic or extrahepatic stone location, presence or absence of bile duct strictures, or type of lithotripter. Cholangitis (n = 4) and acute cholecystitis (n = 1) were the rare adverse effects. CONCLUSIONS: In patients with bile duct calculi that are difficult to extract endoscopically, high-energy extracorporeal shock-wave lithotripsy is a safe and effective therapy regardless of stone size, stone location, or the presence of bile duct stricture.

Adult↗

Human biliary mucin binds to E-selectin: a possible role in modulation of inflammation.

E-selectin, expressed on endothelial cells, mediates adhesion of leukocytes and tumor cells to endothelium. CA19-9 (sialyl-Lewis(a)) and sialyl-Lewis(x) are specific ligands for E-selectin. We have recently shown that mucin-rich culture media from human gallbladder epithelial cells contains CA19-9. In this study, we have tested whether human biliary mucin binds to E-selectin. The ability of mucins to inhibit the adhesion of HL-60 cells to immobilized E-selectin was taken as an index for E-selectin binding. Gallbladder bile, hepatic bile, and culture medium from human gallbladder epithelial cells completely inhibited the adhesion of HL-60 cells to E-selectin. The mucin-rich fractions of human bile exhibited strong inhibition, whereas mucin-free fractions had little effect. In contrast to human bile samples, CA19-9-free medium from cultured dog gallbladder epithelial cells failed to inhibit HL-60 binding. Furthermore, after CA19-9 immunoaffinity chromatography, which selectively extracted CA19-9 from bile, bile samples showed poor inhibition of HL-60 adhesion to immobilized E-selectin. A good correlation was observed between E-selectin binding and CA 19-9 concentrations in bile. Our results show that human bile has E-selectin binding activity that is mediated by the CA19-9 side chain of biliary mucin.

Animals↗

Reduced myocardial cellular damage and lipid peroxidation in off-pump versus conventional coronary artery bypass grafting.

BACKGROUND: The development of new surgical devices and techniques allows off pump coronary artery bypass grafting (OPCAB) without the use of CPB and cardioplegia. This study tested whether OPCAB reduces myocardial cell damage, lipid peroxidation and systemic endothelin release when compared to conventional coronary artery bypass grafting. METHODS: Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13) or were treated conventionally using extracorporeal circulation, blood cardioplegia and hypothermic arrest (29-31 degrees C; n = 13). Troponin I and creatine kinase - MB were determined for cardiac specific cell damage. Myocardial and systemic malondialdhyde levels were measured to account for oxyradical mediated lipid peroxidation. Systemic big-endothelin levels were determined as a marker for endothelial cell activation. RESULTS: A significant reduction of the cardiac specific cell damage was observed in the OPCAB group vs. the CABG group over time in the absence of acute myocardial ischemia or infarction. In addition, systemic and myocardial lipid peroxidation as measured by the malondialdehyde (MDA) levels were lower in the OPCAB group when compared to CABG. Finally, plasma levels of big-Endothelin (big-ET) significantly rose in the CABG but not in the OPCAB group. CONCLUSIONS: The data of the present study indicate that OPCAB revascularization without the use of CPB and cardioplegic arrest reduces myocardial cell damage and lipid peroxidation. It is also associated with a reduced activation of the potent vasoconstrictor peptide endothelin. All of this may contribute to improved myocardial function and faster postoperative recovery from surgical revascularization procedures, particularly in critically ill patients.

Aged↗

Detection of colonic dysplasia by light-induced fluorescence endoscopy: a pilot study.

Light-induced fluorescence endoscopy (LIFE) has been shown to differentiate between normal mucosa and dysplastic lesions, and dysplastic lesions of the colon occult to routine white-light colonoscopy may thus be visualized by LIFE. We compared the sensitivity and specificity of LIFE to routine white-light colonoscopy in patients with colonic dysplasia. In a pilot study 20 patients with colonic adenoma, inflammatory bowel disease, or with a history of colon cancer were screened for colonic dysplasia during routine colonoscopy. Forty-two sites of mucosal abnormalities regarded as suspicious for dysplasia during white-light colonoscopy were additionally examined with a prototype LIFE system. Biopsies were taken from all 42 colonic sites. The LIFE images were classified as positive or negative for dysplasia. Sensitivity and specificity were calculated by correlating positive and negative findings to the histopathological results. Histopathology detected 21 adenomas with low-grade dysplasia and one with high-grade dysplasia. All dysplastic lesions were found by routine white-light endoscopy. The specificity of conventional white-light endoscopy was 80%. Of the 22 dysplastic lesions 20 were detected by LIFE (sensitivity 91%). The specificity of LIFE was 90% (two false-positive results). LIFE combined with conventional endoscopy may thus improve the detection of colonic dysplasia.

Adult↗

Bile acid malabsorption as a cause of chronic diarrhea: diagnostic value of 7alpha-hydroxy-4-cholesten-3-one in serum.

To evaluate the usefulness of 7a-hydroxy-4-cholesten-3-one (HCO) serum concentrations as a diagnostic marker of bile acid malabsorption, we determined the reference range of HCO in 106 normal subjects (age 40.2+/-16.8 years; 55 women, 51 men) and conducted a utility study in 23 patients with chronic diarrhea of unknown origin (age 49.4+/-15.3 years, 13 women, 10 men). The diagnosis of bile acid malabsorption was made on the basis of a decreased retention of [75Se]homocholyltaurine after oral application (75SeHCAT test). HCO (reference range: 6-48 ng/ml) and the 75SeHCAT test yielded the same results in 19/23 (83%) patients. Bile acid malabsorption was identified by an increase of HCO in serum with a sensitivity of 90% and a specificity of 79%. Analysis of HCO in serum may serve as a novel, simple, and sensitive method for the detection of bile acid malabsorption in patients with chronic diarrhea of unknown origin.

Adult↗

Effect of bile acids on lipid peroxidation: the role of iron.

The toxic effect of hydrophobic bile acids is claimed to be in part mediated by lipid peroxidation. Conversely, antioxidant properties of tauroursodeoxycholic acid (TUDC), a hydrophilic bile acid, have been suggested as a possible mechanism by which TUDC confers its beneficial effect in a variety of diseases. We have investigated the effect of taurodeoxycholic acid (TDC), a hydrophobic bile acid and TUDC on lipid peroxidation using a pure lipid system both in the presence and absence of iron ions. Neither TDC nor TUDC showed any effect on spontaneous lipid peroxidation of phosphatidylcholine liposomes or sodium arachidonate solution. This lack of effect excludes the possibility of direct prooxidant or antioxidant properties for TDC and TUDC. Addition of ferrous ions (0.1 mM) to the lipid system brought about a linear increase in lipid peroxidation with time. The presence of TDC caused an increase in the rate and extent of iron-stimulated lipid peroxidation. The propensity of bile acids to increase iron-induced lipid peroxidation was related to hydrophobicity of the individual bile acids, with the highest effect observed with taurolithocholic acid, whereas TUDC did not have any influence. The TDC-induced increase in the iron-stimulated lipid peroxidation was concentration dependent. Addition of TUDC (10 mM) completely abolished the effect of TDC (2 mM) on iron-induced lipid peroxidation. This finding suggests that TUDC does not function as an antioxidant per se but may prevent lipid peroxidation caused by TDC. In conclusion, only in the presence of iron ions, hydrophobic bile acids may enhance lipid peroxidation. TUDC has no antioxidant activity per se but may counter the TDC-induced increase in iron-stimulated lipid peroxidation.

Arachidonic Acid↗

[Chronic inflammatory bowel diseases. Pathophysiology and drug therapy].

Recent studies indicate that the normal intestinal flora, an exaggerated reaction of the intestinal immune system and a decreased epithelial barrier function of the gut play an important role in the pathogenesis of Crohn's disease and ulcerative colitis. The medical therapy of inflammatory bowel disease aims to correct these alterations. Aminosalicylates, corticosteroids, immunosuppressants and antibiotics are the four main groups of substances which are currently used for the therapy of inflammatory bowel diseases. Slow release formulation allow specific targeting of 5-aminosalicylic acid to the inflamed sections of the gut; with budesonid a corticosteroid therapy with minimal systemic side effects is possible. Future therapeutic options include specific immuno-modulatory therapy with cytokines or cytokine antibodies. Maintenance therapy may, conceivably, be performed with probiotics or antioxidants. Therefore, despite continued uncertainty about the cause of inflammatory bowel diseases, recent advances nourish the hope for further improvement of the control of disease activity and a better quality of life for patients with inflammatory bowel diseases.

Adrenal Cortex Hormones↗

[MRI of the small intestine with rapid MRI sequences in Crohn disease after enteroclysis with oral iron particles].

PURPOSE: To evaluate the efficacy of breathhold MRI following enteroclysis with addition of oral magnetic particles to study the extension, detection of stenoses and extraluminal manifestations in Crohn's disease. MATERIAL AND METHODS: 18 patients with Crohn's disease and potential of surgical intervention were studied with enteroclysis with addition of oral magnetic particles. T1-/T2-weighted breathhold MRI w/o spectral fat suppression w/o i.v. Gd-DTPA was applied. RESULTS: Typical findings were marked bowel wall thickening with strong contrast enhancement. 95.8% of affected small bowel segments and 94.7% of stenoses were correctly detected by MRI. All four fistulas were detected and important extraluminal findings were seen in 6/18 patients. Additionally, one ileoileal and two ileosigmoidal adhesions, two extraluminal abscesses and affection of the right ureter were delineated. CONCLUSION: MRI in Crohn's disease offers the potential to avoid radiation exposure in this relatively young patient group. Important additional findings relevant to indication of surgery are seen in approximately one third of cases. The replacement of transduodenal intubation by oral contrast application remains to be further studied.

Administration, Oral↗

Reactive oxygen metabolites promote cholesterol crystal formation in model bile: role of lipid peroxidation.

In animal models of gallstone disease inflammatory alterations of the gallbladder mucosa are regularly found before the first appearance of cholesterol monohydrate crystals in bile. At sites of inflammation granulocytes generate reactive oxygen metabolites (ROM). The aim of our study was to investigate whether ROM may influence the cholesterol monohydrate crystal formation in supersaturated model bile. Superoxide anions (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (.OH) were generated by the interaction of Fe(3+)-EDTA with ascorbic acid (Asc). The influence of ROM on cholesterol crystal formation was studied by measurement of the nucleation time. To check whether lipid peroxidation was induced by the ROM generation, production of malondialdehyde equivalents was measured in bile with the thiobarbituric assay. Furthermore, the lipid pattern of bile after ROM exposure was analyzed by thin layer chromatography. Addition of Fe(3+)-EDTA/Asc to model bile markedly decreased the cholesterol nucleation time (NT) (p < 0.01), caused a significant increase in malonidialdehyde equivalents (p < 0.001) and induced the generation of 4-hydroxy-2,3-trans-nonenal (4-HNE). In an attempt to identify a specific oxygen metabolite responsible for the alterations in bile, the effects of various oxygen radical scavengers were tested. Desferal, which prevents -OH generation by chelation of ferrous iron, completely protected bile against Fe(3+)-EDTA/Asc-induced decrease in NT (p < 0.001), increase in lipid peroxidation (p < 0.001) and generation of 4-HNE. Our results indicate that formation of cholesterol crystals in model bile is enhanced by ROM. Hydroxyl radical induced lipid peroxidation appears to be the mechanism responsible for the crystallisation promoting activity of ROM.

Ascorbic Acid↗

Simvastatin added to ursodeoxycholic acid does not enhance disappearance of gallstone fragments after shock wave therapy.

Inhibitors of the HMG-CoA reductase have been shown to further reduce the biliary cholesterol saturation in patients treated with oral bile acids for cholesterol gallbladder stones. It was the aim of our study to evaluate the efficacy of simvastatin in addition to ursodeoxycholic acid in the dissolution of gallstone fragments after shock wave lithotripsy and adjuvant bile acid dissolution therapy. Eighteen patients with a single radiolucent gallbladder stone and a serum cholesterol of more than 250 mg/dl were randomly assigned to receive either ursodeoxycholic acid alone (750 mg per day, group A, n = 9) or in combination with simvastatin (20 mg per day, group B, n = 9) for the dissolution of the gallstone fragments generated by extracorporeal shock wave lithotripsy. The two groups were well matched regarding their baseline characteristics. At the primary end point of the study 6 months after lithotripsy, there was no difference between the groups in the rate of gallstone disappearance with 4 of 9 patients being stone free in each group. As evaluated by life table analysis, even further follow-up showed no significant difference between the groups (P = 0.8). In group B, serum cholesterol levels decreased by 22% at 3 months (P = 0.01 vs. baseline) and by 24% at six months (P = 0.02) during treatment while no significant change was observed in group A. With both regiments, no adverse effects were observed. While simvastatin added to ursodeoxycholic acid resulted in a decrease of elevated serum cholesterol levels in gallstone patients, it did not enhance stone disappearance after shock wave lithotripsy and adjuvant bile acid dissolution therapy.

Anticholesteremic Agents↗

Quantification of mucin in human gallbladder bile: a fast, specific, and reproducible method.

It is generally accepted that gallbladder mucin (GBM) plays an important role in the pathogenesis of cholesterol gallstone (ChG) disease. However, it remains unclear whether ChG patients have higher GBM concentrations than controls. Discrepant findings regarding biliary mucin concentrations may be due to methodological problems with the assays commonly used. The methods currently used to quantitate mucin in bile have not been systematically evaluated. To establish a reliable method for mucin quantification in bile, we evaluated three mucin assays: the classic Pearson-PAS (periodic acid Schiff) assay, a direct fluorometric assay, and a new PAS or fluorometric assay with the following modifications of the Pearson assay: preincubation of bile samples with TBS containing KSCN and sodium taurocholate and micellation of biliary lipids during gel chromatographic fractionation using 25 mM sodium taurocholate in the elution buffer. SDS-PAGE and monoclonal anti-human-GBM (GBM59) were used to identify mucin. Highly specific and reproducible mucin isolation was achieved with the modified method. We found considerable loss of mucin during the different purification steps in the Pearson method. The direct fluorometric assay showed unspecific fluorometric signal with low molecular constituents of bile. Our experiments showed that human-GBM can be accurately measured after a simple modified chromatographic fractionation followed by a PAS or fluorometric assay.

Bile↗

Gallbladder emptying determines early gallstone clearance after shock-wave lithotripsy.

BACKGROUND/AIMS: Disappearance of gallbladder stones after shock-wave lithotripsy combined with bile acid therapy depends on mechanical evacuation and dissolution of fragments. Many patients with gallstones have impaired gallbladder emptying and may show delayed stone clearance after lithotripsy. METHODS: The effect of gallbladder emptying on gallstone clearance after lithotripsy was prospectively studied in 57 patients with one radiolucent gallbladder stone < or = 20 mm. Gallbladder emptying was assessed sonographically before and after 2 weeks of ursodeoxycholic acid (UDCA) treatment. RESULTS: UDCA increased gallbladder fasting and residual volume and decreased ejection rate but did not affect ejection fraction. Patients with an ejection fraction > 60% achieved complete gallstone clearance after lithotripsy in a higher percentage than patients with smaller ejection fractions (1 month, 31% vs. 7%, P = 0.022; 2 months, 55% vs. 18%, P = 0.003; 3 months, 66% vs. 29%, P = 0.005). Patients who became stone-free within 1 month showed larger ejection fractions than patients with retained fragments (67% +/- 4% vs. 56% +/- 3% before UDCA, P = 0.032; 65% +/- 4% vs. 53% +/- 3% with UDCA, P = 0.017). Further, ejection rate during UDCA therapy was larger in patients with complete gallstone disappearance within 1 month than in patients with delayed fragment clearance (1.57%/min +/- 0.36%/min vs. 0.76%/min +/- 0.09%/min; P = 0.002). CONCLUSIONS: Gallbladder emptying is a major determinant of early gallstone clearance after lithotripsy.

Adult↗

Gallstone recurrence after shock-wave therapy.

BACKGROUND/AIMS: The long-term outcome of nonoperative gallstone therapy depends on both absence of stones and absence of biliary pain. The aim of the present study was to determine the rate of stone recurrence and the rate of symptoms within 5 years after successful shock wave lithotripsy combined with bile acid therapy. METHODS: One hundred consecutive patients (single stones, n = 89; 2 or 3 stones, n = 11) were followed up for a median of 4.3 years after stone disappearance and discontinuation of bile acids. RESULTS: Twenty-three of the 100 patients developed recurrent stones. Calculated by actuarial analysis, the recurrence rate was 7% +/- 3%, 11% +/- 3%, 13% +/- 4%, 20% +/- 5%, and 31% +/- 7% (mean +/- SD) at 1, 2, 3, 4, and 5 years, respectively. The recurrent stones were small (6 +/- 5 mm) and were associated with recurrent biliary pain in 14 (61%) of the 23 patients. Repeated shock wave lithotripsy and/or bile acid medication resulted in stone disappearance in only 10 of 20 patients with recurrence. CONCLUSIONS: The long-term rate of stone recurrence after lithotripsy of primarily solitary gallbladder calculi is lower than expected from post-bile acid dissolution trials. Recurrence of stones frequently is associated with recurrence of biliary pain.

Adult↗

Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease.

There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gallstone formation and mitigate biliary pain in gallstone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gallbladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 x 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05 +/- 0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94 +/- 0.27 versus 0.93 +/- 0.32 mg/ml) or total protein (5.8 +/- 0.9 versus 6.4 +/- 1.3 mg/ml), cholesterol saturation (1.3 +/- 0.2 versus 1.5 +/- 0.2), or nucleation time (2.0 +/- 3.0 versus 1.5 +/- 2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9 +/- 0.6 versus 5.6 +/- 1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Shockwave therapy of gallstones].

Extracorporeal shock-wave lithotripsy (ESWL) is a helpful adjunct for those bile duct stones which cannot be extracted by routine endoscopic measures including mechanical lithotripsy. For very large or impacted stones in the bile duct or stones in the intrahepatic biliary tree, and also for stones located in proximity to a bile duct stenosis, shock-wave therapy has proven to be safe and successful. More than 85% of the patients become free of stones after this therapy; they otherwise would have had to undergo high-risk open bile duct surgery. For gallbladder calculi, the pivotal factor for complete fragment disappearance after shock-wave therapy is sufficient stone disintegration. Only if fragments not larger than 3 mm are achieved, complete expulsion and/or dissolution of these fragments may be expected in a high percentage of the patients. Optimal candidates include patients with a single, radiolucent stone in a well-contracting gallbladder. For this group, ESWL is a safe and effective noninvasive therapeutic alternative.

Cholelithiasis↗

Cholesterol nucleation time in gallbladder bile of patients with solitary or multiple cholesterol gallstones.

Patients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined. The cholesterol nucleation time was significantly (p less than 0.01) longer in the bile from patients with solitary stones (less than 1 to 16 days, median = 2.0 days) than in the bile from patients with multiple stones (less than 1 to 8 days, median = 1.0 days). Moreover, 15 of 71 (21.1%) patients with solitary cholesterol stones but only 1 of 42 (2.4%) patients with multiple cholesterol stones showed a normal (greater than 4 days) nucleation time. However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 +/- 0.65 vs. 1.54 +/- 0.59, mean +/- S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones.

Bile↗