[Evaluation of liver function by means of the glucagon test].
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Biomedical subjects
Publications and source records attributed to G Paumgartner.
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To overcome the geometrical limitations of current methods to calculate gallbladder volume from two-dimensional sonographic images, we evaluated the accuracy and precision of a novel three-dimensional ultrasound system (3D). In vitro accuracy of 3D volumetry (10 mL to 55 mL) was 98.1 +/- 7.1% (mean+/-SD) with a mean difference of 0.7 mL between the measured and the true volume (p < 0.003). Compared with the sum-of-cylinders (SC) and the ellipsoid (EL) methods, 3D was characterized by a significantly smaller systematic bias and closer limits of agreement with the true volume. The variation coefficient was smallest with 3D (2.4%, p < 0.02) and largest with EL (4.2%). In vivo, gallbladder volumes were on average 1.4 mL (9%) smaller with 3D than with SC (p < 0.0001) and 2.4 mL (14%) larger with EL than with SC (p < 0.0001). 3D ultrasonography accurately measures gallbladder volume and emptying.
The value of serum bile acid concentrations for predicting prognosis in cirrhotics was compared with the prognostic significance of clinical and laboratory findings in a prospective 1-year study of 76 patients with cirrhosis. A commercial radioimmunoassay for total serum-conjugated primary bile acids was used. Of 76 patients, 16 died within the follow-up period. The concentration of bile acids in serum more closely correlated with mortality in cirrhosis than the commonly used clinical and laboratory parameters such as the Number Connection Test, ascites, albumin, pseudocholinesterase, bilirubin, prothrombin time and nutritional state. Serum bile acids alone yielded a prediction of mortality comparable to the Child classification. When logistic regression analysis was performed, optimal prediction of prognosis was achieved with the combination of serum bile acids and the Number Connection Test. Serum bile acid levels alone or in combination with the Number Connection Test may be a clinically useful prognostic index in cirrhosis.
Ascitic fluid concentrations of cholesterol, triglycerides and phospholipids, were compared with ascitic fluid total protein in 40 patients with chronic liver disease, 51 patients with various neoplasms and 1 patient with cardiac failure. Seven patients with both chronic liver disease and malignancy were considered separately. The first 54 patients (23 cirrhotic and 31 with malignancy) were used to determine median values and ranges and to define the most suitable cutoff concentrations between both groups. Median values for cholesterol (75 mg per dl), phospholipids 0.79 mmole per liter), triglycerides (75 mg per dl) and protein (3.8 gm per dl) were higher in malignant ascites compared to ascitic fluid concentrations of cholesterol (20 mg per dl), phospholipids (0.33 mmole per liter), triglycerides (51 mg per dl) and protein (1.9 gm per dl) in patients with cirrhosis. The best discrimination values were 48 mg per dl for cholesterol, 0.6 mmole per liter for phospholipids, 65 mg per dl for triglycerides and 2.5 gm per dl for protein. Application of these cutoff points to 38 subsequent patients (17 cirrhotic, 1 with cardiac failure and 20 with malignancy) revealed an efficiency of 86.8% for cholesterol, 86.8% for phospholipids, 68.4% for triglycerides and 79.0% for protein. From the data of all 92 patients, an efficiency of 92.3% for cholesterol, 79.4% for phospholipids, 72.8% for triglycerides and 79.4% for protein was calculated. We conclude that ascitic fluid cholesterol determination offers an excellent, cost-effective discrimination of ascites due to cirrhosis vs. ascites caused by malignancies.
To study the expression of MHC Class II subregion gene products on biliary epithelial cells in primary biliary cirrhosis, frozen sections from liver biopsies of 15 patients with primary biliary cirrhosis were studied immunohistochemically using HLA-D subregion specific monoclonal antibodies L243 (HLA-DR), Leu10 (HLA-DQ) and B7/21 (HLA-DP). Patients with early stages of primary biliary cirrhosis showed expression of HLA-DP, HLA-DR and HLA-DQ subregion gene products on bile duct epithelial cells. In advanced stages of disease, no MHC Class II antigens or only HLA-DR and HLA-DP were expressed on bile duct cells. While normal hepatocytes did not express detectable amounts of MHC Class II antigens, hepatocytes from liver biopsies of four patients with primary biliary cirrhosis showed a distinct staining exclusively with monoclonal antibodies specific for HLA-DR. The expression of MHC Class II antigens on parenchymal cells was independent of a lymphocytic infiltration into the tissue. This study demonstrates that bile ductular cells, but not hepatocytes, express a full set of MHC Class II molecules at least during the early stages of primary biliary cirrhosis. We propose, therefore, that the expression of both HLA-DR and HLA-DQ subregion products on bile duct epithelial cells may be a necessary, although not sufficient, condition for the initiation of an autoimmune process leading to the destruction of intrahepatic bile ducts in primary biliary cirrhosis.
The mechanism of ethinylestradiol-induced biliary secretion of excess cholesterol, a potential causative factor of cholesterol gallstones, is not yet known. It might be related to altered bile acid metabolism, since the rate of cholesterol and phospholipid secreted into bile is thought to be influenced by the hydrophobicity of the bile acid species secreted. We therefore studied the effect of ethinylestradiol on bile acid metabolism and on secretory relationships between taurocholate and cholesterol/phospholipids in bile. Litter-matched Syrian female hamsters (80 to 100 gm body weight) were injected subcutaneously with either 0.2 ml per day corn oil (controls) or a pharmacologic dose of 5 mg per kg per day ethinylestradiol in corn oil (EE-hamsters; n = 6) for 5 days. On Day 6, bile was collected for 60 min (basal secretory rate) via a bile duct fistula after exclusion of the gallbladder. Then, a graded infusion of taurocholate was given for 110 to 130 min. Secretory rates (nmoles.min-1.-1 liver) for bile acids, cholesterol and phospholipids were determined and their mutual "linkage coefficients" (nmoles of secretory increment per 1 nmole of bile acid secreted) calculated by linear regression analysis. EE-hamsters had higher (p less than 0.02) basal secretory rates of cholesterol (0.71 +/- 0.21 vs. 0.45 +/- 0.10) and phospholipids (5.74 +/- 1.04 vs. 4.21 +/- 0.73) than controls at comparable bile flow and bile salt secretion rates. Cholic acid pool size and the fractional composition of bile acid species in bile were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Eighty in vitro experiments were performed with single (n = 51) or multiple (n = 29) gallstones in order to find out which parameters are of prime importance for their disintegration by extracorporeal shock waves. A Dornier lithotripter and an upper limit of 1,500 discharges were employed. Although computed tomography density was significantly lower in cholesterol stones than in the noncholesterol stones (p less than 0.0001) and although the latter were significantly more often radiopaque (p less than 0.0001), we found no clear-cut correlation between the cholesterol content or computed tomography density and the degree of fragmentation of the stones. The most important variable which limited successful disintegration was the total stone volume. In stones with a mean total volume of 0.83 ml +/- 0.25 S.E. (diameter for single stones = 11.5 +/- 0.9 mm), none of the fragments exceeded 2 mm, whereas in stones with a mean volume of 3.6 ml +/- 0.64 (diameter = 17.2 +/- 1.5 mm) at least one fragment larger than 2 mm remained (p less than 0.002). Under the in vitro conditions, fragmentation was similar in multiple and solitary stones, provided the volume of the stones was comparable. These data show that, in general, the number and size of the stones, i.e. their total volume, and much less significantly their chemical composition are the major determinants of fragmentation by extracorporeal shock waves.
Shock wave lithotripsy is a noninvasive treatment for gallstone disease, suitable for about 20% of the patients, and does not require anesthesia. Clearance of the fragments depends on: stone number and size, sufficient fragmentation and bile acid dissolution therapy. Several months are required for complete fragment disappearance. The recurrence rate is relatively low.
Five cases of surgical intervention following extracorporeal shock wave lithotripsy (ESWL) of gallbladder and bile duct stones are reported. This represents an incidence of surgical intervention in 1% of patients with gallbladder stones and in 9% of patients with common bile duct stones who underwent ESWL during a two-and-a-half-year investigation period. There was no mortality. In 2 patients with gallbladder stones and persistent colic after ESWL, elective cholecystectomy was performed. There was no evidence of macroscopic or microscopic damage or bleeding within the wall of the gallbladder. Furthermore, no damage to the liver, common bile duct, duodenum, or stomach was noted. ESWL was applied in 34 patients with common bile duct stones in whom endoscopic sphincterotomy and stone extraction had proved ineffective. Three (9%) of these patients required surgery. In 1 patient, a Dormia basket got stuck and the basket, together with the stone, were removed by choledochotomy. In a second patient, rupture of a juxtapapillary diverticulum occurred 10 days after ESWL and 2 days after endoscopic extraction of stone fragments. At laparotomy, the retroperitoneum was drained. In a third patient with gallbladder and common bile duct stones, acute cholecystitis developed after lithotripsy of common bile duct stones. Cholecystectomy was performed and a t-tube was inserted in the bile duct. In all patients, the postoperative course was uneventful. In our experience, ESWL is a safe procedure with no mortality and an infrequent need for surgical intervention.
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Serum CA 19-9 is increased in patients with different gastrointestinal malignancies. Unfortunately, CA 19-9 is also detected in high concentrations in normal bile causing unspecific serum elevations during inflammatory disease of the biliary tract and cholestasis. In order to identify the source of CA 19-9 in bile, the capacity of cultured human gallbladder epithelial cells (HGBEC) to secrete CA 19-9 was investigated. Cells were harvested from gallbladders removed by cholecystectomy and cultured for up to 14 days in collagen I coated 24-well culture dishes. CA 19-9 was measured in the culture medium by a solid-phase CA 19-9 EIA (Boehringer). In addition, culture medium was separated by Sepharose 4B-Cl, Concanavalin-A (Con-A) and CA 19-9 affinity chromatography. Significant CA 19-9 activity was measured in the culture medium after a 24 hour incubation period. Following separation of the culture medium by Sepharose 4B-Cl and Con-A affinity chromatography, 90% of the CA 19-9 activity was recovered in the exclusion volume (> 2000 kDa) from which 90% were identified as Con-A negative. A close correlation was found between CA 19-9 and concentrations of mucin purified from human gallbladder bile. Furthermore, CA 19-9 affinity chromatography selectively extracted mucins from the culture medium of HGBEC. Finally, addition of the mucin secretagogue bethanechol (6 mM) to the culture medium increased CA 19-9 activity in the medium. In conclusion, normal HGBEC secrete mucins carrying the epitope of CA 19-9. During inflammatory biliary disease unspecific elevation of CA 19-9 in serum may reflect both inflammatory hypersecretion and leakage of biliary mucins into serum.