Biomedical subjects
Publications and source records attributed to G Paumgartner.
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In 97 patients with radiolucent solitary gallbladder stones, the density of the calculi was evaluated by computed tomography (CT) prior to extracorporeal shock wave lithotripsy (ESWL). Sixty-three percent of the stones were isodense to bile (mean 48 +/- SD 11 HU), and 37% could be identified on CT-sections (maximal density 105 +/- 46 HU, mean density at the largest cross-section 53 +/- 31 HU). There was a slight trend toward better stone fragmentation and higher clearance rate in patients with isodense stones. However, the probability of complete fragment clearance was not significantly different in stones with a high or low CT-density. From these data we conclude that stone selection for ESWL and adjuvant bile acid therapy in patients with radiolucent solitary stones as assessed by oral cholecystography is only marginally improved by computed tomography.
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The authors tried to differentiate malignancy-related from nonmalignant ascites with a sequence of sensitive followed by specific ascitic-fluid parameters. There were four results of this study. First, of nine parameters investigated in a first series of 48 patients, 28 with nonmalignant and 20 with malignancy-related ascites, ascitic-fluid cholesterol and fibronectin yielded the best negative predictive value of 92% each. Carcinoembryonic antigen (CEA) and cytologic examination both showed a positive predictive value of 100%. Second, combining cytologic examination (sensitivity, 70%) and CEA determination (sensitivity, 45%) increased the sensitivity to 80%. Third, cytologic findings were negative in all ascitic-fluid samples with a cholesterol concentration below the cutoff value of 45 mg/100 ml. Fourth, based on the results of the first series of 48 patients, the diagnostic sequence with cholesterol as a sensitive parameter, followed by the combination of cytologic examination and CEA determination as specific parameters, was tested in a second series of 71 patients, 37 with nonmalignant and 34 with malignancy-related ascites. Again cytologic examination was negative in all samples with cholesterol levels below 45 mg/100 ml. In the total of 119 patients, this diagnostic sequence did not identify 9% of patients with malignancy-related ascites, and 82% of samples classified as malignancy related by cholesterol levels above 45 mg/100 ml were confirmed by positive cytologic examination and/or CEA level above 2.5 ng/ml. Thus, a diagnostic sequence with ascitic-fluid cholesterol determination, followed by cytologic examination and CEA determination, in samples with cholesterol levels above 45 mg/100 ml should permit a cost-efficient routine differentiation of malignancy-related from nonmalignant ascites.
OBJECTIVE: To evaluate the long-term results of three types of shock wave treatment in patients with radiolucent gallbladder stones. DESIGN: Cohort study. SETTING: Single-center trial. PATIENTS: Of 5824 patients with gallstones, 19% were eligible; 711 patients were treated. INTERVENTIONS: Patients received extracorporeal shock wave lithotripsy as well as adjuvant therapy with bile acids. RESULTS: Lithotripsy was done in three ways, using a water-tank lithotriptor (group A), a water-cushion lithotriptor at low energy levels (group B), and a water-cushion lithotriptor at high energy levels (group C). The rate of complete fragment clearance 9 to 12 months after lithotripsy was done differed significantly among the three groups: Among patients with single stones of 20 mm or less in diameter, the rate of fragment clearance for group A was 76%; for group B, it was 60%; and for group C, it was 83% (P = 0.03). Among patients with single stones of 21 to 30 mm, the rate of fragment clearance for group A was 63%; for group B, it was 32%; and for group C, it was 58% (P less than 0.005). Among patients with two or three stones, the rate of fragment clearance for group A was 38%; for group B, it was 16%; and for group C, it was 46% (P = 0.01). Patients with fragments of 3 mm or less 24 hours after lithotripsy was done showed a higher probability of fragment disappearance than did those with larger fragments (P less than 0.001). The clearance rate was higher in patients who were compliant than in those who were noncompliant with bile acid therapy (P less than 0.001). Adverse effects included liver hematoma in 1 patients, biliary pain attacks in 253 patients (36%), mild biliary pancreatitis in 13 patients (2%), and cholestasis in 7 patients (1%). Elective cholecystectomy was done in 16 patients (2%), and endoscopic sphincterotomy was done in 4 patients (1%). CONCLUSIONS: The rate of complete disappearance of stones after shock wave therapy depends on the size and the number of the initial stones, the diameter of the largest fragment, and the mode of shock wave treatment. Adjuvant therapy with bile acids appears to be important for complete fragment clearance.
Protein kinase C (PK-C) seems to be involved in the regulation of growth and differentiation of normal epithelial cells. Colonic adenomas and carcinomas show increased proliferation and decreased differentiation. We investigated the activity and subcellular distribution of PK-C in biopsies of normal, neoplastic, and malignant colonic epithelium to evaluate alterations in enzyme activity. In the control group (n = 7), the activity of PK-C was highest in the distal ileum (597 pmol/min/mg protein) and declined to the lowest amounts in rectal mucosa (225 pmol/min/mg protein). In patients with colonic adenomas (n = 16), total PK-C activity was significantly reduced as compared to adjacent mucosa (146 versus 336 pmol/min/mg protein, P less than 0.05) and to values determined in the control group (372 pmol/min/mg protein, P less than 0.01). The reduction of total PK-C activity in the adenoma group was even more evident in intraindividual comparison to paired adjacent mucosa (41.8% of adjacent mucosa, P less than 0.001). Specific activity of membrane-associated PK-C was equally decreased in colonic adenomas (36.3 pmol/min/mg protein) when compared to adjacent mucosa (102 pmol/min/mg protein, P less than 0.05) or to the control group (107 pmol/min/mg protein). In patients with colonic carcinomas (n = 10), the amount of total PK-C activity was also decreased (198 pmol/min/mg protein) when compared to adjacent mucosa or to the control group (P less than 0.05). In addition, the amount of membrane-associated PK-C activity (89.1 pmol/min/mg protein) was significantly reduced in carcinoma when compared to adjacent mucosa (P less than 0.05). The ratio of membrane-associated/total PK-C was not altered in adenomas, while in patients bearing carcinomas the relative fraction of membrane-associated PK-C activity was increased in samples from carcinomas and equally from adjacent colonic mucosa (45.0 and 44.6 versus 28.9%, P less than 0.05) when compared to controls. These results indicate that alterations within the protein kinase C pathway occur as early events in the adenoma-carcinoma sequence of intestinal mucosa, suggesting an important role of PK-C in epithelial differentiation and growth.
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Twenty-four patients with symptomatic gallbladder stones (12 radiolucent and 12 calcified) were treated by a combined approach of extracorporeal shock-wave lithotripsy (ESWL) and subsequent instillation of methyl tert-butyl ether (MTBE). The patients received a mean of 1500 +/- 185 shock-wave discharges. The mean instillation time of MTBE was 13 +/- 4.2 hr. Treatment was tolerated without major adverse effects. Within a time period of three to five days eight of 12 patients with pure radiolucent stones and four of 12 with calcified stones became stone-free. After a median follow-up of five months (range: one week to 26 months), a total of 11 patients (92%) with radiolucent stones and of eight patients (66%) of those with calcified stones were free of stones, fragments, or debris. These clearance rates appear high when compared with reports on monotherapy with ESWL or MTBE, suggesting a positive effect of a combined approach in selected patients. Two patients exhibited recurrent stones after six and seven months, respectively.
While it is generally accepted that cholesterol supersaturation of bile is of key importance in the rapid formation of cholesterol crystals, the role of total biliary protein and pH in the pathogenesis of cholesterol gallstones is less well understood. The relation of cholesterol saturation, total protein, and pH was studied in 73 gallbladder bile samples with and 35 gallbladder bile samples without cholesterol crystals. In samples containing crystals, a trend to higher values of cholesterol and to a higher cholesterol saturation index was observed. However, significantly (P = 0.02) higher concentrations of total protein were found in samples with crystals [0.80 +/- 0.40 g/dL (8.0 +/- 4.0 g/L)] than in samples without crystals [0.63 +/- 0.26 g/dL (6.3 +/- 2.6 g/L)]. Moreover, of 22 bile samples with total protein concentrations greater than 10.0 g/L, cholesterol crystals were detected in all but 2. Total lipids, bile acids, phospholipids, and pH values were not significantly different in the two groups of bile samples. It was concluded that high biliary protein concentrations are frequently associated with cholesterol crystals and may, therefore, be a possible risk factor in the pathogenesis of cholesterol gallstones.
Since the hepatitis B virus is noncytopathic, it is generally believed that the individual specific immune response determines the course of infection. The lack of data about hepatitis B virus-specific T-cell reactions in acute infection led us to investigate the specific cellular immune response of infected individuals in terms of proliferation, and gamma-interferon and lymphotoxin production. Our results demonstrate that peripheral blood mononuclear cells (PBMNC) from patients with acute and chronic hepatitis B respond weakly to HBsAg. In contrast, patients with acute hepatitis show a vigorous response to the nucleocapsid antigen (HBcAg) in terms of proliferation and lymphokine production, while only few chronic virus carriers gave a proliferative response. Either of the antigens could activate lymphocytes to produce gamma-interferon and lymphotoxin, cytokines which may modulate antiviral immune response.
In nineteen patients with portal hypertension and oesophageal varices, transmural variceal blood pressure was determined endoscopically by direct puncture of the varices before and after intravenous administration of 20 mg metoclopramide or placebo. No change in pressure was observed after placebo (mean difference -1.3 +/- 24.5%, N.S.), however, metoclopramide reduced the pressure by 17.6 +/- 18.6% (p = 0.02). Our results suggest that metoclopramide may be beneficial for the prevention or treatment of variceal haemorrhage.
The appearance of iso-ursodeoxycholic acid (isoUDCA; 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid) in serum of patients with chronic cholestatic liver disease and of healthy subjects during administration of ursodeoxycholic acid (UDCA) is reported. Comparison of the mass spectrum of the newly appearing bile acid with that of authentic 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid revealed its identity as the 3 beta-epimer of UDCA. The appearance of 13C-isoUDCA in serum after ingestion of 13C-UDCA proved its product precursor relationship with UDCA. The putative intermediate in the epimerization of UDCA to isoUDCA, 3-oxo-7 beta-hydroxy-5 beta-cholan-24-oic acid, was identified in serum of patients with cholestatic liver disease during treatment with UDCA. Serum concentrations of isoUDCA after 4 weeks of UDCA treatment were 1.37 +/- 0.79 mumol/l (mean +/- S.D.) in eight patients with primary biliary cirrhosis (PBC), 1.25 +/- 0.91 mumol/l in six patients with primary sclerosing cholangitis (PSC) and 3.87 +/- 0.44 mumol/l in four healthy controls. The intestinal bacterial flora as well as microsomal enzymes of the liver may be involved in the epimerization of UDCA to isoUDCA as indicated by decreased serum levels of isoUDCA under antibiotic treatment with doxycycline (100 mg/day) in healthy subjects and a correlation (r = 0.873, p less than 0.001) between the hepatic microsomal function measured by the 14C-aminopyrine breath test and the fractional conversion of applied UDCA to isoUDCA (isoUDCA/UDCA + isoUDCA) in patients with PBC or PSC. Future studies of bile acid metabolism under UDCA treatment should include measurement of isoUDCA to further elucidate its biological role.
A comparative study of the effectiveness of two types of lithotripter in fragmenting gall bladder stones is reported. The machines used were a Piezolith 2300, which generates shock waves by the piezoceramic principle, and a Dornier MPL 9000, which produces the shock waves by underwater spark discharge. With each machine, corresponding stones of 45 pairs of weight and volume matched calculi (median volume 0.5 cm3, median diameter 10.5 mm) obtained at cholecystectomy were treated. All stones were successfully disintegrated (fragments smaller than 2 mm) with up to 5400 (median 628) shocks with the Piezolith and 3450 (median 428) shocks with the MPL 9000 lithotripters. With the Piezolith, operating at the highest power setting, a 1.65 fold median higher number of shocks was required for stone fragmentation than with the MPL 9000 at a medium power setting. Stone volume seemed to be the only determinant which affected ease of fragmentation; composition and density of the stones as assessed by computed tomography did not seem to be governing factors.
Cholecystectomy has been hypothesized to cause increased levels of potentially harmful secondary bile acids due to prolonged exposure of primary bile acids to intestinal bacteria. In the present study, we analyzed duodenal bile of the same patients before and after cholecystectomy for keto bile acids and hydroxy bile acids. The ratios of individual keto bile acids to their corresponding precursor hydroxy bile acids were not significantly different before and after cholecystectomy. Keto bile acids constituted 2.5 +/- 1.3 and 2.2 +/- 0.9 mol% of hydroxy bile acids in duodenal bile. 3 alpha-Hydroxy-12-oxo-5 beta-cholanoic acid derived from deoxycholic acid was the main keto bile acid in bile contributing 80 mol% to total keto bile acids. There was a strong positive correlation between 3 alpha-hydroxy-12-oxo-5 beta-cholanoic acid and its precursor deoxycholic acid in bile (r = 0.88; p less than 0.0005). Our findings prove that 7 weeks after cholecystectomy the percentage of keto bile acids in bile as compared to hydroxy bile acids is not increased.
The hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg. We have investigated whether this antigen is a target structure for human T-lymphocytes. Using recombinant HBxAg protein, we found HBxAg-specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals. With HBxAg-specific synthetic polypeptides, several T-cell epitopes were identified. Most were located in the carboxyterminal half of the HBxAg protein. Five T-cell clones specific for a T-cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4-positive, CD8-negative subtype. These data establish for the first time HBxAg as an antigen in the cellular immune response.