Gustav Paumgartner

Shock-wave lithotripsy of gallbladder stones. The first 175 patients

To substantiate the early results of extracorporeal shock-wave fragmentation of gallstones, we used this nonsurgical procedure to treat 175 patients with radiolucent gallbladder calculi. Chenodeoxycholic acid and ursodeoxycholic acid were administered as adjuvant litholytic therapy. The gallstones disintegrated in all patients except one and completely disappeared in 30 percent of all patients within 2 months after lithotripsy, in 48 percent at 2 to 4 months, in 63 percent at 4 to 8 months, in 78 percent at 8 to 12 months, and in 91 percent at 12 to 18 months. In patients with solitary stones up to 20 mm in diameter, the corresponding values were 45, 69, 78, 86, and 95 percent, respectively. Shock-wave therapy had no adverse effects except cutaneous petechiae (14 percent) and transient gross hematuria (3 percent). One third of the patients had one or more episodes of biliary colic before all the fragments disappeared. Two patients had mild pancreatitis, which necessitated endoscopic sphincterotomy in one. The patient with insufficient stone fragmentation underwent elective cholecystectomy; no additional operations were necessary. Extracorporeal shock-wave lithotripsy combined with medical therapy for stone dissolution is a safe and effective treatment in selected patients with radiolucent gallbladder calculi.

Increased Serum Deoxycholic Acid Levels in Men With Colorectal Adenomas

BACKGROUND Epidemiological and animal studies have suggested that the secondary bile acid deoxycholic acid is cocarcinogenic in colorectal cancer, but this hypothesis was not confirmed by case-control studies investigating fecal bile acids. METHODS Individual serum bile acid concentrations were investigated in 25 men and 25 women with colorectal adenomas and in an equal number of age- and sex-matched controls by gas-liquid chromatography. RESULTS Deoxycholic acid levels were significantly higher in the sera of men with colorectal adenomas (1.70 +/- 0.59 vs. 1.16 +/- 0.39 mumol/L, P < 0.0005) and in a combined analysis of both sexes (1.47 +/- 0.78 vs. 1.08 +/- 0.39 mumol/L, P < 0.0025). Six- and 12-month follow-up measurements of deoxycholic acid concentrations in a subgroup of 22 men and 17 women showed higher serum levels in men with adenomas, indicating that measurement of deoxycholic acid concentration may be a reliable parameter to investigate its pathogenetic role in colonic neoplasia. CONCLUSIONS The data of this study support the hypothesis that deoxycholic acid may play a role in the pathogenesis of colorectal cancer.

Hepatitis B virus antigen-specific T-cell activation in patients with acute and chronic hepatitis B

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.

Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease.

Ursodeoxycholic acid (UDCA) is widely used for the treatment of cholestatic liver diseases. Multiple mechanisms of action of UDCA have been described aiming at one or more of the pathogenetic processes of cholestatic liver diseases: (1) protection of injured cholangiocytes against toxic effects of bile acids, (2) stimulation of impaired biliary secretion, (3) stimulation of detoxification of hydrophobic bile acids, and (4) inhibition of apoptosis of hepatocytes. Through one or more of these mechanisms, UDCA slows the progression of primary biliary cirrhosis and improves a number of other cholestatic disorders.

Extracorporeal lithotripsy of pancreatic stones in patients with chronic pancreatitis and pain: a prospective follow up study.

Extracorporeal shock wave lithotripsy of pancreatic duct stones (largest stone 12 (SD) 6 mm) was performed in 24 patients with abdominal pain and a dilated duct system (main pancreatic duct 10 (3) mm). The procedure was well tolerated in all but two patients, who had a mild pancreatitic attack immediately after lithotripsy. Disintegration of the stones was achieved in 21 patients. This allowed complete clearance of the duct system by an endoscopic approach in 10 (42%) patients and partial clearance in 7 (29%) patients. Within a mean follow up period of 24 (14) months half of the patients showed complete or considerable relief of pain and alleviation of symptoms was achieved in seven patients. Relief of pain occurred more often after complete ductal clearance. There were no fatalities within the follow up period. These findings underline the value of a combined non-surgical approach, using endoscopy and adjuvant shock wave lithotripsy to patients with large pancreatic calculi and pain attacks.

Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis

The value of sclerotherapy as prophylaxis against the first episode of variceal hemorrhage has not been established. Therefore, we randomly assigned 133 patients with cirrhosis of the liver (of alcoholic origin in 66 percent), esophageal varices, and no previous intestinal bleeding to either prophylactic sclerotherapy (n = 68) or no prophylaxis (n = 65). The groups were comparable in hepatic function, endoscopic findings, and the pathogenesis of cirrhosis. All patients who subsequently had a first episode of variceal hemorrhage received sclerotherapy whenever possible. During a median follow-up of 22 months, variceal hemorrhage occurred in 28 percent of the patients receiving sclerotherapy and 37 percent of the controls (P = 0.3). Thirty-five percent of the sclerotherapy group and 46 percent of the control group died. The survival curves (Kaplan-Meier) of both groups were similar (P = 0.2). However, among patients with alcoholic and moderately decompensated cirrhosis (Child-Pugh group B), survival was significantly higher in those receiving sclerotherapy, although the risk of bleeding was only marginally reduced by this procedure. We conclude that prophylactic sclerotherapy does not significantly reduce the risk of bleeding from esophageal varices, but that a subgroup of patients with esophageal varices and moderately decompensated alcoholic cirrhosis may benefit from prophylactic sclerotherapy because of factors not solely attributable to prevention of an initial episode of variceal bleeding.

EVIDENCE FOR DOWN-REGULATION OF BETA-2-ADRENOCEPTORS IN CIRRHOTIC PATIENTS WITH SEVERE ASCITES

The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers.

Prediction of variceal hemorrhage in cirrhosis: A prospective follow-up study

Endoscopic, clinical, and laboratory parameters including presence of varices in the gastric fundus, red color sign, diameter and number of variceal columns, platelet count, and the Child status were assessed in 109 patients with cirrhosis and esophageal varices without previous variceal bleeding. During a mean follow-up period of 21 months, the predictive values of these parameters with regard to first bleeding incidence and mortality rate were studied. The incidence of bleeding was 29%, and the mortality rate 46%. Endoscopic criteria (presence of varices in the gastric fundus, presence of the red color sign, and size of the largest varix) as well as alcoholic etiology of cirrhosis showed a significant positive correlation with the bleeding incidence but not with mortality. Contrary to this, two factors of the Child classification (encephalopathy and ascites) and age positively correlated with mortality but not with the bleeding incidence.

Dehydroepiandrosterone sulfate (DHEAS): identification of a carrier protein in human liver and brain

Dehydroepiandrosterone sulfate (DHEAS) is the major circulating steroid in man. Pharmacologically, it exerts marked neuropsychiatric effects. Since no target receptor has been identified, we investigated whether the organic anion transporting polypeptide (OATP), a multispecific steroid carrier, transports DHEAS. Expression of the human liver OATP in Xenopus laevis oocytes resulted in high‐affinity, partially Na+‐dependent uptake of [3H]DHEAS (K m: 6.6 μmol/l). DHEAS transport was inhibited by bromosulfophthalein, bile acids, sulfated estrogens and dexamethasone. Northern blot analysis showed widespread expression of OATP in human brain. These data identify OATP as the first known target protein of DHEAS in human liver and brain.

Effect of phenobarbital on bile flow and bile salt excretion in the rat.

SummaryTreatment of rats with phenobarbital for 3 or 7 days increases bile flow to 150% or 151% of controls. This choleresis is not due to an increase of total bile acid output nor to a change of the bile acid pattern in bile.