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Biomedical subjects

D Jüngst

Publications and source records attributed to D Jüngst.

At least 19 recordsLinked to original sources
PubMed1992

Immunoreactive human chorionic gonadotropin and its free beta subunit in serum and ascites of patients with malignant tumors.

Human chorionic gonadotropin (hCG) is a clinically relevant marker of trophoblastic and nontrophoblastic malignancies. In the present studies, in addition to determining serum hCG, we investigated the presence and properties of hCG immunoreactivity in ascites of patients with nontrophoblastic malignant tumors and, for comparison, in ascites caused by cirrhotic liver disease. Total hCG immunoreactivity [hCG (+hCG-beta)] was found to be elevated above the reference value (greater than 5 IU/liter) in the serum of 2 of 20 patients with cirrhosis and 11 of 20 patients with malignant tumors. For comparison, in ascites, hCG (+hCG-beta) concentrations were frequently higher than in the corresponding serum samples and exceeded 10 IU/liter in 0 of 20 cirrhotic samples and in 16 of 20 malignant samples. In order to elucidate the nature of the hCG immunoreactive material, all samples were then assessed by immunoradiometric assays specific for the intact hCG molecule (holo-hCG) and the free hCG-beta subunit, respectively. In the holo-hCG assay, elevated values were detected in 0 of 20 (0 of 20) cirrhotic ascites (serum) samples and 0 of 20 (1 of 20) malignant ascites (serum) samples. In the free hCG-beta assay, on the other hand, no positive results were obtained in the ascites or serum of 20 patients with liver cirrhosis; however, 8 of 20 serum samples and 16 of 20 ascites samples derived from tumor patients were positive. In accord with the immunological data, gel chromatographical studies of malignant ascites revealed the abundance of free hCG-beta subunit rather than that of holo-hCG. In contrast to malignancy-related ascites, in ascites of patients receiving hCG injections for treatment of infertility, holo-hCG was more abundant than free hCG-beta immunoreactivity. Incubation experiments of purified holo-hCG in ascites for 24 h at -20, 20, or 37 degrees C showed no substantial dissociation of the hCG molecule and release of free hCG-beta immunoreactivity, thus arguing against production of free hCG-beta by degradation of holo-hCG and in favor of its tumor-related secretion. In conclusion, hCG-beta immunoreactivity is frequently elevated in malignancy-related ascites and appears to be related to the presence of free beta subunit of hCG rather than that of the intact hCG molecule. Interestingly, hCG-beta determination in ascites proved to be clearly superior to serum measurement in discriminating between tumor and cirrhosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

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↗
PubMed1992

Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat.

Mesenteric, hepatic and splanchnic extraction of C-terminal and N-terminal atrial natriuretic factor was investigated in male Sprague-Dawley rats. Plasma concentrations (mean +/- S.E.M.) of C-terminal atrial natriuretic factor were 55.0 +/- 6.1 fmol/ml, 31.2 +/- 4.0 fmol/ml and 23.5 +/- 3.3 fmol/ml (n = 12) in the abdominal aorta, the portal vein and the hepatic vein, respectively. N-terminal atrial natriuretic factor plasma levels in these vessels were 3031 +/- 756 fmol/ml, 2264 +/- 661 fmol/ml and 1618 +/- 496 fmol/ml (n = 6), respectively. Although the mesenteric extraction ratio was higher (p less than 0.05) for C-terminal atrial natriuretic factor (42% +/- 6%) than for N-terminal atrial natriuretic factor (28% +/- 4%), there were no significant differences in the hepatic extraction ratio (41% +/- 5% vs. 39% +/- 6%) and the splanchnic extraction ratio (56% +/- 5% vs. 50% +/- 7%). These data suggest a major role of the liver in the splanchnic extraction of C-terminal and of N-terminal atrial natriuretic factor in the rat.

Animals↗
PubMed1992

Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease.

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.

Adult↗
PubMed1992

Pathophysiology of elevated ascites fluid cholesterol in malignant ascites. Increased ascites to serum relation of proteins and lipoproteins in patients with peritoneal carcinomatosis as compared to patients with cirrhosis of the liver.

The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo-A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30-0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11-0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity.

Apolipoprotein A-I↗
PubMed1991

Ascitic fluid analysis for the differentiation of malignancy-related and nonmalignant ascites. Proposal of a diagnostic sequence.

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.

Adult↗
PubMed1991

Role of high total protein in gallbladder bile in the formation of cholesterol gallstones.

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.

Bile↗
PubMed1990

Ascitic fluid concentrations of fibronectin and cholesterol: comparison of differential diagnostic value with the conventional protein determination.

Ascitic fluid concentrations of fibronectin, cholesterol and protein were determined in 95 patients: 38 with cirrhosis of the liver, 10 with miscellaneous nonmalignant diseases, 43 with peritoneal carcinomatosis and 4 with liver metastases or hepatocellular carcinoma. Fibronectin, cholesterol and protein at discrimination values of 7.5 mg/100 ml, 45 mg/100 ml and 3.0 g/100 ml, respectively, separated patients with peritoneal carcinomatosis from patients with cirrhosis with an efficiency of 94%, 90% and 85%, respectively. Thus, ascitic fluid determinations of fibronectin and cholesterol offer good discrimination of cirrhotic ascites from ascites related to peritoneal carcinomatosis, superior to the conventional protein determination. However, the failure of all parameters to distinguish ascites caused by miscellaneous nonmalignant diseases from malignancy-related ascites underscores the importance of highly specific methods to confirm a suspected diagnosis of malignancy-related ascites.

Ascites↗
PubMed1989

Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile.

Rapid aggregation of cholesterol-phospholipid vesicles in gallbladder bile seems to be the first event in the production of cholesterol crystals, a prerequisite for cholesterol gallstone formation. We examined the amount of these vesicles in 33 human gallbladder biles in relation to biliary lipid composition and to the presence of cholesterol crystals. Biliary microscopy detected cholesterol crystals in all 19 biles from patients with cholesterol gallstones but in none of 14 biles from patients with pigment stones. Gel chromatography was used to separate vesicles and micelles in the native bile with an eluting buffer containing 10 mM sodium cholate to prevent disruption of micellar lipids. Cholesterol, phospholipid and bile salt concentrations were measured in every fraction collected. Bile acid, phospholipid, cholesterol and total lipid concentrations were not significantly different in samples with and without cholesterol crystals. The cholesterol saturation index (1.4 +/- 0.11 vs. 1.0 +/- 0.08) was significantly (p less than 0.01) higher in biles with crystals than without crystals. Gel filtration revealed a vesicular peak in addition to micellar fraction in 18 (23.1 +/- 3.2% of total cholesterol) of the 19 biles with crystals but only in three (15.7 +/- 2.4% of total cholesterol) of 14 biles without crystals. There was no relation between biliary lipid concentration or the cholesterol saturation index and the percentage of vesicular cholesterol in biles with or without crystals. The close association of vesicles and crystals in human gallbladder bile supports the contention that vesicles are important in the initial nucleation of cholesterol monohydrate crystals.

Bile↗
PubMed1989

Shock-wave therapy of gastric outlet syndrome caused by a gallstone.

A patient with gastric outlet syndrome (Bouveret's syndrome) caused by a large gallstone impacted in the duodenal bulb was successfully treated by extracorporeal shock-wave lithotripsy. Thus, open abdominal surgery could be avoided. For disintegration of the stone, three consecutive lithotripsy procedures were necessary. Thereafter, stone fragments could be extracted endoscopically. Extracorporeal shock-wave lithotripsy could become a non-surgical alternative in patients with obstruction of the duodenum caused by a gallstone.

Aged↗
PubMed1989

Low-dose ursodeoxycholic acid prolongs cholesterol nucleation time in gallbladder bile of patients with cholesterol gallstones.

The high rate of stone recurrence represents a drawback of non-surgical therapy of cholesterol gallstone disease. Although most studies report that long-term bile acid treatment does not have protective effects, preliminary results suggest that low-dose ursodeoxycholic acid decreases the rate of gallstone recurrence in a subgroup of younger patients. To clarify the underlying mechanism we investigated whether low-dose ursodeoxycholic acid treatment influences biliary cholesterol saturation and/or nucleation time of cholesterol. Ten patients with cholesterol gallstones and functioning gallbladder received 250 mg ursodeoxycholic acid/day at bedtime 6-10 days prior to cholecystectomy. Eleven patients with cholesterol gallstones without treatment served as controls. Cholesterol crystals were present in the gallbladder bile of 7 out of the 10 patients receiving ursodeoxycholic acid and in all control biles. Ursodeoxycholic acid treatment significantly (P less than 0.02) decreased the cholesterol saturation index (mean +/- S.E.: 0.94 +/- 0.05 vs. 1.43 +/- 0.18) and led to an approximately 5-fold prolongation (P less than 0.005) of the cholesterol nucleation time (mean +/- S.E.: 12.0 +/- 2.4 vs. 2.3 +/- 0.7 days). We conclude that low-dose ursodeoxycholic acid might be effective in the prevention of post-dissolution gallstone recurrence by both decreasing cholesterol saturation and prolonging cholesterol nucleation time.

Adult↗
PubMed1988

Role of atrial natriuretic factor, cyclic GMP and the renin-aldosterone system in acute volume regulation of healthy human subjects.

The role of the atrial natriuretic factor (ANF), its second messenger cyclic guanosine monophosphate (cGMP), and the counteracting renin-aldosterone system in acute volume regulation was investigated in 25 healthy human subjects. Central volume stimulation by 1-h head-out water immersion (WI) into a thermoneutral water-bath increased plasma levels of ANF (mean +/- SEM) from 6.0 +/- 0.6 to 13.6 +/- 2.6 fmol ml-1. This was paralleled by a rise of plasma cGMP levels from 1.9 +/- 0.2 to 2.8 +/- 0.4 pmol ml-1, and an increase of urinary cGMP excretion from 340 +/- 64 to 692 +/- 103 pmol min-1. Water immersion reduced plasma aldosterone concentration (PAC) from 13.0 +/- 1.7 to 6.5 +/- 0.8 ng 100 ml-1 and plasma renin activity (PRA) from 5.3 +/- 0.9 to 2.4 +/- 0.3 ng AI ml-1 h-1. Volume stimulation markedly increased diuresis and natriuresis. Whereas the plasma cGMP increase correlated with plasma ANF stimulation, neither ANF nor PRA or PAC correlated with basal or stimulated renal parameters. Water immersion-induced changes in natriuresis and urinary cGMP excretion were correlated. These data suggest a role of ANF and cGMP in acute volume regulation of healthy human subjects.

Adult↗