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Biomedical subjects

G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 127 records · Page 7Linked to original sources
PubMed1991

Efficacy and safety of ursodeoxycholic acid for dissolution of gallstone fragments: comparison with the combination of ursodeoxycholic acid and chenodeoxycholic acid.

A prospective, double-blind, randomized, single-center study was conducted to compare ursodeoxycholic acid alone with the combination of ursodeoxycholic acid and chenodeoxycholic acid for dissolution therapy of gallstone fragments after shock wave lithotripsy. Patients with single radiolucent gallstones up to 30 mm in diameter or up to three stones of similar total volume received either 750 mg ursodeoxycholic acid alone (group A, n = 138) or the combination of 500 mg ursodeoxycholic acid and 500 mg chenodeoxycholic acid (group B, n = 144) in a single bedtime dose. The bile acids were administered from 2 wk before electrohydraulic lithotripsy until 3 mo beyond complete disappearance of all fragments. Patient's characteristics, stones (group A, 82% single stones, maximum diameter 19 +/- 5 mm, mean +/- S.D.; group B, 82% single stones, 18 +/- 5 mm), lithotripsy treatment and follow-up period were not different between the two groups. Between the two groups, no statistically significant difference was found in the time required for complete clearance of the fragments (group A, median time = 15 mo; group B, median time = 13 mo; p = 0.7). At 12 mo after lithotripsy, the probability of complete clearance was 46% +/- 5% in group A and 49% +/- 5% in group B. Diarrhea occurred significantly more often in group B than in group A (p less than 0.001) and was the main reason for withdrawal of randomized medication. Severe adverse effects of the bile acids were not observed. It is concluded that monotherapy with ursodeoxycholic acid is as efficient as the combination of ursodeoxycholic acid and chenodeoxycholic acid for fragment dissolution after lithotripsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗
PubMed1991

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.

Adult↗
PubMed1990

Tauroursodeoxycholic acid inhibits the cytosolic Ca++ increase in human neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine.

The effect of the cytoprotective bile acid tauroursodeoxycholic acid (TUDCA) on basal cytosolic free Ca++ (Ca++)i and receptor-mediated (Ca++)i increase was studied in human polymorphonuclear neutrophils using the fluorescent dye quin2. Basal levels of (Ca++)i were 96 +/- 6 nmol/l (mean +/- SEM, n = 48). TUDCA and its cytotoxic epimer taurochenodeoxycholic acid (TCDCA) at 500 mumols/l increased (Ca++)i by 31 +/- 12 and 27 +/- 7 nmol/l, respectively (n = 6, p less than 0.05). Stimulation of neutrophils with the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10(-7) mol/l) induced a (Ca++)i increase of 200 +/- 32 nmol/l which was inhibited after preincubation with TUDCA (500 mumols/l) or TUDCA + TCDCA (500 mumols/l, each) by 60.1% and 59.5%, respectively, but not with TCDCA (500 mumols/l) alone. The inhibitory effect of TUDCA on FMLP-induced (Ca++)i increase was strongly concentration-dependent and was nearly complete at 1000 mumols/l. Since (Ca++)i is discussed as a mediator of cellular injury we hypothesize that TUDCA may exert its protective effects at least partly via inhibition of (Ca++)i-mediated cytotoxic processes.

Calcium↗
PubMed1990

Early gallstone recurrence rate after successful shock-wave therapy.

Extracorporeal shock-wave lithotripsy combined with adjuvant bile-acid dissolution therapy results in complete clearance of stone fragments in a high percentage of selected patients with radiolucent gallbladder calculi. With the gallbladder in situ, these patients are at risk of stone recurrence. Therefore, the early rate of stone recurrence after successful lithotripsy was evaluated. Fifty-eight of the first 60 consecutive patients who became stone free underwent follow-up examinations at least 1 yr (range, 12-37 mo; mean +/- SD, 18 +/- 6) after discontinuation of adjuvant bile-acid therapy. Five patients reported recurrent biliary pain within 1 yr after lithotripsy, and recurrent gallstones were detected. Fifty-three patients were asymptomatic during the first yr, and no recurrence was detected. Thus, the rate of gallstone recurrence was 9% within 1 yr. The rate of gallstone recurrence up to 3 yr was estimated by actuarial analysis. The probability of stone recurrence was 11% (+/- 4%) at 1.5 yr, and no further increase was observed up to 3 yr. Gallstone recurrence within 1 yr after successful shock-wave therapy has to be expected in approximately the same percentage of patients as has been reported in earlier postdissolution trials. It causes recurrent biliary pain in most cases.

Adult↗
PubMed1990

Assessment of hepatic function. Comparison of caffeine clearance in serum and saliva during the day and at night.

Hepatic microsomal function was assessed by a caffeine clearance test at night and during the day using saliva and serum samples obtained simultaneously. In 26 patients with cirrhosis, 21 patients with noncirrhotic liver disease and 15 control subjects caffeine elimination correlated well during the day and at night (r = 0.915 for serum and 0.917 for saliva). The correlation coefficients for caffeine clearance in saliva and serum were 0.940 during the day and 0.963 overnight. In the cirrhotic patients, clearance differed significantly from noncirrhotic liver disease and controls in saliva samples overnight: 0.51 +/- 0.45 ml/min per kg versus 0.91 +/- 0.44 and 1.41 +/- 0.56, respectively. Comparable results were obtained for serum clearance overnight and clearances during the day. Serum and saliva clearances at night correlated well with the aminopyrine breath test (rs = 0.884 and 0.907, respectively). Overnight caffeine clearance in saliva might be a simple useful method for assessing progression and prognosis of liver disease.

Aminopyrine↗
PubMed1990

Different behaviour of the N-terminal and C-terminal fragment of proatrial natriuretic factor in plasma of healthy subjects as well as of patients with cirrhosis.

N-terminal (atrial natriuretic factor (ANF) 1-98) and C-terminal (ANF 99-126) fragments of proatrial natriuretic factor (NTA and CTA, respectively) were determined in plasma of healthy subjects adopting different postures and in patients with cirrhosis. Seven healthy subjects were investigated while seated and 30 min after assuming a horizontal position. NTA plasma concentrations increased in subjects in the horizontal position (from 734 +/- 250 (SE) fmol/ml to 902 +/- 227 fmol/ml; p less than 0.05). In contrast, CTA plasma concentrations remained unchanged (9.2 +/- 1.3 fmol/ml vs 8.9 +/- 1.6 fmol/ml). In 10 patients with cirrhosis of the liver, NTA concentrations were markedly (p less than 0.001) elevated compared to 11 healthy subjects (2334 +/- 291 fmol/ml vs 743 +/- 155 fmol/ml). However, there was no difference of CTA plasma levels between cirrhotic patients and healthy subjects (8.7 +/- 1.3 fmol/ml vs 8.2 +/- 0.9 fmol/ml). These data demonstrate changes of the plasma concentration of the N-terminal fragment of proatrial natriuretic factor by posture and in liver disease, in contrast to unchanged levels of the C-terminal fragment.

Adult↗
PubMed1990

[Shockwave lithotripsy in gallbladder and bile duct calculi: indications and results].

Extracorporeal shock-wave lithotripsy combined with adjuvant litholytic therapy (ursodeoxycholic acid and chenodeoxycholic acid) is a relatively safe and effective noninvasive therapy for selected patients with symptomatic radiolucent gallbladder stones. The best results (80% stone-free patients within 1 year) are obtained with radiolucent solitary stones with a diameter of less than 20 mm. Shock-wave lithotripsy achieves rapid clearance of stones in about 80% of patients with bile duct calculi in whom endoscopic procedures fail.

Cholelithiasis↗
PubMed1990

The place of lithotripsy and surgery in the management of gallstone disease.

In summary, 10% to 20% of all symptomatic and uncomplicated gallbladder stones can be treated by ESWL under the current entry criteria. Further, ESWL is suitable for patients with bile duct stones in whom the primary endoscopic approach is not successful (about 10%). The algorithm in Figure 7 shows the therapeutic modalities that may be employed if the least invasive therapy is chosen. The different methods shown in this diagram are usually carried out by different specialists including surgeons, gastroenterologists, or radiologists. Therefore, an interdisciplinary approach is desirable. The technology of shock wave therapy of gallbladder stones will be improved in the future, for example the efficacy of stone fragmentation while maintaining a low level of discomfort for the patient. Moreover, repeated shock wave treatments may increase the success rate in patients with multiple stones and possibly in those with slightly calcified stones as well. Repeated procedures for recurrent stones appear feasible. Long-term follow-up studies are needed to define the place of ESWL in the management of gallstone disease. Surgery of the gallbladder remains the "gold standard" of curative therapy of gallbladder stones, against which ESWL and other nonsurgical techniques have to be evaluated. For the therapy of bile duct stones, ESWL is a helpful and effective nonsurgical adjunct.

Animals↗
PubMed1989

Serum unconjugated bile acids in patients with small bowel bacterial overgrowth.

Concentrations of total and unconjugated bile acids in serum were measured fasting and 2 h postprandially in 9 patients with a positive [14C]glycocholate breath test consistent with small bowel bacterial overgrowth and in 13 controls. Gas-liquid chromatography-mass spectrometry (GLC-MS) and enzymatic-fluorometric assays were both used. In contrast to previous work, total serum bile acids were only occasionally elevated in patients with bacterial overgrowth. Total 2 h postprandial unconjugated bile acids, however, were elevated in 7/9 patients when measured by GLC-MS and in 6/9 when measured by the enzymatic-fluorometric method. The best separation between patients and controls was achieved by GLC-MS determinations of 2 h postprandial unconjugated cholic acid or primary bile acids, which were abnormal in 8/9 patients. This study indicates that measurement of serum bile acids may be a useful approach to the diagnosis of bacterial overgrowth, but would require accessible methods for separating and measuring cholic acid or unconjugated primary bile acids in post-prandial sera.

Aged↗
PubMed1989

Atrial natriuretic factor and renin-aldosterone in volume regulation of patients with cirrhosis.

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p less than 0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 +/- 1.3 fmoles per ml to 16.5 +/- 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 +/- 0.6 fmoles per ml to 13.6 +/- 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 +/- 1.3 fmoles per ml to 11.4 +/- 2.3 fmoles per ml) was blunted (p less than 0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis.

Adult↗
PubMed1989

Bile acid metabolism in human hyperthyroidism.

Decreased levels of serum cholesterol are a well-recognized finding in hyperthyroidism. Since the conversion to bile acids is an important pathway for the elimination of cholesterol, we studied primary bile acid kinetics in seven hyperthyroid patients before and after medical treatment. Pool sizes, fractional turnover and synthesis rates of cholic acid and chenodeoxycholic acid were determined after oral administration of 50 mg [13C]cholic acid and 50 mg [13C]chenodeoxycholic acid. 13C/12C isotope ratios in serum were measured by capillary gas chromatography/electron impact mass spectrometry. Compared with the euthyroid state, serum cholesterol levels were distinctly lower in hyperthyroidism (150 +/- 33 vs. 261 +/- 51 mg per dl, p less than 0.01). Thyroid hormone excess caused a 34% reduction in cholic acid synthesis (5.8 +/- 2.8 vs. 7.9 +/- 4.2 mu moles per kg per day, p less than 0.02), which was associated with a 47% decrease in cholic acid pool size (11.7 +/- 3.4 vs. 22.0 +/- 5.2 mu moles per kg, p less than 0.01). Chenodeoxycholic acid kinetics exhibited no apparent changes. Thus, total primary bile acid synthesis was diminished by 20% in hyperthyroidism. After normalization of thyroid function, the ratio of cholic acid/chenodeoxycholic acid pool size increased in all patients. This was paralleled by a rise in the ratio of concentrations of cholic acid/chenodeoxycholic acid in serum. The depression of cholic acid synthesis in the presence of unaltered subjects is compatible with an inhibition of hepatic 12 alpha-hydroxylation by thyroid hormone. Furthermore, evidence is provided that, in man, the low serum cholesterol levels found during hyperthyroidism are not caused by an increased conversion of cholesterol to bile acid.

Aged↗
PubMed1989

Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers.

The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml.kg-1.min-1 in controls to 1.06 and 1.21 ml.kg-1.min-1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine.

Adult↗
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

Colonic N-acetylation of 5-aminosalicylic acid in inflammatory bowel disease.

5-Aminosalicylic acid presently is believed to represent the therapeutically active moiety of the sulfasalazine molecule in the treatment of inflammatory bowel disease. The metabolism of this compound, however, has not been studied in detail. In this paper we provide evidence that 5-aminosalicylic acid is acetylated to N-acetyl-aminosalicylic acid in homogenates from colonic biopsy specimens (370 +/- 20 nmol/g wet wt or 2.9 +/- 0.9 nmol/mg.min, n = 10), whereas acetylation in fecal samples was only small (13.0 +/- 3.0 nmol/g). Mucosal N-acetylation was rapid, cofactor- and pH-dependent, and could be enriched in the cytosolic fraction. In contrast, fecal acetylation was slow and did not depend on the presence of acetyl-coenzyme A. There were neither significant differences of acetylation between patients and controls nor a significant correlation to the individual acetylation phenotype. From our results we believe that presystemic acetylation of 5-aminosalicylic acid may be mainly mediated by a colonic mucosal enzyme and only to a small extent by fecal (bacterial) processes.

Acetylation↗
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↗
PubMed1989

Extracorporeal shock wave lithotripsy of pancreatic stones.

Extracorporeal shock wave lithotripsy of pancreatic stones was performed in eight patients with chronic pancreatitis and a dilated duct system harbouring stones 5 to 20 mm (means 10 (SD) 5 mm) in diameter. After endoscopic sphincterotomy of the pancreatic orifice the stones were disintegrated by shock waves under fluoroscopic control using a kidney lithotripter (Dornier HM3). The procedure was well tolerated by all but one patient, who had a mild pancreatitic attack immediately after lithotripsy. Clearance of the pancreatic duct systems from the larger stones was achieved in seven of eight patients. Half of the patients showed no improvement in the intensity and frequency of pain. The other patients had a marked amelioration of symptoms, however, both immediately and during a mean follow up interval of 11 (eight) months. A selective combined approach by endoscopy and extracorporeal shock wave lithotripsy for the treatment of pancreatic stones seems promising.

Adult↗