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Biomedical subjects

R Raedsch

Publications and source records attributed to R Raedsch.

At least 55 records · Page 3Linked to original sources
PubMed1990

Ursodeoxycholic acid in primary biliary cirrhosis: no evidence for toxicity in the stages I to III.

In an open, exploratory study, the safety of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC) was investigated. Seven patients in stages I to III and two patients in stage IV were treated for 1 year with 1 g/day of UDCA. Clinical symptoms, and alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase (GOT) and aspartate aminotransferase (GTP) levels improved significantly within three months and remained at the lower levels for the period of observation. Results of the galactose elimination capacity (4.7 +/- S.D. 1.4 mg/min per kg) and the aminopyrine breath test (0.60 +/- 0.33% dose/kg per mmol CO2) remained unchanged for 1 year. In all patients total serum bile acids increased and quantitatively UDCA became the most important bile acid. In patients in stages I to III this increase, however, was modest, whereas in patients in stage IV, total serum bile acids reached levels of 140 and 157 mumol/l and UDCA, levels of 90 and 103 mumol/l, respectively. It is concluded that UDCA appears to be safe only in stages I to III and that prognostic stratification based on bile acid levels or on the histological stage of the disease should be an important aspect of controlled clinical trials.

Aged↗
PubMed1989

Precursor lesions of oesophageal cancer in young people in a high-risk population in China.

Young people (15-26 years) were selected from households in a population in China at high risk of oesophageal cancer on the basis of whether a case of oesophageal cancer had (166 participants) or had not (372 participants) occurred in a first-degree relative. In an endoscopic survey 43.5% of the male subjects and 35.9% of the female subjects showed histological signs of chronic oesophagitis. The presence of these precursor lesions was significantly associated in a multivariate logistic model with consumption of burning hot beverages, a family history of oesophageal cancer (including second-degree relatives), infrequent consumption of fresh fruit, and infrequent consumption of dietary staples other than maize.

Adolescent↗
PubMed1989

Taurine and glycine conjugation and sulfation of lithocholate in primary hepatocyte cultures.

Rat primary liver cells were used to study taurine and glycine conjugation and sulfation of lithocholate. After addition of [14C]lithocholate to the tissue culture medium, synthesis and excretion of amidated and/or sulfated products were investigated for up to 24 h. After incubation for 1 h, more than 83% of the labeled bile salt was amidated but not sulfated and between 5 and 11% was sulfated, with more than 80% of the sulfated bile salts being also amidated. After 24 h, the proportion of sulfated lithocholate had increased to about 23% and more than 99% of the lithocholate sulfate was additionally conjugated with glycine or taurine. Both sulfates and non-sulfates were preferably amidated with taurine. We conclude that in primary rat hepatocytes, (1) lithocholate is rapidly and almost completely conjugated with glycine or taurine (amidated), whereas sulfation of lithocholate (and its amidates) proceeds slowly and even after 24 h represents only a small proportion of the total lithocholate metabolites, and (2) sulfated and unsulfated bile salts are both preferably amidated with taurine.

Amides↗
PubMed1989

Similarities in maximal biliary bilirubin output in the normal rat after administration of unconjugated bilirubin or bilirubin diglucuronide.

The rate-limiting step in the overall plasma-to-bile transport of a saturating load of bilirubin is still a matter of controversy. We reassessed the apparent maximal biliary bilirubin excretion following i.v. infusion of unconjugated bilirubin and--for the first time--of highly purified bilirubin diglucuronide in the rat. The bilirubin diglucuronide preparation could be kept in a stable form at -20 degrees C for at least 2 months after addition of 3 mM sodium ascorbate. The biliary bilirubin excretion rates in animals with and without bile depletion in order to induce different flow rates were comparable after infusion of unconjugated bilirubin and of bilirubin diglucuronide. No significant hydrolysis of bilirubin diglucuronide seemed to occur during the hepatic transport of the pigment. Injection of bilirubin diglucuronide into rats which were already being infused with saturating doses of unconjugated bilirubin did not result in increased biliary bilirubin excretion. In contrast, a reversible inhibition of bilirubin output and bile acid-dependent bile flow was observed. If unconjugated and diglucuronidated bilirubin follow the same intracellular routes, the present results would suggest that conjugation did not restrict maximal biliary excretion. However, if exogenously administered diglucuronide utilizes a separate pathway, as was recently proposed, the biliary secretion of this exogenous conjugate might be restricted, presumably due to a toxic effect of the high local concentration of diglucuronide. The pathways utilized by the unconjugated pigment, on the other hand, could be primarily determined by the conjugating capacity.

Animals↗
PubMed1989

Pharmacokinetics of picumast dihydrochloride in patients with liver cirrhosis.

In a randomized parallel group design the pharmacokinetics of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) and its active metabolites M1 and M2 were studied after intravenous or oral administration of a single dose of 10 mg picumast dihydrochloride in two groups of 8 patients with liver cirrhosis. After intravenous administration, the terminal half-life of 65 h was about 4 times longer than in healthy subjects although the total body clearance of 87 ml/min was only 7.4% lower. The 3.6-fold increase in the steady-state volume of distribution (351 l) may be due to a higher uptake by the liver and other tissues and/or to a slower re-diffusion from these tissues into the circulation. Only negligible amounts of picumast dihydrochloride appeared in the urine. Picumast dihydrochloride is almost exclusively eliminated by hepatic metabolism. After oral administration peak concentrations were reached at 1.4 h; plasma elimination half-life was considerably longer (107 h), however, without being significantly different from i.v. administration. The two patient groups differed with respect to their drug metabolizing capacity, therefore the absolute biovailability could not be established. The maximum concentration of the metabolites was reached 1.4 to 3.4 h later than Cmax of the parent drug. As compared to healthy subjects the clearance of the metabolites appeared to the reduced to a greater extent than that of the parent compound, so that under steady-state conditions in patients with liver disease these active metabolites will contribute more to the overall therapeutic effect than in normal individuals. 10.4% to 12.8% of the dose were recovered from the urine als M1.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

[Polyneuropathy following treatment of chronic hepatitis B with vidarabine].

Two patients with chronic hepatitis B received adenine arabinoside, at a dosage of 1000 mg/d for 8 weeks and 700 mg/d for 12 weeks, respectively. At the end of the treatment period both patients had developed severe sensory irritability in the distal parts of the legs: perception of all sensory modalities was impaired. The disorder persisted over the following three years, although in a milder form. Shortly after the onset of the symptoms sensory nerve conduction velocity in both lower legs was not definitely impaired. But six months later it was clearly reduced to below 40 m/sec in the sural nerve, a finding which has persisted a year later. Three years after the first examination both patients are slightly improved, but conduction velocity is not yet normal. The objectively demonstrated long course and the considerable subjective complaints associated with the polyneuropathy argue for a very therapeutic use of adenine arabinoside.

Adult↗
PubMed1988

Biliary excretion of phenprocoumon and metabolites.

To evaluate phenprocoumon elimination its possible biliary excretion was evaluated in addition to the known pathway of renal elimination. Bile samples were obtained during diagnostic endoscopy in patients receiving chronic phenprocoumon therapy and were analyzed for phenprocoumon and its metabolites by HPLC and GC-MS. The following substances were detected, mainly in conjugated form: unchanged phenprocoumon and the metabolites 7-hydroxy-, 4'-hydroxy-, and 6-hydroxy-phenprocoumon. The data provide direct evidence of the biliary elimination of unchanged phenprocoumon and its metabolites in humans.

4-Hydroxycoumarins↗
PubMed1988

Ileal excretion of bile acids: comparison with biliary bile composition and effect of ursodeoxycholic acid treatment.

The amount of bile acid excreted via an ileostomy at the end of the ileum should give an estimate of the amount of bile acid transported to the colon. In the present study, 8 patients with ileostomies at the end of the ileum but without disease or resection of the small intestine excreted 1690 +/- 205 mumol/day (mean +/- SEM) of bile acids from the ileostomies. In comparison with duodenal bile, cholic acid was increased at the end of the ileum and chenodeoxycholic acid decreased; in addition, bile acid sulfates were increased and bile acid glucuronides were decreased. When ursodeoxycholic acid, a bile acid that decreases biliary cholesterol saturation and dissolves gallstones, was administered at a dose of 500 mg to each subject, 59% +/- 8% (mean +/- SEM) of this bile acid was excreted within 24 h from the ileostomies. It is apparent from these studies that absorption of ursodeoxycholic acid from the small intestine is slower than previously anticipated and involves the entire small intestine and probably also the colon.

Adult↗
PubMed1988

Primary and secondary long-term prophylaxis of thromboembolism in outpatients with the low-molecular-weight heparin Kabi 2165.

Bleeding episodes and other side effects may complicate the treatment with oral anticoagulants. We report on the results of 66 patients who were treated with a low molecular weight heparin fraction for up to 19 months. The data of the study demonstrate the effective long-term anticoagulation with low-molecular-weight heparin and the reduced incidence of hemorrhages compared with conventional anticoagulants. Thus, low-molecular-weight heparin may be effectively and safely used for long-term anticoagulation in patients with bleeding problems on conventional anticoagulants.

Clinical Trials as Topic↗
PubMed1988

Prospective study on the distribution of Campylobacter pylori in unselected patients of an endoscopy unit in West Germany.

In recent years a series of publications predominantly from English speaking countries have reported on the colonization of the gastric epithelium with Campylobacter pylori in association with gastritis and ulcer disease. In this prospective study we investigated the distribution of Campylobacter pylori in unselected patients undergoing routine endoscopy at the Department of Gastroenterology of the University of Heidelberg. A total of 175 patients were included in the study. Campylobacter pylori could be demonstrated by microbiological and histological methods in 17% of patients with normal gastric mucosa, in 44% with chronic active gastritis and in 48% with stomach ulcer. In our series only 6/23 patients with duodenal ulcer were Campylobacter pylori positive. Additionally intragastric acidity and concentrations of total bile acids were correlated to the colonization of Campylobacter pylori. Bile acid concentrations were found significantly (p less than 0.001) lower in patients with gastritis when Campylobacter pylori was present. These data suggest an association of Campylobacter pylori with diseases of the stomach also in West Germany and a negative correlation of these organisms to enterogastric bile reflux.

Adult↗
PubMed1987

[Ambulatory long-term prevention of thromboembolism with low-molecular weight heparin].

Patients with severe bleeding complications and other side effects on conventional anticoagulants and strong indication for further anticoagulation were treated with a low molecular weight heparin fragment (Tedelparin). In this paper we report the experiences in 30 patients, who were anticoagulated 1-11 months with this compound. All patients injected themselves a dose ranging from 1 X 2,500 to 1 X 20,000 anti factor Xa units per day. Within 132 months of treatment one patient with good compliance developed thromboembolism. Four patients had bad compliance. Two of them experienced rethrombosis 1 and 8 weeks after starting therapy. Severe haemorrhages did not occur. Two patients had one minor bleeding complication each. Both patients developed several times per year severe haemorrhages with conventional anticoagulants. All excessive subcutaneous haematomas and indurations of the adipose tissue at the injection site of conventional heparin disappeared completely. Low molecular weight heparin can be regarded as an alternative anticoagulant in patients with severe bleeding and other complications on oral anticoagulants and conventional heparin.

Adult↗
PubMed1986

[Composition of gallbladder and bile duct calculi].

The composition of gallbladder and bile duct stones removed at the time of cholecystectomy was analysed in a consecutive series of 45 patients. The type of stones at the two sites was similar in all but two patients. Cholesterol content differed by more than 20% in only six patients. Cholesterol stones were found in the gallbladder of 33 patients, in the bile duct of 36 patients (73 and 80%, respectively); mixed stones in eight and five patients, respectively (18 and 11%); brown-pigment stones in three patients each (7%); black-pigment stones in one patient each (2%). Bile duct stones overlooked during cholecystectomy are thus suitable for litholysis, e.g. by irrigation with monooctanoin, in the majority of cases.

Bile Duct Diseases↗
PubMed1986

Gilbert's syndrome: diagnosis by typical serum bilirubin pattern.

Analysis of serum unconjugated and conjugated bilirubin fractions by routine diazo procedures does not allow a definite diagnosis of Gilbert's syndrome. By the alkaline methanolysis procedure of Blanckaert followed by thin-layer chromatography we were able to discriminate Gilbert's syndrome even in the presence of normal serum bilirubin concentrations from healthy subjects, patients with chronic persistant hepatitis and patients with chronic hemolysis. The relative proportion of unconjugated bilirubin in serum was 95 +/- 2% in patients with Gilbert's syndrome (n = 28), 84 +/- 5% in healthy subjects (n = 29), 75 +/- 6% in patients with chronic persistant hepatitis (n = 7) and 85 +/- 3% in patients with chronic hemolysis (n = 9). The difference between Gilbert's syndrome and the control groups with normal or elevated serum bilirubin was highly significant (p less than 0.001). In Gilbert's syndrome, unconjugated bilirubin ranged between 90 and 99%, in healthy subjects between 72 and 90%, in patients with chronic persistant hepatitis between 68 and 85% and in patients with chronic hemolysis between 81 and 89% of total. An overlap was only seen in one patient with Gilbert's syndrome and in 2 healthy subjects at the 90% level. We conclude that in most patients with Gilbert's syndrome provocation tests are no longer necessary.

Adolescent↗
PubMed1986

Isomers of bilirubin glucuronide in serum and bile before and after relief of common duct obstruction.

Isomers of bilirubin glucuronide with the bilirubin acyl group attached to the C1-, C2-, C3- and C4-positions of the glucuronyl residue are present in bile of patients with extrahepatic cholestasis, whereas in normal bile only C1-isomers are found. In the present study, these bilirubin glucuronide isomers, and the fractions of unconjugated bilirubin, and bilirubin mono- and diconjugates were determined in serum and bile of 8 patients before and after relief of common duct obstruction by endoscopic papillotomy. Before papillotomy we found 39.6% C1-isomers (median value), 22.2% C2-isomers, 19.3% C3-isomers and 11.4% C4-isomers in the bile. The values in serum before papillotomy were comparable. Twenty-four hours after papillotomy, the level of C1-isomers in bile increased significantly to 56.3% (P less than 0.05) with a concomitant decrease of the non-C1-isomers. In contrast, in serum the isomers of bilirubin glucuronide did not change significantly at 24 h after papillotomy. Before papillotomy, the fraction of unconjugated bilirubin in bile was 3.6% of the total, with 15.8% bilirubin monoconjugates and 75.5% bilirubin disconjugates. After papillotomy, unconjugated bilirubin decreased to 1.6% (n.s.) and bilirubin monoconjugates to 11.9% (n.s.), while bilirubin diconjugates increased to 86.1% (P less than 0.05). In serum, the elevated fractions of bilirubin diconjugates and monoconjugates decreased from 38.4 to 32.2% (P less than 0.05) and from 29.6 to 23.4% (n.s.), respectively. In parallel, the fraction of unconjugated bilirubin in serum increased from 24.1 to 37.0% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Colonic absorption of sulfated and nonsulfated bile acids in rat.

Absorption of sulfated and nonsulfated chenodeoxycholic and glycochenodeoxycholic acid was studied in the colon and the data were compared with the absorption rates in the ileum. Absorption of nonsulfated chenodeoxycholic acid in the colon was in the same range of magnitude as in the ileum. Glycochenodeoxycholic acid absorption in the colon was lower than in the terminal ileum. Sulfated bile acids were not absorbed in the colon. In the ileum, absorption of sulfated bile acids was significantly (p less than 0.01) lower than the absorption of nonsulfated bile acids. Little absorption of sulfated bile acids in the ileum and lack of absorption in the colon both contribute to the rapid turnover and excretion of bile acid sulfates.

Animals↗