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Biomedical subjects

E W van der Hoek

Publications and source records attributed to E W van der Hoek.

7 recordsLinked to original sources

Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study.

BACKGROUND/AIMS: Treatment with ursodeoxycholic acid has been shown to decrease the rate of disease progression in patients with primary biliary cirrhosis, although the effect is modest. Since primary biliary cirrhosis has many features of an autoimmune disorder, immunosuppressives added to ursodeoxycholic acid may be of value in the treatment of primary biliary cirrhosis. METHODS: A 1-year randomized, double-blind, placebo-controlled trial was carried out in 50 patients with primary biliary cirrhosis, who had already been treated with ursodeoxycholic acid for at least 1 year, but had not achieved complete disease remission. Patients were randomized to additional prednisone (30 mg per day initially, tapered to 10 mg daily after 8 weeks) and azathioprine (50 mg daily) or placebo. A subgroup of patients received cyclical etidronate and calcium. The principal aim of the study was to assess the short-term benefits and risks of the combined bile acid and low-dose immunosuppressive regimen. Primary endpoints were effects on symptoms, liver biochemistry, liver histology, bone mass and the occurrence of adverse events. RESULTS: Pruritus (p=0.02), alkaline phosphatase, aspartate aminotransferase, IgM and procollagen-III-propeptide improved significantly (all p<0.002) in the combined treatment group as compared to the placebo group. Histological scores for disease activity and disease stage decreased significantly within the combination treatment group (p<0.001). CONCLUSIONS: In patients with primary biliary cirrhosis receiving ursodeoxycholic acid, there is an additional beneficial effect of 1-year treatment with prednisone and azathioprine on symptoms and biochemical, fibrogenetic and histological parameters. These results strongly encourage the evaluation of this triple treatment regimen in long-term controlled trials of adequate size to document its effect on clinical events.

Adult↗

Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth.

Non-invasive methods to detect small intestinal bacterial overgrowth often lack specificity in patients who have undergone an ileal resection or have an accelerated intestinal transit. Since elevated serum unconjugated bile acid levels have been found in patients with clinical signs of bacterial overgrowth, we studied the clinical value of unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Patients with culture-proven bacterial overgrowth had significantly elevated fasting unconjugated serum bile acid levels (median and range: 4.5; 1.4-21.5 mumol l-1) as compared to healthy subjects (0.9; 0.3-1.7 mumol l-1, P less than 0.005), to persons with an accelerated intestinal transit (1.0; 0.3-1.9 mumol l-1, P less than 0.005) and to persons who have undergone an ileal resection (2.1; 0.7-3.6 mumol l-1, P less than 0.005). The same was true 30 and 60 min after ingestion of a Lundh meal. Serum unconjugated bile acid levels above 4 mumol l-1 were found in eight of 10 patients with culture-proven small intestinal bacterial overgrowth whereas serum levels above 4 mumol l-1 were found in none of the patients from the three control groups. These results suggest that determination of unconjugated serum bile acids is of clinical value in the evaluation of patients suspected of small intestine bacterial overgrowth.

Adult↗

Analysis of conjugated and unconjugated bile acids in serum and jejunal fluid of normal subjects.

A reliable method is described for the determination of conjugated and unconjugated bile acids in serum and jejunal fluid. Bile acids are extracted using reverse-phase octadecylsilane bonded silica cartridges and are separated into their unconjugated and conjugated fractions using the lipophilic anion exchanger diethylaminohydroxypropyl Sephadex LH-20 (DEAP-LH-20). The conjugated fraction can be separated into a glycine and a taurine fraction, using the same anion exchanger. The bile acids are measured using a hydroxysteroid dehydrogenase-fluorimetric assay for serum and a hydroxysteroid dehydrogenase-photometric assay for jejunal fluid. The normal fasting serum value of total 3 alpha-hydroxy bile acids amounts to 3.5 +/- 2.8 mumol/l (mean +/- SD, range 1.4-10.8, n = 22). The corresponding unconjugated bile acid fraction amounts to 39.9 +/- 11.2% (range 20.7-64.6%) of total bile acids. The concentration of conjugated bile acids became significantly elevated 30, and 60 min after a standard meal, whereas that of unconjugated bile acids remained unchanged. In jejunal fluid only conjugated bile acids are found, as well in fasting subjects as postprandial, 30 or 60 min after a standard meal.

Bile Acids and Salts↗

Determination of alpha-amylase, trypsin and lipase in duodenal fluid: comparison of methods.

The three most important enzymes present in duodenal fluid, alpha-amylase, trypsin and lipase, were determined by two different methods. Various dilution fluids for these determinations were compared. Some kinetic data are described together with the reproducibility of the assays. For alpha-amylase the Phadebas method was compared with an UV method. Trypsin was determined using an immunoreactive trypsin test and a titrimetric method, while lipase was determined with a titrimetric method and a Cu-soap method. There was very good agreement between the two alpha-amylase methods and between the two trypsin determinations. There was also good agreement between both lipase methods. The advantages and disadvantages of all the methods are discussed.

Amylases↗