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Dive into the research topics where J. Bircher is active.

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Featured researches published by J. Bircher.


European Journal of Clinical Pharmacology | 1988

Increased systemic availability of albendazole when taken with a fatty meal

H. Lange; R. H. Eggers; J. Bircher

SummaryWe have studied the systemic availability of oral albendazole in 6 patients with echinococcosis either fasting or with breakfast. Albendazole sulphoxide, the pharmacologically active principle, was assayed by HPLC.Mean plasma concentrations and AUCs were 4.5 times higher when albendazole was given with breakfast than when administered in the fasting state.We conclude that therapy of echinococcosis with albendazole requires the drug to be taken with meals and that administration on an empty stomach might be more appropriate when intraluminal effects are desired, e.g. for intestinal parasites.


Gastroenterology | 1988

Steady-State Extrarenal Sorbitol Clearance as a Measure of Hepatic Plasma Flow

Joachim Zeeh; Harald Lange; Jaime Bosch; Susanne Pohl; Harald Loesgen; Robert Eggers; Miquel Navasa; Jaime Chesta; J. Bircher

Hepatic plasma flow was assessed with sorbitol (hepatic extraction = 0.96) at steady state. After infusion of 50 mg/min for 3 h, total and renal sorbitol clearances were calculated, and the extrarenal clearance was obtained by taking the difference between the two. In normal volunteers, the mean (+/- SD) extrarenal sorbitol clearance was 10.6 +/- 2.1 ml/min.kg. In patients with various liver diseases, it was correlated more closely to the fractional clearance of indocyanine green (r = 0.83, n = 57) than the galactose elimination capacity (r = 0.66, n = 55). Hepatic vein catheterization showed that the hepatic extraction of sorbitol was always much higher than the extraction of indocyanine green; there was no evidence for extrahepatic, extrarenal sorbitol elimination. On the basis of these findings, sorbitol is kinetically superior to indocyanine green and, although the noninvasively determined extrarenal sorbitol clearance at steady state may not be equal to total hepatic plasma flow, it may at least be regarded as a measure of parenchymal liver plasma flow.


Journal of Laboratory and Clinical Medicine | 1998

Assessment of the hepatic circulation in humans: new concepts based on evidence derived from a D-sorbitol clearance method.

Gianpaolo Molino; Paolo Avagnina; Gustavo Belforte; J. Bircher

D-Sorbitol (SOR) is safe, is easy to measure, and has an exceptionally high extraction ratio in the normal liver of 0.93+/-0.05 (mean+/-SD). Together with the general interest in hepatic hemodynamics, these facts motivated us to review the usefulness of this compound for the assessment of liver plasma flow in humans. We concluded that in subjects without liver disease the nonrenal clearance of SOR-measured noninvasively-very closely approximates hepatic plasma flow. Because of its lower and more variable extraction ratio, indocyanine green should no longer be used without hepatic vein catheterization. Even in patients with cirrhosis, SOR exhibits higher hepatic extraction ratios than indocyanine green. To fully explore the potential of SOR in the evaluation of such patients attention needs to be paid to the complex changes in architecture and function occurring in this disease. In cirrhotics the noninvasively measured nonrenal clearance of SOR presumably approximates the flow through intact and capillarized sinusoids (functional flow) and reflects the amount of blood having functional contact with hepatocytes. The theoretic background of the method, its accuracy, further research needs, and potentials of various approaches are discussed in detail.


European Journal of Clinical Pharmacology | 1992

Urinary caffeine metabolites in man : age-dependent changes and pattern in various clinical situations

D. Ullrich; D. Compagnone; B. Münch; A. Brandes; H. Hille; J. Bircher

SummaryIn an exploratory study the 24-h urinary excretion pattern of caffeine and 14 of its major metabolites was studied in 32 volunteers (adults, adolescents and children), 14 patients either with end stage renal disease or liver cirrhosis, 7 heavy smokers and 27 patients on therapy with cimetidine, allopurinol, theophylline or phenytoin. Caffeine and its metabolites were quantified by UV-absorption after liquid/liquid-extraction and HPLC-separation, which ensured proper analysis of 1-methyluric acid.In adults the renal excretion of caffeine derivatives corresponded to an intake of 509 mg caffeine/day, with 1-methyluric acid as the predominant metabolite. About 69% of caffeine was degraded by the paraxanthine pathway, and theobromine- (19%) and the theophylline pathway (14%) were less important. The ratio of paraxanthine formation to urinary caffeine concentration ( = clearance equivalent) was about 2.2 ml·min−1·kg−1 in adults, and the corresponding ratios for theophylline and theobromine were 0.43 ml·min−1·kg−1 and 0.59 ml·min−1·kg−1, respectively. As expected, caffeine degradation was impaired in patients with cirrhosis and was increased in persons who smoked heavily or who were on phenytoin therapy.The results document the possibility of noninvasively investigating gross differences in caffeine disposition by analysis of the urinary pattern of its metabolites.


Journal of Hepatology | 1985

High oral doses of mebendazole interfere with growth of larval Echinococcus multilocularis lesions

Peter J. Luder; Guidi Robotti; Friedrich P. Meister; J. Bircher

The natural development of the larval stage of Echinococcus multilocularis in man has been studied in 7 patients after presumed radical operation 2 8/12-11 2/12 years prior to detection of a relapse. The volumes of the recurring lesions were assessed by CT-scanning, and assuming linear growth a median increase of 14.8 ml/year (range 3.8-220 ml/year) was calculated. In 6 patients treated for a median duration of 4 5/12 years with high oral doses of mebendazole a median growth rate of -3.0 ml/year (range-470- + 10.2 ml/year) was found, which differed significantly from the natural growth rate (P less than 0.01). Although the patients improved clinically, there was evidence of persistent infection. These data are the first controlled evidence that high oral doses of mebendazole may be parasitostatic in alveolar echinococcosis in man. Although not curative, this pharmacological effect appears to be clinically beneficial.


Journal of Hepatology | 1990

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

E. Lotterer; Adolf Stiehl; R. Raedsch; U.R. Foelsch; J. Bircher

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.


European Journal of Clinical Pharmacology | 1985

Treatment of cystic echinococcosis (Echinococcus granulosus) with mebendazole: Assessment of bound and free drug levels in cyst fluid and of parasite vitality in operative specimens

P. J. Luder; F. Witassek; K. Weigand; J. Eckert; J. Bircher

SummaryChemotherapy of the larval stage of Echinococcus granulosus in man with high oral doses of mebendazole has only been partly successful. In order to improve effective pharmacotherapy of this disease with mebendazole, the optimal time for blood sampling has been assessed and the mebendazole concentrations acting on the parasite have been compared with their viability. The optimal time for blood sampling was analysed in 14 patients during longterm treatment with mebendazole. The plasma level 4 h after the morning dose exhibited the best correlation with the average 24-h concentration, suggesting that the plasma level should be monitored 4 h after the morning dose. In 22 patients undergoing surgery for hydatid disease, the mebendazole concentration in cyst fluid was significantly correlated with its plasma level 4 h after the morning dose. In 13 of them the free drug concentration was determined by equilibrium dialysis and it was almost identical with the free mebendazole concentration in plasma. Results of viability tests in 12 cases revealed viable cysts in 6 cases and possibly viable cysts in 6 other cases. Even patients treated for more than 12 months still had viable cysts.


Journal of Hepatology | 1992

Higher levels of aminoterminal type III procollagen peptide, and laminin in alcoholic in nonalcoholic cirrhosis of equal severity

E. Lotterer; Axel M. Gressner; Jürgen Kropf; E. Grobe; D. von Knebel; J. Bircher

Abstract In vitro models have shown that metabolites of ethanol (acetaldehyde and lactate) stimulate collagen synthesis, thereby, suggesting that they may be important as fibrogenic mediators. The relevance of these findings for fibrogenesis in the human liver in vivo, however, has not as yet been demonstrated. Serum markers for collagen (PIIINP, using radioimmunoassays employing polyclonal antibodies and Fab-fragments (PIIINP-Fab), respectively) and basement membrane (laminin) metabolism were therefore investigated in 25 alcoholic cirrhotics (Pugh-Score: 6.7 ± 1.9 S.D.) and in 19 comparable nonalcoholic cirrhotics (Pugh-Score: 6.3 ± 1.5, n.s.) with only slight evidence for inflammation: GOT 28 ± 22 vs. 24 ± 21 U/l; GPT 24 ± 23 vs. 31 ± 28 U/l; γ-globulins 24 ± 8 vs. 22 ± 5%, respectively (all n.s.). Severity of the disease was assessed by quantitative liver function tests. Levels of PIIINP, PIIINP-Fab and laminin measured by RIA were 21 ± 19 μg/l, 90 ± 42 μg/l and 2.5 ± 0.8 U/ml in alcoholic cirrhosis and 16 ± 6 μg/l, 61 ± 10 μg/l and 1.9 ± 0.4 U/ml in nonalcoholic cirrhosis, respectively (all p p


Journal of Hepatology | 1987

Non-invasive evaluation of portal-systemic shunting in man by d-sorbitol bioavailability

Alberto Cavanna; Gianpaolo Molino; Marco Ballarè; Mauro Torchio; Mario Fracchia; Paolo Avagnina; J. Bircher

Portal-systemic shunting is an important circulatory abnormality in patients with cirrhosis. This study explores the potential of the natural polyol D-sorbitol as test compound for non-invasive assessment of shunting. Ten normal subjects, 10 patients with cirrhosis and 12 cirrhotics with surgical portacaval shunts were studied after oral and intravenous administration of a 2 g dose of sorbitol. As measured by the H2 breath test, removal from the intestinal lumen was complete in both groups. Bioavailability of sorbitol, calculated as ratio of the areas under the plasma concentration/time curve after p.o. and i.v. administration, was zero in normal subjects, 0.29 +/- 0.15 in cirrhotic patients, and 0.38 +/- 0.11 in patients with portacaval shunts. Calculation of bioavailability on the basis of urinary outputs of sorbitol gave similar results. It is concluded that the bioavailability of sorbitol reflects portal-systemic shunting, although the relatively low figures suggest some degree of sorbitol metabolism by enterocytes.


European Journal of Clinical Pharmacology | 1990

Excessive motor impairment two hours after Triazolam in the elderly

H. U. Fisch; G. Baktir; G. Karlaganis; C. Minder; J. Bircher

SummaryThe pharmacokinetics of triazolam 0.25 mg p.o. and psychomotor coordination were compared in nine healthy, elderly volunteers and nine middle aged controls. Motor coordination, as measured by pursuit rotor performance, was impaired in the elderly even before triazolam administration, and in contrast to the controls it deteriorated to a critical level after the drug. Factors associated with the major decrease in psychomotor performance in the elderly volunteers were poor baseline performance, an additional independent-age factor, and the plasma concentration of free triazolam.Although short acting benzodiazepines may have a less detrimental effect on performance on the morning following their intake, there may be serious motor incoordination and falls may occur if the patients have to rise during the night, particularly when the plasma concentration is high, i.e. about 2 h after dosing.

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E. Lotterer

University of Göttingen

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D. von Knebel

University of Göttingen

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B. Möller

Free University of Berlin

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E. Grobe

University of Marburg

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