PubMed Health⌕ Search

Biomedical subjects

J Bircher

Publications and source records attributed to J Bircher.

At least 19 recordsLinked to original sources
PubMed1992

Urinary caffeine metabolites in man. Age-dependent changes and pattern in various clinical situations.

In 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.

Adolescent↗
PubMed1992

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

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; gamma-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 micrograms/l, 90 +/- 42 micrograms/l and 2.5 +/- 0.8 U/ml in alcoholic cirrhosis and 10 +/- 6 micrograms/l, 61 +/- 10 micrograms/l and 1.9 +/- 0.4 U/ml in nonalcoholic cirrhosis, respectively (all p less than 0.01). Differences on PIIINP and PIIINP-Fab remained significant even after accurate matching for galactose elimination capacity, aminopyrine breath test and hepatic sorbitol clearance. Laminin levels were higher in alcoholic cirrhosis only after matching for the hepatic sorbitol clearance (p less than 0.01). The higher levels of serum markers for collagen and basement membrane metabolism in alcoholic vs. nonalcoholic patients with cirrhosis at equal severity of the disease and with only minimal signs of inflammation may be the clinical reflection of a specific fibrogenic effect of ethanol metabolites.

Adult↗
PubMed1992

Individualized dosage of gentamicin: a programmed pocket calculator is useful only when applied properly.

Various methods of gentamicin dosing were compared in order to evaluate factors that prevent achievement of therapeutic peak and trough plasma concentrations in every patient. When standard doses of 3 x 80 mg of gentamicin/day (i.e., 3 x 170 mumol/day) were administered, only 26% of peak and 51% of trough plasma concentrations were within the desired range. This percentage increased for peak levels to 54% (p less than 0.001) when physicians were instructed in the use of a programmed pocket calculator (PPC) and to 70% (p less than 0.001) when in addition the nursing staff was trained. The best results were achieved when dosing and blood sampling were supervised by a single trained person, 76% of initial peak and 71% of initial trough levels being within the therapeutic range. In this group of patients, further dosage adjustments by the PPC achieved 92% of peak levels in the desired range, while no patient had elevated trough levels. Analysis of the factors that led to these results revealed that neither the laboratory nor the PPC are limiting factors for optimal results. The goal of therapeutic plasma concentrations can be achieved, but requires appropriate attention to the accuracy of blood sampling and dosing. For this purpose, a special program, i.e., more than ordinary attention to drug therapy, is needed.

Adolescent↗
PubMed1991

Effect of pentoxifylline on liver plasma flow in normal man.

In ten healthy, male subjects the acute effect of pentoxifylline (a methylxanthine derivative) on liver plasma flow was investigated by the extrarenal sorbitol clearance method and on cardiac output by impedance cardiography. On the placebo day liver plasma flow decreased within 4 h from 769 to 683 ml.min-1 (P less than 0.05) and on the pentoxifylline day (300 mg i.v.) it increased from 764 to 801 ml.min-1 (NS). At the end of the experiment the difference between the groups was also significant (P less than 0.05). There was no significant change in cardiac output, blood pressure or heart rate and individual changes in those values were not correlated with liver plasma flow. There was no correlation either between the plasma concentrations of pentoxifylline or its metabolites and the changes in liver plasma flow. It is concluded that, relative to the spontaneous decrease in liver plasma flow at rest on the placebo day, pentoxifylline increased splanchnic perfusion independent of any change in cardiac output.

Adult↗
PubMed1991

The influence of gestational age on bilirubin conjugation in newborns.

Unconjugated, mono- and diconjugated bilirubin levels were determined in serum soon after birth, and followed up for several days. Fourteen preterm neonates were studied with a gestational age below 33 weeks (n = 7) or between 34 and 37 weeks (n = 7), respectively, as well as 19 full-term newborns either untreated (n = 9) or treated by phototherapy (n = 10). Bilirubin and its derivatives were analysed by alkaline methanolysis and spectrometry after separation by thin-layer chromatography. In normal full-term neonates total and unconjugated bilirubin reached peak levels at days 2-4. Thereafter, a decline of 11% per day was detectable. Monoconjugates in serum amounted to 3.1 +/- 1.1% of total pigment and remained at that level. The relative amount of diconjugates increased from 0.55 +/- 0.25% (2-4th postnatal day) to 1.62 +/- 0.99% (9-13th day of life). The rapid decline of unconjugated bilirubin paralleled by an increase of diconjugates are an expression of the maturation process for bilirubin conjugation. The premature neonates with less than 33 weeks gestation exhibited an increase of unconjugated serum bilirubin up to the 4-5th postnatal day, the decline thereafter amounted 2% per day. The fraction of 2.3 +/- 1.1% monoconjugates was small and exhibited only a moderate increase in the follow up. In contrast diconjugates were undetectable or very low and remained at this level. These results suggest the presence of a more severe immaturity as well as a slower maturation process of bilirubin conjugation in preterm newborns.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗
PubMed1990

Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis.

Ursodeoxycholic acid treatment of patients with primary biliary cirrhosis may lead to relief of pruritus and improvement of biochemical liver tests. The changes in serum and urinary bile acids induced by ursodeoxycholic acid treatment were studied. After 29 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (750 to 1,000 mg/day) for 6 to 12 mo because of an increase in ursodeoxycholic acid, total plasma bile acids increased from 30.5 +/- 6 mumol/L (mean +/- S.E.M.) to 52.7 +/- 11.7 mumol/L (p less than 0.01). The increase in total plasma bile acids correlated significantly with concentrations of plasma bile acid before treatment (p less than 0.01). The concentrations of endogenous bile acids decreased, mainly because of a decrease of cholic acid. During treatment, glycine conjugation increased and taurine conjugation decreased, whereas sulfation and glucuronidation of bile acids were unchanged. In 10 patients with primary biliary cirrhosis in stages III and IV, urinary excretion of bile acids was also studied. After treatment, ursodeoxycholic acid and its 3-beta isomer and C-1-hydroxylated and C-6-hydroxylated derivatives were also excreted. During treatment, urinary excretion of endogenous bile acids decreased. The increase of ursodeoxycholic acid and the decrease of endogenous bile acids may both be related to the improvement of biochemical liver tests in precirrhotic stages of the disease. In cirrhosis, endogenous bile acids in plasma remained high and changes in liver tests were small.

Bile Acids and Salts↗
PubMed1990

The teaching and organisation of clinical pharmacology in European medical schools (W.H.O. Working Group on Clinical Pharmacology).

A World Health Organisation (European Regional Office) working party has been established to review the progress of clinical pharmacology in European countries. As part of this review a questionnaire on the teaching of clinical pharmacology was sent to the Deans of all 350 medical schools in the region. Very few replies were received from U.S.S.R., Greece and Portugal and these countries' returns were not analysed further. The overall compliance rate (excluding these countries) was 82% with a figure of 84% from Western Europe and 74% from Eastern Europe. An average time of 96 h (range 0-320) was devoted to pharmacology teaching in the medical curriculum in Western Europe with 124 (0-240) h in Eastern Europe. In contrast 28 h (0-210) was devoted to clinical pharmacology teaching in Western Europe and 27 h (0-90) in Eastern Europe. On average in Western Europe each medical school had 2 individuals trained in clinical pharmacology with 1.3 posts in the subject and the figures for Eastern Europe were 2.3 and 1.1 respectively. However these figures hide a wide variance in the teaching of clinical pharmacology. Particularly in Western Europe there are a number of medical schools in Italy, Spain and the Federal Republic of Germany (FRG) where clinical pharmacology is not taught and there is a dearth of individuals trained in the subject. Every effort to encourage clinical pharmacology and its teaching should be made, particularly in these countries.

Curriculum↗
PubMed1990

Lack of interference by sorbitol with aminopyrine breath test.

The effect of sorbitol on the aminopyrine breath test was investigated in 13 patients with various liver diseases given a bolus dose of sorbitol 20 mg.kg-1 i.v. 30 min after 14C-aminopyrine and 13 patients without the sorbitol bolus who also underwent an aminopyrine breath test. The time course of 14CO2 exhalation after the bolus of sorbitol did not differ from that in the control group.

Adolescent↗
PubMed1990

Excessive motor impairment two hours after triazolam in the elderly.

The 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.

Adult↗
PubMed1990

Paracetamol test: modification by renal function, urine flow and pH.

Factors which might affect paracetamol disposition have been studied in a heterogenous group of patients in need of mild analgesia in an intensive care unit. Following oral administration of 1 g of paracetamol, plasma and urinary concentrations of the parent compound and metabolites were assessed by HPLC. The renal clearance of paracetamol was significantly correlated with urine flow (r = 0.84) and creatinine clearance (r = 0.77), but not with urine pH. Metabolite output was diminished in patients with reduced renal function. Despite the heterogeneity of patients and the diversity of drug treatment, the urine to plasma paracetamol concentration ratio appeared remarkably constant in patients with normal renal function (9.8 +/- 2.7). It is concluded that the metabolite to paracetamol ratio may only be regarded as a measure of the drug metabolizing capacity in subjects with normal renal function, if factors influencing urine volume and paracetamol absorption are standardized.

Acetaminophen↗
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↗
PubMed1990

Hepatic and extrahepatic disposition of propofol in patients undergoing coronary bypass surgery.

In order to clarify the relative contribution of the liver to the short term disposition of propofol, hepatic blood flow was measured during induction of anaesthesia with an i.v. bolus dose of propofol 2 mg kg-1. Total clearance of the drug was 2390 (SD 340) ml min-1, hepatic extraction 82% and hepatic clearance 1060 (260) ml min-1. During the 60-min period of observation, hepatic extraction of propofol increased from 79% to 92%. It is concluded that, within 1 h, only 44% of the administered dose is removed by the liver. Consequently, drug accumulation may occur with repeated dosing or infusion of propofol. The increase in extraction results presumably from slow release of propofol from the soy-bean emulsion.

Adult↗
PubMed1990

Penetration of ciprofloxacin into the cerebrospinal fluid of patients with uninflamed meninges.

Nine patients with external ventriculostomy and suffering from hydrocephalus, due to non-inflammatory central nervous system diseases, were given ciprofloxacin (200 mg twice daily iv). Ciprofloxacin concentrations in serum and CSF were measured by HPLC. Single-dose pharmacokinetics were determined in three patients, and 60 and 600 min post-dose levels after repeated administration in six patients. CSF concentrations were maximal 60-120 min after the end of the infusion. The CSF elimination half-life was 260-430 min compared with 145-170 in serum. Post-dose levels at 60 min ranged from 0.042 to 0.223 mg/l (median = 0.110). Repeated administration did not lead to substantial increases in serum and CSF concentrations. With respect to MIC90 values reported for bacteria involved in CNS infections, the CSF concentrations of ciprofloxacin obtained under our experimental conditions would be considered subtherapeutic. Thus ciprofloxacin therapy of CNS infections may be inadequate when only minor impairment of the blood-CSF barrier exists.

Adult↗
PubMed1990

Low fractions of mono- and diconjugated bilirubin in patients with beta-thalassemia: an approach to characterize hepatic conjugation capacity.

Unconjugated and mono- and diconjugated bilirubin was determined by alkaline methanolysis and thin-layer chromatography in serum from 16 pediatric patients with homozygous beta-thalassemia (aged 1-23 years), in 14 age-matched controls, and in 26 healthy adults. Total bilirubin amounted to 21 +/- 20 mumol/L in patients with thalassemia compared with 7 +/- 4 mumol/L in healthy children and 11 +/- 3 mumol/L in healthy adults. The fractions of bilirubin conjugates in the various groups were 8 +/- 4% (patients with thalassemia), 18 +/- 5% (age-matched controls; p less than 0.001), and 16 +/- 5% (healthy adults; p less than 0.001). The low fraction of bilirubin conjugates in patients with thalassemia showed no correlation to any other physical or laboratory finding. It is concluded that subnormal values of bilirubin conjugates in thalassemia indicate defective bilirubin conjugation.

Adolescent↗
PubMed1989

Dose equivalence of midazolam and triazolam. A psychometric study based on flicker sensitivity, reaction time and digit symbol substitution test.

The pharmacodynamic potency of oral midazolam, a new ultrashort-acting hypnotic benzodiazepine, has been evaluated relative to a standard dose of triazolam, a well established oral benzodiazepine with a similar pharmacological profile. In a balanced design, double-blind cross-over study 6 healthy volunteers received 3.75, 7.5, and 15 mg midazolam and 0.25 mg triazolam orally, at 8 a.m., at weekly intervals. Drug effects were repeatedly measured over 8 h by a new psychometric method, the threshold amplitude for perception of flickering light (TPF) assessed at 5 and 30 Hz. Auditory reaction time, digit-symbol substitution test (DSST), and self-rating by subjects served as reference standards. Median midazolam doses equivalent to 0.25 mg triazolam, interpolated on dose-response curves for peak effects, were 5.2 mg (TPF 30 Hz), 6.4 mg (TPF 5 Hz), 6.5 mg (DSST), and 7.4 mg (reaction time), respectively. Alternative methods of data analysis gave similar results. Introduction of TPF as a highly reproducible and sensitive measure of the effect of benzodiazepines on the CNS offers new opportunities to compare the relative potencies of different benzodiazepines in man. Since clinical experience has shown 0.25 mg triazolam to be safe and effective, it is concluded that the corresponding single oral dose of midazolam is between 5 and 8 mg.

Adult↗
PubMed1989

Superiority of the Child-Pugh classification to quantitative liver function tests for assessing prognosis of liver cirrhosis.

To evaluate the prognostic value of quantitative liver function tests in comparison with established prognostic variables, the data of 47 patients with liver cirrhosis were analysed. A total of 16 variables, comprising the galactose elimination capacity and the indocyanine green clearance, the Child-Pugh classification, and several clinical and biochemical variables were subjected to Kaplan-Meier life-table analysis and Cox proportional hazards regression analysis. As independent variables, poor prognosis was associated significantly with increasing Child-Pugh score (p less than 0.00001), whereas the galactose elimination capacity (p = 0.03) and the indocyanine green clearance (p less than 0.001) were less sensitive indicators. The regression analysis showed prognostic value in decreasing sequence for Child-Pugh classification, age, sex, history of upper GI haemorrhage, and alkaline phosphatase activity. The quantitative liver function tests evaluated in the present work have less prognostic value than routinely accessible variables.

Adult↗