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Biomedical subjects

J Bircher

Publications and source records attributed to J Bircher.

At least 91 records · Page 5Linked to original sources
PubMed1981

[New aspects in the treatment of cholecysto-and choledolithiasis].

Since gallstone disease is one of the most frequent gastrointestinal disorders (average incidence 27% in males and 47% in females) it is mandatory for practicing physicians to keep abreast of recent progress in therapy. Thus, present treatment is based on the radiologic pattern of radiolucent (cholesterol) and radioopaque (calcium containing) stones. In the young patient, cholecystectomy is recommended for cholecystolithiasis regardless of type of stones, because this procedure is likely in most cases to provide optimal, definitive results at minimal risk. In the elderly, or when the operative risk is aggravated by accompanying disease, an attempt may be made to dissolve cholesterol stones by oral administration of cheno- or ursodeoxycholic acid. Following 18 months to 2 years of medication, the success rate for complete dissolution is approximately 50%.

Aged↗
PubMed1981

Chemotherapy of alveolar echinococcosis. Comparison of plasma mebendazole concentrations in animals and man.

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis. In order to improve therapeutic results the pharmacology of mebendazole has been investigated. Jirds experimentally infected with larval Echinococcus multilocularis were given food containing mebendazole 100 to 1000 ppm. Drug plasma concentrations above 0.25 mumol/l were associated with a reduction in parasite weight to 1 to 10% of that in untreated controls. In treated animals parasite weight was negatively correlated with the plasma mebendazole concentration and with the duration of therapy. In patients on long term therapy with similar doses of mebendazole (16 to 48 mg/kg per day), plasma concentrations were much lower than in jirds. Only 19% of fasting plasma concentrations exceeded 0.25 mumol/l. Plasma concentrations 4 h after the morning dose did not exceed this value in 48% of cases. The results can be explained by the irregular drug absorption and short plasma half life observed in 7 hospitalized patients. It is likely that better results would be obtained if doses of mebendazole were adjusted to produce peak plasma levels exceeding 0.25 mumol/l.

Adult↗
PubMed1981

Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test.

[1-Methyl-14C], [3-Methyl-14C] and [7-Methyl-14C] caffeine were used to investigate demethylation in control rats, and in rats pretreated with phenobarbital or 3-methylcholanthrene, by a 14CO2-exhalation test. Compared to controls, pretreatment with phenobarbital did not enhance demethylation of any of the labelled caffeines. In contrast, induction by 3-methylcholanthrene, presumably of cytochrome P-448, resulted in highly significant increases in peak 14CO2 exhalation rates, 14CO2 disappearance constants and areas under the exhalation rate - time curves. Based on these results, [7-methyl-14C] and [3-methyl-14C] caffeine were chosen for assessing the feasibility of a caffeine breath test in man, using 5 normal volunteers and 2 patients with compensated liver cirrhosis. 14CO2 exhalation curves in cirrhotics were clearly different from those in normal volunteers, being characterised by a slower rise and a lower specific activity of exhaled 14CO2. Since the variability of the levels of the specific activity in subjects with normal livers suggested the influence of extraneous factors, a second group of normal volunteers, smokers and nonsmokers, was investigated. With either labels, the average 14CO2 exhalation rate was doubled in smokers. From these studies in rats and preliminary results in man it is concluded that specifically labelled caffeine is a suitable and promising substrate for studying demethylation by breath analysis. Presumably, caffeine represents a safe and sensitive indicator of the activity of the cytochrome P-448 system.

Adult↗
PubMed1981

Phenytoin therapy for epileptic children: evaluation of salivary and plasma concentrations and of methods of assessing compliance.

Monitoring phenytoin therapy in children is difficult because they fear blood sampling, yet frequent control of phenytoin levels may be necessary because of the age-dependence of phenytoin metabolism. In 22 patients aged between six and 15 years, phenytoin concentrations were studied in mixed saliva and parotid saliva and were compared with plasma levels from blood obtained at the same time. For mixed saliva, the saliva: plasma concentration ratio was 0.11 +/- SD 0.04 and in parotid saliva it was 0.10 +/- 0.06. In addition, compliance was studied in 13 children, each receiving between three and seven different quantities of phenytoin. Clinical judgement about compliance agreed well with the two laboratory measures. A graphic analysis of the relationship between plasma concentration and dosage is proposed as practical method of assessing compliance, because it appears to be both simple and reliable, and therefore suitable for routine use.

Adolescent↗
PubMed1981

A rabbit model allowing access to portal vein, vena cava, aorta and duodenum without anesthesia.

In studies of hepatic first-pass elimination of drugs gastric emptying, intestinal absorption and metabolism may be factors difficult to control. Direct access to the portal vein and to the duodenum without the need for anesthesia could overcome this problem. A rabbit model was, there for, developed with chronically implanted catheters in the portal vein, the aorta, the vena cava and the duodenum but necessitating a left nephrectomy. Hepatic and renal function before and 14 days after the operation showed no significant differences with respect to serum GOT, GPT, K, Na, Cl, PO4, urea-N, and creatinine levels. Arterial catheters were functioning for an average of 55, venous catheters for 49 and portal catheters for 59 days. Autopsy revealed no major pathology. This model permits the separate study of hepatic and intestinal first-pass effects in unanesthetized and unstressed rabbits.

Anesthesia↗
PubMed1981

Preferential reduction of first-pass elimination by ethanol. Model experiments with clomethiazole in the rabbit.

The importance of the route of drug administration for drug ethanol interactions was studied using clomethiazole as model drug. To 10 rabbits equipped with permanently implanted catheters in the portal vein, the vena cava and the aorta respectively, clomethiazole was infused either into the portal vein or the vena cava and either together with i.v. saline or with i.v. ethanol. Arterial plasma clomethiazole and ethanol concentrations were measured by gas-liquid chromatography. After portal clomethiazole infusion, ethanol increased by the relative availability of clomethiazole to 270 +/- 90% (S.D.) of the saline controls, whereas after i.v. clomethiazole infusions the relative availability was increased only to 120 +/- 20% of the corresponding controls. Similarly, ethanol increased average plasma clomethiazole concentrations after 90 min of portal infusion from 5 to 14 nmol/ml, whereas after i.v. clomethiazole infusions the ethanol effect was small, the concentrations increasing only from 28 to 35 nmol/ml. These results are compatible with the concept that an ethanol-induced reduction of the hepatic capacity to metabolize a highly extracted drug is reflected to a much larger extent during first-pass elimination than during systemic clearance. Consequently, clinical toxicity in inebriated subjects is more likely to occur after oral than after parenteral administration of high extraction drugs.

Animals↗
PubMed1980

Plasma concentrations of mebendazole during treatment of echinococcosis: preliminary results.

High oral doses of mebendazole are used experimentally for the treatment of human alveolar and cystic echinococcosis. In order to assess bioavailability of this drug 1.5 g doses were given to 3 volunteers. Measurable plasma concentrations of 17 to 134 nmol/l were found only if mebendazole was given together with a fatty meal. In a patient with cholestasis plasma concentrations were higher than in the 3 normal subjects. In patients on long term treatment the increase in plasma concentration after administration of a 1 g dose varied between 0 and 500 nmol/l. It is concluded that systemic availability of mebendazole is enhanced by concomitant food intake. In view of the large intra- and interindividual variation in plasma concentration, monitoring plasma levels during long term therapy appears advisable.

Administration, Oral↗
PubMed1980

Increased systemic availability of drugs during acute ethanol intoxication: studies with mephenytoin in the dog.

The influence of ethanol on the fate of orally administered drugs which normally undergo a high presystemic elimination is as yet ill-defined. Experiments, therefore, were designed in four nonanesthetized dogs with mephenytoin as model compound. The drug was administered p.o. or i.v., and throughout an 8-hr period ethanol (100 mg kg-1 hr-1) or saline was infused according to a cross-over design. Concentrations of mephenytoin and its main metabolites, nirvanol and p-hydroxymephenytoin, were determined by gas-liquid chromatography. In experiments with oral mephenytoin administration and ethanol infusion, mephenytoin peak plasma concentrations were elevated by 87.0 +/- 15.2% (S.E.M.) (P less than .005, n = 4). Correspondingly, the average area under the plasma concentration time curve was increased to 229% of control (P less than .005). Ethanol also reduced metabolite formation; the area under the plasma concentration time curve for nirvanol was reduced by 40% (P less than .005). Urinary output of nirvanol was diminished to 51% and of p-hydroxymephenytoin to 73% (P less than .05, n = 12). It is concluded that drug ethanol interactions may be particularly prominent for orally administered drugs which normally are subject to a high presystemic elimination. This mechanism might be a clinically relevant cause for ethanol related drug toxicity.

Administration, Oral↗
PubMed1980

[The galactose breath test. Modification of the method and comparison with galactose elimination capacity and plasma disappearance of bromsulphatein (author's transl)].

The paper describes a modification of the galactose breath test (GBT) for assessing liver function. Following iv injection of 0.5 g galactose per kg body weight, together with 2 mu Ci generally 14C-labelled galactose, 14CO2 is collected in regular intervals during one hour. Since 14C-activity in breath exhibits a linear rise during 70--100 minutes, the curve obtained permits calculation of an initial slope, as well as the "standardized specific activity" after 45 min GBT was performed in 8 liver normals, 8 alcoholic cirrhotics, 4 patients with chronic active hepatitis (CAH) and 6 with primary biliary cirrhosis (PBC). The results were compared with the simultaneously measured galactose elimination capacity (GEC) and the initial plasma disappearance (ki) of bromsulphthalein (BSP). In the liver normals, the values for initial slope and standardized specific activity were 1.08 +/- S.D. 0.3 and 0.42 +/- S.D. 0.1, respectively. In comparison, the values obtained in all patients groups were markedly reduced. CAH patients exhibited the most severe decrease; the reduction was smallest in PBC patients. The GBT discriminated well between liver normals and patients with liver disease (p less than 0.001, t-test). The results of the GBT correlated linearly with GEC (r = 0.86 and 0.87, respectively) and with BSP-ki (r = 0.9 and 0.92, respectively). These results suggest that the GBT may be regarded as a quantitative measure of a cystosolic hepatic function.

Aged↗
PubMed1979

Liver function in physically trained subjects: galactose elimination capacity, plasma disappearance of indocyanine green, and aminopyrine metabolism in long-distance runners.

Physical exercise and physical training are known to affect several aspects of hepatic metabolism. To assess whether adaptation to long-lasting exercise modifies microsomal drug metabolism, 8 long-distance runners were compared with a group of medical students having significantly lower maximal rates of oxygen consumption. At rest the hepatic galactose elimination capacity and the indocyanine green plasma disappearance rate used as reference methods were the same in both groups. The plasma clearance of ([14C]dimethylamine) aminopyrine and the kinetics of 14CO2 in breath did not differ either. It is concluded that adaptation to long-lasting exercise can occur without evidence for changes in hepatic galactokinase activity, liver blood flow, or microsomal metabolism of aminopyrine.

Adaptation, Physiological↗