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Biomedical subjects

J Bircher

Publications and source records attributed to J Bircher.

At least 73 records · Page 4Linked to original sources
PubMed1983

In vivo hydroxylation of 3H-acetanilide--evaluation of a new radiospirometric method in the rat.

The proposed in vivo methodology for the investigation of hydroxylation rates consists of of the i.v. administration of tritiated substrates and the collection of tritiated water (HTO) from exhaled air as a measure of HTO accumulation in body water. Specifically, HTO was assessed in exhaled water after i.v. administration of 3H-acetanilide. Over a wide range the half lives of accumulation of HTO in exhaled water (T50) were almost identical with the half lives of elimination of 3H-acetanilide in blood, evaluated by an inverse isotope dilution method (r = 0.96, N = 18). Average T50 amounted to 29 min in controls, was reduced to 20 min after enzyme induction by phenobarbital or 3-methylcholanthrene, and prolonged to 45, 46 and 66 min after bile duct ligation, portacaval shunt and a single dose of ethanol, respectively. It is concluded that the chosen pharmacokinetic approach corrects for the NIH-shift and the results adequately reflect changes in acetanilide hydroxylation related to enzyme induction or inhibition and to liver pathology.

Acetanilides↗
PubMed1983

[Hepatitis B infection: studies on endemic disease in the closed ward of a psychiatric hospital].

Following the occurrence of 3 cases of icteric hepatitis in the period August 1980 to January 1981 in a closed male ward for mentally retarded patients in a psychiatric institution, the present study was undertaken to determine the type, investigate the source and reconstruct the sequence of viral infection, and to make recommendations for its containment. For this purpose, serologic markers for HAV and HBV (including anti HBcIgM) were determined and serum transaminase (AST) measured in March 1981 in all 24 patients (mean age 40) and in the 39 members of the medical, nursing and housekeeping staff (mean age 39). Subsequently, HAV and HBV serologies were repeated after 6 and 9 months respectively. The propositus (B.F.) and the two subsequent cases with overt hepatitis (F.P. and K.E.) showed the serologic constellation of positive HBs, HBe and anti HBcIgM, together with elevated AST levels (600, 800 and 200 I.U. respectively) at the time of clinical illness, consistent with an acute HBV infection. Since 7 (18%) among the staff members were immune to HBV (positive anti HBs and anti HBc) and the remainder sero-negative; the remaining 6, however, showed evidence of active viral replication (S. P. and K. E.), viral infection (F. P. and J. L.) or incomplete immune response (B.F. and G.H.). During the 9 months' follow-up their serologic status did not change, with the exception of 2 (F.P. and B.F.), in whom HBs disappeared. The incidence of anti HAV in patients was 42% and in the staff 44%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Preliminary observations on the biliary elimination of mebendazole and its metabolites in patients with echinococcosis.

The biliary excretion of mebendazole has been investigated in two patients to whom it was given for the treatment of echinococcosis, although it was found to be only partly effective. Oral mebendazole was extensively metabolized and the conjugated parent substance and its metabolites were excreted in the bile. One patient without cholestasis and with normal liver function had an apparent total biliary clearance (776 ml/min) which approached the hepatic plasma flow. The other patient with cholestasis and impairment of the hepatic drug metabolizing capacity showed a drastically reduced apparent total biliary clearance of 3.8 ml/min. The average plasma level of mebendazole was significantly lower in the former and higher in the latter patient (0.06 and 0.91 nmol/ml, respectively). The data suggest that impaired metabolism and/or biliary elimination can account for the higher plasma mebendazole level in patients with liver damage.

Adult↗
PubMed1983

Chemotherapy of larval echinococcosis with mebendazole: microsomal liver function and cholestasis as determinants of plasma drug level.

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis, possibly due to an inadequate plasma concentration of the drug in some patients. In order to improve therapeutic results the influence of liver function on the plasma levels of mebendazole was investigated during long term therapy. Plasma mebendazole concentrations measured before the morning dose (trough values) showed a highly significant, negative correlation both with the aminopyrine breath test (ABT; rs = -0.78, n = 14, p less than 0.001) and the second exponential component of bromsulphthalein elimination (BSP- k2; rs = -0.74, n = 12, p less than 0.01). These relationships also applied over longer than a single day, since trough and peak mebendazole levels observed over an interval of 6 months before and after testing liver function were equally well correlated with ABT and BSP-k2. The daily dosage and other liver function tests seemed to be of minor importance in determining the plasma levels. It was concluded that the microsomal function of the liver and/or cholestasis might be important determinants of plasma mebendazole levels. The results of the study imply that higher and more effective mebendazole concentrations might be achieved by inhibition of the drug metabolizing capacity of the liver rather than by increasing the dose of mebendazole.

Adult↗
PubMed1983

Serum concentrations of amiodarone during long term therapy. Relation to dose, efficacy and toxicity.

In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 mumol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 mumol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 mumol/l. Tentatively, a therapeutic range of 1.5 to 4 mumol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.

Adult↗
PubMed1983

Triazolam concentration-effect relationships in healthy subjects.

Triazolam was used to study the plasma concentration-effect relationship of a benzodiazepine because it has a very short plasma t1/2. A standard hypnotic dose of 0.25 mg was given by mouth to six healthy subjects, and blood samples were drawn when the subjects had to perform a battery of psychologic tests. Only the digit-symbol substitution test, the card-sorting test according to numbers, and the visual analog scale (energetic-lethargic) gave significant results. Analysis of the concentration-effect relationship in individuals indicated a wide scatter of the data. Mean values revealed a trend for a learning effect in the card-sorting test. The results are consistent with the hypothesis that triazolam is well suited for a study of concentration-effect relationships, but better psychologic tests would be desirable.

Adult↗
PubMed1983

Lack of inhibition of clomethiazole metabolism by cimetidine: model experiments in the dog.

The disposition of clomethiazole was studied in six dogs subjected to pretreatment with cimetidine or saline according to a cross-over design. Pretreated dogs received approximately 20 mg/kg of cimetidine p.o. for 4 days and 30 mg/kg i.v. immediately before an intraduodenal infusion of clomethiazole (117 mumol/kg clomethiazole base within 90 min). Compared to controls, cimetidine had no effect on peak plasma concentrations and on areas under the plasma concentration time curves of clomethiazole or of its metabolite 5-acetyl-4-methylthiazole (P greater than 0.05). Identical pretreatment of the same dogs resulted in a 50% inhibition of aminopyrine demethylation (P less than 0.001) as revealed by the aminopyrine breath test. Clomethiazole may be metabolized in the dog through metabolic routes which cannot be inhibited by cimetidine.

Aminopyrine↗
PubMed1983

Non-invasive methods for the assessment of hepatic drug disposition.

Assessment of hepatic drug metabolism by clearance techniques requires frequent blood sampling and has therefore received only limited application. Non-invasive methods enjoy better patient acceptance, but of necessity are indirect and therefore require extensive validation. The clinical usefulness of the aminopyrine breath test is now well established but it may yield abnormal results if the functioning liver cell mass is reduced irrespective of the aetiology of the disease. It is thus primarily an indicator for prognosis rather than diagnosis. It may also be influenced by drug interactions. In view of the different metabolic fate of glyceryl trinitrate this test compound may be used for the non-invasive detection of portal-systemic shunting, rather than for changes in the functional capacity of the liver. Thus, non-invasive tests of hepatic drug disposition can now be used to assess at least two different physiological derangements in patients with liver disease.

Aminopyrine↗
PubMed1982

[1st use of lactitol in the treatment of porto-systemic encephalopathy].

Lactitol (beta-galactosido-sorbitol) is not absorbed in the small bowel but metabolized by colonic bacteria, and should therefore be as effective in the treatment of portal-systemic encephalopathy as lactulose (beta-galactosido-fructose). This hypothesis was tested in a 61-year-old alcoholic with an end-to-side portacaval anastomosis and chronic portal-systemic encephalopathy. Under controlled conditions he was switched from optimized treatment with lactulose to several regimens with lactitol (40-68 g/day), after which he was maintained on the new treatment for 1 year. On lactitol his condition was at least as good as on lactulose, but lactitol produced no taste aversion because it is less sweet. In addition, the patient no longer had nausea after taking the drug because lactitol can be supplied in a nonhygroscopic, chemically pure, crystalline form and therefore is less hyperosmotic than lactulose, which is supplied with contaminations of galactose and lactose. Obviously the data in single case represent only a feasibility study. Nevertheless, the outcome in this patient, together with the advantages of the new sugar, justify the planning of controlled clinical trials.

Esophageal and Gastric Varices↗
PubMed1982

[Positive diagnosis of Gilbert syndrome. Retrospective analysis of 59 cases with special reference to the nicotinic acid test].

The results of a retrospective analysis of 59 patients with Gilbert's syndrome are presented. All the patients were selected on the basis of repeatedly documented, predominantly unconjugated hyperbilirubinemia in the absence of liver or hemolytic disease. The peak incidence of Gilbert's syndrome was in the 15-30 years age group with males predominating almost fivefold. Scleral icterus or a laboratory finding of hyperbilirubinemia represented the major reasons for workup. Presenting symptoms such as fatigue, upper abdominal pain and fat intolerance were largely nonspecific. Whereas minimal values for total serum bilirubin concentrations were, at l.57 +/- 0.56 mg/dl (mean +/- S.D.), often within the normal range (less than 1.2), maximal values were always clearly elevated (2.05 +/- 0.65). The sex difference in bilirubin levels was also maintained in the Gilbert's syndrome, since mean values in women were lower than in men. As expected, neither liver scan nor histology yielded evidence of structural abnormalities. The results of liver function studies such as galactose elimination capacity, aminopyrine breath test, or fasting and postprandial serum bile acids, were all within normal limits. In contrast, the initial plasma disappearance of bromsulphthalein (BSP-k1) was reduced in 6 patients to a mean of 8.7% per min (normal value 12.6 +/- 1.6), which suggests that these subjects belong to the Gilbert type with diminished hepatic clearance of anionic dyes. The hematological investigations, including hemoglobin electrophoresis, Coombs tests and erythrocyte enzymes, yielded normal results. However, osmotic fragility was increased in 5 cases and erythrocyte survival reduced to less than 24 days in 9 cases (of 17 investigated). In 35 patients, a nicotinic acid test was performed in which total serum bilirubin rose within 3 hours from a mean of 1.66 +/- 0.7 to 3.51 +/- 0.75 mg/dl. Between the third and fifth hour bilirubin levels plateaued, yielding retention values of 98%, 92% and 92% respectively. These retention values may be considered in indirect estimate of bilirubin clearance. Retentions exceeding 70% after 5 hours correspond to bilirubin clearances of less than 20 ml/min, representing evidence in favour of the diagnosis of Gilbert's syndrome.

Acetylation↗
PubMed1982

Treatment of human echinococcosis with mebendazole. Preliminary observations in 28 patients.

Preliminary results of a long-term, prospective therapeutic trial with mebendazole in 28 patients mainly with inoperable echinococcosis are reported. The course of disease was monitored closely and plasma mebendazole levels were checked regularly. A major problem is the lack of reliable methods for defining and measuring early success or failure of therapy. Most of the patients improved clinically. No marked change of parasitic lesions was observed except in one patient with constantly low plasma mebendazole levels who deteriorated. No serious side effects occurred. The preliminary results are encouraging and suggest that mebendazole has a "parasitostatic" effect on larval growth.

Adult↗
PubMed1982

Noninvasive assessment of portal-systemic shunting: evaluation of a method to investigate systemic availability of oral glyceryl trinitrate by digital plethysmography.

The systemic availability of oral glyceryl trinitrate may be a measure of the fraction of portal blood bypassing the hepatocytes through portal-systemic shunts. In order to test this hypothesis without the need for blood sampling, measurements of drug concentrations in plasma were replaced by assessments of pharmacologic effects by using digital plethysmography. Dose-response curves resulting from graded intravenous infusions of glyceryl trinitrate (8 and 25 microgram/min) were used as standard of comparison for the pharmacologic response resulting from an oral dose of 800 microgram. In 9 normal volunteers, systemic availability of oral glyceryl trinitrate was 2 +/- 4% SD. In 7 patients with end-to-side portacaval shunts it was 94 +/- 18%, in 3 patients with distal splenorenal shunts 57 +/- 11%, and in 10 patients with cirrhosis of the liver it varied between 15% and 85%. Systemic availability of glyceryl trinitrate was negatively correlated with the initial plasma disappearance rate of sulfobromophthalein (r = -0.72, p less than 0.01). No significant correlation was found with the galactose elimination capacity (r = -0.12, n = 17). The lack of systemic availability of glyceryl trinitrate in healthy volunteers together with an availability close to 100% after end-to-side shunts is compatible with a very high hepatic extraction of the test compound by the normal liver, and with the idea that the systemic availability of of oral glyceryl trinitrate comes close to representing portal-systemic shunting. The procedure is rapid, essentially noninvasive, and well tolerated by patients.

Administration, Oral↗