Divergence of ethanol and acetaldehyde kinetics and of the disulfiram-alcohol reaction between subjects with and without alcoholic liver disease.

Despite standardization, marked interindividual variation in the severity of the disulfiram-alcohol reaction (DAR) has been observed. We studied the DAR in 51 consecutive alcoholics with (n = 16) and without (n = 35) significant alcoholic liver disease. Clinical signs of the DAR were much weaker in the patients with compared with those patients without liver disease.

Caffeine demethylation measured by breath analysis in experimental liver injury in the rat.

To assess the effects of experimental liver injury on caffeine metabolism, 1 muCi/kg b.w. of [3-methyl 14C]-caffeine (together with 5 mg/kg b.

[What does the alcoholic patient need from his family physician?].

Chronic alcoholics are all too often not recognized in general practice. Diagnosis is only possible if the doctor assumes potential alcoholism in all his patients. Because of the tendency of the patient and often his family to deny alcohol dependence, diagnosis is only possible by taking psychiatric, somatic and psychosocial aspects into consideration in addition to an independent history.

Microsomal liver function declines steadily after kidney grafting: a three to five year follow-up.

We have previously shown that the functioning hepatocyte mass (galactose elimination capacity, GEC) and microsomal liver functions (non-renal clearances of unbound prednisolone and cyclosporin A) are impaired in renal allograft recipients (N = 28) one month and one year after successful transplantation. To assess the natural history of these hepatic functional derangements, we reinvestigated 21 patients with stable renal function three to five years following grafting. GEC remained with 6.

Chronic rejection and extrahepatic biliary tract obstruction 8 years after orthotopic liver transplantation using the gallbladder-conduit technique.

A case of delayed biliary obstruction and cholangitis, occurring in the setting of chronic allograft rejection, 8 years after liver transplantation using the gallbladder-conduit, is presented. Extrahepatic biliary obstruction may be seen in the late follow-up of liver grafting and rejection phenomena may play a significant role in the development of such obstruction.

[Ambulatory, disulfiram-(Antabuse)-assisted management of the alcoholic patient].

The treatment of patients suffering from alcoholism is notoriously difficult. Ambulatory supportive therapy using disulfiram and supervised by the practicing physician has many advantages. Foremost among these is the maintenance of the patient within his working and social environment.

Use of quantitative liver function tests--caffeine clearance and galactose elimination capacity--after orthotopic liver transplantation.

To establish the potential value of quantitative tests of liver function following orthotopic liver transplantation (OLT), a total of 100 determinations of caffeine clearance (CafCl) and galactose elimination capacity (GEC) were made in ten OLT recipients early in the post-operative course (days 2, 4, 6, 8 and 12) and later when clinically stable (3-12 months). Values were compared with a reference range in six normal volunteers in whom it was shown that the standard doses of caffeine (125 mg) and galactose (0.5 g per kg body weight) could be given together without interference.

Increased urinary excretion of bile alcohol glucuronides in patients with primary biliary cirrhosis.

The bile alcohol glucuronides in urine of 12 patients with primary biliary cirrhosis (PBC), 10 patients with chronic active hepatitis (CAH), and 6 healthy volunteers were analyzed by capillary gas-liquid chromatography-mass spectrometry. In all subjects studied, the major urinary bile alcohol was found to be 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol (C26 pentol). In PBC patients, the excretion of C26 pentol (main isomer) was significantly increased above values observed in healthy volunteers (mean +/- SD = 5.

Impaired liver function in stable renal allograft recipients.

Hepatic failure as a cause of death is increased in stable renal allograft recipients when compared with patients on dialysis. In order to assess the magnitude and the natural history of the hepatic functional derangement, the kinetics of xenobiotics which are metabolized by cytosolic (galactose) or microsomal (prednisolone, cyclosporine A) enzymes were determined in 28 consecutive stable kidney transplant patients 1 month and 1 year after transplantation. Renal transplant patients had a decreased mean (+/- S.

Use of salivary levels to predict clearance of caffeine in patients with cystic fibrosis.

The quantification of liver function is possible using the approach of salivary caffeine clearance. Hepatopathy sometimes complicates cystic fibrosis (CF), thus suggesting the use of this diagnostic tool in CF as well. Since in CF some compounds are poorly absorbed or abnormally metabolized, and the function of salivary glands or renal tubuli partly impaired, caffeine was measured in urine, blood, and saliva after a single oral dose of 3 mg/kg in CF patients.

The 30-minute aminopyrine breath test: optimization of sampling times after intravenous administration of 14C-aminopyrine.

In a retrospective analysis of 78 well-defined patients, the procedure of the aminopyrine breath test was evaluated. After intravenous administration of 14C-aminopyrine (1.5 microCi, 1 mg) 14CO2 was sampled at 15-min intervals for 1 h.

Overnight salivary caffeine clearance: a liver function test suitable for routine use.

The feasibility of measuring caffeine clearance from saliva (SCl) was assessed in ambulatory patients with liver disease and in a control group, and the results were compared with quantitative liver function tests. For this purpose, the subjects were given 280 mg caffeine p.o.

[Cardiovascular and metabolic changes in the antabuse-alcohol reaction: basis for the diagnosis of degree of severity].

The clinical symptoms and signs, certain metabolic aspects (including ethanol, acetaldehyde and glucose concentrations in plasma) and hemodynamic parameters (cardiac rate, blood pressure and cardiac output) were assessed in 16 ambulatory alcoholics (3 female, 13 male, average age 46 years) following pretreatment with disulfiram (total dose 1.2 to 2.4 g) and oral administration of 0.

Perhexiline-induced lipidosis in the dark Agouti (DA) rat. An animal model of genetically determined neurotoxicity.

Perhexiline maleate, an antianginal compound, may cause severe adverse effects such as weight loss, hepatic dysfunction and peripheral neuropathy in a small proportion of patients. Since present evidence suggests that poor debrisoquine hydroxylators are at risk, we designed an experimental study comparing its neurotoxic effects in dark Agouti (DA) rats, with poor hydroxylation of debrisoquine with that in Sprague Dawley (SD) rats, which are vigorous hydroxylators. Light and electron microscopic investigations revealed neurotoxic changes in DA rats after cumulative doses which did not cause any changes in SD rats.

Effect of dietary caffeine on airway reactivity in asthma.

The potential influence of dietary caffeine on bronchoprovocation challenges with carbachol was examined in 7 patients with asymptomatic asthma. In a double-blind fashion placebo or caffeine (6 mg/kg body weight; equivalent to approximately 4 cups of coffee) solved in orange juice was administered, and carbachol challenges were performed. The average peak serum concentration achieved 60 min after dosing was 7.

Polymorphic debrisoquine and mephenytoin hydroxylation in patients with pulmonary hypertension of vascular origin after aminorex fumarate.

During the period 1967 to 1971 an increase in the incidence of pulmonary hypertension of vascular origin (PHVO) was observed in Austria, Federal Republic of Germany, and Switzerland. Most patients had been given aminorex fumarate and a possible link was suspected. We therefore investigated the possibility of genetically-determined drug hydroxylation deficiencies (debrisoquine or mephenytoin type) in these patients as an explanation for the development of PHVO.

Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquin hydroxylation.

Dextromethorphan hydrobromide, 25 mg po, was given to 268 unrelated Swiss subjects to study urinary drug and metabolite profiles. Rates of O-demethylation yielding the main metabolite dextrorphan were expressed by the urinary dextromethorphan/dextrorphan metabolic ratio. We found a bimodal distribution of this parameter in our population study, which indicates that there are two phenotypes for dextromethorphan O-demethylation.

Fasting plasma caffeine concentration. A guide to the severity of chronic liver disease.

Fasting plasma caffeine concentrations (FPCC) were measured in 86 outpatients being examined for suspected or known liver disease. Seven patients (8%) who avoided caffeine consumption had nonmeasurable FPCC; they were dropped from further consideration. The remaining 79 subjects were divided into 4 diagnostic groups: surgical shunt (n = 11); alcoholic, posthepatitic, or primary biliary cirrhosis (n = 29); miscellaneous liver disease (n = 23); and normal liver (n = 16).

[Quantification of the drug-metabolizing enzyme system in liver diseases: a comparison between antipyrine saliva clearance and the aminopyrine breath test].

The metabolic activity of the hepatic cytochrome P450 system was studied in 53 ambulatory subjects. 18 of these were cirrhotics and 23 had non-cirrhotic liver disease, documented by biopsy, serologic, ultrasound or computerized tomography findings, and characterized by quantitative liver function tests, such as galactose elimination capacity and indocyanine green fractional clearance. For comparison, 12 normal control subjects were also included.

The disulfiram-alcohol reaction: factors determining and potential tests predicting severity.

13 ambulatory alcoholics (3 women, 10 men) who consented to alcohol-aversive treatment with disulfiram were subjected to detailed investigations before, during, and after the disulfiram-alcohol reaction (DAR). The studies included quantitative estimation of liver function (aminopyrine breath test, ABT; galactose elimination capacity, GEC) prior to the DAR, measurement of alcohol and acetaldehyde plasma levels together with pulse rate and blood pressure during the DAR, and the effects of disulfiram on erythrocyte acetaldehyde-oxidizing capacity (AOC). As expected, the severity of the DAR showed considerable interindividual variation.

[Foreign substances as indicators of liver function].

The need to use xenobiotics to quantify liver function is based on the fact that the serum levels of endogenous tracers (such as transaminases, alkaline phosphatase, bilirubin and bile acids) cannot be interpreted in pharmacokinetic terms, since information is lacking on volume of distribution and on rate of synthesis and of disposition. Methods are now available which allow practically non-invasive estimation of (minimal) hepatic perfusion by indocyanine green fractional clearance, of portosystemic shunt flow by finger pulse photometry following nitroglycerin administration, of microsomal capacity by the aminopyrine breath test (ABT) or caffeine clearance, and of cytosolic function by galactose elimination capacity (GEC). Assessment of inherited hydroxylation deficiency of the debrisoquine type is best performed with dextromethorphan, and of the acetylator phenotype with sulfadimidine.