Prediction of fatality in fulminant hepatic failure.

Thirty-three consecutive patients admitted to the intensive care liver unit of Rigshospitalet with acute hepatic encephalopathy induced by viral hepatitis, drugs, or pregnancy were studied. All were treated with a standard anticoma regime. The 20 patients (61%) who died had a higher bilirubin level and lower total cholic acid conjugation and glycine cholic acid conjugation (p less than 0.

Inactive proenzyme to tissue-type plasminogen activator from human melanoma cells, identified after affinity purification with a monoclonal antibody.

The human 66 000 mol. wt. plasminogen activator (HPA66; tissue-type plasminogen activator) has been purified from melanoma cells by a one-step affinity method with a monoclonal antibody.

Lack of interaction between cimetidine and carbamazepine.

In order to investigate a possible interaction between cimetidine and carbamazepine (CBZ) 7 otherwise healthy epileptic patients on a long-term monotherapy with CBZ were given cimetidine (1 g daily) for 7 days. No significant alterations in steady-state plasma concentration of CBZ and the 10,11-epoxide metabolite (CBZ-E) were demonstrated.

Cholic acid conjugation test and quantitative liver function in acute liver failure.

In 33 patients with acute hepatic encephalopathy due to toxic or viral hepatitis the following analyses were performed: (24-14C)cholic acid conjugation and sulfation, plasma phenazone clearance, galactose elimination capacity, and concentrations of glycocholic acid and glycolithocholic acid sulfate in plasma. The (24-14C)cholic acid conjugation in patients with viral hepatitis was significantly lower in fatal cases than in patients who survived (p less than 0.002).

Aqueous two-phase partition studies of glucocorticoid receptors exposed to limited trypsination.

In a previous investigation the properties of glucocorticoid receptors exposed to partial proteolysis by chymotrypsin were studied by aqueous two-phase partitioning (Andreasen, P.A. and Gehring, U.

Monoclonal antibody to human 66,000 molecular weight plasminogen activator from melanoma cells. Specific enzyme inhibition and one-step affinity purification.

Hybridomas producing a monoclonal IgG1 antibody to a human plasminogen-activating enzyme with an apparent mol. wt. of 66,000 (66 K, HPA66) from human melanoma cells were obtained by fusion of NSI-Ag 4/1 mouse myeloma cells with spleen cells from a mouse immunized with a partially purified preparation of the enzyme.

Inhibition of the activation of the rat liver cytosolic glucocorticoid receptor by Li+.

By the use of aqueous two-phase partitioning and DNA-Sepharose chromatography, Li+ has been found to cause a partial inhibition of the activation of the rat liver glucocorticoid receptor in vitro. During incubations of cytosol with 0.4 M KCl at 0 degrees C, the LiCl-concentration giving half-maximal effect is approx.

Changes in net charge of glucocorticoid receptors by activation, and evidence for a biphasic activation kinetics.

The kinetics of glucocorticoid receptor activation and the changes in molecular properties of the receptors by the activation were studied, employing aqueous two-phase partitioning of rat thymocyte, rat liver and mouse S49.1 lymphoma cell cytosol labelled with tritiated glucocorticoid. By a mathematical analysis of the time-course of the receptor partition coefficient during activation, we demonstrate that at least two different receptor conversions take place during this process.

A simple method for determination of antipyrine clearance.

Antipyrine clearance (Cl(AP)) is widely used for assessment of microsomal liver function. The usual procedure involves collection of 4 to 7 samples of plasma or saliva obtained during 24 to 48 hr. To determine whether this procedure could be simplified it was compared with one based on a single sample (sCl(AP)) and an estimated volume of distribution (V(D)) in 142 persons.

Drug-induced liver disease in Denmark. An analysis of 572 cases of hepatotoxicity reported to the Danish Board of Adverse Reactions to Drugs.

During the decade 1968-1978 the Danish Board of Adverse Reactions to Drugs received 572 (6% of the total number) reports on hepatotoxicity. Halothane amounted to one fourth of the reported cases. Among the 94 psychotropic-induced adverse drug reactions 54 cases were attributed to chlorpromazine, 10 to tricyclic antidepressants, and only 2 to benzodiazepines.

Activation and partial proteolysis of variant glucocorticoid receptors, studied by two-phase partitioning.

In cultured lines of mouse lymphoma cells, resistant to glucocorticoids is frequently associated with the occurrence of glucocorticoid receptors with an abnormally low affinity (nt-) or an abnormally high affinity (nti) for nuclei and DNA. We have investigated whether the abnormal affinities for DNA are correlated with alterations in charge and surface properties of the receptors, that would be revealed through the partition coefficient in aqueous dextran/poly(ethylene glycol) two-phase systems. We have found that none of the receptor variants is defective in the activation step per se, and that only the nti receptors are abnormal in partition properties.

The hepatic glutathione content in liver diseases.

We measured the total glutathione content in 38 liver biopsies from patients undergoing diagnostic liver biopsy to study whether liver diseases result in decreased glutathione content making the liver more sensitive to different toxic damages. The glutathione concentrations ranged from 20.2 to 41.

A specific adenine nucleotide effect on the rat liver glucocorticoid receptor, demonstrated by aqueous two-phase partitioning.

The effect of mononucleotides on the cytosolic rat liver glucocorticoid receptor has been studied by the use of aqueous dextran-poly(ethylene glycol) two-phase partitioning. During incubations in 0.4 M KCl at 0 degrees C, millimolar concentrations of ADP and ATP, but not AMP, CTP, UTP and GTP, inhibit the increase in the receptor partition coefficient associated with receptor activation.

Cimetidine clearance and bioavailability in hepatic cirrhosis.

Nine patients with compensated alcoholic and nonalcoholic cirrhosis of the liver and 11 patients with peptic ulcer received 200 mg of cimetidine orally and intravenously. No differences were observed in cimetidine clearance between the group with peptic ulcer (556 +/- 44 ml/min, mean +/- SEM) and the group with cirrhosis (606 +/- 64 ml/min). The bioavailability of cimetidine was unchanged (84 +/- 4% and 97 +/- 7%).

Aqueous two-phase partition studies of the glucocorticoid receptor: activation and pH-dependent changes of rat liver glucocorticoid-receptor complex in partly purified preparations.

1. The activation of the glucocorticoid receptor of rat liver cytosol was studied by the use of partitioning in an aqueous dextran-poly(ethylene glycol) two-phase system. a, Incubation unde conditions generally found to stimulate the activation results in a time-dependent increase of the partition coefficient of the glucocorticoid-receptor complex in the two-phase system.

Effect of long-term disulfiram administration on rat liver.

No hepatotoxicity was demonstrated after 90 days in rats treated with two dose levels of disulfiram. A reversible inhibition of microsomal p-nitroanisole demethylase activity was found. In phenobarbital-treated rats disulfiram 100 mg/kg did not alter the induction response as indicated by the cytochrome P-450 content, but inhibited the p-nitroanisole activity to control levels.

Functioning liver mass in uncomplicated and fulminant acute hepatitis.

The galactose elimination capacity and the plasma clearance of phenazone were investigated in 24 patients with uncomplicated acute hepatitis and in 8 patients who survived and in 26 who died of fulminant hepatitis. The galactose elimination capacity was 52% of the normal mean value on admission to the hospital in uncomplicated hepatitis, 47% in patients who survived fulminant hepatitis, and 22% in the fatal cases, while the plasma clearance of phenazone was 43%, 22%, and 10%, respectively. Both quantitative liver function tests showed rapid improvement in most cases of uncomplicated acute hepatitis and in the patients who survived fulminant hepatitis.

Hepatic clearance measurements and pharmacokinetics.

This review emphasizes the need for well-defined models for hepatic pharmacokinetics and discusses the interpretation of hepatic clearance measurements. Such recent approaches are subjected to theoretical and experimental comparisons. The pharmacokinetic consequences, including a classification of drugs according to hepatic clearance, are outlined.