Search PubMed⌕ Search

Biomedical subjects

W Stremmel

Publications and source records attributed to W Stremmel.

At least 217 records · Page 12Linked to original sources
PubMed1992

Prospective randomized controlled trial of sequential treatment with corticoids and alpha-interferon versus treatment with interferon alone in patients with chronic active hepatitis B.

OBJECTIVES: A randomized controlled trial was conducted to prospectively compare the efficacy of sequential treatment with corticoids and alpha-interferon versus treatment with interferon (IFN) alone in patients with chronic hepatitis B. METHODS: Sixty patients with chronic active hepatitis B and positive serum HBV-DNA were randomized into two treatment groups (n = 20, respectively) and one control group (no treatment; n = 20). In one treatment group, patients received first an oral corticoid (2 weeks 40 mg/day and further 2 weeks 20 mg/die prednisolone); thereafter interferon-alpha (Intron A, Essex) was given as three subcutaneous injections of 2 million units per week for 3 months. In patients in whom therapy did not eliminate HBe-Ag and HBV-DNA two months after its end, a similar sequential treatment was given with the same corticoid dose but a higher IFN dose of 5 MU. In the other treatment group patients were given three subcutaneous injections of 5 MU IFN per week for 4 months. The sequential corticoid/IFN treatment at a dose of 3 x 2 MU IFN resulted in seroconversion of HBe-Ag in only 4 of 20 patients (20%). Of the remaining 16 patients 14 subjects received a repetitive corticoid/IFN therapy with the same corticoid dose but with a 3 x 5 MU dose of IFN. RESULTS: With the higher IFN dose, 6 of 14 patients had a seroconversion of HBe-Ag. Therapy with 3 x 5 MU IFN without prior corticoids resulted in a seroconversion in 8 of 20 patients (40%). Calculated for both doses, the sequential corticoid/IFN therapy eliminated HBe-Ag and HBV-DNA in 10/20 patients (50%); therapy with IFN alone was almost as effective (40% seroconversion) (p > 0.05 for comparison of seroconversion rates by chi 2-test). Seroconversion of HBe-Ag and elimination of HBV-DNA occurred in parallel and were associated with a decrease of serum transaminases and a regression of inflammatory activity on rebiopsy. In the control group there was no spontaneous seroconversion of HBs-Ag, HBe-Ag or HBV-DNA. CONCLUSIONS: The present results show that in many patients who failed to respond to a sequential therapy with corticoids and 2 MU IFN, the higher IFN dose of 5 MU effectively eliminated HBe-Ag and HBV-DNA. Sequential corticoid/IFN therapy and therapy with IFN alone eliminated HBe-Ag and HBV-DNA in a similar percentage of patients. Further statistical analysis showed that, in particular, patients with low transaminases benefit from prior corticoid treatment. In all groups, patients with low serum HBV-DNA and a short history of infection had the best treatment results.

Adolescent↗
PubMed1992

[Liver function tests in a clinical comparison].

Various liver function tests were evaluated in regard to a quantitative estimation of the impairment of liver function related to the Child-Pugh classification in 32 patients with cirrhosis. Only the ICG-test revealed significant differences between healthy subjects and cirrhotic patients in stadium Child A, B and C. When ICG-dye retention values were plotted as a function of the individual score units of the Child-Pugh classification, a linear relationship with a correlation coefficient of 0.7 was obtained. In contrast to the ICG-test, the MEGX- and galactose elimination capacity (GEC)-test as well as static parameters of liver function (cholinesterase activity, prealbumin concentration, coagulation factor V and VII) resulted in less significant differentiation of the various Child classes. The MEGX-test, GEC, concentration of prealbumin, coagulation factor V and VII were only weakly correlated to the score units of the Child-Pugh index. The results of this study indicate that of all evaluated parameters only the ICG-test is suitable for objective and graduated analysis of liver function in patients with cirrhosis.

Cholinesterases↗
PubMed1992

[Pathogenesis of Wilson's disease].

Wilson disease is due to a genetically determined impairment of copper excretion from liver into bile resulting in copper overload of the organism. The chromosomal defect and the primary defect of copper metabolism is not yet defined. When during the course of the disease the cytoplasmatic copper binding sites of hepatocytes are saturated, excess of "free" copper is accumulating. It induces liver cell damage and necrosis followed by the development of fibrosis and cirrhosis. The accumulation process of excess free copper in hepatocytes is accompanied by a redistribution into the lysosomal compartment of the cells as well as by release of free copper into blood. This increase of the free serum copper concentration leads during the course of the disease to an elevated copper burden of other organs. This results in a variety of symptoms, of which liver disease and neurologic disturbances are of major significance in regard to clinical presentation and prognosis of the patients.

Ceruloplasmin↗
PubMed1991

Wilson disease: clinical presentation, treatment, and survival.

OBJECTIVE: To evaluate the diagnostic features, clinical course, and overall long-term survival of patients with Wilson disease. DESIGN: Retrospective cohort study with a mean follow-up period of 14.2 years. SETTING: A university medical center and a community hospital. PATIENTS: Fifty-one consecutive patients with Wilson disease were evaluated between 1957 and 1989. INTERVENTIONS: Patients were treated with D-penicillamine (600 to 1800 mg/d). Two patients with end-stage liver disease had liver transplantation. MAIN RESULTS: Initial symptoms occurred at a mean age of 15.5 years. At diagnosis, the most common neurologic signs were dysarthria, tremor, writing difficulties, and ataxia followed by hypersalivation and headache. Somatic symptoms included abdominal pain, hepatomegaly, splenomegaly, cirrhosis of the liver, and thrombocytopenia. The mean serum concentrations of ceruloplasmin and copper were 44 mg/L and 4.7 mumol/L, respectively. The mean basal urinary copper excretion was 5.5 mumol/d, and the mean hepatic copper concentration was 19.6 mumol/g dry weight. Free serum copper concentration (mean, 2.7 mumol/L) was a reliable indicator of disease and was useful in assessing the effectiveness of therapy (values less than 1.6 mumol/L). Treatment with D-penicillamine improved most of the hematologic and neurologic abnormalities but had little effect on hepatomegaly and splenomegaly and did not reverse cirrhosis. Two patients died of fulminant hepatic failure during the observation period, whereas two others with end-stage liver disease had successful liver transplantation and remain asymptomatic. Long-term survival of patients with Wilson disease was similar to that of age- and sex-matched controls. CONCLUSION: Our results suggest that long-term treatment of patients with Wilson disease with D-penicillamine can relieve symptoms and improve prognosis.

Adolescent↗
PubMed1991

Antiarrhythmic drugs impair hepatic uptake and secretory function by different mechanisms in the isolated perfused rat liver.

In the present study the effect of various antiarrhythmic drugs on hepatic perfusion parameters, uptake capacity of organic anions and biliary secretion using the isolated perfused rat liver was examined. Infusion of verapamil (VP), diltiazem, N-propyl-ajmaline (NPAB), and quinidine at pharmacological doses induced consistently a 1.4-1.6-fold increase in portal pressure accompanied by a approximately 60% decrease in bile flow and a approximately 65% inhibition of biliary taurocholate (TC) excretion. Furthermore, hepatic uptake of oxygen, bromosulphthalein (BSP), and TC was significantly reduced. All these effects were dose-dependent and reversible upon withdrawal of the drugs. Studies of the hepatic circulation using a Trypan blue staining technique demonstrated a patchy perfusion pattern during infusion of the antiarrhythmic drugs as compared to the homogenously stained control organ. The hemodynamic alterations and the impairment of the hepatic initial uptake function could be entirely prevented by concomitant administration of the vasodilator papaverine. Bile flow and biliary TC excretion, however, were still inhibited under these conditions. The present results indicate that antiarrhythmic drugs produce cholestasis in the isolated perfused rat liver independently of their adverse effect on hepatic hemodynamics.

Animals↗
PubMed1991

Fatty acid uptake in normal human myocardium.

Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an "unstirred layer" were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 +/- 0.024 mumol/g and 0.37 +/- 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells.

Animals↗
PubMed1991

Epidemiology, clinical course and treatment of chronic viral hepatitis.

Chronic hepatitis may take the form of a hepatitis B infection, a delta virus infection, or a non-A, non-B hepatitis including hepatitis C. All the viruses involved are transmitted predominantly by parenteral or sexual routes. New insights into the structure of the hepatitis B virus (HBV) and the immune response mechanisms of the organism permit a clear definition of the replicative state of the virus, and allow predictions to be made about the outcome of the disease. Development of cirrhosis and hepatocellular carcinoma are the major complications associated with impaired life expectancy. Recently, the hepatitis C virus (HCV) was identified as the agent responsible for most cases of chronic non-A, non-B hepatitis. The development of an assay for the detection of HCV-antibodies facilitated the diagnosis of this type of hepatitis. Moreover, the use of screening tests for hepatitis B and hepatitis C in blood donors will decrease the risk of acquiring hepatitis via contaminated blood products. Treatment of chronic hepatitis B and C with alpha-interferon has shown promising results. However, the dosage schedule, the period of treatment, and the selection of patients needs to be evaluated in further studies.

Hepacivirus↗
PubMed1990

Intestinal absorption of unconjugated dihydroxy bile acids: non-mediation by the carrier system involved in long chain fatty acid absorption.

Experiments were performed using isolated mucosal cells from the rat jejunum or using the perfused jejunum in the anesthetized rat to test whether lipophilic unconjugated dihydroxy bile acids are absorbed from the proximal small intestine via the same carrier mechanism involved in the uptake of long chain fatty acids. With isolated jejunal mucosal cells, the cellular uptake rate of deoxycholic acid or chenodeoxycholic acid increased linearly with time, showed no evidence of saturation, and was not decreased by the presence of a monospecific antibody to the membrane fatty acid binding protein. In contrast, oleate uptake was saturable, was inhibited by the same antibody, but was not affected by the presence of chenodeoxycholic acid or deoxycholic acid. Bile acid uptake by isolated enterocytes occurred at one-eighth the rate of fatty acid uptake if expressed in relation to total solute concentration; if expressed in relation to monomeric concentration, initial bile acid uptake was four orders of magnitude slower than fatty acid uptake. In the isolated perfused jejunal segment, chenodeoxycholic acid and deoxycholic acid uptake was not influenced by the presence of the antibody to membrane fatty acid binding protein, whereas absorption of oleate was inhibited by more than 70%. These experiments indicate that absorption of unconjugated lipophilic dihydroxy bile acids in the rodent jejunum does not involve the carrier mediated uptake mechanism involved in the absorption of long chain fatty acids--the mechanism is likely to be passive nonionic diffusion.

Animals↗
PubMed1990

Cellular uptake of conjugated bilirubin and sulfobromophthalein (BSP) by the human hepatoma cell line Hep G2 is mediated by a membrane BSP/bilirubin binding protein.

Cellular influx kinetics of 4-50 microM bilirubin diglucuronide and sulfobromophthalein (BSP) by the human hepatoma cell line Hep G2 was examined at 37 degrees C. In confluent monolayer cultures, cellular influx of increasing concentrations of conjugated bilirubin and BSP revealed similar saturation kinetics with Km values of 9.9 and 12.1 microM, and Vmax values of 0.512 and 0.473 nmol.mg cell protein-1.min-1, respectively. Uptake of [3H]bilirubin diglucuronide was competitively inhibited by unlabeled BSP, and was temperature dependent with maximal cellular influx rates at 37 degrees C. When the confluent monolayer cultures were pretreated with a monospecific antibody to the rat liver BSP/bilirubin binding membrane protein, initial uptake rates of conjugated and unconjugated bilirubin as well as of BSP were significantly inhibited, whereas uptake of oleate was not affected. Furthermore, immunoblot analysis of the homogenate of Hep G2 cells with the same antibody revealed predominant reactivity with a 55 kDa protein. These data suggest that cellular uptake of bilirubin and related cholephilic organic anions by the human hepatoma cell line Hep G2 is mediated by a specific 55 kDa membrane BSP/bilirubin binding protein.

Bilirubin↗
PubMed1990

Uptake of palmitic acid by rabbit alveolar type II cells.

Alveolar type II cells require a source of palmitic acid for synthesis of dipalmitoyl phosphatidylcholine (DPPC), a major constituent of pulmonary surfactant. Previous studies indicated that maximal rates of DPPC synthesis are achieved only if exogenous palmitate is available to the type II cell. Little is known of the mechanisms by which fatty acids enter type II cells. To determine if uptake is mediated by a membrane carrier system, as described in other cell types, we examined the kinetics of palmitate uptake. Using freshly isolated rabbit type II cells, we demonstrated that radiolabeled palmitate uptake was maximal and linear for 45 s; after 1 min the apparent rate of uptake declined. The initial uptake phase was taken as a measure of cellular fatty acid influx because intracellular radiolabeled palmitate remained 80% nonesterified at this time but was 55% esterified by 2 min. Cellular influx of palmitate showed saturation kinetics with increasing concentration of nonalbumin bound palmitate. Michaelis constant was 52.6 nM, and maximum velocity was 152 pmol.10(6) cells-1.min-1. The hypothesis that saturable cellular influx of palmitate is likely linked to the previously identified membrane fatty acid binding protein (MFABP) was supported by Western-blot analysis of rat lung tissue with an antibody to MFABP that demonstrated the presence of this carrier protein in lung tissue. These data suggest that palmitate uptake by type II cells is saturable and may be mediated by a membrane-associated carrier as described in other cell types.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Iron uptake by human upper small intestine microvillous membrane vesicles. Indication for a facilitated transport mechanism mediated by a membrane iron-binding protein.

To investigate the hypothesis that iron absorption in man involves a carrier-mediated cellular uptake mechanism, influx velocity (Vo) of 59Fe3+ by isolated human microvillous membrane (MVM) vesicles of the upper small intestine was examined. Vo revealed saturation kinetics (Km = 315 nM; Vmax = 361 pmol Fe3+ x min-1 x mg protein-1) was temperature dependent and inhibited by pronase pretreatment of MVM. In the presence of an inwardly directed Na(+)-gradient a typical overshoot phenomenon with maximal uptake at 30-40 s was observed. The suggestion of an active, carrier-mediated uptake mechanism for iron was pursued by isolation of a 160-kD iron-binding protein from solubilized human MVM proteins. This glycoprotein was assembled as a trimer composed of 54-kD monomers. A monospecific antibody against the 54-kD subunit inhibited vesicular influx of Fe3+ into MVM by greater than 50%. Immunofluorescence and immunoblot analysis confirmed the localization of the protein in brush border plasma membranes. It was detectable in human intestinal mucosa and liver, but not in esophagus. These data indicate that the translocation of Fe3+ across human MVM represents a facilitated transport mechanism which is, at least in part, mediated by a membrane iron-binding protein.

Biological Transport↗