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E L Renner

Publications and source records attributed to E L Renner.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Does the primary disease recur following liver transplantation?].

A number of underlying diseases may recur after orthotopic liver transplantation. While the recurrence of cholestatic diseases such as primary biliary cirrhosis and primary sclerosing cholangitis is still debated, and occurs, if at all, rarely and late after transplantation, the chronic viral hepatitides and the liver tumors recur frequently and in general early after grafting. Except for hepatitis B and tumor recurrence, recurrent diseases have rarely an impact on survival and/or quality of life in medium terms. The frequency of the often fatal hepatitis-B reinfection can be minimized by passive immunoprophylaxis and appropriate patient selection, that of tumor recurrence by thorough patient selection. Relapses occur only rarely after transplantation for post-alcoholic cirrhosis, provided stringent selection criteria, including a period of documented sobriety > or = 6 month prior to transplantation, are applied. Thus, except for chronic hepatitis B with ongoing viral replication and most liver cancers, the possibility of recurrent disease is not a contraindication to liver transplantation.

Cholangitis, Sclerosing↗
PubMed1995

[Does acute graft rejection modify subsequent function of a transplanted liver?].

While in kidney, heart and pancreas transplantation the impairment of graft function associated with acute rejection is only partially reversible upon successful antirejection therapy, little is known about the effect of acute rejection on late graft function after liver transplantation. Our data however gives similar findings in regards to conventional and quantitative liver function tests in patients with or without acute rejection more than 12 months after liver transplantation. This may most likely be attributable to the unique regeneration potential of the adult human liver.

Acute Disease↗
PubMed1994

[Can the quality of a modest liver transplantation program compare to international standards? Results in Inselspital Berne].

Today, orthotopic liver transplantation is the treatment of choice for the endstage of various liver diseases, and a 1-year survival rate of over 80% is reported in international surveys. The liver transplant program of the Inselspital is very small compared to international centers and this may raise questions about the results and the justification for such a program. In a 24-month period, 20 liver transplants (including 2 retransplants) have been performed in 18 patients at the Inselspital. 2 patients (11%) died 20 and 268 days respectively after transplantation. 2 patients (11%) had significant morbidity 502 and 529 days respectively after transplantation. After a median follow-up of 11.5 months postoperatively, 14 (80% of all patients) lived an independent life. 9 (50%) were fully reintegrated in the household or in their profession and 5 others (30%) were working part time. We conclude that even a small liver transplant program based only on routine resources can achieve results comparable to international standards.

Adult↗
PubMed1994

[Treatment of autoimmune chronic active hepatitis and of primary biliary cirrhosis].

Several subtypes of autoimmune chronic active hepatitis can be distinguished today, one variant of which seems to be associated with active hepatitis C virus infection. Except for the latter, all types respond well to immunosuppressive therapy with prednisone (+/- azathioprine). Therapy has been shown to prolong survival, but the disease nevertheless often progresses to cirrhosis. For conservative therapy of primary biliary cirrhosis, D-penicillamine is contraindicated and several immunosuppressants investigated are associated with unacceptable side effects; ursodeoxycholic acid, colchicine and perhaps methotrexate seem to be promising, but none has been proven to prolong survival. Therefore, patients with primary biliary cirrhosis should still be included in therapeutic trials. In the advanced stages of both diseases liver transplantation remains an effective therapy.

Adrenal Cortex Hormones↗
PubMed1994

Hepatocellular Na+/H+ exchange is activated early, transiently and at a posttranscriptional level during rat liver regeneration.

In hepatocytes in vitro, Na+/H+ exchange, an important regulator of intracellular pH, is activated by epidermal growth factor, but its activity during liver regeneration in vivo is unknown. We therefore compared activity and regulation of Na+/H+ exchange in hepatocytes isolated after two-thirds partial hepatectomy or sham surgery, respectively, by measuring intracellular pH (fluorimetry) and steady state Na+/H+ exchange mRNA levels (Northern blotting). Resting intracellular pH increased from 7.06 +/- 0.02 to 7.12 +/- 0.02 (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Na+/H+ exchange-mediated rates of intracellular pH recovery from an acid load increased from 0.075 +/- 0.018 to 0.151 +/- 0.018 pH units/min (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Because intracellular buffering capacity was not affected, this reflects increased Na+/H+ exchange activity. The inverse relationship between Na+/H+ exchange activity and intracellular pH was shifted by about 0.1 pH units toward more alkaline pH values 2 hr but not 20 hr after partial hepatectomy, whereas steady-state Na+/H+ exchange mRNA levels remained unchanged. In conclusion, hepatocellular Na+/H+ exchange is activated early, transiently and at a posttranscriptional level during liver regeneration induced in the rat by partial hepatectomy.

Animals↗
PubMed1994

Hepatocellular Na+/H+ exchange is activated at transcriptional and posttranscriptional levels in rat biliary cirrhosis.

BACKGROUND/AIMS: Rat hepatocyte Na+/H+ exchange is activated in vitro by growth factors and in vivo following partial hepatectomy. This study explored by which mechanism(s) it is activated in a cirrhosis model characterized by chronic stimulation of hepatocyte proliferation. METHODS: Rat hepatocytes were isolated 4 weeks after bile duct ligation or sham operation. Intracellular pH (pHi) was fluorimetrically determined, and plasma membranes and messenger RNA (mRNA) were prepared from isolated hepatocytes by standard methods. RESULTS: Resting pHi was higher in bile duct-ligated than in control rats (7.42 +/- 0.03 vs. 7.06 +/- 0.04; P < 0.001). Although plasma membrane lipid composition and intracellular buffering capacity were similar, initial Na+/H+ exchange-mediated rates of pHi recovery following acid loading were higher in bile duct-ligated than in control rats (0.098 +/- 0.011 vs. 0.055 +/- 0.005 pH units/min; P < 0.05). The antiporter's set point was shifted approximately 0.3 pH units towards more alkaline values and its steady-state mRNA levels were doubled after bile duct ligation. CONCLUSIONS: Hepatocellular Na+/H+ exchange is transcriptionally and posttranscriptionally activated in rat biliary cirrhosis further supporting a relationship between hepatocyte proliferation and Na+/H+ exchange activation.

Animals↗
PubMed1993

Influence of Helicobacter pylori, sex, and age on serum gastrin and pepsinogen concentrations in subjects without symptoms and patients with duodenal ulcers.

The relation between Helicobacter pylori (H pylori) infection and fasting gastrin and pepsinogen-I and -II concentrations was evaluated in 278 volunteers without symptoms and the results were compared with the values obtained in 35 patients with duodenal ulcers. H pylori infection was determined with the 13C-urea breath test in subjects without symptoms and with endoscopy, biopsy (histology and culture), and quick urease test (CLO-test) in patients with duodenal ulcers. Gastrin and pepsinogen-I and -II concentrations were assayed with specific radioimmunoassay systems. The results clearly indicate that fasting gastrin and pepsinogen-I and -II concentrations were significantly higher in H pylori positive compared with H pylori negative subjects. Neither age nor sex affected basal gastrin and pepsinogen concentrations in H pylori negative subjects. Fasting gastrin, pepsinogen-I and -II concentrations in serum samples were similar in H pylori positive persons with no symptoms and those with duodenal ulcers suggesting that similar mechanisms are involved in increasing plasma concentrations of these variables in both populations. Hypergastrinaemia and hyperpepsinogenaemia are therefore probably secondary to active H pylori infection.

Adult↗
PubMed1993

[Autoimmune chronic active hepatitis].

Autoimmune chronic active hepatitis is a rare type of chronic active hepatitis which occurs with a bimodal age distribution (10 to 30 or > or = 50 years) most frequently in women. It is characterized by negative markers for other possible (e.g. viral) etiologies, hypergammaglobulinemia and a number of circulating autoantibodies. According to the latter, several subgroups can be discriminated today. Histology shows chronic active hepatitis with chronic, sometimes plasma-cell-rich infiltration of portal tracts and piece-meal necroses. Symptoms and signs are classically non-specific and include general malaise, lethargy and fatigue. Accompanying autoimmune diseases may be present. The disease is today, however, also frequently diagnosed in an early, asymptomatic stage. Cause(s) and pathogenetic mechanism(s) of the increasingly heterogeneous appearing disease remain unknown. Recent observations seem to indicate that as yet undetermined (exogenous) substance(s) and the hepatitis C virus may, at least in certain subgroups, trigger autoimmune reactions, which may then perpetuate on the basis of a permissive (immuno)genetic background. Untreated, the disease is, in general, progressive, leads to cirrhosis and shows a mortality of up to > or = 50% in 2 to 4 years. Signs potentially indicating a nonfavorable prognosis include high inflammatory activity and the presence of cirrhosis at diagnosis. Typically, immunosuppressive therapy with corticosteroids (with or without azathioprine) results in remission of inflammatory, but usually not fibro-genetic activity with its potential for cirrhosis. Exacerbations after cessation of treatment are not infrequent (> or = 50%), and indefinite therapy is required in a number of patients, despite its potential for unwanted effects (e.g. osteopenia). Such therapy may increase the 5-year survival rate to > 80%. Liver transplantation remains the sole therapeutic option in end stage disease.

Autoantibodies↗
PubMed1992

[Biological markers of alcoholism].

Since most patients with an alcohol problem downplay their alcohol consumption, reliable tests for detection of alcohol abuse would be of value in clinical practice. Single determinations of common laboratory tests such as gamma-glutamyl transpeptidase, transaminases or mean corpuscular volume are only of limited reliability in detecting alcohol abuse. Most newer parameters, including the serum ASAT/ALAT ratio, the ratio of mitochondrial to total ASAT in serum, and serum levels of acetaldehyde-hemoglobin adducts or of antibodies against acetaldehyde adducts, still do not allow us to discriminate reliably enough between alcoholic and nonalcoholic liver diseases. beta-hexosaminidase activity and desialylated transferrin levels in serum appear to be the most promising tests for detecting alcohol abuse in the future. They require, however, additional validation and technical simplification respectively before they are suitable for daily clinical use. Thus, it remains valid that no single test can replace a careful history, clinical examination and laboratory results in detecting patients with alcohol problems.

Acetaldehyde↗
PubMed1992

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 6.07 +/- 0.86 mg/min x kg significantly (P less than 0.001) below that in healthy controls (7.52 +/- 0.78 mg/min x kg), but did not significantly change during follow-up (5.93 +/- 0.96 and 6.26 +/- 0.94 mg/min x kg at 1 year and 1 month, respectively). In contrast, the non-renal clearance of unbound prednisolone declined steadily during follow-up averaging 4.98 +/- 0.71 ml/min x kg at three to five (compared to 5.83 +/- 1.51 and 6.80 +/- 1.73 ml/min x kg at one year and one month, respectively). These values were lower (P less than 0.01) than those observed in healthy control subjects (7.56 +/- 1.59 ml/min x kg). The total body clearance of cyclosporin A decreased similarly with time averaging 4.5 +/- 1.2 ml/min x kg at three to five years (compared to 4.9 +/- 1.2 and 5.9 +/- 2.1 ml/min x kg at 1 year and 1 month, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

[Increased liver enzymes: what should be done?].

The transaminases, alkaline phosphatase (AP) and gamma-glutamyl transferase (G-GT) are most widely used as indicators of hepatobiliary disease. Elevated serum levels of transaminases (AST and ALT) usually indicate hepatocellular damage. ALT elevations, however, can also be of extrahepatic origin (muscle). The ratio of the transaminases in serum (AST/ALT) and the mitochondrial isoenzyme of AST are frequently higher in alcoholic than in non-alcoholic liver diseases. Serum activities of AP and G-GT are elevated in cholestasis: Both enzymes, however, are not liver-specific and G-GT activity is induced by alcohol and certain drugs. A hepatic enzyme pattern (predominant transaminase elevation) should be discriminated from a cholestatic pattern (predominant AP and G-GT elevation). The most frequent diagnoses in asymptomatic patients with accidentally detected, mostly mild to moderate transaminase elevations are: alcoholic liver disease, (mostly chronic) viral hepatitis, and already much less frequently, drug induced liver disease and non-alcoholic steatosis. Solely if the respective investigations are negative or/and the transaminases stay elevated for greater than or equal to 6 months despite strict alcohol abstinence, omission of any potentially hepatotoxic drug or weight reduction are further steps justified.

Alanine Transaminase↗
PubMed1992

[Symptomatic cholecystolithiasis: 1992 therapy options].

Modern treatment of symptomatic cholecystolithiasis requires a knowledge of several nonsurgical and surgical treatment options. Extracorporeal shock-wave lithotripsy and oral bile acid therapy offer the possibilities of noninvasive, outpatient treatment in approximately 20% of all symptomatic gallstone patients at a low complication rate. The percutaneous interventional techniques such as contact dissolution by means of ether or mechanical stone removal may in principle be used in a higher percentage of patients but are considerably more invasive. None of the nonsurgical techniques can exclude the relative risk of gallstone recurrence. Laparoscopic cholecystectomy constitutes a major progress in the surgical treatment of gallstone disease, since it is much less invasive than conventional cholecystectomy and requires a much shorter hospital stay and recovery time. The laparoscopic technique is primarily indicated in patients with symptomatic, uncomplicated cholecystolithiasis. Nevertheless, the range of indications is expanding as experience with this technique increases. Under certain circumstances, laparoscopic cholecystectomy is already being combined with endoscopic sphincterotomy in the presence of bile duct calculi. Conventional cholecystectomy remains the treatment of choice for complicated cases.

Bile Acids and Salts↗
PubMed1991

Quantitation of intrinsic drug-metabolizing capacity in human liver biopsy specimens: support for the intact-hepatocyte theory.

Hepatic drug metabolism is decreased in patients with severe liver disease, but it is unclear to what extent this is due to altered hepatic blood flow or reduced intrinsic metabolic capacity. In this study we quantitated in needle-biopsy specimens the intrinsic capacity of liver tissue from 67 patients with mild liver disease (n = 36), chronic active hepatitis (n = 16) and cirrhosis (n = 15) to metabolize two model compounds in vitro. Hydroxylation of the low-extraction drug bufuralol resulted in the formation of 251 +/- 25 nmol 1'OH-bufuralol/gm wet wt/hr in mildly diseased liver tissue and was significantly (p less than 0.01) reduced in liver tissue exhibiting chronic active hepatitis (166 +/- 23 nmol/gm wet wt/hr) and cirrhosis (124 +/- 21 nmol/gm wet wt/hr). The formation rates of monoethylglycinexylidide, the main metabolite of the high-extraction drug lidocaine, varied widely and were not significantly different among the three groups. To relate the drug-metabolizing capacity to the hepatocyte content of liver tissue, morphometrical study was performed in the biopsy pieces originally submitted. The metabolic activity of each biopsy piece was then related to the fractional volume of hepatocytes it was calculated to contain. In mildly diseased liver tissue 355 +/- 35 nmol 1'OH-bufuralol/ml hepatocytes x hr or 12.4 +/- 1.0 mumol monoethylglycinexylidide/ml hepatocytes x hr- and in cirrhotic liver tissue 306 +/- 49 nmol 1'OH-bufuralol/ml hepatocytes x hr or 15.3 +/- 3.0 mumol monoethylglycinexylidide/ml hepatocytes x hr--were formed, respectively, and these differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

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.D.) galactose elimination capacity at 1 month (6.26 +/- 0.94 mg per min x kg) and at 1 year (5.93 +/- 0.96 mg per min x kg), when compared with a different group of 28 healthy control subjects (7.52 +/- 0.78 mg per min x kg, p less than 0.001) and a decreased total body clearance of prednisolone at 1 month (2.13 +/- 0.34 ml per min x kg vs. 2.71 +/- 0.43 ml per min x kg in controls, p less than 0.001), which further decreased over the following year to 1.76 +/- 0.32 ml per min x kg (p less than 0.001). The clearance of cyclosporine A declined significantly during the first year of successful transplantation (5.9 +/- 2.1 ml per min x kg vs. 4.9 +/- 1.2 ml per min x kg, p less than 0.05). In conclusion, a substantial proportion of stable renal transplant recipients have decreased cytosolic and microsomal liver functions despite the absence of clinical and laboratory evidence of significant liver disease.

Cyclosporins↗
PubMed1989

Na+-H+ exchange activity in rat hepatocytes: role in regulation of intracellular pH.

Amiloride-sensitive Na+-H+ exchange has been identified in basolateral membrane vesicles from rat liver, but little is currently known about its regulation or its role in maintenance of resting intracellular pH (pHi) in intact hepatocytes. We have assessed Na+-H+ exchange activity in isolated or cultured rat hepatocytes in nominally HCO3- free solution under basal conditions and after intracellular acidification by an NH4Cl pulse by measuring 1) pHi, using the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxy fluorescein, 2) net H+ efflux by pH-stat titration, and 3) amiloride-inhibitable 22Na uptake. Under resting conditions, Na+-H+ exchange did not contribute measurably to Na+ uptake and accounted for less than 20% of net H+ efflux. Hepatocyte pHi averaged 7.07 +/- 0.03, significantly above H+ electrochemical equilibrium (6.92 +/- 0.08) determined using an electrogenic proton ionophore. Transient removal of extracellular Na+ or exposure to amiloride reversibly lowered pHi by 0.09 +/- 0.01 and 0.12 +/- 0.03 pH units, respectively, within 5-10 min. After intracellular acidification by an NH4Cl pulse, Na+ uptake rate increased about twofold, the increase being entirely amiloride inhibitable. Net H+ efflux increased about threefold, and 70% of the increase was amiloride inhibitable. Recovery of pHi after an NH4Cl pulse was reversibly blocked by exposure to amiloride or removal of Na+. Na+-H+ exchange activity (calculated from the rate of change in pHi and intracellular buffering capacity) was inversely related to pHi and was estimated to approach zero at pHi 7.25-7.50.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1989

Rat hepatocytes exhibit basolateral Na+/HCO3- cotransport.

Primary cultures and plasma membrane vesicles were used to characterize Na+ and HCO3- transport by rat hepatocytes. Na+ uptake into hepatocytes was stimulated approximately 10-fold by 25 mM extracellular HCO3-.HCO3--stimulated Na+ uptake was saturable, abolished by 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS), and unaffected by amiloride or Cl- removal. Neither propionate nor acetate reproduced this effect of HCO3-. 22Na efflux from preloaded hepatocytes was similarly increased approximately 10-fold by an in greater than out HCO3- concentration gradient. 22Na efflux was also increased by valinomycin and an in greater than out K+ concentration gradient in the presence but not absence of HCO3-. Intracellular pH (pHi) measured with the pH-sensitive fluorochrome 2',7'-bis-(2-carboxyethyl)-5-(and 6-)carboxyfluorescein (BCECF) decreased at a rate of 0.227 (+/- 0.074 SEM) pH units/min when extracellular HCO3- concentration was lowered from 25 to 5 mM at constant PCO2. This intracellular acidification rate was decreased 50-60% in the absence of Na+ or presence of SITS, and was unaffected by amiloride or Cl- removal. Membrane hyperpolarization produced by valinomycin and an in greater than out K+ concentration gradient caused pHi to fall; the rate of fall was decreased 50-70% by Na+ removal or SITS, but not amiloride. An inside positive K+ diffusion potential and a simultaneous out greater than in HCO3- gradient produced a transient 4,4'-diisothiocyano-2,2' disulfonic acid stilbene (DIDS) sensitive, amiloride-insensitive 22Na accumulation in basolateral but not canalicular membrane vesicles. Rat hepatocytes thus exhibit electrogenic basolateral Na+/HCO3- cotransport.

Animals↗
PubMed1989

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 = 5.2 +/- 3.5 mumol/24 h, range 1.0-13.4; versus 0.6 +/- 0.3, range 0.4-1.0). In addition, PBC patients excreted increased amounts of other bile alcohols such as isomers of C26 pentol, pentahydroxylated C27 bile alcohols (5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol) and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol) and a hexahydroxylated C26 bile alcohol (27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol). In CAH patients, the excretion of the C26 pentol main isomer ranged from 0.3 to 2.0 mumol/24 h (mean +/- SD = 0.7 +/- 0.5) and did not significantly differ from that in healthy volunteers. Moreover, the bile alcohol profile was comparable to those found in healthy volunteers and PBC patients. These findings show that total urinary bile alcohol glucuronide excretion is significantly increased in primary biliary cirrhosis. A PBC-specific urinary bile alcohol profile, however, does not exist.

Adult↗