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Biomedical subjects

M Rössle

Publications and source records attributed to M Rössle.

At least 73 records · Page 4Linked to original sources

[Intrahepatic portacaval anastomosis by the transjugular approach. Use of the Palmaz endoprosthesis].

This new, non-operative procedure has been devised to create an intrahepatic shunt between a main portal branch and the right hepatic vein. First, the portal bifurcation is located by sagittal sonography and its position is marked on the skin. Then one of the main portal branches is punctured from the right hepatic vein by the transjugular route, and the puncture tract is expanded by balloon dilatation. This channel is kept open by placement of one or several Palmaz stents. Ten cirrhotic patients (age range: 60-84 years) unfit for surgical portocaval shunting and presenting with recurrent variceal bleeding after sclerotherapy were successfully treated by this method without any related death. During a 1 to 8 months follow-up, 9 of the 10 shunts have remained perfectly patent, but more time is required to determine the place of this method for secondary management of cirrhotic variceal bleeding.

Aged↗

[Modelling the transjugular intrahepatic portosystemic shunt using a metal prosthesis: requirements of the stent].

Non-operative percutaneous treatment of portal hypertension as ultima ratio therapy in liver cirrhosis has now been established in 16 cases. After transjugular puncture of a main branch of the portal vein via a liver vein, recollapse of the parenchymal track after predilation was prevented by implantation of a Palmaz stent. This type of stent enables remodelling of the individual length of the parenchymal track in the liver by overlapping placement of several stents. In our experience the Palmaz stent seems to be very efficient in keeping the shunt patent. First, its smooth inner surface after dilation guarantees laminar flow within the stent as a precondition for homogeneous endothelialization of the inner surface. Second, overlapping placement of the stents allows precise covering of the individual length of the shunt. Third shunt diameters can be established by using different sized balloons. The range is 7-10 mm. Fourth this type of stent has a high degree of resistance to eccentric or concentric compression by the surrounding tissue.

Adult↗

Synaptic membrane complex carbohydrates in experimental hepatic encephalopathy.

To evaluate further the status of synaptic plasma membranes (SPMs) in the brain in the syndrome of hepatic encephalopathy (HE) lipid- and protein-bound sialic acid and ganglioside and protein composition were investigated in SPMs from the brains of six rabbits with galactosamine-induced fulminant hepatic failure and five normal rabbits. HE was associated with no appreciable changes in the chromatographic pattern of gangliosides or the concentration of protein-bound sialic acid, but the syndrome was associated with a 20% increase in lipid-bound sialic acid and, as assessed electrophoretically, an increase in the concentration of a protein with a molecular weight of about 70 kDa. Thus, changes in the composition of complex carbohydrates and protein in SPMs occur in a model of HE. The findings raise the possibility that nonhumoral factors, such as increased sialylation of glycolipids, contribute to the generation of abnormal neurotransmission in HE.

Animals↗

[Autoradiography determination of the GABA(A) receptor density in the brain of rats with portacaval shunt].

Quantitative autoradiography was used to assess the densities of gamma-aminobutyric acid (GABAA) receptors in the brains of rats with a portacaval end-to-side shunt (PCA). The shunt alone induced only mild encephalopathy with ataxia and decreased locomotion. Aggravation of the encephalopathy was achieved by gavage feeding of packed erythrocytes or by induction of severe hyperammonemia by intraperitoneal injection of urease. Gavage feeding of erythrocytes led to severe encephalopathy in about 50% of the animals with PCA. The combination of PCA and urease treatment caused severe encephalopathy in every animal. The serum ammonia concentration increased 5 times normal by PCA alone, 20 times normal by gavage feeding of erythrocytes and more than 30 times normal by urease-treatment of the PCA-animals. For autoradiography, coronal slices were cut at the level of the hippocampal formation and through the cerebellum. Radioligand binding was measured using as a ligand 3H-muscimol, a specific GABAA receptor agonist. The specific binding of 3H-muscimol was assessed densitometrically in several microregions of cerebral cortex, hippocampus and cerebellar cortex. No significant differences were observed between the magnitude of ligand binding to specific microregions of brains from normal animals, animals with PCA without overt encephalopathy and animals with severe encephalopathy induced by a combination of PCA and gavage feeding of erythrocytes or urease treatment.

Ammonia↗

[Hemodynamic consequences of portal decompression: which is the optimal shunt?].

Increased sinusoidal resistance in cirrhosis results in a decrease of the portal and a compensatory increase of the arterial blood supply to the liver. With increasing vascular resistance and development of extrahepatic collaterals stagnation and even reversion of the portal blood flow may occur. In the latter condition, the arterial blood leaves the liver through two routes: 1) through the sinusoids and the hepatic veins, and 2) through the portal vein. Experimental and clinical studies revealed that the arterio-portal pathway is metabolically inferior to the regular arterio-hepatic-venous pathway. This suggests a decrease in liver function with an increased incidence of hepatic encephalopathy (HE) in patients with reversed portal blood flow. Based on these findings, surgical shunts may be classified according to their effect on the arterial liver perfusion. The end-to-side shunt and the distal splenorenal shunt (DSRS) do not cause diversion of the arterial liver perfusion. In contrast, side-to-side shunts, with the portal vein available as an outflow tract, consistently lead to diversion of the arterial blood supply resulting in reversed portal blood flow. Thus, side-to-side shunts are supposed to have an increased incidence of HE due to decreased liver function. This hypothesis is supported by 7 controlled and randomized studies which reveal comparable results of end-to-side shunts and DSRS but significant disadvantages of side-to-side shunts compared to DSRS.

Hemodynamics↗

[The intrahepatic portosystemic shunt. Initial clinical experiences with patients with liver cirrhosis].

A new nonoperative catheter technique to perform an intrahepatic portosystemic shunt by transjugular approach was applied to ten patients with recurrent bleeding from oesophageal and fundal varices. Therefore a balloon-expandable stent was placed between a portal vein and a hepatic vein. Implantation of the stent was successful in seven of the ten patients. Two of these seven patients died 10 and 11 days, respectively, after the procedure, one of them in consequence of respiratory failure, the other due to an uncontrollable bleeding from the site of the percutaneous transhepatic puncture because of a marked clotting disorder. The intrahepatic shunt construction led to a mean reduction of the pressure gradient between portal and hepatic vein of 40%. No recurrence of variceal haemorrhage occurred during the average follow-up time of 5.6 months (3-9 months). One patient developed several episodes of portosystemic encephalopathy. The transjugular intrahepatic portosystemic shunt is effective in the treatment of portal hypertension and might become an alternative to shunt surgery.

Adult↗

Autoradiographic analysis of GABA-benzodiazepine receptors in an animal model of acute hepatic encephalopathy.

To complement analogous studies using conventional ligand-membrane binding assays, the densities of gamma-aminobutyric acid and benzodiazepine receptors in the brain have been assessed using an autoradiographic technique in an animal model of hepatic encephalopathy. Hepatic encephalopathy due to fulminant hepatic failure was induced in rabbits by the intravenous injection of galactosamine. The specific binding of three radiolabeled ligands was assessed densitometrically in several microregions of cerebral cortex, hippocampus and cerebellum. [3H]Muscimol was used to assess gamma-aminobutyric acid receptor density and [3H]flunitrazepam or [3H]Ro 15-1788 was used to assess benzodiazepine receptor density. No significant differences were observed between the magnitude of binding of the three ligands to each of the microregions of brain from control rabbits and rabbits in Stage III or IV hepatic encephalopathy. These findings suggest that the behavioral expression of hepatic encephalopathy in the model studied is not dependent upon an increase in the number of gamma-aminobutyric acid or benzodiazepine receptors, but do not conflict with the hypothesis that gamma-aminobutyric acid-ergic tone is increased in hepatic encephalopathy.

Acute Disease↗

Cortical benzodiazepine receptor binding in a rabbit model of hepatic encephalopathy: the effect of Triton X-100 on receptor solubilization.

Increased benzodiazepine (BZ) receptor density has been reported in brains of rabbits with hepatic encephalopathy (HE) due to galactosamine (GalN)-induced fulminant hepatic failure (FHF). These data were generated using detergent-Triton X-100-treated neural membranes. While performing further studies it was noted that the increase in BZ receptor density was not demonstrable when Triton X-100 preparation was not employed. Accordingly the binding of [3H] flunitrazepam, a BZ ligand, to neural membranes from cortices of normal rabbits and rabbits with HE due to (GalN)-induced FHF was studied with and without detergent preparation. Scatchard plot analysis of the binding data indicated that when no detergent was employed, the apparent affinity and density of BZ receptors were similar for control membranes and membranes from animals in HE. BZ receptors from animals in HE were shown to be more resistant to solubilization by Triton than control membranes. These findings (a) afford a potential explanation for the apparent increase in density of BZ receptors in this model when Triton treatment of neural membranes is utilized and (b) suggest that recent evidence for increased GABAergic tone in the syndrome of HE is not dependent on an increased density of BZ receptors.

Animals↗

[The transjugular intrahepatic portosystemic stent-shunt. A new nonsurgical percutaneous method].

In a 49-year-old male patient suffering from severe symptoms of end-stage portal hypertension and Child's stage C metabolic status, an intrahepatic stent-assisted portosystemic shunt was established for the first time exclusively by means of interventional radiology. Via transjugular access, a modified Brockenbrough needle was used to puncture the right branch of the portal vein via the right liver vein. As a target, a Dormia-basket was used that had previously been exposed in the right main portal branch. After successful puncture and balloon dilation of the artificial tract, two Palmaz stents were implanted to keep the tract permanently open. The portosystemic pressure gradient dropped from 38 to 18 mm Hg. The clinical status of the patient improved substantially during the following days. However, the patient died on day 11 after the procedure because of sudden onset of acute respiratory distress arising from acute nosocomial fungus and cytomegalovirus infection worsened by his primary immunoincompetence. Autopsy demonstrated a totally patent shunt without superficial thrombus. Microscopically, a thin endothelial layer on the inner shunt surface was found to be present.

Humans↗

[Tryptophan metabolism in liver diseases: a pharmacokinetic and enzymatic study].

Tryptophan is considered to be one of the agents involved in the pathogenesis of hepatic encephalopathy. In our study, we evaluated tryptophan metabolism in liver disease. A bolus of 1.5 g of L-tryptophan was administered intravenously to 14 patients with noncirrhotic liver disease, 40 patients with liver cirrhosis, and 8 healthy volunteers. As pharmacokinetic parameters, the half life, clearance, and volume of distribution of free and total tryptophan were determined using a biexponential formula. In addition, the activity of liver tryptophan pyrrolase, the key enzyme of tryptophan metabolism, was measured in liver biopsy specimens of 15 patients with noncirrhotic liver disease, 8 patients with cirrhosis of the liver, and 4 patients with histologically normal livers. Healthy subjects and patients with noncirrhotic liver disease both showed similar results in measured and calculated data. In contrast, patients with cirrhosis revealed significant alterations of the pharmacokinetic parameters of free and total tryptophan: the half-life was increased by 195% and 176%, the clearance was decreased by 73% and 34%, respectively, and the activity of tryptophan pyrrolase was decreased by 22%. The tryptophan transfer in cirrhosis amounted to only 0.75 +/- 0.03 g per 24 h compared with 2.6 +/- 0.34 g per 24 h in healthy individuals. The findings demonstrate that patients with cirrhosis show a marked reduction in their ability to metabolize tryptophan. This should be taken into account in the oral and parenteral nutrition of those patients.

Adult↗

The disposition of intravenous L-tryptophan in healthy subjects and in patients with liver disease.

The disposition of free and of total tryptophan following an intravenous load of 1.5 g of L-tryptophan was evaluated in eight patients with non-cirrhotic liver disease, 40 patients with cirrhosis of the liver (21 Child's A, 15 Child's B, 4 Child's C) and in 14 healthy subjects. Cirrhosis affected disposition of tryptophan by (a) decreasing the clearance of both free and total tryptophan by 64% (P less than 0.001) and 34% (P less than 0.01), respectively, (b) by increasing the apparent volume of distribution of total tryptophan by 42% (P less than 0.01) by expansion of the peripheral compartment, resulting in (c) a threefold increase in the half-life of tryptophan. Apart from a reduction in free tryptophan clearance, these changes in tryptophan disposition were not apparent in patients with non-cirrhotic liver disease. Elevated fasting free tryptophan plasma concentrations are an indicator of impaired tryptophan metabolism in cirrhosis. They result from a decreased hepatic clearance of tryptophan rather than from a reduction in tryptophan protein binding. This study emphasises the markedly differing pharmacokinetic behaviour of tryptophan in cirrhotic patients compared with normal subjects and with patients with non-cirrhotic liver disease.

Adult↗

Mesocaval and distal splenorenal shunts: effect on hepatic function, hepatic hemodynamics, and portal systemic encephalopathy.

The effect of the mesocaval interposition shunt (n = 12) and the distal splenorenal shunt (n = 9) on the wedged hepatic venous pressure, the estimated hepatic blood flow, quantitative hepatic function, and the rate of portal systemic encephalopathy was evaluated in 21 patients who had bled from esophageal varices. After mesocaval shunt the wedged hepatic venous pressure was significantly reduced by 42% (from 26 +/- 3 mm Hg to 15 +/- 5 mm Hg, P less than 0.001) compared to 16% only (from 25 +/- 3 mm Hg to 21 +/- 2 mm Hg, P less than 0.005) after distal splenorenal shunt. The estimated hepatic blood flow also decreased significantly after mesocaval shunt by 61% (from 1.45 +/- 0.46 l/min to 0.56 +/- 0.25 l/min, P less than 0.001) compared to 29% (from 1.29 +/- 0.32 l/min to 0.91 +/- 0.39 l/min, P less than 0.05) after distal splenorenal shunt. Despite significantly different influences of both types of shunt operations on wedged hepatic venous pressure and estimated hepatic blood flow (P less than 0.001), postoperative changes of hepatic function were comparable in both groups of patients. The galactose elimination capacity, the initial plasma disappearance rate of Bromsulphalein, and the plasma ratio of valine, leucine, and isoleucine to phenylalanine and tyrosine were reduced by 13%, 26%, and 29%, respectively, after mesocaval shunt, compared to 12%, 25%, and 17% after distal splenorenal shunt. Only two patients of the mesocaval shunt group with the largest decrease in estimated hepatic blood flow developed portal systemic encephalopathy postoperatively, and the distal splenorenal shunt patients with their minor hemodynamic sequelae remained free of portal systemic encephalopathy.

Adult↗

Amino acid, ammonia and neurotransmitter concentrations in hepatic encephalopathy: serial analysis in plasma and cerebrospinal fluid during treatment with an adapted amino acid solution.

We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations of amino acids (AA) and ammonia in plasma and cerebrospinal fluid (CSF) and of the neurotransmitters norepinephrine, dopamine and 5-hydroxytryptamine (5-HT) as well as the 5-hydroxyindole acetic acid (5-HIAA) in CSF before and at the end of a 3-day period of treatment with infusions enriched with branched chain amino acids (BCAA). The subjects studied were 13 patients with alcoholic cirrhosis and hepatic encephalopathy stages 1-3 (n = 8) and stage 4 (n = 5). The patients in coma stages 1-3 recovered during the treatment (survivors), those in coma stage 4 died before the study period was finished (non-survivors). The data emerging from this study show: Alterations of AA concentrations are much more pronounced in the CSF than in the plasma. In the case of tryptophan the alterations in plasma and CSF were inverse. Before the treatment the CSF-plasma ratios of the concentrations of BCAA and aromatic amino acids (AAA) are increased reflecting an activated transport of both the BCAA and AAA through the blood-brain barrier. High dose BCAA nearly normalized CSF concentrations and CSF-plasma ratios of AAA assuming that the treatment brought about an effective competition of cerebral uptake between BCAA and AAA. The CSF concentrations of ammonia and glutamine decreased significantly during treatment while the plasma concentrations changed only moderately. As to the neurotransmitters, only the concentrations of 5-HT and its metabolite 5-HIAA correlated with the clinical picture and with the concentration of their precursor AA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of cimetidine on the hepatic extraction of indocyanine green, the portal pressure and the systemic circulation in patients with cirrhosis of the liver.

The effect of cimetidine on hepatic and systemic haemodynamic parameters was studied in seven patients with portal hypertension due to alcohol-induced cirrhosis of the liver and in one patient with peliosis hepatis following oral contraceptive steroids. The intravenous administration of cimetidine (350 mg as bolus, followed by 2 mg/min over 60 min) reduced the hepatic extraction of continuously infused indocyanine green (ICG) by 27%; this was statistically significant (P less than 0.01). Since the ICG clearance, calculated independently of hepatic perfusion, was lowered by 19%, this effect seems to be mainly due to a reduced capacity of the liver to remove the dye from the blood, rather than due to changes in perfusion. Cimetidine did not influence the elevated portal pressure in the patients with cirrhosis, or the normal pressure in the patient with peliosis hepatis. No significant effect was observed on heart rate, mean arterial pressure, pulmonary artery pressure, pulmonary capillary pressure and cardiac output. These studies indicate that the reduction of the hepatic ICG extraction following cimetidine is more the result of an inhibited capacity of the liver to remove the dye than of changes in the hepatic perfusion or in the systemic circulation.

Adult↗