Pharmacokinetics of trapidil in patients with chronic liver disease.

The pharmacokinetics of trapidil were studied in 15 patients with chronic liver disease (12 with hepatic cirrhosis, 2 with alcoholic fatty liver, 1 with liver fibrosis). Trapidil was administered intravenously as a 100-mg bolus. Serum samples were analyzed for trapidil by means of high-performance liquid chromatography. Mean pharmacokinetic parameters were compared with those found in a previous study of 12 healthy volunteers. Total plasma clearance was decreased significantly in patients with hepatic cirrhosis (96 mL/ min versus 258 mL/min in healthy individuals and 252 mL/min in patients with noncirrhotic liver disease). No difference in clearance was observed between patients with compensated or decompensated cirrhosis, and portal hypertension did not affect this clearance of trapidil. It can be concluded that trapidil clearance is a parameter that is very sensitive to alterations in hepatic clearance caused by liver cirrhosis, and that the dosage of trapidil should be adjusted accordingly in such patients.

[Palliative endoscopic treatment of malignant occlusive jaundice with a balloon expandable metal stent]. / Endoskopische Palliativbehandlung des malignen Verschlussikterus mit ballonexpandierbarem Metallstent.

Balloon-expandable Strecker-stents were endoscopically inserted in 13 patients (8 females, 5 men; mean age 75.2 [55-99] years) suffering from malignant obstructive jaundice. The stent implantation was difficult in one patient because of trouble to retract the balloon carrying the stent. A prompt regression of the cholestasis resulted in 11 patients. Two patients with long-distance stenoses of the common hepatic duct showed a persistent icterus due to an incomplete drainage of the stenoses. Therefore a second stent was implanted by means of transhepatic procedure in one case. Additional early complications such as cholangitis did not occur within four weeks after insertion. During the follow-up of four up to 41 weeks (mean follow-up 15.2 weeks) we observed late complications in five patients: stent migration in one patient after 10 weeks; relapsed jaundice in four patients 11 up to 41 weeks after stent implantation (the reason of jaundice was unknown for these patients were not again sent to our hospital because of their bad conditions). Six patients were alive without evidence of icterus on the date of examination. Considering data from the literature Strecker-stent implantations have been rarely performed in biliary duct stenosis till now. But the results demonstrate that an effective drainage of bile duct stenoses can be achieved in a high percentage by means of balloon-expandable metal stents. The insertion of the stent can be rather easily performed in stenoses situated in Vater's papilla and common bile duct provided that the guide wire has passed the stenosis.

[Endoscopic sclerosing of esophageal varices--technique, possibilities and limits of the method]. / Endoskopische Osophagusvarizensklerosierung--Technik, Möglichkeiten und Grenzen der Methode.

The paper intends to give a survey of the significance of endoscopic sclerotherapy in gastro-esophageal varices. The control of an acute bleeding can be achieved in a high percentage (70-95%). However, the hospital mortality has persisted in 30% depending on early rebleeding episodes and alterations in hepatic function. Controlled trials have confirmed a lowering of rebleeding risk as well as an improved survival by repeated sclerotherapy. The effectiveness of prophylactic sclerosing before the first bleeding is uncertain because of contrary results published. A prophylactic application seems to be favourable in patients at high risk of bleeding only.

[Portal hypertensive gastropathy--a rare cause of upper gastrointestinal hemorrhage]. / Die portal-hypertensive Gastropathie--eine wenig beachtete Ursache der oberen Gastrointestinalblutung.

There is evidence that the portal-hypertensive gastropathy is a clinical complication of portal hypertension and a distinct clinical entity being different from various types of gastritis. According to endoscopical findings one can differentiate 4 stages: I = superficial reddening on the surface of the gastric rugae, II = white reticular pattern separating areas of prominent pink oedematous mucosa (snake-skin or mosaic pattern), III = cherry red spots, IV = diffuse bleeding. These alterations occurring more prominently in the gastric fundus are caused by venous and capillary ectasia and by arteriovenous shunts. The potential of diffuse mucosal bleeding distinct from variceal haemorrhage is of clinical importance. Additionally, congestive mucosa seems to be more vulnerable to noxious agents in the gastric lumen. For therapy propranolol has been recommended.

Prophylactic endoscopic sclerotherapy of esophageal varices--a prospective randomized trial.

Sixty-three patients with degree III or IV esophageal varices and the so-called red color sign, but without previous bleeding were randomly assigned to either prophylactic sclerotherapy (PST) (n = 30) or to a control group (n = 33). In 58 cases the portal hypertension was caused by liver cirrhosis (40% alcoholics). The two groups were comparable with respect to demographic data and endoscopic appearance, causes and severity of liver damage. Sclerotherapy was performed as combined intra-and paravariceal injections of 2 or 3% polidocanol. All patients, both in the treatment and in the control groups, who bled from varices after randomization, received sclerotherapy until the varices were eradicated, and remained in their groups. After a mean follow-up of 44.5 months, the bleeding rate in the PST group was significantly lower (30% vs 75%, p less than 0.01). The difference became significant from the second year onward. Fourteen patients of the PST group and 19 of the controls died (4 and 14, respectively, p less than 0.05 as a result of the bleeding). Life table analysis (Kaplan-Meier) revealed no differences in survival between the two groups. At the present time PST cannot yet be recommended as a method for clinical routine use.

[Prostacyclin and thromboxane synthesis in liver tissue in chronic liver diseases]. / Prostazyklin- und Thromboxansynthese im Lebergewebe bei chronischen Lebererkrankungen.

This paper reports on investigations of the formation of PGI2 and TXA2 using their stabile products 6-keto-PGF1 alpha and TXB2 (RIA) in liver biopsy specimens of 46 patients suffering from fatty liver (n = 19), chronic hepatitis B (n = 11), liver cirrhosis (n = 13), and miscellaneous diseases (n = 3). The measured formation rates in chronic liver disease were evaluated in comparison to a reference group (n = 19) consisting of minimal liver lesions. The 6-keto-PGF1 alpha formation correlating to the degree of the portal inflammation in the liver (morphometric evaluation). The same trend existed in relation to the intralobular inflammation. The results presented suggest in respect of analogous data in animal experiments that PGI2 is predominantly generated in mesenchymal cells of the liver and, presumably influences the course of liver diseases.

[Therapy strategy in bleeding esophageal varices]. / Therapiestrategie bei blutenden Osophagusvarizen.

In the therapeutic regimen in the haemorrhage of the oesophageal varices the sclerotherapy part from measures for the combat against shock and prophylaxis of the liver coma occupies a central position both for control of haemorrhage and for avoiding recidivations of haemorrhages. Advantages of the method are the relatively good efficacy, the small rate of serious complications and a relatively good practicability. Furthermore, liver function, portal circulation and course of the in most cases underlying liver cirrhosis are not negatively influenced. On the basis of the hiherto got experiences the value of the prophylactic sclerosation of oesophageal varices before a bleeding cannot yet be reliably assessed.

[Pedicled fibroma of the extrahepatic bile ducts]. / Gestieltes Fibrom der extrahepatischen Gallenwege.

It is reported on the very rare occurrence of a benign tumor in common hepatic bile duct of a 33-year-old woman, associated with obstructive jaundice. Clinical diagnosis and treatment are described, histological typing like fibroblastic tumor with neurogenic parts are discussed and a short review of the literature is given.

Immunoglobulin allotypes and immunoreactivity in chronic liver disease.

The immunoglobulin allotypes Gm (a; x; f) and Km 1 have been estimated in 194 patients with chronic liver disease, and compared with the frequency distribution of a representative reference group (Gm : n = 2171; Km : n = 2179). In relation to the Gm phenotypes we have investigated the cell-mediated immunoreactivity by the E rosette test, lymphocyte transformation test and migration inhibition test. Virus-induced chronic liver disease showed significantly higher prevalence of the phenotypes Gm a+x-f+ and Gm a+x+f+ as well as of the marker Km + 1 (p less than or equal to 5%; chi 2-test). In auto-immune chronic liver disease we observed a decrease in the phenotype Gm a+x-f+ while the factor Km + 1 was significantly multiplied. Patients with cryptogenic and alcoholic hepatopathy showed no differences in comparison with the reference group. In the progressive forms of the chronic liver disease (chronic active hepatitis, liver cirrhosis) Gm a+x+f+ was significantly more frequent. The investigations concerning cell-mediated immunity in different Gm allotypes generally showed a trend to increased reactivity in Gm a+x+ in comparison with Gm a-x- in non-alcoholic liver disease. It is possible to presume different genetic and immunologic situations in the various liver diseases as endogenous factors promoting the disease.

[Adenosine deaminase activity--an indicator of inflammation in liver disease]. / Die Adenosindesaminase-Aktivität--ein Entzündungsindikator bei Lebererkrankungen.

Inflammatory liver diseases display higher levels in serum ADA activity compared to non-inflammatory ones. The most pronounced increases in activity are found in acute virus-induced hepatitis, in active liver cirrhoses, extremely high levels in some liver tumours. Due to correlative relations, the ADA is mainly attributed to the mesenchymal parameters by factor analysis. This can be validated by assessment of histological criteria. The highest correlation coefficient could be demonstrated for ADA in relation to all parameters under investigation by means of the semi-quantitatively evaluated mesenchymal reaction within the histological section. The determination of the serum ADA is valuable in assessing the inflammatory reaction of the liver and for diagnosing active cirrhosis in particular. Increases in activity based on an elevated nucleic acid metabolism in tumours and regenerative processes have to be taken into consideration. This interpretation is evidenced by correlative relations between the activity of ADA in liver biopsy homogenate specimen and the hepatic inflammatory reaction.

Haptoglobin type and liver disease.

The haptoglobin phenotype has been estimated in patients suffering from chronic liver disease (n = 222) and acute hepatitis (n = 59) in comparison with the haptoglobin pattern of a normal population (n = 1726). The frequency of Hp 1-1 was significantly increased in non-alcoholic chronic liver disease (p = 5%; chi 2-test) in contrast to alcoholic disease. The highest incidence of Hp 1-1 occurred in cryptogenic cases (p = 1%). The follow-up of patients suffering from acute hepatitis failed to indicate any relationship between the haptoglobin phenotype and the course of hepatitis. The results suggest that Hp 1-1 is a genetic marker of special kinds of chronic liver diseases.

[Genetic studies in etiologically different chronic liver diseases]. / Genetische Untersuchungen bei ätiologisch unterschiedlichen chronischen Leberkrankheiten.

In 198 patients with chronic liver diseases of different etiology 16 genetic feature systems were investigated (blood groups, erythrocytic enzymes, immunoglobulin allotypes, proteins). In comparison to a representative normal population significant differences of the frequency of the distribution of phenotypes of various systems were found. In these cases is remarkable that association between genetic markers and hepatopathies were above all proved in their classification according to etiopathogenetic criteria. We evaluate our findings as a reference to the importance of genetic factors in the development of chronic liver diseases.

[Rational procedures in the differential diagnosis of jaundice]. / Rationales Vorgehen in der Differentialdiagnose des Ikterus.

In jaundice after exclusions of prehepatic and functional hepatogenic hyperbilirubinaemias the sonography should pre-eminently be used as a riskless, economical and qualified investigation method, taking into consideration clinical and laboratory-chemical data. If sonographically the findings of an intrahepatic cholostatis are shown, in therapeutic relevance the histological clarification must follow. Only in unequivocal focal changes of the liver (perhaps thin needle puncture) further investigations are unnecessary. If there are findings of an extrahepatic cholostasis, in a not unequivocal sonographic result or before a surgical intervention further aimed investigations, such as ERCP, PTC and CT, are necessary for the exact clarification of the cause of the obstruction of the bile ducts.

[Changes in phagocytic performance of neutrophilic granulocytes in chronic liver diseases of various etiologies]. / Veränderungen der Phagozytoseleistung neutrophiler Granulozyten bei chronischen Lebererkrankungen verschiedener Atiologie.

The phagocytic functions and the nitroblue-tetrazolium (NBT)-reduction of heat inactivated Saccharomyces cerevisiae blastospores by polymorphnuclear leukocytes in 92 patients with chronic liver diseases and 21 normal human subjects was investigated. The percentage of phagocytizing leukocytes and the number of phagocytized yeast particles/100 leukocytes was only significantly reduced in active alcoholic cirrhosis. A relationship between this findings and highly enhanced sIgA levels of this group is discussed. The NBT-reduction is impaired in all groups with liver disease, the decrease is significant in chronic persistent hepatitis and all groups with alcoholic etiology. The detection of a positive correlation to unspecific stimulation of lymphocytes by PHA and negative correlation to leukocyte migration inhibition by PHA suggested the implication of reactions of cell mediated immunity in NBT-reaction. No relations between phagocytosis, NBT-reaction and autologous serum factors was estimated.

[Gastroesophageal reflux--cause of hemorrhaging esophageal varices?]. / Gastroösophagealer Reflux--Ursache der Osophagusvarizenblutung?

The results of the examinations do not depend on the peptic theory of the haemorrhage of the oesophageal varices in patients with liver cirrhosis, since the relative frequency of reflux troubles and of gastrooesophageal reflux in patients with liver cirrhosis and haemorrhage of the oesophageal varices was not found greater than in patients with liver cirrhosis and oesophageal varices without haemorrhage as well as the combination of reflux oesophagitis and oesophageal varices was rarely to be observed in the endoscopic material.

[Experiences with endoscopic sclerosing of esophageal varices]. / Erfahrungen mit der endoskopischen Osophagusvarizensklerosierung.

In this paper is reported on endoscopic sclerotherapy in 35 patients, which have been treated from March 1980 to March 1983. The efficacy of submucosal (paravascular) wall sclerosis wasn't sufficient. We achieved better results in the prevention of esophageal variceal bleeding with combined para- and intravascular injections of sclerosant.