[Gastroenterology in the former GDR (1975-1990) and the changes after German reunification]. / DDR-Gastroenterologie 1975-1990 und Wiedervereinigung.

This short overview sketches the state of Gastroenterology in the GDR (1975 - 1990) from the point of view of an East-German contemporary witness. The "Society for Gastroenterology/GDR" (GfG) has played a decisive role for the development of the Gastroenterology in the GDR. The society promoted medical education and constitutions of gastroenterological centers, fostered gastroenterological research and controlled the standards for the recognition of Gastroenterology as a state-accepted medical sub-discipline. An extensive program of scientific and educative events included two-annual meetings of scientific congresses, the "Berka-Talks", endoscopic workshops" and featured special symposia such as for Hepatology, Pancreatology and gastro-intestinal Microbiology. Temporary working groups developed technical and professional legal advice. Although the GfG was a full member of the respective international organizations (OMGE, ASNEMGE, ESGE), it was almost impossible building up reliable international contacts in a mutual interest. Especially, contacts with colleagues representing the "German Society of Digestion and Metabolic Diseases" (DGVS) were impeded. With the political changes of 1989/1990, an association of the two German Societies for Gastroenterology seemed within reach. At a meeting in Halle (Saale) (March, 22nd, 1990), representatives of DGVS and GfG quickly agreed on modalities to merge the two societies. After the 45th meeting of the DGVS (October 3rd-6th, Essen) more than 600 GDR physicians could join the BRD society under accommodating conditions. The GfG had fulfilled its historical function as a "bridge" during the division of Germany with dignity and was suspended (November, 24nd,1990).

Occurrence of acetaldehyde protein adducts formed in various organs of chronically ethanol fed rats: an immunohistochemical study.

We investigated the pathophysiological role of acetaldehyde protein adducts formed in vivo in organs of chronically alcohol fed male Wistar rats. Thirty male Wistar rats were fed on rodent pellets and 15% alcohol (V/V) for 5, 8 and 12 months, respectively before they were sacrificed. Further 30 male rats were chosen as the control group. We tested several organs by histological and immunohistochemical methods. Using immunohistological analysis, in the 12 months groups the basal membranes of glomerula, the membranes of liver, skeleton muscle and heart cells, and the gut were stained positively for acetaldehyde adducts. Using Western blotting of liver cell fractions (mitochondria/ lysosomes; microsomes; cytosol) adducts in charateristic molecular weight regions were detected. Approximately 30% of the sera of experimental rats contained antibodies against the acetaldehyde adducts formed in vivo. Immunologically detectable acetaldehyde adducts could be found in all rat organs tested. The stage of alcohol disease attained in this experiment after 12 months of ethanol feeding is described as the initial phase of manifestations of disturbances that are seen also in the carbohydrate metabolism.

Effects of twelve months ethanol feeding on rat liver metabolic activity.

Thirty male Wistar rats were fed with 15% ethanol (V/V) for one year. Thirty other male animals were the control group. To determine the possible metabolic disturbances caused by chronic ethanol feeding in blood we measured in blood metabolic parameters, and in a liver perfusion assay the hepatic insulin clearance and hepatic urea production in these animals. Between the ethanol-fed and the control animals there were significant differences in the following parameters: blood insulin concentration (47 vs. 2 microU/ml) and activities of amino acid transferases in liver homogenates at the end of the perfusion experiments (ASAT, 5950 vs. 70; ALAT, 3632 vs. 93 U/l). The other parameters were still normal in the ethanol-fed animals. Thus in these experiments after 12 months of 15% (V/V) ethanol feeding the rats still showed only a state of beginning metabolic disturbances in the liver. The results are discussed under consideration of the formation of acetaldehyde protein adducts in all rat organs investigated, namely, liver, kidney, heart and skeleton muscle, gut and spleen.

A histochemical study of the distribution of dextran 500 in human corneas during organ culture.

PURPOSE: The aim of this histochemical study was to demonstrate the absorption of dextran 500 and its distribution in the cornea after storage under standard eye bank conditions. Furthermore, an attempt was made to distinguish between the soluble and insoluble parts of dextran 500 absorbed by the cornea, in order to see how much dextran remains in the cornea after transplantation. METHODS: Forty-nine fresh and 65 organ-cultured human corneas were investigated. The corneas were cultured for 28 days in a dextran-free medium, followed by a period of 1-14 days in a medium containing 5% dextran 500. Cryosections were stained by aqueous PAS and a modified alcoholic PAS to determine the amount of dextran. RESULTS: Dextran was not found in the epithelium, stroma or endothelium of fresh human corneas. By contrast, extra- and intracellular positive staining reactions were detected in corneas following storage in a medium containing dextran. Dextran 500 absorption was relatively diffuse in the epithelium after storage in a dextran medium. Initial accumulations were found in the stroma near Bowman's and Descemet's membranes and also in the central part of the cornea, as the period of culture in the medium containing dextran lengthened. We also observed interaction between the stroma and endothelium: decreasing amounts in the endothelium were followed by an increase of same in the stroma. Intracellular deposits of dextran were detected after only one day. A much greater part of the extracellular dextran than previously described was found to be insoluble. CONCLUSIONS: As the amount of dextran in the cornea increases over a longer storage time, we conclude that the period of storage in a medium containing dextran should be limited to four days. The fact that the cornea is saturated with dextran after seven days has been shown in further studies to interfere with mitochondrial function and may also cause severe post-operative swelling of the transplant, hence leading to a longer recovery period for the patient.

Changes of dipeptidylpeptidase IV as a membrane marker of lymphocytes in acute and chronic liver diseases--biochemical and cytochemical investigations.

Lymphocytic dipeptidylpeptidase IV (DPP-IV, E.C. 3.4.14.5) is described as a marker enzyme of immunostimulant T-lymphocytes as well as functional characteristic of interleukin-2-producing cells. Cytochemical staining of DPP-IV positive lymphocytes and measurements of DPP-IV activity in mononuclear cells and in sera of patients suffering from different kinds of liver diseases were performed to evaluate the average activities in positive cells. The results demonstrated that this serine exopeptidase exhibits extremely low activity in autoimmune chronic hepatopathies. On the contrary, hepatitis-B-associated liver diseases were connected with markedly increased values. Furthermore, significant differences of DPP-IV activity were found in different kinds of acute and chronic liver diseases. These findings are discussed in connection with the participation of dipeptidylpeptidase IV in impaired immunoregulation of the altered liver.

Aldehyde dehydrogenase (E.C. 1.2.1.3) in chronic alcoholic liver diseases.

Acetaldehyde dehydrogenase (ALDH) activity in liver biopsy specimens was considerably reduced in alcoholic cirrhosis (n = 5), elevated in alcoholic fatty liver (n = 11)--probably due to enzyme induction--only slightly elevated in alcoholic hepatitis (n = 6), but unaffected in non-alcoholic liver diseases (n = 23) in comparison with specimens obtained from patients with minimal liver lesions. We will argue as a working hypothesis that alcoholics with induced ALDH activity will mainly develop fatty liver, whereas reduced hepatic ALDH appears to be a reason for elevated acetaldehyde levels followed by additional liver injury and progression at least for alcoholic cirrhosis.

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.

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.

Levamisole therapy in chronic hepatitis--results of a multicentric double blind trial.

The effectiveness of levamisole in the immunmodulatory treatment of chronic hepatitis was assessed in a multicentric double blind trial. Twenty patients received in the first week 50 mg, in the second 100 mg and thereafter 150 mg, levamisole on two days every week for 6 months, 20 others received a placebo. Five patients dropped out (non-compliance 1, pregnancy 1, adverse effects 3). The diagnoses were confirmed by clinical, biochemical immunological and histological data. After 6 months 26 subjects allowed us to take a control liver biopsy. The results showed that the rate of improved, unchanged and impaired cases was not significantly different in the levamisole and placebo groups. No correlation was found between etiology, activity or histological type of chronic hepatitis, skin test reactivity (DNCB, PPD, Streptokinase) and therapeutic effect, respectively. Clinical improvement was not associated with the elimination of HBs antigen. In general levamisole was well tolerated, but we saw one case of severe agranulocytosis.

[Discriminant studies of immunoglobulins in diseases of the liver and biliary tract]. / Diskriminantnye issledovaniia immunoglobulinov pri zabolevaniiakh pecheni i zhelchnykh putei

Discriminant-analytical studies of immunoglobulins G, A and M in 54 persons with a healthy liver and in 476 persons with various diseases of the liver and biliary tracts, and also calculation of correlations between the extent of proliferation of the hepatic mesenchyma and the concentrations of serum immunoglobulin led to the following conclusions: changes in the behaviour of immunoglobulins were specific of the organ and the disease, of limited significance in the diagnosis of diseases of the liver and biliary tracts. Dependence of the quantitative values of immunoglobulins on the activity of hepatic mesenchyma permitted to determine the significance of the indices for the observation over the course of the disease and for its prognosis. However, in the assessment of these changes one should take into consideration the influence produced on the immunoglobulinogram of extrahepatic concomitant disease, and also different individual capacity of the organism to immunoglobulin synthesis.

[Effects of prostaglandins on toxic and inflammatory liver diseases. A short review]. / Effekte von Prostaglandinen auf toxische und entzündliche Leberaffektionen. Eine kurzgefasste Ubersicht.

This short review deals with actions of prostaglandins (PG) and leukotrienes (LT) in liver injury. According to experimental data PGs of the E- and I-series seem to play an important role as metabolic, cytoprotective, antifibrogenic, immunomodulating and hemodynamic regulatory factors having interest in human pathology. In human cirrhosis with portal hypertension elevated PGI levels promote the formation of a collateral circulation. Some studies suggest that renal PGs could be involved in the regulation of renal hemodynamics in cirrhosis and have probably pathogenetic value in the development of the hepatorenal syndrome. LTs act as mediators of inflammatory liver reactions. Conclusively, one can predict that eicosanoid research will lead to some progress in clinical hepatology.

[Pathogenesis and therapy of ascites in liver cirrhosis]. / Pathogenese und Therapie des Ascites bei Leberzirrhose.

This paper reviews pathogenetic factors which contribute to the development of therapy-resistant ascites in liver cirrhosis. Main principles are known as "Overfilling"--and "Underfilling"-hypotheses followed by disturbances of different kinds of mediators influencing renal blood flow and natriuresis. The endpoint of a cascade is the development of a hepatorenal syndrome which is connected with therapeutic resistance against diuretics. Therefore, other therapeutic methods (paracentesis, reinfusion) must be taken in to account in order to improve prognosis of such cases.

[Multivariant discriminance analytical computation methods for the evaluation of clinico-chemical parameters in liver and biliary tract diseases]. / Beitrag multivariater diskriminanzanalytischer Rechenverfahren zur Aussage klinisch-chemischer Parameter bei Leber-und Gallenwegserkrankungen

Multivariate variance and discriminance-analytic investigations on the value of evidence of clinico-chemical tests in the diagnostics of diseases of the liver and the biliary tract gave the following results: 1. By means of clinico-chemical methods and discriminance-analytic functions we succeed in 50% of the cases in formulating a correct diagnosis, in more than 75% of the cases a correct probability diagnosis (3 first places in the rank of diagnoses). Sensitivity and specificity of discrimination were established for 15 classes of diagnoses. 2. Due to the intercorrelations of test results biochemical maximum programmes contain numerous redundant parameters measured on diagnostic information values. With the help of a test for indispensability (redundance test) among 20 parameters owy 5-6 were characterized as indispensable. An optimal combination of parameters should not transgress an extent of 14 tests. 3. Results of reclassifications with discriminance analytic functions confirmed that the discriminance analysis is an extraordinarily suitable method for the computer-supported finding of a decision, on which basis aimed additional investigations might be performed.

[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.

[Rational laboratory diagnosis of cholestasis syndrome]. / Rationale Laboratoriumsdiangostik des Cholestase-Syndroms.

Laboratory diagnostics efficiently applied is of decisive importance for a great deal of questions in spite of the technical and endoscopic methods which are available today in the field of examinations. By means of a screening programme consisting of ALAT, gamma-GT, ChE at a sensitivity of > 90% alterations in both the hepatobiliary system and cholestasis can be recognized with sufficient reliability. Clinical data and a defined laboratory routine programme as a second step in diagnostics results in reliable indication for distinction between obstructive and non-obstructive cholestasis which can be promoted by computer-aided techniques. On the basis of such pre-selections special laboratory methods (differential diagnosis of consecutive non-obstructive cholestasis in liver diseases) or invasive methods to clarify their reason and localization diagnostics of biliary obstruction can then be applied in a well-directed manner to obtain a definite nosologic diagnosis. Effective diagnostic procedures in this three-step programme are described.

[Pathophysiology and laboratory diagnosis of cholestasis]. / Pathophysiologie und Labordiagnostik der Cholestase.

Cholestasis--defined as a reduction or stasis of bile flow with corresponding rise of bile substances in blood--can be caused by obstructive and non-obstructive mechanisms. Common pathomechanisms, manifesting mainly in centrolobular liver areas, can be classified with regards to the subcellular location of the cholestatic components: Impairment of sinusoidal and lateral hepatocyte membrane; disturbance of bonds, storage, transport and secretion of bile substances (particularly reduction of bile-acid dependent and non-dependent bile flow); impaired bile acid and drug metabolism as a result of hypoactive, hypertrophied endoplasmatic reticulum; impairment of the mitochondrial energy metabolism; alteration of the canalicular membrane; impairment of filaments and "tight junctions"; the building of precipitates resulting from disturbed micellar function; impairment of ductulus permeability with reabsorption of bile.--These pathomechanisms explain the behaviour of biochemical and cholestatic-specific symptoms in blood-plasma, inclusive the appearance of abnorm substances whose diagnostic values are illustrated.