Jejunal microflora in patients with chronic alcohol abuse.

The types and numbers of bacteria were examined in aspirates from the jejunums of 27 chronic alcoholics and 13 hospitalized control patients of comparable age distribution without alcohol abuse or diseases of the liver. Samples of jejunal juice were aspirated in the fasting state. The mean number of microorganisms obtained during anaerobic incubation was distinctly higher in the alcoholics (log10, mean +/- SD: alcoholics 4.9 +/- 2.2, controls 3.2 +/- 1.5, p less than 0.025). A similar difference was found for the number of aerobic bacteria (alcoholics 4.7 +/- 1.9, controls 3.3 +/- 2.1, p less than 0.05). Significant counts (greater than 10(5)/ml) of bacteria obtained during anaerobic incubation were more frequent in the alcoholics (48.1%) than in the controls (7.6%, p less than 0.001). Coliform microorganisms were cultured much more frequently from the jejunal fluid of the alcoholics (alcoholics 55.6%, controls 15.4%, p less than 0.025). In addition the incidence of Gram-negative anaerobic bacteria and endospore-forming rods was higher in the aspirates from alcoholics (p less than 0.05). In both groups the number of microorganisms in jejunal fluid correlated closely with the pH found in the gastric juice. No correlation was found between the numbers or types of microorganisms in the jejunum and the type or degree of liver disease in the alcoholics. It is concluded that bacterial overgrowth might contribute to functional and/or morphological abnormalities of the small intestine commonly found in patients with chronic alcohol abuse.

The liver in hereditary haemorrhagic teleangiectasia: an inborn error of vascular structure with multiple manifestations: a reappraisal.

Hereditary haemorrhagic teleangiectasia (Rendu-Osler-Weber disease) is an inborn error of vascular structure with multiple manifestations. Its incidence is about 1-2:100 000 in the European population. The incidence of telangiectases and/or fistula formation was estimated to be 1 in 10 carriers of the Osler trait. The findings in the family reported herewith suggest a much higher incidence if angiography is more frequently performed. Apart from the skin and mucous membrane, teleangiectases and/or arteriovenous fistulas may be present in the lungs, intestinal tract, spleen, kidney, brain, and bones. The liver apparently is more involved than was orginally suspected. The vascular derangement includes teleangiectases, arteriovenous fistulas, and connective tissue formation with fibrosis and atypical cirrhosis. In intestinal bleeding laser coagulation seems to be very efficient. The pathogenesis of teleangiectases is not known but involves several factors such as special formation of venules, capillaries and arterioles, abnormal perivascular connective tissue and endothelial cells.

The rationale in the treatment of peptic ulcer disease.

1) In chronic gastric ulcer bed rest, leaving out smoking and carbenoxolone have increased the rate of healing. 2) In chronic duodenal ulcer it has yet to be shown that any medical measure so far significantly altered the course of the disease. 3) The surgical approach to the treatment of chronic duodenal ulcer is based upon three principles, all of them aiming at reducing the acid-pepsin secretion: a) Removal of the acid secreting mucosa decreases the acid secretory capacity of the stomach; b) Removal of the pyloric antrum eliminates the main source of gastrin, the major known humoral excitant of acid secretion; c) Section of the vagi probably renders the acid secreting cells less responsive to humoral stimulation (Brooks). The major problem, however, which is the prevention of recurrent duodenal ulcer is yet unsolved. There is some hope that the new receptor blocking agent metiamid is the first step, and there is even more hope in that the proceedings of this symposium will show us further steps forward.

[Successful treatment of cardiac failure in haemochromatosis by prednisolone and phlebotomies (author's transl)]. / Erfolgreiche Behandlung einer schweren digitalisrefraktären Herzinsuffizienz bei Hämochromatose mit Kortikosteroiden und Aderlässen.

In a female 53 year old patient with severe heart failure in haemochromatosis, not responding to digitalis, treatment with prednisolone (40 mg/da) and phlebotomies eventually led to a permanent remission. She is symptom free 4 years after the event. Phlebotomy every 4--6 weeks is the only actual treatment.

Increased consumption of refined carbohydrates in patients with Crohn's disease.

The nutritional habits of 63 patients with Crohn's disease (C.d.) were explored by means of questionnaires and compared with a control group of 63 persons matched as to age, sex and social status. Before the disease was recognized patients with C.d. consumed 742 grams/week (g/w) sweets and 1380 g/w pastries, during the disease 482 g/w sweets and 905 g/w pastries. The controls only consumed 285 g/w sweets and 563 g/w pastries. The differences between both groups are highly significant. There existed no significant difference in the intake of other foodstuffs such as proteins, fats, vegetables or alcohol. The high intake of refined carbohydrates in patients with C.d. may be partly responsible for its increasing incidence in the developed countries. This might be due to the sugar content as such and/or the food additives.

Effect of acute and chronic ethanol administration on the content of coenzymes linked to energy transfer in the liver of rats fed standard or low-protein diet.

1) In rats fed a standard diet or a protein restricted diet the effect of acute and chronic ethanol administration on liver content of adenine nucleotides was studied. In the long-term experiments the total liver content of NAD and NADP was additionally determined. 2) a single oral ethanol load does not significantly influence the total adenine nucleotide content. Liver AMP content increases immediately following ethanol ingestion about 2-fold and remains elevated for 12 hours. ATP content and ATP/ADP ratio are significantly reduced within 30 minutes after ethanol administration. Both return to initial values after 2 hours adn decrease again thereafter. 3) The increase in the AMP content is dose dependent, i.e. it is more pronounced after small doses of ethanol and is not observed when blood ethanol concentrations are very high. The elevation of the AMP levels during ethanol oxidation is interpreted as a consequence of increased ATP consumption and of inhibition of citric acid cycle. 4) In animals fed nearly protein-free diet, total adenine nucleotide content and ATP content are distinctly reduced. An increase in AMP concentration is not observed in these rats where ethanol oxidation is markedly inhibited. 5) Chronic ethanol application does neither in rats kept on a standard diet nor in those fed a protein restricted regimen affect the liver content of total adenine nucleotides or ATP. Similarly the total content of NAD and NADP shows no major changes. 6) It is concluded that the relatively small alterations in total liver adenine nucleotide content and in the different adenine nucleotide fractions are not important for ethanol-induced fat accumulation or other disturbances in the liver.

[Liver fibrosis. 1 (author's transl)]. / Die Leberfibrose Teil 1.

The mortality of liver cirrhosis has doubled during the past two decades and is still increasing in most of the European countries. One important feature and precursor of liver cirrhosis is liver fibrosis. Its aetiology includes a wide spectrum of well known causes, in Europe most frequently alcohol, virus infection, and chemical agents. The pathomechanism of liver fibrosis is unknown. Diagnostic and therapeutic approaches for early detection and treatment have been recently developed applying the results of pathobiochemical, cellular and clinical research. The composition of the increased hepatic connective tissue suggests the involvement of myofibroblasts and shows similarities to atherosclerotic plaques and lung fibrosis. The isolation, purification and cultivation of cells from liver biopsies offers new avenues for the study of fibroplastic cells. Clinical studies are now facilitated, since products of the collagen synthetic pathway -- procollagen peptides--can be measured in serum with a sensitive radioimmunoassay. Further prospective studies including additional parameters of fibroplasia, such as N-acetyl-beta-D-glucosaminidase, lysyloxidase and prolylhydroxylase will have to demonstrate the diagnostic value of such methods. Even today, they should be applied in therapeutic trials of chronic fibrotic liver diseases. Better knowledge of the molecular regulation of connective tissue, and the use of new animal models and cellular system support a successful search for new therapeutic tools. Above all, limitation of alcohol consumption, vaccination for viral hepatitis and elimination of chemical agents offer the prevention of fibrosis, which calls for major efforts on a nation-wide scale.

Effect of alcohol on microsomal cortisol 4en-5 alpha-reductase in the liver of rats fed on a standard or low protein diet.

Alcohol feeding (40% of total calories over a period of 9 days) increases microsomal cortisol-5 alpha-reductase activity in rat liver distinctly. It is assumed that this is an adaptive response to an increased release of cortisol caused by alcohol administration. Cortisol-5 alpha-reductase activity is decreased to one third of control values in rats fed an isocaloric, low protein diet. The response to alcohol feeding is susta ined in these animals. Phenobarbital treatment (80 mg/kg x day) stimulates 5 alpha-reduction of cortisol per g of microsomes almost twofold. The activity calculated per total liver increases 4-fold. Alcohol administration has no additional effect on cortisol-5alpha-reductase in phenobarbital-treated rats.

[Androgen metabolism and Leydig-cell function in acute and chronic liver disease (author's transl)]. / Androgenstoffwechsel und Leydig-Zellfunktion bei akuten und chronischen Lebererkrankungen

Diurnal variations of plasma testosterone and urinary excretion rates of testosterone-, androsterone-, aetiocholanolone-, and DHA-glucuronide, as well as DHA-sulphate were measured before and after selective Leydig-cell stimulation (with 3 X 5000 IU human gonadotrophin) in eight patients with alcoholic liver cirrhosis, ten with acute hepatitis and four with haemochromatosis. The circadian variation of plasma testosterone and the maximal testosterone concentration after human gonadotrophin stimulation were decreased in patients with cirrhosis and haemochromatosis, while in those with acute hepatitis the diurnal variations were evened out, whereas individual values were within the normal range. Urinary excretion of free testosterone and testosterone glucuronide was significantly reduced in those with cirrhosis and haemochromatosis before and after stimulation. The urinary pattern of C19 steroid metabolites was markedly changed in favour of the 5 alpha-steroids in acute heaptitis, cirrhosis, and haemochromatosis.

[Liver fibrosis. 2]. / Die Leberfibrose Teil 2.

The mortality of liver cirrhosis has doubled during the past two decades and is still increasing in most of the European countries. One important feature and precursor of liver cirrhosis is liver fibrosis. Its aetiology includes a wide spectrum of well known causes, in Europe most frequently alcohol, virus infection, and chemical agents. The pathomechanism of liver fibrosis is unknown. Diagnostic and therapeutic approaches for early detection and treatment have been recently developed applying the results of pathobiochemical, cellular and clinical research. The composition of the excess hepatic connective tissue suggests the involvement of myofibroblasts and shows similarities to atherosclerotic plaques and lung fibrosis. The isolation, purification and cultivation of cells from liver biopsies offers new avenues for the study of fibroplastic cells. Clinical studies are now facilitated, since products of the collagen synthetic pathway - procollagen peptides - can be measured in serum with a sensitive radioimmunoassay. Further prospective studies including additional parameters of fibroplasia, such as N-acetyl-beta-D-glucosaminidase, lysyl-oxidase and prolyl-hydroxylase will have to demonstrate the diagnostic value of such methods. Even today, they should be applied in therapeutic trials of chronic fibrotic liver diseases. Better knowledge of the molecular regulation of connective tissue and the use of new animal models and cellular systems support a successful search for new therapeutic tools. Above all, limitation of alcohol consumption, vaccination for viral hepatitis and elimination of chemical agents offer the prevention of fibrosis, which calls for major efforts on a nation-wide scale.

[Dietary habits of patients with ulcerative colitis (author's transl)]. / Ernährungsgewohnheiten der Patienten mit Colitis ulcerosa.

The nutritional habits of 114 patients with ulcerative colitis were investigated by means of questionnaires and compared with a control group of 114 persons matched to age, sex and social status. The differences between both groups can be explained by an adaptation of dietary habits of patients with chronic inflammatory bowel disease (ulcerative colitis). Patients with ulcerative colitis consumed significantly more cereal products and potatoes but significantly less milk products, coffee, tea, fruit-juice, lemonade, vegetables, fruit and alcohol than the control group.