Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay.

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.

Macrolipasemia: a rare cause of persistently elevated serum lipase.

This report describes a variant form of lipase found in a patient with cryptogenic liver cirrhosis. Serum lipase in this patient showed persistently increased activity with simultaneously normal activity of amylase. Results of exclusion chromatography demonstrate that the lipase activity in the serum of this patient eluted as a macromolecule. Since macromolecular complexes were not fixed by protein A, it seems unlikely that lipase is attached to IgG. Tests of the sera from 20 patients with raised serum lipase activity in acute pancreatitis or an acute episode of chronic pancreatitis revealed, in two patients, that a small but reproducible proportion of the total lipase activity eluted in the region of the macrolipase. In addition, 10% and 18% of the total lipase activity was found in the elution region of the macrolipase in two commercial pooled sera used for quality control. The results show that, in rare cases, macrolipasemia must be considered a possible cause of raised serum lipase activity.

Chromogenic endotoxin assay in plasma. Selection of plasma pretreatment and production of standard curves.

The aim of this study was to define the optimal conditions for the plasma pretreatment and to improve the production of standard curves for plasma endotoxin determination by a chromogenic substrate assay. Endotoxin standard from E. coli O 111:B 4 (0-50 ng/l) was added to pyrogen-free water or to plasma samples from 12 healthy subjects and 24 alcoholics, before pretreatment by heating (75 degrees C, 5 minutes) or with perchloric acid (0.32 mol/l). When endotoxin standard curves were determined using a microprocessor-controlled reader, the slopes of the curves obtained with plasma differed from those with pyrogen-free water. The slope of the standard curve prepared with plasma samples from different patients exhibited marked interindividual variations. Compared with the heating method, the perchloric acid method gave more variable results and a lower recovery of added endotoxin, especially in plasma from alcoholics. The results permit the following conclusion: 1. For plasma endotoxin determination, a standard curve should be prepared for each individual plasma sample. 2. The endotoxin standard should be added before pretreatment of the plasma. 3. Pretreatment of the plasma by heating at 75 degrees C for 5 minutes provides more reliable results than pretreatment with perchloric acid.

Effect of acute ethanol ingestion on human gastric luminal prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha.

In healthy human volunteers we evaluated the effect of a single oral dose of 1 g/kg of alcohol (12.5%, v/v) on the output of prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha in the gastric juice. In control experiments performed at intervals of 5-8 days, the subjects received the identical volume of water. Ninety minutes after the ingestion of alcohol, or water, first the basal secretion and subsequently the secretion after injection of pentagastrin (6 micrograms/kg, i.m.) were collected over periods of 60 min. The concentrations of the three prostaglandins were determined by radio-immunoassay. After ingestion of alcohol, the volume of gastric juice in response to pentagastrin stimulation was reduced by 24.6%, as compared with the control period. Ingestion of alcohol led to a significant reduction in the concentration of prostaglandin E2 (-42.7%) after stimulation with pentagastrin. The prostaglandin E2 output per hour was markedly inhibited by the ingestion of alcohol, both in the basal period (-47%) and after stimulation with pentagastrin (-55%). While stimulation with pentagastrin did not influence the secretion of PGE2 or PGF2 alpha, the output of 6-keto-PGF1 alpha increased appreciably (+88%) after the administration of pentagastrin. Alcohol also significantly (-28%) inhibited the secretion of 6-keto-PGF1 alpha in the period following the administration of pentagastrin. It is supposed that the inhibition of the secretion of prostaglandin E2 and 6-keto-prostaglandin F1 alpha by acute alcohol ingestion, might be of significance for the development of alcohol-induced mucosal damage in the stomach.

Effect of acute and chronic alcohol feeding on prostaglandin E2 biosynthesis in the small intestine of the rat.

The effect of acute and chronic alcohol ingestion on the PGE2 synthesis and PGE2 content in the duodenum and ileum was studied in rats. Following a single oral load of 20% alcohol (v/v; 4 g/kg body weight) the synthesis of PGE2 in isolated microsomes from both parts of the small intestine did not differ from that in control rats during the first 8 hours, but was increased significantly after 24 hours. Feeding a liquid diet containing alcohol (37% of total calories) for 1 week led to enhanced PGE2 synthesis in the duodenum. After feeding the diet for 6 and 12 weeks the rate of PGE2 synthesis was significantly reduced in the duodenum (-73% and -55%) and ileum (-34% and -45%) as compared with the control group. The PGE2 content of the tissue was not significantly changed 24 hours after the single alcohol load and after 1 week of feeding the alcohol-containing diet. However, after 6 and 12 weeks' feeding, the PGE2 content was reduced in both parts of the small intestine. The results suggest a biphasic response to alcohol of PGE2 synthesis in the small intestine. The increased rate of PGE2 synthesis in the initial phase might reflect an adaptive response to the injurious effect of alcohol which cannot be maintained after long-term ingestion of alcohol.

Effect of acute and chronic ethanol administration in rats on PGE2 formation in microsomes from stomach and small intestine.

Prostaglandin E2 formation and content has been measured in the stomach and small intestine of rats after acute and chronic ethanol ingestion. Chronic ethanol administration for 6 and 12 weeks inhibits PGE2 synthesis and reduces PGE2 content (12 weeks) in all parts of the upper gastrointestinal tract, while after ethanol ingestion up to 1 week PGE2 synthesis is decreased only in the stomach.

[Bowenoid papulosis and carcinoma in situ of the cervix uteri in sex partners. An example of the transmissibility of HPV-16 infection]. / Bowenoide Papulose und Carcinoma in situ der Cervix uteri bei Sexualpartnern. Ein Beispiel für die Ubertragbarkeit der HPV-16-Infektion.

The development of bowenoid papules in a 20-year-old man and a carcinoma in situ of the portio uteri of the 22-year-old female sexual partner is reported. In both lesions HPV-16 DNA could be detected by molecular biological means. This observation led us to the conclusion that HPV 16 had been transmitted sexually. The same seems to be true for HPV-11-induced condylomata acuminata, which appeared on the external genitalia of both patients after recuperation from the HPV-16-induced lesions and conisation treatment. The clinical significance of this observation and its consequences for dermatologists and gynecologists are discussed.