Organic carbon-14 in the Amazon river system.

Coarse and fine suspended particulate organic materials and dissolved humic and fulvic acids transported by the Amazon River all contain bomb-produced carbon-14, indicating relatively rapid turnover of the parent carbon pools. However, the carbon-14 contents of these coexisting carbon forms are measurably different and may reflect varying degrees of retention by soils in the drainage basin.

Assessment of pretransplant prognosis in patients with cirrhosis.

The objective of this prospective study was to assess the prognostic value of dynamic liver function tests and traditional methods of evaluating liver function in potential candidates for hepatic transplantation. Patients who underwent orthotopic liver transplantation within the follow-up period of 120 days were excluded. The study included 107 adult and 57 pediatric patients with cirrhosis. Postnecrotic cirrhosis was present in 107 and biliary cirrhosis in 57 of 164 patients. During the follow-up period, 26 of 164 patients died of their liver disease. At the time of inclusion, we recorded monoethylglycinexylidide (MEGX) formation from lidocaine, indocyanine green (ICG) half-life, bilirubin and albumin serum concentration, activity of cholinesterase and alkaline phosphatase, prothrombin time, the clinical complication of ascites, and--in adults--the Pugh score also. These variables were subjected as covariates to a survival analysis (Cox proportional hazards regression model) using separately the data from adults, pediatric patients, all patients with postnecrotic cirrhosis, and all patients with biliary cirrhosis. In all of these four subgroups there was a significant relationship between MEGX and ICG test results and the 120-day survival. In the stepwise analysis, none of the remaining parameters contributed to a further relevant improvement of our predictive ability when added to the values of ICG and MEGX. Our results suggest that the ICG and the MEGX test are superior to conventional liver function tests and the Pugh score in assessing short-term prognosis in cirrhotics independently from the etiology of the underlying liver disease. These findings may have important implications for determining the optimum timing of transplantation.

Effect of liposome-entrapped methotrexate on Ehrlich ascites tumor cells and uptake in primary liver cell tumor.

A therapeutically useful concentration (0,5 mg/ml) of Methotrexate was prepared in negatively charged artificial liposomes (lecithine: cholesterol: dicetylphosphate=5:5:1 molar ratios). Entrapment yield after separation on Sepharose 6B is nearly 100%. In contrast to free Methotrexate the liposome entrapped folic acid antagonist is eliminated only slowly by the kidneys and after intravenous application it is unevenly distributed in the body of mice, the highest concentrations being found in liver and spleen. Daily injections (7.5 mg/kg/day) of entrapped Methotrexate for 5 days into the tail vein of Ehrlich ascites tumor bearing mice reduced both tumor cell count and the production of ascites fluid about fourfold as compared to mice receiving the same dose of Methotrexate in the free form. Six hours after intravenous application of liposome entrapped Methotrexate the tissue concentration in normal liver is ca. 20-fold higher than when the same amount is applied in the free state. On the other hand, only a little uptake of liposome entrapped Methotrexate was detected in the tissue of nitrosamine-induced primary liver tumor when compared to normal liver tissue of rats.

Tests of bile-acid and vitamin B12 metabolism in ileal Crohn's disease.

The bile-acid breath test, fecal analysis of labeled bile acids, and Schilling test were used to study bile-acid and vitamin B12 metabolism in 31 patients with ileal Crohn's disease. Results of the bile-acid breath test were positive for 42% of the patients; Schilling test, 42%; fecal analysis of bile-acid labels, 19%. Combination of the tests increased the percentage of positive cases to 65. About 50% of the patients who had positive breath tests had evidence of normal bile-acid absorption, indicating increased bile-acid deconjugation by small-intestinal bacteria. The other 50% had evidence of various degrees of bile-acid malabsorption. Disease activity did not correlate with results of any test. Extent of ileal involvement correlated with results of the bile-acid tests, but not with those of the Schilling test. The study demonstrates that there is a wide spectrum of disturbances of bile-acid and vitamin B12 metabolism in ileitis, and that the tests should be useful in the diagnostic evaluation of patients with proven or questionable Crohn's disease who have diarrhea and malabsorptive abnormalities that could be related to disturbances of bile-acid and vitamin B12 metabolism.

Progress in the enzyme diagnosis of liver disease: reality or illusion?

This paper discusses the progress of enzyme diagnosis by different examples. These include: the requirement for improved enzymological screening, despite the introduction of a test for hepatitis C; the imbalance between the popularity of "unexplained chronic aminotransferase elevations" and efforts to solve the inherent problems; the inadequate attempts to use the metabolic changes in the hepatocytes to improve diagnosis, prognosis, and pathophysiological understanding of viral liver diseases; the remarkable investigations into the 2'-5'-oligoadenylate synthetase for better control of interferon therapy in chronic viral hepatitis; the use of enzymes as markers of etiology, particularly for the detection of alcohol induced liver diseases; the continuing preference for the aminotransferases in this scenario although the ratios of aspartate aminotransferase over alanine aminotransferase, or of mitochondrial aspartate aminotransferase over total aspartate aminotransferase activity, largely depend on the severity and intralobular localization of damage and the stage of the liver disease.

Advances in the enzyme diagnosis of pancreatic diseases.

This paper reviews recent developments of analytical methods for the determination of alpha-amylase, of its isoenzymes, and of lipase. The evaluation of severity and etiology of acute pancreatitis by enzyme assays, e.g., pancreatic elastase 1, phospholipase A2, and routine enzymes are discussed. The limited significance of enzyme determinations as compared to imaging and endoscopic procedures for the diagnosis of chronic pancreatitis is demonstrated. Indirect "tubeless" tests for the evaluation of pancreatic exocrine insufficiency with respect to the secretion of chymotrypsin (chymotrypsin in stool and NBT-PABA test) and cholesterol esterase (pancreolauryl test) are reviewed. Finally, the superiority of morphologic investigations over biochemical tests for the timely detection of pancreatic carcinoma is shown.

Creatine kinase (EC-No.2.7.3.2) and creatine kinase isoenzymes during pregnancy and labor and in the cord blood.

Total CK and CK isoenzyme activity in serum was investigated during pregnancy, labor and after delivery as well as in cord blood. Total CK was decreased in the second trimester of pregnancy but increased in late pregnancy. Low CK-MB activity in serum was found in patients with early labor pains. CK-BB activity could never be detected during pregnancy. Total CK and isoenzyme activity increased after delivery. The rise of total CK and CK-MB in maternal serum is directly correlated with the following: type of delivery, duration of labor, parity of the mother, and birth weight. From this it can be deduced that postpartum CK levels depend on skeletal muscle activity as well as on the activity of uterine muscle. Prematures and infants "small for date" have significantly lower total CK and slightly more elevated CK-BB activity in cord blood than children of normal maturity. CK-BB activity is much more pronounced in high risk patients with low Apgar score.

Gabexate mesilate and camostate: new inhibitors of phospholipase A2 and their influence on the alpha-amylase activity in serum of patients with acute pancreatitis.

The new synthetic polyvalent protease inhibitors gabexate mesilate (ethyl-p[6-guanidinohexanoyloxy]-benzoate methansulfonate) and camostate (N,N-dimethylcarbamoylmethyl-4-[4-guanidinobenzoyloxy]-phenylacetate methansulfonate) were tested for possible inhibition of phospholipase A2 activity. In a pilot study, we treated 17 patients suffering from acute pancreatitis with continuous intravenous administration of gabexate mesilate, 450 mg/d. The results were compared with a placebo group (same standard therapy) of 21 patients suffering from acute pancreatitis. In vitro experiments showed that, at concentrations between 10(-4) and 5 X 10(-4) mol/L (depending on the enzyme assay employed) for gabexate mesilate and between 10(-3) and 5 X 10(-4) mol/L for camostate, a 50% reduction in phospholipase A2 activity was effected. Comparing the two groups of acute pancreatitis patients after 6 days of treatment with gabexate mesilate, we observed a statistically significantly lower alpha-amylase activity in the serum of treated patients compared with the placebo group.

Standardization by reference methods: a German viewpoint.

The problems of applying optimized as well as standardized methods to the determination of enzyme activities in modern clinical laboratories are described. The failure of the so-called 'New Concept of Reference Method Values' in the quality assessment of enzyme assays is evidenced, and the advantages of standardized methods rather than only standard materials is demonstrated. Finally, the great similarities among European national recommended methods for enzyme assay is emphasized by a comparison of results obtained in estimating 5 enzymes.

Glutamate dehydrogenase: biochemical and clinical aspects of an interesting enzyme.

The molecular properties and possible metabolic functions of glutamate dehydrogenase (GLDH-EC 1.4.1.3) are described. The distribution of this enzyme in the body and particularly in the liver are outlined. The significance of these properties for GLDH release into the extracellular space, for the distribution and elimination of the enzyme and, foremost, for the assay of GLDH as a diagnostic indicator of hepatic and biliary disease are shown. Analytical methods are reviewed.

Diagnostic application of mitochondrial enzymes and isoenzymes.

Evolutionary, topological and metabolic aspects of mitochondrial enzymes and isoenzymes are reviewed, and the structural and functional heterogeneity of mitochondria is demonstrated. Primary deficiencies of mitochondrial enzymes are described and the need for their proper recognition is illustrated. Species differences of secondary dysfunction of mitochondrial enzymes are shown. The release of mitochondrial enzymes is compared to that of cytosolic enzymes from liver and heart muscle cells and the diagnostic significance of assays of mitochondrial enzymes in serum is evidenced. Possible mechanisms of mitochondrial enzyme release from cells and unresolved questions pertaining to this process are discussed in light of potential diagnostic utility of mitochondrial enzymes in serum.

Metabolic responses to lipid infusions in patients with liver cirrhosis.

Energy expenditure, whole body substrate oxidation rates and arterial substrate concentrations were measured in 14 patients with liver cirrhosis and 13 control subjects before and during sequential infusions of a long chain (LCT) or a medium chain triglyceride emulsion (MCT) without and with concomitant insulin plus glucose infusions. Resting energy expenditure, basal substrate oxidation rates and the arterial concentrations of glucose, lactate, triglycerides and ketones were normal, whereas plasma free fatty acids and glycerol were both increased in patients with liver cirrhosis. The arterial plasma triglyceride and free fatty acid concentrations as well as whole body lipid oxidation rate rose in response to LCT in both groups and the maximum lipid oxidation rate was 1.1 or 1.3 mg/kg fat free mass x min in controls and in cirrhotics, respectively (n.s.). Concomitantly, glucose oxidation rate fell to 65% of basal values in controls (p < 0.01), but remained nearly unchanged in the cirrhotic group (89% of the basal value; n.s.). The increase in plasma ketones was reduced to 67% of control values in liver cirrhosis (p < 0.01). Only a slight effect on energy expenditure was observed in both groups. When compared to controls, liver cirrhosis impaired insulin-induced increases in glucose disposal (-30%, p < 0.01) and in non oxidative glucose metabolism (-93%, p < 0.01). Concomitantly, normal increases in energy expenditure, glucose oxidation rate and the arterial plasma lactate concentrations and normal decreases in lipolysis, lipid oxidation and ketogenesis were observed in patients with liver cirrhosis. When lipids were given together with glucose, energy expenditure and lipid oxidation increased in controls, but glucose was the preferred fuel oxidised and lipid-induced thermogenesis was reduced in the cirrhotic group. Using a 50% MCT-emulsion, plasma free fatty acid concentrations further increased, but energy expenditure and lipid oxidation remained unchanged in both groups and further increases in plasma ketones were only observed in controls. Infusing glycerol in a subgroup of patients showed no thermogenic effect and a reduced glycerol clearance in liver cirrhosis.

[Hepatobiliary sequential-scintigraphy--progress in the evaluation of postcholecystectomy complains (author's transl)]. / Hepatobiliäre Sequenzszintigraphie--Fortschritte in der Abklärung von Rest- und Nachbeschwerden Cholezystektomierter.

The hepatobiliary sequential-scintigraphy is a nuclear diagnostic procedure useful in assessing the function of liver and biliary system. 40 patients with and 20 patients without complains following cholecystectomy were examined. The value of this method in establishing biliary causes for such complains is demonstrated by typical cases. Simplicity and safety in application as well as diagnostic sensitivity should place the method in the first place evaluating postcholecystectomy complains. Succeeding indirect and direct radiologic techniques then may be used systematically with benefit for the patient and physician. Results indicate, that the procedure will be essential as well in evaluation as in analysis of nature and frequency of such complains by its superior presentation of intrahepatic bilestasis and functional mechanisms of the biliary system including the sphincter of Oddi.

[Kinetics of whole-body water and bromide space in patients with liver cirrhosis (author's transl)]. / Kinetik des Ganzkörperwassers und des Bromidraumes bei Leberzirrhotikern.

The kinetics of extracellular water (82Br) and total body water (THO) in controls and patients with liver cirrhosis are studied. Analysis of the plasma activity of the radionuclides as a function of time shows that distribution volumes and kinetics can be described by a linear open three-compartment model and that the volumes are of about equal size. Measuring is carried out in the central compartment in which the radionuclides are injected as a bolus. In cirrhotic patients equilibration into a third compartment is attained about four times slower than in controls. Elimination is reduced by about the same factor. Reduced diffusion and effective blood flow in the cirrhotic patients are discussed as possible reasons for the differences.

CO2 laser management of laryngeal stenosis.

The introduction of the carbon dioxide laser as an endoscopic surgical instrument has stimulated interest in its application for removal of stenotic lesions of the larynx. Clinical reports have indicated mixed results in the efficacy of this treatment modality. Nineteen large dogs received acute subglottic injuries from a high-speed electric drill and electrocautery. All animals developed obstructing lesions from 7 to 21 days after injury. With at least weekly removal of granulation tissue and dilations, all animals developed mature subglottic and/or posterior commissure scars. Two animals required tracheostomy. The 15 animals in the experimental group underwent 16 laser procedures. Three animals had vaporization of one third of the scar, three of one half of the scar, and three had total circumferential vaporization. Five animals underwent microtrapdoor flap procedures. Of these, four had a single flap and one had three separate flaps created. In the remaining animal in the experimental group a glottic web developed, which was totally ablated. In one animal treated with a microtrapdoor flap procedure a posterior sinus tract also developed and was treated with laser ablation. The animals undergoing segmental resection of scar demonstrated no improvement in airway size. Those undergoing total resection experienced a worsening of the condition. Those undergoing microtrapdoor flap repair demonstrated moderate improvement in airway size. It can be concluded that large areas of scar removal in the larynx by the CO2 laser will result in prompt recurrence and possible worsening of the scar and smaller submucosal resection of the scar, with preservation of mucosa by the microtrapdoor flap technique, may be helpful in improving the airway.

Whole-gut irrigation as antiendotoxinaemic therapy in inflammatory bowel disease.

Marked endotoxaemia was found in 12 patients suffering from severe relapse of chronic inflammatory bowel disease. These patients did not respond satisfactorily to conservative treatment. Whole gut irrigation was employed to reduce drastically the absorbable endotoxin pool in the gut. Following the lavage the condition of all the patients thus treated improved. Plasma endotoxins dropped rapidly, serum iron increased, and in 7 febrile patients body temperature normalized. The results obtained suggest a beneficial use of whole gut irrigation as a therapeutic means in endotoxaemia associated with inflammatory bowel disease.

Epidemiology and treatment of gastric Campylobacter pylori infection: more questions than answers.

Two-hundred and ten consecutive patients undergoing routine gastroscopy were additionally investigated for evidence of Campylobacter pylori (C.p.). 106 patients were positive in one or more tests: 99.1% using a rapid urease detecting test (CLO-test), 80.2% histology, 78.3% cytology and 60% culture. We found no difference between the CLO-test results from biopsies taken from different parts of the stomach in individual patients. C.p. was found in 100% of patients with significant chronic antral gastritis, 67.7% with gastric ulcers, 65% with duodenal ulcers and in 12.1% of normal individuals. The C.p. infection was apparently eliminated in 50% of cases treated with bismuth subsalicylate (BSS) for four weeks. The combination of BSS with amoxicillin, tinidazole or an H2-receptor antagonist offered no advantage over BSS alone. Treatment with BSS led to improvement in symptoms and histological findings including healing of ulcers in patients with or without persistent C.p. infection. The recurrence of C.p. infection after apparently successful treatment was, however, 75% in 4 weeks. In conclusion, C.p. infection correlates strongly with the presence of chronic gastritis, and significantly with gastric and duodenal ulceration. The best diagnostic approach is the combination of a rapid urease detecting test and histology. C.p. infection is of long duration and difficult to eliminate. The most effective treatment for C.p. infection remains BSS as single agent.

Energy expenditure in children with type I diabetes: evidence for increased thermogenesis.

The aim of the study was to assess whether increased energy expenditure causes the negative energy balance (tissue catabolism) commonly seen in children with insulin dependent (type I) diabetes. Resting metabolic rate and thermogenesis induced by adrenaline were measured in five healthy children and 14 children with type I diabetes who were all free of clinical signs of late complications of diabetes mellitus but differed in their degree of glycaemic control (in eight glycated haemoglobin concentration was less than 10% and in the six others greater than or equal to 10%). When compared with the control subjects children with type I diabetes had normal resting metabolic rates but their urinary nitrogen excretion was significantly raised (11.5 (SD 5.4) mg/min in those with glycated haemoglobin concentration less than 10%, 11.6 (5.2) mg/min in those with concentration greater than or equal to 10% v 5.4 (3.0) mg/min in control subjects). During the infusion of adrenaline the diabetic children showed a threefold and sustained increase in thermogenesis and disproportionate increases in the work done by the heart, in lipid oxidation rate, and in plasma concentrations of glucose, free fatty acids, and ketone bodies. The increased thermogenic effect of adrenaline did not correlate with the degree of glycaemic control. Increased thermogenesis may explain the tissue wasting commonly seen in children with type I diabetes during intercurrent stress.

The influence of colostral leukocytes on the immune system of the neonatal calf. III. Effects on phagocytosis.

The influence of colostral leukocytes on the activity of phagocytic cells from the blood of calves, in particular the concentration of neutrophils (PMN) in blood, ingestion of Streptococcus agalactiae, reduction of NBT-dye and activity of lysozyme, was investigated for four weeks using four groups. The calves received either complete colostrum (COL+, n = 16), cell depleted colostrum (COL-, n = 16), cell-supplemented milk-substitute (MS+, n = 7) or pure milk-substitute (MS-, n = 6). Calves of the COL+ group had a significantly lower PMN concentration in their blood on day 2 and a significantly higher activity of lysozyme during their first three weeks of life as compared to the COL- animals. A postnatal increase in number of ingested Streptococcus agalactiae test bacteria per 100 phagocytic cells occurred later in the COL+ calves than in the COL-. No difference between both COL groups in NBT-reduction was observed. The calves of the MS+ group showed higher lysozyme activity and a retarded increase in the ingestion of test bacteria during the first week of life as compared to the MS-. The MS+ group had a transient neutrophilia on the second day of life while the concentration of PMN was not altered in the MS- from the first to the second day.

The influence of colostral leukocytes on the immune system of the neonatal calf. I. Effects on lymphocyte responses.

The influence of colostral leukocytes on lymphocyte counts in the blood of calves and on lymphocyte responses, in particular the Concanavalin A-induced blastogenic response in vitro and the formation of antibodies against sheep erythrocytes, was investigated for four weeks postnatum using four experimental groups. The calves received either complete colostrum (COL+, n = 16), cell-depleted colostrum (COL-, n = 16), colostral cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during their first three days of life. In contrast to the calves fed with cell-depleted colostrum (COL-) the calves fed with complete colostrum (COL+) showed no decrease of lymphocyte numbers in the blood on the second day of life, uniform blastogenic responses to two different Concanavalin A concentrations, slightly enhanced antibody formation against sheep erythrocytes and a high spontaneous proliferation of mononuclear cells during the first week of life. In the calves fed with milk-substitute supplemented with colostral cells (MS+) a higher blastogenic response to Concanavalin A and an intensified formation of antibodies against sheep erythrocytes was observed as compared to the MS- calves. A passage of vital colostral lymphocytes through the intestinal wall is postulated. They seem to stimulate and regulate the blastogenic response and enhance the T-helper cell-dependent formation of antibodies against sheep erythrocytes in calves.