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Biomedical subjects

S Skrede

Publications and source records attributed to S Skrede.

At least 73 records · Page 4Linked to original sources

Diagnostic and prognostic value of laboratory tests assessed in a follow-up study of 200 patients with liver disease.

Two hundred patients with liver disease were re-studied after six to eight years. The initial routine diagnosis (mainly based on morphological criteria) was confirmed in almost 80% of cases of chronic liver disease. In chronic active hepatitis, agreement was found in 86%. An alternative classification based on cluster analysis of clinical chemical results from the first admission was also to a great extent confirmed by the follow-up study. Discriminant analysis of clinical chemical data correctly allocated 94% of patients with alcoholic cirrhosis (who had low haptoglobin and albumin) into groups with different prognosis. Clinical chemical results differed between verified and non-verified cases of primary biliary cirrhosis. By retrospective examination , we found that 15 of 16 patients with this disease or chronic active hepatitis who were initially misclassified by biopsy findings could be correctly diagnosed by discriminant analysis of clinical chemical results.

Biopsy↗

A long-term follow-up study of the hepatic copper and serum ceruloplasmin concentrations in patients with chronic liver disease.

Hepatic copper content, measured by neutron activation analysis, has been studied in 70 patients during a median observation period of 3 years. In 15 patients with chronic active hepatitis the median hepatic copper content was 39 micrograms/g dry weight at the start and 28 micrograms/g dry weight at the end of the observation period, during which the clinical condition was improved in most patients. The hepatic copper content did not change significantly (41 versus 54 micrograms/g dry weight) in 28 patients with hepatobiliary disorders associated with inflammatory bowel disease. In 27 patients with primary biliary cirrhosis the median hepatic copper concentration was initially 176 micrograms/g dry weight, and at the follow up 186 micrograms/g dry weight. Serum ceruloplasmin was elevated in most of the patients with hepatobiliary disorders associated with inflammatory bowel disease and in all the patients with primary biliary cirrhosis and remained at high levels throughout the observation period. In primary biliary cirrhosis the hepatic copper content was correlated with bilirubin and alkaline phosphatases but not with ceruloplasmin, coagulation factors, or aminotransferases. Ceruloplasmin was not significantly correlated with other "liver tests". We conclude that the hepatic copper content and serum ceruloplasmin were remarkably constant during 3 years of observation in various liver disorders. Our study gave no evidence of a hepatotoxic effect of copper, since no relation between the initial hepatic copper concentration and the clinical course could be detected.

Ceruloplasmin↗

The effect of a standardized work load on 'liver tests' in patients with chronic active hepatitis.

Since opinions differ about the effect of physical activity in chronic liver disease, we performed a submaximal ergometric exercise test in 17 patients with chronic active hepatitis in clinical remission while receiving immunosuppressive therapy and in 5 patients with portacaval shunts. The calculated oxygen consumption was low in most patients. Blood samples were drawn before the exercise and 4 h, 24 h, and 48 h after. No changes occurred in serum ALAT, ASAT, ALP, CK, GT, or prealbumin. The clinical condition was not influenced by the exercise test. We conclude that moderate physical activity, at least of short duration, is well tolerated by patients with chronic active hepatitis.

Adult↗

The levels of serum enzymes, plasma proteins and lipids in normal infants and small children.

A group of 291 children aged 3 weeks to 6 1/2 years was examined at a public maternal and child health center and 260 of them - who were considered to be healthy - were included in the present study. By venipuncture, serum was obtained for the analysis of 6 enzymes, and plasma for the estimation of 9 proteins and for lipid analyses. In different age groups, high levels were found for alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatine kinase and gamma-glutamyl transferase. Haptoglobin, alpha 1-antitrypsin, prealbumin and transferrin were present at low concentrations during the first months of life. Transferrin rose later in childhood to above adult levels. Only immunoglobulin M showed a sex difference, with higher values for girls. Breast-fed infants had higher (non-fasting) concentrations of cholesterol and triglycerides than formula-fed babies, and they also had higher levels of aspartate aminotransferase and alanine aminotransferase.

Blood Proteins↗

Synthesis of sterols and proteins in liver biopsies from obese patients subjected to gastric or jejunoileal bypass operations.

Incorporation of 14C-acetate into digitonin-precipitable sterols and of 3H-leucine into proteins was examined in per- or post-operative liver biopsies from morbidly obese patients subjected to either gastric or jejunoileal bypass operations. Biopsies obtained from non-obese patients without liver disease served as controls. Incorporation of precursors into sterols and proteins in peroperative biopsies from obese patients (mean weight, 131 kg) did not differ from that of control subjects (mean weight, 64 kg). However, biopsies obtained from eight patients 11-53 months after jejunoileal bypass (mean weight loss, 32% of initial weight) showed an eightfold increased 14C incorporation into sterols, whereas incorporation of 3H-leucine into proteins did not differ from that of the control group. The results in postoperative biopsies (3-12 months) from 9 patients subjected to gastric bypass (mean weight loss, 25% of initial weight) did not differ significantly from those in 15 controls. The markedly stimulated biosynthesis of sterols in patients with jejunoileal bypass might reflect increased faecal excretion of cholesterol and bile acids, causing reduced feedback control mediated by bile acids and cholesterol.

Adolescent↗

Usefulness of serum nucleotide pyrophosphatase and phosphodiesterase I activities in classifying liver disease.

Nucleotide pyrophosphatase and phosphodiesterase I activities were determined in sera from 126 patients with different types of liver disease and in two additional groups of patients with intra- and extrahepatic cholestasis, respectively. Both activities probably represent the same enzyme, and were positively correlated with alkaline phosphatase, lipoprotein X, and several other tests reflecting cholestasis. Also, we found by discriminant analysis that tests for cholestasis frequently replaced the results of both enzymes. In some groups of liver disease, nucleotide pyrophosphatase and phosphodiesterase I were correlated with the concentrations of prealbumin and albumin. The sensitivity of phosphodiesterase I (and nucleotide phosphatase) is rather low when compared with alkaline phosphatase, and we do not recommend it for use in the clinical routine. Nevertheless, it appears to be of potential value for studies on classification of liver diseases, adding information to a panel of 20 commonly used "liver tests" by appearing in some of the best four test-sets for distinguishing between groups of liver disease by discriminant analysis.

Blood Chemical Analysis↗

Assay of intermediates in bile acid biosynthesis using isotope dilution--mass spectrometry: hepatic levels in the normal state and in cerebrotendinous xanthomatosis.

The synthesis of 2H4-labeled 5 beta-cholestane-3 alpha, 7 alpha-diol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, 7 alpha-hydroxy-4-cholesten-3-one, and 7 alpha,12 alpha-dihydroxy-4-cholesten-3-one is described. A mixture of these compounds, together with 2H3-labeled 5-cholestene-3 beta, 7 alpha-diol, was added to extracts of different subcellular fractions of liver. After purification by high performance liquid chromatography and conversion into trimethylsilyl ethers, the amounts of different endogenous unlabeled steroids were determined by selected ion monitoring. In normal liver, the concentration of 5-cholestene-3 beta, 7 alpha-diol (about 0.1-0.2 microgram/ml protein) was higher than the concentration of the other steroids (about 0.01-0.05 microgram/mg protein). The concentration of the different steroids was highest in the microsomal fraction of the liver homogenate. In a liver sample from a patient with cerebrotendinous xanthomatosis (CTX), the amounts of the 12 alpha-hydroxylated steroids were considerably higher than in the normal liver. The levels of 7 alpha-hydroxy-4-cholesten-3-one and 5 beta-cholestane-3 alpha, 7 alpha-diol were similar or only slightly higher than in the liver of the control patients. The concentration of 5-cholestene-3 beta, 7 alpha-diol was very high in the mitochondrial fraction of the CTX-liver. The findings are in accordance with the previous demonstration that the basic metabolic defect in CTX is a lack of the mitochondrial 26-hydroxylase. The results are further compatible with the contention that 7 alpha,26-dihydroxy-4-cholesten-3-one is an important intermediate in the normal bile acid biosynthesis.

Bile Acids and Salts↗

Release from intracellular enzymes from cutaneous cells after non-necrotizing damage by ultraviolet light.

Experimental blisters were produced with suction on normal human skin and simultaneously on skin inflamed after exposure to middle wave ultraviolet light. Total proteins and marker enzymes for the plasma membrane, cytosol, lysosomes, peroxisomes, mitochondria, and microsomes were assayed in the blister fluid. In blisters on erythematous skin, a large increase of lactate dehydrogenase from cytosol was noted. A small increase of the plasma membrane marker phosphodiesterase I and some increase of alpha-mannosidase from lysosomes was found. No significant increase in total proteins or in microsomal marker enzymes were not detectable. It is concluded that cutaneous cells to some extent may lose intracellular enzymes without visible signs of irreversible damage (necrosis), but that an UVB-induced injury/regeneration cycle probably explains the enzyme release.

Aged↗

Reversible cellular damage by dimethyl sulfoxide reflected by release of marker enzymes for intracellular fractions.

Irritative human skin reactions were induced by dimethyl sulfoxide (DMSO). Suction blisters were raised on these areas within 1.5 h after their induction and simultaneously on normal skin. The activities of marker enzymes for subcellular fractions in the suction blisters were determined. In suction blisters raised on the DMSO induced wheals significantly higher values of the cytosol enzyme lactate dehydrogenase and also some higher values of the lysosomal marker alpha-mannosidase were found than in blisters produced on normal skin. Membrane-bound marker enzymes for subcellular fractions were not elevated. Since the skin is macroscopically completely normal 24 h after application of DMSO, our results indicate that the induction of a certain membrane damage with release of intracellular enzymes does not necessarily lead to cellular necrosis.

Aged↗

The relation between the levels of HDL cholesterol and the capacity for removal of triglycerides.

In twenty-two men with "normal" findings clinically, by exercise ECG and laboratory tests, we performed an i.v. fat tolerance test, measurement of LCAT activity and the activities of post-heparin triglyceride lipases, and estimated serum lipids. HDL cholesterol was positively correlated to lipoprotein lipase (r=0.50, p < 0.05) and to the fractional removal rate of exogenous fat (r=0.59, p < 0.01), and negatively to the fasting levels of triglycerides (r=-0.65, p < 0.01). LCAT was neither correlated to HDL cholesterol nor to the fat removal rate. Our reseults confirm that a high triglyceride removal capacity is closely correlated to a high level of HDL. The association between the catabolism of triglyceride-rich lipoproteins and HDL was thus further substantiated.

Cholesterol↗

Cerebrotendinous xanthomatosis: a defect in mitochondrial 26-hydroxylation required for normal biosynthesis of cholic acid.

Oxidation of side chain of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was studied in a patient with cerebrotendinous xanthomatosis (CTX) and in control subjects, using various subcellular fractions of liver homogenate and a method based on isotope dilution-mass spectrometry. In the control, 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was converted into 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid by the mitochondrial fraction, and into 5 beta-cholestane-3 alpha,7 alpha,12 alpha,-25-tetrol by the microsomal fraction. In the CTX patient, liver mitochondria were completely devoid of 26-hydroxylase activity. The same mitochondrial fraction catalyzed 25-hydroxylation of vitamin D3. The microsomal fraction of liver of the subject with CTX contained more than 50-fold the normal amount of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol. The basic metabolid defect in CTX appears to be a lack of the mitochondrial 26-hydroxylase. The excretion in the bile of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 alpha,25-pentol observed in CTX patients may be secondary to the accumulation of the major substrate for the 26-hydroxylase, i. e., 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, and exposure of this substrate to the normally less active microsomal 25-and 24-hydroxylases. It is concluded that the major pathway in the biosynthesis of cholic acid in human liver involves a mitochondrial C27-steroid 26-hydroxylation.

Cholestanols↗

Pyometra in the dog--a pathophysiological investigation. V. The presence of intrahepatic cholestasis and an "acute phase reaction.".

An investigation on the pathophysiological mechanisms underlying the hypoalbuminaemia and the hypercholesterolaemia of the pyometra syndrome in dogs was performed on 15 patients. The control material consisted of blood from 15 and urine from 6 healthy dogs. The presence of intrahepatic cholestasis in most of the dogs was indicated by an increase of serum alkaline phosphatases and phosphodiesterase I, and by the morphological demonstration of bile pigment retention in liver biopsy material. Serum cholesterol (total- and free-) was positively correlated with serum phospholipids, alkaline phosphatases and phosphodiesterase I, as regularly seen in cholestatic syndromes. Fibrinogen and alpha 2-globulins were increased in most patients. Albumin was inversely related to these parameters, and the main cause of the hypoalbuminaemia was probably the presence of an "acute phase reaction". The levels of coagulation factors in plasma were not lowered. Enzyme markers of hepatocellular injury (ALAT, OCT) were not increased, but on the contrary significantly lowered. The possible presence of enzyme inhibitors as the cause of the decrease of ALAT and OCT is discussed.

Animals↗