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Biomedical subjects

E Christensen

Publications and source records attributed to E Christensen.

At least 163 records · Page 9Linked to original sources
PubMed1989

Glutaric aciduria type I: enzymatic and neuroradiologic investigations of two kindreds.

Two kindreds with glutaric aciduria type I were investigated. Of 20 family members who underwent neurologic examination and organic acid analysis of urine, 18 had glutaryl-coenzyme A dehydrogenase (GDH) activity determined in cultured skin fibroblasts and 12 had computed tomographic brain scans. Six homozygotes were identified who had undetectable GDH activity and identical biochemical profiles (consisting of glutaric and 3-hydroxyglutaric aciduria, reduced serum carnitine concentrations, and frontotemporal atrophy). Serial computed tomographic brain scans of one homozygous infant demonstrated the sequential postnatal development of this atrophy during 3 years before the development of clinical manifestations. In three of the six homozygotes, including the father in one kindred, there were no clinical manifestations of glutaric aciduria type I. These findings raise questions about the value of prenatal diagnosis in predicting clinical manifestations in homozygous newborn infants.

Adult↗
PubMed1989

Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis. Survival and prognostic factors.

Hepatic encephalopathy and gastrointestinal (GI) bleeding are the most serious complications in cirrhosis. The purpose of this study was to examine survival after the first episode of GI bleeding or coma, or both, and to identify variables associated with the subsequent survival in 284 consecutive patients with cirrhosis admitted to one division of hepatology over a period of 81 months. Patients who only bled had markedly longer survival than those who only had coma, whereas those who had both bleeding and coma had by far the poorest survival, only 15% being alive 1 year later. Several other variables showed a significant association with survival. In a Cox multiple regression analysis the following four variables showed significant association with a short survival: coma and bleeding at the episode, ascites, low prothrombin index, and high serum creatinine. The prognostic index derived from the Cox model, which was validated by a split-sample testing technique, may be used to refine prognostic estimation in this subgroup of severely ill cirrhotic patients.

Adult↗
PubMed1988

The Zellweger syndrome: deficient chain-shortening of erucic acid (22:1 (n-9)) and adrenic acid (22:4 (n-6)) in cultured skin fibroblasts.

In the Zellweger syndrome where peroxisomes are absent, extremely long fatty acids (24:0 and 26:0) accumulate in tissues suggesting that these fatty acids are normally beta-oxidized in the peroxisomes. Previous studies with rat hepatocytes suggest that peroxisomes are also important in oxidation of C22 unsaturated fatty acids. This study shows that cultured fibroblasts from normal human controls shorten [14-14C]erucic acid (22:1(n-9)) to oleic acid (18:1(n-9)) efficiently while Zellweger fibroblasts are deficient in chain-shortening. [2-14C]Adrenic acid (22:4(n-6)) is oxidized in control fibroblasts probably by chain-shortening to arachidonic acid (20:4(n-6)). Only a little adrenic acid is oxidized in Zellweger fibroblasts. Linolenic acid (18:3(n-3)) is desaturated and chain-elongated in both control and Zellweger fibroblasts. The results support the view that peroxisomes play a normal physiological role in the shortening of C22 unsaturated fatty acids and that this function is deficient in Zellweger fibroblasts.

Cells, Cultured↗
PubMed1988

Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine.

Seven phenylketonuria (PKU) patients aged 15-24 years were allowed unrestricted diet for 3 weeks. Three of these patients performed well on unrestricted diet according to visual reaction time variability (RTv 50-100 ms) and did not show significant changes when returning to the phenylalanine-restricted diet (RTv 70-100 ms). Neither did the concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) change significantly. Four of the patients, however, performed rather poorly (RTv 120-220 ms) on unrestricted diet and improved significantly (P less than 0.03) when the diet was restored (RTv 70-150 ms). The improvements were accompanied by significant (P less than 0.01 and P less than 0.02) increases (mean 52% and 109%) in CSF levels of HVA and 5-HIAA. Five PKU patients aged 15-23 years were allowed unrestricted diet or unrestricted diet supplemented with various amounts of tyrosine (106-194 mg/kg per 24 h). Two of these patients performed very well on unrestricted diet (RTv 60 ms) and showed little change when the unrestricted diet was supplemented with tyrosine (RTv 70 ms and 80 ms). The three other patients, who performed rather poorly (RTv 120-220 ms), improved significantly (P less than 0.03) when the unrestricted diet was supplemented with tyrosine (RTv 70-140 ms). HVA in CSF increased significantly (P less than 0.01) with the tyrosine supplement when the amount exceeded a threshold of approximately 80 mg/kg per 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis.

Circulating noradrenaline is increased in patients with cirrhosis, especially in decompensated patients with ascites. Eighty-one patients with alcoholic cirrhosis were followed for up to 8 years in order to establish a possible relationship between plasma catecholamines, haemodynamics, and routine clinical and biochemical variables and survival. Forty-seven (58%) of the patients died during the follow-up period. Univariate analysis showed that plasma noradrenaline and adrenaline concentrations, portal pressure, indocyanine green clearance, serum sodium, bilirubin, and albumin concentrations, and the presence of ascites or cardiovascular disease were of significant prognostic value. In a multivariate analysis (Cox regression model), plasma noradrenaline concentration, portal pressure, serum bilirubin concentration, and the presence of ascites and cardiovascular disease remained significant independent predictors of survival. The results suggest that determination of the circulating level of noradrenaline and portal pressure may add to the prognostic information on survival obtained from routine tests. Thus, the activity of the sympathetic nervous system may indicate the severity of cirrhosis with respect to survival.

Adult↗
PubMed1988

Fat consumption and schizophrenia.

This report describes the statistical association between the average ratings of course and outcome of schizophrenia in 8 national centres participating in the World Health Organization international 2-year follow-up study (1) and the amount of fat in the average national diets as published by the Food and Agriculture Organization of the United Nations (2). Highly significant correlations were found between favourable ratings of course and outcome of schizophrenia and a low percentage of total fat (r = 0.80-0.90; P less than 0.05) and of fat from land animals and birds (composed mainly of saturated fat) (r = 0.91-0.95; P less than 0.01). High percentage of fat from vegetables, fish and seafood (having a relatively high content of unsaturated fatty acids) tended to be associated with a favourable course and outcome (r = 0.23-0.50; P greater than 0.10). A multivariate analysis revealed that 97% (P = 0.0002) of the variation in the overall outcome of schizophrenia between the national centres could be explained by the combined variation in the percentages of fat from land animals and birds and from vegetables, fish and seafood, respectively, in the national diets. These results suggest that the course and outcome of schizophrenia may be influenced through diet. They should encourage investigators to perform controlled clinical trials of low-fat diets with a sufficient amount of essential fatty acids.

Dietary Fats↗
PubMed1988

Regulation of the metabolism of polyunsaturated fatty acids.

The object of the present work has been to assess some aspects of the control of the metabolism of polyunsaturated fatty acids. In these studies we have used isolated cells; hepatocytes and cardiac myocytes from rat, and lymphocytes and fibroblasts from humans. Attention has focused on the importance of dietary and hormonal factors which can exert an effect shortly after activation of fatty acid, and thus may determine whether the fatty acid will be desaturated, chain-elongated, directly esterified or oxidized. Both the short-term and long-term regulation excerted by dietary fat have been studied in both rat and human. Profound sex-differences exist in fatty acid esterification, oxidation and fatty acid composition in lipoproteins. It is suggested that these differences, at least in part are due to a different content of intracellular fatty acid binding proteins in female and male liver. The peroxisomal retroconversion of C22-unsaturated fatty acids to their C20-homologues is probably involved in the regulation of fatty acid composition in membrane phospholipids, being a sort of "overflow valve". In several somewhat different diseases the patients have no peroxisomes or their peroxisomes are defective. In these peroxisomal diseases the beta-oxidation of very long-chain fatty acids is deficient. In this present work we show that fibroblast from patients with the peroxisomal diseases, Zellweger disease, X-linked adrenoleukodystrophy and neonatal adrenoleukodystrophy differ in their ability to shorten C22-fatty acids.

Animals↗
PubMed1988

Individual therapy-dependent prognosis based on data from controlled clinical trials in chronic liver disease.

In a given disease the manifestations and course of disease may vary markedly between the patients. This complicates prediction of the prognosis and treatment effect in individual patients. Most controlled clinical trials present only the "average" effect e.g. the therapy-dependent survival in the studied patient group. To estimate the therapy-dependent prognosis in individual patients it is necessary to utilize the covariation between survival time and variables characterizing each patient including the therapy given. This paper describes current methods for identification of variables which covary with survival time (prognostic variables) or the effect of therapy (therapeutic variables). Analyzing data from two large controlled clinical trials in patients with chronic liver disease: 1) the multicenter trial of prednisone versus placebo in cirrhosis conducted by the Copenhagen Study group for Liver diseases (CSL-1) and 2) the multinational trial of azathioprine versus placebo in primary biliary cirrhosis (PBC-1) we have developed indices for prediction of prognosis and therapeutic effect using Cox's multiple regression model for censored survival data. Using the indices one can estimate the therapy-dependent prognosis in new patients from their base-line data. Furthermore, a time-dependent index by which the risk of a given patient can be estimated repeatedly to update prognosis during the course of the disease is presented. To simplify application "pocket charts" have been devised by which a prognostic index for a patient can easily be obtained at the bedside. By simple graphs, a prognostic index can be translated to estimates of the probability of surviving a given time or the median survival time predicted for the patient. The indices have been validated by comparing the survival predicted by the indices with the observed survival in new patients or using data splitting. The results allow a more differentiated treatment strategy based on the characteristics of the individual patient. Even if the results apply to chronic liver disease, the general principles are valid for study of the individual therapy-dependent prognosis in other diseases.

Actuarial Analysis↗
PubMed1987

Adenine phosphoribosyltransferase deficiency: a case diagnosed by GC-MS identification of 2,8-dihydroxyadenine in urinary crystals.

Light microscopy of the urinary sediment from a child suffering from urinary tract disease showed massive crystalluria. Most of the sediment consisted of characteristic round and brownish crystals. 2,8-Dihydroxyadenine was identified in the crystals by means of gas chromatography-mass spectrometry. The diagnosis of adenine phosphoribosyltransferase deficiency was established by the finding of a very low activity of this enzyme in erythrocytes from the patient, and of half the normal activity in the patients. The patient was first treated with a diet low in purine and with a high liquid intake. She stayed symptomless on this regimen, but the crystalluria persisted. On low doses of allopurinol the crystalluria disappeared.

Adenine↗
PubMed1987

Glutaric aciduria type I: clinical heterogeneity and neuroradiologic features.

We present four patients, two pairs of siblings, with glutaric aciduria type I (GA I). All four had undetectable glutaryl-CoA dehydrogenase activity on fibroblast culture and massive urinary excretion of glutaric acid. All had serum carnitine deficiency at time of diagnosis except one patient who was diagnosed neonatally. All had a unique pattern of frontotemporal atrophy on CT. Remarkably, in both sibling pairs, one child was asymptomatic. This suggests that the biochemical markers hitherto identified with GA I do not encompass the entire scope of the metabolic or enzymatic abnormalities. Alternatively, as yet unidentified mechanisms might spare or delay the destructive process.

Atrophy↗
PubMed1987

Variables predicting elevated portal pressure in alcoholic liver disease. Results of a multivariate analysis.

In 46 alcoholic patients the association of wedged-to-free hepatic-vein pressure with other variables (clinical, histologic, hemodynamic, and liver function data) was studied by means of multiple regression analysis, taking the wedged-to-free hepatic-vein pressure as the dependent variable. Four variables showed significant independent association with the wedged-to-free hepatic-vein pressure: indocyanine green clearance (p = 0.031), degree of necrosis (p = 0.023), degree of hepatic architectural destruction (graded as: preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) (p = 2.3 X 10(-6) and sex (p = 0.0024), male sex being associated with higher wedged-to-free hepatic-vein pressure. The multiple coefficient of determination (R2) was 0.63; thus, 63% of the variation in the wedged-to-free hepatic-vein pressure was 'explained' by variation in these four variables.

Adult↗
PubMed1987

Prediction of outcome of pancreaticogastrostomy for pain in chronic pancreatitis.

On the basis of 18 preoperative variables obtained consecutively in 31 patients undergoing drainage operation for pain in chronic pancreatitis, a preoperative discriminant score for satisfactory/unsatisfactory result is set up. The patient most likely to be free of pain after the operation has no preoperative use of tranquilizers, no diabetes, little dilatation of the pancreatic duct, no small pseudocysts, but daily use of opiates. This is probably not a matter of causal connection but rather an expression of common underlying pathophysiological mechanism(s), somatic or psychological. A pocket chart for the practical use in the preoperative assessment index is designed.

Adolescent↗
PubMed1986

Mitochondrial and peroxisomal oxidation of arachidonic and eicosapentaenoic acid studied in isolated liver cells.

The partitioning between peroxisomal and mitochondrial beta-oxidation of [1-14C]eicosapentaenoic acid (20:5(n-3] and [1-14C]arachidonic acid (20:4(n-6)) was studied. In hepatocytes from fasted rats approximately 70% of the fatty acid substrate was oxidized with oleic, linoleic, eicosapentaenoic and docosahexaenoic (22:6(n-3)) acid, even more with adrenic (22:4(n-6)) and less with arachidonic acid. When the mitochondrial oxidation was suppressed by fructose refeeding and by (+)-decanoylcarnitine, the fatty acid oxidation in per cent of that in cells from fasted rats was with 18:1(n-9) 7%, 18:2(n-6) 8%, 20:4(n-6) 12%, 20:5(n-3) 20%, 22:4(n-6) 57% and for 22:6(n-3) 29%. The fraction of 14C recovered in palmitate and other newly synthesized fatty acids after fructose refeeding decreased in the order 22:4(n-6) greater than 22:6(n-3) greater than 20:5(n-3) greater than 20:4(n-6) and was very small with 18:1(n-9) and 18:2(n-6). In cells from both fed and fructose-refed animals 20:5(n-3) was efficiently elongated to 22:5(n-3) and 22:6(n-3). 20:5(n-3) and 20:4(n-6) were not elongated after fasting. The phospholipid incorporation with [1-14C]20:5(n-3) decreased during prolonged incubations while it remained stable with [1-14C]arachidonic acid. The results suggest that peroxisomes contribute more to the oxidation of 20:5(n-3) than with 20:4(n-6) although both substrates are probably oxidized mainly in the mitochondria.

Animals↗