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Biomedical subjects

E Christensen

Publications and source records attributed to E Christensen.

At least 181 records · Page 10Linked to original sources
PubMed1986

Prenatal diagnosis of Zellweger syndrome and related disorders: impaired degradation of phytanic acid.

Normal amniocytes and chorionic villous cells in culture are able to produce 14CO2 from exogenous [1-14C] phytanic acid. In contrast, cells from four fetuses at risk for the cerebro-hepato-renal (Zellweger) syndrome and related disorders showed a greatly reduced activity, indicating a block in oxidation of the fatty acid. Our data confirm that phytanic acid oxidase activity measurement can be used for the prenatal assessment of this group of disorders.

Adult↗
PubMed1986

Use of a prognostic index in evaluation of liver transplantation for primary biliary cirrhosis.

In the Cambridge/King's College Hospital program, one of the main criteria for recommendation of a liver transplant for a patient with primary biliary cirrhosis (PBC), as in other types of end-stage liver disease, has been the overall assessment that survival was likely to be less than one year. In the present study, a recently developed prognostic model, based on six variables, was used retrospectively to estimate the likely survival without transplantation of the first 29 patients receiving a transplant for PBC. Median estimated survival time for the complete group of patients was five months and in only four patients was survival in the absence of transplantation estimated to be more than one year. Comparison of actual survival curves after transplantation with the estimated survival in the absence of such a procedure shows that, despite an initial higher mortality related to surgery and the immediate postoperative period, grafting was associated with a statistically significant improvement in overall survival. No correlation between the outcome after transplantation and the severity of preexisting liver disease, (as assessed by the expected survival) could be determined, but further assessment of preoperative variables is warranted.

Adult↗
PubMed1986

Riboflavin responsive multiple acyl-CoA dehydrogenation deficiency. Assessment of 3 years of riboflavin treatment.

A boy with riboflavin-responsive beta-oxidation deficiency (multiple acyl-CoA dehydrogenation deficiency) was assessed clinically and biochemically after 3 years of continuous riboflavin medication. He was diagnosed at the age of three years after an attack of a Reye's syndrome-like disease. During the 3 years of assessment he has experienced no serious disease; although short episodes of fatigue and loss of appetite have been noted. His mental and physical development has been normal. Biochemically the abnormal excretion of organic acid metabolites, characteristic of the acyl-CoA dehydrogenation deficiency, has been continuously present. Quantitatively there has been a trend to a more simple picture with ethylmalonic acid as the predominant metabolite. However, because of the large within-day variation in the excretion of all the metabolites, changes following diet and riboflavin trials must be interpreted with caution in these patients.

Acyl Coenzyme A↗
PubMed1986

Updating prognosis and therapeutic effect evaluation in cirrhosis with Cox's multiple regression model for time-dependent variables.

A multivariate Cox regression analysis with time-dependent variables has been performed on the data of 415 patients with cirrhosis included in a controlled clinical trial of 10-15 mg prednisone daily versus placebo. The analysis showed that a poor prognosis was associated with a low prothrombin index, marked ascites, GI bleeding, high age, high daily alcohol consumption, high bilirubin and alkaline phosphatase and low albumin values, little liver connective tissue inflammation, and poor nutritional status. Prothrombin index and ascites showed significant interaction with the treatment in such a manner that high prothrombin index and absence of ascites were associated with a beneficial effect of prednisone, whereas low prothrombin index and presence of ascites were associated with a harmful effect of prednisone treatment. The final model was validated in independent patients by comparing their actual survival with that predicted from the model, using a split-sample testing technique. The prognostic factors were combined with an index that can be used to update prognosis whenever changes occur in the clinical status of a patient during the course of the disease. The probability of surviving the next 3 or 6 months can be estimated from the prognostic index at any time during the course. The index may be of value for the correct timing of special therapeutic procedures such as liver transplantation.

Adult↗
PubMed1986

Eicosapentaenoic- and arachidonic acid metabolism in isolated liver cells.

The oxidation and esterification of 14C labelled eicosapentaenoic acid (20:5,n-3) and arachidonic acid (20:4,n-6) in isolated liver cells has been studied. The bioconversion of C18 and C22 polyunsaturated fatty acids to 20:5(n-3) and 20:4(n-6) is also discussed. Adrenic acid (22:4,n-6) and docosahexaenoic acid (22:6,n-3) are retroconverted to 20:4(n-6) and 20:5(n-3) respectively by peroxisomal beta-oxidation. 20:4(n-6) and 20:5(n-3) are both mainly oxidized in the mitochondria. The peroxisomal contribution to the oxidation of 20:5,n-3 is however larger than with 18:2(n-6) and 18:1(n-9) which are predominantly oxidized by mitochondrial beta-oxidation. Isolated liver cells oxidize more 20:5(n-3) and esterify less than observed with 20:4(n-6) as substrate. In liver cells from essential fatty acid deficient animals 20:5(n-3) and 20:4(n-6) are both efficiently directed to the phospholipids. In hepatocytes from animals fed a diet rich in 18:2(n-6) and 18:3(n-3) arachidonic acid is still to a large extent esterified in the phospholipids while 20:5(n-3) only to a small extent is esterified in this lipid fraction. 18:2(n-6) is much more efficiently esterified in the phospholipids than is 18:3(n-3) which is also rapidly removed from the phospholipids. The delta 4 desaturase activity is increased in essential fatty acid deficiency similar to delta 6 desaturase. The competition between 18:3(n-3) and 18:2(n-6) for delta 6 desaturation in combination with a much higher dietary intake of 18:2(n-6) than of 18:3(n-3) may limit the conversion of dietary 18:3(n-3) to 20:5(n-3).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial.

The effect of azathioprine on survival of patients with primary biliary cirrhosis was studied prospectively in a multinational, double-blind, randomized clinical trial including 248 patients of whom 127 received azathioprine and 121 placebo. There were 57 deaths in the azathioprine group and 62 in the placebo group. The actual survival was slightly longer during azathioprine than during placebo treatment. Using Cox multiple regression analysis and adjusting for slight imbalance between the two treatment groups, the therapeutic effect of azathioprine was statistically significant (p = 0.01), with azathioprine reducing the risk of dying to 59% of that observed during placebo treatment (95% confidence interval 40%-90%) or improving survival time by 20 mo in the average patient. Furthermore, azathioprine slowed down progressing incapacitation. Side effects of azathioprine were relatively few. The analysis revealed that the following five variables independently implied poor prognosis: high serum bilirubin, old age, cirrhosis, low serum albumin, and central cholestasis. These factors were combined to a "prognostic index" for prediction of outcome in new patients. The index was validated on independent patient data. On the basis of these results we recommend azathioprine as a routine treatment of primary biliary cirrhosis.

Actuarial Analysis↗
PubMed1985

A therapeutic index that predicts the individual effects of prednisone in patients with cirrhosis.

Our aim was to construct an index that accurately predicts the degree of benefit or harm that prednisone therapy holds for patients with liver cirrhosis. The admission and survival data of 488 patients with cirrhosis who participated in a controlled clinical trial of prednisone in a dosage of 10-15 mg daily (251 patients) versus placebo (237 patients) and who were observed for up to 12 yr were analyzed using Cox's multiple regression model. Four variables each provided significant therapeutic information: antinuclear factor (p = 0.02) and large piecemeal necroses (p = 0.02) were associated with a beneficial effect, whereas ascites (p = 0.0004) and large regenerative nodules (p = 0.0007) were associated with a harmful effect of prednisone. From these four variables a therapeutic index was constructed. For a given patient the therapeutic index is a measure of how big the effect will be if prednisone is given. The gain in survival time obtained by administering prednisone according to the therapeutic index was estimated to be 349 yr, mainly confined to 217 patients with a significant positive (121) or negative (96) therapeutic index. The therapeutic index may prove useful for the optimal administration of prednisone treatment in new patients with cirrhosis.

Antibodies, Antinuclear↗
PubMed1985

Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis.

One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or histological features examined, except the serum alanine aminotransferase activity which was greater in those on active treatment. In this trial we have been unable to establish any therapeutic benefit from the drug.

Clinical Trials as Topic↗
PubMed1985

Early features of primary biliary cirrhosis: an analysis of 85 patients.

A standardized clinical, laboratory, and histological assessment was carried out on 85 patients with primary biliary cirrhosis within 1 year of developing symptoms. Presenting symptoms included pruritus (n = 30), jaundice (n = 9), variceal bleeding (n = 6), ascites (n = 5), fatigue (n = 4), and abdominal pain (n = 4). Ten patients had symptoms not immediately suggestive of hepatic etiology and a further 17 were asymptomatic, the diagnosis being made fortuitously. Eighty four percent were not incapacitated and 52 were anicteric. Less than half were pigmented, 22% had xanthoma, and only 12% were deeply jaundiced. In contrast, all had significant laboratory abnormalities with alkaline phosphatase activity greater than 400 IU/L in 60% and IgM greater than 2.5 g/L in 75%. Mitochondrial antibody was detectable in 83% with a titer greater than 1:160 in 70%. Cirrhosis was present in 24 patients, nine of whom were anicteric and a further 11 had fibrosis or scarring.

Adult↗