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E Christensen

Publications and source records attributed to E Christensen.

At least 109 records · Page 6Linked to original sources
PubMed1994

[A comparison of 2 new rapid methods for determination of HbA1C concentration in patients with diabetes mellitus].

We have evaluated a new immunoturbidimetric assay (DCA 2000 HbA1c system, Bayer, Denmark) for determination of HbA1c. The aim of the study was to evaluate accuracy, precision and feasibility for the DCA 2000 method when employed in a diabetes centre by a technical assistant and at a general practitioner's by non lab staff. The results were compared with a high performance liquid chromatographic method (HPLC, AUTO A1C, Kyoto Daiichi Kagaku Co., Kyoto, Japan) which is the current laboratory method, and therefore used as reference. Assay time for the DCA 2000 method was nine minutes, while the HbA1c result was displayed within four minutes by HPLC. Blood samples were drawn after informed consent from 118 patients during a period of two months at the out-patient clinic of the Dept. of Paediatrics, Glostrup Hospital (n = 67) and at a general practitioner's (n = 51). Each sample was analyzed twice by each method on two consecutive days. In the HbA1c range from four to 14% (n = 67) the average within-assay precision (SD) for the HPLC method was 0.13%, whilst it was 0.23% for the DCA 2000 method (p < 0.001). The within-assay precision was low and acceptable, and for both methods it was independent of the current HbA1c concentration. For the DCA method precision was almost similar (p > 0.07) when carried out by a technical assistant (SD: 0.20%) and by non lab staff (SD: 0.25%). Interbatch variations for HbA1c results investigated with two different batches of reagents within a month were SD 0.30% (HbA1c range: 4.9-5.9%, n = 30) and SD 0.44% (HbA1c range: 10.5-12.1%, n = 30) for these two preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1994

Prenatal diagnosis of glutaryl-CoA dehydrogenase deficiency: experience using first-trimester chorionic villus sampling.

We have performed prenatal diagnosis for glutaryl-CoA dehydrogenase (GDH) deficiency in 16 pregnancies at risk by measuring the enzyme activity in chorionic villus samples. In most cases, GDH activity was measured both in uncultured chorionic villus samples and in cultured chorionic cells. In 4 of the 16 cases, an affected fetus was predicted, while the remaining cases were found to be normal. In three of the four affected cases, GDH activity was measured in both uncultured and cultured chorionic cells and the correct diagnosis established by both measurements. In the fourth case, only cultured cells were investigated because the chorionic villus sample was too small for the direct assay. All four pregnancies predicted to be affected were interrupted and the diagnoses confirmed on the aborted material in three of the cases. In the fourth case, no material was available for investigation. Of the 12 pregnancies predicted to be unaffected, ten cases resulted in the birth of healthy unaffected babies while two pregnancies are still in progress.

Amniocentesis↗
PubMed1994

Prognostic variables in patients with cirrhosis and oesophageal varices without prior bleeding.

As identification of patients at risk of bleeding or death is essential for prophylaxis, we determined the prognostic influence of various patient characteristics on the risk of bleeding and death. Fifty-five patients with cirrhosis and oesophageal varices without previous bleeding were included in the study and followed up after an average observation period of 446 days (range: 5-1211 days). A total of 55 clinical, biochemical, haemodynamic, and endoscopic variables were classified as systemic haemodynamic, portal haemodynamic, or metabolic. Using univariate analysis, the following variables showed a significant relation with an increased risk of bleeding or death: high plasma volume (p < 0.02), high azygos blood flow (p < 0.004), elevated hepatic venous pressure gradient (p < 0.02), marked prominence of varices (p < 0.05), poor nutritional status (p < 0.0001), decreased clotting factor 2,7,10 (p < 0.002), poor incapacitation index (p < 0.004), low serum albumin (p < 0.005), increased serum bilirubin (p = 0.05), elevated alkaline phosphatases (p < 0.02), low arterial oxygen saturation (p = 0.02), and encephalopathy (p < 0.007). In a Cox regression model, poor nutritional status (p < 0.00005), increased serum bilirubin (p < 0.001), short central circulation time (p < 0.03), low serum albumin (p < 0.02), and decreased clotting factor 2, 7, 10 (p < 0.05) were independently associated with a higher risk. In conclusion, the results support the prognostic value of metabolic variables as described earlier. The prognostic significance of central circulation time stresses the importance of the hyperdynamic systemic circulation in assessing the increased risk of bleeding or death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The treatment effect of alpha interferon in chronic hepatitis B is independent of pre-treatment variables. Results based on individual patient data from 10 clinical controlled trials. European Concerted Action on Viral Hepatitis (Eurohep).

Alpha interferon induces HBeAg seroconversion in about one third of treated patients and has become an established treatment of chronic hepatitis B. A number of smaller studies have suggested that response to treatment is more likely to occur in patients with higher levels of transaminases, with recent (adult) onset, a history of acute hepatitis, low levels of HBV DNA and in heterosexual males. The aim of this European co-operative study was to estimate the effect of alpha interferon more accurately and to evaluate the influence of host pre-treatment variables on the effect of interferon. Individual data were collected from 751 patients from 10 controlled clinical trials on alpha interferon (lymphoblastoid or recombinant) treatment for chronic hepatitis B. Alpha interferon was administered to 496 patients, while 255 were untreated controls. Individual patient data were analysed by survival analysis (log rank test and Cox regression analysis), stratified by trial, with the disappearance of HBeAg as the major endpoint. The results showed that the HBeAg disappearance rate with or without interferon treatment was higher in patients with high aminotransferase levels, with a history of acute hepatitis and in male heterosexual patients disregarding HIV status. If HIV-positive patients were excluded, the effect of sexual orientation was not significant. Therapy with alpha interferon increased the a priori HBeAg disappearance rate by a factor of 1.76; the relative treatment effect of alpha interferon was independent of the tested pretreatment host variables, but dependent on the total (intended) interferon dose (low dose < or = 200 MU/m2 increased HBeAg disappearance by a factor 1.37; medium/high dose > or = 200 MU/m2 increased HBeAg disappearance by a factor 2.05). In conclusion, this meta-analysis suggests that the effect of alpha interferon is less than previously assumed and independent of pretreatment host variables tested. It confirms the higher therapeutic benefit of a total dose exceeding 200 MU/m2 and of selection of patients based on disease activity and immune reactivity. Although all patient seem to have the same relative benefit, the absolute benefit of alpha interferon treatment seems to be greatest in patients with high transaminase levels and with a history of acute hepatitis.

Adult↗
PubMed1994

Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. The Investigators of the European Concerted Action on Viral Hepatitis (EUROHEP).

A multicenter longitudinal study was performed to assess the survival of hepatitis B surface antigen positive compensated cirrhosis, primarily in relation to hepatitis B virus replication and hepatitis delta virus infection, and to construct a prognostic index based on entry characteristics. This cohort study involved nine university medical centers in Europe. Three hundred and sixty-six Caucasian HBsAg positive patients with cirrhosis who had never had clinical manifestations of hepatic decompensation were enrolled and followed for a mean period of 72 months (6 to 202 months). Inclusion criteria were biopsy-proven cirrhosis, information on serum hepatitis B e antigen and antibody to hepatitis D virus at the time of diagnosis and absence of complications of cirrhosis. At entry 35% of the patients were HBeAg positive, 48% of the patients tested were HBV-DNA positive and 20% anti-HDV positive. Death occurred in 84 (23%) patients, mainly due to liver failure (45 cases) or hepatocellular carcinoma (23 cases). The cumulative probability of survival was 84% and 68% at 5 and 10 years, respectively. Cox's regression analysis identified six variables that independently correlated with survival: age, albumin, platelets, splenomegaly, bilirubin and HBeAg positivity at time of diagnosis. According to the contribution of each of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. No difference in survival of hepatitis D virus infected and uninfected patients was observed. Termination of hepatitis B virus replication and/or biochemical remission during follow up correlated with a highly significant better survival. These data show that in compensated cirrhosis B, hepatitis B virus replication, age and indirect indicators of poor hepatic reserve and established portal hypertension significantly worsen the clinical course of the disease, whereas hepatitis D virus infection does not influence the prognosis. The highly significant improvement in life expectancy following cessation of hepatitis B virus replication and biochemical remission favors antiviral therapy in those patients with a guarded prognosis, as estimated by a prognostic index.

Adult↗
PubMed1993

A fibroblast glutaryl-CoA dehydrogenase assay using detritiation of 3H-labelled glutaryl-CoA: application in the genotyping of the glutaryl-CoA dehydrogenase locus.

A method described earlier for measuring glutaryl-CoA dehydrogenase activity in fibroblasts has been further developed. This assay uses the detritiation of [2,3,4-3H]glutaryl-CoA both with and without added artificial electron acceptors as a measure of glutaryl-CoA dehydrogenase activity. Fibroblasts from patients with glutaryl-CoA dehydrogenase deficiency, as determined by the 14CO2 release assay, showed very low detritiation of [2,3,4-3H]glutaryl-CoA without added artificial electron acceptor. Obligate heterozgotes for glutaryl-CoA dehydrogenase deficiency showed detritiation activity intermediate between homozygotes and normal individuals. Addition of an electron acceptor to the assay mixture had no influence on the activity in homozygotes for glutaryl-CoA dehydrogenase deficiency but more than doubled the detritiation activity in obligate heterozygotes and in normal individuals. No difference in detritiation activity could be detected between glutaryl-CoA dehydrogenase deficient patients with a high urinary excretion of glutaric acid and patients with almost no excretion of glutaric acid. In all glutaryl-CoA dehydrogenase deficient cell lines tested the loss of decarboxylation activity was also accompanied by a loss of dehydrogenation activity. The detritiation assay was equivalent to, or even better than, the 14CO2 release assay in distinguishing between homozygotes and heterozygotes for glutaryl-CoA dehydrogenase deficiency.

Cells, Cultured↗
PubMed1993

Incorporation of stearic acid (18:0) and palmitic acid (16:0) in phospholipid molecular species studied in isolated rat liver cells.

The incorporation of [1-14C]16:0 and [1-14C]18:0 in the molecular species of PC and PE in isolated rat liver cells was studied. More [14C]18:0 than [14C]16:0 was esterified both in PC and PE. Also the chain elongated and desaturated products (16:1, 18:0 and 18:1) were incorporated. The main molecular phospholipid species formed from [14C]18:0 were 18:0-18:2, 18:0-20:4 and 18:0-22:6. 18:0-18:0 species was not detected, independent of the substrate concentration (0.1-0.9 mM). With [14C]16:0 at low substrate concentration (0.1 mM) the dominating species are 16:0-18:2, 16:0-20:4 and 16:0-22:6. These species were detected already after 10 min. The same main species are formed both in PC and PE, but the relative amounts differ. In PC the combination with 18:2 is most abundant for both saturated fatty acid substrates. In PE 18:0-20:4 dominates when 18:0 is the substrate, and 16:0-22:6 when 16:0 is. At higher substrate concentrations (0.4-0.9 mM) 16:0 is also esterified in 16:0-16:0. This molecular species is efficiently degraded in the cells within 2-3 h, in contrast to the other species formed. The results suggest that 16:0 and 18:0 are directly incorporated in the sn-1 position in physiologically important phospholipid molecular species. With an excess of 16:0, 16:0-16:0 is also formed in substantial amounts, but this uncommon species is thereafter removed.

Animals↗
PubMed1993

Molecular analysis of the mutations in five unrelated patients with the Lesch Nyhan syndrome.

We have identified the mutations in the hypoxanthine phosphoribosyltransferase (hprt) gene in five patients with the Lesch Nyhan syndrome (LN) by direct sequencing of hprt cDNA and genomic DNA. Three of the mutations affect splicing of exons 1, 2, and 9, respectively, while two are missense mutations in exons 3 and 8. All 5 mutations result in profound hprt deficiency as measured in fibroblast lysates. However, small differences in the clinical phenotype are seen between the patients. All these mutations are unique and have not been reported previously.

Adolescent↗
PubMed1993

Magnetic resonance imaging in juvenile Canavan disease.

We present a 2-year-old boy and a 6-year-old girl with mild Canavan disease (CD). Aspartoacylase activity in skin fibroblasts was deficient. Magnetic resonance imaging (MRI) of the brain did not show the prominent leucodystrophy previously reported in CD, but there was a hyperintense signal from the lentiform nuclei and the heads of the caudate nuclei on the T2-weighted MR images. This suggests a specific vulnerability of the corpus striatum in these patients. In the older patient, the white matter became affected at the age of 6 years. Proton magnetic resonance spectroscopy (1H-MRS) of white matter revealed a normal concentration of N-acetyl-L-aspartate (NAA) and a markedly decreased concentration of choline containing compounds (Cho) in the boy but a normal ratio of NAA to Cho in the girl. We conclude that deficient NAA catabolism affects myelin metabolism. This may present as changes in the striatum and/or as a low concentration of Cho before leucodystrophy appears on MRI.

Amidohydrolases↗
PubMed1993

Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. PBC1 and PBC2 trial groups.

BACKGROUND: The precision of current prognostic models in primary biliary cirrhosis (PBC) is rather low, partly because they are based on data from just one time during the course of the disease. The aim of this study was to design a new, more precise prognostic model by incorporating follow-up data in the development of the model. METHODS: We have performed Cox regression analyses with time-dependent variables in 237 PBC patients followed up regularly for up to 11 years. The validity of the obtained models was tested by comparing predicted and observed survival in 147 independent PBC patients followed for up to 6 years. RESULTS: In the obtained model the following time-dependent variables independently indicated a poor prognosis: high bilirubin, low albumin, ascites, gastrointestinal bleeding, and old age. When including histological variables, cirrhosis, central cholestasis, and low immunoglobulin (Ig)M also indicated a poor prognosis. The survival predicted by the models agreed well with the survival observed in the independent PBC patients. The time-dependent models predicted better than our previously published time-fixed model. CONCLUSIONS: Using the time-dependent Cox models, one can estimate a more precise probability of surviving the next 1, 3, or 6 months for any given patient at any time during the course of the disease. This may improve monitoring of PBC patients.

Azathioprine↗