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J Böttcher

Publications and source records attributed to J Böttcher.

36 records · Page 2Linked to original sources

Lipoprotein-X in patients with cirrhosis: its relationship to cholestasis and hypercholesterolemia.

Lipoprotein-X (Lp-X) is an abnormal low-density lipoprotein frequently found in liver disease. It is regarded as the most sensitive and specific biochemical parameter for the diagnosis of intra- and extrahepatic cholestasis. Moreover, Lp-X is supposed to contribute to the development of hypercholesterolemia in cholestatic liver disease, because it fails to inhibit de novo cholesterol synthesis. This investigation will focus on the relationship between the presence of Lp-X and serum lipid concentrations in cirrhosis. The significance of Lp-X in the diagnosis of cholestasis, compared with alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), and bilirubin levels, will be assessed as well. The present cross-sectional study includes 212 patients with histopathologically proven cirrhosis. The detection of Lp-X and the quantification of -, beta-, and pre-beta-cholesterol was based on agar gel electrophoresis and polyanion precipitation. For the characterization of liver function, the concentrations of albumin and bilirubin, the activities of liver enzymes, and coagulation times were assessed. In a subgroup of 40 individuals, liver biopsies were re-evaluated to confirm or exclude intrahepatic cholestasis. As a result, there was no association between the appearance of Lp-X and total cholesterol concentrations. While all patients with Lp-X showed intrahepatic cholestasis (predictive value of the positive test = 1), only 16 of 28 patients with cholestasis formed Lp-X (sensitivity = 0.57). The activities of AP and of GGT, as well as the concentrations of bilirubin, were strongly elevated in most patients, with and without cholestasis. The predictive values of AP, GGT, and bilirubin were 0.77, 0.69, and 0.74 for the positive test and 0.5, 0, and 0.6 for the negative test, respectively. We conclude that Lp-X is not related to hypercholesterolemia in cirrhosis. The positive, but not the negative, Lp-X test has high predictive value for the diagnosis of cholestasis in cirrhosis. The biochemical parameters traditionally used for the assessment of extrahepatic cholestasis, AP, GGT, and bilirubin, do not support the diagnosis of intrahepatic cholestasis caused by cirrhosis.

Adult↗

Identification of high- and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients.

The clinical relevance of malnutrition and hypermetabolism in end-stage liver disease, as well as their effects on survival after liver transplantation (LTx), are largely unknown. This study investigates the prognostic value of nutritional and metabolic parameters obtained before LTx for survival after LTx. One hundred fifty patients with end-stage liver disease undergoing LTx were assessed prospectively and followed for a mean period of 46 +/- 16 months after LTx. All patients were randomized into a study group and a validation group, each comprising 75 patients. Body composition analysis (24-hour urinary creatinine excretion, anthropometry, bioelectrical impedance analysis), deviation of measured from predicted resting energy expenditure (deltaREE), year of transplantation, and several variables known to be of prognostic relevance in patients with liver disease undergoing conservative treatment were analyzed. Kaplan-Meier and log rank analysis showed that hypermetabolic patients (deltaREE > +20%) and patients with a body cell mass (BCM) < 35% of body weight tended to have reduced survival after LTx. A risk profile on the basis of deltaREE and BCM identified patients with high risk (5-year survival rate, 54%) and low risk (5-year survival rate, 88%; P < .01). The predictive power of this risk profile was independent of the presence of ascites and clinical edema, and its validity was confirmed in the validation group (P < .01). The Child-Pugh score was not of prognostic value. We conclude that a poor nutritional state, as well as hypermetabolism, adversely affects survival after LTx. These potentially treatable presurgical factors deserve close attention in interventional studies.

Adult↗

An ELISA based on whole virus for the detection of antibodies to small-ruminant lentiviruses.

A new ELISA kit was developed, based on highly purified whole-virus antigen derived from the Swiss maedi-visna virus strain OLV. The sensitivity, specificity and accuracy of this assay were compared with that of an established ELISA based on recombinant GAG (group-specific antigens)-GST (glutathione S-transferase) fusion protein expressed in E. coli (GAG-GST ELISA). The whole-virus ELISA exhibits at least comparable specificity (99.3%) but higher sensitivity (98.6 versus 86.3%) and agreement with the 'true' status beyond chance in the detection of antiviral antibodies in serum from goats. Antibodies in milk samples are detected with higher specificity (98.9 versus 97.8%) but lower sensitivity (91.4 versus 98.2%) than in GAG-GST ELISA. The specificity of the new ELISA in the detection of antibodies in serum might be superior, since a set of 40 samples falsely rated positive in GAG-GST ELISA in routine diagnostic work was negative in the new ELISA. In both assays, milk samples can be tested instead of serum, although with slightly reduced sensitivity in the new ELISA. The major advantage of the new test kit is the low number of equivocal samples needing confirmation in a supplementary test. Results obtained with sheep sera indicate that the new ELISA kit is also suitable for the detection of antibodies to maedi-visna virus.

Animals↗

Diagnosis of bovine virus diarrhoea by two enzyme-linked immunosorbent assays.

Two enzyme-linked immunosorbent assays (ELISAs) for the diagnosis of bovine virus diarrhoea (BVD) are described: CHEKIT-BVD-VIRUS and CHEKIT-BVD-SERO. The first test detects virus antigen in leucocytes, resulting in identification of persistently-infected animals, while the second detects antibodies to BVD virus (BVDV). It is well known that even persistently-infected animals may have antibodies to heterologous BVDV strains. These animals are still negative to the CHEKIT-BVD-SERO test because of immunotolerance to conserved virus antigens. Data on these two tests are summarised and a scheme is presented for the diagnosis of BVD using a combination of these two tests.

Animals↗

Energy expenditure and substrate metabolism in liver cirrhosis.

Increased energy needs, a reduced synthesis of endogenous substrates and a limited energy yield from exogenous substrates characterize the metabolic dilemma in patients with liver cirrhosis. The metabolic features observed in cirrhosis are highly variable and cannot be considered as clear-cut phenomena. They obviously differ in certain aspects from the metabolic situations known from starvation or type 2 diabetes mellitus. This is not contrary to the idea that cirrhosis may resemble certain aspects of these 'standard' situations. Cirrhosis-induced disturbances in fuel homeostasis cannot be predicted from clinical and biochemical parameters of the disease. Most of the metabolic picture is present at a very early stage of liver disease. Many metabolic features are independent of the clinical course of liver disease, suggesting that they are an early and extra-hepatic manifestation. A better understanding of the variance of cirrhosis-induced alterations in metabolism may come from characterization of the metabolic 'genotype' which adds to disease-related factors in the individual patient.

Body Temperature Regulation↗

[Use of a modified "antigen-capture" enzyme immunoassay for the identification of virus persistence in cattle infected with bovine virus diarrhea (BVD)].

Bovine viral diarrhoea (BVD)/mucosal disease (MD) is an economically important infectious disease of cattle, and persistently infected animals are of central epidemiological significance. The identification of these animals is a prerequisite for further sanitary measures in affected herds. In order to process large numbers of samples an antigen capture enzyme immunoassay (AC-ELISA) for the detection of bovine viral diarrhoea viral antigen in peripheral blood leukocytes of cattle of all ages has been developed. In this communication an improved method for the preparation of samples is described. A total of 563 blood samples was tested using the AC-ELISA and a routine virus isolation procedure on susceptible bovine cells. When compared to virus isolation in cell culture, the sensitivity of the AC-ELISA was 97%. From the samples that were virus negative in cell culture, 99.1% were also negative in the AC-ELISA. There is some evidence that the AC-ELISA discriminated between transiently and persistently infected animals.

Animals↗

[Acute dysphagia].

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Acute Disease↗

Investigations on antipyrine metabolism V. Differentiation of two isomeric hydroxyantipyrine glucuronides by field desorption and fast atom bombardment mass spectrometry.

The glucuronide conjugates of the two isomeric antipyrine phase I metabolites of antipyrine in man, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine have been analysed by field desorption and fast atom bombardment mass spectrometry. These isomers could be clearly distinguished on the basis of their fragmentation behaviour which was found to correlate with that observed under pyrolysis electron impact conditions.

Antipyrine↗

Isolation and characterization of the four antipyrine glucuronides and determination of their urinary excretion pattern in man by a reversed-phase h.p.l.c. assay.

A large-scale procedure for the isolation of four urinary glucuronides in antipyrine metabolism is described; the isolated compounds are used as standards in a direct h.p.l.c. assay. The four glucuronides were characterized by u.v. and 1H-n.m.r. spectroscopy, and after hydrolysis by a t.l.c. assay of the corresponding aglycones. A reversed-phase h.p.l.c. assay procedure has been developed for the direct quantification of the four antipyrine glucuronides; this separates 3-hydroxymethyl-antipyrine glucuronide, 4,4'-dihydroxy-antipyrine glucuronide, norantipyrine glucuronide and 4-hydroxy-antipyrine glucuronide in a single run. Urinary elimination patterns of these glucuronides have been determined in five female and five male volunteers after antipyrine (1200 mg) administration. The direct assay of urinary glucuronides enables the simultaneous determination of glucuronidation activities and four different phase-I metabolites of antipyrine in vivo.

Adult↗

Quantitation of norantipyrine sulphate and norantipyrine glucuronide as major metabolites of antipyrine in man and rat.

Two assay procedures are described for the quantitation of norantipyrine sulphate and norantipyrine glucuronide present in biological material. One, a selective acid hydrolytic assay procedure that affords the discriminative determination of both conjugates without prior separation, measures free norantipyrine by tlc-uv. The other is a tlc separation procedure for intact norantipyrine conjugates, which, in conjunction with radiolabelled material, derived from [3-14C]antipyrine, enables the direct quantitation of both conjugates independently. In man, about 25% of dose of antipyrine (1200 mg) was excreted as norantipyrine glucuronide within 48 h. The amount of norantipyrine sulphate was small. In the rat, norantipyrine sulphate represented about 15-20% of the dose of antipyrine (40-50 mg kg-1); no norantipyrine glucuronide was formed. Free norantipyrine has not been detected in urine of either species after antipyrine dosage. Pretreatment with 3-methylcholanthrene in the rat substantially enhanced excretion of norantipyrine sulphate, whereas induction with phenobarbitone was without effect on the microsomal N-demethylation of antipyrine. The lability of free norantipyrine was examined under different conditions and contrasted with the relative stability of norantipyrine conjugates. Two of the main degradation products of norantipyrine were identified as 4-phenylazo-norantipyrine and a 4,4'-bipyrazole-derivative.

Adult↗

Investigations on antipyrine metabolism. II--Analysis of conjugated metabolites of antipyrine in rat and human urine by off-line combination of liquid chromatography and field desorption mass spectrometry.

The complex pattern of conjugates in the metabolism of antipyrine in man and rat has been investigated using an off-line combination of liquid chromatography and field desorption mass spectrometry. Using this approach, field desorption mass spectrometry enables the direct identification of underivatized glucuronides and sulphates in antipyrine metabolism on the basis of the corresponding protonated or cationized molecules representing the base peaks in the field desorption mass spectra. All conjugated metabolites of antipyrine established so far--four glucuronides and three sulphates--were identified in extracts of urine after stepwise purification by column chromatography and subsequent mass spectrometric analysis.

Adult↗

Preparative isolation and purification of urinary conjugates in antipyrine metabolism in man and rat.

A series of six major urinary conjugates in the metabolism of antipyrine in man and rat has been investigated. A preparative isolation procedure has been developed using chromatography of methanolic extracts from urine on silica gel. In a two-step chromatographic procedure, methanolic extracts are first separated in 1) a "free fraction", containing unconjugated phase-I-metabolites and unchanged antipyrine, 2) a sulfate fraction and 3) a glucuronide fraction. Sulfate and glucuronide fraction, respectively, are each subjected to a second run for separation into their three components. Thus, the following conjugates have been prepared: 4-hydroxy-antipyrine sulfate, norantipyrine sulfate, 4,4'-dihydroxy-antipyrine sulfate, and 4-hydroxy-antipyrine glucuronide, norantipyrine glucuronide, 3-hydroxymethyl-antipyrine glucuronide. Methodology is also applicable to bile fluid and liver perfusate. Stability of isolated conjugates against acid hydrolysis has been studied to show that strongly marked differences exist in this series of conjugates. Field desorption mass spectrometry has been used for the direct identification of intact conjugates in an underivatized form. Using 13C-NMR, the structure of norantipyrine glucuronide has been established as an 5-enol glucuronide. By analogy, a structure of 5-enol sulfate is proposed for norantipyrine sulfate. From a semiquantitative examination by TLC of urine extracts from man and rat, it becomes apparent, that in the rat, at the dose level studied, sulfate formation is the predominant conjugation pathway. In man, glucuronides are the most prominent type of conjugates. Formation of sulfates is minimal up to a dose of 15 mg/kg antipyrine.

Adult↗

Quantitation and urinary pattern of 4,4'-dihydroxy-antipyrine, 4-hydroxy-antipyrine and 3-hydroxymethyl-antipyrine, as main metabolites of antipyrine in man and rat.

A t.l.c.-assay has been developed for the simultaneous determination from the urine of man and animals of three major hydroxylated metabolites of antipyrine (4,4'-dihydroxy-antipyrine, 4-hydroxy-antipyrine, 3-hydroxymethyl-antipyrine). The methodology is also applicable to bile fluid, liver perfusate and liver homogenate. Genuine conjugates are cleaved by acid hydrolysis and free, acid stable metabolites are extracted. Extracts are subjected to t.l.c. and the chromatograms analysed quantitatively by u.v.-reflectance measurements using authentic materials as standards. Calibration curves are linear with a correlation coefficient r greater than 0.990. Recovery for each metabolite is greater than 95%. Reproducibility of the method is good, with variation coefficients in the range of 3-7%, depending on concentration. The sensitivity of the method is sufficient for practical needs. The specificity of the procedure was confirmed using radio-labelled antipyrine. In man, 4-hydroxy-antipyrine is the principal hydroxylation product in this series, accounting for about 35-40% of the dose. 3-Hydroxymethyl-antipyrine makes up for about 13-17% and 4,4'-dihydroxy-antipyrine represents 3-6% of the dose of antipyrine. In the rat, 4-hydroxy-antipyrine accounts for about 15-31%, 3-hydroxymethyl-antipyrine for 22-28% and 4,4'-dihydroxy-antipyrine for up to 11-18% of the dose. Variation of this pattern in different strains is moderate. In both species, the major portion of phase-I metabolites is excreted as conjugates. Part of them appears in a free form.

Adult↗

Evoked potentials and immunoglobulin abnormalities in multiple sclerosis.

We studied 80 patients with definite, probable, or possible multiple sclerosis, using visual and somatosensory evoked cortical potentials as indicators of manifest or silent plaques. The findings were related to the intracerebral production of immunoglobulin G expressed by the CSF IgG index. Combining the results of evoked potentials and cerebrospinal fluid (CSF) findings, the patients were reclassified. Eight of 18 patients with clinically probable multiple sclerosis were then deemed definite, and 17 of the 42 possible cases were deemed probable. No relation was found between the presumed number of lesions and the rate of intracerebral IgG synthesis.

Adult↗

4,4'-Dihydroxyphenazone as an urinary metabolite of phenazone in different species including man.

4,4'-Dihydroxyphenazone (4-hydroxy-1-4'-hydroxyphenyl)-2,3-dimethyl-3-pyrazoline-5-one) was isolated as a metabolite of phenazone (antipyrine) after acid hydrolysis of rat urine. This was characterized and identified by NMR, MS, IR, UV, Fp and epsilon270. After dosage with phenazone, 4,4'-dihydroxyphenazone is excreted in conjugated form by man, rabbit, guinea pig and rat. In the rat it is further shown, that conjugates of 4,4'-dihydroxyphenazone are formed by glucuronidation as well as by sulfatation. The metabolite seems to add substantially to the overall metabolic pattern of phenazone in these species.

Animals↗

[Intramural gas collection in the small bowel (author's transl)].

Intramural gas collection in a bowel segment is an important roentgenological sign, consistent with necrosis of the bowel wall. This is demonstrated by an example of jejunal volvulus and an inflammatory conglomeration of intestine. The diagnostic interpretation must be completed by the clinical picture and other signs of intestinal ischemia.

Abdomen, Acute↗