Biomedical subjects

H Schlebusch

Publications and source records attributed to H Schlebusch.

At least 37 records · Page 2Linked to original sources

PubMed1997

Comparability of a new turbidimetric digoxin test with other immunochemical tests and with HPLC--a multicenter evaluation.

A new turbidimetric inhibition immunoassay for digoxin (Tina-quant [a] Digoxin, Boehringer Mannheim) was evaluated in seven laboratories. It can be performed without sample pretreatment with ready-to-use reagents on nondedicated analyzers in combination with routine clinical chemistry. The studies revealed a good analytical performance: lower limit of detection 0.12 microg/L (3 SD from mean of blank); linearity up to 7.5 microg/L; median between-run CVs 8.1% (0.6 microg/L), 2.8% (1.5 microg/L), 1.9% (3 microg/L); mean analytical recovery in control sera 98-102%; slopes from 0.97 to 1.09 and intercepts from -0.28 to 0.10 microg/L in comparison with four immunoassays; and a high resistance to common interferents. The test was more resistant to digoxin-like immunoreactive factor (DLIF) interference than other methods, showing cross-reactivity only in some intensive care patient samples. Among 192 patients in whom DLIF is expected (e.g., pregnant women, patients with renal failure, newborns), 90% of results were < or =0.26 microg/L digoxin. Cortisol showed no cross-reactivity and digoxigenin had a low reactivity. An interlaboratory survey revealed a good comparability of the Tina-quant [a] test with the median of all methods (slope 0.99, intercept -0.06 microg/L). An HPLC method for digoxin based on isocratic separation of samples on an RP-18 column followed by detection by an immunoassay yielded a reasonable comparability with the immunochemical tests with noncritical samples. Divergent results of immunoassays caused by DLIFs or different cross-reactivities with digoxin metabolites or derivatives can be explained by the use of this HPLC method.

Anticoagulants↗

PubMed1997

[Modification of transplacental digoxin transfer in the isolated placental lobule].

Digoxin is widely used in the transplacental therapy of fetal tachyarrhythmia. Unfortunately, in cases with severe cardiac insufficiency and hydrops fetalis, transplacental passage of digoxin is often hampered and therapy therefore ineffective. The present study was designed to establish the isolated placental lobule to quantify transplacental digoxin passage under different experimental conditions. Ten human placentas were obtained immediately after delivery, and a lobule was dually perfused after cannulating a small artery and vein of the chorionic plate and piercing four catheters through the corresponding basal plate. Flow rates were 12 ml/min in the maternal circuit and 6 (I) respectively 3 ml/min (II) in the fetal circuit. The maternal circuit was spiked with digoxin to 6.18 +/- 0.40 ng/ml, and transplacental passage was calculated from repeated fetal and maternal perfusate samples (Fluorescence-Polarization-Immunoassay; TDx, Abbott Laboratories). Within three hours of recirculating perfusion with a fetal flow rate of 6 ml/min (I), digoxin concentrations in the maternal circuit (400 ml) declined to 3.56 +/- 0.09 ng/ml, whereas digoxin levels in the fetal compartment (200 ml) increased to 2.58 +/- 0.37 ng/ml. With a fetal perfusion rate of 3 ml/min (II), the efflux of digoxin out of the maternal circuit was lower (p < 0.05) and the influx in the total compartment was reduced (fetal digoxin concentrations reached only 26.9 +/- 10.6% vs. 39.1 +/- 5.5% of the initial maternal digoxin concentrations). These data suggest that severe fetal cardiac insufficiency with reduced placental perfusion may be in part responsible for the decrease of transplacental digoxin passage in fetuses with hydrops.

Anti-Arrhythmia Agents↗

PubMed1996

Digoxin transfer across the isolated placenta is influenced by maternal and fetal albumin concentrations.

The aim of this study was to evaluate the influence of different maternal and fetal albumin concentrations on the transplacental transfer and the placental tissue accumulation of digoxin. Digoxin passage across the isolated lobules of 15 human placentae was calculated from repeated fetal and maternal perfusate samples, and placental tissue digoxin concentrations were measured at the end of the experiments. Metildigoxin (Lanitop) was added to the maternal medium at a concentration of 5.70 +/- 0.73 ng mL-1, and maternal and fetal perfusate albumin (BSA) concentrations were kept equal either at a high concentration of 21 g L-1 (Group I; n = 5) or at a low concentration of 3 g L-1 (Group III; n = 5), or differed with a materno-fetal gradient of 21:3 g L-1 (Group II; n = 5). In the experiments with low maternal albumin concentrations (Group III), digoxin concentrations in the maternal circuit decreased to 3.56 ng mL-1, whereas digoxin concentrations in the fetal circuit reached 2.59 ng mL-1 over a 3-h period. With maternal BSA concentrations of 21 g L-1 (Group I and Group II), the decrease in digoxin concentration in the maternal circuit was lower (P < 0.05), and digoxin tissue concentrations at the end of the experiments were smaller (0.45 +/- 0.07 and 0.42 +/- 0.03 v. 0.82 +/- 0.32 ng mg-1 protein, Group I and Group II v. Group III respectively; P < 0.05). Comparing only those lobules with similar high concentrations of maternal protein, fetal BSA concentrations of 21 g L-1 resulted in a greater increase in digoxin concentrations in the fetal circuit (end-feto to initial-maternal digoxin concentrations of 0.44 +/- 0.08 v. 0.37 +/- 0.04 ng mg-1 protein (Group I v. Group II respectively), although this was not significant. The data suggest that maternal and fetal serum albumin concentrations may have an influence on transplacental digoxin transfer, and this should be considered when treating fetuses with cardiac disease transplacentally with glycosides.

Anti-Arrhythmia Agents↗

PubMed1995

A monoclonal antiidiotypic antibody ACA 125 mimicking the tumor-associated antigen CA 125 for immunotherapy of ovarian cancer.

A new concept of oncological immunotherapy comprises the attempt to trigger the immune system of the host into a response against tumor cells. Antiidiotypic antibodies bearing the internal image of an antigen expressed on the surface of the tumor seem to be most suited for this purpose. We have generated a murine antiidiotypic antibody (ACA 125) functionally imitating the tumor-associated antigen CA 125, which can be detected in about 80% of ovarian carcinomas. The hybridoma cell was adapted to serum-free medium and antibody was produced in a hollow fiber cell culture system (Technomouse). ACA 125 (Ab2) shows high affinity for the paratope of Ab1 (affinity constant: 2.3 x 10(9) liters/mol) and binding of Ab2 to Ab1 is completely inhibited by the nominal antigen. Application of F(ab')2 fragments of ACA 125 to rats lead to an anti-CA 125 immunity by production of IgG and IgM antiantiidiotypic antibodies (Ab3) that bind to both ACA 125 and CA 125. Furthermore the induction of a non-MHC-restricted cell-mediated cytotoxicity for human ovarian adenocarcinoma cell line NIH-OVCAR3 (expressing CA 125 on its surface) could be proved; additionally complement-dependent cytotoxicity (CDC) as well as an antibody-dependent cellular cytotoxicity (ADCC) was observed. Thus, monoclonal antiidiotypic antibody ACA 125 fulfills recent criteria for an antibody, which might be successful in immunotherapy using the anti-idiotypic network approach.

Animals↗

PubMed1994

Idiotypic cascades after injection of the monoclonal antibody OC125. A study in a mouse model.

In an animal model, we evaluated the possibility to induce antibodies directed against the tumor-associated antigen CA125 by immunization with the anti-CA125 antibody OC125 via activation of the idiotypic network. Our results show that Balb/c mice, immunized by repeated administrations of F(ab')2-fragments of the OC125 antibody (Ab1), produced anti-idiotypic antibodies (Ab2). The binding of these antibodies to the OC125 could be completely inhibited by the antigen CA125, suggesting that the anti-idiotypic antibodies imitate the original target antigen of the OC125. After induction of these paratope-binding anti-idiotypic antibodies (Ab2 beta), a murine IgG-anti-CA125 (Ab3) response arose in the same mice. The induction of idiotypic cascades offers the possibility of immunization against tumor-associated antigens without using the original antigen and breaking antitumor tolerance.

Animals↗

PubMed1993

[Folic acid supply in pregnancy--results of a prospective longitudinal study].

After discussing the problem of folic acid requirements and supply during pregnancy, the results of a longitudinal study on 162 pregnant women are presented. By measuring biochemical and morphological changes in two subgroups (non-substituted vs unspecifically substituted), the necessity of a substitution with folic acid is discussed, as there might be additional requirements for the pregnant and the foetal organism. Concentrations of folic acid in the maternal plasma and in the erythrocytes as well as the segmentation rate and hypersegmentation of the granulocytes show a clear decrease in pregnancy. At the same time there was a significant difference between the subjects substituted and not substituted; the foetus and newborn levels were much higher than their mothers' concentrations. Moreover, there was a correlation between red cells folic acid levels in the last trimester and duration and outcome of pregnancy. These results indicate a substitution with folic acid for certain populations in pregnancy, which are highlighted.

Adolescent↗

PubMed1993

Calibrators and control samples for bilirubinometers.

The different matrix properties of neonatal serum and commercial control samples can lead to considerable errors in the calibration and control of bilirubinometers. These difficulties can be avoided by calibration with serum from healthy adults which is supplemented with unconjugated bilirubin. But this procedure is impracticable for most routine laboratories. Under certain preconditions, control samples, with bilirubin concentrations determined with correctly calibrated bilirubinometers or spectrophotometers, are also suitable as calibrators. This was established by determination of the bilirubin concentration of 16 different control samples, using both the reference method and correctly calibrated bilirubinometers or spectrophotometers in three or four specialist laboratories. This was also confirmed in several interlaboratory surveys, some involving up to 72 laboratories. The results of these investigations show that a control sample should be used for the calibration of a bilirubinometer only if it meets the following preconditions: 1. There should be no significant difference between the bilirubin values determined with the reference method and with a correctly calibrated spectrophotometer or bilirubinometer. 2. The bilirubin concentration should lie in the range 230-300 mumol/l. The photometric response of bilirubinometers has a limited linear range, so that analytical results greater than 300 mumol/l must be rated as basically unreliable.

Bilirubin↗

PubMed1993

Idiotypic cascades after injection of the monoclonal antibody OC125: a study in a mouse model. Induction of antibodies against OC125 and CA125 after immunization with an anti-CA 125 (MAb OC125) monoclonal antibody by activation of the idiotypic network.

By immunization of mice with the anti-CA 125 monoclonal antibody OC125, we tried to induce antibodies directed against the tumour-associated antigen CA125, via activation of the idiotypic network. Mice immunized by repeated administrations of F(ab')2-fragments of the OC125 antibody produced anti-idiotypic antibodies, imitating the original target antigen of the OC125. After induction of these anti-idiotypic antibodies (Ab2 beta) a murine IgG-anti-CA125 (Ab3) response was detected. The induction of idiotypic cascades offers the possibility of immunization against tumour-associated antigens, without using the original antigen and breaking antitumour tolerance.

Animals↗

PubMed1993

Effects of thromboxane A2 receptor blockade on oliguric ischemic acute renal failure in conscious rats.

To investigate the potential pathogenetic and therapeutic roles of thromboxane A2 (TXA2) and its receptor blockade, respectively, in the early phase of ischemic acute renal failure (ARF), renal function, TXB2 excretion, and the effects of the specific TXA2 receptor antagonist sulotroban (SU) in a model of unilateral renal artery occlusion in conscious female Sprague-Dawley rats were studied. Occlusion of the left renal artery for 1 h in untreated (i.e., vehicle-treated) rats (N = 8) resulted in oliguric ARF. In SU-treated rats (N = 8), the drug was given as an i.v. bolus of 5 mg/kg body wt, followed by a continuous infusion of 0.5 mg/min.kg body wt from 1 h before and during ischemia and for 6 h after reflow. After 1 h of ischemia, urine volume of left ischemic kidneys from untreated rats had decreased from 13.2 +/- 2.8 to 1.0 +/- 0.3 and 0.5 +/- 0.2 microL/min.100 g at 2 and 6 h of reflow, respectively, and GFR had decreased from 0.32 +/- 0.04 mL/min.100 g body wt to undetectable values. At 6 h of reflow, medullary Na-K-ATPase was slightly (P < 0.05) reduced in left ischemic kidneys, whereas medullary and papillary enzyme activities were compensatorily increased (P < 0.01) in right intact kidneys. The ADP/O ratio of cortical mitochondria was 41% (P < 0.05) and ATP synthesis was 77% (P < 0.01) lower than in right intact kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1992

Impact of antihypertensive therapy with isradipine and metoprolol on early markers of hypertensive nephropathy.

In a double-blind, randomized trial with 26 male white patients with essential hypertension in World Health Organization Stages I and II, we examined the impact of calcium entry blockade (5 to 10 mg/day isradipine, N = 14) and beta-blockade (100 to 200 mg/day metoprolol, N = 12) on early markers of hypertensive nephropathy before and after 7 weeks' treatment. Excretion of total protein, albumin, alpha 1-microglobuline, and N-acetyl-beta-glucosaminidase (NAG) were measured in the 24-h urine by radial immunodiffusion and fluorimetric method, respectively. Before therapy, 8 of 26 patients had microproteinuria (31%), six had microalbuminuria (22%), six had elevated urinary NAG activity (22%), and three had elevated alpha 1-microglobulin excretion (11%). In these subjects anti-hypertensive therapy led to a fall in proteinuria (296 +/- 56 v 127 +/- 116 mg/day, P less than .01), albuminuria (44 +/- 24 v 25 +/- 12 mg/day, P less than .05), and NAG excretion (45 +/- 22 v 28 +/- 5, P less than .05). The higher the pretreatment value, the greater the fall was in proteinuria (r = +0.55, P less than .01), albuminuria (r = 0.80, P less than .001), and NAG excretion (r = 0.60, P less than .01). We did not observe any significant difference in clinical characteristics, blood pressure, or urinary excretion of protein, albumin, or NAG between the two treatment groups, either before or after therapy. Thus, antihypertensive therapy reduced excretion of total protein, albumin, and NAG activity in hypertensive patients with elevated pretreatment values, potentially indicating reversal of early hypertensive nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗

PubMed1992

Endogenous digoxin-like immunoreactive factors (DLIF) as measured by the CEDIA digoxin assay and a fluorescence polarization immunoassay.

The sensitivity of a new homogeneous enzyme immunoassay for the determination of digoxin (CEDIA Digoxin assay) and a fluorescence polarization immunoassay (FPIA) to interference by digoxin-like immunoreactive factors (DLIF) was studied in sera from pregnant women, newborns, patients undergoing hemodialysis and patients with renal insufficiency, but without hemodialysis. None of the patients had been treated with digoxin or digitoxin. Cross-reactivity of DLIF in the CEDIA assay was generally lower than in the FPIA. Data on the distribution DLIF of values and method comparisons showed that sera of the four patient groups reacted in a completely different way in both assays, suggesting that the nature of DLIF in the four groups is not identical. Addition of digoxin to sera of patients not treated with this drug resulted in a reduction of the apparent DLIF concentration in the CEDIA assay and the FPIA. This shows that DLIF interference may be less pronounced in sera of patients undergoing digoxin therapy compared to untreated persons. Although the CEDIA assay is less sensitive to DLIF interference than the FPIA, further efforts are needed to reduce the extent of this interference.

Adult↗

PubMed1992

Results of the multicenter evaluation of a novel homogeneous immunoassay for digoxin based on the cloned enzyme donor immunoassay technology.

A new CEDIA assay for the measurement of digoxin in serum on random access analyzers was evaluated by twelve laboratories in Europe and the United States. Studies on the analytical range, reproducibility, calibration stability, recovery in controls, interlaboratory comparability, comparability with routine methods, and the effect of various interfering factors have been performed and the results are presented in this paper. The analytical performance was comparable to that of routine methods provided the manual pipetting step for pre-incubation was performed with accurate pipettes. A major advantage of the CEDIA Digoxin assay in terms of convenience is the simple two-point calibration procedure. Moreover, digoxin can be determined within 15 minutes after receiving the samples on random access analyzers like Boehringer Mannheim/Hitachi analysis systems. Thus, the CEDIA Digoxin assay represents an attractive alternative to the measurement of digoxin on dedicated immunochemical assay systems.

Calibration↗

PubMed1992

[Reference values for IgE concentration in serum of children. Method: ImmunoCAP-FEIA system].

UNLABELLED: Age specific IgE reference values were determined in serum of 224 children by the aid of the ImmunoCAP fluorescence enzyme immunoassay method. RESULTS: Cord blood: less than 0.35 kU/l; Till 0.5 year: less than 2.0 kU/l; 0.5-2 years: up to 3.8 kU/l; 2-5 years: up to 16.0 kU/l; 5-8 years: up to 26.2 kU/l; 8-12 years: up to 34.6 kU/l; 12-16 years: up to 26.3 kU/l. These IgE reference values can be used for the diagnosis of pathological elevated IgE concentrations in serum of children.

Adolescent↗

PubMed1991

Elevated serum activity of N-acetyl-beta-glucosaminidase in essential hypertension: diagnostic value and reversal to normal values after antihypertensive therapy.

Previous studies have shown that urinary N-acetyl-beta-glucosaminidase (NAG) is elevated in patients with hypertension, even without renal disease. To elucidate the value of measuring NAG, both in urine and serum of hypertensive patients, we measured NAG activity in the serum, plasma, and 24-hour urine by the fluorimetric method in 84 patients with uncomplicated essential hypertension before and after 6 months of effective treatment. NAG activities of these hypertensive patients were compared with those of 102 healthy normotensive subjects and 97 patients with various renal diseases and controlled hypertension. Serum NAG activity was clearly greater in patients with essential hypertension (427 +/- 124 U/mL) than in normotensive subjects (380 +/- 109 U/mL) or patients with renal disorders (393 +/- 115 U/mL) (P less than or equal to 0.004). The greater was the diastolic pressure in the hypertensive group, the greater was serum NAG activity (r = +0.30, P = 0.004). Hypertensive patients with high serum NAG activity were further characterized by a more exaggerated increase in systolic pressure (34 +/- 16 v 25 +/- 15 mm Hg, P = 0.051) and total peripheral resistance (19% +/- 18% v 12% +/- 13%, P = 0.042) in response to the cold pressor test and by a greater increase in systolic pressure (56 +/- 15 v 45 +/- 13 mm Hg, P = 0.009) and diastolic pressure (11 +/- 7 v 6 +/- 9, P = 0.043) in response to bicycle exercise testing than the group with low serum NAG activity. In contrast, urinary NAG activity tended to be only slightly higher in patients with essential hypertension than in the normotensive control group (33 +/- 31 v 23 +/- 29 U/mg creatinine [cr], P = 0.062), whereas patients with renal diseases had clearly increased urinary NAG activity (87 +/- 105 U/mg cr) (P less than 0.001). Following effective antihypertensive therapy, serum NAG activity decreased in patients with essential hypertension to values of normotensive control subjects (from 427 +/- 124 U/mL to 386 +/- 106 U/mL, P less than 0.01). A significant decrease in serum NAG activity was observed in patients with both initially high as well as low pretreatment serum NAG activities (P less than 0.001 and P less than 0.02, respectively). Urinary NAG activity overall was unchanged by antihypertensive treatment. We conclude that in patients with mild essential hypertension, serum NAG activity was already elevated (whereas urinary NAG activity was not) and was normalized by effective antihypertensive treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylglucosaminidase↗

PubMed1991

Enzymatic determination of bilirubin in serum of newborns--any advantage over previous methods?

Using a Hitachi 705 Selective Analyzer at 25 degrees C, precision and accuracy of the enzymatic determination of total bilirubin (DRI-STAT) in serum of newborns was studied. Imprecision (day-to-day) was unacceptably high using daily calibration, but could be reduced by using a fixed factor. Accuracy was checked by analysis of 70 newborn sera with the 'Candidate Reference Method' and DRI-STAT. It could be improved using calibrators with reference method values. Haemoglobin interference was studied by addition of different derivatives of fetal haemoglobin (oxihaemoglobin, desoxihaemoglobin, haemiglobin) to pools of newborn sera and control samples. DRI-STAT is more susceptible to interference by oxihaemoglobin than other routine methods. No difference was found in the influence of oxhihaemoglobin and desoxihaemoglobin; haemiglobin interferes significantly less.

Bilirubin↗

PubMed1991

Determination of digoxin in the blood of pregnant women, fetuses and neonates before and during anti-arrhythmic therapy, using four immunochemical methods.

Four immunochemical methods for digoxin assay were used to analyse control samples, 33 amniotic fluid samples, 57 samples from digitalis-treated, non-pregnant women, 90 pregnancy serum samples, and 72 samples of fetal or neonatal serum with or without digoxin therapy. One hundred and five samples were also submitted to ultrafiltration before analysis. Three methods (RIA, TDX, AMERLITE) showed practically the same precision, while the precision of the DELFIA was markedly inferior. In the analysis of serum samples from digoxin-treated, non-pregnant women, RIA and TDX gave practically the same values, whereas AMERLITE and DELFIA gave significantly higher values. Pregnancy serum and fetal serum contain "digoxin-like immunoreactive factors", and the qualitative and quantitative effects of these interfering factors are different for each of the four methods. The greatest sensitivity to "digoxin-like immunoreactive factors" is shown by TDX and DELFIA, while the lowest interference by "digoxin-like immunoreactive factors" is found in the analysis of ultrafiltered samples, using the TDX method. The composition of the "digoxin-like immunoreactive factors" in pregnancy serum and in fetal serum is altered by digoxin therapy, and these changes have different effects on the various analytical methods. The concentration of "digoxin-like immunoreactive factors" in the serum of fetuses receiving digoxin is markedly lower than that of healthy fetuses. For the reliable monitoring of digoxin therapy in the maternal and fetal circulation, the blood samples must be submitted to ultrafiltration before analysis.

Amniotic Fluid↗

PubMed1991

[Evaluation of the bilirubinometer Hico-Bilimat A 700].

The Hico-Bilimeter A 700 is a simple filter photometer for the determination of total bilirubin in neonatal serum, reading the absorbance of the undiluted sample at two wavelengths. Precision of the measurements is good, with linearity acceptable up to a concentration of 18 mg/dl. Compared to the values obtained with the reference method the results below 18 mg/dl are 16% too high on average; above 18 mg/dl the scatter of results is markedly increased. Even a moderate hemolysis shows a distinct influence on the measurements. Using the instrument tested no reliable results could be obtained, especially in hemolytic samples.

Bilirubin↗

PubMed1991

[Comparison of thyrotropin (TSH), thyroxine (TT4) and triiodothyronine (TT3) concentration in capillary and venous blood serum in children and adolescents].

The thyrotropin, thyroxine and triiodothyronine concentration was compared in sera from capillary and venous blood (n = 50) using a luminescence-enhanced enzyme immuno assay. The results showed a good correlation (TSH, r = 0.991, TT4, r = 0.988, TT3, r = 0.975) and a linear relationship. It is concluded that serum of capillary blood can be used for the in vitro diagnosis of thyroid function.

Adolescent↗