Save the children by treating their mothers (PriVileG-M-study) - study protocol: a sequentially randomized controlled trial of individualized psychotherapy and telemedicine to reduce mental stress in pregnant women and young mothers and to improve Child's health.

BACKGROUND: As early as pregnancy, maternal mental stress impinges on the child's development and health. Thus, this may cause enhanced risk for premature birth, lowered fetal growth, and lower fetal birth weight as well as enhanced levels of the stress hormone cortisol and lowered levels of the bonding hormone oxytocin. Maternal stress further reduces maternal sensitivity for the child's needs which impairs the mother-child-interaction and bonding. Therefore, prevention and intervention studies on mental stress are necessary, beginning prenatally and applying rigorous research methodology, such as randomized controlled trials, to ensure high validity. METHODS: A randomized controlled trial is used to assess the impact of psychotherapy and telemedicine on maternal mental stress and the child's mental and physical health. Mentally stressed pregnant women are randomized to an intervention (IG) and a not intervened control group. The IG receives an individualized psychotherapy starting prenatal and lasting for 10 months. Afterwards, a second randomization is used to investigate whether the use of telemedicine can stabilize the therapeutic effects. Using ecological momentary assessments and video recordings, the transfer into daily life, maternal sensitivity and mother-child-bonding are assessed. Psycho-biologically, the synchronicity of cortisol and oxytocin levels between mother and child are assessed as well as the peptidome of the colostrum and breast milk, which are assumed to be essential for the adaptation to the extra-uterine environment. All assessments are compared to an additional control group of healthy women. Finally, the results of the study will lead to the development of a qualification measure for health professionals to detect mental stress, to treat it with low-level interventions and to refer those women with high stress levels to mental health professionals. DISCUSSION: The study aims to prevent the transgenerational transfer of psychiatric and somatic disorders from the mother to her child. The effects of the psychotherapy will be stabilized through telemedicine and long-term impacts on the child's and mothers' mental health are enhanced. The combination of psychotherapy, telemedicine and methodologies of ecological momentary assessment, video recording and bio banking are new in content-related and methodological manner. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017065. Registered 02 May 2019. World Health Organization, Universal Trial Number: U1111-1230-9826. Registered 01 April 2019.

Chronic Toxicity of 4-Nonylphenol to Two Unionid Mussels in Water-Only Exposures.

Limited studies indicate that mussels are generally insensitive to organic chemicals; however, these studies were conducted in acute or short-term exposures, and little is known about the chronic sensitivity of mussels to organic chemicals. We evaluated the chronic (28 days) toxicity of 4-nonylphenol (4-NP) to two commonly tested species of mussels: fatmucket (Lampsilis siliquoidea) and rainbow mussel (Villosa iris). By the end of the 28 days chronic exposures, mean survival was ≥93% in all treatments, but the mean dry weight and biomass of mussels at the highest exposure concentrations were significantly reduced relative to the control. The 20% effect concentrations were similar between the two species. When compared to all other tested species, fatmucket and rainbow mussels are among the top four most sensitive species to 4-NP. However, U.S. Environmental Protection Agency chronic water quality criterion of 6.6 µg 4-NP/L should protect the two mussel species.

Risk factors for necrobiosis lipoidica in Type 1 diabetes mellitus.

AIMS: To compare the clinical and metabolic characteristics of patients with Type 1 diabetes and necrobiosis lipoidica with those of patients with Type 1 diabetes who do not have necrobiosis lipoidica. A multicentre analysis was performed. METHODS: Clinical and laboratory data were obtained from 64 133 patients (aged 0-25 years) with Type 1 diabetes with and without necrobiosis lipoidica who were registered in the German/Austrian Diabetes Prospective Documentation Initiative registry. Data were analysed using multivariable regression modelling. Age, diabetes duration, treatment year and sex were considered as confounding factors. RESULTS: Results adjusted for demographic variables are presented. In patients with necrobiosis lipoidica, metabolic control was worse (HbA1c 72 vs. 67 mmol/mol, 8.7% vs. 8.3%; P = 0.0065) and the duration of diabetes was longer [6.24 (3.28-9.97) vs. 5.11 (2.08-8.83) years; P = 0.014; not adjusted]. Patients with necrobiosis lipoidica required higher insulin doses than those without (1.02 vs. 0.92 U/kg/day; P < 0.0001). There was no significant difference in the frequency of microvascular complications (microalbuminuria and retinopathy) between the groups. Furthermore, 24.8% and 17.5% of patients with Type 1 diabetes with and without necrobiosis lipoidica, respectively, had elevated thyroid antibodies (P = 0.051). Necrobiosis lipoidica was correlated with coeliac disease in patients with Type 1 diabetes (3.4% vs. 1.0%; P = 0.0035). CONCLUSIONS: Our data indicate a strong correlation between hyperglycaemia and the development of necrobiosis lipoidica. We postulate that the underlying pathogenic processes differ from those leading to microalbuminuria and retinopathy, and additional immunological mechanisms may play a role.

Diabetes in Patients with ß-thalassemia or other Hemoglobinopathies - Analysis from the DPV Database.

Background: Diabetes mellitus is a common endocrinopathy in patients with thalassemia major, but the occurrence of hemoglobinopathies is rare in Germany and Western Europe. The longitudinal German-Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry allows a comprehensive characterization of this group of patients. Patients/methods: Patients from the DPV-registry aged<30 years with thalassemia major or other hemoglobinopathies were compared to patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) using the statistical software SAS 9.4. Results: 94 patients (0.13% of patients) with hemoglobinopathies are registered in DPV. 82.4% of 17 patients with thalassemia major, 100% of 12 patients with sickle cell disease (SCD) and >90% of 65 patients with other hemoglobinopathies receive insulin treatment. In the majority of patients with thalassemia major, hemosiderosis is documented. Patients with thalassemia major developed diabetes at a median age of 14.6 [IQR 8.4-18.0] years (9.0 years [5.3-12.5] in T1D; 18.7 years [14.2-25.6] in TD2; both p<0.01). They show high HbA1c/fructosamine levels and frequent hypoglycemia, reflecting poor metabolic control. Conclusion: Diabetes in thalassemia major is probably caused by hemosiderosis due to polytransfusion, while patients with SCD/thalassemia minor are most likely affected by T1D. The high rate of hypoglycemia in patients with ß-thalassemia major may be caused by liver fibrosis and a lack of hepatic glycogen stores.

Introducing excess body weight in childhood and adolescence and comparison with body mass index and waist-to-height ratio.

BACKGROUND: Weight status in children and adolescents is commonly defined using age- and gender-corrected standard deviation scores for body mass index (BMI-SDS, also called z-scores). Values are not reliable for the extremely obese however. Moreover, paediatricians and parents may have difficulties understanding z-scores, and while percentiles are easier to gauge, the very obese have values above the 99th percentile, making distinction difficult. The notion of excess body weight (EBW) is increasingly applied in adult patients, mainly in the context of bariatric surgery. However, a clear definition is not available to date for the paediatric population. METHODS: A simple definition of EBW for children and adolescents is introduced, with median weight as a function of height, age and gender (characterized by an asterisk): EBW (%) = 100x(weight-median weight*)/median weight*. EBW is compared with BMI-SDS and waist-to-height ratio (WHtR). Using two data sources (APV registry and German Health Interview and Examination Survey for Children and Adolescents (KiGGS)) including more than 14,000 children, the relationships between these anthropometric and various metabolic parameters are analysed for a group of overweight/obese children who have sought obesity therapy (APV), for the general paediatric population and for the subset of overweight/obese children from the general population (KiGGS). RESULTS: The three anthropometric parameters are strongly correlated, with the linear correlation coefficients exceeding 0.8 in the general population and 0.75 in those seeking obesity therapy. Moreover, their relationship to metabolic parameters is quite similar regarding correlations and area under the curve from receiver operating characteristic analyses. CONCLUSIONS: EBW has similar predictive value for metabolic or cardiovascular comorbidities compared with BMI and WHtR. As it is reliable at the extreme end of the obesity spectrum, easily communicable and simple to use in daily practice, it would make a very useful addition to existing tools for working with obese children and adolescents. Its usefulness in assessing weight change needs to be studied however.

Quantitative analysis of the intra- and inter-subject variability of the whole salivary proteome.

BACKGROUND AND OBJECTIVE: Interest in human saliva is increasing for disease-specific biomarker discovery studies. However, protein composition of whole saliva can grossly vary with physiological and environmental factors over time and it comprises human as well as bacterial proteins. MATERIAL AND METHODS: We compared intra- and inter-subject variabilities using complementary gel-based (two-dimensional difference gel electrophoresis, 2-D DIGE) and gel-free (liquid chromatography tandem mass spectrometry, LC-MS/MS) proteomics profiling of saliva. Unstimulated whole saliva of four subjects was examined at three different time-points (08.00 h, 12.00 h and 17.00 h) and variability of the saliva proteome was analyzed on two successive days by LC-MS/MS. RESULTS: In the 2-D DIGE experiment, the median coefficient of variation (CV) for intra-subject variability was significantly lower (CV of 0.39) than that for inter-subject variability (CV of 0.57; CV of technical replicates 0.17). LC-MS/MS data confirmed the significantly lower variation within subjects over time (CV of 0.37) than the inter-subject variability (CV of 0.53; CV of technical replicates 0.11), and that the inter-subject variability was not time-dependent. CONCLUSION: Both techniques revealed similar trends of variations on technical, intra- and inter-subject level but provided peptide and protein focused information and should thus be used as complementary approaches. The data presented indicate that 2-D DIGE as well as LC-MS/MS approaches are suitable for biomarker screening in saliva.

Regulation of interferon-inducible proteins by doxorubicin via interferon γ-Janus tyrosine kinase-signal transducer and activator of transcription signaling in tumor cells.

Activation of the immune system is a way for host tissue to defend itself against tumor growth. Hence, treatment strategies that are based on immunomodulation are on the rise. Conventional cytostatic drugs such as the anthracycline doxorubicin can also activate immune cell functions of macrophages and natural killer cells. In addition, cytotoxicity of doxorubicin can be enhanced by combining this drug with the cytokine interferon-γ (IFNγ). Although doxorubicin is one of the most applied cytostatics, the molecular mechanisms of its immunomodulation ability have not been investigated thoroughly. In microarray analyses of HeLa cells, a set of 19 genes related to interferon signaling was significantly over-represented among genes regulated by doxorubicin exposure, including signal transducer and activator of transcription (STAT) 1 and 2, interferon regulatory factor 9, N-myc and STAT interactor, and caspase 1. Regulation of these genes by doxorubicin was verified with real-time polymerase chain reaction and immunoblotting. An enhanced secretion of IFNγ was observed when HeLa cells were exposed to doxorubicin compared with untreated cells. IFNγ-neutralizing antibodies and inhibition of Janus tyrosine kinase (JAK)-STAT signaling [aurintricarboxylic acid (ATA), (E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490), STAT1 small interfering RNA] significantly abolished doxorubicin-stimulated expression of interferon signaling-related genes. Furthermore, inhibition of JAK-STAT signaling significantly reduced doxorubicin-induced caspase 3 activation and desensitized HeLa cells to doxorubicin cytotoxicity. In conclusion, we demonstrate that doxorubicin induces interferon-responsive genes via IFNγ-JAK-STAT1 signaling and that this pathway is relevant for doxorubicin's cytotoxicity in HeLa cells. Immunomodulation is a promising strategy in anticancer treatment, so this novel mode of action of doxorubicin may help to further improve the use of this drug among different types of anticancer treatment strategies.

Neural mechanisms of brain-computer interface control.

Brain-computer interfaces (BCIs) enable people with paralysis to communicate with their environment. Motor imagery can be used to generate distinct patterns of cortical activation in the electroencephalogram (EEG) and thus control a BCI. To elucidate the cortical correlates of BCI control, users of a sensory motor rhythm (SMR)-BCI were classified according to their BCI control performance. In a second session these participants performed a motor imagery, motor observation and motor execution task in a functional magnetic resonance imaging (fMRI) scanner. Group difference analysis between high and low aptitude BCI users revealed significantly higher activation of the supplementary motor areas (SMA) for the motor imagery and the motor observation tasks in high aptitude users. Low aptitude users showed no activation when observing movement. The number of activated voxels during motor observation was significantly correlated with accuracy in the EEG-BCI task (r=0.53). Furthermore, the number of activated voxels in the right middle frontal gyrus, an area responsible for processing of movement observation, correlated (r=0.72) with BCI-performance. This strong correlation highlights the importance of these areas for task monitoring and working memory as task goals have to be activated throughout the BCI session. The ability to regulate behavior and the brain through learning mechanisms involving imagery such as required to control a BCI constitutes the consequence of ideo-motor co-activation of motor brain systems during observation of movements. The results demonstrate that acquisition of a sensorimotor program reflected in SMR-BCI-control is tightly related to the recall of such sensorimotor programs during observation of movements and unrelated to the actual execution of these movement sequences.

Laccase-induced derivatization of unprotected amino acid L-tryptophan by coupling with p-hydroquinone 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide.

We have studied the enzymatic derivatization of amino acids by use of the polyphenol oxidase laccase. Derivatization of L-tryptophan was achieved by enzymatic crosslinking with the laccase substrate 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide. The main product (yield up to 70%) was identified as the quinoid compound 2-[2-(2-hydroxy-ethylcarbamoyl)-3,6-dioxo-cyclohexa-1,4-dienylamino]-3-(1H-indol-3-yl)- propionic acid and demonstrates that laccase-catalyzed C-N-coupling occurred on the amino group of the aliphatic side chain. These enzyme based reactions provide a simple and fast method for the derivatization of unprotected amino acids.

Threshold duration of ischemia for myogenic tone in middle cerebral arteries: effect on vascular smooth muscle actin.

BACKGROUND AND PURPOSE: We investigated the effect of different periods of ischemia on the myogenic tone of middle cerebral arteries (MCAs) and tested the hypothesis that ischemia disrupts the actin cytoskeleton in vascular smooth muscle. METHODS: The MCA occlusion model was used in male Wistar rats (n=27) to induce different periods of ischemia (15, 30, and 120 minutes) with 24 hours of reperfusion. Successful occlusion was determined by laser-Doppler flowmetry. MCAs were then studied in vitro with a specialized arteriograph system that allowed control of transmural pressure and measurement of lumen diameter. After equilibration for 1 hour at transmural pressure of 75 mm Hg, lumen diameter was measured, and the amount of spontaneous myogenic tone was determined. Arteries were then fixed with 10% formalin while still pressurized in the arteriograph bath and stained for filamentous (F-) actin with fluorescently labeled phalloidin, a specific probe for F-actin. The amount of F-actin was quantified by confocal microscopy. RESULTS: The amount of tone was similar between control and 15 minutes of ischemia (27.0+/-2.0% and 25.3+/-1.7%, respectively; P>0.05) but was significantly diminished after 30 and 120 minutes (11.7+/-2.0% and 8.5+/-2.0%, respectively; P<0.01 versus control). F-actin content also decreased at the longer ischemic periods and correlated significantly with vascular tone (P=0.04) such that the lesser the tone, the lesser was the F-actin content. Fluorescence intensity for control and 15, 30, and 120 minutes of ischemia was (x10(7)) 3.21+/-0.25, 2.54+/-0.32 (P>0.05), 2.32+/-0.15 (P<0.01), and 2.22+/-0.16 (P<0.01), respectively. CONCLUSIONS: These results demonstrate that ischemia disrupts the actin cytoskeleton in smooth muscle and diminishes vascular tone of MCAs in a threshold-dependent manner. This effect likely exacerbates brain tissue damage during stroke, including infarction and edema formation.

The effect of D-ser (TBU)6-LH-RH-EA10 upon gonadotropin release in normally cyclic women.

D-Ser (TBU)6-LH-RH-EA10 (HOE 766) was found to be approximately 40-times as effective as LH-RH in stimulating LH and FSH release in normally cyclic women. The most pronounced reaction was seen in the late follicular phase, the least one in the early follicular phase. Maximal serum gonadotropin levels were found 4 h after the injection of HOE 766. When 5 microgram was injected every 8 h for 3 days, the initially high release of LH and FSH declined progressively to almost nil.

Ambient solar UV radiation causes mortality in larvae of three species of Rana under controlled exposure conditions.

Recent reports concerning the lethal effects of solar ultraviolet-B (UV-B) (290-320 nm) radiation on amphibians suggest that this stressor has the potential to impact some amphibian populations. In this study embryos and larvae of three anuran species, Rana pipiens, Rana clamitans and Rana septentrionalis, were exposed to full-spectrum solar radiation and solar radiation filtered to attenuate UV-B radiation or UV-B and ultraviolet-A (UV-A) (290-380 nm) radiation to determine the effects of each wavelength range on embryo and larval survival. Ambient levels of solar radiation were found to be lethal to all three species under exposure conditions that eliminated shade and refuge. Lethality was ameliorated by filtration of UV-B radiation alone, demonstrating that ambient UV-B radiation is sufficient to cause mortality. Although several studies have qualitatively demonstrated the lethality of UV-B to early life stage amphibians this study demonstrates that the larval life stages of the three species tested are more sensitive than the embryonic stages. This suggests that previous reports that have not included the larval life stage may underestimate the risk posed to some anuran populations by increasing UV-B exposure. Furthermore, this study reports quantitative UV-B dosimetry data, collected in conjunction with the exposures, which can be used to begin the assessment of the impact of environmental changes which increase UV-B exposure of these anurans.

The role of polyols in cerebral cell volume regulation in hypernatremic and hyponatremic states.

To clarify the role of the sugar polyols, sorbitol and myo-inositol, in cerebral cell volume regulation, we studied the effect of sorbinil, an inhibitor of aldose and aldehyde reductase, on the size of the cerebral water compartments in rats with hypernatremia, hyponatremia and normonatremia. Experimental animals were pretreated with sorbinil, while comparison rats received the drug vehicle. Rats were made hypernatremic for 96 h by water deprivation and injections of hypertonic saline, while hyponatremia was provoked over 48 h by daily administration of 5% dextrose in water and vasopressin. Sorbinil treatment was continued throughout the hyper- and hyponatremic periods. The severity of hypernatremia and hyponatremia was similar in sorbinil-treated and corresponding vehicle-treated rats. Brain electrolyte content and the size of the cerebral intracellular water compartment were comparable in sorbinil-treated rats vs. controls under hypernatremic and hyponatremic conditions. Sorbinil reduced the cerebral sorbitol content by approximately 50%, irrespective of the serum Na+ concentration. In contrast, sorbinil had no effect on brain myo-inositol content which rose by 114% during chronic hypernatremia (P less than 0.0001). Cerebral levels of myo-inositol did not decline in hyponatremic rats. We conclude that (1) sorbitol is not an essential cerebral osmolyte; and (2) myo-inositol is involved in the maintenance of brain cell volume during severe hypernatremia but not under hyponatremic conditions.

Anaerobic formation and degradation of toxic aromatic compounds in agricultural and communal sewage deposits.

Relatively high concentrations of phenol, p-cresol, phenylacetic acid and other aromatic compounds were found in agricultural and communal sewage deposits. These toxic aromatic compounds are products of the bacterial degradation of aromatic amino acids under anaerobic conditions. In laboratory experiments at 26 degrees C and under N2-atmosphere, the same aromatics were formed from the amino acid tyrosine and from gelatine in assays inoculated with sewage sludge. After exhaustion of tyrosine and gelatine, respectively, concentrations of the accumulated phenol and other aromatics remained stable for months, i.e., phenol, p-cresol, phenylacetic acid etc. are dead-end products of the bacterial metabolism under these conditions. After addition of sodium nitrate the aromatic compounds are metabolically decomposed by denitrification within weeks.

Oxidation of triphenylarsine to triphenylarsineoxide by Trichoderma harzianum and other fungi.

Arsenic resistant strains of bacteria and fungi were isolated from soil contaminated by chemical warfare agents. Until now, no metabolic products of microbial attack against the phenyl residues of the model substrate triphenylarsine (TP) were found if it was incubated together with these strains in liquid culture assays. However, one of the isolated fungi, Trichoderma harzianum As 11, was found to oxidize TP to triphenylarsineoxide (TPO). The yeast Trichosporon mucoides SBUG 801 and the white-rot fungus Phanerochaete chrysosporium were also able to oxidize the As(III) in TP. In addition, P. chrysosporium transformed phenylarsineoxide (PAO) to phenylarsonic acid (PAA) under O2-atmosphere. By means of a respirometer system, the oxidation of TP by T. harzianum As 11 was confirmed by a significantly higher consumption of oxygen in the presence of these compounds. HPLC analysis of the oxidation products TPO and PAA in the medium of the assays provided evidence for the transfer reaction of As(III) to As(V) in organic bonds. The oxidation products TPO and PAA are more hydrophilic than TP and PAO. Therefore, it was concluded that particular fungi contribute to the mobilization of arsenic in soil contaminated by chemical warfare agents.

Effect of selected environmental factors on degradation and mineralization of biaryl compounds by the bacterium Ralstonia pickettii in soil and compost.

By varying selected environmental factors, the degradation and mineralization of biaryl compounds by the bacterium Ralstonia pickettii in soil and compost were investigated. An optimized soil moisture and enhanced bioavailability by using the nonionic surfactant Tween 80 were of great importance for the degradation rates of biaryl compounds like biphenyl and 4-chlorobiphenyl by cells of Ralstonia picketti SBUG 290 inoculated into soil. Additionally, degradation of these compounds by the investigated strain in soil was strongly dependent upon the medium of precultivation. Also the influence of temperature and soil pH-value was tested. In contrast to the used soil, the autochthonous flora of the compost seemed to have a higher physiological activity. All investigated compounds (biphenyl, 4-chlorobiphenyl and dibenzofuran) were degraded quickly in compost. Inoculation with the investigated bacterium did not enhance the degradation rates significantly.

Videoendoscopic assessment of dynamic laryngeal function during exercise in horses with grade-III left laryngeal hemiparesis at rest: 26 cases (1992-1995).

OBJECTIVE: To evaluate laryngeal function by means of videoendoscopy during high-speed treadmill exercise in racehorses with grade-III left laryngeal hemiparesis at rest and to determine outcome of treatment. DESIGN: Retrospective study. ANIMALS: 26 racehorses. PROCEDURE: Videoendoscopy of the larynx was performed while horses were at rest and exercising on a treadmill. Horses were classified as having grade-IIIA, -IIIB, or -IIIC laryngeal hemiparesis on the basis of the degree of arytenoid cartilage abduction maintained during exercise. Postoperative racing performance was determined by evaluating race records and conducting telephone surveys. RESULTS: 20 (77%) horses had grade-IIIC laryngeal hemiparesis (i.e., severe dynamic laryngeal collapse during exercise). Eighteen underwent surgery, and racing performance was improved in 9. Five (19%) horses had grade-IIIB laryngeal hemiparesis (i.e., left arytenoid cartilage and vocal fold were maintained in an incompletely abducted position during exercise). Four underwent surgery, and racing performance was improved in 1. One (4%) horse had grade-IIIA laryngeal hemiparesis (i.e., full abduction of arytenoid cartilage during exercise); surgery was not performed. CLINICAL IMPLICATIONS: Videoendoscopy is useful in determining dynamic laryngeal function in racehorses with grade-III laryngeal hemiparesis at rest.

Injury to the origin of the gastrocnemius muscle as a possible cause of lameness in four horses.

Four horses were evaluated because of hind limb lameness. Two had a distinct gait abnormality at the walk characterized by lateral rotation of the point of the calcaneus and medial rotation of the toe during the stance phase. Nuclear scintigraphy revealed a focal area of intense radioisotope uptake in the caudodistal aspect of the femur in all 4 horses, and 3 of the horses had a corresponding proliferative reaction on the caudodistal cortex of the femur on radiographs. In all 4 horses, a diagnosis of injury to the origin of the gastrocnemius muscle was made. Three of the horses returned to athletic endeavors after an extended period of rest and a gradual return to exercise. The fourth improved after 5 months of rest but became lame again when returned to exercise and was euthanatized.

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.

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

We evaluated a CEDIA assay for the determination of digitoxin in serum on random access analyzers. The multicenter evaluation included studies on the analytical range, calibration stability and reproducibility of the new assay. Moreover, recovery in controls, transferability of results obtained in different laboratories, comparability with routine methods, and the effect of various interfering factors have been analyzed. Summarized the analytical performance was comparable to that of routine methods. The CEDIA Digitoxin assay represents an attractive alternative to established digitoxin immunoassays because it can be performed on random access analyzers, thus permitting the simultaneous determination of digitoxin and other serum analytes without sample splitting.