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Torsten Arndt

Publications and source records attributed to Torsten Arndt.

14 recordsLinked to original sources
PubMed2006

Modulation of human motor cortex excitability by single doses of amantadine.

Amantadine-sulfate has been used for several decades to treat acute influenza A, Parkinson's disease (PD), and acute or chronic drug-induced dyskinesia. Several mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate (NMDA)-receptor antagonism, blockage of potassium channels, dopamine receptor agonism, enhancement of noradrenergic release, and anticholinergic effects have been described. We used transcranial magnetic stimulation (TMS) to evaluate the effect of single doses of amantadine on human motor cortex excitability in normal subjects. Using a double-blind, placebo-controlled, crossover study design, motor thresholds, recruitment curves, cortical stimulation-induced silent period (CSP), short intracortical inhibition (ICI), intracortical facilitation (ICF), and late inhibition (L-ICI) in 14 healthy subjects were investigated after oral doses of 50 and 100 mg amantadine with single and paired pulse TMS paradigms. Spinal cord excitability was investigated by distal latencies and M-amplitudes of the abductor digiti minimi muscle. After intake of amantadine, a significant dose-dependent decrease of ICF was noticed as well as a significant increase of L-ICI as compared to placebo. The effect on ICF and L-ICI significantly correlated with amantadine serum levels. ICI was slightly increased after amantadine intake, but the effect failed to be significant. Furthermore, amantadine had no significant effects on motor thresholds, MEP recruitment curves, CSP, or peripheral excitability. In conclusion, a low dose of amantadine is sufficient in modulating human motor cortex excitability. The decrease of ICF and increase of L-ICI may reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic and GABA-ergic circuits. Although amantadine has several mechanisms of action, the NMDA-receptor antagonism seems to be the most relevant effect on cortical excitability. As L-ICI can be influenced by this type of drug, it may be an interesting parameter for studies of motor learning and use-dependent plasticity.

Adult↗
PubMed2006

Argininosuccinate lyase deficiency (ASL) and carbohydrate-deficient transferrin (CDT): experience with four independent CDT analysis methods--misleading results given by the %CDT TIA assay.

BACKGROUND: Chronic liver disease can cause false-positive carbohydrate-deficient transferrin (CDT) results mimicking chronic alcohol abuse. We tested whether argininosuccinate lyase deficiency (ASL), a genetic disorder of the urea cycle with hepatomegaly and biochemical hepatitis, causes increased CDT results and whether this depends on the analytical method. METHODS: Seven serum samples from four ASL patients without alcohol abuse were analyzed by capillary electrophoresis, HPLC, particle-enhanced immunonephelometry with monoclonal CDT antibodies, and microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay with transferrin antibodies (%CDT TIA). RESULTS: Increased CDT results (two out of four patients or five out of seven samples) were obtained by the %CDT TIA assay, but not by the remaining three CDT tests. The corresponding serum samples showed increased fractions of trisialotransferrin by HPLC (as the IFCC reference method for CDT analysis). One sample contained an elevated trisialotransferrin but a normal CDT also in the %CDT TIA test. One patient had a normal trisialotransferrin and a normal CDT as assayed by each of the four CDT methods. CONCLUSIONS: Argininosuccinate lyase deficiency is not itself a cause for increased CDT values. Increased fractions of trisialotransferrin in ASL patients appear to interfere with CDT analysis by the %CDT TIA assay. This can give false-positive CDT results. Since this can appear not only in ASL patients, microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay using transferrin but not CDT antibodies by the %CDT TIA assay should no longer be used for CDT measurement without confirmatory analysis by HPLC or capillary electrophoresis.

Adolescent↗
PubMed2006

Primary biliary cirrhosis is not a clinical condition for increased carbohydrate-deficient transferrin: experience with four independent CDT analysis methods.

BACKGROUND: Primary biliary cirrhosis (PBC) is considered as an important cause for increased carbohydrate-deficient transferrin (CDT). The underlying pathomechanism is difficult to explain by the pathogenesis and/or consequences of PBC. We tested whether PBC causes increased CDT results with current CDT analysis methods and, if so, whether this depends on the CDT analysis principle. METHODS: 48 serum samples from PBC patients were analyzed by HPLC, microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay, particle-enhanced immunonephelometry with monoclonal CDT antibodies, and capillary electrophoresis. The test-specific decision limits were used for categorization of the CDT analysis results into normal and increased values. RESULTS: HPLC: 47 normal/1 increased, microcolumn+TIA: 46 normal/2 increased, particle-enhanced immunonephelometry: 41 normal/7 increased, capillary electrophoresis: 48 normal CDT results. After combining an immunological CDT test (microcolumn+TIA or particle-enhanced immunonephelometry) as the screening method with a physico-chemical CDT test (HPLC or electrophoresis) as the confirmatory method, 1 case remained with increased CDT values by the screening (value 2.6%, cut-off 2.5%, particle-enhanced immunonephelometry) and confirmatory (value 1.8%, cut-off 1.75%, HPLC) analysis. CONCLUSIONS: PBC should no longer be overstressed as an important cause for false-positive CDT results regarding chronic alcohol abuse. In the presence of odd CDT results, PBC should be considered in the anamnestic exploration. However, PBC is not by itself a cause for increased CDT values.

Adult↗
PubMed2005

Determination of serum amantadine by liquid chromatography-tandem mass spectrometry.

BACKGROUND: Amantadine (1-adamantylamine) is used for treatment of influenza, hepatitis C, parkinsonism, and multiple sclerosis. Current amantadine analysis by HPLC or gas chromatography (GC) requires a laborious sample pretreatment with extraction and/or derivatization steps. We established an LC-MS/MS method without protein precipitation, centrifugation, extraction and derivatization steps. MATERIAL AND METHODS: 50 microl sample+50 microl of 0.4 mg/l 1-(1-adamantyl)pyridinium bromide as internal standard+1000 microl water (96-well plate). Of this 25 microl+500 microl water (96-well plate; final serum dilution 1:462). LC-MS/MS: Surveyor MS pump, Autosampler, triple-quadrupole TSQ Quantum mass spectrometer (Thermo Electron). Autosampling: 2 microl of each sample. Chromatography: isocratic water/acetonitrile (60/40 v/v) with 5 g/l formic acid, flow rate 0.2 ml/min, run time 3 min, Phenomenex Luna C8(2) (100 x 2.0 mm (i.d.); 3-microm bead size) column. Mass spectrometry: electrospray atmospheric pressure ionization, positive ion and selective reaction monitoring mode, ion transitions m/z 152.0-->135.1 (at 22 eV amantadine) and 214.1-->135.1 (at 26 eV internal standard). RESULTS: Calibration curves were constructed with spiked serum samples (amantadine 50-1000 microg/l, r>0.99). No carry over (5000 microg/l). No ion suppression with retention times similar to those of amantadine (1.8 min) and the internal standard (2.1 min). Detection limit 20 mg/l, linearity 20-5000 mg/l, intra-assay/inter-assay CV<6%/<8%, recovery 99-101%. Method comparison: LC-MS/MS=1.23 x GC-45 (Passing-Bablok regression). No significant bias between GC and LC-MS/MS (Bland-Altman plot). CONCLUSION: We consider the sample pretreatment without deproteination, derivatization and centrifugation steps and the specificity of the tandem mass spectrometry as the most important points of our amantadine analysis method.

Amantadine↗
PubMed2004

Forensic analysis of carbohydrate-deficient transferrin (CDT): implementation of a screening and confirmatory analysis concept is hampered by the lack of CDT isoform standards.

The aim of the study was to test combinations of commercially available carbohydrate-deficient transferrin (CDT) assays for their usefulness as screening and confirmatory CDT analysis systems. A set of 292 serum samples from routine CDT analysis was analyzed by two assays based on anion-exchanger microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay (ChronAlcoI.D. and %CDT TIA) and a high-performance liquid chromatography with on-line sample preparation (ClinRep CDT on-line). The CDT analysis results were divided into four groups based on the test-specific borderlines of the compared methods: NN with negative CDT results by both tests, PN with positive screening but negative confirmation results, NP with negative screening and positive confirmation results, and PP with positive results by both tests. Regardless of the test combination and whether applying the lower or upper limits of the borderlines, approximately one-third of contradictory (positive screening and negative confirmation or vice versa corresponding to groups PN and NP) were obtained. This was not due to analytical outliers (only 6 of 292 serum samples). Indeed, parametric and non-parametric ANOVA analysis pointed to different calibrations and/or recoveries of the three CDT assays. Our data give again evidence for the urgent need of an international CDT isoform standard material. At this time, we cannot recommend a combination of the three tests for screening and confirmatory analysis in forensic CDT testing.

Alcoholism↗
PubMed2002

A prolonged time interval between blood sample collection and centrifugation causes an increase in serum carbohydrate-deficient transferrin.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) is used for the laboratory diagnosis of chronic alcohol abuse. Non-optimal preanalysis can cause an increase in CDT and false positive results. The aim of our study was to determine whether CDT results change over time between collection of the blood sample and centrifugation, and whether shipment of whole blood samples is a potential source of false positive CDT reports. MATERIAL/METHODS: 152 blood samples were drawn from 38 persons (4 tubes per person, one venipuncture) and randomly assigned to 4 groups with different time intervals between blood sample collection and centrifugation (1h, 24h, 48h, 144h). CDT analysis was done using the ChronAlcoI.D. assay. The statistical analysis was based on box-plots, ANOVA and Kruskal-Wallis ANOVA. RESULTS: The means and medians of CDT increased with the time of whole blood storage. ANOVA analysis of between-group differences was significant for mean CDT concentrations between 1 and 144 hours of whole blood storage. There was no correlation between CDT and free hemoglobin as a measure of hemolysis. An interference of hemolysis with CDT measurement can be excluded as the main cause of increased CDT results with whole blood storage time. Whether an in vitro degradation of the transferrin N-glycan chains causes the CDT increase should be evaluated by isoelectric focusing of the transferrin isoforms in a further study. CONCLUSIONS: Storage or shipment of whole blood samples can shift initially normal CDT values to borderline and borderline to pathological CDT results.

Blood↗
PubMed2002

Further arguments against including trisialo-Fe2-transferrin in carbohydrate-deficient transferrin (CDT): a study on male alcoholics and hazardous drinkers.

BACKGROUND: We attempted to determine whether including trisialo-Fe2-transferrin in carbohydrate-deficient transferrin (CDT) affects the diagnostic accuracy of CDT as a marker of chronic excessive alcohol intake. MATERIAL/METHODS: The criterion standard tests for the diagnosis of alcoholism and alcohol intake were the Composite International Diagnostic Interview (CIDI) and the Timeline-Followback (TLFB). The study groups (alcohol intake in each of the last 4 weeks before blood sampling) were comprised of 56 controls (< or = 280 g/week, no alcoholism), 54 hazardous drinkers (>280 g/week, no alcoholism), 63 alcoholics (>280 g/week, alcoholism diagnosis). CDT analysis was performed with %CDTri-TIA, which includes about 50% of trisialo-Fe2-transferrin in CDT, and ChronAlcoI.D, which excludes this transferrin isoform from CDT. RESULTS: Depending on the cut-offs for the CDT/transferrin ratio (upper or lower limit of the test-specific borderlines) and on the patient group, the diagnostic sensitivity was 28.1%-72.3% for %CDTri-TIA, as opposed to 50.0%-82.5% for ChronAlcoI.D. The diagnostic accuracy was 62.8%-78.5% for %CDTri-TIA and 71.8%-86.6% for ChronAlcoI.D. The latter test consistently showed higher diagnostic sensitivity and accuracy than %CDTri-TIA. The diagnostic specificity was 85.7%-98.2% for %CDTri-TIA and 91.1%-92.2% for ChronAlcoI.D. The areas under the ROC curve were 0.810%-0.885 for %CDTri-TIA and 0.867%-0.896 for ChronAlcoI.D. CONCLUSIONS: The present study and data from the literature indicate that including parts of trisialo-Fe2-transferrin by the %CDTri-TIA test significantly reduces the diagnostic sensitivity and thus accuracy of CDT as a marker of chronic excessive alcohol use.

Adult↗