Torsten Arndt

Bioscientia - Institut für Medizinische Diagnostik GmbH, Frankfurt, Hesse, Germany

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Publications (49)144.12 Total impact

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    ABSTRACT: Ethyl glucuronide (EtG) in urine is considered a marker of recent alcohol consumption. Using immunoassays for EtG screening without confirmatory analysis bears a risk of getting false-positives as shown for trichloroethyl glucuronide from chloral hydrate medication and 1-propyl glucuronide from propanol-based hand disinfection. The aim of the study was to check whether glucuronides of frequently used aliphatic short chain alcohols aside from EtG and 1-propyl glucuronide can cross-react with the DRI(®) Ethyl Glucuronide Assay.
    Forensic Science International 05/2014; 241C:84-86. DOI:10.1016/j.forsciint.2014.05.015 · 2.12 Impact Factor
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    ABSTRACT: Ethyl glucuronide (EtG) in urine is considered a specific marker of recent ethanol consumption. There is an ongoing debate about whether inhalation or transdermal resorption of sanitizer ethanol is the underlying cause for positive EtG findings after hand disinfection. Desderman(®) pure (Schülke & Mayr GmbH, Norderstedt) with 78.2g 96% (v/v) ethanol/100g and approx. 10% 2-propanol was used for multiple hand disinfection without and under an exhauster. Simulating a common working day in a clinic, 5 co-workers of our lab used the sanitizer 32 fold within 8h and 2 persons were merely exposed to the sanitizer vapor but without any dermal sanitizer contact. Any additional ethanol intake or exposition was reliably excluded. Spot urine was collected at baseline, after 1, 2, 4, 6 … 14, and finally 24h after the first sanitizer use. A validated LC-MS/MS was used for MRM and MS(3) of EtG and qualitative analyses of ethyl sulfate and 2-propyl glucuronide. Multiple hand disinfection caused positive EtG findings of up to 2.1mg/L or 1.7mg/g creatinine in 4 out of 5 test persons and even of 0.6mg/L or 0.8mg/g for 2 controls which were merely exposed to the sanitizer vapor but without any sanitizer contact. EtG results between the clinical (0.5mg/g) and the forensic (0.1mg/g) cut-off were obtained even 6h after the last sanitizer exposition. An exhauster prevented the sanitizer vapor inhalation and reduced the EtG excretion to mostly below the detection limit of 0.02mg/g. The maximum value was 0.09mg/g. Ethyl sulfate and 2-propyl glucuronide (2-PpG) were detectable only in the EtG positive samples. 2-PpG is a metabolite of 2-propanol, which is quite frequently used in disinfectants. Thus, the detection of this substance can be used in cases of odd EtG results as an indicator of (unintended) sanitizer exposition. Ethanol from hand sanitizers is predominantly incorporated by the respiratory tract but not via the skin. It can cause a distinct ethyl glucuronide excretion and thus analytically true-positive but forensically false-positive EtG findings in the urine of ethanol abstaining persons. Since accidental ethanol inhalation can occur quite frequently in the working place or even private household, such a situation should always be considered when EtG is used as a marker of recent ethanol consumption.
    Forensic science international 02/2014; 237C:126-130. DOI:10.1016/j.forsciint.2014.02.007 · 2.12 Impact Factor
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    ABSTRACT: Background Ethyl glucuronide (EtG) in urine is considered a marker of recent alcohol consumption. Using immunoassays for EtG screening without confirmatory analysis bears a risk of getting false-positives as shown for trichloroethyl glucuronide from chloral hydrate medication and 1-propyl glucuronide from propanol-based hand disinfection. The aim of the study was to check whether glucuronides of frequently used aliphatic short chain alcohols aside from EtG and 1-propyl glucuronide can cross-react with the DRI® Ethyl Glucuronide Assay. Methods Aliquots of EtG-free urine were individually spiked with methyl β-d-glucuronide, 1-propyl β-d-glucuronide, 2-propyl β-d-glucuronide, 1-butyl β-d-glucuronide, 2-butyl β-d-glucuronide, and tert-butyl β-d-glucuronide. To check the response rate of the DRI® Ethyl Glucuronide Assay to its target analyte, EtG was also added to a native EtG-free urine sample. The spiked alcohol glucuronide concentrations (seven levels up to 10 mg/L) and the DRI® Ethyl Glucuronide Assay results were evaluated by Passing–Bablok regression analysis. The 95% confidence interval ranges for the slope of the regression function were considered a measure of cross-reaction of the individual alcohol glucuronides with the enzyme immunoassay. Results 2-Propyl glucuronide showed a cross-reactivity of 69–84% at the 95% probability level, methyl glucuronide, 1-propyl glucuronide, and 1- and 2-butyl glucuronide of 4–9%, and tert-butyl glucuronide almost no cross-reactivity. The response rate for EtG was 87–94% at the 95% probability level. Conclusion The DRI® Ethyl Glucuronide Assay shows cross-reaction rates with aliphatic short chain alcohol glucuronides aside from EtG which bear a risk of getting false-positives regarding ethanol consumption. Mass spectrometric detection of EtG is mandatory for confirmation of positive immunological EtG screenings.
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    ABSTRACT: Ethyl glucuronide (EtG) in hair is considered as a specific marker of ethanol consumption. Prompted by a report of positive EtG hair testings due to hair treatment with an EtG containing hair lotion, commercially available herbal hair tonics from supermarkets, drug-stores, and health food stores were analyzed for the presence of EtG and ethyl sulfate (EtS). LC-MS/MS (QTRAP 5500 mass spectrometer) was done in multiple reaction monitoring (MRM), enhanced product ion (EPI) and MS(3) mode. The lower limit of quantitation was 0.05mg/L for EtG and the cut-off for the detection of EtS 0.01mg/L. Altogether 11 hair tonics from 8 manufacturers were tested, with 1 product in 3 different lots. EtG ranged between 0.07 and 1.06mg/L (7 products from 4 manufacturers) and was almost identical in the 3 lots of 1 product (1.01-1.06mg/L). EtS was found in 3 out of the 11 hair tonics. EtG is quite frequently present in commercially available herbal hair tonics. Using EtG in hair as a marker of alcohol (ab)use, one has to consider external sources of EtG and has to assess the use of hair care products, esp. if the patient denies any ethanol intake. Whether EtS is a more reliable alcohol (ab)use marker, as sometimes discussed, should be critically assessed against the background of its broad use in large amounts in industrial chemistry.
    Forensic science international 09/2013; 231(1-3):195-8. DOI:10.1016/j.forsciint.2013.05.010 · 2.12 Impact Factor
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    ABSTRACT: BACKGROUND: Urine ethyl glucuronide (EtG) is considered as a specific marker of recent ethanol consumption. We describe false-positive DRI(®) EIA EtG enzyme immunoassay results caused by propyl glucuronides in urine after using a propanol-based hand sanitizer. METHODS: EtG screening was done with the DRI(®) EIA EtG assay (Microgenics), using a cut-off of 0.5mg/L as recommended by the manufacturer and of 0.1mg/L as demanded by the German Regulations for Reissuing Drivers Licenses. Confirmatory EtG analysis was done with the ClinMass(®) EtG LC-MS/MS testkit (Recipe), extended by the mass transitions 235.1→75.1, 235.1→85.1, and 235.1→113.1 for the detection of the 1- and 2-propyl glucuronides. Self-experiments were done by staff members of our lab (n=7), using 3mL Sterillium(®) Classic Pure (30g/100g 1-propanol and 45g/100g 2-propanol) for hand sanitation every quarter of an hour for 8h according to DIN EN 1500:2011-05 with and without an exhauster and by passive inhalation of the sanitizer vapor. Spot urine samples were taken immediately before and up to 24h after the first sanitizer use. RESULTS: False-positive immunoassay results of up to 4mg/L or 2.3mg/g creatinine were obtained after normal use of the sanitizer and also after passive inhalation of the sanitizer vapor (up to 0.89mg/L or 0.61mg/g). Immunoassay results were positive even after 4-fold use of the sanitizer (up to 0.14mg/L or 0.38mg/g) and up to 6h after the last sanitizer contact (maximum 0.63mg/L and 0.33mg/g for sanitizer users and 0.25mg/g after passive inhalation). Spiking of EtG-free urine with 1-propyl glucuronide (Athena Environmental Sciences) between 0.05 and 10mg/L clearly demonstrated a cross reaction of the immunoassay of approx. 10% as compared to EtG. LC-MS/MS of urines with a positive immunoassay EtG result did not show EtG signals, but distinct signals of 1-propyl glucuronide (n-propyl glucuronide) and 2-propyl glucuronide (iso-propyl glucuronide). An exhauster effectively prevented the inhalation of the sanitizer vapor, the formation of propyl glucuronides and thus false-positive DRI(®) EIA EtG screening results, proving that propyl alcohols are almost exclusively taken up by respiration. CONCLUSIONS: The widespread use of propanol-containing products such as hand sanitizers may lead to sufficient uptake of propyl alcohols and excretion of significant amounts of propyl glucuronides to yield false-positive DRI(®) EIA EtG screening results. Thus, positive EtG immunoassay results have to be controlled by mass-spectrometry, in clinical cases at least if ethanol intake is denied by the patient.
    Forensic science international 11/2012; 223(1-3). DOI:10.1016/j.forsciint.2012.10.024 · 2.12 Impact Factor
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    ABSTRACT: A drug and alcohol withdrawal rehabilitation centre requested an analysis for "Krypton" in urine of a former opiate-addictive woman. She showed an altered clinical picture and behaviour with miosis, itchiness, agitation, and moderate euphoria after 3 months of until than successful treatment. Literature search revealed that "Krypton" is said to contain "Kratom" (leaves of Mitragyna speciosa), but could also contain O-desmethyltramadol (European Monitoring Centre for Drugs and Drug Addiction thematic paper "Spice"). Immunological drug screenings were done with test strips (nal von minden, Regensburg, Germany) and with cloned enzyme donor immunoassay (Microgenics, Passau, Germany). "Kratom" alkaloids and tramadol (metabolites) were analyzed by LC-MS/MS (ThermoFisher Scientific Quantum Ultra Triple Quadrupole mass spectrometer). Immunoassays were negative for amphetamines, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, ethylglucuronide, methadone (metabolite), opiates, oxycodone, and THC-COOH, and test strips were negative for tramadol and its metabolites (cut-off 10 mg/L for O-desmethyltramadol). LC-MS/MS detected the "Kratom" alkaloids mitragynine, speciociliatine, speciogynine, mitraciliatine, and paynantheine and approximately 9mg/L O-desmethyltramadol, but no tramadol and N-desmethyltramadol. The detection of M. speciosa alkaloids is a proof of "Kratom" abuse. Confronted with the analysis data, the patient admitted to have consumed 3-4 infusions of "Krypton". The origin of the O-desmethyltramadol is unclear. Tramadol abuse is unlikely since tramadol and N-desmethyltramadol (physiologically occurring in urine after tramadol intake) were not detectable. Consumption of a "Krypton" product spiked with O-desmethyltramadol could explain our findings and the patient's clinical picture. This would be in agreement with a most recent report about spiking apparently natural herbal mixtures with the synthetic opioid O-desmethyltramadol. Analysis of "Kratom" abuse should not be restricted to M. speciosa alkaloids, but should also consider synthetic drugs which could be added to the herbal mixtures. Mass spectrometry based drug screenings will gain importance to keep pace with the dynamic drug market.
    Forensic science international 11/2010; 208(1-3):47-52. DOI:10.1016/j.forsciint.2010.10.025 · 2.12 Impact Factor
  • T Arndt
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    ABSTRACT: Statistical data from a wide cohort of subjects should provide arguements for a more valid interpretation of urine-creatinine concentrations as laboratory marker of urine dilution. Unselected, consecutive urine-creatinine concentrations from 11,811 women and 13,009 men in a clinical chemistry laboratory (mainly from clinical trials and employment medicine departments) and from 7300 women and 12,456 men in a toxicological chemistry laboratory (mainly from drug screenings for re-issuing drivers licenses or from employment medicine departments) were evaluated by descriptive and comparative statistics. Women (clinical chemistry lab, toxicological chemistry lab): mean 723 mg/L, 921 mg/L; median 568 mg/L, 728 mg/L; 2.5-97.5% percentile range 189-2198 mg/L, 129-2690 mg/L. Men (clinical chemistry lab, toxicological chemistry lab): mean 975 mg/L, 1395 mg/L; median 802 mg/L, 1241 mg/L; 2.5-97.5% percentile range 256-2660 mg/L, 204-3520 mg/L. The rate of urine-creatinine concentrations of >3000 mg/L (up to 3-fold of the upper limit of the reference range) was higher for men in both laboratories and for both genders in the toxicological chemistry lab compared with the clinical chemistry lab (toxicological chemistry lab: 697 for men (5.6%) and 111 for women (1.5%), clinical chemistry lab: 200 for men (1.5%) and 93 for women (0.8%)). Conclusions: Utmost caution should be taken when interpreting urinary creatinine concentrations that fall below so-called cut-offs. Cut-offs greater than the gender-specific 2.5% percentiles bear a high risk of misinterpretation regarding urine adulteration. Such cut-offs are no longer acceptable. At present, the borderline range of >50mg/L to <200mg/L given by the Australian Standard AS/NZS4308:2008 and indicating dilute urines but are not implicated in adulteration seems to fit best with the clinical and forensic requirements. Nevertheless, using gender-independent urine-creatinine concentration cut-offs can discriminate women since women have in general lower muscle mass and thus lower urinary creatinine concentrations compared with men. Future concepts of drug screen in urine should use gender-specific and creatinine-adjusted decision limits.
    Forensic science international 02/2009; 186(1-3):48-51. DOI:10.1016/j.forsciint.2009.01.010 · 2.12 Impact Factor
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    ABSTRACT: Urine-ethyl glucuronide (EtG) concentrations are considered as a specific marker of recent alcohol consumption. We describe false-positive EtG screening results by the DRI ethyl glucuronide enzyme immunoassay caused by chloral hydrate intake. Urine-EtG-screening: DRI EtG enzyme immunoassay (Thermo Fisher Scientific Microgenics) on a Hitachi 912 analyzer. EtG- and ethyl sulfate (EtS) confirmatory analysis: LC-MS/MS with an ESI source in the negative ionization, selective reaction monitoring mode. Patient: ethanol-abstaining women under buprenorphine-treatment (medication with levetiracetam, gabapentin, clomethiazol and chloral hydrate). Proband: self-medication with 500 mg chloral hydrate after a 5-day ethanol abstinence. EtG analysis for both in subsequent urines. Check for cross reactions of the pharmaceuticals with the EtG immunoassay by addition of pure substance (2 g/L each) to EtG-free urine. EtG concentrations up to 8.0 mg/L or 7.0 mg/g creatinine (cut-off 0.5 mg/L or mg/g) for the patient and up to 0.28 mg/L or 0.35 mg/g for the control subject (after 500 mg chloral hydrate) were obtained by the immunoassay. LC-MS/MS could not confirm these EtG results. In fact, EtG and/or EtS were not detectable in any of the urine samples by LC-MS/MS (lower limit of detection 0.01 mg/L). Cross reactions of the pharmaceuticals, incl. the chloral hydrate metabolites trichloroethanol and trichloroacetic acid, with the DRI EtG immunoassay results were ruled out (by spiking experiments) as the underlying cause for the false-positive EtG immunoassay results. Trichloroethyl glucuronide as an important chloral hydrate metabolite remains the most probable cross reacting substance with the DRI EtG immunoassay (unproven because of lack in pure standard). The chloral hydrate self-medication experiment clearly points to an association of the false-positive EtG immunoassay results and chloral hydrate intake. Chloral hydrate medication has to be considered as a cause for false-positive EtG screening results by the DRI EtG immunoassay even in cases with regular chloral hydrate treatment (250-1000 mg) and the more in patients with chloral hydrate tolerance (taking g/day). It is recommended that positive EtG immunoassay results always be confirmed by a more specific technique such as LC-MS/MS, including ethyl sulfate as a second minor ethanol metabolite.
    Forensic science international 01/2009; 184(1-3):e27-9. DOI:10.1016/j.forsciint.2008.10.022 · 2.12 Impact Factor
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    ABSTRACT: An incomplete separation of disialotransferrin (CDT) and trisialotransferrin (a non-CDT isoform) may cause false-positive CDT results in alcohol abuse testing. We describe a currently unknown disialotransferrin-trisialotransferrin-bridging phenomenon (di-tri-bridge) appearing with high prevalence in serum from liver cirrhosis patients. Twenty one consecutive serum samples with a di-tri-bridge encountered in routine CDT HPLC (Clin-Rep(R)-CDT-on-line, Recipe) were investigated by a candidate reference CDT HPLC method, by capillary electrophoresis (Capillarys-CDT, Sebia) and by transferrin genotyping. Patients clinical background was assessed by telephone interview. Out of 21 consecutive serum samples showing a di-tri-bridge (and increased trisialotransferrin fractions) in HPLC as well as in CE analysis, 19 were from patients with a liver cirrhosis history. Genotyping (where applicable by the availability of DNA: n=12) yielded most frequently homozygous transferrin C1 (6x), proving that the di-tri-bridge cannot be explained by genetic transferrin variants in these samples. Other genotypes found were C2 (1x), C1C2 (4x), C1C3 (1x). The frequently seen di-tri-bridging phenomenon in transferrin HPLC analysis for patients with liver cirrhosis is not explained by genetic transferrin variants or by an increased trisialotransferrin fraction. Although further studies are needed to assess the relationship between this phenomenon and liver cirrhosis, our observation could be helpful in development of a biomarker for liver cirrhosis.
    Clinica Chimica Acta 09/2008; 394(1-2):42-6. DOI:10.1016/j.cca.2008.03.033 · 2.82 Impact Factor
  • Clinical Chemistry and Laboratory Medicine 06/2008; 46(5):727-728. DOI:10.1515/CCLM.2008.143 · 2.96 Impact Factor
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    ABSTRACT: Carbohydrate-deficient transferrin (CDT) is the most specific serum marker of chronic alcohol abuse so far. There is little knowledge about extreme CDT values of >20% and the more >30% CDT. Serum CDT/transferrin ratios from 19,236 serum samples sent to our laboratory for routine CDT analysis were determined by HPLC. About 75% of these serum samples were from traffic or employment medicine investigations. A CDT value frequency histogram was computed and extreme CDT values were clinically validated. Fourteen thousand four hundred and sixty-one CDT results were normal (< or =1.7%) and 4775 increased (1.8-36.9% CDT). Most frequent normal and increased results were 0.9% CDT (n=1964) and 1.8% CDT (n=356). CA. 70% of the pathological results were between 1.8% and 5.0% CDT, ca. 88% between 1.8% and 10.0% CDT, and 98% between 1.8% and 20.0%. CDT values >20.0% appeared in 79 cases and results >30.0% in two cases (33.8% and 36.9%). In each case of CDT values >20%, chronic alcohol abuse was the underlying cause as confirmed by anamnestic exploration. CDT/transferrin ratios are usually <20%. Higher values can appear in rare cases. CDT results >30% can be due to alcohol abuse but should be considered as remarkable single observations. Visualization of the transferrin isoform patterns by HPLC allows the detection of pathological transferrin isoform patterns and of genetic transferrin variants. This is essential for a reliable interpretation of (extreme) CDT values. CDT analysis by immunoassays without physico-chemical confirmatory analysis is no longer acceptable.
    Forensic science international 02/2008; 175(1):27-30. DOI:10.1016/j.forsciint.2007.05.001 · 2.12 Impact Factor
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    ABSTRACT: Carbohydrate-deficient transferrin (asialo-+monosialo-+disialotransferrin, CDT) is currently the most specific laboratory marker of chronic alcohol abuse. We tested whether previous findings of false-positive CDT results for anorexia nervosa patients have been due to invalid CDT analysis methods or anorexia nervosa by itself. Serum CDT from 49 anorexia nervosa patients, 14 bulimia nervosa patients and 22 healthy controls (all adolescent, female and age-matched) was determined in a retrospective study by HPLC (Clin-Rep-CDT-in-serum-online, cut-off > or =1.8%, Recipe), by capillary electrophoresis (Capillarys-CDT, cut-off > or =1.3%, Sebia) and (due to limited surplus serum volume for a subset of 18 anorexia nervosa patients with increased trisialotransferrin detected by HPLC) by immunoassay based on anion-exchange CDT and non-CDT fractionation (%CDT-TIA, cut-off > or =2.6% CDT, Bio-Rad). HPLC and capillary electrophoresis: No false-positive CDT results were obtained. Asialo- and monosialotransferrin were not detected and disialotransferrin (CDT) was in each case clearly below the test-specific cut-offs. Trisialotransferrin (a non-CDT isoform) was increased (cut-off > or =5.0% for HPLC) in 33 anorexia patients, 2 bulimia patients and 2 controls. %CDT-TIA: 8 false-positive CDT results of > or =2.6% out of the 18 samples tested (CDT-range/mean/median 2.6-4.6/3.2/2.8%). Anorexia nervosa does not cause by itself increased CDT results. False-positive CDT values from the past are most likely due to an incomplete separation of trisialotransferrin from CDT and thus overdetermination of CDT. Immunological CDT testing without confirmatory analysis by HPLC or CE is no longer acceptable.
    Clinica Chimica Acta 05/2007; 379(1-2):150-3. DOI:10.1016/j.cca.2007.01.013 · 2.82 Impact Factor
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    ABSTRACT: An alcohol-associated change in the serum transferrin glycoform pattern, carbohydrate-deficient transferrin (CDT), is used as a biomarker of chronic moderate to heavy alcohol consumption. A current limitation in CDT analysis is the lack of standardization, which hampers clinical and analytical comparison between studies. This situation prompted initiation of a Working Group (WG) on CDT Standardization under the auspices of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The standardization work aims to define and validate the analyte, select a reference method, work out procedures for the production of reference materials, and make suggestions for the clinical usage of CDT. The first recommendation of the WG is that disialotransferrin should be the primary target molecule for CDT measurement and the single analyte on which CDT standardization is based. It is further recommended that HPLC should be the analytical principle considered as the basis of an interim reference method until a suitable mass spectrometric reference method is established. In clinical use, CDT should be expressed in a relative amount (% CDT), to compensate for variations in the total transferrin concentration.
    Clinical Chemistry and Laboratory Medicine 02/2007; 45(4):558-62. DOI:10.1515/CCLM.2007.107 · 2.96 Impact Factor
  • Torsten Arndt · Sven Stanzel · Adrian C Sewell
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    ABSTRACT: Human serum transferrin shows different transferrin isoforms with e.g. a varying amount of glycosylation, resulting in asialo-, mono-, di-, up to octasialotransferrin. We wanted to examine whether there are age-dependent differences in this transferrin isoform distribution. Serum samples from a total of 126 paediatric patients (mean/median/minimum/maximum: 6.8/6.0/0.5/14 years) grouped in seven age groups (<2 years, 3-4 years, up to 13-14 years) were analyzed on an HPLC (Recipe Chemicals & Instruments GmbH, Munich, Germany). Means, medians and percentiles were computed for each transferrin isoform and tested for statistically significant differences between the age groups. CDT corresponded to disialotransferrin (since asialo- and monosialotransferrins were not detectable) and did not show statistically significant differences between the 7 age groups. The latter is also true for trisialo- and tetrasialotransferrin whereas pentasialotransferrin shows a statistically significant decrease with age. We suggest that age-independent decision limits, e.g. the 95% percentiles for disialotransferrin (1.1%) and trisialotransferrin (5.3%), can be used for the differentiation between normal and increased fractions of these isoforms until paediatric reference ranges have been established. The presence of asialo- and monosialotransferrin in paediatric serum should be considered as abnormal.
    Clinical laboratory 01/2007; 53(9-12):575-82. · 1.08 Impact Factor
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    ABSTRACT: 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.
    Neuropsychopharmacology 01/2007; 31(12):2758-66. DOI:10.1038/sj.npp.1301122 · 7.83 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    Clinica Chimica Acta 12/2006; 373(1-2):117-20. DOI:10.1016/j.cca.2006.05.015 · 2.82 Impact Factor
  • Torsten Arndt · Thomas Keller
    Psychiatry Research 12/2006; 144(2-3):245-6; author reply 247-8. DOI:10.1016/j.psychres.2006.07.013 · 2.68 Impact Factor
  • Torsten Arndt · Ursula Meier · Markus Nauck · Axel M Gressner
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    ABSTRACT: 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. 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. 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. 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.
    Clinica Chimica Acta 11/2006; 372(1-2):184-7. DOI:10.1016/j.cca.2006.04.023 · 2.82 Impact Factor
  • Torsten Arndt
    Clinica Chimica Acta 03/2006; 364(1-2):367-8. DOI:10.1016/j.cca.2005.09.017 · 2.82 Impact Factor
  • Torsten Arndt · Brunhilde Guessregen · Axel Hohl · Janine Reis
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    ABSTRACT: 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. 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). 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). 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.
    Clinica Chimica Acta 10/2005; 359(1-2):125-31. DOI:10.1016/j.cccn.2005.03.040 · 2.82 Impact Factor

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728 Citations
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  • 2000–2014
    • Bioscientia - Institut für Medizinische Diagnostik GmbH
      Frankfurt, Hesse, Germany
  • 2006
    • University of Salzburg
      Salzburg, Salzburg, Austria
  • 1995–1998
    • Philipps University of Marburg
      Marburg, Hesse, Germany