2014
Tewald, F
Diagnostik der Lyme-Borreliose Artikel
In: Der Mikrobiologe, Bd. 24, Nr. 1, S. 13, 2014, ISSN: 0943-674X.
@article{Tewald.2014,
title = {Diagnostik der Lyme-Borreliose},
author = {F Tewald},
url = {http://www.zbmed.de/ccmedimages/2014/ZBMED-20143155155-5.pdf},
issn = {0943-674X},
year = {2014},
date = {2014-01-01},
journal = {Der Mikrobiologe},
volume = {24},
number = {1},
pages = {13},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hofmann, J; Meier, M; Enders, Martin; Führer, A; Ettinger, J; Klempa, B; Schmidt, S; Ulrich, R G; Kruger, D H
Hantavirus disease in Germany due to infection with Dobrava-Belgrade virus genotype Kurkino Artikel
In: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Bd. 20, Nr. 10, S. O648-O655, 2014, ISSN: 1198-743X.
@article{Hofmann.2014,
title = {Hantavirus disease in Germany due to infection with Dobrava-Belgrade virus genotype Kurkino},
author = {J Hofmann and M Meier and Martin Enders and A F\"{u}hrer and J Ettinger and B Klempa and S Schmidt and R G Ulrich and D H Kruger},
issn = {1198-743X},
year = {2014},
date = {2014-01-01},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {20},
number = {10},
pages = {O648-O655},
abstract = {Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes
2013
Enders, M; Handrick, W
Syphilis Buchabschnitt
In: Friese, K; Mylonas, Ioannis; Schulze, A (Hrsg.): Infektionserkrankungen der Schwangeren und des Neugeborenen, Bd. 3, S. 371–385, Springer-Verlag, Berlin, Heidelberg, 2013, ISBN: 13 978-3-540-78324-4.
@incollection{Enders.2013,
title = {Syphilis},
author = {M Enders and W Handrick},
editor = {K Friese and Ioannis Mylonas and A Schulze},
isbn = {13 978-3-540-78324-4},
year = {2013},
date = {2013-01-01},
booktitle = {Infektionserkrankungen der Schwangeren und des Neugeborenen},
volume = {3},
pages = {371--385},
publisher = {Springer-Verlag},
address = {Berlin, Heidelberg},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
Enders, M; Bartelt, U; Knotek, F; Bunn, K; Strobel, S; Dietz, K; Enders, G
In: Clinical and vaccine immunology : CVI, Bd. 20, Nr. 3, S. 420–426, 2013, ISSN: 1556-6811.
@article{Enders.2013b,
title = {Performance of the Elecsys Rubella IgG assay in the diagnostic laboratory setting for assessment of immune status},
author = {M Enders and U Bartelt and F Knotek and K Bunn and S Strobel and K Dietz and G Enders},
doi = {10.1128/CVI.00688-12.},
issn = {1556-6811},
year = {2013},
date = {2013-01-01},
journal = {Clinical and vaccine immunology : CVI},
volume = {20},
number = {3},
pages = {420--426},
abstract = {Rubella in early pregnancy bears a high risk for congenital defects (e.g., cataracts, hearing loss, and heart disease) and for long-term sequelae in the newborn. Despite implementation of vaccination programs in many regions, the threat of devastating consequences from congenital rubella virus infection remains and careful screening of maternal immune status before and during pregnancy helps to reduce the risk. This study compared the performance of the Elecsys Rubella IgG assay with that of other assays routinely used for screening. Samples from 1,090 women undergoing routine antenatal care were tested using the Elecsys and Enzygnost Rubella IgG assays and the hemagglutination inhibition test. Samples with hemagglutination inhibition titers of textless32 (n = 148) were additionally tested using the Vidas, AxSYM, Liaison, and Architect Rubella IgG assays. Agreement of qualitative results from the Elecsys, Enzygnost, and hemagglutination inhibition assays was good in all samples. All assays showed 100.0% specificity. In samples with hemagglutination inhibition titers of textless32, the Elecsys, AxSYM, and Enzygnost assays showed higher sensitivity (textgreater90.0%) than the other immunoassays (78.6 to 82.4%). The Elecsys assay reported significantly higher rubella virus IgG levels than the other immunoassays across the whole set of 1,090 samples, with the largest bias and deviation from limits of agreement in Bland-Altman analysis. In conclusion, the Elecsys assay is highly sensitive and specific with regard to qualitative results and suitable for routine automated screening. However, given the considerable variation between quantitative results from different immunoassays, testing methods should be documented and the same assay used throughout an individual's antenatal follow-up wherever possible},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Rubella in early pregnancy bears a high risk for congenital defects (e.g., cataracts, hearing loss, and heart disease) and for long-term sequelae in the newborn. Despite implementation of vaccination programs in many regions, the threat of devastating consequences from congenital rubella virus infection remains and careful screening of maternal immune status before and during pregnancy helps to reduce the risk. This study compared the performance of the Elecsys Rubella IgG assay with that of other assays routinely used for screening. Samples from 1,090 women undergoing routine antenatal care were tested using the Elecsys and Enzygnost Rubella IgG assays and the hemagglutination inhibition test. Samples with hemagglutination inhibition titers of textless32 (n = 148) were additionally tested using the Vidas, AxSYM, Liaison, and Architect Rubella IgG assays. Agreement of qualitative results from the Elecsys, Enzygnost, and hemagglutination inhibition assays was good in all samples. All assays showed 100.0% specificity. In samples with hemagglutination inhibition titers of textless32, the Elecsys, AxSYM, and Enzygnost assays showed higher sensitivity (textgreater90.0%) than the other immunoassays (78.6 to 82.4%). The Elecsys assay reported significantly higher rubella virus IgG levels than the other immunoassays across the whole set of 1,090 samples, with the largest bias and deviation from limits of agreement in Bland-Altman analysis. In conclusion, the Elecsys assay is highly sensitive and specific with regard to qualitative results and suitable for routine automated screening. However, given the considerable variation between quantitative results from different immunoassays, testing methods should be documented and the same assay used throughout an individual's antenatal follow-up wherever possible
Enders, M; Handrick, W; Schroten, H
Syphilis Buchabschnitt
In: Berner, R; Bialek, R; Borte, M; Forster, J; Heininger, U; Liese, J G; Nadal, D; Roos, R; Scholz, H (Hrsg.): DGPI Handbuch, Bd. 6, S. 521–526, Georg Thieme Verlag, Stuttgart, New York, 2013, ISBN: 978-3-13-144716-6.
@incollection{Enders.2013c,
title = {Syphilis},
author = {M Enders and W Handrick and H Schroten},
editor = {R Berner and R Bialek and M Borte and J Forster and U Heininger and J G Liese and D Nadal and R Roos and H Scholz},
isbn = {978-3-13-144716-6},
year = {2013},
date = {2013-01-01},
booktitle = {DGPI Handbuch},
volume = {6},
pages = {521--526},
publisher = {Georg Thieme Verlag},
address = {Stuttgart, New York},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
Enders, G; Mylonas, I; Schulze, A; Friese, K
Zytomegalie Buchabschnitt
In: Friese, K; Mylonas, I; Schulze, A (Hrsg.): Infektionserkrankungen der Schwangeren und des Neugeborenen, S. 243–267, Springer, Wien, 2013, ISBN: 978-3-540-78324-4.
@incollection{Enders.2013d,
title = {Zytomegalie},
author = {G Enders and I Mylonas and A Schulze and K Friese},
editor = {K Friese and I Mylonas and A Schulze},
doi = {10.1007/978-3-540-78325-1textunderscore 19},
isbn = {978-3-540-78324-4},
year = {2013},
date = {2013-01-01},
booktitle = {Infektionserkrankungen der Schwangeren und des Neugeborenen},
pages = {243--267},
publisher = {Springer},
address = {Wien},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
Witteborn, K; Schoner, K; Enders, M; Gembruch, U; Arabin, B
In: Case Reports in perinatal medicine, Bd. 3, Nr. 1, S. 65–70, 2013.
@article{Witteborn.2013,
title = {Human parvovirus B19 infection causing discrepant prenatal findings and outcome in monochorionic diamniotic twins},
author = {K Witteborn and K Schoner and M Enders and U Gembruch and B Arabin},
doi = {10.1515/crpm-2013-0040},
year = {2013},
date = {2013-01-01},
urldate = {2013-01-01},
journal = {Case Reports in perinatal medicine},
volume = {3},
number = {1},
pages = {65--70},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Enders, G; Daiminger, A; Bäder, U; Exler, S; Schimpf, Y; Enders, M
In: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, Bd. 56, Nr. 2, S. 102–107, 2013.
@article{Enders.2013e,
title = {The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy},
author = {G Enders and A Daiminger and U B\"{a}der and S Exler and Y Schimpf and M Enders},
doi = {10.1016/j.jcv.2012.09.015},
year = {2013},
date = {2013-01-01},
urldate = {2013-01-01},
journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},
volume = {56},
number = {2},
pages = {102--107},
abstract = {BACKGROUND: Primary CMV infections in pregnancy are usually asymptomatic and only detected by serology. Estimating the onset of infection is a major diagnostic goal, since primary infections around conception and in early gestation hold a higher risk for congenital disease than those in later pregnancy. OBJECTIVES: To assess the ability of serological supplementary CMV assays to date the onset of primary infection. STUDY DESIGN: From our routine diagnosis we identified 61 pregnant women (n=188 serum samples) with precisely determined onset of CMV primary infection either by IgG seroconversion (n=24) or by significant IgG antibody rise (n=37). One hundred and forty-seven sera were investigated using the VIDAS((R)) CMV IgG avidity EIA (BioMerieux) and 83 sera using the recomBlot CMV IgG with avidity (Mikrogen). RESULTS: Both assays proofed to be reliable in terms of timing the onset of CMV primary infection. An avidity index (AI) in the VIDAS avidity EIA of textless40% indicated primary infection within the last 20 weeks (positive predictive value 93.4%; 99/106), whereas an intermediate AI excluded primary infection within the last 12 weeks (negative predictive value 88.2%; 15/17). The recomBlot showed high reliability (PPV 96.9%; 31/33) for timing the onset of infection within the last 14 weeks. Avidity testing by blot however could not be interpreted in 11 of 47 sera (23.4%). CONCLUSION: For timing the onset of infection (before or in early pregnancy) CMV avidity testing is most helpful if carried out within the first trimester up to the beginning of second trimester},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Primary CMV infections in pregnancy are usually asymptomatic and only detected by serology. Estimating the onset of infection is a major diagnostic goal, since primary infections around conception and in early gestation hold a higher risk for congenital disease than those in later pregnancy. OBJECTIVES: To assess the ability of serological supplementary CMV assays to date the onset of primary infection. STUDY DESIGN: From our routine diagnosis we identified 61 pregnant women (n=188 serum samples) with precisely determined onset of CMV primary infection either by IgG seroconversion (n=24) or by significant IgG antibody rise (n=37). One hundred and forty-seven sera were investigated using the VIDAS((R)) CMV IgG avidity EIA (BioMerieux) and 83 sera using the recomBlot CMV IgG with avidity (Mikrogen). RESULTS: Both assays proofed to be reliable in terms of timing the onset of CMV primary infection. An avidity index (AI) in the VIDAS avidity EIA of textless40% indicated primary infection within the last 20 weeks (positive predictive value 93.4%; 99/106), whereas an intermediate AI excluded primary infection within the last 12 weeks (negative predictive value 88.2%; 15/17). The recomBlot showed high reliability (PPV 96.9%; 31/33) for timing the onset of infection within the last 14 weeks. Avidity testing by blot however could not be interpreted in 11 of 47 sera (23.4%). CONCLUSION: For timing the onset of infection (before or in early pregnancy) CMV avidity testing is most helpful if carried out within the first trimester up to the beginning of second trimester
Lüthgens, K; Merz, E; Hackelöer, B J; Thode, C; Eiben, B; Kagan, K O
In: Ultraschall in der Medizin (Stuttgart, Germany : 1980), Bd. 34, Nr. 2, S. 151–156, 2013.
@article{Luthgens.2013,
title = {Comparison of three first trimester screening algorithms for trisomy 21 with and without adjustment for maternal characteristics},
author = {K L\"{u}thgens and E Merz and B J Hackel\"{o}er and C Thode and B Eiben and K O Kagan},
doi = {10.1055/s-0032-1312954},
year = {2013},
date = {2013-01-01},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {34},
number = {2},
pages = {151--156},
abstract = {PURPOSE
Comparison of three algorithms (DoE 2007 and DoE 2011 algorithm of the FMF Germany and MoM algorithm of the FMF UK) in first trimester biochemical screening for trisomy 21 based on maternal and gestational age, free \ss-hCG, and PAPP-A and assessment of relevant maternal characteristics.
MATERIALS AND METHODS
Data from 22 449 euploid singleton pregnancies undergoing combined screening for trisomy 21 at 11 to 13 weeks of gestation were examined. The measured maternal free textgreekb-hCG and PAPP-A concentrations were converted into DoE 2007 and DoE 2011 values according to the algorithm of the FMF Germany and into MoM values according to the algorithm of the FMF UK. In each pregnancy, patient-specific risks and false-positive rates (FPR) were computed according to the three algorithms and were stratified according to gestational age, maternal ethnicity, maternal weight, and smoking status.
RESULTS
Free \ss-hCG and PAPP-A MoM and DoE 2011 were acceptably independent from maternal characteristics and gestational age, while there was a strong relationship between maternal weight and the DoE 2007 values. For a risk cut-off that corresponds to an overall 5 % FPR rate for each algorithm, the FPR in each group were around 5 % at gestational week 11 - 13. The FPR of the DoE 2007 algorithm increased linearly with maternal weight from 3.6 % in women of 50 kg or less to 11.8 % in women of more than 110 kg.
CONCLUSION
Especially maternal weight has a significant impact on the risk calculation. In contrast to the DoE 2007 algorithm, the DoE 2011 and MoM algorithms both adjust for maternal weight.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE
Comparison of three algorithms (DoE 2007 and DoE 2011 algorithm of the FMF Germany and MoM algorithm of the FMF UK) in first trimester biochemical screening for trisomy 21 based on maternal and gestational age, free ß-hCG, and PAPP-A and assessment of relevant maternal characteristics.
MATERIALS AND METHODS
Data from 22 449 euploid singleton pregnancies undergoing combined screening for trisomy 21 at 11 to 13 weeks of gestation were examined. The measured maternal free textgreekb-hCG and PAPP-A concentrations were converted into DoE 2007 and DoE 2011 values according to the algorithm of the FMF Germany and into MoM values according to the algorithm of the FMF UK. In each pregnancy, patient-specific risks and false-positive rates (FPR) were computed according to the three algorithms and were stratified according to gestational age, maternal ethnicity, maternal weight, and smoking status.
RESULTS
Free ß-hCG and PAPP-A MoM and DoE 2011 were acceptably independent from maternal characteristics and gestational age, while there was a strong relationship between maternal weight and the DoE 2007 values. For a risk cut-off that corresponds to an overall 5 % FPR rate for each algorithm, the FPR in each group were around 5 % at gestational week 11 - 13. The FPR of the DoE 2007 algorithm increased linearly with maternal weight from 3.6 % in women of 50 kg or less to 11.8 % in women of more than 110 kg.
CONCLUSION
Especially maternal weight has a significant impact on the risk calculation. In contrast to the DoE 2007 algorithm, the DoE 2011 and MoM algorithms both adjust for maternal weight.
Comparison of three algorithms (DoE 2007 and DoE 2011 algorithm of the FMF Germany and MoM algorithm of the FMF UK) in first trimester biochemical screening for trisomy 21 based on maternal and gestational age, free ß-hCG, and PAPP-A and assessment of relevant maternal characteristics.
MATERIALS AND METHODS
Data from 22 449 euploid singleton pregnancies undergoing combined screening for trisomy 21 at 11 to 13 weeks of gestation were examined. The measured maternal free textgreekb-hCG and PAPP-A concentrations were converted into DoE 2007 and DoE 2011 values according to the algorithm of the FMF Germany and into MoM values according to the algorithm of the FMF UK. In each pregnancy, patient-specific risks and false-positive rates (FPR) were computed according to the three algorithms and were stratified according to gestational age, maternal ethnicity, maternal weight, and smoking status.
RESULTS
Free ß-hCG and PAPP-A MoM and DoE 2011 were acceptably independent from maternal characteristics and gestational age, while there was a strong relationship between maternal weight and the DoE 2007 values. For a risk cut-off that corresponds to an overall 5 % FPR rate for each algorithm, the FPR in each group were around 5 % at gestational week 11 - 13. The FPR of the DoE 2007 algorithm increased linearly with maternal weight from 3.6 % in women of 50 kg or less to 11.8 % in women of more than 110 kg.
CONCLUSION
Especially maternal weight has a significant impact on the risk calculation. In contrast to the DoE 2007 algorithm, the DoE 2011 and MoM algorithms both adjust for maternal weight.
Henquell, C; Mirand, A; Richter, J; Schuffenecker, I; Böttiger, B; Diedrich, S; Terletskaia-Ladwig, E; Christodoulou, C; Peigue-Lafeuille, H; Bailly, J-L
In: Journal of virology, Bd. 87, Nr. 22, S. 12249–12259, 2013.
@article{Henquell.2013,
title = {Phylogenetic patterns of human coxsackievirus B5 arise from population dynamics between two genogroups and reveal evolutionary factors of molecular adaptation and transmission},
author = {C Henquell and A Mirand and J Richter and I Schuffenecker and B B\"{o}ttiger and S Diedrich and E Terletskaia-Ladwig and C Christodoulou and H Peigue-Lafeuille and J-L Bailly},
doi = {10.1128/JVI.02075-13},
year = {2013},
date = {2013-01-01},
journal = {Journal of virology},
volume = {87},
number = {22},
pages = {12249--12259},
abstract = {The aim of this study was to gain insights into the tempo and mode of the evolutionary processes that sustain genetic diversity in coxsackievirus B5 (CVB5) and into the interplay with virus transmission. We estimated phylodynamic patterns with a large sample of virus strains collected in Europe by Bayesian statistical methods, reconstructed the ancestral states of genealogical nodes, and tested for selection. The genealogies estimated with the structural one-dimensional gene encoding the VP1 protein and nonstructural 3CD locus allowed the precise description of lineages over time and cocirculating virus populations within the two CVB5 clades, genogroups A and B. Strong negative selection shaped the evolution of both loci, but compelling phylogenetic data suggested that immune selection pressure resulted in the emergence of the two genogroups with opposed evolutionary pathways. The genogroups also differed in the temporal occurrence of the amino acid changes. The virus strains of genogroup A were characterized by sequential acquisition of nonsynonymous changes in residues exposed at the virus 5-fold axis. The genogroup B viruses were marked by selection of three changes in a different domain (VP1 C terminus) during its early emergence. These external changes resulted in a selective sweep, which was followed by an evolutionary stasis that is still ongoing after 50 years. The inferred population history of CVB5 showed an alternation of the prevailing genogroup during meningitis epidemics across Europe and is interpreted to be a consequence of partial cross-immunity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The aim of this study was to gain insights into the tempo and mode of the evolutionary processes that sustain genetic diversity in coxsackievirus B5 (CVB5) and into the interplay with virus transmission. We estimated phylodynamic patterns with a large sample of virus strains collected in Europe by Bayesian statistical methods, reconstructed the ancestral states of genealogical nodes, and tested for selection. The genealogies estimated with the structural one-dimensional gene encoding the VP1 protein and nonstructural 3CD locus allowed the precise description of lineages over time and cocirculating virus populations within the two CVB5 clades, genogroups A and B. Strong negative selection shaped the evolution of both loci, but compelling phylogenetic data suggested that immune selection pressure resulted in the emergence of the two genogroups with opposed evolutionary pathways. The genogroups also differed in the temporal occurrence of the amino acid changes. The virus strains of genogroup A were characterized by sequential acquisition of nonsynonymous changes in residues exposed at the virus 5-fold axis. The genogroup B viruses were marked by selection of three changes in a different domain (VP1 C terminus) during its early emergence. These external changes resulted in a selective sweep, which was followed by an evolutionary stasis that is still ongoing after 50 years. The inferred population history of CVB5 showed an alternation of the prevailing genogroup during meningitis epidemics across Europe and is interpreted to be a consequence of partial cross-immunity.
Terletskaia-Ladwig, E; Meier, S; Enders, M
In: Journal of virological methods, Bd. 189, Nr. 2, S. 341–347, 2013, ISSN: 0166-0934.
@article{TerletskaiaLadwig.2013,
title = {Improved high-throughput virus neutralisation assay for antibody estimation against pandemic and seasonal influenza strains from 2009 to 2011},
author = {E Terletskaia-Ladwig and S Meier and M Enders},
doi = {10.1016/j.jviromet.2013.03.001},
issn = {0166-0934},
year = {2013},
date = {2013-01-01},
journal = {Journal of virological methods},
volume = {189},
number = {2},
pages = {341--347},
abstract = {An automatable focus-reduction neutralisation test (AFRNT) for detecting influenza neutralising antibodies in serum was developed. The assay used immunoperoxidase staining and automated foci counting with AID Diagnostika ViruSpot software. Human serum samples (n=108) were collected before and after vaccination with Pandemrix or Begrivac and were tested by AFRNT and a haemagglutination inhibition assay (HI) using seasonal and pandemic influenza vaccine strains from 2009 to 2011. Much attention has been given to the factors that influence detection of neutralising titre, such as viral quantification and the use of receptor destroying enzyme (RDE) for serum treatment. Foci counting enabled precise virus quantification and the development of a highly sensitive assay. Pre-treatment of the human sera with RDE significantly reduced the neutralising titres against all strains, with the exception of the seasonal H1N1 (2009/2010) strain. An HI titre of 1:40, which is associated with a 50% clinical protection against influenza, was equivalent to an AFRNT titre of 1:100-1:200. In conclusion, the AFRNT is rapid, highly sensitive, and fully automatable; therefore, this test is perfectly suitable for the high-throughput detection of influenza-neutralising antibodies},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
An automatable focus-reduction neutralisation test (AFRNT) for detecting influenza neutralising antibodies in serum was developed. The assay used immunoperoxidase staining and automated foci counting with AID Diagnostika ViruSpot software. Human serum samples (n=108) were collected before and after vaccination with Pandemrix or Begrivac and were tested by AFRNT and a haemagglutination inhibition assay (HI) using seasonal and pandemic influenza vaccine strains from 2009 to 2011. Much attention has been given to the factors that influence detection of neutralising titre, such as viral quantification and the use of receptor destroying enzyme (RDE) for serum treatment. Foci counting enabled precise virus quantification and the development of a highly sensitive assay. Pre-treatment of the human sera with RDE significantly reduced the neutralising titres against all strains, with the exception of the seasonal H1N1 (2009/2010) strain. An HI titre of 1:40, which is associated with a 50% clinical protection against influenza, was equivalent to an AFRNT titre of 1:100-1:200. In conclusion, the AFRNT is rapid, highly sensitive, and fully automatable; therefore, this test is perfectly suitable for the high-throughput detection of influenza-neutralising antibodies
2012
Weiffenbach, J; Bald, R; Gloning, K P; Minderer, S; Gärtner, B C; Weidner, A; Hanke, M; Enders, M
In: The Journal of infectious diseases, Bd. 205, Nr. 5, S. 782–788, 2012.
@article{Weiffenbach.2012,
title = {Serological and virological analysis of maternal and fetal blood samples in prenatal human parvovirus B19 infection},
author = {J Weiffenbach and R Bald and K P Gloning and S Minderer and B C G\"{a}rtner and A Weidner and M Hanke and M Enders},
doi = {10.1093/infdis/jir855},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {The Journal of infectious diseases},
volume = {205},
number = {5},
pages = {782--788},
abstract = {BACKGROUND: Intrauterine parvovirus B19 (B19V) infection can be asymptomatic or may cause severe fetal complications. Information on serological and virological findings of infection in the fetus is scarce. METHODS: We determined B19V-DNA and anti-B19V antibodies in maternal and fetal blood samples obtained from 41 pregnancies that were complicated by prenatal B19V infection. Most fetuses presented with moderate to severe anemia or hydrops. RESULTS: At the time of fetal blood sampling, all mothers were B19V-DNA positive and B19V-IgG positive. B19V-IgM was detected in 95% of maternal blood samples. B19V-DNA, B19V-IgM, and B19V-IgG were detected in 100%, 28%, and 24% of fetal blood samples, respectively. The probability of a positive B19V-IgG or B19V-IgM finding in fetal blood increased with gestational age. B19V-IgG levels in maternal blood did not correlate with the likelihood of a positive B19V-IgG test in the fetus. The presence of B19V-IgG in fetal blood was accompanied by lower B19V-DNA levels and less severe clinical findings. CONCLUSIONS: The lack of B19V-IgG in fetuses with B19V-derived anemia or hydrops is most likely due to a limited materno-fetal transfer of IgG and a poor fetal antibody response. Fetal B19V infection is poorly controlled in the absence of specific antibodies},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Intrauterine parvovirus B19 (B19V) infection can be asymptomatic or may cause severe fetal complications. Information on serological and virological findings of infection in the fetus is scarce. METHODS: We determined B19V-DNA and anti-B19V antibodies in maternal and fetal blood samples obtained from 41 pregnancies that were complicated by prenatal B19V infection. Most fetuses presented with moderate to severe anemia or hydrops. RESULTS: At the time of fetal blood sampling, all mothers were B19V-DNA positive and B19V-IgG positive. B19V-IgM was detected in 95% of maternal blood samples. B19V-DNA, B19V-IgM, and B19V-IgG were detected in 100%, 28%, and 24% of fetal blood samples, respectively. The probability of a positive B19V-IgG or B19V-IgM finding in fetal blood increased with gestational age. B19V-IgG levels in maternal blood did not correlate with the likelihood of a positive B19V-IgG test in the fetus. The presence of B19V-IgG in fetal blood was accompanied by lower B19V-DNA levels and less severe clinical findings. CONCLUSIONS: The lack of B19V-IgG in fetuses with B19V-derived anemia or hydrops is most likely due to a limited materno-fetal transfer of IgG and a poor fetal antibody response. Fetal B19V infection is poorly controlled in the absence of specific antibodies
Baylis, S A; Ma, L; Padley, D J; Heath, A B; Yu, M W
In: Vox sanguinis, Bd. 102, Nr. 3, S. 204–211, 2012, ISSN: 0042-9007.
@article{Baylis.2012,
title = {Collaborative study to establish a World Health Organization International genotype panel for parvovirus B19 DNA nucleic acid amplification technology (NAT)-based assays},
author = {S A Baylis and L Ma and D J Padley and A B Heath and M W Yu},
doi = {10.1111/j.1423-0410.2011.01541.x},
issn = {0042-9007},
year = {2012},
date = {2012-01-01},
journal = {Vox sanguinis},
volume = {102},
number = {3},
pages = {204--211},
abstract = {BACKGROUND AND OBJECTIVES
The aim of the collaborative study was to evaluate a panel of plasma samples containing different genotypes of parvovirus B19 (B19V) for use in nucleic acid amplification technology (NAT)-based assays.
MATERIALS AND METHODS
The panel of samples [Center for Biologics Evaluation and Research Parvovirus B19 Genotype Panel 1; National Institute for Biological Standards and Control (NIBSC) code number 09/110] comprises four different members, i.e. Member 1, Member 2, Member 3, and Member 4 (M1-M4); these represent genotypes 1, 2, 3a B19V, and a negative plasma control, respectively. Thirty-five laboratories from 13 different countries participated in the study. Participants assayed the panel members concurrently with the 2nd World Health Organization (WHO) International Standard for B19V DNA (NIBSC code 99/802) on four separate occasions.
RESULTS
A total of 44 sets of data were returned, 34 from quantitative assays and 10 from qualitative assays. The majority of assays used were in-house and based on real-time PCR. The results showed that all three genotypes were detected consistently by the majority of participants, although a small number of assays detected genotypes 2 and 3 less efficiently, or not at all. Real-time stability studies have indicated that the panel of B19V samples is stable under normal conditions of storage, i.e. $\leq$-70°C.
CONCLUSIONS
The four-member panel is intended for use in evaluating the ability of NAT assays to detect different B19V genotypes (M1-M3). Based on the results of the collaborative study, the panel was established as the 1st WHO International Reference Panel for parvovirus B19 genotypes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND OBJECTIVES
The aim of the collaborative study was to evaluate a panel of plasma samples containing different genotypes of parvovirus B19 (B19V) for use in nucleic acid amplification technology (NAT)-based assays.
MATERIALS AND METHODS
The panel of samples [Center for Biologics Evaluation and Research Parvovirus B19 Genotype Panel 1; National Institute for Biological Standards and Control (NIBSC) code number 09/110] comprises four different members, i.e. Member 1, Member 2, Member 3, and Member 4 (M1-M4); these represent genotypes 1, 2, 3a B19V, and a negative plasma control, respectively. Thirty-five laboratories from 13 different countries participated in the study. Participants assayed the panel members concurrently with the 2nd World Health Organization (WHO) International Standard for B19V DNA (NIBSC code 99/802) on four separate occasions.
RESULTS
A total of 44 sets of data were returned, 34 from quantitative assays and 10 from qualitative assays. The majority of assays used were in-house and based on real-time PCR. The results showed that all three genotypes were detected consistently by the majority of participants, although a small number of assays detected genotypes 2 and 3 less efficiently, or not at all. Real-time stability studies have indicated that the panel of B19V samples is stable under normal conditions of storage, i.e. $łeq$-70°C.
CONCLUSIONS
The four-member panel is intended for use in evaluating the ability of NAT assays to detect different B19V genotypes (M1-M3). Based on the results of the collaborative study, the panel was established as the 1st WHO International Reference Panel for parvovirus B19 genotypes.
The aim of the collaborative study was to evaluate a panel of plasma samples containing different genotypes of parvovirus B19 (B19V) for use in nucleic acid amplification technology (NAT)-based assays.
MATERIALS AND METHODS
The panel of samples [Center for Biologics Evaluation and Research Parvovirus B19 Genotype Panel 1; National Institute for Biological Standards and Control (NIBSC) code number 09/110] comprises four different members, i.e. Member 1, Member 2, Member 3, and Member 4 (M1-M4); these represent genotypes 1, 2, 3a B19V, and a negative plasma control, respectively. Thirty-five laboratories from 13 different countries participated in the study. Participants assayed the panel members concurrently with the 2nd World Health Organization (WHO) International Standard for B19V DNA (NIBSC code 99/802) on four separate occasions.
RESULTS
A total of 44 sets of data were returned, 34 from quantitative assays and 10 from qualitative assays. The majority of assays used were in-house and based on real-time PCR. The results showed that all three genotypes were detected consistently by the majority of participants, although a small number of assays detected genotypes 2 and 3 less efficiently, or not at all. Real-time stability studies have indicated that the panel of B19V samples is stable under normal conditions of storage, i.e. $łeq$-70°C.
CONCLUSIONS
The four-member panel is intended for use in evaluating the ability of NAT assays to detect different B19V genotypes (M1-M3). Based on the results of the collaborative study, the panel was established as the 1st WHO International Reference Panel for parvovirus B19 genotypes.
Buxmann, H; Stackelberg, O M; Schlosser, R L; Enders, G; Gonser, M; Meyer-Wittkopf, M; Hamprecht, K; Enders, M
In: Journal of perinatal medicine, Bd. 40, Nr. 4, S. 439–446, 2012.
@article{Buxmann.2012,
title = {Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis},
author = {H Buxmann and O M Stackelberg and R L Schlosser and G Enders and M Gonser and M Meyer-Wittkopf and K Hamprecht and M Enders},
doi = {10.1515/jpm-2011-0257},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {Journal of perinatal medicine},
volume = {40},
number = {4},
pages = {439--446},
abstract = {AIMS: The aim of this study was to investigate the current prenatal textquotedbloff-label usetextquotedbl of cytomegalovirus hyperimmunoglobulin (CMV-HIG) in the prevention and treatment of congenital CMV (cCMV) infection, including the long-term outcome of the children. METHODS: This retrospective observational study comprised mothers and their children, born between January 1, 2006, and October 30, 2010. Prenatal CMV-HIG was administered after diagnosis of primary CMV infection of the mother. Clinical and virological data were collected from maternal and pediatric medical and laboratory reports. Follow-up was 12-36 months after birth. RESULTS: Forty-two women and 43 children met the study criteria. In total, 40 mothers and six unborn infants received 115 doses of CMV-HIG. The treatment group (TG; CMV-DNA polymerase chain reaction-positive amniotic fluid) included four mothers; the multinomial group (MG; CMV-positive mother and unknown CMV status of fetus) included 38 mothers (39 infants). For the four unborn infants in TG, CMV-HIG was administered either intraumbilically or into the amniotic fluid; three of the four mothers received intravenous CMV-HIG. Three children in TG remained CMV-positive and were asymptomatic at birth and during follow-up. One infant in TG had symptomatic cCMV infection in utero, at birth, and during follow-up. In MG, 37 of 38 women received intravenous CMV-HIG and two of 39 infants received CMV-HIG in utero. In total, 9 (23.1%) of 39 children in MG were positive for cCMV (including a terminated pregnancy). All eight instances of cCMV infection at birth in MG were asymptomatic at birth and during follow-up. The fetus from the terminated pregnancy showed no sonographic symptoms of cCMV infection. No severe side effect occurred in 115 CMV-HIG applications. CONCLUSION: CMV-HIG was well tolerated. Compared with published untreated mother-child pairs, we observed a trend toward a smaller risk for intrauterine CMV transmission following CMV-HIG application. Signs of prenatal cCMV disease were not reversed after CMV-HIG},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
AIMS: The aim of this study was to investigate the current prenatal textquotedbloff-label usetextquotedbl of cytomegalovirus hyperimmunoglobulin (CMV-HIG) in the prevention and treatment of congenital CMV (cCMV) infection, including the long-term outcome of the children. METHODS: This retrospective observational study comprised mothers and their children, born between January 1, 2006, and October 30, 2010. Prenatal CMV-HIG was administered after diagnosis of primary CMV infection of the mother. Clinical and virological data were collected from maternal and pediatric medical and laboratory reports. Follow-up was 12-36 months after birth. RESULTS: Forty-two women and 43 children met the study criteria. In total, 40 mothers and six unborn infants received 115 doses of CMV-HIG. The treatment group (TG; CMV-DNA polymerase chain reaction-positive amniotic fluid) included four mothers; the multinomial group (MG; CMV-positive mother and unknown CMV status of fetus) included 38 mothers (39 infants). For the four unborn infants in TG, CMV-HIG was administered either intraumbilically or into the amniotic fluid; three of the four mothers received intravenous CMV-HIG. Three children in TG remained CMV-positive and were asymptomatic at birth and during follow-up. One infant in TG had symptomatic cCMV infection in utero, at birth, and during follow-up. In MG, 37 of 38 women received intravenous CMV-HIG and two of 39 infants received CMV-HIG in utero. In total, 9 (23.1%) of 39 children in MG were positive for cCMV (including a terminated pregnancy). All eight instances of cCMV infection at birth in MG were asymptomatic at birth and during follow-up. The fetus from the terminated pregnancy showed no sonographic symptoms of cCMV infection. No severe side effect occurred in 115 CMV-HIG applications. CONCLUSION: CMV-HIG was well tolerated. Compared with published untreated mother-child pairs, we observed a trend toward a smaller risk for intrauterine CMV transmission following CMV-HIG application. Signs of prenatal cCMV disease were not reversed after CMV-HIG
Lüthgens, K; Hoopmann, M; Alkier, R; Abele, H; Yazdi, B; Kagan, K-O
In: Ultraschall in der Medizin (Stuttgart, Germany : 1980), Bd. 33, Nr. 7, S. E57-E61, 2012.
@article{Luthgens.2012,
title = {Screening auf Trisomie 18 und Trisomie 13 durch das kombinierte Anwenden der Risiko-Algorithmen f\"{u}r Trisomie 21, 18 und 13},
author = {K L\"{u}thgens and M Hoopmann and R Alkier and H Abele and B Yazdi and K-O Kagan},
doi = {10.1055/s-0031-1299083},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {33},
number = {7},
pages = {E57-E61},
abstract = {PURPOSE
Assessment of first-trimester combined screening for trisomy 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13.
MATERIALS AND METHODS
First-trimester combined screening based on maternal and gestational age, fetal NT, PAPP-A and free textgreekb-hCG was assessed in 39 ,004 pregnancies. Patient-specific risks for trisomy 21, 18, 13 were computed based on the current FMF London algorithm.
RESULTS
The study population consisted of 38 ,751 singleton pregnancies including 39 cases with trisomy 18 or 13. In the aneuploid group, median delta NT was 0.72 mm, PAPP-A was 0.21 MoM and free textgreekb-hCG was 0.33 MoM. Although only 41 % of the NT measurements of fetuses with trisomy 18 or 13 were above the 95th percentile, the detection rates for trisomy 18 or 13 were 82 % with the trisomy 18/13 algorithm and 56.4 % with the trisomy 21 algorithm. The respective false-positive rates were 0.7 % and 4.7 %. The combination of the trisomy 18/13 and the trisomy 21 algorithm with the same cut-offs led to a detection rate of 94.9 % at an overall false-positive rate of 5.0 %.
CONCLUSION
Despite a substantial underestimation of the fetal NT, the combined use of the trisomy 18/13 and the trisomy 21 algorithm of the FMF London leads to a detection rate for trisomy 18/13 of about 95 % for a false-positive rate of 5.0 %.
ZIEL:: Beurteilung der Testg\"{u}te des kombinierten Ersttrimester-Screenings auf Trisomien 18 und 13 bei gemeinsamer Verwendung der Risikoalgorithmen f\"{u}r Trisomie 21, 18 und 13 in einem deutschen Patientenkollektiv.
MATERIAL UND METHODEN
Bei 39 004 Schwangerschaften wurde zwischen 2002 und 2007 im Rahmen des Ersttrimester-Screenings die fetale NT, PAPP-A und freies textgreekb-hCG gemessen. Im Rahmen dieser Studie erfolgte die erneute Auswertung der Trisomie-21-, -18- und -13-Risiken mit dem aktuellen Algorithmus der FMF London.
ERGEBNISSE
38 751 Einlingsschwangerschaften, darunter 39 F\"{a}lle einer Trisomie 18 oder Trisomie 13, konnten in die Auswertung einbezogen werden. In diesen F\"{a}llen lag die mediane delta NT bei 0,72 mm, PAPP-A bei 0,21 MoM und das freie textgreekb-hCG bei 0,33 MoM. Die NT lag nur bei 41 % der Trisomie-18/13-F\"{a}lle oberhalb der 95. Perzentile. Die alleinige Anwendung des Trisomie-18/13-Algorithmus f\"{u}hrte bei einem Cut-off von 1:100 zu einer Detektionsrate f\"{u}r die Trisomien 18/13 von 82 % bei einer Falsch-Positivrate von 0,7 %. Bei alleiniger Verwendung des Trisomie-21-Algorithmus mit einem Cut-off 1:200 wurden bei einer Falsch-Positivrate von 4,7 % 56,4 % der Trisomie-18/13-F\"{a}lle erkannt. Bei kombinierter Anwendung beider Algorithmen mit gleichen Cut-off-Werten stieg die Trisomie-18/13-Detektionsrate auf etwa 94,9 %. Die Falsch-Positivrate stieg dabei aber nur um 0,3 auf 5,0 %.
SCHLUSSFOLGERUNG
Die gemeinsame Anwendung des Trisomie-21-, -18- und -13-Algorithmus der FMF London f\"{u}hrt unter Routinebedingungen trotz der Untersch\"{a}tzung der NT zu einer 95 %-Detektionsrate f\"{u}r die Trisomien 18 und 13.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE
Assessment of first-trimester combined screening for trisomy 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13.
MATERIALS AND METHODS
First-trimester combined screening based on maternal and gestational age, fetal NT, PAPP-A and free textgreekb-hCG was assessed in 39 ,004 pregnancies. Patient-specific risks for trisomy 21, 18, 13 were computed based on the current FMF London algorithm.
RESULTS
The study population consisted of 38 ,751 singleton pregnancies including 39 cases with trisomy 18 or 13. In the aneuploid group, median delta NT was 0.72 mm, PAPP-A was 0.21 MoM and free textgreekb-hCG was 0.33 MoM. Although only 41 % of the NT measurements of fetuses with trisomy 18 or 13 were above the 95th percentile, the detection rates for trisomy 18 or 13 were 82 % with the trisomy 18/13 algorithm and 56.4 % with the trisomy 21 algorithm. The respective false-positive rates were 0.7 % and 4.7 %. The combination of the trisomy 18/13 and the trisomy 21 algorithm with the same cut-offs led to a detection rate of 94.9 % at an overall false-positive rate of 5.0 %.
CONCLUSION
Despite a substantial underestimation of the fetal NT, the combined use of the trisomy 18/13 and the trisomy 21 algorithm of the FMF London leads to a detection rate for trisomy 18/13 of about 95 % for a false-positive rate of 5.0 %.
ZIEL:: Beurteilung der Testgüte des kombinierten Ersttrimester-Screenings auf Trisomien 18 und 13 bei gemeinsamer Verwendung der Risikoalgorithmen für Trisomie 21, 18 und 13 in einem deutschen Patientenkollektiv.
MATERIAL UND METHODEN
Bei 39 004 Schwangerschaften wurde zwischen 2002 und 2007 im Rahmen des Ersttrimester-Screenings die fetale NT, PAPP-A und freies textgreekb-hCG gemessen. Im Rahmen dieser Studie erfolgte die erneute Auswertung der Trisomie-21-, -18- und -13-Risiken mit dem aktuellen Algorithmus der FMF London.
ERGEBNISSE
38 751 Einlingsschwangerschaften, darunter 39 Fälle einer Trisomie 18 oder Trisomie 13, konnten in die Auswertung einbezogen werden. In diesen Fällen lag die mediane delta NT bei 0,72 mm, PAPP-A bei 0,21 MoM und das freie textgreekb-hCG bei 0,33 MoM. Die NT lag nur bei 41 % der Trisomie-18/13-Fälle oberhalb der 95. Perzentile. Die alleinige Anwendung des Trisomie-18/13-Algorithmus führte bei einem Cut-off von 1:100 zu einer Detektionsrate für die Trisomien 18/13 von 82 % bei einer Falsch-Positivrate von 0,7 %. Bei alleiniger Verwendung des Trisomie-21-Algorithmus mit einem Cut-off 1:200 wurden bei einer Falsch-Positivrate von 4,7 % 56,4 % der Trisomie-18/13-Fälle erkannt. Bei kombinierter Anwendung beider Algorithmen mit gleichen Cut-off-Werten stieg die Trisomie-18/13-Detektionsrate auf etwa 94,9 %. Die Falsch-Positivrate stieg dabei aber nur um 0,3 auf 5,0 %.
SCHLUSSFOLGERUNG
Die gemeinsame Anwendung des Trisomie-21-, -18- und -13-Algorithmus der FMF London führt unter Routinebedingungen trotz der Unterschätzung der NT zu einer 95 %-Detektionsrate für die Trisomien 18 und 13.
Assessment of first-trimester combined screening for trisomy 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13.
MATERIALS AND METHODS
First-trimester combined screening based on maternal and gestational age, fetal NT, PAPP-A and free textgreekb-hCG was assessed in 39 ,004 pregnancies. Patient-specific risks for trisomy 21, 18, 13 were computed based on the current FMF London algorithm.
RESULTS
The study population consisted of 38 ,751 singleton pregnancies including 39 cases with trisomy 18 or 13. In the aneuploid group, median delta NT was 0.72 mm, PAPP-A was 0.21 MoM and free textgreekb-hCG was 0.33 MoM. Although only 41 % of the NT measurements of fetuses with trisomy 18 or 13 were above the 95th percentile, the detection rates for trisomy 18 or 13 were 82 % with the trisomy 18/13 algorithm and 56.4 % with the trisomy 21 algorithm. The respective false-positive rates were 0.7 % and 4.7 %. The combination of the trisomy 18/13 and the trisomy 21 algorithm with the same cut-offs led to a detection rate of 94.9 % at an overall false-positive rate of 5.0 %.
CONCLUSION
Despite a substantial underestimation of the fetal NT, the combined use of the trisomy 18/13 and the trisomy 21 algorithm of the FMF London leads to a detection rate for trisomy 18/13 of about 95 % for a false-positive rate of 5.0 %.
ZIEL:: Beurteilung der Testgüte des kombinierten Ersttrimester-Screenings auf Trisomien 18 und 13 bei gemeinsamer Verwendung der Risikoalgorithmen für Trisomie 21, 18 und 13 in einem deutschen Patientenkollektiv.
MATERIAL UND METHODEN
Bei 39 004 Schwangerschaften wurde zwischen 2002 und 2007 im Rahmen des Ersttrimester-Screenings die fetale NT, PAPP-A und freies textgreekb-hCG gemessen. Im Rahmen dieser Studie erfolgte die erneute Auswertung der Trisomie-21-, -18- und -13-Risiken mit dem aktuellen Algorithmus der FMF London.
ERGEBNISSE
38 751 Einlingsschwangerschaften, darunter 39 Fälle einer Trisomie 18 oder Trisomie 13, konnten in die Auswertung einbezogen werden. In diesen Fällen lag die mediane delta NT bei 0,72 mm, PAPP-A bei 0,21 MoM und das freie textgreekb-hCG bei 0,33 MoM. Die NT lag nur bei 41 % der Trisomie-18/13-Fälle oberhalb der 95. Perzentile. Die alleinige Anwendung des Trisomie-18/13-Algorithmus führte bei einem Cut-off von 1:100 zu einer Detektionsrate für die Trisomien 18/13 von 82 % bei einer Falsch-Positivrate von 0,7 %. Bei alleiniger Verwendung des Trisomie-21-Algorithmus mit einem Cut-off 1:200 wurden bei einer Falsch-Positivrate von 4,7 % 56,4 % der Trisomie-18/13-Fälle erkannt. Bei kombinierter Anwendung beider Algorithmen mit gleichen Cut-off-Werten stieg die Trisomie-18/13-Detektionsrate auf etwa 94,9 %. Die Falsch-Positivrate stieg dabei aber nur um 0,3 auf 5,0 %.
SCHLUSSFOLGERUNG
Die gemeinsame Anwendung des Trisomie-21-, -18- und -13-Algorithmus der FMF London führt unter Routinebedingungen trotz der Unterschätzung der NT zu einer 95 %-Detektionsrate für die Trisomien 18 und 13.
Rabenau, HF; Schwebke, I; Steinmann, J; Eggers, M; Rapp, I; Neumann-Haefelin, D
Quantitative Prüfung der viruziden Wirksamkeit chemischer Desinfektionsmittel auf nicht-porösen Oberflächen: Leitlinie der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. Artikel
In: Hygiene + Medizin, Bd. 37, Nr. 3, S. 78–85, 2012, ISSN: 0172-3790.
@article{Rabenau.2012,
title = {Quantitative Pr\"{u}fung der viruziden Wirksamkeit chemischer Desinfektionsmittel auf nicht-por\"{o}sen Oberfl\"{a}chen: Leitlinie der Deutschen Vereinigung zur Bek\"{a}mpfung der Viruskrankheiten (DVV) e.V.},
author = {HF Rabenau and I Schwebke and J Steinmann and M Eggers and I Rapp and D Neumann-Haefelin},
issn = {0172-3790},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {Hygiene + Medizin},
volume = {37},
number = {3},
pages = {78--85},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Schaumburg, F; Köck, R; Mellmann, A; Richter, L; Hasenberg, F; Kriegeskorte, A; Friedrich, A W; Gatermann, S; Peters, G; von Eiff, C; Becker, K
In: Journal of clinical microbiology, Bd. 50, Nr. 10, S. 3186–3192, 2012, ISSN: 0095-1137.
@article{Schaumburg.2012,
title = {Population dynamics among methicillin-resistant Staphylococcus aureus isolates in Germany during a 6-year period},
author = {F Schaumburg and R K\"{o}ck and A Mellmann and L Richter and F Hasenberg and A Kriegeskorte and A W Friedrich and S Gatermann and G Peters and C von Eiff and K Becker},
doi = {10.1128/JCM.01174-12},
issn = {0095-1137},
year = {2012},
date = {2012-01-01},
journal = {Journal of clinical microbiology},
volume = {50},
number = {10},
pages = {3186--3192},
abstract = {Methicillin-resistant Staphylococcus aureus (MRSA) originated from the health care setting but is now emerging in communities without health care contact (CA-MRSA) or in livestock (LA-MRSA). The impact on the whole MRSA population was assessed in a German prospective multicenter study. Thirty-three laboratories consecutively collected up to 50 MRSA isolates from infection or carriage during two sampling periods in 2004 to 2005 and 2010 to 2011. Patient-related data were collected using a standardized questionnaire. Methicillin resistance was confirmed by the detection of mecA or its homologue mecA(LGA251). The spa type and major virulence factors were analyzed for each isolate. In total, 1,604 (2004 to 2005) and 1,603 (2010 to 2011) MRSA isolates were analyzed; one isolate from each sampling period harbored mecA(LGA251). LA-MRSA increased significantly (odds ratio [OR] = 22.67, 95% confidence interval [CI] = 8.51 to 85.49, P textless 0.0005) and spread over Germany, originating from northwestern regions. Panton-Valentine leukocidin-positive CA-MRSA rose significantly, particularly in southern Germany, but the proportion in 2010 to 2011 remained low (2.7%},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Methicillin-resistant Staphylococcus aureus (MRSA) originated from the health care setting but is now emerging in communities without health care contact (CA-MRSA) or in livestock (LA-MRSA). The impact on the whole MRSA population was assessed in a German prospective multicenter study. Thirty-three laboratories consecutively collected up to 50 MRSA isolates from infection or carriage during two sampling periods in 2004 to 2005 and 2010 to 2011. Patient-related data were collected using a standardized questionnaire. Methicillin resistance was confirmed by the detection of mecA or its homologue mecA(LGA251). The spa type and major virulence factors were analyzed for each isolate. In total, 1,604 (2004 to 2005) and 1,603 (2010 to 2011) MRSA isolates were analyzed; one isolate from each sampling period harbored mecA(LGA251). LA-MRSA increased significantly (odds ratio [OR] = 22.67, 95% confidence interval [CI] = 8.51 to 85.49, P textless 0.0005) and spread over Germany, originating from northwestern regions. Panton-Valentine leukocidin-positive CA-MRSA rose significantly, particularly in southern Germany, but the proportion in 2010 to 2011 remained low (2.7%
Enders, G; Daiminger, A; Lindemann, L; Knotek, F; Bäder, U; Exler, S; Enders, M
In: Medical microbiology and immunology, Bd. 201, Nr. 3, S. 303–309, 2012, ISSN: 0300-8584.
@article{Enders.2012,
title = {Cytomegalovirus (CMV) seroprevalence in pregnant women, bone marrow donors and adolescents in Germany, 1996-2010},
author = {G Enders and A Daiminger and L Lindemann and F Knotek and U B\"{a}der and S Exler and M Enders},
doi = {10.1007/s00430-012-0232-7},
issn = {0300-8584},
year = {2012},
date = {2012-01-01},
journal = {Medical microbiology and immunology},
volume = {201},
number = {3},
pages = {303--309},
abstract = {In Germany, studies on the IgG seroprevalence in pregnancy and in women of childbearing age are rare. Therefore, we retrospectively evaluated the CMV IgG seropositive rate in 40,324 pregnant women as well as in 31,093 female and male bone marrow donors over 15 consecutive years (1996-2010). Furthermore, the result of a study conducted in 1999 investigating 1,305 healthy adolescents with known ethnicity was included. The overall CMV IgG seroprevalence in pregnant women (15-50~years) was 42.3%. Age-dependent analysis revealed a significantly higher seropositive rate (55.6%) in young women (15-25~years) than in those aged 26-40~years (37-42%) and in women older than 40~years (48.3%). Over the study period of 15~years, the rate of seroprevalence in pregnant women declined significantly (textgreekq(2) test~textless~0.01) from 44.3% in the first interval period (1996-2000), to 42.8% (2001-2005) and to 40.9% (2006-2010). The most influencing factor on CMV seropositivity appeared to be the socioeconomic status (SES), which we characterized by type of health insurance: Seroprevalence in women with low, middle and upper SES was 91.8, 46.9 and 33.7%, respectively. Female bone marrow donors of childbearing age (15-45~years) showed a significantly higher seropositive rate of 36.5% than age-matched male donors (28.6%). In adolescents aged 13-16~years, no gender-specific differences were recognized. Concerning ethnicity, youngsters with German descent had a significantly lower seroprevalence (29.9%) than those with non-German descent (67.4%).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In Germany, studies on the IgG seroprevalence in pregnancy and in women of childbearing age are rare. Therefore, we retrospectively evaluated the CMV IgG seropositive rate in 40,324 pregnant women as well as in 31,093 female and male bone marrow donors over 15 consecutive years (1996-2010). Furthermore, the result of a study conducted in 1999 investigating 1,305 healthy adolescents with known ethnicity was included. The overall CMV IgG seroprevalence in pregnant women (15-50~years) was 42.3%. Age-dependent analysis revealed a significantly higher seropositive rate (55.6%) in young women (15-25~years) than in those aged 26-40~years (37-42%) and in women older than 40~years (48.3%). Over the study period of 15~years, the rate of seroprevalence in pregnant women declined significantly (textgreekq(2) test~textless~0.01) from 44.3% in the first interval period (1996-2000), to 42.8% (2001-2005) and to 40.9% (2006-2010). The most influencing factor on CMV seropositivity appeared to be the socioeconomic status (SES), which we characterized by type of health insurance: Seroprevalence in women with low, middle and upper SES was 91.8, 46.9 and 33.7%, respectively. Female bone marrow donors of childbearing age (15-45~years) showed a significantly higher seropositive rate of 36.5% than age-matched male donors (28.6%). In adolescents aged 13-16~years, no gender-specific differences were recognized. Concerning ethnicity, youngsters with German descent had a significantly lower seroprevalence (29.9%) than those with non-German descent (67.4%).
Schoenenberger, AW; Schoenenberger-Berzins, R; auf der Maur, C; Suter, PM; Vergopoulos, A; Erne, P
In: Clinical research in cardiology : official journal of the German Cardiac Society, Bd. 101, Nr. 3, S. 159–164, 2012.
@article{Schoenenberger.2012,
title = {Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study},
author = {AW Schoenenberger and R Schoenenberger-Berzins and C auf der Maur and PM Suter and A Vergopoulos and P Erne},
doi = {10.1007/s00392-011-0376-2},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {Clinical research in cardiology : official journal of the German Cardiac Society},
volume = {101},
number = {3},
pages = {159--164},
abstract = {BACKGROUND
Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in long-term thiamine deficiency, which may further compromise cardiac function. This study evaluated the effect of high dose thiamine supplementation in heart failure patients.
METHODS
Nine patients with diuretic treatment for symptomatic chronic heart failure and a left ventricular ejection fraction (LVEF) textless40% were randomly assigned to receive thiamine (300~mg/day) or placebo for 28~days. After a wash-out of 6~weeks, the patients crossed-over to a second treatment period. The primary outcome was a change in LVEF.
RESULTS
Mean age was 56.7~$pm$~9.2~years (range 44.9-75.4~years). Baseline LVEF was similar for both treatment groups (29.5% in the thiamine group and 29.5% in the placebo group, P~=~0.911). After 28~days of thiamine treatment, the LVEF increased to 32.8% which was significantly (P~=~0.024) different from the LVEF in the placebo group (28.8%). This corresponds to a treatment effect for LVEF of 3.9% in absolute terms.
CONCLUSIONS
This study suggests that thiamine supplementation has beneficial effects on cardiac function in patients with diuretic drugs for symptomatic chronic heart failure. Subclinical thiamine deficiency is probably an underestimated issue in these outpatients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND
Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in long-term thiamine deficiency, which may further compromise cardiac function. This study evaluated the effect of high dose thiamine supplementation in heart failure patients.
METHODS
Nine patients with diuretic treatment for symptomatic chronic heart failure and a left ventricular ejection fraction (LVEF) textless40% were randomly assigned to receive thiamine (300~mg/day) or placebo for 28~days. After a wash-out of 6~weeks, the patients crossed-over to a second treatment period. The primary outcome was a change in LVEF.
RESULTS
Mean age was 56.7~$pm$~9.2~years (range 44.9-75.4~years). Baseline LVEF was similar for both treatment groups (29.5% in the thiamine group and 29.5% in the placebo group, P~=~0.911). After 28~days of thiamine treatment, the LVEF increased to 32.8% which was significantly (P~=~0.024) different from the LVEF in the placebo group (28.8%). This corresponds to a treatment effect for LVEF of 3.9% in absolute terms.
CONCLUSIONS
This study suggests that thiamine supplementation has beneficial effects on cardiac function in patients with diuretic drugs for symptomatic chronic heart failure. Subclinical thiamine deficiency is probably an underestimated issue in these outpatients.
Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in long-term thiamine deficiency, which may further compromise cardiac function. This study evaluated the effect of high dose thiamine supplementation in heart failure patients.
METHODS
Nine patients with diuretic treatment for symptomatic chronic heart failure and a left ventricular ejection fraction (LVEF) textless40% were randomly assigned to receive thiamine (300~mg/day) or placebo for 28~days. After a wash-out of 6~weeks, the patients crossed-over to a second treatment period. The primary outcome was a change in LVEF.
RESULTS
Mean age was 56.7~$pm$~9.2~years (range 44.9-75.4~years). Baseline LVEF was similar for both treatment groups (29.5% in the thiamine group and 29.5% in the placebo group, P~=~0.911). After 28~days of thiamine treatment, the LVEF increased to 32.8% which was significantly (P~=~0.024) different from the LVEF in the placebo group (28.8%). This corresponds to a treatment effect for LVEF of 3.9% in absolute terms.
CONCLUSIONS
This study suggests that thiamine supplementation has beneficial effects on cardiac function in patients with diuretic drugs for symptomatic chronic heart failure. Subclinical thiamine deficiency is probably an underestimated issue in these outpatients.
Strohhäcker, J; Eggers, M
In: Hygiene + Medizin, Bd. 37, Nr. 7/8, S. 320, 2012, ISSN: 0172-3790.
@article{Strohhacker.2012,
title = {Praxisnaher Test zur Pr\"{u}fung der viruziden Wirksamkeit von chemischen Instrumentendesinfektionsmitteln zur Aufbereitung von transvaginalen Ultraschallsonden. Practice-oriented test to establish virucidal effectiveness of chemical disinfectants on transvaginal ultrasound probe equipment},
author = {J Strohh\"{a}cker and M Eggers},
url = {http://www.zbmed.de/ccmedimages/2012/ZBMED-20128245153-3.pdf},
issn = {0172-3790},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {Hygiene + Medizin},
volume = {37},
number = {7/8},
pages = {320},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Terletskaia-Ladwig, E; Eggers, M
In: Hygiene + Medizin, Bd. 37, Nr. 7/8, S. 312, 2012, ISSN: 0172-3790.
@article{TerletskaiaLadwig.2012,
title = {Saisonale Verteilung von viralen Erregern - Konsequenzen f\"{u}r das Hygienemanagement. Seasonal distribution of viral pathogens - consequences for hygiene management},
author = {E Terletskaia-Ladwig and M Eggers},
url = {http://www.zbmed.de/ccmedimages/2012/ZBMED-20128245153-3.pdf},
issn = {0172-3790},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {Hygiene + Medizin},
volume = {37},
number = {7/8},
pages = {312},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tewald, F
Diagnostische Fallstricke bei Borrelieninfektionen Artikel
In: Ars Medici, Bd. 102, Nr. 17, S. 878, 2012.
@article{Tewald.2012,
title = {Diagnostische Fallstricke bei Borrelieninfektionen},
author = {F Tewald},
url = {http://www.zbmed.de/ccmedimages/2012/ZBMED-20129125152-1.pdf},
year = {2012},
date = {2012-01-01},
journal = {Ars Medici},
volume = {102},
number = {17},
pages = {878},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Kagan, K O; Hoopmann, M; Abele, H; Alkier, R; Lüthgens, K
In: Ultrasound in obstetrics & gynecology, Bd. 40, Nr. 5, S. 530–535, 2012, ISSN: 0960-7692.
@article{Kagan.2012,
title = {First-trimester combined screening for trisomy 21 with different combinations of placental growth factor, free textgreekb-human chorionic gonadotropin and pregnancy-associated plasma protein-A},
author = {K O Kagan and M Hoopmann and H Abele and R Alkier and K L\"{u}thgens},
doi = {10.1002/uog.11173},
issn = {0960-7692},
year = {2012},
date = {2012-01-01},
journal = {Ultrasound in obstetrics \& gynecology},
volume = {40},
number = {5},
pages = {530--535},
abstract = {OBJECTIVE
To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening.
METHODS
PlGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free textgreekb-human chorionic gonadotropin (textgreekb-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PlGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free textgreekb-hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free textgreekb-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free textgreekb-hCG and PlGF, and detection and false-positive rates were calculated.
RESULTS
Median PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P textless 0.0001). There was no significant dependency between PlGF-MoM and either gestational age at the time of blood sampling (r = 0.087},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE
To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening.
METHODS
PlGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free textgreekb-human chorionic gonadotropin (textgreekb-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PlGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free textgreekb-hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free textgreekb-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free textgreekb-hCG and PlGF, and detection and false-positive rates were calculated.
RESULTS
Median PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P textless 0.0001). There was no significant dependency between PlGF-MoM and either gestational age at the time of blood sampling (r = 0.087
To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening.
METHODS
PlGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free textgreekb-human chorionic gonadotropin (textgreekb-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PlGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free textgreekb-hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free textgreekb-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free textgreekb-hCG and PlGF, and detection and false-positive rates were calculated.
RESULTS
Median PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P textless 0.0001). There was no significant dependency between PlGF-MoM and either gestational age at the time of blood sampling (r = 0.087
Trojan, A; Vergopoulos, A; Breitenstein, U; Seifert, B; Rageth, C; Joechle, W
In: Breast care (Basel, Switzerland), Bd. 7, Nr. 1, S. 25–31, 2012, ISSN: 1661-3791.
@article{Trojan.2012,
title = {The Discriminatory Value of CYP2D6 Genotyping in Predicting the Dextromethorphan/Dextrorphan Phenotype in Women with Breast Cancer},
author = {A Trojan and A Vergopoulos and U Breitenstein and B Seifert and C Rageth and W Joechle},
doi = {10.1159/000336551},
issn = {1661-3791},
year = {2012},
date = {2012-01-01},
urldate = {2012-01-01},
journal = {Breast care (Basel, Switzerland)},
volume = {7},
number = {1},
pages = {25--31},
abstract = {BACKGROUND: The growth inhibitory effect of tamoxifen is used for the treatment of breast cancer. Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. We investigated the relationship of CYP2D6 genotypes to the metabolism of dextromethorphan (DM), which is frequently used as a surrogate marker for the formation of endoxifen. METHODS: The CYP2D6 genotype was determined by polymerase chain reaction (PCR) in previously untreated patients with hormone receptor-positive invasive breast cancer considered to receive antihormonal therapy. The DM/dextrorphan (DX) urinary excretion ratios were obtained in a subset of patients by high-pressure liquid chromatography (HPLC)-mediated urine analysis after intake of 25 mg DM. The relationships of genotype and corresponding phenotype were statistically analyzed for association. RESULTS: From 151 patients predicted based on their genotype data for the 'traditional' CYP2D6 phenotype classes poor, intermediate, extensive and ultrarapid, 83 patients were examined for their DM/DX urinary ratios. The genotype-based poor metabolizer status correlated with the DM/DX ratios, whereas the intermediate, extensive and ultrarapid genotypes could not be distinguished based on their phenotype. Citalopram intake did not significantly influence the phenotype. CONCLUSIONS: The DM metabolism can be reliably used to assess the CYP2D6 enzyme activity. The correlation with the genotype can be incomplete and the metabolic ratios do not seem to be compromised by citalopram. DM phenotyping may provide a standardized tool to better assess the CYP2D6 metabolic capacity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The growth inhibitory effect of tamoxifen is used for the treatment of breast cancer. Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. We investigated the relationship of CYP2D6 genotypes to the metabolism of dextromethorphan (DM), which is frequently used as a surrogate marker for the formation of endoxifen. METHODS: The CYP2D6 genotype was determined by polymerase chain reaction (PCR) in previously untreated patients with hormone receptor-positive invasive breast cancer considered to receive antihormonal therapy. The DM/dextrorphan (DX) urinary excretion ratios were obtained in a subset of patients by high-pressure liquid chromatography (HPLC)-mediated urine analysis after intake of 25 mg DM. The relationships of genotype and corresponding phenotype were statistically analyzed for association. RESULTS: From 151 patients predicted based on their genotype data for the 'traditional' CYP2D6 phenotype classes poor, intermediate, extensive and ultrarapid, 83 patients were examined for their DM/DX urinary ratios. The genotype-based poor metabolizer status correlated with the DM/DX ratios, whereas the intermediate, extensive and ultrarapid genotypes could not be distinguished based on their phenotype. Citalopram intake did not significantly influence the phenotype. CONCLUSIONS: The DM metabolism can be reliably used to assess the CYP2D6 enzyme activity. The correlation with the genotype can be incomplete and the metabolic ratios do not seem to be compromised by citalopram. DM phenotyping may provide a standardized tool to better assess the CYP2D6 metabolic capacity.
Hof, H; Oberdorfer, K; Mertes, T; Miller, B; Schwarz, R; Regnath, T; Schmidt-Wieland, T; Wellinghausen, N; Holfelder, M
In: Deutsche Medizinische Wochenschrift, Bd. 137, Nr. 43, S. 2229–2231, 2012, ISSN: 0012-0472.
@article{Hof.2012,
title = {Laborerhebung zur H\"{a}ufigkeit von Pneumocystis jirovecii - Zwar ein besonderer Pilz, aber auch ein seltener Erreger?},
author = {H Hof and K Oberdorfer and T Mertes and B Miller and R Schwarz and T Regnath and T Schmidt-Wieland and N Wellinghausen and M Holfelder},
doi = {10.1055/s-0032-1327231},
issn = {0012-0472},
year = {2012},
date = {2012-01-01},
journal = {Deutsche Medizinische Wochenschrift},
volume = {137},
number = {43},
pages = {2229--2231},
abstract = {Pneumocystsis jirovecii is a peculiar fungus for a variety of reasons. This opportunistic pathogen multiplies in humans only under certain conditions; a defect in the T-cell defense system creates a predisposition to this infection. In 2010 a data survey (IFT as well as PCR) from a few laboratories in Germany revealed 412 positive individuals. Even if only a few patients test positive for the colonization stage of this pathogen, the sheer number of individuals testing positive for other stages of infection indicate that the incidence of pneumocystosis in immunocompromised patients in Germany is underestimated.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pneumocystsis jirovecii is a peculiar fungus for a variety of reasons. This opportunistic pathogen multiplies in humans only under certain conditions; a defect in the T-cell defense system creates a predisposition to this infection. In 2010 a data survey (IFT as well as PCR) from a few laboratories in Germany revealed 412 positive individuals. Even if only a few patients test positive for the colonization stage of this pathogen, the sheer number of individuals testing positive for other stages of infection indicate that the incidence of pneumocystosis in immunocompromised patients in Germany is underestimated.