Retrospective study of false positive results in in vitro genotoxicity studies

2013 ◽  
Vol 221 ◽  
pp. S131
Author(s):  
Hana Hofman-Hüther
Keyword(s):  
Retrospective Study ◽  
False Positive ◽  
Positive Results ◽  
In Vitro Genotoxicity

scholarly journals Unreliable Measurement of Basophil Maximum Leukotriene Release with the Bühlmann CAST 2000 Enzyme-Linked Immunosorbent Assay Kit

2006 ◽  
Vol 13 (3) ◽  
pp. 420-422 ◽  
Author(s):  
S. E. Burastero ◽  
C. Paolucci ◽  
D. Breda ◽  
G. Monasterolo ◽  
R. E. Rossi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Immunosorbent Assay ◽  
False Positive ◽  
Positive Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Positive Results

ABSTRACT The Bühlmann CAST 2000 enzyme-linked immunosorbent assay is a potentially useful assay for measuring sulfidoleukotrienes released in vitro by allergen-challenged basophils. However, we observed that the positive-control reagent yielded positive signals in cell-free systems. These false-positive results depended on using a mouse anti-FcεRI monoclonal antibody and were prevented by degranulation-inducing reagents other than mouse monoclonal antibodies.

Way forward in case of a false positive in vitro genotoxicity result for a cosmetic substance?

2014 ◽  
Vol 28 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Tatyana Y. Doktorova ◽  
Gamze Ates ◽  
Mathieu Vinken ◽  
Tamara Vanhaecke ◽  
Vera Rogiers
Keyword(s):  
False Positive ◽  
In Vitro Genotoxicity

scholarly journals P034 Inter-scorer concordance impacts MSLT results

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A32-A32
Author(s):  
N Eriksson ◽  
P Teuwen ◽  
E Mateus ◽  
C Shim ◽  
A Scott
Keyword(s):  
Retrospective Study ◽  
Positive Result ◽  
False Positive ◽  
Sleep Latency ◽  
Spearman Correlation ◽  
Percentage Agreement ◽  
Medical Interpretation ◽  
Rem Latency ◽  
Multiple Sleep Latency ◽  
Positive Results

Abstract Introduction A retrospective study on the effect of inter-scorer concordance and impact of analysing polysomnography (PSG) data prior to the Multiple Sleep Latency Test (MSLT) on clinical interpretation of Narcolepsy (N) and Idiopathic Hypersomnolence (IH). Methods Data of four individuals was randomly selected from a cohort of patients that participated in MSLT studies. De-identified MSLT fragments from four nap periods (n=16) were scored in two groups: analysis of PSG conducted prior to the respective MSLT fragments, and analysis without access to prior PSG. Individual scorers were compared to a master score set, by consensus from two experienced sleep scientists. Spearman correlation and percentage agreement statistics were applied to calculate the inter-scorer concordance in sleep latency and REM latency. Mann-Whitney test was utilised to assess differences between the two groups. A positive result was assigned as: mean (n=4) sleep latency of <10min (IH), and mean (n=4) sleep latency of <8min including (n=2) SOREMs (N). Results From 16 sets of data, four false positive results were identified when PSG was not analysed prior to scoring the MSLT fragments. Additionally, statistically significant differences were present when PSG analysis was conducted prior to scoring MSLT sleep latency and REM latency data. Discussion These results support a recommendation that PSG analysis (sleep and REM latency) should be encouraged prior to MSLT studies and performed by the same sleep scientist. Furthermore, including MSLT data in intra-lab concordance activities is important, particularly in relation to medical interpretation and practice.

False-positive galactomannan antigen testing in pulmonary nocardiosis

2020 ◽  
Author(s):  
Arnon Haran ◽  
Violeta Temper ◽  
Marc Assous ◽  
Michael Bergel ◽  
Noga Chahanian ◽  
...  
Keyword(s):  
At Risk ◽  
Early Diagnosis ◽  
False Positive ◽  
Clinical Sample ◽  
Lavage Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pulmonary Nocardiosis ◽  
First Time ◽  
Positive Results

Abstract Early diagnosis of invasive aspergillosis (IA) is facilitated by detection of galactomannan (GM) in serum and bronchoalveolar lavage fluid (BALF) using an enzyme-linked immunosorbent assay (ELISA). Although accurate, false positive results have been reported with these tests in numerous contexts. We report for the first time the occurrence of false positive GM ELISA due to nocardiosis, initially in a clinical sample of BALF from a patient with pulmonary nocardiosis, and subsequently corroborated by in vitro reactivity of 26% of tested isolates. Since patients at risk for IA are also at risk for nocardiosis, this finding has important clinical implications. Lay Summary Early diagnosis of aspergillosis has been facilitated by the routine use of antibody-based detection of galactomannan in various bodily fluids. We report for the first time the occurrence of false positive results of this assay in the context of nocardiosis.

scholarly journals Validation of the 3D reconstructed human skin Comet assay, an animal-free alternative for following-up positive results from standard in vitro genotoxicity assays

Mutagenesis ◽  
2020 ◽  
Author(s):  
Stefan Pfuhler ◽  
Ralph Pirow ◽  
Thomas R Downs ◽  
Andrea Haase ◽  
Nicola Hewitt ◽  
...  
Keyword(s):  
Comet Assay ◽  
Human Skin ◽  
Assessment Process ◽  
Predictive Capacity ◽  
Industrial Sectors ◽  
Positive Results ◽  
In Vitro Genotoxicity

Abstract As part of the safety assessment process, all industrial sectors employ genotoxicity test batteries, starting with well-established in vitro assays. However, these batteries have limited predictive capacity for the in vivo situation, which may result in unnecessary follow-up in vivo testing or the loss of promising substances where animal tests are prohibited or not desired. To address this, a project involving regulators, academia and industry was established to develop and validate in vitro human skin-based genotoxicity assays for topically exposed substances, such as cosmetics ingredients. Here, we describe the validation of the 3D reconstructed skin (RS) Comet assay. In this multicenter study, chemicals were applied topically three times to the skin over 48 h. Isolated keratinocytes and fibroblasts were transferred to slides before electrophoresis and the resulting comet formation was recorded as % tail DNA. Before decoding, results of the validation exercise for 32 substances were evaluated by an independent statistician. There was a high predictive capacity of this assay when compared to in vivo outcomes, with a sensitivity of 77 (80)%, a specificity of 88 (97)% and an overall accuracy of 83 (92)%. The numbers reflect the calls of the performing laboratories in the coded phase, whereas those in parenthesis reflect calls according to the agreed evaluation criteria. Intra- and inter-laboratory reproducibility was also very good, with a concordance of 93 and 88%, respectively. These results generated with the Phenion® Full-Thickness skin model demonstrate its suitability for this assay, with reproducibly low background DNA damage and sufficient metabolic capacity to activate pro-mutagens. The validation outcome supports the use of the RS Comet assay to follow up positive results from standard in vitro genotoxicity assays when the expected route of exposure is dermal. Based on the available data, the assay was accepted recently into the OECD test guideline development program.

False positive amphetamines and 3,4-methylenedioxymethamphetamine immunoassays in the presence of metoprolol—two cases reported in clinical toxicology

2019 ◽  
Vol 44 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Marion Leclercq ◽  
Marion Soichot ◽  
Brigitte Delhotal-Landes ◽  
Emmanuel Bourgogne ◽  
Hervé Gourlain ◽  
...  
Keyword(s):  
False Positive ◽  
Parent Drug ◽  
Cross Reactivity ◽  
Molecular Structures ◽  
Gas Chromatography Mass Spectrometry ◽  
Medication History ◽  
In Vitro Investigation ◽  
Urine Drug ◽  
Positive Results

Abstract Amphetamines, frequently used recreational drugs with high risk of toxicity, are commonly included in urine drug screens. This screening is based on enzyme immunoassay, which is a quick and easy-to-perform technique, but may lack specificity resulting from cross-reactivity with other compounds, causing false positive results. We present two cases of presumed false positive MULTIGENT® amphetamine/methamphetamine and MULTIGENT® ecstasy (Abbott®) immunoassays with the beta-blocker metoprolol. Both metoprolol-poisoned patients presented positive urine screening despite no history of drug abuse. No confirmation for amphetamine molecular structures was found with gas chromatography–mass spectrometry. The cross-reactivity was further investigated by doping urine samples with metoprolol and its two major phase-I metabolites. Metoprolol showed positive results for both amphetamine and MDMA tests at low concentrations (200 and 150 μg/mL, respectively). Metoprolol metabolites cross-reacted with the amphetamines immunoassay only, but at higher concentrations (i.e., 2000 μg/mL for α-hydroxymetoprolol and 750 μg/mL for O-demethylmetoprolol). In conclusion, false positive results in amphetamines and MDMA immunoassays are possible in the presence of metoprolol. Toxicologists should be aware of frequent analytical interferences with immunoassays and a detailed medication history should be taken into consideration for interpretation. In vitro investigation of suspected cross-reactivity should include not only the parent drug but also its related metabolites.

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