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Michael J Rieder - One of the best experts on this subject based on the ideXlab platform.
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dress induced by amoxicillin clavulanate in two pediatric patients confirmed by lymphocyte Toxicity Assay
Allergy Asthma & Clinical Immunology, 2021Co-Authors: Arun Dhir, Abdelbaset A Elzagallaai, Michael J Rieder, Hasandeep Kular, Bruce Carleton, Raymond H Mak, Tiffany WongAbstract:Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious delayed hypersensitivity reaction that can be caused by antibiotic exposure. The reaction typically develops in 2 to 6 weeks. The pathophysiology is thought to involve toxic drug metabolites acting as a hapten, triggering a systemic response. The diagnosis is made clinically but can be confirmed using Assays such as the lymphocyte Toxicity Assay (LTA), which correlates cell death upon exposure to drug metabolites with susceptibility to hypersensitivity reactions. Case 1 involves a previously healthy 11-month-old male with first exposure to amoxicillin-clavulanate, prescribed for seven days to treat a respiratory infection. The patient developed DRESS fourteen days after starting the drug and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Parental samples were also tested, showing both maternal and paternal susceptibility. Neither parent reported prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. The parents were advised to avoid penicillin class antibiotics and be monitored closely for DRESS if they are exposed. Case 2 involves an 11-year-old female with atopic dermatitis with first exposure to amoxicillin-clavulanate, prescribed for ten days to treat a secondary bacterial skin infection. She developed DRESS eleven days after starting antibiotics and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Maternal samples were also tested and showed sensitivity. The mother reported no prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. Amoxicillin-clavulanate is a commonly used antibiotic and the cases we have described suggest that it should be recognized as a potential cause of DRESS in pediatric patients. Furthermore, these cases contribute to current literature supporting that there may be a shorter latent period in DRESS induced by antibiotics. We have also shown that the LTA can be a helpful tool to confirm DRESS reactions, and that testing may have potential implications for family members.
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the predictive value of the in vitro platelet Toxicity Assay ipta for the diagnosis of hypersensitivity reactions to sulfonamides a case control study
Clinical and Translational Allergy, 2014Co-Authors: Abdelbaset A Elzagallaai, Gideon Koren, Michael J RiederAbstract:Background Drug hypersensitivity reactions (DHRs) are rare but potentially fatal types of adverse drug reactions (ADRs) that develop in susceptible patients following exposure to certain drugs including sulfonamides. The diagnosis of this type of ADRs is challenging and currently depends on clinical expertise. A safe and reliable in vitro test to diagnose DHRs would be a major advance in patient care and in evaluation of possible serious ADRs during drug development and clinical trials. Current available in vitro tests including the lymphocyte Toxicity Assay (LTA) and the lymphocyte transformation test (LTT) are cumbersome and expensive, and their predictive values are undefined. We have recently developed a novel in vitro diagnostic test for DHRs, the in vitro platelet Toxicity Assay (iPTA) to test patient susceptibility to DHS. The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamide antibiotics.
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the predictive value of the in vitro platelet Toxicity Assay ipta for the diagnosis of hypersensitivity reactions to sulfonamides
The Journal of Clinical Pharmacology, 2013Co-Authors: Abdelbaset A Elzagallaai, Gideon Koren, Michael J RiederAbstract:Drug hypersensitivity reactions (DHRs) are rare but potentially fatal adverse drug reactions (ADRs). A reliable test to diagnose DHRs would be a major advance in the clinical care for patients and in the evaluation of ADRs during drug development as well as for mechanistic studies of drug hypersensitivity. Available in vitro tests including the lymphocyte Toxicity Assay (LTA) have been used but are time-consuming, cumbersome, and expensive. We have developed a novel diagnostic test for DHRs, the in vitro platelet Toxicity Assay (iPTA). The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamides. We recruited 66 individuals (36 DHS-sulfa patients and 30 healthy controls) to participate in the study. Blood samples were obtained and LTA and iPTA were performed in parallel. There was concentration-dependent Toxicity in the cells of patients when incubated with the reactive hydroxylamine metabolite of sulfamethoxazole for both the LTA and iPTA (P < .05). The iPTA was more sensitive than conventional LTA test in detecting susceptibility of patient cells to in vitro Toxicity (P < .05). The novel iPTA has considerable potential as an investigative tool for DHS as it is more sensitive and cheaper, requiring no special reagents.
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Predictive Value of the Lymphocyte Toxicity Assay in the Diagnosis of Drug Hypersensitivity Syndrome
Molecular Diagnosis & Therapy, 2010Co-Authors: Abdelbaset A Elzagallaai, Michael J Rieder, Zahra Jahedmotlagh, Blanca R. Pozzo-magaña, Sandra R. Knowles, Asuri N. Prasad, Neil H. Shear, Gideon KorenAbstract:Background: Drug hypersensitivity syndrome (DHS) is a rare but potentially fatal adverse drug reaction that develops in susceptible patients following exposure to certain drugs. Because of the variable clinical picture of DHS and its resemblance to other diseases, the diagnosis of DHS is challenging. The lymphocyte Toxicity Assay (LTA) is an in vitro test that has been used in the diagnosis of DHS. However, its predictive values are still controversial because of the lack of a ‘gold standard’ test to measure it against. Objectives : To determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the LTA in the diagnosis of DHS due to different classes of drugs, based on systemic reexposure as a gold standard, and to evaluate the current clinical utility of the LTA in clinical practice. Methods: Potential participants were identified from their medical records and contacted to obtain their consent to participate in the study. One hundred forty-seven patients were recruited and interviewed by telephone to identify events of re-exposure and their consequences. These data were used to determine true positive, false positive, true negative, and false negative results of the test, which were then used to estimate the predictive value of the test. Results: We identified 26 re-exposure events in 22 patients: 4 were true positives, 17 were true negatives, 1 was a false positive, and 4 were false negatives, as determined by systemic re-exposure. Although the number of identified re-exposures limited the ability to calculate the predictive values, our data provide an estimate of the clinical value of the test for the diagnosis of DHS. The data also highlight the effect of the type of drug involved in the reaction on the predictive value of the test. Conclusion: The LTA is potentially a valuable diagnostic tool for DHS; however, its sensitivity, specificity, NPV, and PPV seem to vary according to the drug involved in the reaction.
Abdelbaset A Elzagallaai - One of the best experts on this subject based on the ideXlab platform.
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dress induced by amoxicillin clavulanate in two pediatric patients confirmed by lymphocyte Toxicity Assay
Allergy Asthma & Clinical Immunology, 2021Co-Authors: Arun Dhir, Abdelbaset A Elzagallaai, Michael J Rieder, Hasandeep Kular, Bruce Carleton, Raymond H Mak, Tiffany WongAbstract:Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious delayed hypersensitivity reaction that can be caused by antibiotic exposure. The reaction typically develops in 2 to 6 weeks. The pathophysiology is thought to involve toxic drug metabolites acting as a hapten, triggering a systemic response. The diagnosis is made clinically but can be confirmed using Assays such as the lymphocyte Toxicity Assay (LTA), which correlates cell death upon exposure to drug metabolites with susceptibility to hypersensitivity reactions. Case 1 involves a previously healthy 11-month-old male with first exposure to amoxicillin-clavulanate, prescribed for seven days to treat a respiratory infection. The patient developed DRESS fourteen days after starting the drug and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Parental samples were also tested, showing both maternal and paternal susceptibility. Neither parent reported prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. The parents were advised to avoid penicillin class antibiotics and be monitored closely for DRESS if they are exposed. Case 2 involves an 11-year-old female with atopic dermatitis with first exposure to amoxicillin-clavulanate, prescribed for ten days to treat a secondary bacterial skin infection. She developed DRESS eleven days after starting antibiotics and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Maternal samples were also tested and showed sensitivity. The mother reported no prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. Amoxicillin-clavulanate is a commonly used antibiotic and the cases we have described suggest that it should be recognized as a potential cause of DRESS in pediatric patients. Furthermore, these cases contribute to current literature supporting that there may be a shorter latent period in DRESS induced by antibiotics. We have also shown that the LTA can be a helpful tool to confirm DRESS reactions, and that testing may have potential implications for family members.
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the predictive value of the in vitro platelet Toxicity Assay ipta for the diagnosis of hypersensitivity reactions to sulfonamides a case control study
Clinical and Translational Allergy, 2014Co-Authors: Abdelbaset A Elzagallaai, Gideon Koren, Michael J RiederAbstract:Background Drug hypersensitivity reactions (DHRs) are rare but potentially fatal types of adverse drug reactions (ADRs) that develop in susceptible patients following exposure to certain drugs including sulfonamides. The diagnosis of this type of ADRs is challenging and currently depends on clinical expertise. A safe and reliable in vitro test to diagnose DHRs would be a major advance in patient care and in evaluation of possible serious ADRs during drug development and clinical trials. Current available in vitro tests including the lymphocyte Toxicity Assay (LTA) and the lymphocyte transformation test (LTT) are cumbersome and expensive, and their predictive values are undefined. We have recently developed a novel in vitro diagnostic test for DHRs, the in vitro platelet Toxicity Assay (iPTA) to test patient susceptibility to DHS. The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamide antibiotics.
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the predictive value of the in vitro platelet Toxicity Assay ipta for the diagnosis of hypersensitivity reactions to sulfonamides
The Journal of Clinical Pharmacology, 2013Co-Authors: Abdelbaset A Elzagallaai, Gideon Koren, Michael J RiederAbstract:Drug hypersensitivity reactions (DHRs) are rare but potentially fatal adverse drug reactions (ADRs). A reliable test to diagnose DHRs would be a major advance in the clinical care for patients and in the evaluation of ADRs during drug development as well as for mechanistic studies of drug hypersensitivity. Available in vitro tests including the lymphocyte Toxicity Assay (LTA) have been used but are time-consuming, cumbersome, and expensive. We have developed a novel diagnostic test for DHRs, the in vitro platelet Toxicity Assay (iPTA). The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamides. We recruited 66 individuals (36 DHS-sulfa patients and 30 healthy controls) to participate in the study. Blood samples were obtained and LTA and iPTA were performed in parallel. There was concentration-dependent Toxicity in the cells of patients when incubated with the reactive hydroxylamine metabolite of sulfamethoxazole for both the LTA and iPTA (P < .05). The iPTA was more sensitive than conventional LTA test in detecting susceptibility of patient cells to in vitro Toxicity (P < .05). The novel iPTA has considerable potential as an investigative tool for DHS as it is more sensitive and cheaper, requiring no special reagents.
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Predictive Value of the Lymphocyte Toxicity Assay in the Diagnosis of Drug Hypersensitivity Syndrome
Molecular Diagnosis & Therapy, 2010Co-Authors: Abdelbaset A Elzagallaai, Michael J Rieder, Zahra Jahedmotlagh, Blanca R. Pozzo-magaña, Sandra R. Knowles, Asuri N. Prasad, Neil H. Shear, Gideon KorenAbstract:Background: Drug hypersensitivity syndrome (DHS) is a rare but potentially fatal adverse drug reaction that develops in susceptible patients following exposure to certain drugs. Because of the variable clinical picture of DHS and its resemblance to other diseases, the diagnosis of DHS is challenging. The lymphocyte Toxicity Assay (LTA) is an in vitro test that has been used in the diagnosis of DHS. However, its predictive values are still controversial because of the lack of a ‘gold standard’ test to measure it against. Objectives : To determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the LTA in the diagnosis of DHS due to different classes of drugs, based on systemic reexposure as a gold standard, and to evaluate the current clinical utility of the LTA in clinical practice. Methods: Potential participants were identified from their medical records and contacted to obtain their consent to participate in the study. One hundred forty-seven patients were recruited and interviewed by telephone to identify events of re-exposure and their consequences. These data were used to determine true positive, false positive, true negative, and false negative results of the test, which were then used to estimate the predictive value of the test. Results: We identified 26 re-exposure events in 22 patients: 4 were true positives, 17 were true negatives, 1 was a false positive, and 4 were false negatives, as determined by systemic re-exposure. Although the number of identified re-exposures limited the ability to calculate the predictive values, our data provide an estimate of the clinical value of the test for the diagnosis of DHS. The data also highlight the effect of the type of drug involved in the reaction on the predictive value of the test. Conclusion: The LTA is potentially a valuable diagnostic tool for DHS; however, its sensitivity, specificity, NPV, and PPV seem to vary according to the drug involved in the reaction.
Karine Le Ménach - One of the best experts on this subject based on the ideXlab platform.
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Integrated monitoring of chemicals and their effects on four sentinel species, Limanda limanda, Platichthys flesus, Nucella lapillus and Mytilus sp., in Seine Bay: A key step towards applying biological effects to monitoring
Marine Environmental Research, 2017Co-Authors: Thierry Burgeot, Farida Akcha, Dominique Menard, Craig Robinson, Véronique Loizeau, Christophe Brach-papa, Concepción Martínez-gòmez, Jérémie Le Goff, Hélène Budzinski, Karine Le MénachAbstract:The International workshop on Integrated Assessment of CONtaminants impacts on the North sea (ICON) provided a framework to validate the application of chemical and biological assessment thresholds (BACs and EACs) in the Seine Bay in France. BioAssays (oyster larval anomalies, Corophium arenarium Toxicity Assay and DR Calux) for sediment and biomarkers: ethoxyresorufin-O-deethylase (EROD) activity, acetylcholinesterase (AChE) activity, lysosomal membrane stability (LMS), DNA strand breaks using the Comet Assay, DNA adducts, micronucleus (MN), PAH metabolites, imposex, intersex and fish external pathologies were analysed in four marine sentinel species (Platichthys flesus, Limanda limanda, Mytilus sp. and Nucella lapilus). Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and heavy metals were analysed in biota and sediment. Results for sediment and four species in 2008–2009 made it possible to quantify the impact of contaminants using thresholds (Environmental Assessment Criteria/EAC2008: 70% and EAC2009: 60%) and effects (EAC2008: 50% and EAC2009: 40%) in the Seine estuary. The Seine estuary is ranked among Europe's most highly polluted sites.
Dayong Wang - One of the best experts on this subject based on the ideXlab platform.
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translocation transfer and in vivo safety evaluation of engineered nanomaterials in the non mammalian alternative Toxicity Assay model of nematode caenorhabditis elegans
RSC Advances, 2013Co-Authors: Yunli Zhao, Dayong WangAbstract:Translocation, transfer, and safety evaluation of engineered nanomaterials in non-mammalian alternative Assay model of Caenorhabditis elegans are summarized and discussed. Due to the extensive applications of engineered nanomaterials (ENMs) in industry, agriculture, medicine and public health, environmental exposure of ENMs to human and environmental organisms is inevitable, therefore studies on translocation, transfer, and toxicology of ENMs receive wide interest. Modelling the nematode C. elegans, a widely recognized non-mammalian alternative Toxicity Assay system has been proven to be valuable in environmental safety evaluation, toxicological study, and examination of translocation and transfer of toxicants. In this review, we summarize and discuss the values and contributions of C. elegans in studies on environmental safety evaluation, toxicology, and translocation and transfer of ENMs. We introduced acute and chronic Toxicity Assay systems and discussed environmental safety assessment of specific ENMs at predicted environmental relevant concentrations, and influences of chemical properties of ENMs, exposure routes, developmental, genetic or physiological state, and environmental factors on nanoToxicity formation in nematodes. We then discussed the toxicological mechanisms of ENMs mainly with respect to roles of oxidative stress in normal and stress conditions and signaling pathways, reproductive toxicology, neurotoxicology, and translocation, distribution, transfer and metabolism of ENMs in C. elegans. Ways to eliminate or reduce the toxicities of specific ENMs by chemical modification with surface designs were further discussed. Finally, four important challenges have been raised and discussed by surrounding the aspects of environmental safety assessment, toxicological mechanisms, and designs of new safe ENMs.
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small sizes of tio2 nps exhibit adverse effects at predicted environmental relevant concentrations on nematodes in a modified chronic Toxicity Assay system
Journal of Hazardous Materials, 2012Co-Authors: Wei Wang, Meng Tang, Dayong WangAbstract:Abstract In Caenorhabditis elegans, although acute Toxicity of TiO2 nanoparticles (TiO2-NPs) at high concentrations has been investigated, we still know little about chronic Toxicity of TiO2-NPs. Our data here showed that acute TiO2-NPs exposure in the range of μg/L had no obviously adverse effects on nematodes, but the chronic toxicities of large sizes (60 nm and 90 nm) of TiO2-NPs in the range of μg/L were detected in nematodes in a modified chronic Toxicity Assay system. Moreover, chronic toxicities of small sizes (4 nm and 10 nm) of TiO2-NPs in the range of ng/L were observed in nematodes with locomotion behavior and ROS production as endpoints. In nematodes chronically exposed to small sizes of TiO2-NPs at predicted environmental relevant concentrations, locomotion behavior was significantly (P l -cysteine) inhibited both the induction of ROS production and the decrease of locomotion behaviors observed in nematodes chronically exposed to small sizes of TiO2-NPs at predicted environmental relevant concentrations. Therefore, chronic exposure to small sizes of TiO2-NPs at predicted environmental relevant concentrations can cause adverse effects on nematodes, and formation of such adverse effects may be largely due to the induction of oxidative stress.
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chromium exhibits adverse effects at environmental relevant concentrations in chronic Toxicity Assay system of nematode caenorhabditis elegans
Chemosphere, 2012Co-Authors: Dayong WangAbstract:Abstract Here we investigated whether the Assay system (10-d) in Caenorhabditis elegans can be used to evaluate chronic Toxicity of chromium (Cr(VI)) at environmental relevant concentrations ranging from 5.2 μg L −1 to 260 μg L −1 . The results indicated that lethality, locomotion behavior as revealed by head thrash, body bend, and forward turn, metabolism as revealed by pumping rate and mean defecation cycle length, intestinal autofluorescence, and ROS production were severely altered in Cr chronically exposed nematodes at environmental relevant concentrations. The most surprising observations were that head thrash, body bend, intestinal autofluorescence, and ROS production in 13 μg L −1 Cr exposed nematodes were significantly influenced. The observed adverse effects of Cr on survival, locomotion behavior, and metabolism were largely due to forming severe intestinal autofluorescence and ROS production. Therefore, our findings demonstrate the usefulness of chronic Toxicity Assay system in C. elegans in evaluating the chronic Toxicity of toxicants at environmental relevant concentrations.
Gideon Koren - One of the best experts on this subject based on the ideXlab platform.
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the predictive value of the in vitro platelet Toxicity Assay ipta for the diagnosis of hypersensitivity reactions to sulfonamides a case control study
Clinical and Translational Allergy, 2014Co-Authors: Abdelbaset A Elzagallaai, Gideon Koren, Michael J RiederAbstract:Background Drug hypersensitivity reactions (DHRs) are rare but potentially fatal types of adverse drug reactions (ADRs) that develop in susceptible patients following exposure to certain drugs including sulfonamides. The diagnosis of this type of ADRs is challenging and currently depends on clinical expertise. A safe and reliable in vitro test to diagnose DHRs would be a major advance in patient care and in evaluation of possible serious ADRs during drug development and clinical trials. Current available in vitro tests including the lymphocyte Toxicity Assay (LTA) and the lymphocyte transformation test (LTT) are cumbersome and expensive, and their predictive values are undefined. We have recently developed a novel in vitro diagnostic test for DHRs, the in vitro platelet Toxicity Assay (iPTA) to test patient susceptibility to DHS. The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamide antibiotics.
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the predictive value of the in vitro platelet Toxicity Assay ipta for the diagnosis of hypersensitivity reactions to sulfonamides
The Journal of Clinical Pharmacology, 2013Co-Authors: Abdelbaset A Elzagallaai, Gideon Koren, Michael J RiederAbstract:Drug hypersensitivity reactions (DHRs) are rare but potentially fatal adverse drug reactions (ADRs). A reliable test to diagnose DHRs would be a major advance in the clinical care for patients and in the evaluation of ADRs during drug development as well as for mechanistic studies of drug hypersensitivity. Available in vitro tests including the lymphocyte Toxicity Assay (LTA) have been used but are time-consuming, cumbersome, and expensive. We have developed a novel diagnostic test for DHRs, the in vitro platelet Toxicity Assay (iPTA). The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamides. We recruited 66 individuals (36 DHS-sulfa patients and 30 healthy controls) to participate in the study. Blood samples were obtained and LTA and iPTA were performed in parallel. There was concentration-dependent Toxicity in the cells of patients when incubated with the reactive hydroxylamine metabolite of sulfamethoxazole for both the LTA and iPTA (P < .05). The iPTA was more sensitive than conventional LTA test in detecting susceptibility of patient cells to in vitro Toxicity (P < .05). The novel iPTA has considerable potential as an investigative tool for DHS as it is more sensitive and cheaper, requiring no special reagents.
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Predictive Value of the Lymphocyte Toxicity Assay in the Diagnosis of Drug Hypersensitivity Syndrome
Molecular Diagnosis & Therapy, 2010Co-Authors: Abdelbaset A Elzagallaai, Michael J Rieder, Zahra Jahedmotlagh, Blanca R. Pozzo-magaña, Sandra R. Knowles, Asuri N. Prasad, Neil H. Shear, Gideon KorenAbstract:Background: Drug hypersensitivity syndrome (DHS) is a rare but potentially fatal adverse drug reaction that develops in susceptible patients following exposure to certain drugs. Because of the variable clinical picture of DHS and its resemblance to other diseases, the diagnosis of DHS is challenging. The lymphocyte Toxicity Assay (LTA) is an in vitro test that has been used in the diagnosis of DHS. However, its predictive values are still controversial because of the lack of a ‘gold standard’ test to measure it against. Objectives : To determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the LTA in the diagnosis of DHS due to different classes of drugs, based on systemic reexposure as a gold standard, and to evaluate the current clinical utility of the LTA in clinical practice. Methods: Potential participants were identified from their medical records and contacted to obtain their consent to participate in the study. One hundred forty-seven patients were recruited and interviewed by telephone to identify events of re-exposure and their consequences. These data were used to determine true positive, false positive, true negative, and false negative results of the test, which were then used to estimate the predictive value of the test. Results: We identified 26 re-exposure events in 22 patients: 4 were true positives, 17 were true negatives, 1 was a false positive, and 4 were false negatives, as determined by systemic re-exposure. Although the number of identified re-exposures limited the ability to calculate the predictive values, our data provide an estimate of the clinical value of the test for the diagnosis of DHS. The data also highlight the effect of the type of drug involved in the reaction on the predictive value of the test. Conclusion: The LTA is potentially a valuable diagnostic tool for DHS; however, its sensitivity, specificity, NPV, and PPV seem to vary according to the drug involved in the reaction.