Journal of Medical Toxicology最新文献

{"title":"Confirmed Fatal Colchicine Poisoning in an Adolescent with Blood and Bile Concentrations-Implications for GI Decontamination?","authors":"Joshua Trebach, Molly Boyd, Andres Crane, Phil DiSalvo, Rana Biary, Robert S Hoffman, Mark K Su","doi":"10.1007/s13181-023-00946-2","DOIUrl":"10.1007/s13181-023-00946-2","url":null,"abstract":"<p><strong>Introduction: </strong>Colchicine is commonly used to treat diseases like acute gouty arthritis. However, colchicine has a very narrow therapeutic index, and ingestions of > 0.5mg/kg can be deadly. We report a fatal acute colchicine overdose in an adolescent. Blood and postmortem bile colchicine concentrations were obtained to better understand the degree of enterohepatic circulation of colchicine.</p><p><strong>Case report: </strong>A 13-year-old boy presented to the emergency department after acute colchicine poisoning. A single dose of activated charcoal was administered early but no other doses were attempted. Despite aggressive interventions such as exchange transfusion and veno-arterial extracorporeal membrane oxygenation (VA-ECMO), the patient died 8 days later. Postmortem histology was notable for centrilobular necrosis of the liver and a cardiac septal microinfarct. The patient's blood colchicine concentration on hospital days 1 (~30 hours post-ingestion), 5, and 7 was 12ng/mL, 11ng/mL, and 9.5ng/mL, respectively. A postmortem bile concentration obtained during autopsy was 27ng/mL.</p><p><strong>Discussion: </strong>Humans produce approximately 600mL of bile daily. Assuming that activated charcoal would be able to adsorb 100% of biliary colchicine, using the bile concentration obtained above, only 0.0162mg of colchicine per day would be able to be adsorbed and eliminated by activated charcoal in this patient.</p><p><strong>Conclusion: </strong>Despite supportive care, activated charcoal, VA-ECMO, and exchange transfusion, modern medicine may not be enough to prevent death in severely poisoned colchicine patients. Although targeting enterohepatic circulation with activated charcoal to enhance elimination of colchicine sounds attractive, the patient's low postmortem bile concentration of colchicine suggests a limited role of activated charcoal in enhancing elimination of a consequential amount of colchicine.</p>","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9705210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation.","authors":"Andrew A Monte, Alexis Vest, Julie A Reisz, Danielle Berninzoni, Claire Hart, Layne Dylla, Angelo D'Alessandro, Kennon J Heard, Cheyret Wood, Jack Pattee","doi":"10.1007/s13181-023-00951-5","DOIUrl":"10.1007/s13181-023-00951-5","url":null,"abstract":"<p><strong>Background: </strong>Acetaminophen (APAP) is the most common cause liver injury following alcohol in US patients. Predicting liver injury and subsequent hepatic regeneration in patients taking therapeutic doses of APAP may be possible using new 'omic methods such as metabolomics and genomics. Multi'omic techniques increase our ability to find new mechanisms of injury and regeneration.</p><p><strong>Methods: </strong>We used metabolomic and genomic data from a randomized controlled trial of patients administered 4 g of APAP per day for 14 days or longer with blood samples obtained at 0 (baseline), 4, 7, 10, 13 and 16 days. We used the highest ALT as the clinical outcome to be predicted in our integrated analysis. We used penalized regression to model the relationship between genetic variants and day 0 metabolite level, and then performed a metabolite-wide colocalization scan to associate the genetically regulated component of metabolite expression with ALT elevation. Genome-wide association study (GWAS) analyses were conducted for ALT elevation and metabolite level using linear regression, with age, sex, and the first five principal components included as covariates. Colocalization was tested via a weighted sum test.</p><p><strong>Results: </strong>Out of the 164 metabolites modeled, 120 met the criteria for predictive accuracy and were retained for genetic analyses. After genomic examination, eight metabolites were found to be under genetic control and predictive of ALT elevation due to therapeutic acetaminophen. The metabolites were: 3-oxalomalate, allantoate, diphosphate, L-carnitine, L-proline, maltose, and ornithine. These genes are important in the tricarboxylic acid cycle (TCA), urea breakdown pathway, glutathione production, mitochondrial energy production, and maltose metabolism.</p><p><strong>Conclusions: </strong>This multi'omic approach can be used to integrate metabolomic and genomic data allowing identification of genes that control downstream metabolites. These findings confirm prior work that have identified mitochondrial energy production as critical to APAP induced liver injury and have confirmed our prior work that demonstrate the importance of the urea cycle in therapeutic APAP liver injury.</p>","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Articles You Might Have Missed.","authors":"Kelsey Martin,&nbsp;Miya A Smith,&nbsp;Daniel Rivera,&nbsp;Serah Mbugua","doi":"10.1007/s13181-023-00948-0","DOIUrl":"https://doi.org/10.1007/s13181-023-00948-0","url":null,"abstract":"","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9515150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Our Appreciation and Gratitude to Journal of Medical Toxicology (JMT) Peer Reviewers in 2022.","authors":"Mark B Mycyk","doi":"10.1007/s13181-023-00939-1","DOIUrl":"10.1007/s13181-023-00939-1","url":null,"abstract":"","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Cardiovascular and Adverse Effects of Glucagon for the Management of Suspected Beta Blocker Toxicity: a Case Series\".","authors":"Marlis Gnirke, Brian G Wiener, Silas W Smith","doi":"10.1007/s13181-023-00935-5","DOIUrl":"10.1007/s13181-023-00935-5","url":null,"abstract":"","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Welcome to the 2023 ACMT Annual Scientific Meeting-San Diego, CA.","authors":"Katherine L Boyle, Michael S Toce, Alison Meyn, Adrienne Dunavin, Maryann Mazer-Amirshahi","doi":"10.1007/s13181-023-00932-8","DOIUrl":"10.1007/s13181-023-00932-8","url":null,"abstract":"","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Suspected Suicides and Nonfatal Suicide Attempts Reported to United States Poison Control Centers Before and During the COVID-19 Pandemic.","authors":"Hailee R Ciccotti,&nbsp;Henry A Spiller,&nbsp;Marcel J Casavant,&nbsp;Sandhya Kistamgari,&nbsp;Alexandra R Funk,&nbsp;Gary A Smith","doi":"10.1007/s13181-023-00933-7","DOIUrl":"https://doi.org/10.1007/s13181-023-00933-7","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the characteristics and compared the trends of pediatric suspected suicide and nonfatal suicide attempts reported to United States (US) poison control centers (PCCs) before and during the first year of the COVID-19 pandemic.</p><p><strong>Methods: </strong>An interrupted time series analysis using an ARIMA model was conducted to evaluate the trends of suspected suicides and nonfatal suicide attempts among children 6-19 years old reported to the National Poison Data System during March 2020 through February 2021 (pandemic period) compared with March 2017 through February 2020 (pre-pandemic period).</p><p><strong>Results: </strong>The annual number of cases of suspected suicides and nonfatal suicide attempts increased by 4.5% (6095/136,194) among children 6-19 years old during March 2020 through February 2021 compared with the average annual number during the previous three pre-pandemic years. There were 11,876 fewer cases than expected from March 2020 to February 2021, attributable to a decrease in cases during the initial three pandemic months. The average monthly and average daily number of suspected suicides and nonfatal suicide attempts among children 6-12 years old and 13-19 years old was higher during school months than non-school months and weekdays than weekends during both the pre-pandemic and pandemic periods.</p><p><strong>Conclusions: </strong>There was a greater than expected decrease in the number of suspected suicides and nonfatal suicide attempts among children 6-19 years old reported to US PCCs during the early pandemic months, followed by an increase in cases. Recognizing these patterns can help guide an appropriate public health response to similar future crises.</p>","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delta-8-Tetrahydrocannabinol Exposure and Confirmation in Four Pediatric Patients.","authors":"Kerollos Shaker, Andrea Nillas, Ross Ellison, Kelsey Martin, Jordan Trecki, Roy Gerona, Kim Aldy","doi":"10.1007/s13181-022-00927-x","DOIUrl":"10.1007/s13181-022-00927-x","url":null,"abstract":"<p><strong>Introduction: </strong>Delta-8-tetrahydrocannabinol (THC) is a known isomer of delta-9-THC, both found naturally in the Cannabis sativa plant and thought to have similar potency. Delta-8-THC products are widely accessible in retail shops which may lead to a rise in pediatric exposures with substantial clinical effects.</p><p><strong>Case report: </strong>This is a case series of four pediatric patients that were seen between June and September 2021. The patients presented with varied clinical symptoms including confusion, somnolence, seizure-like activity, hypotension, and tachycardia after exposure to delta-8-THC products obtained in retail shops. Basic urine drug screen immunoassays revealed positive results for cannabinoids in all patients. Subsequent confirmatory drug analysis of residual biological samples of blood and/or urine was sent to the University of California San Francisco Clinical Toxicology and Environment Biomonitoring Laboratory with the assistance of the Drug Enforcement Administration's Toxicology Testing Program (DEA TOX). Confirmatory testing revealed 11-nor-9-carboxy-delta-8-THC, the metabolite of delta-8-THC. Delta-9-THC and its metabolites were not detected on confirmatory testing in any of the cases.</p><p><strong>Discussion: </strong>Clinical effects of delta-8-THC in children include but are not limited to altered mental status, seizure-like activity, and vital sign abnormalities. Delta-8-THC exposure may lead to a positive urine drug screen for cannabinoids, but confirmatory testing is needed to differentiate from delta-9-THC.</p>","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Nonfatal Opioid, Cocaine, Methamphetamine, and Polydrug Exposure and Clinical Presentations Reported to the Toxicology Investigators Consortium Core Registry, January 2010-December 2021.","authors":"Emily Glidden, Kyle Suen, Desiree Mustaquim, Alana Vivolo-Kantor, Jeffery Brent, Paul Wax, Kim Aldy","doi":"10.1007/s13181-022-00924-0","DOIUrl":"10.1007/s13181-022-00924-0","url":null,"abstract":"<p><strong>Introduction: </strong>To characterize and compare opioid-only, cocaine-only, methamphetamine-only, opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure and to examine clinical presentations, leading to a better understanding of overdose effects involving these drug exposures.</p><p><strong>Methods: </strong>We examined drug exposures in the Toxicology Investigators Consortium (ToxIC) Core Registry from January 2010 to December 2021, a case registry of patients presenting to participating healthcare sites that receive a medical toxicology consultation. Demographic and clinical presentations of opioid-only, cocaine-only, methamphetamine-only, and opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure consultations were described; differences between single and polydrug exposure subgroups were calculated to determine statistical significance. Clinical presentations associated with exposures were evaluated through calculated adjusted relative risk.</p><p><strong>Results: </strong>A total of 3,883 consultations involved opioids, cocaine, methamphetamine, opioid-and-cocaine exposure, or opioid-and-methamphetamine exposure. Opioid-only (n = 2,268, 58.4%) and methamphetamine-only (n = 712, 18.3%) comprised most consultations. There were significant differences in clinical presentations between exposure subgroups. Opioid-and-cocaine exposure consultations were 8.15 times as likely to present with a sympathomimetic toxidrome than opioid-only. Conversely, opioid-and-cocaine exposure and opioid-and-methamphetamine exposure were 0.32 and 0.42 times as likely to present with a sympathomimetic toxidrome compared to cocaine-only and methamphetamine-only consultations, respectively. Opioid-and-cocaine exposure was 0.67 and opioid-and-methamphetamine exposure was 0.74 times as likely to present with respiratory depression compared to opioid-only consultations. Similarly, opioid-and-cocaine exposure was 0.71 and opioid-and-methamphetamine exposure was 0.78 times as likely to present with CNS depression compared to opioid-only consultations.</p><p><strong>Conclusions: </strong>Used in combination, opioids and stimulants may mask typical clinical presentations of one another, misattributing incorrect drugs to overdose in both clinical treatment and public health surveillance.</p>","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9666182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration in Cerebral Metabolism in a Rodent Model of Acute Sub-lethal Cyanide Poisoning.","authors":"Oladunni Alomaja, Frances S Shofer, John C Greenwood, Sarah Piel, Carly Clayman, Clementina Mesaros, Shih-Han Kao, Samuel S Shin, Johannes K Ehinger, Todd J Kilbaugh, David H Jang","doi":"10.1007/s13181-022-00928-w","DOIUrl":"10.1007/s13181-022-00928-w","url":null,"abstract":"<p><strong>Introduction: </strong>Cyanide exposure can occur in various settings such as industry and metallurgy. The primary mechanism of injury is cellular hypoxia from Complex IV (CIV) inhibition. This leads to decreased ATP production and increased reactive oxygen species production. The brain and the heart are the organs most affected due to their high metabolic demand. While the cardiac effects of cyanide are well known, the cerebral effects on cellular function are less well described. We investigated cerebral metabolism with a combination of brain respirometry, microdialysis, and western blotting using a rodent model of sub-lethal cyanide poisoning.</p><p><strong>Methods: </strong>Twenty rodents were divided into two groups: control (n = 10) and sub-lethal cyanide (n = 10). Cerebral microdialysis was performed during a 2 mg/kg/h cyanide exposure to obtain real-time measurements of cerebral metabolic status. At the end of the exposure (90 min), brain-isolated mitochondria were measured for mitochondrial respiration. Brain tissue ATP concentrations, acyl-Coenzyme A thioesters, and mitochondrial content were also measured.</p><p><strong>Results: </strong>The cyanide group showed significantly increased lactate and decreased hypotension with decreased cerebral CIV-linked mitochondrial respiration. There was also a significant decrease in cerebral ATP concentration in the cyanide group and a significantly higher cerebral lactate-to-pyruvate ratio (LPR). In addition, we also found decreased expression of Complex III and IV protein expression in brain tissue from the cyanide group. Finally, there was no change in acyl-coenzyme A thioesters between the two groups.</p><p><strong>Conclusions: </strong>The key finding demonstrates mitochondrial dysfunction in brain tissue that corresponds with a decrease in mitochondrial function, ATP concentrations, and an elevated LPR indicating brain dysfunction at a sub-lethal dose of cyanide.</p>","PeriodicalId":16429,"journal":{"name":"Journal of Medical Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}