Steven C Curry

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Scholarly Contributions

Books

• Curry, S. (2016). Salicylates, in Brent J, Burkhart K, Dargan P, Hatten B, Megarbane B, Palmer R, White J, eds: Critical Care Toxicology, 2nd edition. doi:10.1007/978-3-319-20790-2_11-1

Chapters

• Curry, S. (2017). Cyanide: hydrogen cyanide, inorganic cyanide salts, and nitriles. In Critical Care Toxicology(pp 1929-1949). Springer.
• Curry, S. (2017). Hematologic syndromes: hemolysis, methemolgoinemia, and sulfhemoglobinemia. In Critical Care Toxicology(pp 643-659). Springer.
• Curry, S. (2017). Salicylates. In Critical Care Toxicology(pp 1251-1267). Springer.
• Curry, S. (2017). Sodium nitroprusside. In Critical Care Toxicology(pp 843-850). Springer.
• Curry, S. (2017). Thrombolytics, heparin and derivatives, and antiplatelet agents. In Critical Care Toxicology(pp 1341-1359). Apringer.

Journals/Publications

• Curry, S. (2018). A computerized scoring system to improve assessment of heparin-induced thrombycytopenia risk. Journal of Thrombosis and Haemostasis.
• Curry, S. (2018). The relationship betwen circulating acetaminophen-protein adduct concentrations and alanine aminotransferase activities in patients with and without acetaminophen overdose and toxicity. Journal of Medical Toxicology.
• Curry, S. (2019). Evaluation and tretment of acetaminophen toxicity. Advances in Pharmacology.
• Duan, L., Ramachandran, A., Akakpo, J. Y., Weemhoff, J. L., Curry, S. C., & Jaeschke, H. (2019). Role of extracellular vesicles in release of protein adducts after acetaminophen-induced liver injury in mice and humans. Toxicology letters, 301, 125-132.
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  Formation of acetaminophen (APAP) protein adducts are a critical feature of APAP hepatotoxicity, and circulating protein adducts have recently been utilized in bioassays for identification of APAP overdose in humans. Despite their clinical significance, mechanisms of adduct release into the circulation are not well understood. Extracellular vesicles (EVs) are discrete membrane bound vesicles, which package cellular cargo and function in extracellular transport. Clarification of their role in transport of APAP adducts is relevant since adduct packaging within these vesicles could shield them from detection by antibody based methods, resulting in under-estimating adduct levels. Hence, this study evaluated EV release after APAP overdose in primary mouse hepatocytes and human HepaRG cells in vitro, in mice and APAP overdose patients in vivo and examined their role in transport of APAP-protein adducts. EVs were characterized by size and protein composition and the levels of APAP-protein adducts were measured. Significant elevations in circulating EV numbers were observed 6 h after APAP overdose in vivo and by 4 h in primary mouse hepatocytes in culture. EVs were also elevated in media from HepaRG cells by 24 h after APAP exposure, an effect recapitulated in APAP overdose patients, where EV numbers were elevated compared to healthy controls. Although APAP-protein adducts were elevated in circulation and media parallel to the increased exosome release, no detectable adducts were observed within EVs. This suggests that although APAP overdose enhances EV release from hepatocytes in mice and humans, it is not a significant mechanism of release of APAP protein adducts into circulation.
• Gallo, T., Curry, S. C., Padilla-Jones, A., Heise, C. W., Ramos, K. S., Woosley, R. L., & Raschke, R. A. (2018). A Computerized Scoring System to Improve Assessment of Heparin-induced Thrombocytopenia Risk. Journal of thrombosis and haemostasis : JTH.
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  Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse drug event associated with life-threatening thrombotic complications. The four T's (4Ts) score is widely used to estimate the risk for HIT and guide diagnostic testing, but it is not easily amenable to computerized clinical decision support (CDS) implementation.
• Curry, S. (2017). A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system. BMJ Open Quality, 1-5.
• Curry, S. (2017). Plasma biomarkers to study mechanisms of liver injury in patients with hypoxic hepatitis.. Liver International, 37(3), 377-384. doi:10:1111/liv.13202
• Raschke, R. A., Gallo, T., Curry, S. C., Whiting, T., Padilla-Jones, A., Warkentin, T. E., & Puri, A. (2017). Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia. Journal of thrombosis and haemostasis : JTH.
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  Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT.
• Raschke, R. A., Groves, R. H., Khurana, H. S., Nikhanj, N., Utter, E., Hartling, D., Stoffer, B., Nunn, K., Tryon, S., Bruner, M., Calleja, M., & Curry, S. C. (2017). A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system. BMJ open quality, 6(2), e000080.
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  Sepsis is a leading cause of mortality and morbidity in hospitalised patients. The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals report sepsis bundle compliance rate as a quality process measure in October 2015. The specific aim of our study was to improve the CMS sepsis bundle compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare system within 1 year. The study included all adult inpatients with sepsis sampled according to CMS specifications from October 2015 to September 2016. The CMS sepsis bundle compliance rate was tracked monthly using statistical process control charting. A baseline rate of 28.5% with 99% control limits was established. We implemented multiple interventions including computerised decision support systems (CDSSs) to increase compliance with the most commonly missing bundle elements. Compliance reached 42% (99% statistical process control limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was not sustained after CMS changed specifications of the outcome measure. Difficulties encountered elucidate shortcomings of our study methodology and of the CMS sepsis bundle compliance rate as a quality process measure.
• Curry, S. (2016). A new F(ab')2 antivenom for the treatment of crotaline envenomation in children. Am J Emerg Med, 34(10), 2003-2006.
• Lasoff, D. R., Ruha, A. M., Curry, S. C., Koh, C., & Clark, R. F. (2016). A new F(ab')2 antivenom for the treatment of crotaline envenomation in children. The American journal of emergency medicine, 34(10), 2003-2006.
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  To evaluate the efficacy and safety of a new F(ab')2 antivenom preparation in the treatment of Crotalinae envenomation in children.
• Thomas, K. C., Wilkins, D. G., Curry, S. C., Grey, T. C., Andrenyak, D. M., McGill, L. D., & Rollins, D. E. (2016). Detection of Acetaminophen-Protein Adducts in Decedents with Suspected Opioid-Acetaminophen Combination Product Overdose. Journal of forensic sciences, 61(5), 1301-6.
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  Acetaminophen overdose is a leading cause of drug-induced liver failure in the United States. Acetaminophen-protein adducts have been suggested as a biomarker of hepatotoxicity. The purpose of this study was to determine whether protein-derived acetaminophen-protein adducts are quantifiable in postmortem samples. Heart blood, femoral blood, and liver tissue were collected at autopsy from 22 decedents suspected of opioid-acetaminophen overdose. Samples were assayed for protein-derived acetaminophen-protein adducts, acetaminophen, and selected opioids found in combination products containing acetaminophen. Protein-derived APAP-CYS was detected in 17 of 22 decedents and was measurable in blood that was not degraded or hemolyzed. Heart blood concentrations ranged from 11 ng/mL (0.1 μM) to 7817 ng/mL (28.9 μM). Protein-derived acetaminophen-protein adducts were detectable in liver tissue for 20 of 22 decedents. Liver histology was also performed for all decedents, and no evidence of centrilobular hepatic necrosis was observed.
• Weemhoff, J. L., Woolbright, B. L., Jenkins, R. E., McGill, M. R., Sharpe, M. R., Olson, J. C., Antoine, D. J., Curry, S. C., & Jaeschke, H. (2016). Plasma biomarkers to study mechanisms of liver injury in patients with hypoxic hepatitis. Liver international : official journal of the International Association for the Study of the Liver.
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  Hypoxic hepatitis is a clinical condition precipitated by prolonged periods of oxygen deprivation to the liver. It can have several underlying causes. Despite its prevalence in critically ill patients, which can reach upwards of 10%, very little is known about the mechanisms of injury. Thus, we set out to measure previously identified circulating biomarkers in an attempt to describe mechanisms of injury following hypoxic hepatitis.
• Cook, S. F., King, A. D., Chang, Y., Murray, G. J., Norris, H. R., Dart, R. C., Green, J. L., Curry, S. C., Rollins, D. E., & Wilkins, D. G. (2015). Quantification of a biomarker of acetaminophen protein adducts in human serum by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: clinical and animal model applications. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 985, 131-41.
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  The aims of this study were to develop, validate, and apply a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantification of protein-derived 3-(cystein-S-yl)-acetaminophen (APAP-Cys) in human serum. Formation of acetaminophen (APAP) protein adducts is thought to be a critical, early event in the development of APAP-induced hepatotoxicity, and quantification of these protein adducts in human serum represents a valuable tool for assessment of APAP exposure, metabolism, and toxicity. In the reported procedure, serum samples were first dialyzed or passed through gel filtration columns to remove APAP-Cys not covalently bound to proteins. Serum eluates were then subjected to enzymatic protease digestion to liberate protein-bound APAP-Cys. Norbuprenorphine-D3 was utilized as an internal standard (IS). APAP-Cys and IS were recovered from digested serum by protein precipitation with acetonitrile, and sample extracts were analyzed by HPLC-ESI-MS/MS. The method was validated by assessment of intra- and inter-assay accuracy and imprecision on two different analytical instrument platforms. APAP-Cys could be accurately quantified from 0.010 to 10μM, and intra- and inter-assay imprecision were
• Curry, S. C., Brooks, D. E., Skolnik, A. B., Gerkin, R. D., & Glenn, S. (2015). Effect of a medical toxicology admitting service on length of stay, cost, and mortality among inpatients discharged with poisoning-related diagnoses. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(1), 65-72.
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  There are no published studies that have compared quality outcomes of hospitalized poisoned patients primarily under the care of physician medical toxicologists to patients treated by non-toxicologists. We hypothesized that inpatients primarily cared for by medical toxicologists would exhibit shorter lengths of stay (LOS), lower costs, and decreased mortality. Patients discharged in 2010 and 2011 from seven hospitals within the same health care system and greater metropolitan area with Medicare severity diagnosis-related groups for "poisoning and toxic effects of drugs" with and without major comorbidities or complications (917 & 918, respectively) were identified from a Premier® database. The database contained severity-weighted comparisons between expected and observed outcomes for each patient. Outcome parameters were differences between expected and observed LOS, cost, and percent mortality. These were then compared among groups of patients primarily admitted and cared for by (1) medical toxicologists at one hospital (Banner Good Samaritan Medical Center, BGS), (2) non-toxicologists at BGS, and (3) non-toxicologists at six other hospitals. Records of 3,581 patients contained complete data for assessment of at least one outcome measure. Patients cared for by medical toxicologists experienced favorable differences in LOS, costs, and mortality compared with other patient groups (p 
• Curry, S. C., Padilla-Jones, A., O'Connor, A. D., Ruha, A. M., Bikin, D. S., Wilkins, D. G., Rollins, D. E., Slawson, M. H., Gerkin, R. D., & , A. A. (2015). Prolonged Acetaminophen-Protein Adduct Elimination During Renal Failure, Lack of Adduct Removal by Hemodiafiltration, and Urinary Adduct Concentrations After Acetaminophen Overdose. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(2), 169-78.
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  Elevated concentrations of serum acetaminophen-protein adducts, measured as protein-derived acetaminophen-cysteine (APAP-CYS), have been used to support a diagnosis of APAP-induced liver injury when histories and APAP levels are unhelpful. Adducts have been reported to undergo first-order elimination, with a terminal half-life of about 1.6 days. We wondered whether renal failure would affect APAP-CYS elimination half-life and whether continuous venovenous hemodiafiltration (CVVHDF), commonly used in liver failure patients, would remove adducts to lower their serum concentrations. Terminal elimination half-lives of serum APAP-CYS were compared between subjects with and without renal failure in a prospective cohort study of 168 adults who had ingested excessive doses of APAP. APAP-CYS concentrations were measured in plasma ultrafiltrate during CVVHDF at times of elevated serum adduct concentrations. Paired samples of urine and serum APAP-CYS concentrations were examined to help understand the potential importance of urinary elimination of serum adducts. APAP-CYS elimination half-life was longer in 15 renal failure subjects than in 28 subjects with normal renal function (41.3 ± 2.2 h versus 26.8 ± 1.1 h [mean ± SEM], respectively, p 
• McGill, M. R., Cao, M., Svetlov, A., Sharpe, M. R., Williams, C. D., Curry, S. C., Farhood, A., Jaeschke, H., & Svetlov, S. I. (2014). Argininosuccinate synthetase as a plasma biomarker of liver injury after acetaminophen overdose in rodents and humans. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, 19(3), 222-30.
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  New biomarkers are needed in acetaminophen (APAP) hepatotoxicity. Plasma argininosuccinate synthetase (ASS) is a promising candidate.
• McGill, M. R., Li, F., Sharpe, M. R., Williams, C. D., Curry, S. C., Ma, X., & Jaeschke, H. (2014). Circulating acylcarnitines as biomarkers of mitochondrial dysfunction after acetaminophen overdose in mice and humans. Archives of toxicology, 88(2), 391-401.
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  Acetaminophen (APAP) is a widely used analgesic. However, APAP overdose is hepatotoxic and is the primary cause of acute liver failure in the developed world. The mechanism of APAP-induced liver injury begins with protein binding and involves mitochondrial dysfunction and oxidative stress. Recent efforts to discover blood biomarkers of mitochondrial damage have identified increased plasma glutamate dehydrogenase activity and mitochondrial DNA concentration in APAP overdose patients. However, a problem with these markers is that they are too large to be released from cells without cell death or loss of membrane integrity. Metabolomic studies are more likely to reveal biomarkers that are useful at early time points, before injury begins. Similar to earlier work, our metabolomic studies revealed that acylcarnitines are elevated in serum from mice after treatment with toxic doses of APAP. Importantly, a comparison with furosemide demonstrated that increased serum acylcarnitines are specific for mitochondrial dysfunction. However, when we measured these compounds in plasma from humans with liver injury after APAP overdose, we could not detect any significant differences from control groups. Further experiments with mice showed that N-acetylcysteine, the antidote for APAP overdose in humans, can reduce acylcarnitine levels in serum. Altogether, our data do not support the clinical measurement of acylcarnitines in blood after APAP overdose due to the standard N-acetylcysteine treatment in patients, but strongly suggest that acylcarnitines would be useful mechanistic biomarkers in other forms of liver injury involving mitochondrial dysfunction.
• Ruha, A. M., Curry, S. C., & Levine, M. (2014). In reply. Annals of emergency medicine, 63(1), 93.
• Ward, J., Kanchagar, C., Veksler-Lublinsky, I., Lee, R. C., McGill, M. R., Jaeschke, H., Curry, S. C., & Ambros, V. R. (2014). Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proceedings of the National Academy of Sciences of the United States of America, 111(33), 12169-74.
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  We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.
• Woolbright, B. L., McGill, M. R., Staggs, V. S., Winefield, R. D., Gholami, P., Olyaee, M., Sharpe, M. R., Curry, S. C., Lee, W. M., Jaeschke, H., & , A. L. (2014). Glycodeoxycholic acid levels as prognostic biomarker in acetaminophen-induced acute liver failure patients. Toxicological sciences : an official journal of the Society of Toxicology, 142(2), 436-44.
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  Acetaminophen (APAP)-induced acute liver failure (ALF) remains a major clinical problem. Although a majority of patients recovers after severe liver injury, a subpopulation of patients proceeds to ALF. Bile acids are generated in the liver and accumulate in blood during liver injury, and as such, have been proposed as biomarkers for liver injury and dysfunction. The goal of this study was to determine whether individual bile acid levels could determine outcome in patients with APAP-induced ALF (AALF). Serum bile acid levels were measured in AALF patients using mass spectrometry. Bile acid levels were elevated 5-80-fold above control values in injured patients on day 1 after the overdose and decreased over the course of hospital stay. Interestingly, glycodeoxycholic acid (GDCA) was significantly increased in non-surviving AALF patients compared with survivors. GDCA values obtained at peak alanine aminotransferase (ALT) and from day 1 of admission indicated GDCA could predict survival in these patients by receiver-operating characteristic analysis (AUC = 0.70 for day 1, AUC = 0.68 for peak ALT). Of note, AALF patients also had significantly higher levels of serum bile acids than patients with active cholestatic liver injury. These data suggest measurements of GDCA in this patient cohort modestly predicted outcome and may serve as a prognostic biomarker. Furthermore, accumulation of bile acids in serum or plasma may be a result of liver cell dysfunction and not cholestasis, suggesting elevation of circulating bile acid levels may be a consequence and not a cause of liver injury.
• Cohen, J. P., Ruha, A. M., Curry, S. C., Biswas, K., Westenberger, B., Ye, W., Caldwell, K. L., Lovecchio, F., Burkhart, K., & Samia, N. (2013). Plasma and urine dimercaptopropanesulfonate concentrations after dermal application of transdermal DMPS (TD-DMPS). Journal of medical toxicology : official journal of the American College of Medical Toxicology, 9(1), 9-15.
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  2,3-Dimercaptopropane-1-sulfonate (DMPS) is a metal chelator approved in Europe for oral or intravenous use for heavy metal poisoning. Transdermally applied DMPS (TD-DMPS) is used by some alternative practitioners to treat autism, despite the absence of evidence for its efficacy. We found no literature evaluating the pharmacokinetics of the transdermal route of delivery or the ability of TD-DMPS to enhance urinary mercury elimination. We hypothesized that TD-DMPS is not absorbed. Eight adult volunteers underwent application of 1.5-3 drops/kg of TD-DMPS. Subjects provided 12-h urine collections the day before and day of application. Subjects underwent blood draws at 0, 30, 60,90, 120, and 240 min after TD-DMPS application. Plasma and urine were assayed for the presence of DMPS. Urine was assayed for any change in urinary mercury excretion after DMPS. One control subject ingested 250 mg of oral DMPS and underwent the same urine and blood collections and analyses. No subject had detectable urine DMPS or increased urine mercury excretion after TD-DMPS. One subject had detectable levels of DMPS in the 30-min plasma sample, suspected to be contamination. All other samples for that subject and the other seven subjects showed no detectable plasma DMPS. The control subject had detectable urine and plasma DMPS levels and increased urine mercury excretion. These results indicate that TD-DMPS is not absorbed. There was no increase in urine mercury excretion after TD-DMPS. Our results argue that TD-DMPS is an ineffective metal chelator.
• Levine, M., Curry, S. C., Padilla-Jones, A., & Ruha, A. M. (2013). Critical care management of verapamil and diltiazem overdose with a focus on vasopressors: a 25-year experience at a single center. Annals of emergency medicine, 62(3), 252-8.
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  Verapamil or diltiazem overdose can cause severe morbidity and death, and there exist limited human data describing management and outcome of a large number of such patients. This article describes the management and outcome of patients with nondihydropyridine calcium-channel blocker overdose, with an emphasis on vasopressor dosing, at a single center.
• Raschke, R. A., Curry, S. C., Warkentin, T. E., & Gerkin, R. D. (2013). Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and Bayes theorem. Chest, 144(4), 1269-75.
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  Heparin-induced thrombocytopenia (HIT) is diagnosed using clinical criteria and detection of platelet-activating anti-platelet factor 4/heparin (anti-PF4/H) antibodies, usually through a surrogate enzyme-linked immunosorbent assay (ELISA). The high false-positive rate (FPR) of this ELISA prompted us to reexamine its interpretation.
• Levine, M., Curry, S. C., Ruha, A. M., Pizon, A. F., Boyer, E., Burns, J., Bikin, D., & Gerkin, R. D. (2012). Ethylene glycol elimination kinetics and outcomes in patients managed without hemodialysis. Annals of emergency medicine, 59(6), 527-31.
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  Ethylene glycol remains an important toxic cause of metabolic acidosis and acute renal failure. Traditionally, inhibition of alcohol dehydrogenase along with hemodialysis has been used for treatment. Because of reported long elimination half-life of ethylene glycol during alcohol dehydrogenase inhibition, hemodialysis has been used in patients who are otherwise doing well to clear ethylene glycol. We study ethylene glycol elimination kinetics in patients treated with fomepizole, but without hemodialysis.
• McGill, M. R., Sharpe, M. R., Williams, C. D., Taha, M., Curry, S. C., & Jaeschke, H. (2012). The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. The Journal of clinical investigation, 122(4), 1574-83.
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  Acetaminophen (APAP) overdose is the predominant cause of acute liver failure in the United States. Toxicity begins with a reactive metabolite that binds to proteins. In rodents, this leads to mitochondrial dysfunction and nuclear DNA fragmentation, resulting in necrotic cell death. While APAP metabolism is similar in humans, the later events resulting in toxicity have not been investigated in patients. In this study, levels of biomarkers of mitochondrial damage (glutamate dehydrogenase [GDH] and mitochondrial DNA [mtDNA]) and nuclear DNA fragments were measured in plasma from APAP-overdose patients. Overdose patients with no or minimal hepatic injury who had normal liver function tests (LTs) (referred to herein as the normal LT group) and healthy volunteers served as controls. Peak GDH activity and mtDNA concentration were increased in plasma from patients with abnormal LT. Peak nuclear DNA fragmentation in the abnormal LT cohort was also increased over that of controls. Parallel studies in mice revealed that these plasma biomarkers correlated well with tissue injury. Caspase-3 activity and cleaved caspase-3 were not detectable in plasma from overdose patients or mice, but were elevated after TNF-induced apoptosis, indicating that APAP overdose does not cause apoptosis. Thus, our results suggest that mitochondrial damage and nuclear DNA fragmentation are likely to be critical events in APAP hepatotoxicity in humans, resulting in necrotic cell death.
• Brooks, D. E., Levine, M., O'Connor, A. D., French, R. N., & Curry, S. C. (2011). Toxicology in the ICU: Part 2: specific toxins. Chest, 140(4), 1072-85.
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  This is the second of a three-part series that reviews the generalized care of poisoned patients in the ICU. This article focuses on specific agents grouped into categories, including analgesics, anticoagulants, cardiovascular drugs, dissociative agents, carbon monoxide, cyanide, methemoglobinemia, cholinergic agents, psychoactive medications, sedative-hypnotics, amphetamine-like drugs, toxic alcohols, and withdrawal states. The first article discussed the general approach to the toxicology patient, including laboratory testing; the third article will cover natural toxins.
• Lavonas, E. J., Ruha, A. M., Banner, W., Bebarta, V., Bernstein, J. N., Bush, S. P., Kerns, W. P., Richardson, W. H., Seifert, S. A., Tanen, D. A., Curry, S. C., Dart, R. C., & , R. M. (2011). Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC emergency medicine, 11, 2.
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  Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.
• Levine, M., Ruha, A. M., Graeme, K., Brooks, D. E., Canning, J., & Curry, S. C. (2011). Toxicology in the ICU: part 3: natural toxins. Chest, 140(5), 1357-70.
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  This is the third article of a three-part series that reviews the care of poisoned patients in the ICU. This article focuses on natural toxins, such as heavy metals and those produced by plants, mushrooms, arthropods, and snakes. The first article discussed the general approach to the patient, including laboratory testing; the second article focused on specific toxic agents, grouped into categories.
• Ruha, A. M., Curry, S. C., Albrecht, C., Riley, B., & Pizon, A. (2011). Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom. Toxicon : official journal of the International Society on Toxinology, 57(1), 53-9.
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  North American rattlesnake envenomations commonly produce defibrination, coagulopathy and/or thrombocytopenia, which may be reversed following treatment with Crotalidae Polyvalent Immune Fab Ovine (FabAV). Despite initial resolution with FabAV, late onset or recurrence of venom-induced hematologic effects may occur. Time at which onset of late hematotoxicity may first be detected is unknown. The purpose of this study was to identify the incidence and time of onset of recurrent or new late hypofibrinogenemia, coagulopathy, or thrombocytopenia in a cohort of rattlesnake envenomation patients seen in outpatient follow-up after treatment with FabAV, and to report hematologic outcomes in these patients.
• Smith, J. C., & Curry, S. C. (2011). Prolonged toxicity after amitriptyline overdose in a patient deficient in CYP2D6 activity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 7(3), 220-3.
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  Amitriptyline and its metabolite, nortriptyline, are metabolized, in part, by CYP2D6, a polymorphic enzyme. About 8% of Caucasians are deficient in CYP2D6 activity.
• Quan, A. N., Quan, D., & Curry, S. C. (2010). Improving Crotalidae polyvalent immune Fab reconstitution times. The American journal of emergency medicine, 28(5), 593-5.
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  Crotalidae polyvalent immune Fab (CroFab) is used to treat rattlesnake envenomations in the United States. Time to infusion may be a critical factor in the treatment of these bites. Per manufacturer's instructions, 10 mL of sterile water for injection (SWI) and hand swirling are recommended for reconstitution. We wondered whether completely filling vials with 25 mL of SWI would result in shorter reconstitution times than using 10-mL volumes and how hand mixing compared to mechanical agitation of vials or leaving vials undisturbed.
• Raschke, R. A., Gerkin, R. D., Curry, S. C., & Baratz, D. M. (2010). Operating characteristics of pulmonary capillary wedge pressure for pulmonary arterial hypertension. Chest, 137(3), 740.
• Dart, R. C., Borron, S. W., Caravati, E. M., Cobaugh, D. J., Curry, S. C., Falk, J. L., Goldfrank, L., Gorman, S. E., Groft, S., Heard, K., Miller, K., Olson, K. R., O'Malley, G., Seger, D., Seifert, S. A., Sivilotti, M. L., Schaeffer, T., Tomassoni, A. J., Wise, R., , Bogdan, G. M., et al. (2009). Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Annals of emergency medicine, 54(3), 386-394.e1.
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  We developed recommendations for antidote stocking at hospitals that provide emergency care.
• Ruha, A. M., & Curry, S. C. (2009). Recombinant factor VIIa for treatment of gastrointestinal hemorrhage following rattlesnake envenomation. Wilderness & environmental medicine, 20(2), 156-60.
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  North American rattlesnakes possess venom with primarily cytotoxic and hemotoxic properties. When persons are envenomated by these snakes, thrombocytopenia and coagulopathy commonly occur, yet patients rarely develop severe bleeding. This report describes a 44-year-old Native American man bitten on the index finger by an unknown species of rattlesnake. The man developed massive gastrointestinal hemorrhage that was ultimately treated with recombinant factor VIIa. He presented to an emergency department with a depressed level of consciousness, a blood pressure of 60/20 mm Hg, and heart rate of 148 beats per minute. He was diaphoretic and vomiting bright red blood. Initial laboratory results revealed thrombocytopenia and coagulopathy. Despite aggressive fluid resuscitation and administration of blood and antivenom in the emergency department, the patient continued to have profuse upper gastrointestinal bleeding, with hemoglobin as low as 1.8 g/dL. He received fluids, antivenom, and multiple blood products, with cessation of bleeding after administration of recombinant factor VIIa. Esophagogastroduodenoscopy revealed a single Mallory-Weiss tear as the source of hemorrhage. The patient stabilized after 6 hours of aggressive resuscitation but over the next several days developed several complications, including acute renal failure and gram-negative sepsis. The patient died on hospital day 5. In cases of life-threatening hemorrhage after rattlesnake envenomation in which traditional therapy with antivenom and aggressive supportive measures fail, recombinant factor VIIa should be considered as an additional therapeutic option to achieve hemostasis.
• Ruha, A. M., Brooks, D. E., & Curry, S. C. (2009). Letters on "Predictors of mortality in patients with delerium tremens". Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 16(1), 91-2; author reply 92-3.
• Ruha, A. M., Curry, S. C., Gerkin, R. D., Caldwell, K. L., Osterloh, J. D., & Wax, P. M. (2009). Urine mercury excretion following meso-dimercaptosuccinic acid challenge in fish eaters. Archives of pathology & laboratory medicine, 133(1), 87-92.
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  Public awareness of methylmercury in fish has caused patients to seek testing for mercury poisoning. In some patients, the diagnosis of mercury poisoning has been made based on urine mercury excretions following oral dosing of meso-dimercaptosuccinic acid (DMSA), a metal chelator. However, studies comparing urine mercury excretion following DMSA in healthy non-fish eaters with healthy fish eaters could not be located.
• Lo Vecchio, F., Gerkin, R. D., & Curry, S. C. (2008). CO poisoning and hyperbaric oxygen therapy: more studies need to be done. American journal of respiratory and critical care medicine, 178(3), 314; author reply 314-5.
• Lovecchio, F., Cannon, R. D., Algier, J., Ruha, A. M., Curry, S. C., Wallace, K. L., & Graeme, K. A. (2007). Bee swarmings in children. The American journal of emergency medicine, 25(8), 931-3.
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  Africanized honeybees (Apis mellifera scutellata) are now found in the southern and southwestern United States. Swarmings can result in hundreds to thousands of stings delivering a venom load capable of producing multisystem organ failure and death. The literature on mass envenomations is scarce, being limited to case reports and case series. There are no prospective studies on mass envenomations in children.
• LoVecchio, F., Sawyers, B., Thole, D., Beuler, M. C., Winchell, J., & Curry, S. C. (2004). Outcomes following abuse of methanol-containing carburetor cleaners. Human & experimental toxicology, 23(10), 473-5.
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  Carbureter cleaners may contain methanol and are abused via inhalation. Toxicity resulting from the methanol component of these products is poorly described.
• Ruha, A. M., Curry, S. C., Beuhler, M., Katz, K., Brooks, D. E., Graeme, K. A., Wallace, K., Gerkin, R., Lovecchio, F., Wax, P., & Selden, B. (2002). Initial postmarketing experience with crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation. Annals of emergency medicine, 39(6), 609-15.
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  We describe our postmarketing experience with patients receiving Crotalidae polyvalent immune Fab (CroFab; FabAV) antivenom for treatment of rattlesnake envenomation.
• Ruha, A. M., Tanen, D. A., Graeme, K. A., Curry, S. C., Miller, M. B., Gerkin, R., Reagan, C. G., & Brandon, T. A. (2002). Hypertonic sodium bicarbonate for Taxus media-induced cardiac toxicity in swine. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 9(3), 179-85.
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  To determine whether intravenous (IV) hypertonic sodium bicarbonate is effective in the reversal of QRS widening associated with severe Taxus intoxication.
• Lovecchio, F., Curry, S. C., Graeme, K. A., Wallace, K. L., & Suchard, J. (2001). Intravenous pyridoxine-induced metabolic acidosis. Annals of emergency medicine, 38(1), 62-4.
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  Pyridoxine hydrochloride, the antidote for isonicotinic acid hydrazide (INH)--induced seizures, is available in solution at a concentration of 100 mg/mL at a pH of less than 3. Pyridoxine is often infused rapidly in large doses for INH-induced seizures. Effects of pyridoxine infusion on base deficit in amounts given for INH poisoning have not been studied in human subjects. We hypothesized that this infusion would result in transient worsening of acidosis.
• Ruha, A. M., Tanen, D. A., Suchard, J. R., & Curry, S. C. (2001). Combined ingestion and subcutaneous injection of elemental mercury. The Journal of emergency medicine, 20(1), 39-42.
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  A 40-year-old man with a history of schizophrenia and inflammatory soft tissue lesions after self-injection of elemental mercury presented to the Emergency Department. Multiple skin abscesses associated with fever required operative debridement. An incidental finding of oral mercury ingestion was followed clinically and did not result in complications. Exposure to elemental mercury through injection or ingestion is an uncommon event, but one the Emergency Physician may encounter. Subcutaneous mercury injection should be managed with local wound debridement, whereas ingestions are rarely of clinical significance.
• Tanen, D. A., Ruha, A. M., Graeme, K. A., Curry, S. C., & Fischione, M. A. (2001). Rattlesnake envenomations: unusual case presentations. Archives of internal medicine, 161(3), 474-9.
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  Rattlesnake envenomations are common in some areas of the United States. Although fatal rattlesnake envenomations are rare and usually preventable, morbidity may be significant. Patients may present with localized edema, hypotension, coagulopathy, or thrombocytopenia. Patients with progressive swelling or severe coagulopathy are typically treated with Crotalidae polyvalent antivenin. We present a series of 4 patients with unusual complications of rattlesnake envenomation to illustrate the wide spectrum of disease that may be encountered. These case presentations include anaphylaxis to rattlesnake venom, an acute airway emergency, progressive and marked edema with a large pleural fluid collection, and death.
• Tanen, D. A., Graeme, K. A., & Curry, S. C. (2000). Crack cocaine ingestion with prolonged toxicity requiring electrical pacing. Journal of toxicology. Clinical toxicology, 38(6), 653-7.
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  We report a 38-year-old man who experienced prolonged toxicity lasting over 16 hours from the time of ingestion of 1/4 ounce of crack cocaine. His illness included status epilepticus, wide and narrow complex bradyarrhythmias, ventricular arrhythmias, and delayed hyperthermia. His bradyarrhythmias were refractory to medicinal intervention and responsive to application of an external pacemaker. The patient recovered to his baseline state over the ensuing 48 hours.
• Tanen, D. A., LoVecchio, F., & Curry, S. C. (2000). Failure of intravenous N-acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial. Annals of emergency medicine, 35(4), 369-73.
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  To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in human volunteers.
• Tanen, D. A., Ruha, A. M., Curry, S. C., Graeme, K. A., & Reagan, C. G. (2000). Hypertonic sodium bicarbonate is effective in the acute management of verapamil toxicity in a swine model. Annals of emergency medicine, 36(6), 547-53.
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  This study was conducted to determine whether hypertonic sodium bicarbonate would improve the hypotension associated with severe verapamil toxicity compared with volume expansion.
• LoVecchio, F., Welch, S., Klemens, J., Curry, S. C., & Thomas, R. (1999). Incidence of immediate and delayed hypersensitivity to Centruroides antivenom. Annals of emergency medicine, 34(5), 615-9.
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  To assess the incidence and course of immediate and delayed hypersensitivity to Centruroides antivenom.
• Tanen, D. A., Curry, S. C., & Laney, R. F. (1999). Renal failure and corrosive airway and gastrointestinal injury after ingestion of diluted diquat solution. Annals of emergency medicine, 34(4 Pt 1), 542-5.
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  A 66-year-old man ingested 200 mL of Dexol Industries Weed and Grass Killer Concentrate (Torrance, CA), which contains 1.84% diquat dibromide, a herbicide structurally similar to paraquat. He remained asymptomatic for 8 hours, and then a sore throat and vomiting developed. Twenty hours after ingestion, esophagitis, mucositis, epiglottitis, and acute renal failure developed, from which he slowly recovered. This is the first report of systemic diquat toxicity from ingestion of a diluted diquat solution.
• LoVecchio, F., & Curry, S. C. (1998). Dexfenfluramine overdose. Annals of emergency medicine, 32(1), 102-3.
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  Dexfenfluramine (Redux), the dextro-rotatory (+) steroisomer of fenfluramine, was previously approved for the treatment of weight control in the United States. We report a case of acute dexfenfluramine ingestion characterized by coma, clonus, and respiratory failure.
• LoVecchio, F., Curry, S. C., & Bagnasco, T. (1998). Butyrolactone-induced central nervous system depression after ingestion of RenewTrient, a "dietary supplement". The New England journal of medicine, 339(12), 847-8.
• Holstege, C. P., Miller, M. B., Wermuth, M., Furbee, B., & Curry, S. C. (1997). Crotalid snake envenomation. Critical care clinics, 13(4), 889-921.
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  Over 5000 Americans suffer from snake bites annually, and of these, nearly one quarter are from poisonous species. Although these cases are undeniably reported, death appears to occur in only a few cases each year, and often reflects delay in obtaining medical care. Two families of venomous snake indigenous to the United States account for most envenomations: Crotalidae (pit vipers or new world vipers) and Elapidae. This article focuses on the snakes of the Crotalidae family.
• Braitberg, G., & Curry, S. C. (1995). Seizure after isolated fluoxetine overdose. Annals of emergency medicine, 26(2), 234-7.
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  Previous case reports of seizures following fluoxetine overdose have not adequately ruled out ingestion of other substances and have lacked documentation of increased serum drug levels. We present a case of seizure following fluoxetine overdose in a previously well patient with a clear history of sole ingestion. We ruled out the presence of other substances with comprehensive drug screening and documented increased serum levels of fluoxetine and its active metabolite.
• Reust, C. S., Curry, S. C., & Guidry, J. R. (1991). Lovastatin use and muscle damage in healthy volunteers undergoing eccentric muscle exercise. The Western journal of medicine, 154(2), 198-200.
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  We did a double-blind, placebo-controlled crossover study of 10 healthy young men taking no medications to determine if ingesting lovastatin is associated with more severe muscle damage after exercise. Five men in the first group took 40 mg of lovastatin daily for 30 days while those in the second group took an identical-appearing placebo. Each volunteer then walked downhill on a -14-degree incline on a treadmill at 3 km per hour for an hour. After a 2-week rest, the subjects were crossed over. Serial serum creatine kinase activity was measured immediately before and 8, 24, 48, 72, 120, and 144 hours after each treadmill session. With each subject serving as his own control, peak mean serum creatine kinase activity (/+- SEM) following treadmill after lovastatin therapy was similar to that following placebo (168.4 +/- 25.8 U per liter versus 146.7 +/- 14.7 U per liter, respectively [P = .9]). With an alpha value of .05, we had greater than a 99% chance of detecting a difference in the rise of serum creatine kinase activity of 200 U per liter between groups. Our data suggest that lovastatin is not an independent risk factor for developing exercise-induced muscle damage using this model of exercise in our study population.
• Selden, B. S., Curry, S. C., Clark, R. F., Johnson, B. C., Meinhart, R., & Pizziconi, V. B. (1991). Transplacental transport of N-acetylcysteine in an ovine model. Annals of emergency medicine, 20(10), 1069-72.
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  Acetaminophen freely crosses the placenta, and acetaminophen ingestion is the most frequent intentional overdose in pregnancy. Although most patients do well after maternal treatment with the antidote N-acetylcysteine (NAC), fetal death with massive hepatic necrosis has occurred. It has never been shown whether NAC crosses the placenta to yield fetal plasma levels equal to those associated with hepatoprotective effects in human beings. Our study objective was to evaluate this in a widely accepted large animal model for maternal-fetal research. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment was performed using four domestic sheep at near-term gestation.
• Selden, B. S., Clark, R. F., & Curry, S. C. (1990). Marijuana. Emergency medicine clinics of North America, 8(3), 527-39.
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  Marijuana remains a complex, poorly understood drug with many effects. Although its acute psychological effects are well described, data linking cannabis use to chronic psychiatric or social problems and decreased driving or workplace safety are much less clear. Current laboratory procedures have not yet been shown useful to demonstrate acute intoxication, so they remain screening instruments for those interested in detecting cannabis use for other reasons. Although both acute and chronic effects of marijuana use have been described, they appear to be less than other commonly abused substances, including tobacco and alcohol. The rare acute complications that present to the Emergency Department can be managed with conservative measures.
• Bond, G. R., Curry, S. C., & Dahl, D. W. (1989). Dimethylsulphoxide-induced encephalopathy. Lancet (London, England), 1(8647), 1134-5.
• Riffer, E., Curry, S. C., & Gerkin, R. (1987). Successful treatment with antivenin of marked thrombocytopenia without significant coagulopathy following rattlesnake bite. Annals of emergency medicine, 16(11), 1297-9.
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  We cared for two rattlesnake bite victims who developed platelet counts of 21,000/mm3 and 22,000/mm3. Both had only mild defibrination without evidence of intravascular clotting. In both cases, the administration of antivenin was followed promptly by a sustained rise in platelet counts.
• Selden, B. S., & Curry, S. C. (1987). Prolonged succinylcholine-induced paralysis in organophosphate insecticide poisoning. Annals of emergency medicine, 16(2), 215-7.
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  A case of prolonged succinylcholine-induced paralysis in a child with organophosphate insecticide poisoning is presented. Three hours and 15 minutes of apnea after the administration of succinylcholine was attributed to a decreased rate of succinylcholine metabolism from inhibition of pseudocholinesterase by the insecticide. Only one similar case has been reported previously in the English medical literature. If succinylcholine is to be used in patients with organophosphate poisoning, a prolonged paralysis should be anticipated.

Presentations

• Curry, S., Raschke, R. A., Gallo, T., Curry, S., Raschke, R. A., & Gallo, T. (2019, May). Heparin-induced thrombocytopenia computerized risk score in laboratory-tested patients. ABRC Research Conference. Phoenix, AZ.

Poster Presentations

• Curry, S., Curry, S., Heise, C., Heise, C., Gallo, T., & Gallo, T. (2019, Nov). Identifying target populations for pharmacogenomic testing implementation using a benefit tool. Re-imagine Health: Is my fate in my genes. Phoenix, AZ.

Other Teaching Materials

• Curry, S. (2018. Continuous IV methylene blue infusions for refractory methemoglobinemia. Internet Toxicology Blog.
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  See post.
• Curry, S. (2018. Cyanomythology. Toxicology internet blog post.
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  see post