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Matthew Lewin
Ophirex, Inc, USA

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Journal article
Published: 08 August 2021 in Toxicon: X
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Snakebite envenoming is a major cause of morbidity and mortality in rural communities throughout the tropics. Generally, the main clinical features of snakebites are local swelling, tissue necrosis, shock, spontaneous systemic hemorrhage, incoagulable blood, paralysis, rhabdomyolysis, and acute kidney injury. These clinical manifestations result from complex biochemical venom constituents comprising of cytotoxins, hemotoxins, neurotoxins, myotoxins, and other substances. Timely diagnosis of envenoming and identification of the responsible snake species is clinically challenging in many parts of the world and necessitates prompt and thorough clinical assessment, which could be supported by the development of reliable, affordable, widely-accessible, point-of-care tests. Conventional antivenoms based on polyclonal antibodies derived from animals remain the mainstay of therapy along with supportive medical and surgical care. However, while antivenoms save countless lives, they are associated with adverse reactions, limited potency, and are relatively inefficacious against presynaptic neurotoxicity and in preventing necrosis. Nevertheless, major scientific and technological advances are facilitating the development of new molecular and immunologic diagnostic tests, as well as a new generation of antivenoms comprising human monoclonal antibodies with broader and more potent neutralization capacity and less immunogenicity. Repurposed pharmaceuticals based on small molecule inhibitors (e.g., marimastat and varespladib) used alone and in combination against enzymatic toxins, such as metalloproteases and phospholipase A2s, have shown promise in animal studies. These orally bioavailable molecules could serve as early interventions in the out-of-hospital setting if confirmed to be safe and efficacious in clinical studies. Antivenom access can be improved by the usage of drones and ensuring constant antivenom supply in remote endemic rural areas. Overall, the improvement of clinical management of snakebite envenoming requires sustained, coordinated, and multifaceted efforts involving basic and applied sciences, new technology, product development, effective clinical training, implementation of existing guidelines and therapeutic approaches, supported by improved supply of existing antivenoms.

ACS Style

Muhammad Hamza; Cecilie Knudsen; Christeine Ariaranee Gnanathasan; Wuelton Monteiro; Matthew R. Lewin; Andreas H. Laustsen; Abdulrazaq G. Habib. Clinical management of snakebite envenoming: Future perspectives. Toxicon: X 2021, 11, 100079 .

AMA Style

Muhammad Hamza, Cecilie Knudsen, Christeine Ariaranee Gnanathasan, Wuelton Monteiro, Matthew R. Lewin, Andreas H. Laustsen, Abdulrazaq G. Habib. Clinical management of snakebite envenoming: Future perspectives. Toxicon: X. 2021; 11 ():100079.

Chicago/Turabian Style

Muhammad Hamza; Cecilie Knudsen; Christeine Ariaranee Gnanathasan; Wuelton Monteiro; Matthew R. Lewin; Andreas H. Laustsen; Abdulrazaq G. Habib. 2021. "Clinical management of snakebite envenoming: Future perspectives." Toxicon: X 11, no. : 100079.

Journal article
Published: 06 July 2020
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Lee T Erickson; Thea Litschka-Koen; Jonathan Pons; Tommaso Celeste Bulfone; Gideon Bhendile; Shannon Fuller; Eoin Harrington; Jerry Harrison; Stephen Samuel; Matthew Lewin. The 'Snake song': a pilot study of musical intervention in Eswatini. 2020, 20, 5494 .

AMA Style

Lee T Erickson, Thea Litschka-Koen, Jonathan Pons, Tommaso Celeste Bulfone, Gideon Bhendile, Shannon Fuller, Eoin Harrington, Jerry Harrison, Stephen Samuel, Matthew Lewin. The 'Snake song': a pilot study of musical intervention in Eswatini. . 2020; 20 (3):5494.

Chicago/Turabian Style

Lee T Erickson; Thea Litschka-Koen; Jonathan Pons; Tommaso Celeste Bulfone; Gideon Bhendile; Shannon Fuller; Eoin Harrington; Jerry Harrison; Stephen Samuel; Matthew Lewin. 2020. "The 'Snake song': a pilot study of musical intervention in Eswatini." 20, no. 3: 5494.

Conference abstract
Published: 19 June 2020 in Toxicon
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L.L. Gilliam; J.N. Gilliam; R.W. Carter; S.P. Samuel; J.M. Gutierrez; D.J. Williams; Y.V. Surovsteva; T. Bulfone; M.R. Lewin. Varespladib (LY315920) effectively reverses experimental neuro-myotoxic effects in a pig model of lethal envenoming by Taipan (O. scutellatus) and Mojave rattlesnake (C. scutulatus). Toxicon 2020, 182, S2 -S3.

AMA Style

L.L. Gilliam, J.N. Gilliam, R.W. Carter, S.P. Samuel, J.M. Gutierrez, D.J. Williams, Y.V. Surovsteva, T. Bulfone, M.R. Lewin. Varespladib (LY315920) effectively reverses experimental neuro-myotoxic effects in a pig model of lethal envenoming by Taipan (O. scutellatus) and Mojave rattlesnake (C. scutulatus). Toxicon. 2020; 182 ():S2-S3.

Chicago/Turabian Style

L.L. Gilliam; J.N. Gilliam; R.W. Carter; S.P. Samuel; J.M. Gutierrez; D.J. Williams; Y.V. Surovsteva; T. Bulfone; M.R. Lewin. 2020. "Varespladib (LY315920) effectively reverses experimental neuro-myotoxic effects in a pig model of lethal envenoming by Taipan (O. scutellatus) and Mojave rattlesnake (C. scutulatus)." Toxicon 182, no. : S2-S3.

Journal article
Published: 20 February 2020 in Toxins
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The phospholipase A2 (PLA2) inhibitor Varespladib (LY315920) and its orally bioavailable prodrug, methyl-Varespladib (LY333013) inhibit PLA2 activity of a wide variety of snake venoms. In this study, the ability of these two forms of Varespladib to halt or delay lethality of potent neurotoxic snake venoms was tested in a mouse model. The venoms of Notechis scutatus, Crotalus durissus terrificus, Bungarus multicinctus, and Oxyuranus scutellatus, all of which have potent presynaptically acting neurotoxic PLA2s of variable quaternary structure, were used to evaluate simple dosing regimens. A supralethal dose of each venom was injected subcutaneously in mice, followed by the bolus intravenous (LY315920) or oral (LY333013) administration of the inhibitors, immediately and at various time intervals after envenoming. Control mice receiving venom alone died within 3 h of envenoming. Mice injected with O. scutellatus venom and treated with LY315920 or LY333013 survived the 24 h observation period, whereas those receiving C. d. terrificus and B. multicinctus venoms survived at 3 h or 6 h with a single dose of either form of Varespladib, but not at 24 h. In contrast, mice receiving N. scutatus venom and then the inhibitors died within 3 h, similarly to the control animals injected with venom alone. LY315920 was able to reverse the severe paralytic manifestations in mice injected with venoms of O. scutellatus, B. multicinctus, and C. d. terrificus. Overall, results suggest that the two forms of Varespladib are effective in abrogating, or delaying, neurotoxic manifestations induced by some venoms whose neurotoxicity is mainly dependent on presynaptically acting PLA2s. LY315920 is able to reverse paralytic manifestations in severely envenomed mice, but further work is needed to understand the significance of species-specific differences in animal models as they compare to clinical syndromes in human and for potential use in veterinary medicine.

ACS Style

José María Gutiérrez; Matthew R. Lewin; David. J. Williams; Bruno Lomonte. Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms. Toxins 2020, 12, 131 .

AMA Style

José María Gutiérrez, Matthew R. Lewin, David. J. Williams, Bruno Lomonte. Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms. Toxins. 2020; 12 (2):131.

Chicago/Turabian Style

José María Gutiérrez; Matthew R. Lewin; David. J. Williams; Bruno Lomonte. 2020. "Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms." Toxins 12, no. 2: 131.

Conference abstract
Published: 30 January 2019 in Toxicon
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ACS Style

Matthew R. Lewin; Tommaso Bulfone. Varespladib (LY315920) rescues mice from rapidly lethal doses of venoms from five vipers, suggesting direct and indirect mechanisms for its therapeutic effect in a mouse model of snakebite envenomation. Toxicon 2019, 158, S32 .

AMA Style

Matthew R. Lewin, Tommaso Bulfone. Varespladib (LY315920) rescues mice from rapidly lethal doses of venoms from five vipers, suggesting direct and indirect mechanisms for its therapeutic effect in a mouse model of snakebite envenomation. Toxicon. 2019; 158 ():S32.

Chicago/Turabian Style

Matthew R. Lewin; Tommaso Bulfone. 2019. "Varespladib (LY315920) rescues mice from rapidly lethal doses of venoms from five vipers, suggesting direct and indirect mechanisms for its therapeutic effect in a mouse model of snakebite envenomation." Toxicon 158, no. : S32.

Journal article
Published: 17 November 2018 in Toxins
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There is a clear, unmet need for effective, lightweight, shelf-stable and economical snakebite envenoming therapies that can be given rapidly after the time of a snake’s bite and as adjuncts to antivenom therapies in the hospital setting. The sPLA2 inhibitor, LY315920, and its orally bioavailable prodrug, LY333013, demonstrate surprising efficacy and have the characteristics of an antidote with potential for both field and hospital use. The efficacy of the active pharmaceutical ingredient (LY315920) and its prodrug (LY333013) to treat experimental, lethal envenoming by Micrurus fulvius (Eastern coral snake) venom was tested using a porcine model. Inhibitors were administered by either intravenous or oral routes at different time intervals after venom injection. In some experiments, antivenom was also administered alone or in conjunction with LY333013. 14 of 14 animals (100%) receiving either LY315920 (intravenous) and/or LY333013 (oral) survived to the 120 h endpoint despite, in some protocols, the presence of severe neurotoxic signs. The study drugs demonstrated the ability to treat, rescue, and re-rescue animals with advanced manifestations of envenoming. Low molecular mass sPLA2 inhibitors were highly effective in preventing lethality following experimental envenoming by M. fulvius. These findings suggest the plausibility of a new therapeutic approach to snakebite envenoming, in this example, for the treatment of a coral snake species for which there are limitations in the availability of effective antivenom.

ACS Style

Matthew R. Lewin; Lyndi L. Gilliam; John Gilliam; Stephen P. Samuel; Tommaso C. Bulfone; Philip E. Bickler; José María Gutiérrez. Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom. Toxins 2018, 10, 479 .

AMA Style

Matthew R. Lewin, Lyndi L. Gilliam, John Gilliam, Stephen P. Samuel, Tommaso C. Bulfone, Philip E. Bickler, José María Gutiérrez. Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom. Toxins. 2018; 10 (11):479.

Chicago/Turabian Style

Matthew R. Lewin; Lyndi L. Gilliam; John Gilliam; Stephen P. Samuel; Tommaso C. Bulfone; Philip E. Bickler; José María Gutiérrez. 2018. "Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom." Toxins 10, no. 11: 479.

Communication
Published: 20 September 2018 in Toxins
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There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.

ACS Style

Matthew R. Lewin; José María Gutiérrez; Stephen P. Samuel; María Herrera; Wendy Bryan-Quirós; Bruno Lomonte; Philip E. Bickler; Tommaso C. Bulfone; David J. Williams. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins 2018, 10, 380 .

AMA Style

Matthew R. Lewin, José María Gutiérrez, Stephen P. Samuel, María Herrera, Wendy Bryan-Quirós, Bruno Lomonte, Philip E. Bickler, Tommaso C. Bulfone, David J. Williams. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins. 2018; 10 (10):380.

Chicago/Turabian Style

Matthew R. Lewin; José María Gutiérrez; Stephen P. Samuel; María Herrera; Wendy Bryan-Quirós; Bruno Lomonte; Philip E. Bickler; Tommaso C. Bulfone; David J. Williams. 2018. "Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom." Toxins 10, no. 10: 380.

Journal article
Published: 02 August 2018 in The American Journal of Tropical Medicine and Hygiene
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The cost-effectiveness of the standard of care for snakebite treatment, antivenom, and supportive care has been established in various settings. In this study, based on data from South Indian private health-care providers, we address an additional question: "For what cost and effectiveness values would adding adjunct-based treatment strategies to the standard of care for venomous snakebites be cost-effective?" We modeled the cost and performance of potential interventions (e.g., pharmacologic or preventive) used adjunctively with antivenom and supportive care for the treatment of snakebite. Because these potential interventions are theoretical, we used a threshold cost-effectiveness approach to explore this forward-looking concept. We examined economic parameters at which these interventions could be cost-effective or even cost saving. A threshold analysis was used to examine the addition of new interventions to the standard of care. Incremental cost-effectiveness ratios were used to compare treatment strategies. One-way, scenario, and probabilistic sensitivity analyses were conducted to analyze parameter uncertainty and define cost and effectiveness thresholds. Our results suggest that even a 3% reduction in severe cases due to an adjunct strategy is likely to reduce the cost of overall treatment and have the greatest impact on cost-effectiveness. In this model, for example, an investment of $10 of intervention that reduces the incidence of severe cases by 3%, even without changing antivenom usage patterns, creates cost savings of $75 per individual. These findings illustrate the striking degree to which an adjunct intervention could improve patient outcomes and be cost-effective or even cost saving.

ACS Style

Benjamin J. Herzel; Stephen P. Samuel; Tommaso C. Bulfone; C. Soundara Raj; Matthew Lewin; James G. Kahn. Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies. The American Journal of Tropical Medicine and Hygiene 2018, 99, 404 -412.

AMA Style

Benjamin J. Herzel, Stephen P. Samuel, Tommaso C. Bulfone, C. Soundara Raj, Matthew Lewin, James G. Kahn. Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies. The American Journal of Tropical Medicine and Hygiene. 2018; 99 (2):404-412.

Chicago/Turabian Style

Benjamin J. Herzel; Stephen P. Samuel; Tommaso C. Bulfone; C. Soundara Raj; Matthew Lewin; James G. Kahn. 2018. "Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies." The American Journal of Tropical Medicine and Hygiene 99, no. 2: 404-412.

Review article
Published: 30 July 2018 in Journal of Tropical Medicine
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The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential prereferral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses, and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors with brief exploration of other potential drug targets on venom molecules.

ACS Style

Tommaso C. Bulfone; Stephen P. Samuel; Philip E. Bickler; Matthew R. Lewin. Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite. Journal of Tropical Medicine 2018, 2018, 1 -10.

AMA Style

Tommaso C. Bulfone, Stephen P. Samuel, Philip E. Bickler, Matthew R. Lewin. Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite. Journal of Tropical Medicine. 2018; 2018 ():1-10.

Chicago/Turabian Style

Tommaso C. Bulfone; Stephen P. Samuel; Philip E. Bickler; Matthew R. Lewin. 2018. "Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite." Journal of Tropical Medicine 2018, no. : 1-10.

Case report
Published: 21 December 2017 in Clinical Case Reports
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Parotid swelling, an unusual and poorly understood sign, is associated with poor prognosis in the setting of Russell's viper envenomation. The large, aggressive Russell's viper is one of the most deadly snakes causing severe hematological and neurological manifestations. Research into this sign should be initiated and understanding could lead to improved outcomes.

ACS Style

Maanoj N. Sasidaran; Stephen P. Samuel; Soundararaj ChinnaRaju; Michael Antonysamy; Tommaso C. Bulfone; Matthew R. Lewin. Parotid swelling after Russell's viper envenomation: an unusual and poor prognostic sign. Clinical Case Reports 2017, 6, 262 -266.

AMA Style

Maanoj N. Sasidaran, Stephen P. Samuel, Soundararaj ChinnaRaju, Michael Antonysamy, Tommaso C. Bulfone, Matthew R. Lewin. Parotid swelling after Russell's viper envenomation: an unusual and poor prognostic sign. Clinical Case Reports. 2017; 6 (2):262-266.

Chicago/Turabian Style

Maanoj N. Sasidaran; Stephen P. Samuel; Soundararaj ChinnaRaju; Michael Antonysamy; Tommaso C. Bulfone; Matthew R. Lewin. 2017. "Parotid swelling after Russell's viper envenomation: an unusual and poor prognostic sign." Clinical Case Reports 6, no. 2: 262-266.

Communication
Published: 25 August 2016 in Toxins
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Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2) activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2) inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases) could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite.

ACS Style

Matthew Lewin; Stephen Samuel; Janie Merkel; Philip Bickler. Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation. Toxins 2016, 8, 248 .

AMA Style

Matthew Lewin, Stephen Samuel, Janie Merkel, Philip Bickler. Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation. Toxins. 2016; 8 (9):248.

Chicago/Turabian Style

Matthew Lewin; Stephen Samuel; Janie Merkel; Philip Bickler. 2016. "Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation." Toxins 8, no. 9: 248.

Journal article
Published: 01 July 2016 in Toxicon
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Matthew R. Lewin; Stephen P. Samue; Janie Merkel; Philip Bickler. Varespladib (LY315920) appears to be a very potent, broad-spectrum, inhibitor of snake venom PLA2s from six continents. Toxicon 2016, 117, 103 -104.

AMA Style

Matthew R. Lewin, Stephen P. Samue, Janie Merkel, Philip Bickler. Varespladib (LY315920) appears to be a very potent, broad-spectrum, inhibitor of snake venom PLA2s from six continents. Toxicon. 2016; 117 ():103-104.

Chicago/Turabian Style

Matthew R. Lewin; Stephen P. Samue; Janie Merkel; Philip Bickler. 2016. "Varespladib (LY315920) appears to be a very potent, broad-spectrum, inhibitor of snake venom PLA2s from six continents." Toxicon 117, no. : 103-104.

Journal article
Published: 02 October 2015 in Journal of Neuroscience Methods
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The hornworm Manduca sexta exhibits a defensive strike to noxious assaults, a response that is robust and is easily observed by experimenters. Von Frey filaments and methods typical for studying nociception in other animals were used to assess the strike response in M. sexta. A series of von Frey filaments was applied to the body wall in ascending order and the data generated were used to determine the strike threshold by (i) the up-and-down method, (ii) the first response method, and (iii) the simplified up-and-down order method (SUDO). The effect of a noxious pinch on strike threshold was assessed. To our knowledge none of these methods has been used on M. sexta previously, making the use of the up-and-down and SUDO methods the first in an invertebrate. The use of the first response method has been used in other invertebrates, and the method appears equally suited to M. sexta. All three methods were successful in monitoring the threshold sensitivity to touch, which was lowered (sensitized) by tissue damage induced with a pinch. Sensitization lasted 19 h. All three methods of assessing nociception were successfully applied to quantify the defensive strike response in M. sexta, although the SUDO method required empirical assessment of which filament to start the test sequence with. The results revealed both short- and long-term sensitization. These methods should prove to be useful for quantifying sensitization in M. sexta.

ACS Style

Marissa Zubia McMackin; Matthew R. Lewin; Dennis R. Tabuena; F. Eric Arreola; Christopher Moffatt; Megumi Fuse. Use of von Frey filaments to assess nociceptive sensitization in the hornworm, Manduca sexta. Journal of Neuroscience Methods 2015, 257, 139 -146.

AMA Style

Marissa Zubia McMackin, Matthew R. Lewin, Dennis R. Tabuena, F. Eric Arreola, Christopher Moffatt, Megumi Fuse. Use of von Frey filaments to assess nociceptive sensitization in the hornworm, Manduca sexta. Journal of Neuroscience Methods. 2015; 257 ():139-146.

Chicago/Turabian Style

Marissa Zubia McMackin; Matthew R. Lewin; Dennis R. Tabuena; F. Eric Arreola; Christopher Moffatt; Megumi Fuse. 2015. "Use of von Frey filaments to assess nociceptive sensitization in the hornworm, Manduca sexta." Journal of Neuroscience Methods 257, no. : 139-146.

Journal article
Published: 01 September 2014 in Parkinsonism & Related Disorders
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Matthew R. Lewin; Diana P. Blum. No evidence of neuroprotection? Perhaps not…perhaps so. Parkinsonism & Related Disorders 2014, 20, 1037 .

AMA Style

Matthew R. Lewin, Diana P. Blum. No evidence of neuroprotection? Perhaps not…perhaps so. Parkinsonism & Related Disorders. 2014; 20 (9):1037.

Chicago/Turabian Style

Matthew R. Lewin; Diana P. Blum. 2014. "No evidence of neuroprotection? Perhaps not…perhaps so." Parkinsonism & Related Disorders 20, no. 9: 1037.

Research article
Published: 14 May 2014 in Journal of Tropical Medicine
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Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice.Methods. Mice received intraperitoneal injections ofNaja najavenom 2.5 to 10 times the estimated LD50 and then received 5 μL neostigmine (0.5 mg/mL) or 5 μL normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized.Results. 100% of control mice died. Untreated mice injected with 2.5× LD50Naja najadied at average 193 minutes after injection, while 10 of 15 (67%) of treated mice survived and were behaviorally normal by 6 hours (P<0.02). In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P=0.01) and for 10× LD50 mice, survival increased from 30 to 175 minutes (P<0.02).Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted.

ACS Style

Matthew R. Lewin; Stephen P. Samuel; David S. Wexler; Philip Bickler; Sakthivel Vaiyapuri; Brett D. Mensh. Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model ofNaja naja(Indian Cobra) Envenomation. Journal of Tropical Medicine 2014, 2014, 1 -6.

AMA Style

Matthew R. Lewin, Stephen P. Samuel, David S. Wexler, Philip Bickler, Sakthivel Vaiyapuri, Brett D. Mensh. Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model ofNaja naja(Indian Cobra) Envenomation. Journal of Tropical Medicine. 2014; 2014 ():1-6.

Chicago/Turabian Style

Matthew R. Lewin; Stephen P. Samuel; David S. Wexler; Philip Bickler; Sakthivel Vaiyapuri; Brett D. Mensh. 2014. "Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model ofNaja naja(Indian Cobra) Envenomation." Journal of Tropical Medicine 2014, no. : 1-6.

Journal article
Published: 01 February 2014 in Annals of Emergency Medicine
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Matthew R. Lewin. Subluxation of clinical skills. Annals of Emergency Medicine 2014, 63, 271 .

AMA Style

Matthew R. Lewin. Subluxation of clinical skills. Annals of Emergency Medicine. 2014; 63 (2):271.

Chicago/Turabian Style

Matthew R. Lewin. 2014. "Subluxation of clinical skills." Annals of Emergency Medicine 63, no. 2: 271.

Journal article
Published: 24 July 2013 in Clinical Case Reports
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Neurotoxic snake envenomation can result in respiratory failure and death. Early treatment is considered important to survival. Inexpensive, heat‐stable, needle‐free, antiparalytics could facilitate early treatment of snakebite and save lives, but none have been developed. An experiment using aerosolized neostigmine to reverse paralysis suggests how early interventions could be developed.

ACS Style

Matthew R. Lewin; Philip Bickler; Tom Heier; John Feiner; Lance Montauk; Brett Mensh. Reversal of experimental paralysis in a human by intranasal neostigmine aerosol suggests a novel approach to the early treatment of neurotoxic envenomation. Clinical Case Reports 2013, 1, 7 -15.

AMA Style

Matthew R. Lewin, Philip Bickler, Tom Heier, John Feiner, Lance Montauk, Brett Mensh. Reversal of experimental paralysis in a human by intranasal neostigmine aerosol suggests a novel approach to the early treatment of neurotoxic envenomation. Clinical Case Reports. 2013; 1 (1):7-15.

Chicago/Turabian Style

Matthew R. Lewin; Philip Bickler; Tom Heier; John Feiner; Lance Montauk; Brett Mensh. 2013. "Reversal of experimental paralysis in a human by intranasal neostigmine aerosol suggests a novel approach to the early treatment of neurotoxic envenomation." Clinical Case Reports 1, no. 1: 7-15.

Journal article
Published: 30 September 2011 in The American Journal of Emergency Medicine
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Most research on the seasonality of acute coronary syndrome (ACS) has been were reported from hospital-based data. We aimed to investigate the seasonal distribution of ACS in Beijing and to elucidate the relations between ACS occurrence and climatic parameters in a prehospital setting. We retrospectively reviewed the electronic prehospital medical records from the Beijing's emergency medical service system spanning August 1, 2005, to July 31, 2007. Case data were analyzed by month and season with χ² test. The effects of climatic factors on the occurrence of ACS were analyzed by Poisson regression with generalized linear model. During the 2-year study period, a total of 7037 ACS events were identified, including 4135 male patients (58.8%) and 2902 female patients (41.2%). Significant variations were observed in the monthly (P < .001) and seasonal (P < .001) distribution of ACS. The highest seasonal incidence occurred in winter and lowest in autumn. Significant negative correlations were noticed between the number of ACS events and daily mean temperature (P < .001) and between the number of ACS events and barometric pressure (P < .001). Comparing to the baseline level (temperature of 25°C to approximately 31°C; barometric pressure of 1026 to approximately 1048 hectopascal (hPa)), an increase of 41.3% of daily ACS incidence was associated with temperature lower than 2°C (-10.0°C to approximately 2.0°C), and an increase of 19.8% was associated with barometric pressure under 1006 hPa (991.0 to approximately 1006 hPa). There are clear monthly and seasonal rhythms of ACS in Beijing metropolitan area. Temperature and barometric pressure are negatively related with the occurrence of ACS.

ACS Style

Yi Li; Tiekuan Du; Matthew R. Lewin; Houli Wang; Xu Ji; Yanping Zhang; Tengda Xu; Lingjie Xu; Jack S. Wu. The seasonality of acute coronary syndrome and its relations with climatic parameters. The American Journal of Emergency Medicine 2011, 29, 768 -774.

AMA Style

Yi Li, Tiekuan Du, Matthew R. Lewin, Houli Wang, Xu Ji, Yanping Zhang, Tengda Xu, Lingjie Xu, Jack S. Wu. The seasonality of acute coronary syndrome and its relations with climatic parameters. The American Journal of Emergency Medicine. 2011; 29 (7):768-774.

Chicago/Turabian Style

Yi Li; Tiekuan Du; Matthew R. Lewin; Houli Wang; Xu Ji; Yanping Zhang; Tengda Xu; Lingjie Xu; Jack S. Wu. 2011. "The seasonality of acute coronary syndrome and its relations with climatic parameters." The American Journal of Emergency Medicine 29, no. 7: 768-774.

Review
Published: 01 January 2011 in The American Journal of Emergency Medicine
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Although the decision to use nuclear medicine (NM) modalities in the acute care setting is limited by several factors, there are instances in which the use of NM techniques can provide elegant and efficient solutions to otherwise expensive and resource consuming situations. Herein, we describe the indications and NM techniques used for the evaluation of low-risk patients with chest pain, suspected pulmonary embolus, acute cholecystitis, gastrointestinal bleeding, acute scrotum, and the radiographically occult fracture.

ACS Style

Behrang Amini; Chirag B. Patel; Matthew R. Lewin; Taegyeong Kim; Ronald E. Fisher. Diagnostic nuclear medicine in the ED. The American Journal of Emergency Medicine 2011, 29, 91 -101.

AMA Style

Behrang Amini, Chirag B. Patel, Matthew R. Lewin, Taegyeong Kim, Ronald E. Fisher. Diagnostic nuclear medicine in the ED. The American Journal of Emergency Medicine. 2011; 29 (1):91-101.

Chicago/Turabian Style

Behrang Amini; Chirag B. Patel; Matthew R. Lewin; Taegyeong Kim; Ronald E. Fisher. 2011. "Diagnostic nuclear medicine in the ED." The American Journal of Emergency Medicine 29, no. 1: 91-101.

Review
Published: 21 December 2010 in PLOS Neglected Tropical Diseases
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ACS Style

Joseph Tonna; Matthew R. Lewin; Brett Mensh. A Case and Review of Noma. PLOS Neglected Tropical Diseases 2010, 4, e869 .

AMA Style

Joseph Tonna, Matthew R. Lewin, Brett Mensh. A Case and Review of Noma. PLOS Neglected Tropical Diseases. 2010; 4 (12):e869.

Chicago/Turabian Style

Joseph Tonna; Matthew R. Lewin; Brett Mensh. 2010. "A Case and Review of Noma." PLOS Neglected Tropical Diseases 4, no. 12: e869.