The Experts below are selected from a list of 534 Experts worldwide ranked by ideXlab platform

Eric J. Lavonas - One of the best experts on this subject based on the ideXlab platform.

  • ethical considerations in design of a study to evaluate a us food and drug administration approved indication antivenom versus placebo for copperhead envenomation
    Clinical Trials, 2014
    Co-Authors: Charles J Gerardo, Eric J. Lavonas, Ross E Mckinney
    Abstract:

    Background:In 2000, the US Food and Drug Administration approved CroFab® Crotalidae Polyvalent Immune Fab, ovine (FabAV), which had received orphan drug designation, for use in patients with minimal to moderate North American crotaline envenomations including copperhead snakes. As existing evidence on the effectiveness of FabAV for this indication is limited, wide practice variation in its use exists. In order to provide more definitive clinical evidence as to the role of this treatment, a new randomized, placebo-controlled trial of FabAV specifically for copperhead bites was initiated.Purpose:In light of the existing US Food and Drug Administration approval, ethical considerations of participation in this trial have been raised. We discuss the ethical principles pertinent to this randomized, placebo-controlled trial with placebo arm. We apply an accepted framework for ethical research to this trial. Due to the evidence gap in the literature, wide-ranging treatment recommendations by medical experts, and ...

  • medically significant late bleeding after treated crotaline envenomation a systematic review
    Annals of Emergency Medicine, 2014
    Co-Authors: Eric J. Lavonas, Vaishali Khatri, Thomas R King, Richard C Dart, Claire Daugherty, Becki Bucherbartelson
    Abstract:

    Study objective We estimate the proportion of patients with crotaline snake envenomation who are treated with Crotalidae polyvalent immune Fab (ovine) antivenom and who develop medically significant late bleeding. Methods We performed a systematic review of all published cohort studies of North American crotaline snake envenomation patients treated with Fab antivenom. We searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to April 30, 2012. Data were extracted by 2 trained researchers. Late bleeding was defined as bleeding that began or recurred after initial control of the envenomation syndrome. Medically significant late bleeding was defined a priori as late bleeding treated with RBC transfusion, vasoactive drug infusion, surgery, or rehospitalization or associated with a hemoglobin decrease of greater than or equal to 3 g/dL, hematocrit decrease of greater than or equal to 8%, disability, or death. Summary incidence and 95% confidence intervals (CIs) were calculated with a random-effects Poisson regression model. Results Nineteen unique cohort studies were identified. Four studies collected data prospectively, and in 9 studies, patients were followed actively after hospital discharge. A total of 1,017 subjects were enrolled in these cohort studies. Late bleeding was reported in 9 subjects (0.9%; 95% CI 0.4% to 2.2%), of whom 5 subjects (0.5%; 95% CI 0.1% to 1.7%) had medically significant late bleeding. Three patients received RBC transfusion; no deaths or permanent sequelae were reported. Estimates of risk may be affected by underreporting. Conclusion Medically significant late bleeding appears to be uncommon in snakebite victims treated with Fab antivenom.

  • incidence of immediate hypersensitivity reaction and serum sickness following administration of crotalidae polyvalent immune fab antivenom a meta analysis
    Academic Emergency Medicine, 2012
    Co-Authors: Tammi H Schaeffer, Vaishali Khatri, Liza M Reifler, Eric J. Lavonas
    Abstract:

    OBJECTIVES: Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation. METHODS: The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration. RESULTS: The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21). CONCLUSIONS: In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline envenomations appear to be lower than previously reported, at 0.08 and 0.13, respectively.

  • incidence of immediate hypersensitivity reaction and serum sickness following administration of crotalidae polyvalent immune fab antivenom a meta analysis
    Academic Emergency Medicine, 2012
    Co-Authors: Tammi H Schaeffer, Vaishali Khatri, Liza M Reifler, Eric J. Lavonas
    Abstract:

    ACADEMIC EMERGENCY MEDICINE 2012; 19:121–131 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives:  Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation. Methods:  The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration. Results:  The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21). Conclusions:  In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline envenomations appear to be lower than previously reported, at 0.08 and 0.13, respectively.

  • unified treatment algorithm for the management of crotaline snakebite in the united states results of an evidence informed consensus workshop
    BMC Emergency Medicine, 2011
    Co-Authors: Eric J. Lavonas, Sean P. Bush, Anne Michelle Ruha, William Banner, Vikhyat S Bebarta, Jeffrey N Bernstein, William Kerns, William H Richardson
    Abstract:

    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. A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm. A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy. Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

Shosaku Hattori - One of the best experts on this subject based on the ideXlab platform.

  • The Finding of a Group IIE Phospholipase A2 Gene in a Specified Segment of Protobothrops flavoviridis Genome and Its Possible Evolutionary Relationship to Group IIA Phospholipase A2 Genes
    MDPI AG, 2014
    Co-Authors: Kazuaki Yamaguchi, Yasuyuki Fukumaki, Shosaku Hattori, Takahito Chijiwa, Naoki Ikeda, Hiroki Shibata, Naoko Oda-ueda, Motonori Ohno
    Abstract:

    The genes encoding group IIE phospholipase A2, abbreviated as IIE PLA2, and its 5' and 3' flanking regions of Crotalinae snakes such as Protobothrops flavoviridis, P. tokarensis, P. elegans, and Ovophis okinavensis, were found and sequenced. The genes consisted of four exons and three introns and coded for 22 or 24 amino acid residues of the signal peptides and 134 amino acid residues of the mature proteins. These IIE PLA2s show high similarity to those from mammals and Colubridae snakes. The high expression level of IIE PLA2s in Crotalinae venom glands suggests that they should work as venomous proteins. The blast analysis indicated that the gene encoding OTUD3, which is ovarian tumor domain-containing protein 3, is located in the 3' downstream of IIE PLA2 gene. Moreover, a group IIA PLA2 gene was found in the 5' upstream of IIE PLA2 gene linked to the OTUD3 gene (OTUD3) in the P. flavoviridis genome. It became evident that the specified arrangement of IIA PLA2 gene, IIE PLA2 gene, and OTUD3 in this order is common in the genomes of humans to snakes. The present finding that the genes encoding various secretory PLA2s form a cluster in the genomes of humans to birds is closely related to the previous finding that six venom PLA2 isozyme genes are densely clustered in the so-called NIS-1 fragment of the P. flavoviridis genome. It is also suggested that venom IIA PLA2 genes may be evolutionarily derived from the IIE PLA2 gene

  • unique structural characteristics and evolution of a cluster of venom phospholipase a2 isozyme genes of protobothrops flavoviridis snake
    Gene, 2010
    Co-Authors: Naoki Ikeda, Kazumi Matsubara, Yoichi Matsuda, Shosaku Hattori, Takahito Chijiwa, Naoko Odaueda, Motonori Ohno
    Abstract:

    Abstract Protobothrops flavoviridis (Crotalinae) venom gland phospholipase A 2 (PLA 2 ) isozyme genes have evolved in an accelerated manner to acquire diverse physiological activities in their products. For elucidation of the multiplication mechanism of PLA 2 genes, a 25,026 bp genome segment harboring five PLA 2 isozyme genes was obtained from Amami-Oshima P. flavoviridis liver and sequenced. The gene PfPLA 2 encoded [Lys 49 ]PLA 2 called BPII, the gene PfPLA 4 neurotoxic [Asp 49 ]PLA 2 called PLA-N, the gene PfPLA 5 basic [Asp 49 ]PLA 2 called PLA-B, and PfPLA 1(ψ) and PfPLA 3(ψ) were the inactivated genes. The 5′ truncated reverse transcriptase (RT) elements, whose intact forms constitute long interspersed nuclear elements (LINEs), were found in close proximity to the 3′ end of PLA 2 genes and named PLA 2 gene-coupled RT fragments (PcRTFs). The facts that PcRTFs have the stem–loop and repetitive sequence in the 3′ untranslated region (UTR) which is characteristic of CR1 LINEs suggest that PcRTFs are the debris of P. flavoviridis ancestral CR1 LINEs, denoted as Pf CR1s. Since the associated pairs of PLA 2 genes and PcRTFs are arranged in tandem in the 25,026 bp segment, it is thought that an ancestral PLA 2 gene- Pf CR1 unit ( PfPLA - Pf CR1) which was produced by retrotransposition of Pf CR1 by itself to the 3′ end of PLA 2 gene duplicated several times to form a multimer of PfPLA - Pf CR1, a cluster of PLA 2 genes, in the period after Crotalinae and Viperinae snakes branched off. Recombinational hot spot of a 37 bp segment, named Scomb , was found in the region 548 bp upstream from the TATA box of PLA 2 genes. Thus, it could be assumed that multiplication of PfPLA - Pf CR1 occurred by unequal crossing over of the segment, - Scomb - PfPLA - Pf CR1- Scomb- . The Pf CR1 moieties were afterward disrupted in the 5′ portion to PcRTFs. The detection of two types of PcRTFs different in length which were produced by elimination of two definitive sequences in Pf CR1 moiety possibly by gene conversion clearly supports such process but not multiplication of the PLA 2 gene-PcRTF unit.

  • amino acid sequence of a basic aspartate 49 phospholipase a2 from trimeresurus flavoviridis venom and phylogenetic analysis of Crotalinae venom phospholipases a2
    Toxicon, 2005
    Co-Authors: Takahito Chijiwa, Tomohisa Ogawa, Shosaku Hattori, Naoko Odaueda, Nikolai N Nikandrov, Motonori Ohno
    Abstract:

    Abstract Trimeresurus flavoviridis snakes inhabit the southwestern islands of Japan: Amami-Oshima, Tokunoshima and Okinawa. A phospholipase A 2 (PLA 2 ) of basic nature (pI 8.5) was isolated from the venom of Amami-Oshima T. flavoviridis . Its amino acid sequence determined by the ordinary procedures was completely in accord with that predicted from the nucleotide sequence of the cDNA previously cloned from Amami-Oshima T. flavoviridis venom gland, which was named PLA-B′. It consists of 122 amino acid residues and has aspartate at position 49. It induced edema in a mouse footpad assay and caused necrosis in mouse skeletal muscles. PLA-B′ is similar in sequence to PLA-B (Tokunoshima) and PL-Y (Okinawa), both basic [Asp 49 ]PLA 2 s, with a few amino acid substitutions, indicating occurrence of interisland mutation. Although PLA 2 s of Crotalinae subfamily were phylogenetically classified into four types, PLA2 (acidic or neutral [Asp 49 ]PLA 2 ) type, basic [Asp 49 ]PLA 2 type, neurotoxic [Asp 49 ]PLA 2 type and [Lys 49 ]PLA 2 type, it was ascertained that PLA 2 s of PLA2 type and [Lys 49 ]PLA 2 type are most essential as toxic components for Crotalinae snake venoms and that basic [Asp 49 ]PLA 2 -type PLA 2 s are uniquely contained only in the venoms of T. flavoviridis species. Prediction of physiological activities of some PLA 2 s was made based on their location in the phylogenetic tree. Relationship of divergence of PLA 2 s via accelerated evolution followed by less rapid mutation and physiological activities was discussed.

  • interisland mutation of a novel phospholipase a2 from trimeresurus flavoviridis venom and evolution of Crotalinae group ii phospholipases a2
    Journal of Molecular Evolution, 2003
    Co-Authors: Takahito Chijiwa, Masanobu Deshimaru, Tomohisa Ogawa, Shosaku Hattori, Sachiko Hamai, Shoji Tsubouchi, Naoko Odaueda, Hiroshi Kihara, Susumu Tsunasawa, Motonori Ohno
    Abstract:

    Trimeresurus flavoviridis (Crotalinae) snakes inhabit the southwestern islands of Japan: Amami-Oshima, Tokunoshima, and Okinawa. Affinity and conventional chromatographies of Amami-Oshima T. flavoviridis venom led to isolation of a novel phospholipase A2 (PLA2). This protein was highly homologous (91%) in sequence to trimucrotoxin, a neurotoxic PLA2, which had been isolated from T. mucrosquamatus (Taiwan) venom, and exhibited weak neurotoxicity. This protein was named PLA-N. Its LD50 for mice was 1.34 µg/g, which is comparable to that of trimucrotoxin. The cDNA encoding PLA-N was isolated from both the Amami-Oshima and the Tokunoshima T. flavoviridis venom-gland cDNA libraries. Screening of the Okinawa T. flavoviridis venom-gland cDNA library with PLA-N cDNA led to isolation of the cDNA encoding one amino acid-substituted PLA-N homologue, named PLA-N(O), suggesting that interisland mutation occurred and that Okinawa island was separated from a former island prior to dissociation of Amami-Oshima and Tokunoshima islands. Construction of a phylogenetic tree of Crotalinae venom group II PLA2’s based on the amino acid sequences revealed that neurotoxic PLA2’s including PLA-N and PLA-N(O) form an independent cluster which is distant from other PLA2 groups such as PLA2 type, basic [Asp49]PLA2 type, and [Lys49]PLA2 type. Comparison of the nucleotide sequence of PLA-N cDNA with those of the cDNAs encoding other T. flavoviridis venom PLA2’s showed that they have evolved in an accelerated manner. However, when comparison was made within the cDNAs encoding Crotalinae venom neurotoxic PLA2‘s, their evolutionary rates appear to be reduced to a level between accelerated evolution and neutral evolution. It is likely that ancestral genes of neurotoxic PLA2’s evolved in an accelerated manner until they had acquired neurotoxic function and since then they have evolved with less frequent mutation, possibly for functional conservation.

  • accelerated evolution of trimeresurus okinavensis venom gland phospholipase a2 isozyme encoding genes
    Gene, 1996
    Co-Authors: Ikuo Nobuhisa, Kinichi Nakashima, Masanobu Deshimaru, Tomohisa Ogawa, Yasuyuki Shimohigashi, Yasuyuki Fukumaki, Yoshiyuki Sakaki, Shosaku Hattori, Hiroshi Kihara, Motonori Ohno
    Abstract:

    Abstract Three Trimeresurus okinavensis (To; himehabu snake, Crotalinae) venom gland phospholipase A2 (PLA2) isozymeencoding genes, gPLA2-o1, gPLA2-o2 and gPLA2-o3, were isolated from its genomic DNA library. The nucleotide (nt) sequence analysis revealed that two of the three genes (gPLA2-o2) and (gPLA2-o3) occasionally have been converted to inactivated genes by introduction of one base insertion or substitution. It was confirmed from Southern blot analysis that the To haploid genome contains only three venom gland PLA2 isozyme genes herein isolated. Comparison of these genes showed that nonsynonymous nt substitutions have occurred more frequently than synonymous nt substitutions in the protein-coding regions, except for the signal-peptide coding domain, implying that To venom gland PLA2isozyme genes have evolved via accelerated evolution. Such an evolutionary feature of To venom gland PLA2 isozyme genes proves the general universality of accelerated evolution previously drawn for venom gland PLA2 isozyme genes of other Crotalinae snakes. The variability in the mature protein-coding regions of three To venom gland PLA2 isozyme genes appears to have been brought about by natural selection for point mutations.

Motonori Ohno - One of the best experts on this subject based on the ideXlab platform.

  • The Finding of a Group IIE Phospholipase A2 Gene in a Specified Segment of Protobothrops flavoviridis Genome and Its Possible Evolutionary Relationship to Group IIA Phospholipase A2 Genes
    MDPI AG, 2014
    Co-Authors: Kazuaki Yamaguchi, Yasuyuki Fukumaki, Shosaku Hattori, Takahito Chijiwa, Naoki Ikeda, Hiroki Shibata, Naoko Oda-ueda, Motonori Ohno
    Abstract:

    The genes encoding group IIE phospholipase A2, abbreviated as IIE PLA2, and its 5' and 3' flanking regions of Crotalinae snakes such as Protobothrops flavoviridis, P. tokarensis, P. elegans, and Ovophis okinavensis, were found and sequenced. The genes consisted of four exons and three introns and coded for 22 or 24 amino acid residues of the signal peptides and 134 amino acid residues of the mature proteins. These IIE PLA2s show high similarity to those from mammals and Colubridae snakes. The high expression level of IIE PLA2s in Crotalinae venom glands suggests that they should work as venomous proteins. The blast analysis indicated that the gene encoding OTUD3, which is ovarian tumor domain-containing protein 3, is located in the 3' downstream of IIE PLA2 gene. Moreover, a group IIA PLA2 gene was found in the 5' upstream of IIE PLA2 gene linked to the OTUD3 gene (OTUD3) in the P. flavoviridis genome. It became evident that the specified arrangement of IIA PLA2 gene, IIE PLA2 gene, and OTUD3 in this order is common in the genomes of humans to snakes. The present finding that the genes encoding various secretory PLA2s form a cluster in the genomes of humans to birds is closely related to the previous finding that six venom PLA2 isozyme genes are densely clustered in the so-called NIS-1 fragment of the P. flavoviridis genome. It is also suggested that venom IIA PLA2 genes may be evolutionarily derived from the IIE PLA2 gene

  • unique structural characteristics and evolution of a cluster of venom phospholipase a2 isozyme genes of protobothrops flavoviridis snake
    Gene, 2010
    Co-Authors: Naoki Ikeda, Kazumi Matsubara, Yoichi Matsuda, Shosaku Hattori, Takahito Chijiwa, Naoko Odaueda, Motonori Ohno
    Abstract:

    Abstract Protobothrops flavoviridis (Crotalinae) venom gland phospholipase A 2 (PLA 2 ) isozyme genes have evolved in an accelerated manner to acquire diverse physiological activities in their products. For elucidation of the multiplication mechanism of PLA 2 genes, a 25,026 bp genome segment harboring five PLA 2 isozyme genes was obtained from Amami-Oshima P. flavoviridis liver and sequenced. The gene PfPLA 2 encoded [Lys 49 ]PLA 2 called BPII, the gene PfPLA 4 neurotoxic [Asp 49 ]PLA 2 called PLA-N, the gene PfPLA 5 basic [Asp 49 ]PLA 2 called PLA-B, and PfPLA 1(ψ) and PfPLA 3(ψ) were the inactivated genes. The 5′ truncated reverse transcriptase (RT) elements, whose intact forms constitute long interspersed nuclear elements (LINEs), were found in close proximity to the 3′ end of PLA 2 genes and named PLA 2 gene-coupled RT fragments (PcRTFs). The facts that PcRTFs have the stem–loop and repetitive sequence in the 3′ untranslated region (UTR) which is characteristic of CR1 LINEs suggest that PcRTFs are the debris of P. flavoviridis ancestral CR1 LINEs, denoted as Pf CR1s. Since the associated pairs of PLA 2 genes and PcRTFs are arranged in tandem in the 25,026 bp segment, it is thought that an ancestral PLA 2 gene- Pf CR1 unit ( PfPLA - Pf CR1) which was produced by retrotransposition of Pf CR1 by itself to the 3′ end of PLA 2 gene duplicated several times to form a multimer of PfPLA - Pf CR1, a cluster of PLA 2 genes, in the period after Crotalinae and Viperinae snakes branched off. Recombinational hot spot of a 37 bp segment, named Scomb , was found in the region 548 bp upstream from the TATA box of PLA 2 genes. Thus, it could be assumed that multiplication of PfPLA - Pf CR1 occurred by unequal crossing over of the segment, - Scomb - PfPLA - Pf CR1- Scomb- . The Pf CR1 moieties were afterward disrupted in the 5′ portion to PcRTFs. The detection of two types of PcRTFs different in length which were produced by elimination of two definitive sequences in Pf CR1 moiety possibly by gene conversion clearly supports such process but not multiplication of the PLA 2 gene-PcRTF unit.

  • amino acid sequence of a basic aspartate 49 phospholipase a2 from trimeresurus flavoviridis venom and phylogenetic analysis of Crotalinae venom phospholipases a2
    Toxicon, 2005
    Co-Authors: Takahito Chijiwa, Tomohisa Ogawa, Shosaku Hattori, Naoko Odaueda, Nikolai N Nikandrov, Motonori Ohno
    Abstract:

    Abstract Trimeresurus flavoviridis snakes inhabit the southwestern islands of Japan: Amami-Oshima, Tokunoshima and Okinawa. A phospholipase A 2 (PLA 2 ) of basic nature (pI 8.5) was isolated from the venom of Amami-Oshima T. flavoviridis . Its amino acid sequence determined by the ordinary procedures was completely in accord with that predicted from the nucleotide sequence of the cDNA previously cloned from Amami-Oshima T. flavoviridis venom gland, which was named PLA-B′. It consists of 122 amino acid residues and has aspartate at position 49. It induced edema in a mouse footpad assay and caused necrosis in mouse skeletal muscles. PLA-B′ is similar in sequence to PLA-B (Tokunoshima) and PL-Y (Okinawa), both basic [Asp 49 ]PLA 2 s, with a few amino acid substitutions, indicating occurrence of interisland mutation. Although PLA 2 s of Crotalinae subfamily were phylogenetically classified into four types, PLA2 (acidic or neutral [Asp 49 ]PLA 2 ) type, basic [Asp 49 ]PLA 2 type, neurotoxic [Asp 49 ]PLA 2 type and [Lys 49 ]PLA 2 type, it was ascertained that PLA 2 s of PLA2 type and [Lys 49 ]PLA 2 type are most essential as toxic components for Crotalinae snake venoms and that basic [Asp 49 ]PLA 2 -type PLA 2 s are uniquely contained only in the venoms of T. flavoviridis species. Prediction of physiological activities of some PLA 2 s was made based on their location in the phylogenetic tree. Relationship of divergence of PLA 2 s via accelerated evolution followed by less rapid mutation and physiological activities was discussed.

  • interisland mutation of a novel phospholipase a2 from trimeresurus flavoviridis venom and evolution of Crotalinae group ii phospholipases a2
    Journal of Molecular Evolution, 2003
    Co-Authors: Takahito Chijiwa, Masanobu Deshimaru, Tomohisa Ogawa, Shosaku Hattori, Sachiko Hamai, Shoji Tsubouchi, Naoko Odaueda, Hiroshi Kihara, Susumu Tsunasawa, Motonori Ohno
    Abstract:

    Trimeresurus flavoviridis (Crotalinae) snakes inhabit the southwestern islands of Japan: Amami-Oshima, Tokunoshima, and Okinawa. Affinity and conventional chromatographies of Amami-Oshima T. flavoviridis venom led to isolation of a novel phospholipase A2 (PLA2). This protein was highly homologous (91%) in sequence to trimucrotoxin, a neurotoxic PLA2, which had been isolated from T. mucrosquamatus (Taiwan) venom, and exhibited weak neurotoxicity. This protein was named PLA-N. Its LD50 for mice was 1.34 µg/g, which is comparable to that of trimucrotoxin. The cDNA encoding PLA-N was isolated from both the Amami-Oshima and the Tokunoshima T. flavoviridis venom-gland cDNA libraries. Screening of the Okinawa T. flavoviridis venom-gland cDNA library with PLA-N cDNA led to isolation of the cDNA encoding one amino acid-substituted PLA-N homologue, named PLA-N(O), suggesting that interisland mutation occurred and that Okinawa island was separated from a former island prior to dissociation of Amami-Oshima and Tokunoshima islands. Construction of a phylogenetic tree of Crotalinae venom group II PLA2’s based on the amino acid sequences revealed that neurotoxic PLA2’s including PLA-N and PLA-N(O) form an independent cluster which is distant from other PLA2 groups such as PLA2 type, basic [Asp49]PLA2 type, and [Lys49]PLA2 type. Comparison of the nucleotide sequence of PLA-N cDNA with those of the cDNAs encoding other T. flavoviridis venom PLA2’s showed that they have evolved in an accelerated manner. However, when comparison was made within the cDNAs encoding Crotalinae venom neurotoxic PLA2‘s, their evolutionary rates appear to be reduced to a level between accelerated evolution and neutral evolution. It is likely that ancestral genes of neurotoxic PLA2’s evolved in an accelerated manner until they had acquired neurotoxic function and since then they have evolved with less frequent mutation, possibly for functional conservation.

  • accelerated evolution of trimeresurus okinavensis venom gland phospholipase a2 isozyme encoding genes
    Gene, 1996
    Co-Authors: Ikuo Nobuhisa, Kinichi Nakashima, Masanobu Deshimaru, Tomohisa Ogawa, Yasuyuki Shimohigashi, Yasuyuki Fukumaki, Yoshiyuki Sakaki, Shosaku Hattori, Hiroshi Kihara, Motonori Ohno
    Abstract:

    Abstract Three Trimeresurus okinavensis (To; himehabu snake, Crotalinae) venom gland phospholipase A2 (PLA2) isozymeencoding genes, gPLA2-o1, gPLA2-o2 and gPLA2-o3, were isolated from its genomic DNA library. The nucleotide (nt) sequence analysis revealed that two of the three genes (gPLA2-o2) and (gPLA2-o3) occasionally have been converted to inactivated genes by introduction of one base insertion or substitution. It was confirmed from Southern blot analysis that the To haploid genome contains only three venom gland PLA2 isozyme genes herein isolated. Comparison of these genes showed that nonsynonymous nt substitutions have occurred more frequently than synonymous nt substitutions in the protein-coding regions, except for the signal-peptide coding domain, implying that To venom gland PLA2isozyme genes have evolved via accelerated evolution. Such an evolutionary feature of To venom gland PLA2 isozyme genes proves the general universality of accelerated evolution previously drawn for venom gland PLA2 isozyme genes of other Crotalinae snakes. The variability in the mature protein-coding regions of three To venom gland PLA2 isozyme genes appears to have been brought about by natural selection for point mutations.

Steven A. Seifert - One of the best experts on this subject based on the ideXlab platform.

  • unpredicted late new onset thrombocytopenia and hypofibrinogenemia in fab antivenom treated rattlesnake envenomation
    Toxicon, 2020
    Co-Authors: Steven A. Seifert, D N Mascarenas, L Fullerton, Brandon J Warrick, Susan Smolinske
    Abstract:

    The use of Fab antivenom (Crotalidae Polyvalent Immune Fab (Ovine) (CroFab); Boston Scientific) against North American Crotalidae envenomation is associated with the development of late- (≥4 days post-envenomation), new-onset of hematological abnormalities. Although attempts have been made to identify predictive indicators during the acute phase of an envenomation, of patients who are not at-risk of late-, new-onset of hematological abnormalities, there has been at least one prior report of a patient who developed thrombocytopenia that was unpredicted by current indicators. We add three cases of unpredicted, late-, new-onset of hematological abnormalities in patients with Fab-treated rattlesnake bite.

  • comparison of f ab 2 versus fab antivenom for pit viper envenomation a prospective blinded multicenter randomized clinical trial
    Clinical Toxicology, 2015
    Co-Authors: Sean P. Bush, Steven A. Seifert, Richard F Clark, Anne Michelle Ruha, David L Morgan, Brandon Lewis, Thomas C Arnold, William J Meggs, Eric A Toschlog, Stephen W Borron
    Abstract:

    Background . Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab ’ ) 2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab ’ ) 2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods . We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab ’ ) 2 with maintenance doses [F(ab ’ ) 2 /F(ab ’ ) 2 ], or F(ab ’ ) 2 with placebo maintenance doses [F(ab ’ ) 2 /placebo], versus Fab with maintenance doses [Fab/Fab]. The primary effi cacy endpoint was coagulopathy (platelet count 150 K/mm 3 , fi brinogen level 150 mg/dL) between end of maintenance dosing and day 8. Results . 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p 0.05) in the F(ab ’ ) 2 /F(ab ’ ) 2 cohort and 2/38 (5.3%, p 0.05) in the F(ab ’ ) 2 /placebo cohort. The lowest heterologous protein exposure was with F(ab ’ ) 2 /placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions . In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab ’ ) 2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

  • a randomized multicenter trial of Crotalinae polyvalent immune fab ovine antivenom for the treatment for crotaline snakebite in the united states
    JAMA Internal Medicine, 2001
    Co-Authors: Richard C Dart, Steven A. Seifert, Leslie V. Boyer, Richard F Clark, Steven C Curry, Edward L Hall, Patrick E Mckinney, Jude Mcnally, Craig S Kitchens
    Abstract:

    Background Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). Methods A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. Results The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P Conclusions In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

  • recurrence phenomena after immunoglobulin therapy for snake envenomations part 2 guidelines for clinical management with crotaline fab antivenom
    Annals of Emergency Medicine, 2001
    Co-Authors: Leslie V. Boyer, Steven A. Seifert, Jeffrey S Cain
    Abstract:

    Abstract Recurrent local and coagulopathic effects (worsening after clinical improvement) have been described after treatment with Fab antivenom for envenomation by North American crotaline snakes. Although similar phenomena have been described previously in snakebite, few studies have examined recurrence or its management. Recurrence is consistent with known venom and antivenom kinetics and dynamics. The clinical significance of late coagulopathy after snakebite is uncertain, but clinically significant bleeding is a possibility. Prevention and treatment of recurrence with Fab antivenom require repeated dosing for at least 18 hours, with close monitoring of at-risk patients in the follow-up period. Duration of therapy depends on individual risk factors and coagulation response. [Boyer LV, Seifert SA, Cain JS. Recurrence phenomena after immunoglobulin therapy for snake envenomations: part 2. Guidelines for clinical management with crotaline Fab antivenom. Ann Emerg Med. February 2001;37:196-201.]

  • recurrence phenomena after immunoglobulin therapy for snake envenomations part 2 guidelines for clinical management with crotaline fab antivenom
    Annals of Emergency Medicine, 2001
    Co-Authors: Leslie V. Boyer, Steven A. Seifert, Jeffrey S Cain
    Abstract:

    Recurrent local and coagulopathic effects (worsening after clinical improvement) have been described after treatment with Fab antivenom for envenomation by North American crotaline snakes. Although similar phenomena have been described previously in snakebite, few studies have examined recurrence or its management. Recurrence is consistent with known venom and antivenom kinetics and dynamics. The clinical significance of late coagulopathy after snakebite is uncertain, but clinically significant bleeding is a possibility. Prevention and treatment of recurrence with Fab antivenom require repeated dosing for at least 18 hours, with close monitoring of at-risk patients in the follow-up period. Duration of therapy depends on individual risk factors and coagulation response.

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  • a new f abʹ 2 antivenom for the treatment of crotaline envenomation in children
    American Journal of Emergency Medicine, 2016
    Co-Authors: Daniel Lasoff, Anne Michelle Ruha, Steven C Curry, Cynthia Koh, Richard F Clark
    Abstract:

    Abstract Study objective To evaluate the efficacy and safety of a new F(abʹ)2 antivenom preparation in the treatment of Crotalinae envenomation in children. Methods We present a case series of children younger than 16 years who suffered Crotalinae envenomation and were treated with a new F(abʹ)2 antivenom. Envenomated children treated with the new antivenom were assessed for efficacy of the product, defined as improvement of any hemotoxicity (hypofibrinogenemia, defined as fibrinogen Results Twenty-one children received the F(abʹ)2 antivenom. Efficacy was achieved in all children receiving the product with initial control of swelling and improvement in those with hemotoxicity. No patients suffered anaphylaxis or any other serious adverse events from the F(abʹ)2 treatment. There were no cases of recurrent hemotoxicity recorded in the study between time of initial control and postinfusion day 15. Conclusions In this series of children, the F(abʹ)2 antivenom appeared to be both safe and effective in the treatment of hemotoxicity and local tissue toxicity (swelling) from Crotalinae envenomation.

  • initial postmarketing experience with crotalidae polyvalent immune fab for treatment of rattlesnake envenomation
    Annals of Emergency Medicine, 2002
    Co-Authors: Anne Michelle Ruha, Steven C Curry, Michael C Beuhler, Ken Katz, Daniel E Brooks, Kimberlie A Graeme, Kevin L Wallace, Richard Gerkin, Frank Lovecchio, Paul M Wax
    Abstract:

    Abstract Study Objective: We describe our postmarketing experience with patients receiving Crotalidae polyvalent immune Fab (CroFab; FabAV) antivenom for treatment of rattlesnake envenomation. Methods: The charts of 28 patients admitted between March 1 and September 9, 2001, with rattlesnake envenomation and treated with FabAV were reviewed for demographic information, time until antivenom treatment, laboratory findings, evidence of hypersensitivity reaction, length of hospital stay, and readmission to the hospital. Results: All patients had swelling, 20 patients had elevated prothrombin times (>14 seconds), 12 patients had low fibrinogen levels ( 3 ) on presentation. The total dose of FabAV ranged from 10 to 47 vials per patient. Hypofibrinogenemia was resistant to FabAV in some patients. On follow-up, recurrence of coagulopathy was detected in 3 patients, and recurrence of thrombocytopenia was detected in 1 patient. Two patients demonstrated delayed-onset severe thrombocytopenia. Recurrence or delayed-onset toxicity might have been underestimated because of incomplete follow-up in some patients. No acute hypersensitivity reactions occurred. Two patients reported mild symptoms of possible serum sickness on follow-up. Conclusion: FabAV effectively controlled the effects of envenomation; however, initial control of coagulopathy was difficult to achieve in some cases, and recurrence or delayed-onset hematotoxicity was common. When initially managing hematotoxicity, a trend toward normalization of laboratory values might be a more reasonable end point for FabAV treatment than attainment of normal reference values in nonbleeding patients. [Ruha A-M, Curry SC, Beuhler M, Katz K, Brooks DE, Graeme KA, Wallace K, Gerkin R, LoVecchio F, Wax P, Selden B. Initial postmarketing experience with Crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation. Ann Emerg Med. June 2002;39:609-615.]

  • a randomized multicenter trial of Crotalinae polyvalent immune fab ovine antivenom for the treatment for crotaline snakebite in the united states
    JAMA Internal Medicine, 2001
    Co-Authors: Richard C Dart, Steven A. Seifert, Leslie V. Boyer, Richard F Clark, Steven C Curry, Edward L Hall, Patrick E Mckinney, Jude Mcnally, Craig S Kitchens
    Abstract:

    Background Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). Methods A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. Results The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P Conclusions In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

  • crotalid snake envenomation
    Critical Care Clinics, 1997
    Co-Authors: Christopher P Holstege, Mary Beth Miller, Mary Wermuth, Brent Furbee, Steven C Curry
    Abstract:

    Over 5000 Americans suffer snake bites annually, and of these, nearly one quarter are from poisonous species. Although these cases are undeniably underreported, death appears to occur in only a few cases each year, 75 and often reflects delay in obtaining medical care. 47 Two families of venomous snakes indigenous to the United States account for most envenomations: (1) Crotalidae (pit vipers or new world vipers) and (2) Elapidae. Elapids are brightly colored and have front, fixed-fanged snakes, that inhabit the southeastern and southwestern United States. They are responsible for less than 0.5% of the envenomations that occur 104 and are not discussed further. The focus of this article is on the snakes of the family Crotalidae (Table 1) Crotalids possess triangular-shaped heads, elliptical-shaped pupils during daylight, and a single row of subcaudal scales. They also possess infrared heat-sensing pits, thus the name "pit viper," which enable them to locate prey, guide the direction of strike, and possibly determine the amount of venom to be released. 10 Three genera of crotalids inhabit the United States: (1) Crotalus, (2) Sistrurus, and (3) Agkistrodon. Members of the genera Crotalus and Sistrurus possess rattles on their tails and are collectively referred to as rattlesnakes. The rattleless members of Agkistrodon comprise cottonmouths (water moccasins) and copperheads (Fig. 1).