Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos
Identifieur interne : 002C98 ( Pmc/Corpus ); précédent : 002C97; suivant : 002C99Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos
Auteurs : M. Eddleston ; F. Worek ; P. Eyer ; H. Thiermann ; L. Von Meyer ; K. Jeganathan ; M. H. R. Sheriff ; A. H. Dawson ; N. A. BuckleySource :
- QJM: An International Journal of Medicine [ 1460-2725 ] ; 2009.
Abstract
Url:
DOI: 10.1093/qjmed/hcp119
PubMed: 19737786
PubMed Central: 2766103
Links to Exploration step
PMC:2766103Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Poisoning with the <italic>S</italic>-Alkyl organophosphorus insecticides profenofos and prothiofos</title><author><name sortKey="Eddleston, M" sort="Eddleston, M" uniqKey="Eddleston M" first="M." last="Eddleston">M. Eddleston</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Worek, F" sort="Worek, F" uniqKey="Worek F" first="F." last="Worek">F. Worek</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Eyer, P" sort="Eyer, P" uniqKey="Eyer P" first="P." last="Eyer">P. Eyer</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Thiermann, H" sort="Thiermann, H" uniqKey="Thiermann H" first="H." last="Thiermann">H. Thiermann</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Von Meyer, L" sort="Von Meyer, L" uniqKey="Von Meyer L" first="L." last="Von Meyer">L. Von Meyer</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Jeganathan, K" sort="Jeganathan, K" uniqKey="Jeganathan K" first="K." last="Jeganathan">K. Jeganathan</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Sheriff, M H R" sort="Sheriff, M H R" uniqKey="Sheriff M" first="M. H. R." last="Sheriff">M. H. R. Sheriff</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Dawson, A H" sort="Dawson, A H" uniqKey="Dawson A" first="A. H." last="Dawson">A. H. Dawson</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Buckley, N A" sort="Buckley, N A" uniqKey="Buckley N" first="N. A." last="Buckley">N. A. Buckley</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19737786</idno><idno type="pmc">2766103</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766103</idno><idno type="RBID">PMC:2766103</idno><idno type="doi">10.1093/qjmed/hcp119</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">002C98</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002C98</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Poisoning with the <italic>S</italic>-Alkyl organophosphorus insecticides profenofos and prothiofos</title><author><name sortKey="Eddleston, M" sort="Eddleston, M" uniqKey="Eddleston M" first="M." last="Eddleston">M. Eddleston</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Worek, F" sort="Worek, F" uniqKey="Worek F" first="F." last="Worek">F. Worek</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Eyer, P" sort="Eyer, P" uniqKey="Eyer P" first="P." last="Eyer">P. Eyer</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Thiermann, H" sort="Thiermann, H" uniqKey="Thiermann H" first="H." last="Thiermann">H. Thiermann</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Von Meyer, L" sort="Von Meyer, L" uniqKey="Von Meyer L" first="L." last="Von Meyer">L. Von Meyer</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Jeganathan, K" sort="Jeganathan, K" uniqKey="Jeganathan K" first="K." last="Jeganathan">K. Jeganathan</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Sheriff, M H R" sort="Sheriff, M H R" uniqKey="Sheriff M" first="M. H. R." last="Sheriff">M. H. R. Sheriff</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Dawson, A H" sort="Dawson, A H" uniqKey="Dawson A" first="A. H." last="Dawson">A. H. Dawson</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author><author><name sortKey="Buckley, N A" sort="Buckley, N A" uniqKey="Buckley N" first="N. A." last="Buckley">N. A. Buckley</name><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation><affiliation><nlm:aff id="AFF1"></nlm:aff></affiliation></author></analytic><series><title level="j">QJM: An International Journal of Medicine</title><idno type="ISSN">1460-2725</idno><idno type="eISSN">1460-2393</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Many organophosphorus (OP) insecticides have either two <italic>O</italic>-methyl or two <italic>O</italic>-ethyl groups attached to the phosphorus atom. This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. However, several OP insecticides are atypical and do not have these structures.</p><p><bold>Aim:</bold> We aimed to describe the clinical course and responsiveness to therapy of people poisoned with two <italic>S</italic>-alkyl OP insecticides—profenofos and prothiofos.</p><p><bold>Design:</bold> We set up a prospective cohort of patients with acute profenofos or prothiofos self-poisoning admitted to acute medical wards in two Sri Lankan district hospitals. Clinical observation was carried out throughout their inpatient stay; blood samples were taken in a subgroup for assay of cholinesterases and insecticide.</p><p><bold>Results:</bold> Ninety-five patients poisoned with profenofos and 12 with prothiofos were recruited over 5 years. Median time to admission was 4 (IQR 3–7) h. Eleven patients poisoned with profenofos died (11/95; 11.6%, 95% CI 5.9–20); one prothiofos patient died (1/12; 8.3%, 95% CI 0.2–38). Thirteen patients poisoned with profenofos required intubation for respiratory failure (13/95; 13.7%, 95% CI 7.5–22); two prothiofos-poisoned patients required intubation. Both intubations and death occurred late compared with other OP insecticides. Prolonged ventilation was needed in those who survived—a median of 310 (IQR 154–349) h. Unexpectedly, red cell AChE activity on admission did not correlate with clinical severity—all patients had severe AChE inhibition (about 1% of normal) but most had only mild cholinergic features, were conscious, and did not require ventilatory support.</p><p><bold>Conclusions:</bold> Compared with other commonly used OP insecticides, profenofos and prothiofos are of moderately severe toxicity, causing relatively delayed respiratory failure and death. There was no apparent response to oxime therapy. The lack of correlation between red cell AChE activity and clinical features suggests that this parameter may not always be a useful marker of synaptic AChE activity and severity after OP pesticide poisoning.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jeyaratnam, J" uniqKey="Jeyaratnam J">J Jeyaratnam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gunnell, D" uniqKey="Gunnell D">D Gunnell</name></author><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Phillips, Mr" uniqKey="Phillips M">MR Phillips</name></author><author><name sortKey="Konradsen, F" uniqKey="Konradsen F">F Konradsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Mohamed, F" uniqKey="Mohamed F">F Mohamed</name></author><author><name sortKey="Senarathna, L" uniqKey="Senarathna L">L Senarathna</name></author><author><name sortKey="Von Meyer, L" uniqKey="Von Meyer L">L von Meyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Backer, M" uniqKey="Backer M">M Backer</name></author><author><name sortKey="Thiermann, H" uniqKey="Thiermann H">H Thiermann</name></author><author><name sortKey="Szinicz, L" uniqKey="Szinicz L">L Szinicz</name></author><author><name sortKey="Mast, U" uniqKey="Mast U">U Mast</name></author><author><name sortKey="Klimmek, R" uniqKey="Klimmek R">R Klimmek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Thiermann, H" uniqKey="Thiermann H">H Thiermann</name></author><author><name sortKey="Szinicz, L" uniqKey="Szinicz L">L Szinicz</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roberts, Dm" uniqKey="Roberts D">DM Roberts</name></author><author><name sortKey="Seneviratne, R" uniqKey="Seneviratne R">R Seneviratne</name></author><author><name sortKey="Mohamed, F" uniqKey="Mohamed F">F Mohamed</name></author><author><name sortKey="Patel, R" uniqKey="Patel R">R Patel</name></author><author><name sortKey="Abeysinghe, M" uniqKey="Abeysinghe M">M Abeysinghe</name></author><author><name sortKey="Hittarage, A" uniqKey="Hittarage A">A Hittarage</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Juszczak, E" uniqKey="Juszczak E">E Juszczak</name></author><author><name sortKey="Buckley, Na" uniqKey="Buckley N">NA Buckley</name></author><author><name sortKey="Senarathna, L" uniqKey="Senarathna L">L Senarathna</name></author><author><name sortKey="Mohamed, F" uniqKey="Mohamed F">F Mohamed</name></author><author><name sortKey="Dissanayake, W" uniqKey="Dissanayake W">W Dissanayake</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Juszczak, E" uniqKey="Juszczak E">E Juszczak</name></author><author><name sortKey="Alder, N" uniqKey="Alder N">N Alder</name></author><author><name sortKey="Mohamed, F" uniqKey="Mohamed F">F Mohamed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Dawson, A" uniqKey="Dawson A">A Dawson</name></author><author><name sortKey="Karalliedde, L" uniqKey="Karalliedde L">L Karalliedde</name></author><author><name sortKey="Dissanayake, W" uniqKey="Dissanayake W">W Dissanayake</name></author><author><name sortKey="Hittarage, A" uniqKey="Hittarage A">A Hittarage</name></author><author><name sortKey="Azher, S" uniqKey="Azher S">S Azher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Persson, He" uniqKey="Persson H">HE Persson</name></author><author><name sortKey="Sjoberg, Gk" uniqKey="Sjoberg G">GK Sjoberg</name></author><author><name sortKey="Haines, Ja" uniqKey="Haines J">JA Haines</name></author><author><name sortKey="Pronczuk De Garbino, J" uniqKey="Pronczuk De Garbino J">J Pronczuk de Garbino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davies, Joj" uniqKey="Davies J">JOJ Davies</name></author><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Buckley, Na" uniqKey="Buckley N">NA Buckley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Mast, U" uniqKey="Mast U">U Mast</name></author><author><name sortKey="Kiderlen, D" uniqKey="Kiderlen D">D Kiderlen</name></author><author><name sortKey="Diepold, C" uniqKey="Diepold C">C Diepold</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Sheriff, Mhr" uniqKey="Sheriff M">MHR Sheriff</name></author><author><name sortKey="Buckley, Na" uniqKey="Buckley N">NA Buckley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Buckley, Na" uniqKey="Buckley N">NA Buckley</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Dawson, Ah" uniqKey="Dawson A">AH Dawson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Mk" uniqKey="Johnson M">MK Johnson</name></author><author><name sortKey="Jacobsen, D" uniqKey="Jacobsen D">D Jacobsen</name></author><author><name sortKey="Meredith, Tj" uniqKey="Meredith T">TJ Meredith</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Heath, Ajw" uniqKey="Heath A">AJW Heath</name></author><author><name sortKey="Ligtenstein, Da" uniqKey="Ligtenstein D">DA Ligtenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Srinivas Rao, Ch" uniqKey="Srinivas Rao C">CH Srinivas Rao</name></author><author><name sortKey="Venkateswarlu, V" uniqKey="Venkateswarlu V">V Venkateswarlu</name></author><author><name sortKey="Surender, T" uniqKey="Surender T">T Surender</name></author><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Buckley, Na" uniqKey="Buckley N">NA Buckley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author><author><name sortKey="Mohamed, F" uniqKey="Mohamed F">F Mohamed</name></author><author><name sortKey="Davies, Joj" uniqKey="Davies J">JOJ Davies</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Sheriff, Mhr" uniqKey="Sheriff M">MHR Sheriff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdaniel, Kl" uniqKey="Mcdaniel K">KL McDaniel</name></author><author><name sortKey="Moser, Vc" uniqKey="Moser V">VC Moser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knaak, Jb" uniqKey="Knaak J">JB Knaak</name></author><author><name sortKey="Dary, Cc" uniqKey="Dary C">CC Dary</name></author><author><name sortKey="Power, F" uniqKey="Power F">F Power</name></author><author><name sortKey="Thompson, Cb" uniqKey="Thompson C">CB Thompson</name></author><author><name sortKey="Blancato, Jn" uniqKey="Blancato J">JN Blancato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glickman, Ah" uniqKey="Glickman A">AH Glickman</name></author><author><name sortKey="Wing, Kd" uniqKey="Wing K">KD Wing</name></author><author><name sortKey="Casida, Je" uniqKey="Casida J">JE Casida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leader, H" uniqKey="Leader H">H Leader</name></author><author><name sortKey="Casida, Je" uniqKey="Casida J">JE Casida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wing, Kd" uniqKey="Wing K">KD Wing</name></author><author><name sortKey="Glickman, Ah" uniqKey="Glickman A">AH Glickman</name></author><author><name sortKey="Casida, Je" uniqKey="Casida J">JE Casida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Segall, Y" uniqKey="Segall Y">Y Segall</name></author><author><name sortKey="Casida, Je" uniqKey="Casida J">JE Casida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wing, Kd" uniqKey="Wing K">KD Wing</name></author><author><name sortKey="Glickman, Ah" uniqKey="Glickman A">AH Glickman</name></author><author><name sortKey="Casida, Je" uniqKey="Casida J">JE Casida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thiermann, H" uniqKey="Thiermann H">H Thiermann</name></author><author><name sortKey="Szinicz, L" uniqKey="Szinicz L">L Szinicz</name></author><author><name sortKey="Eyer, F" uniqKey="Eyer F">F Eyer</name></author><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Felgenhauer, N" uniqKey="Felgenhauer N">N Felgenhauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thiermann, H" uniqKey="Thiermann H">H Thiermann</name></author><author><name sortKey="Szinicz, L" uniqKey="Szinicz L">L Szinicz</name></author><author><name sortKey="Eyer, P" uniqKey="Eyer P">P Eyer</name></author><author><name sortKey="Zilker, T" uniqKey="Zilker T">T Zilker</name></author><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thiermann, H" uniqKey="Thiermann H">H Thiermann</name></author><author><name sortKey="Worek, F" uniqKey="Worek F">F Worek</name></author><author><name sortKey="Szinicz, L" uniqKey="Szinicz L">L Szinicz</name></author><author><name sortKey="Haberkorn, M" uniqKey="Haberkorn M">M Haberkorn</name></author><author><name sortKey="Eyer, F" uniqKey="Eyer F">F Eyer</name></author><author><name sortKey="Felgenhauer, N" uniqKey="Felgenhauer N">N Felgenhauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gotoh, M" uniqKey="Gotoh M">M Gotoh</name></author><author><name sortKey="Sakata, M" uniqKey="Sakata M">M Sakata</name></author><author><name sortKey="Endo, T" uniqKey="Endo T">T Endo</name></author><author><name sortKey="Hayashi, H" uniqKey="Hayashi H">H Hayashi</name></author><author><name sortKey="Seno, H" uniqKey="Seno H">H Seno</name></author><author><name sortKey="Suzuki, O" uniqKey="Suzuki O">O Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seno, H" uniqKey="Seno H">H Seno</name></author><author><name sortKey="Hattori, H" uniqKey="Hattori H">H Hattori</name></author><author><name sortKey="Kumazawa, T" uniqKey="Kumazawa T">T Kumazawa</name></author><author><name sortKey="Ishii, A" uniqKey="Ishii A">A Ishii</name></author><author><name sortKey="Watanabe, K" uniqKey="Watanabe K">K Watanabe</name></author><author><name sortKey="Suzuki, O" uniqKey="Suzuki O">O Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miyazaki, T" uniqKey="Miyazaki T">T Miyazaki</name></author><author><name sortKey="Yashiki, M" uniqKey="Yashiki M">M Yashiki</name></author><author><name sortKey="Chikasue, F" uniqKey="Chikasue F">F Chikasue</name></author><author><name sortKey="Kojima, T" uniqKey="Kojima T">T Kojima</name></author><author><name sortKey="Hibino, H" uniqKey="Hibino H">H Hibino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sakata, M" uniqKey="Sakata M">M Sakata</name></author><author><name sortKey="Gotoh, M" uniqKey="Gotoh M">M Gotoh</name></author><author><name sortKey="Ubukata, K" uniqKey="Ubukata K">K Ubukata</name></author><author><name sortKey="Hayashi, H" uniqKey="Hayashi H">H Hayashi</name></author><author><name sortKey="Kotaki, M" uniqKey="Kotaki M">M Kotaki</name></author><author><name sortKey="Omote, T" uniqKey="Omote T">T Omote</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paudyal, Bp" uniqKey="Paudyal B">BP Paudyal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Tj" uniqKey="Lin T">TJ Lin</name></author><author><name sortKey="Walter, Fg" uniqKey="Walter F">FG Walter</name></author><author><name sortKey="Hung, Dz" uniqKey="Hung D">DZ Hung</name></author><author><name sortKey="Tsai, Jl" uniqKey="Tsai J">JL Tsai</name></author><author><name sortKey="Hu, Sc" uniqKey="Hu S">SC Hu</name></author><author><name sortKey="Chang, Js" uniqKey="Chang J">JS Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Inoue, S" uniqKey="Inoue S">S Inoue</name></author><author><name sortKey="Saito, T" uniqKey="Saito T">T Saito</name></author><author><name sortKey="Mase, H" uniqKey="Mase H">H Mase</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y Suzuki</name></author><author><name sortKey="Takazawa, K" uniqKey="Takazawa K">K Takazawa</name></author><author><name sortKey="Yamamoto, I" uniqKey="Yamamoto I">I Yamamoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, T" uniqKey="Tanaka T">T Tanaka</name></author><author><name sortKey="Tanaka, N" uniqKey="Tanaka N">N Tanaka</name></author><author><name sortKey="Kita, T" uniqKey="Kita T">T Kita</name></author><author><name sortKey="Kasai, K" uniqKey="Kasai K">K Kasai</name></author><author><name sortKey="Sato, H" uniqKey="Sato H">H Sato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roberts, Dm" uniqKey="Roberts D">DM Roberts</name></author><author><name sortKey="Karunarathna, A" uniqKey="Karunarathna A">A Karunarathna</name></author><author><name sortKey="Buckley, Na" uniqKey="Buckley N">NA Buckley</name></author><author><name sortKey="Manuweera, G" uniqKey="Manuweera G">G Manuweera</name></author><author><name sortKey="Sheriff, Mhr" uniqKey="Sheriff M">MHR Sheriff</name></author><author><name sortKey="Eddleston, M" uniqKey="Eddleston M">M Eddleston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zheng, Ry" uniqKey="Zheng R">RY Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Sy" uniqKey="Chen S">SY Chen</name></author><author><name sortKey="Wang, Hf" uniqKey="Wang H">HF Wang</name></author><author><name sortKey="Yin, Y" uniqKey="Yin Y">Y Yin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wan, Wg" uniqKey="Wan W">WG Wan</name></author><author><name sortKey="Zheng, Sc" uniqKey="Zheng S">SC Zheng</name></author><author><name sortKey="Zou, Hj" uniqKey="Zou H">HJ Zou</name></author><author><name sortKey="Ma, Sd" uniqKey="Ma S">SD Ma</name></author><author><name sortKey="Tao, Gz" uniqKey="Tao G">GZ Tao</name></author><author><name sortKey="Xu, Zf" uniqKey="Xu Z">ZF Xu</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">QJM</journal-id><journal-id journal-id-type="publisher-id">qjmedj</journal-id><journal-id journal-id-type="hwp">qjmed</journal-id><journal-title-group><journal-title>QJM: An International Journal of Medicine</journal-title></journal-title-group><issn pub-type="ppub">1460-2725</issn><issn pub-type="epub">1460-2393</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19737786</article-id><article-id pub-id-type="pmc">2766103</article-id><article-id pub-id-type="doi">10.1093/qjmed/hcp119</article-id><article-id pub-id-type="publisher-id">hcp119</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original papers</subject></subj-group></article-categories><title-group><article-title>Poisoning with the <italic>S</italic>-Alkyl organophosphorus insecticides profenofos and prothiofos</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Eddleston</surname><given-names>M.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF1"><sup>2</sup></xref><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Worek</surname><given-names>F.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Eyer</surname><given-names>P.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref><xref ref-type="aff" rid="AFF1"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Thiermann</surname><given-names>H.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Von Meyer</surname><given-names>L.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jeganathan</surname><given-names>K.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sheriff</surname><given-names>M. H. R.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref><xref ref-type="aff" rid="AFF1"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dawson</surname><given-names>A. H.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref><xref ref-type="aff" rid="AFF1"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Buckley</surname><given-names>N. A.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref><xref ref-type="aff" rid="AFF1"><sup>10</sup></xref></contrib></contrib-group><aff id="AFF1">From the<sup>1</sup>National Poisons Information Service – Edinburgh, Royal Infirmary of Edinburgh,<sup>2</sup>Clinical Pharmacology Unit, University of Edinburgh, UK,<sup>3</sup>South Asian Clinical Toxicology Research Collaboration, Sri Lanka,<sup>4</sup>Bundeswehr Institute of Pharmacology and Toxicology,<sup>5</sup>Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilians University, Munich, Germany,<sup>6</sup>Department of Legal Medicine, Ludwig Maximilians University, Munich, Germany,<sup>7</sup>Anuradhapura General Hospital, Anuradhapura,<sup>8</sup>Depatment of Clinical Medicine, University of Colombo, Sri Lanka,<sup>9</sup>School of Public Health, University of Newcastle and<sup>10</sup>Department of Medicine, University of New South Wales, Sydney, Australia</aff><author-notes><corresp>Address correspondence to M. Eddleston, CPU, QMRI E3.15, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. email: <email>eddlestonm@yahoo.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>8</day><month>9</month><year>2009</year></pub-date><pub-date pub-type="pmc-release"><day>8</day><month>9</month><year>2009</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>102</volume><issue>11</issue><fpage>785</fpage><lpage>792</lpage><history><date date-type="received"><day>5</day><month>4</month><year>2009</year></date><date date-type="rev-recd"><day>31</day><month>7</month><year>2009</year></date></history><permissions><copyright-statement>© The Author(s) 2009. Published by Oxford University Press.</copyright-statement><copyright-year>2009</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.5/uk/"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/2.5/uk/">http://creativecommons.org/licenses/by-nc/2.5/uk/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p><bold>Background:</bold> Many organophosphorus (OP) insecticides have either two <italic>O</italic>-methyl or two <italic>O</italic>-ethyl groups attached to the phosphorus atom. This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. However, several OP insecticides are atypical and do not have these structures.</p><p><bold>Aim:</bold> We aimed to describe the clinical course and responsiveness to therapy of people poisoned with two <italic>S</italic>-alkyl OP insecticides—profenofos and prothiofos.</p><p><bold>Design:</bold> We set up a prospective cohort of patients with acute profenofos or prothiofos self-poisoning admitted to acute medical wards in two Sri Lankan district hospitals. Clinical observation was carried out throughout their inpatient stay; blood samples were taken in a subgroup for assay of cholinesterases and insecticide.</p><p><bold>Results:</bold> Ninety-five patients poisoned with profenofos and 12 with prothiofos were recruited over 5 years. Median time to admission was 4 (IQR 3–7) h. Eleven patients poisoned with profenofos died (11/95; 11.6%, 95% CI 5.9–20); one prothiofos patient died (1/12; 8.3%, 95% CI 0.2–38). Thirteen patients poisoned with profenofos required intubation for respiratory failure (13/95; 13.7%, 95% CI 7.5–22); two prothiofos-poisoned patients required intubation. Both intubations and death occurred late compared with other OP insecticides. Prolonged ventilation was needed in those who survived—a median of 310 (IQR 154–349) h. Unexpectedly, red cell AChE activity on admission did not correlate with clinical severity—all patients had severe AChE inhibition (about 1% of normal) but most had only mild cholinergic features, were conscious, and did not require ventilatory support.</p><p><bold>Conclusions:</bold> Compared with other commonly used OP insecticides, profenofos and prothiofos are of moderately severe toxicity, causing relatively delayed respiratory failure and death. There was no apparent response to oxime therapy. The lack of correlation between red cell AChE activity and clinical features suggests that this parameter may not always be a useful marker of synaptic AChE activity and severity after OP pesticide poisoning.</p></abstract></article-meta></front><body><sec sec-type="intro"><title>Introduction</title><p>Pesticide self-poisoning is a major global health problem, killing 250–350 000 people each year.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> Organophosphorus (OP) insecticide poisoning is a particularly severe problem, accounting for around 2/3 of deaths.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref></p><p>The majority of OP insecticides can be grouped according to their chemical structure as a diethoxy OP [with two O–C<sub>2</sub>H<sub>5</sub> groups attached to the phosphorus that binds to and inhibits acetylcholinesterase (AChE)] or a dimethoxy OP (with two O–CH<sub>3</sub> groups) (see <xref ref-type="fig" rid="F2">Figure 2</xref> of Eddleston <italic>et al.</italic><xref ref-type="bibr" rid="B4"><sup>4</sup></xref>). The identity of these alkyl groups has fundamental effects on the pharmacodynamics of poisoning and treatment, determining to a large extent whether oximes effectively reactivate OP-inhibited AChE.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup><fig id="F1" position="float"><label>Figure 1.</label><caption><p>Characteristics and structure of (<bold>A</bold>) profenofos and (<bold>B</bold>) prothiofos.</p></caption><graphic xlink:href="hcp119f1"></graphic></fig><fig id="F2" position="float"><label>Figure 2.</label><caption><p><bold>(A</bold>) Timing of intubation; (<bold>B</bold>) duration of ventilation and (<bold>C</bold>) timing of death post-ingestion in profenofos and prothiofos poisoned patients. For 2C, patients were separated according to whether they were intubated (circles) or not (squares) before death.</p></caption><graphic xlink:href="hcp119f2"></graphic></fig></p><p>However, a few OP insecticides do not fit into these categories, including profenofos and prothiofos (<xref ref-type="fig" rid="F1">Figure 1</xref>). Both are highly lipid soluble, moderately toxic OP insecticides. Of note, they have an <italic>S</italic>-alkyl (S–C<sub>3</sub>H<sub>7</sub>) group attached to the phosphorus, in addition to the more typical O–C<sub>2</sub>H<sub>5</sub> group. Although <italic>in vitro</italic> studies with human red cells have been done,<sup><xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> the consequences of this different structure on AChE inhibition and reactivation with oximes <italic>in vivo</italic> are unknown. We therefore prospectively studied patients with a history of <italic>S</italic>-alkyl OP poisoning to better understand its clinical course. Cholinesterase inhibition and re-activation with pralidoxime was studied in a subgroup of profenofos poisoned patients.</p></sec><sec sec-type="materials|methods"><title>Materials and Methods</title><sec sec-type="subjects"><title>Patients</title><p>Study patients were consecutive patients admitted to two Sri Lankan hospitals with a history of acute poisoning with profenofos 50% emulsifiable concentrate (EC50) or prothiofos EC50, as indicated by the patient or relatives, the transferring doctor or the pesticide bottle. We have previously noted the ingestion history to be highly accurate.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup> They formed part of a cohort from which patients were recruited to RCTs of routine activated charcoal administration (ISRCTN02920054) and high-dose pralidoxime (ISRCTN-55264358) that showed no effect.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup> Ethics approval was obtained from the Oxfordshire Clinical Research Ethics Committee and Faculty of Medicine Ethics Committee, Colombo.</p><p>Patients were treated using a standard protocol that has been described earlier.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup> They were resuscitated with fluids and atropine to raise the systolic blood pressure above 80 mmHg, the heart rate above 80 b.p.m. and clear the lungs of audible secretions and wheeze. Symptomatic patients who required atropine initially received pralidoxime chloride 1g q6h for 1–3 days. From May 2004, symptomatic patients requiring atropine were eligible for an RCT of high-dose pralidoxime chloride (2 g loading dose over 20 min followed by 0.5 g/h for up to 7 days, or until atropine had not been required for 12–24 h) vs. saline placebo. Three profenofos poisoned patients were recruited; symptomatic patients not recruited to the trial received pralidoxime chloride 1g q6h for 1–3 days.</p><p>Patients remained under the care of the consultant physicians. Management protocols were agreed between the ward doctors and study team. Decisions about intubation and transfer of patients to intensive care were made by the medical team independently of the study doctors. All decisions were made on the basis of the patient's clinical condition and not the particular OP ingested.</p><p>All patients were seen regularly by full time study doctors at least every 3 h and more according to clinical need. Significant events (intubation, seizures and death) were recorded at the time of the event. Patients were also seen on a study ward round twice each day and their condition over the previous 12 h were recorded. We did not produce a Poison Severity Score<xref ref-type="bibr" rid="B12"><sup>12</sup></xref> routinely for patients; in a previous study, we noted that the Glasgow Coma Score (GCS) was as good as the Poison Severity Score in predicting outcome.<xref ref-type="bibr" rid="B13"><sup>13</sup></xref></p><p>Patients were first managed on the medical ward. Seriously ill patients, as judged by the ward's medical staff on basis of GCS and cardiorespiratory function, were transferred to the intensive care unit (ICU) as beds became available. Each hospital had 2–8 ICU beds for medical patients; there was always difficulty in obtaining a bed. This article describes all patients with <italic>S</italic>-alkyl poisoning, whether they were admitted to ICU or not.</p><p>Criteria for intubation were tidal volume <180 ml/breath using a Wright's respirometer, respiratory rate <10 breaths/min or failure of a Guedel airway to preserve airway patency. Arterial blood gases were not available to guide therapy; pulse oximetry was sometimes available. Hypotensive patients, not responding to atropine and fluid resuscitation, were treated with high doses of dopamine plus dobutamine as necessary by infusion pump. Norepinephrine and epinephrine infusions were not used; bolus epinephrine was administered for cardiac arrest.</p></sec><sec><title>Toxicological analysis</title><p>Blood samples were taken on admission, and at regular intervals thereafter, from patients recruited to the pralidoxime RCT and from patients admitted during two periods (9 May–10 July 2002 and 2–26 December 2002). Lab assay capacity limited the sample number that could be handled and determined the short period of sampling.</p><p>For red cell AChE measurement, 0.2 ml of EDTA blood was diluted at the bedside into 4 ml of cooled saline and rapidly frozen to –20°C. Red cell AChE activity is usually 600–700 mU/µmol Hb; a small study of Caucasians reported a mean of 651 ± 18 mU/µmol Hb.<xref ref-type="bibr" rid="B14"><sup>14</sup></xref> We selected a value of 600 mU/µmol Hb to be the lower limit of normal for this study. Plasma was then separated from a second EDTA blood sample and frozen at –20°C. All analyses were done in Munich. AChE activity was assayed according to a modified Ellman method, using ethopropazine to inhibit butyrylcholinesterase (BuChE) activity.<xref ref-type="bibr" rid="B14"><sup>14</sup></xref> Re-activatability of AChE (ageing) and BuChE were assessed as described.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup> A median BuChE value of 6000 mU/ml was taken as normal for this study.<xref ref-type="bibr" rid="B15"><sup>15</sup></xref> Profenofos was quantified in plasma by gas chromatography with a lower limit of quantitation of 0.05 nmol/ml plasma.</p></sec><sec><title>Statistics</title><p>Data analysis was performed in Prism v4. Clinical characteristics were summarized using counts (percentages) for categorical variables and the median [interquartile range (IQR)] for non-normally distributed continuous variables.</p></sec></sec><sec sec-type="results"><title>Results</title><p>Between 31 March 2002 and 26 March 2007, 14 034 patients with acute poisoning were prospectively reviewed on admission to Anuradhapura and Polonnaruwa General Hospitals, Sri Lanka. One hundred and seven had ingested an <italic>S</italic>-alkyl OP insecticide—95 profenofos and 12 prothiofos.</p><p>The median age of the patients was 32 years (IQR 24–45); 82 (76.6%) were male. They presented a median of 4 h (IQR 3–7) post-ingestion. Fifty-seven (53.3%) had previously received atropine; of these patients 11 (10.3% of all patients) had received pralidoxime chloride in the transferring hospital. On admission to the secondary hospital, around one-third (37/107; 34.6%) were symptomatic, requiring atropine for cholinergic features. However, very few were severely poisoned with reduced consciousness<xref ref-type="bibr" rid="B13"><sup>13</sup></xref>—median GCS was high (15/15; IQR 15–15) with only 8/107 having a GCS <9.</p><sec><title>Mortality and respiratory failure</title><p>Eleven patients poisoned with profenofos died (11/95; 11.6%, 95% CI 5.9–20); one prothiofos patient died (1/12; 8.3%, 95% CI 0.2–38). Deaths from profenofos poisoning occurred in a median of 29 (IQR 17–113) h post-ingestion (<xref ref-type="fig" rid="F2">Figure 2</xref>C); none occurred within 11 h of ingestion. The death from prothiofos occurred 67 h post-ingestion.</p><p>Thirteen patients poisoned with profenofos required intubation for a low tidal volume (<180 ml/breath), bradypnoea, or failure of a Guedel airway to preserve airway patency (13/95; 13.7%, 95% CI 7.5–22). Two prothiofos-poisoned patients required intubation (2/12; 16.7% 95% CI 2.1–48). Intubation for profenofos poisoning occurred in a median of 9.2 (IQR 5.2–26) h post-ingestion (<xref ref-type="fig" rid="F2">Figure 2</xref>A). Seven intubated patients with profenofos poisoning (7/13, 53.8%) survived. The two intubations for prothiofos poisoning occurred 11 and 30 h post-ingestion; one intubated patient survived. Of the seven profenofos-poisoned patients who survived, median duration of ventilation was 320 h (IQR 140–353) (<xref ref-type="fig" rid="F2">Figure 2</xref>B). The intubated patient with prothiofos poisoning who survived was intubated for 300 h.</p></sec><sec><title>Cholinesterase inhibition and reactivation</title><p>Cholinesterases were assayed in 10 patients with profenofos poisoning (<xref ref-type="fig" rid="F3">Figure 3</xref>). Proof of profenofos exposure was sought and found in five patients. Median plasma concentration in admission samples was 3.35 (range 0.67– 7.31) μmol/l.
<fig id="F3" position="float"><label>Figure 3.</label><caption><p>Cholinesterase inhibition in 10 profenofos patients. Inhibition of both cholinesterases was nearly complete on admission; there was no response to loading doses of 1–2 g of pralidoxime chloride. Three patients subsequently died. <bold>(A)</bold> <italic>In vivo</italic> AChE activity; (<bold>B)</bold> <italic>Ex vivo</italic> AChE activity showing non-aged AChE; (<bold>C</bold>) BuChE activity; (<bold>D</bold>) AChE inhibitory activity in plasma, indicating presence of active OP. Few samples were available after 72 h. Mean ± SD.</p></caption><graphic xlink:href="hcp119f3"></graphic></fig></p><p>Red cell AChE was almost completely inhibited on admission, with a median activity of 7 (IQR 1–30) mU/µmol Hb—approximately 1% of normal activity (<xref ref-type="fig" rid="F3">Figure 3</xref>A). Remarkably, unlike dimethoxy and diethoxy OP poisoning,<xref ref-type="bibr" rid="B16"><sup>16</sup></xref> there was no re-activation of red cell AChE [median activity at baseline: 25 (IQR 3.5–81) mU/µmol Hb; median activity at 1-h post-pralidoxime: 19 (IQR 8–33) mU/µmol Hb] in the four patients who received 1–2 g loading dose of pralidoxime.</p><p>This lack of response to oximes suggested that nearly all the inhibited red cell AChE was already aged on admission. <italic>In vitro</italic> assays with very high doses of obidoxime<xref ref-type="bibr" rid="B14"><sup>14</sup></xref> confirmed that the enzyme was aged: median non-aged red cell AChE at baseline was 25 (IQR 9–100) mU/µmol Hb (<xref ref-type="fig" rid="F3">Figure 3</xref>B), indicating that > 95% of red cell AChE was aged.</p><p>BuChE was similarly completely inhibited on admission. Median plasma BuChE on admission in the 10 patients was 33 (IQR 9–73) mU/ml, <1% of estimated normal activity. It started to rise after 2–3 days as inhibitory activity in plasma faded (<xref ref-type="fig" rid="F3">Figure 3</xref>).</p><p>Despite such severe red cell AChE inhibition, these patients were very well on admission. Only two of the 10 had a GCS score less than 15/15 on admission; two patients had no symptoms of poisoning after receiving bolus doses of atropine in the transferring hospital. This is surprising considering the generally held view that red cell AChE activity is a good marker of neuromuscular function in OP poisoning.<xref ref-type="bibr" rid="B17"><sup>17</sup></xref></p></sec></sec><sec sec-type="discussion"><title>Discussion</title><p>This study shows that the <italic>S</italic>-alkyl OP insecticides profenofos and prothiofos are likely to be of moderately severe toxicity as emulsifiable concentrates, lying between high toxicity OPs such as dimethoate and monocrotophos and lower toxicity OPs such as chlorpyrifos.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B18">18</xref></sup> However, most importantly and unexpectedly, many patients were well on admission and none required immediate intubation, despite (in profenofos poisoned patients) almost complete inhibition of red cell AChE activity. Few subsequently required intubation, and both intubation and death occurred late compared with other OPs.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> This is very different to chlorpyrifos and quinalphos poisoning in which red cell AChE is also severely inhibited on admission,<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup> but the majority of intubations occur at this time.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref></p><p>The reason for this remarkable discordance between red cell AChE activity and clinical picture on presentation in profenofos poisoning is unclear. Clinical presentation results from AChE inhibition in tissues other than the blood, particularly the neuromuscular junction and CNS. It is possible that profenofos does not penetrate the CNS. One rat study has reported that severe blood cholinesterase inhibition was associated with only mild CNS AChE inhibition after profenofos poisoning.<xref ref-type="bibr" rid="B20"><sup>20</sup></xref> However, blood cholinesterase activity reported for control animals in this article was very low, suggesting methodological problems. The high partition coefficient for the OPs (<xref ref-type="fig" rid="F1">Figure 1</xref>) should not preclude them from penetrating the CNS.<xref ref-type="bibr" rid="B21"><sup>21</sup></xref> Furthermore, the clinical severity of profenofos poisoning correlated with brain AChE activity in a study of chickens.<xref ref-type="bibr" rid="B22"><sup>22</sup></xref></p><p>Another explanation may relate to differential toxicity of the chiral profenofos enantiomers. <italic>In vitro</italic>, the (+)-profenofos enantiomer inhibits AChE 23-fold more potently than the (–)-enantiomer, while the (–)-enantiomer is 23-fold more potent <italic>in vivo</italic>.<xref ref-type="bibr" rid="B23"><sup>23</sup></xref> The reason for this dichotomy was attributed to stereo-specific metabolism <italic>in vivo</italic> with preferential oxidative activation of the (–)-enantiomer to a more potent inhibitor of AChE than the non-activated (+)-enantiomer.<xref ref-type="bibr" rid="B24"><sup>24</sup></xref> This putative active metabolite has been tentatively assigned a phosphorothiolate <italic>S</italic>-oxide structure (R–S(O)–P(O)–).<xref ref-type="bibr" rid="B25"><sup>25</sup></xref> It has not been isolated because it rapidly converts to the phosphinyl-oxysulfenate (R–S–O–P(O)–), which is unlikely to be a phosphorylating agent.<sup><xref ref-type="bibr" rid="B24">24</xref>,<xref ref-type="bibr" rid="B25">25</xref></sup> Hence, the putative highly active <italic>S</italic>-oxide metabolite resembles a fast-acting ‘hit-and-run’ compound.</p><p>AChE inhibited by the (+)-profenofos enantiomer or (–)-phosphorothiolate <italic>S</italic>-oxide shows very different post-inhibitory reactions. While the former yields an enzyme that undergoes rapid spontaneous and oxime-induced reactivation, AChE inhibited by the latter ages rapidly and is refractory to re-activation.<sup><xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> If these rapid reactions occur in the blood under physiological conditions, we hypothesize that the (–)-profenofos <italic>S</italic>-oxide is used up in venous blood and does not appear in arterial blood. Consequently, neuronal AChE inhibition will result from the action of the (+)-enantiomer of profenofos. This compound, although a potent AChE inhibitor, shows rather rapid spontaneous re-activation that is similar to dimethoxyphosphoryl–AChE. Hence, inhibition of AChE will gradually fade and residual AChE-activity may remain at a level that does not cause severe poisoning.</p><p>This hypothesis may explain the presence of almost completely inhibited and aged red cell AChE in patients with mild cholinergic toxicity soon after profenofos ingestion. It also suggests that oximes may be clinically useful despite complete red cell AChE ageing. However, experimental proof is required to test this hypothesis. This should be possible by measuring profenofos enantiomers in matched venous and arterial blood samples from profenofos poisoned animals or humans, and measuring the neuromuscular function and the response to oximes.</p><p>Of note, our findings indicate that red cell AChE activity may not always be an accurate marker of synaptic function or OP poisoning severity, as we and others have proposed previously.<sup><xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup> The evidence for the usefulness of red cell AChE as a marker in OP pesticide poisoning is limited. An unpublished retrospective study in 16 patients demonstrated that red cell AChE correlated with plasma atropine concentration and presumably AChE activity in muscarinic synapses.<xref ref-type="bibr" rid="B29"><sup>29</sup></xref> A neurophysiological study in 34 patients showed that it correlated with patterns of neuromuscular transmission.<xref ref-type="bibr" rid="B28"><sup>28</sup></xref> Both studies included patients taking a variety of diethoxy and dimethoxy OPs. There is a lack of studies reporting a useful correlation between red cell AChE and clinical severity.</p><p>Neither profenofos nor prothiofos poisoning appears to be a major clinical problem. There are just four case reports, all fatal, in the literature.<xref ref-type="bibr" rid="B30 B31 B32 B33"><sup>30–33</sup></xref> Three other papers have reported cases in India,<xref ref-type="bibr" rid="B18"><sup>18</sup></xref> Nepal<xref ref-type="bibr" rid="B34"><sup>34</sup></xref> and Taiwan.<xref ref-type="bibr" rid="B35"><sup>35</sup></xref> This case series is by far the biggest published to date. Acephate (CAS 30560-19-1) and methamidophos (CAS 10265-92-6) are the two other <italic>S</italic>-alkyl OPs, the latter a metabolite of the former. Whilst acephate poisoning appears to be uncommon, with relatively few case reports,<sup><xref ref-type="bibr" rid="B18">18</xref>,<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B37">37</xref></sup> methamidophos is highly toxic and has killed many people in Sri Lanka,<xref ref-type="bibr" rid="B38"><sup>38</sup></xref> Taiwan<xref ref-type="bibr" rid="B35"><sup>35</sup></xref> and China.<xref ref-type="bibr" rid="B39 B40 B41"><sup>39–41</sup></xref> Although <italic>in vitro</italic> studies have been done,<sup><xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B24">24</xref></sup> no <italic>in vivo</italic> human data have been published about cholinesterase inhibition with these <italic>S</italic>-alkyl OPs.</p><p>Limitations of this article include the small number of prothiofos-poisoned patients, lack of AChE activity data for these patients, and the lack of facilities for close monitoring of patients that might have allowed better description of cause of death. In addition, the number of profenofos-poisoned patients recruited to the RCT and therefore having their blood cholinesterase and plasma OP measured was small. However, the very low AChE activity in this group was very consistent and there appears no reason to think that they are unrepresentative of the whole case series.</p></sec><sec sec-type="conclusions"><title>Conclusion</title><p>Self-poisoning with the <italic>S</italic>-alkyl OPs profenofos and prothiofos is moderately dangerous when compared with other OP pesticides. Most importantly, red cell AChE activity in profenofos-poisoned patients is not re-activated by pralidoxime and did not correlate with clinical severity, suggesting that this marker may not be generally valid for OP poisoning. It will be useful now to find ways of measuring CNS AChE activity, alongside neuromuscular and red cell AChE activity, in animal models of OP poisoning and human patients to determine the relative role of each enzyme.</p></sec><sec><title>Funding</title><p>Funded by Wellcome Trust (grant 063560 to M.E.); Wellcome Trust/National Health and Medical Research Council International Collaborative Research (071669 to SACTRC).</p><p><italic>Conflict of interest</italic>: None declared.</p></sec></body><back><ack><title>Acknowledgements</title><p>We thank the directors, consultant physicians, and medical and nursing staff of the study hospitals for their support; Renate Heilmair and Elisabeth Topoll for technical assistance, and the Oxford–Colombo Collaboration and SACTRC study doctors and coordinators for their immensely valuable work.</p></ack><ref-list><title>References</title><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jeyaratnam</surname><given-names>J</given-names></name></person-group><article-title>Acute pesticide poisoning: a major global health problem</article-title><source>World Health Stat Q</source><year>1990</year><volume>43</volume><fpage>139</fpage><lpage>44</lpage><pub-id pub-id-type="pmid">2238694</pub-id></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gunnell</surname><given-names>D</given-names></name><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Phillips</surname><given-names>MR</given-names></name><name><surname>Konradsen</surname><given-names>F</given-names></name></person-group><article-title>The global distribution of fatal pesticide self-poisoning: systematic review</article-title><source>BMC Public Health</source><year>2007</year><volume>7</volume><fpage>357</fpage><pub-id pub-id-type="pmid">18154668</pub-id></element-citation></ref><ref id="B3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name></person-group><article-title>Patterns and problems of deliberate self-poisoning in the developing world</article-title><source>Q J Med</source><year>2000</year><volume>93</volume><fpage>715</fpage><lpage>31</lpage></element-citation></ref><ref id="B4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Mohamed</surname><given-names>F</given-names></name><name><surname>Senarathna</surname><given-names>L</given-names></name><name><surname>von Meyer</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study</article-title><source>Lancet</source><year>2005</year><volume>366</volume><fpage>1452</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">16243090</pub-id></element-citation></ref><ref id="B5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eyer</surname><given-names>P</given-names></name></person-group><article-title>The role of oximes in the management of organophosphorus pesticide poisoning</article-title><source>Toxicol Rev</source><year>2003</year><volume>22</volume><fpage>165</fpage><lpage>90</lpage><pub-id pub-id-type="pmid">15181665</pub-id></element-citation></ref><ref id="B6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Backer</surname><given-names>M</given-names></name><name><surname>Thiermann</surname><given-names>H</given-names></name><name><surname>Szinicz</surname><given-names>L</given-names></name><name><surname>Mast</surname><given-names>U</given-names></name><name><surname>Klimmek</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning</article-title><source>Hum Exp Toxicol</source><year>1997</year><volume>16</volume><fpage>466</fpage><lpage>72</lpage><pub-id pub-id-type="pmid">9292287</pub-id></element-citation></ref><ref id="B7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Thiermann</surname><given-names>H</given-names></name><name><surname>Szinicz</surname><given-names>L</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name></person-group><article-title>Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes</article-title><source>Biochem Pharmacol</source><year>2004</year><volume>68</volume><fpage>2237</fpage><lpage>48</lpage><pub-id pub-id-type="pmid">15498514</pub-id></element-citation></ref><ref id="B8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roberts</surname><given-names>DM</given-names></name><name><surname>Seneviratne</surname><given-names>R</given-names></name><name><surname>Mohamed</surname><given-names>F</given-names></name><name><surname>Patel</surname><given-names>R</given-names></name><name><surname>Abeysinghe</surname><given-names>M</given-names></name><name><surname>Hittarage</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Deliberate self-poisoning with the chlorphenoxy herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA)</article-title><source>Ann Emerg Med</source><year>2005</year><volume>46</volume><fpage>275</fpage><lpage>84</lpage><pub-id pub-id-type="pmid">16126140</pub-id></element-citation></ref><ref id="B9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Juszczak</surname><given-names>E</given-names></name><name><surname>Buckley</surname><given-names>NA</given-names></name><name><surname>Senarathna</surname><given-names>L</given-names></name><name><surname>Mohamed</surname><given-names>F</given-names></name><name><surname>Dissanayake</surname><given-names>W</given-names></name><etal></etal></person-group><collab>for the Ox-Col Poisoning Study collaborators</collab><article-title>Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial</article-title><source>Lancet</source><year>2008</year><volume>371</volume><fpage>579</fpage><lpage>86</lpage><pub-id pub-id-type="pmid">18280328</pub-id></element-citation></ref><ref id="B10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Juszczak</surname><given-names>E</given-names></name><name><surname>Alder</surname><given-names>N</given-names></name><name><surname>Mohamed</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Pralidoxime in acute organophosphorus insecticide poisoning–a randomised controlled trial</article-title><source>PLoS Med</source><year>2009</year><volume>6</volume><fpage>e1000104</fpage><pub-id pub-id-type="pmid">19564902</pub-id></element-citation></ref><ref id="B11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Dawson</surname><given-names>A</given-names></name><name><surname>Karalliedde</surname><given-names>L</given-names></name><name><surname>Dissanayake</surname><given-names>W</given-names></name><name><surname>Hittarage</surname><given-names>A</given-names></name><name><surname>Azher</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Early management after self-poisoning with an organophosphorus or carbamate pesticide - a treatment protocol for junior doctors</article-title><source>Crit Care</source><year>2004</year><volume>8</volume><fpage>R391</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">15566582</pub-id></element-citation></ref><ref id="B12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Persson</surname><given-names>HE</given-names></name><name><surname>Sjoberg</surname><given-names>GK</given-names></name><name><surname>Haines</surname><given-names>JA</given-names></name><name><surname>Pronczuk de Garbino</surname><given-names>J</given-names></name></person-group><article-title>Poisoning severity score. Grade of acute poisoning</article-title><source>J Toxicol Clin Toxicol</source><year>1998</year><volume>36</volume><fpage>205</fpage><lpage>13</lpage><pub-id pub-id-type="pmid">9656975</pub-id></element-citation></ref><ref id="B13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Davies</surname><given-names>JOJ</given-names></name><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Buckley</surname><given-names>NA</given-names></name></person-group><article-title>Predicting outcome in organophosphorus poisoning with a poison severity score or Glasgow Coma Scale</article-title><source>Q J Med</source><year>2008</year><volume>101</volume><fpage>371</fpage><lpage>9</lpage></element-citation></ref><ref id="B14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Mast</surname><given-names>U</given-names></name><name><surname>Kiderlen</surname><given-names>D</given-names></name><name><surname>Diepold</surname><given-names>C</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name></person-group><article-title>Improved determination of acetylcholinesterase activity in human whole blood</article-title><source>Clin Chim Acta</source><year>1999</year><volume>288</volume><fpage>73</fpage><lpage>90</lpage><pub-id pub-id-type="pmid">10529460</pub-id></element-citation></ref><ref id="B15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Sheriff</surname><given-names>MHR</given-names></name><name><surname>Buckley</surname><given-names>NA</given-names></name></person-group><article-title>Predicting outcome using butyrylcholinesterase activity in organophosphorus pesticide self-poisoning</article-title><source>Q J Med</source><year>2008</year><volume>101</volume><fpage>467</fpage><lpage>74</lpage></element-citation></ref><ref id="B16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Buckley</surname><given-names>NA</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Dawson</surname><given-names>AH</given-names></name></person-group><article-title>Medical management of acute organophosphorus pesticide poisoning</article-title><source>Lancet</source><year>2008</year><volume>371</volume><fpage>597</fpage><lpage>607</lpage><pub-id pub-id-type="pmid">17706760</pub-id></element-citation></ref><ref id="B17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johnson</surname><given-names>MK</given-names></name><name><surname>Jacobsen</surname><given-names>D</given-names></name><name><surname>Meredith</surname><given-names>TJ</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Heath</surname><given-names>AJW</given-names></name><name><surname>Ligtenstein</surname><given-names>DA</given-names></name><etal></etal></person-group><article-title>Evaluation of antidotes for poisoning by organophosphorus pesticides</article-title><source>Emerg Med</source><year>2000</year><volume>12</volume><fpage>22</fpage><lpage>37</lpage></element-citation></ref><ref id="B18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Srinivas Rao</surname><given-names>CH</given-names></name><name><surname>Venkateswarlu</surname><given-names>V</given-names></name><name><surname>Surender</surname><given-names>T</given-names></name><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Buckley</surname><given-names>NA</given-names></name></person-group><article-title>Insecticide poisoning in south India - opportunities for prevention and improved medical management</article-title><source>Trop Med Int Health</source><year>2005</year><volume>10</volume><fpage>581</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">15941422</pub-id></element-citation></ref><ref id="B19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eddleston</surname><given-names>M</given-names></name><name><surname>Mohamed</surname><given-names>F</given-names></name><name><surname>Davies</surname><given-names>JOJ</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Sheriff</surname><given-names>MHR</given-names></name><etal></etal></person-group><article-title>Respiratory failure in acute organophosphorus pesticide self-poisoning</article-title><source>Q J Med</source><year>2006</year><volume>99</volume><fpage>513</fpage><lpage>22</lpage></element-citation></ref><ref id="B20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McDaniel</surname><given-names>KL</given-names></name><name><surname>Moser</surname><given-names>VC</given-names></name></person-group><article-title>Differential profiles of cholinesterase inhibition and neurobehavioral effects in rats exposed to fenamiphos or profenofos</article-title><source>Neurotoxicol Teratol</source><year>2004</year><volume>26</volume><fpage>407</fpage><lpage>15</lpage><pub-id pub-id-type="pmid">15113602</pub-id></element-citation></ref><ref id="B21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Knaak</surname><given-names>JB</given-names></name><name><surname>Dary</surname><given-names>CC</given-names></name><name><surname>Power</surname><given-names>F</given-names></name><name><surname>Thompson</surname><given-names>CB</given-names></name><name><surname>Blancato</surname><given-names>JN</given-names></name></person-group><article-title>Physicochemical and biological data for the development of predictive organophosphorus pesticide QSARs and PBPK/PD models for human risk assessment</article-title><source>Crit Rev Toxicol</source><year>2004</year><volume>34</volume><fpage>143</fpage><lpage>207</lpage><pub-id pub-id-type="pmid">15112752</pub-id></element-citation></ref><ref id="B22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Glickman</surname><given-names>AH</given-names></name><name><surname>Wing</surname><given-names>KD</given-names></name><name><surname>Casida</surname><given-names>JE</given-names></name></person-group><article-title>Profenofos insecticide bioactivation in relation to antidote action and the stereospecificity of acetylcholinesterase inhibition, reactivation, and aging</article-title><source>Toxicol Appl Pharmacol</source><year>1984</year><volume>73</volume><fpage>16</fpage><lpage>22</lpage><pub-id pub-id-type="pmid">6710513</pub-id></element-citation></ref><ref id="B23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Leader</surname><given-names>H</given-names></name><name><surname>Casida</surname><given-names>JE</given-names></name></person-group><article-title>Resolution and biological activity of the chiral isomers of O-(4-bromo-2-chlorophenyl)O-ethyl phosphorothioate (profenofos insecticide)</article-title><source>J Agric Food Chem</source><year>1982</year><volume>30</volume><fpage>546</fpage><lpage>51</lpage></element-citation></ref><ref id="B24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wing</surname><given-names>KD</given-names></name><name><surname>Glickman</surname><given-names>AH</given-names></name><name><surname>Casida</surname><given-names>JE</given-names></name></person-group><article-title>Oxidative bioactivation of S-alkyl phosphorothiolate pesticides: stereospecificity of profenofos insecticide activation</article-title><source>Science</source><year>1983</year><volume>219</volume><fpage>63</fpage><lpage>5</lpage><pub-id pub-id-type="pmid">6849116</pub-id></element-citation></ref><ref id="B25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Segall</surname><given-names>Y</given-names></name><name><surname>Casida</surname><given-names>JE</given-names></name></person-group><article-title>Oxidative phosphorothiolates to phosphinyloxysulfonates probably via phosphorothiolate S-oxides</article-title><source>Tetrahedron Lett</source><year>1982</year><volume>23</volume><fpage>139</fpage><lpage>42</lpage></element-citation></ref><ref id="B26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wing</surname><given-names>KD</given-names></name><name><surname>Glickman</surname><given-names>AH</given-names></name><name><surname>Casida</surname><given-names>JE</given-names></name></person-group><article-title>Phosphorothiolate pesticides and related compounds: oxidative bioactivation and aging of the inhibited acetylcholinesterase</article-title><source>Pestic Biochem Physiol</source><year>1984</year><volume>21</volume><fpage>22</fpage><lpage>30</lpage></element-citation></ref><ref id="B27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thiermann</surname><given-names>H</given-names></name><name><surname>Szinicz</surname><given-names>L</given-names></name><name><surname>Eyer</surname><given-names>F</given-names></name><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Felgenhauer</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Modern strategies in therapy of organophosphate poisoning</article-title><source>Toxicol Lett</source><year>1999</year><volume>107</volume><fpage>233</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">10414801</pub-id></element-citation></ref><ref id="B28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thiermann</surname><given-names>H</given-names></name><name><surname>Szinicz</surname><given-names>L</given-names></name><name><surname>Eyer</surname><given-names>P</given-names></name><name><surname>Zilker</surname><given-names>T</given-names></name><name><surname>Worek</surname><given-names>F</given-names></name></person-group><article-title>Correlation between red blood cell acetylcholinesterase activity and neuromuscular transmission in organophosphate poisoning</article-title><source>Chem Biol Interact</source><year>2005</year><volume>157-8</volume><fpage>345</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">16263103</pub-id></element-citation></ref><ref id="B29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thiermann</surname><given-names>H</given-names></name><name><surname>Worek</surname><given-names>F</given-names></name><name><surname>Szinicz</surname><given-names>L</given-names></name><name><surname>Haberkorn</surname><given-names>M</given-names></name><name><surname>Eyer</surname><given-names>F</given-names></name><name><surname>Felgenhauer</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>On the atropine demand in organophosphate poisoned patients</article-title><source>J Toxicol Clin Toxicol</source><year>2003</year><volume>41</volume><fpage>457</fpage></element-citation></ref><ref id="B30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gotoh</surname><given-names>M</given-names></name><name><surname>Sakata</surname><given-names>M</given-names></name><name><surname>Endo</surname><given-names>T</given-names></name><name><surname>Hayashi</surname><given-names>H</given-names></name><name><surname>Seno</surname><given-names>H</given-names></name><name><surname>Suzuki</surname><given-names>O</given-names></name></person-group><article-title>Profenofos metabolites in human poisoning</article-title><source>Forensic Sci Int</source><year>2001</year><volume>116</volume><fpage>221</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">11182275</pub-id></element-citation></ref><ref id="B31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seno</surname><given-names>H</given-names></name><name><surname>Hattori</surname><given-names>H</given-names></name><name><surname>Kumazawa</surname><given-names>T</given-names></name><name><surname>Ishii</surname><given-names>A</given-names></name><name><surname>Watanabe</surname><given-names>K</given-names></name><name><surname>Suzuki</surname><given-names>O</given-names></name></person-group><article-title>Quantitation of postmortem profenofos levels</article-title><source>J Toxicol Clin Toxicol</source><year>1998</year><volume>36</volume><fpage>63</fpage><lpage>5</lpage><pub-id pub-id-type="pmid">9541046</pub-id></element-citation></ref><ref id="B32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miyazaki</surname><given-names>T</given-names></name><name><surname>Yashiki</surname><given-names>M</given-names></name><name><surname>Chikasue</surname><given-names>F</given-names></name><name><surname>Kojima</surname><given-names>T</given-names></name><name><surname>Hibino</surname><given-names>H</given-names></name></person-group><article-title>A case of death from prothiophos poisoning</article-title><source>Forensic Sci Int</source><year>1988</year><volume>38</volume><fpage>13</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">3192132</pub-id></element-citation></ref><ref id="B33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sakata</surname><given-names>M</given-names></name><name><surname>Gotoh</surname><given-names>M</given-names></name><name><surname>Ubukata</surname><given-names>K</given-names></name><name><surname>Hayashi</surname><given-names>H</given-names></name><name><surname>Kotaki</surname><given-names>M</given-names></name><name><surname>Omote</surname><given-names>T</given-names></name></person-group><article-title>Prothiofos metabolites in human poisoning</article-title><source>J Toxicol Clin Toxicol</source><year>1999</year><volume>37</volume><fpage>327</fpage><lpage>32</lpage><pub-id pub-id-type="pmid">10384797</pub-id></element-citation></ref><ref id="B34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paudyal</surname><given-names>BP</given-names></name></person-group><article-title>Organophosphorus poisoning</article-title><source>JNMA J Nepal Med Assoc</source><year>2008</year><volume>47</volume><fpage>251</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">19079407</pub-id></element-citation></ref><ref id="B35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>TJ</given-names></name><name><surname>Walter</surname><given-names>FG</given-names></name><name><surname>Hung</surname><given-names>DZ</given-names></name><name><surname>Tsai</surname><given-names>JL</given-names></name><name><surname>Hu</surname><given-names>SC</given-names></name><name><surname>Chang</surname><given-names>JS</given-names></name><etal></etal></person-group><article-title>Epidemiology of organophosphate pesticide poisoning in Taiwan</article-title><source>Clin Toxicol</source><year>2008</year><volume>46</volume><fpage>794</fpage><lpage>801</lpage></element-citation></ref><ref id="B36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Inoue</surname><given-names>S</given-names></name><name><surname>Saito</surname><given-names>T</given-names></name><name><surname>Mase</surname><given-names>H</given-names></name><name><surname>Suzuki</surname><given-names>Y</given-names></name><name><surname>Takazawa</surname><given-names>K</given-names></name><name><surname>Yamamoto</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Rapid simultaneous determination for organophosphorus pesticides in human serum by LC-MS</article-title><source>J Pharm Biomed Anal</source><year>2007</year><volume>44</volume><fpage>258</fpage><lpage>64</lpage><pub-id pub-id-type="pmid">17337150</pub-id></element-citation></ref><ref id="B37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tanaka</surname><given-names>T</given-names></name><name><surname>Tanaka</surname><given-names>N</given-names></name><name><surname>Kita</surname><given-names>T</given-names></name><name><surname>Kasai</surname><given-names>K</given-names></name><name><surname>Sato</surname><given-names>H</given-names></name></person-group><article-title>Acephate in biological fluids of two autopsy cases after ingestion of the chemical</article-title><source>J Forensic Sci</source><year>2005</year><volume>50</volume><fpage>933</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">16078501</pub-id></element-citation></ref><ref id="B38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roberts</surname><given-names>DM</given-names></name><name><surname>Karunarathna</surname><given-names>A</given-names></name><name><surname>Buckley</surname><given-names>NA</given-names></name><name><surname>Manuweera</surname><given-names>G</given-names></name><name><surname>Sheriff</surname><given-names>MHR</given-names></name><name><surname>Eddleston</surname><given-names>M</given-names></name></person-group><article-title>Influence of pesticide regulation on acute poisoning deaths in Sri Lanka</article-title><source>Bull World Health Organ</source><year>2003</year><volume>81</volume><fpage>789</fpage><lpage>98</lpage><pub-id pub-id-type="pmid">14758405</pub-id></element-citation></ref><ref id="B39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zheng</surname><given-names>RY</given-names></name></person-group><article-title>[Clinical features of delayed polyneuropathy induced by acute methamidophos toxicosis in 74 cases]</article-title><source>Zhonghua Nei Ke Za Zhi</source><year>1990</year><volume>29</volume><fpage>79</fpage><lpage>82</lpage><comment>125</comment><pub-id pub-id-type="pmid">2170085</pub-id></element-citation></ref><ref id="B40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>SY</given-names></name><name><surname>Wang</surname><given-names>HF</given-names></name><name><surname>Yin</surname><given-names>Y</given-names></name></person-group><article-title>[The reporting system of acute pesticides poisoning and general situation of pesticides poisoning in China]</article-title><source>Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi</source><year>2005</year><volume>23</volume><fpage>336</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">16266507</pub-id></element-citation></ref><ref id="B41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wan</surname><given-names>WG</given-names></name><name><surname>Zheng</surname><given-names>SC</given-names></name><name><surname>Zou</surname><given-names>HJ</given-names></name><name><surname>Ma</surname><given-names>SD</given-names></name><name><surname>Tao</surname><given-names>GZ</given-names></name><name><surname>Xu</surname><given-names>ZF</given-names></name><etal></etal></person-group><article-title>[Different therapeutic efficacy of pralidoxime chloride PAM-Cl on AChE against acute toxicity of methamidophos, dichlorovs and omethoate]</article-title><source>Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi</source><year>2007</year><volume>25</volume><fpage>586</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">18070496</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002C98 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 002C98 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:2766103
|texte= Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:19737786" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |