Evaluation of surrogate markers of impending death in the galactosamine-sensitized murine model of bacterial endotoxemia
When evaluating vaccines for efficacy against gram-negative endotoxemia, the challenge has historically required death of a large percentage of test subjects. We attempted to identify surrogate markers of impending death to allow for early euthanasia without interfering with experimental data collec...
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| Veröffentlicht in: | Laboratory animal science (Chicago) 1999-10, Vol.49 (5), p.545-550 |
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| creator | Krarup, A Chattopadhyay, P Bhattacharjee, A K Burge, J R Ruble, G R |
| description | When evaluating vaccines for efficacy against gram-negative endotoxemia, the challenge has historically required death of a large percentage of test subjects. We attempted to identify surrogate markers of impending death to allow for early euthanasia without interfering with experimental data collection.
Galactosamine-sensitized mice (n = 140) were inoculated intraperitoneally with various dosages of endotoxin, and development of clinical signs of disease--body temperature, body weight, hunched posture, ruffled coat, inability to ambulate, and loss of consciousness--was evaluated.
Wide fluctuations in body temperature (+/- 4 degrees C) were observed in survivors and nonsurvivors. Posture, coat, and body weight were not accurate predictors of death. Only inability to ambulate, with a positive predictive value of 100% (11 of 11), accurately predicted death in the experimental mice of this study.
Using this surrogate marker, loss of ability to ambulate, 11 of 13 mice that developed this sign could have been euthanized early, preventing anywhere from 2 to 22 h of potential distress prior to death. |
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Galactosamine-sensitized mice (n = 140) were inoculated intraperitoneally with various dosages of endotoxin, and development of clinical signs of disease--body temperature, body weight, hunched posture, ruffled coat, inability to ambulate, and loss of consciousness--was evaluated.
Wide fluctuations in body temperature (+/- 4 degrees C) were observed in survivors and nonsurvivors. Posture, coat, and body weight were not accurate predictors of death. Only inability to ambulate, with a positive predictive value of 100% (11 of 11), accurately predicted death in the experimental mice of this study.
Using this surrogate marker, loss of ability to ambulate, 11 of 13 mice that developed this sign could have been euthanized early, preventing anywhere from 2 to 22 h of potential distress prior to death.</description><identifier>ISSN: 0023-6764</identifier><identifier>PMID: 10551457</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Biomarkers ; Body Temperature ; Body Weight ; Death ; Endotoxemia - mortality ; Endotoxins - administration & dosage ; Escherichia coli ; Female ; Galactosamine - administration & dosage ; Hair ; Klebsiella pneumoniae ; Locomotion ; Mice ; Mice, Inbred BALB C ; Posture ; Pseudomonas aeruginosa ; Unconsciousness</subject><ispartof>Laboratory animal science (Chicago), 1999-10, Vol.49 (5), p.545-550</ispartof><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10551457$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krarup, A</creatorcontrib><creatorcontrib>Chattopadhyay, P</creatorcontrib><creatorcontrib>Bhattacharjee, A K</creatorcontrib><creatorcontrib>Burge, J R</creatorcontrib><creatorcontrib>Ruble, G R</creatorcontrib><title>Evaluation of surrogate markers of impending death in the galactosamine-sensitized murine model of bacterial endotoxemia</title><title>Laboratory animal science (Chicago)</title><addtitle>Lab Anim Sci</addtitle><description>When evaluating vaccines for efficacy against gram-negative endotoxemia, the challenge has historically required death of a large percentage of test subjects. We attempted to identify surrogate markers of impending death to allow for early euthanasia without interfering with experimental data collection.
Galactosamine-sensitized mice (n = 140) were inoculated intraperitoneally with various dosages of endotoxin, and development of clinical signs of disease--body temperature, body weight, hunched posture, ruffled coat, inability to ambulate, and loss of consciousness--was evaluated.
Wide fluctuations in body temperature (+/- 4 degrees C) were observed in survivors and nonsurvivors. Posture, coat, and body weight were not accurate predictors of death. Only inability to ambulate, with a positive predictive value of 100% (11 of 11), accurately predicted death in the experimental mice of this study.
Using this surrogate marker, loss of ability to ambulate, 11 of 13 mice that developed this sign could have been euthanized early, preventing anywhere from 2 to 22 h of potential distress prior to death.</description><subject>Animals</subject><subject>Biomarkers</subject><subject>Body Temperature</subject><subject>Body Weight</subject><subject>Death</subject><subject>Endotoxemia - mortality</subject><subject>Endotoxins - administration & dosage</subject><subject>Escherichia coli</subject><subject>Female</subject><subject>Galactosamine - administration & dosage</subject><subject>Hair</subject><subject>Klebsiella pneumoniae</subject><subject>Locomotion</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Posture</subject><subject>Pseudomonas aeruginosa</subject><subject>Unconsciousness</subject><issn>0023-6764</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kDtPwzAUhT2AaCn8BeSJLZJjN3Y8oqo8pEosMEdOfNMa_Ai2gwq_HlfAcq706btnOGdoSQhlFRd8vUCXKb0RQgRlzQVa1KRp6nUjlui4_VR2VtkEj8OI0xxj2KsM2Kn4DjGdoHETeG38HmtQ-YCNx_kAeK-sGnJIyhkPVQKfTDbfoLGbYyHYBQ329N8XDaJRFpeakMMRnFFX6HxUNsH1312h1_vty-ax2j0_PG3udtVEicgVb-Wgm6HVQMlA6pJrLiiQVnOi5Sgka_VYAkTfDHpkvdStrGuuxoJLshW6_e2dYviYIeXOmTSAtcpDmFPHJWWcSlbEmz9x7h3oboqmbPDV_W_FfgAf22fa</recordid><startdate>19991001</startdate><enddate>19991001</enddate><creator>Krarup, A</creator><creator>Chattopadhyay, P</creator><creator>Bhattacharjee, A K</creator><creator>Burge, J R</creator><creator>Ruble, G R</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19991001</creationdate><title>Evaluation of surrogate markers of impending death in the galactosamine-sensitized murine model of bacterial endotoxemia</title><author>Krarup, A ; Chattopadhyay, P ; Bhattacharjee, A K ; Burge, J R ; Ruble, G R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p207t-689cd5c8de20c01e204672e08d60d9f7938df938e7b5cdf3b9d89116afdf96af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Biomarkers</topic><topic>Body Temperature</topic><topic>Body Weight</topic><topic>Death</topic><topic>Endotoxemia - mortality</topic><topic>Endotoxins - administration & dosage</topic><topic>Escherichia coli</topic><topic>Female</topic><topic>Galactosamine - administration & dosage</topic><topic>Hair</topic><topic>Klebsiella pneumoniae</topic><topic>Locomotion</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Posture</topic><topic>Pseudomonas aeruginosa</topic><topic>Unconsciousness</topic><toplevel>online_resources</toplevel><creatorcontrib>Krarup, A</creatorcontrib><creatorcontrib>Chattopadhyay, P</creatorcontrib><creatorcontrib>Bhattacharjee, A K</creatorcontrib><creatorcontrib>Burge, J R</creatorcontrib><creatorcontrib>Ruble, G R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Laboratory animal science (Chicago)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krarup, A</au><au>Chattopadhyay, P</au><au>Bhattacharjee, A K</au><au>Burge, J R</au><au>Ruble, G R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of surrogate markers of impending death in the galactosamine-sensitized murine model of bacterial endotoxemia</atitle><jtitle>Laboratory animal science (Chicago)</jtitle><addtitle>Lab Anim Sci</addtitle><date>1999-10-01</date><risdate>1999</risdate><volume>49</volume><issue>5</issue><spage>545</spage><epage>550</epage><pages>545-550</pages><issn>0023-6764</issn><abstract>When evaluating vaccines for efficacy against gram-negative endotoxemia, the challenge has historically required death of a large percentage of test subjects. We attempted to identify surrogate markers of impending death to allow for early euthanasia without interfering with experimental data collection.
Galactosamine-sensitized mice (n = 140) were inoculated intraperitoneally with various dosages of endotoxin, and development of clinical signs of disease--body temperature, body weight, hunched posture, ruffled coat, inability to ambulate, and loss of consciousness--was evaluated.
Wide fluctuations in body temperature (+/- 4 degrees C) were observed in survivors and nonsurvivors. Posture, coat, and body weight were not accurate predictors of death. Only inability to ambulate, with a positive predictive value of 100% (11 of 11), accurately predicted death in the experimental mice of this study.
Using this surrogate marker, loss of ability to ambulate, 11 of 13 mice that developed this sign could have been euthanized early, preventing anywhere from 2 to 22 h of potential distress prior to death.</abstract><cop>United States</cop><pmid>10551457</pmid><tpages>6</tpages></addata></record> |
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| ispartof | Laboratory animal science (Chicago), 1999-10, Vol.49 (5), p.545-550 |
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| language | eng |
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| source | MEDLINE; IngentaConnect Free/Open Access Journals |
| subjects | Animals Biomarkers Body Temperature Body Weight Death Endotoxemia - mortality Endotoxins - administration & dosage Escherichia coli Female Galactosamine - administration & dosage Hair Klebsiella pneumoniae Locomotion Mice Mice, Inbred BALB C Posture Pseudomonas aeruginosa Unconsciousness |
| title | Evaluation of surrogate markers of impending death in the galactosamine-sensitized murine model of bacterial endotoxemia |
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