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var title_f6_22_6496="TEE sinus venosus defect";

var content_f6_22_6496=[" <div id=\"graphicsToolbar\">",


" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
" <div id=\"graphicsLinks\">",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic2\" style=\"width: 1040px;\">",
" <div class=\"videoplayer\" h264=\"./images/CARD/73621/sinvetee_conv.mp4?
title=TEE+sinus+venosus+defect\" style=\"width:320px;height:256px\">",
" </div>",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Sinus venosus defect viewed by transesophageal echocardiogram",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" Direct immunofluorescence of a biopsy specimen from a patient with urticarial
vasculitis, demonstrating IgM deposits along the dermal-epidermal junction as well
as involving blood vessel walls in the dermis.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_22_6498=[""].join("\n");
var outline_f6_22_6498=null;
var title_f6_22_6499="Dermatofibroma dermoscopy";
var content_f6_22_6499=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
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" <a href=\"?imageKey=DERM
%2F67214&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
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%2F67214&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
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" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 524px\">",
" <div class=\"ttl\">",
" Dermoscopic structures of dermatofibroma",
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" </div>",
" <div class=\"lgnd\">",
" Peripheral delicate pigment network with a central scar-like area.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Drs. Ashfaq Marghoob and Natalia Jaimes.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_22_6499=[""].join("\n");
var outline_f6_22_6499=null;
var title_f6_22_6500="Rabies immune globulin (human): Drug information";
var content_f6_22_6500=[" <noscript>",
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" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"drugTitle\">",
" Rabies immune globulin (human): Drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?20/3/20531?source=see_link\">",
" see \"Rabies immune globulin (human): Patient drug information\"",
" </a>",
" and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?40/29/41427?
source=see_link\">",
" see \"Rabies immune globulin (human): Pediatric drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F216777\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" HyperRAB&reg; S/D;",
" </li>",
" <li>",
" Imogam&reg; Rabies-HT",
" </li>",
" </ul>",
" </div>",
" <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F216778\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: Canada",
" </span>",
" <ul>",
" <li>",
" HyperRAB&reg; S/D;",
" </li>",
" <li>",
" Imogam&reg; Rabies Pasteurized",
" </li>",
" </ul>",
" </div>",
" <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F216787\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacologic Category",
" </span>",
" <ul>",
" <li>",
" Blood Product Derivative;",
" </li>",
" <li>",
" Immune Globulin",
" </li>",
" </ul>",
" </div>",
" <div class=\"block doa drugH1Div\" id=\"F216779\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Adult",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Postexposure prophylaxis:",
" </b>",
" Local wound infiltration: 20 units/kg in a single dose, RIG should always be
administered as part of rabies vaccine regimen. If anatomically feasible, the full
rabies immune globulin dose should be infiltrated around and into the wound(s);
remaining volume should be administered I.M. at a site distant from the vaccine
administration site. If rabies vaccine was initiated without rabies immune
globulin, rabies immune globulin may be administered through the seventh day after
the administration of the first dose of the vaccine. Administration of RIG is not
recommended after the seventh day post vaccine since an antibody response to the
vaccine is expected during this time period.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
" <b>",
" Note:",
" </b>",
" Not for use in persons with a history of pre-exposure vaccination, history of
postexposure prophylaxis, or previous vaccination with rabies vaccine and
documentation of antibody response.",
" </p>",
" </div>",
" <div class=\"block dop drugH1Div\" id=\"F216783\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Pediatric",
" </span>",
" <p>",
" (For additional information",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?40/29/41427?
source=see_link\">",
" see \"Rabies immune globulin (human): Pediatric drug information\"",
" </a>",
" )",
" </p>",
" <p style=\"text-indent:0em;display:inline\">",
" Refer to adult dosing.",
" </p>",
" </div>",
" <div class=\"block doe drugH1Div\" id=\"F216780\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Geriatric",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Refer to adult dosing.",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F216767\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosage Forms: U.S.",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Injection, solution [preservative free]:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" HyperRAB&reg; S/D: 150 units/mL (2 mL, 10 mL) [solvent/detergent treated]",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Imogam&reg; Rabies-HT: 150 units/mL (2 mL, 10 mL) [heat treated]",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F216755\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Generic Equivalent Available: U.S.",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No",
" </p>",
" </div>",
" <div class=\"block adm drugH1Div\" id=\"F216770\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Administration",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Do not administer I.V.",
" </p>",
" <p style=\"text-indent:0em;\">",
" Postexposure wound infiltration: If anatomically feasible, the full rabies
immune globulin dose should be infiltrated around and into the wound(s); remaining
volume should be administered I.M. in the deltoid muscle of the upper arm or
lateral thigh muscle. The gluteal area should be avoided to reduce the risk of
sciatic nerve damage. Do not administer rabies vaccine in the same syringe or at
the same administration site as RIG.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" Measles-containing vaccines should be given &ge;4 months after rabies immune
globulin.",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F216768\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Part of postexposure prophylaxis of persons with rabies exposure. Provides
passive immunity until active immunity with rabies vaccine is established. Not for
use in persons with a history of pre-exposure vaccination, history of postexposure
prophylaxis, or previous vaccination with rabies vaccine and documentation of
antibody response.",
" </p>",
" </div>",
" <div class=\"block ars drugH1Div\" id=\"F216785\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Adverse Reactions Significant",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Frequency not defined.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Central nervous system: Fever (mild), headache, malaise",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Dermatologic: Angioneurotic edema, rash",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Local: Injection site: Pain, stiffness, soreness, tenderness",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Renal: Nephrotic syndrome",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Miscellaneous: Anaphylaxis",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F216772\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Contraindications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" There are no contraindications listed within the FDA-approved manufacturer's
labeling.",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F216759\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warnings/Precautions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Concerns related to adverse effects:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Anaphylaxis/hypersensitivity reactions: Hypersensitivity and
anaphylactic reactions can occur; immediate treatment (including epinephrine
1:1000) should be available. Use with caution in patients with isolated
immunoglobulin A deficiency or a history of systemic hypersensitivity to human
immunoglobulins.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Disease-related concerns:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Bleeding disorders: Use with caution in patients with thrombocytopenia
or coagulation disorders; I.M. injections may be contraindicated.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Dosage form specific issues:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Human plasma: Product of human plasma; may potentially contain
infectious agents which could transmit disease. Screening of donors, as well as
testing and/or inactivation or removal of certain viruses, reduces the risk.
Infections thought to be transmitted by this product should be reported to the
manufacturer.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Other warnings/precautions:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Administration: Not for intravenous administration.",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F13299975\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Metabolism/Transport Effects",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" None known.",
" </p>",
" </div>",
" <div class=\"block dri drugH1Div\" id=\"F216763\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Drug Interactions",
" </span>",
" <br/>",
" <br/>",
" <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
" (For additional information:",
" <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
" Launch Lexi-Interact&trade; Drug Interactions Program",
" </a>",
" )",
" </div>",
" <div class=\"lexi\" id=\"lexiInteractImgB\">",
" <img border=\"0\" height=\"17\"
src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Vaccines (Live): Immune Globulins may diminish the therapeutic effect of
Vaccines (Live). Management: Live organism vaccination should be withheld for up
to 6 months following immune globulin administration. Live vaccine given
immediately prior to immune globulin may require repeat vaccination.",
" <b>",
" Exceptions:",
" </b>",
" Yellow Fever Vaccine.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F216765\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Risk Factor",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" C (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
" show table",
" </a>",
" )",
" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F6801328\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Implications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Reproduction studies have not been conducted. Pregnancy is not a
contraindication to postexposure prophylaxis.",
" </p>",
" </div>",
" <div class=\"block fee drugH1Div\" id=\"F16323774\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Injection",
" </b>",
" (HyperRAB S/D Intramuscular)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 150 units/mL (2 mL): $595.24",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Injection",
" </b>",
" (Imogam Rabies-HT Intramuscular)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 150 units/mL (2 mL): $492.37",
" </p>",
" </div>",
" <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F216774\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" International Brand Names",
" </span>",
" <ul>",
" <li>",
" Bayer Bayrab Rabies Immune Globulin (PH);",
" </li>",
" <li>",
" Bayrab (PK);",
" </li>",
" <li>",
" Hyperrab S D (IL);",
" </li>",
" <li>",
" Imogam (AU);",
" </li>",
" <li>",
" Imogam Rabia (AR, PY);",
" </li>",
" <li>",
" Imogam Rabies (BF, BG, BJ, CI, EE, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU,
MW, NE, NG, PH, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW);",
" </li>",
" <li>",
" PARS (IN);",
" </li>",
" <li>",
" Rabigam (ZA);",
" </li>",
" <li>",
" Rabuman Berna (PH, TH)",
" </li>",
" </ul>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F216758\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Mechanism of Action",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Rabies immune globulin is a solution of globulins dried from the plasma or
serum of selected adult human donors who have been immunized with rabies vaccine
and have developed high titers of rabies antibody. It generally contains 10% to 18%
of protein of which not less than 80% is monomeric immunoglobulin G.",
" </p>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <div class=\"reference\">",
" &ldquo;A New Rabies Vaccine,&rdquo;",
" <i>",
" Med Lett Drugs Ther",
" </i>",
" , 1998, 40(1029):64-5.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6500/abstract-text/9653425/pubmed\" id=\"9653425\"
target=\"_blank\">",
" 9653425",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Centers for Disease Control, &ldquo;Recommendations of the Advisory
Committee on Immunization Practices (ACIP): General Recommendations on
Immunization,&rdquo;",
" <i>",
" MMWR Recomm Rep",
" </i>",
" , 2002, 51(RR-2):1-36.",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Centers for Disease Control and Prevention, &ldquo;Human Rabies Prevention -
United States, 2008 Recommendations of the Advisory Committee on Immunization
Practices (ACIP),&rdquo;",
" <i>",
" MMWR Recomm Rep",
" </i>",
" , 2008, 57(RR-3):1-28.",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Centers for Disease Control and Prevention, &ldquo;Use of a Reduced (4-Dose)
Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies,&rdquo;",
" <i>",
" MMWR Recomm Rep",
" </i>",
" , 2010, 59(RR-2):1-9. Available at",
" <a href=\"file://www.cdc.gov/mmwr/PDF/rr/rr5902.pdf\" target=\"_blank\">",
" file://www.cdc.gov/mmwr/PDF/rr/rr5902.pdf",
" </a>",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6500/abstract-text/20300058/pubmed\" id=\"20300058\"
target=\"_blank\">",
" 20300058",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Cohen V, Jellinek SP, Teperikidis L, et al, &ldquo;Room-Temperature Storage
of Medications Labeled for Refrigeration,&rdquo;",
" <i>",
" Am J Health-Syst Pharm",
" </i>",
" , 2007, 64(16):1711-15.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6500/abstract-text/17687059/pubmed\" id=\"17687059\"
target=\"_blank\">",
" 17687059",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Dreesen DW and Hanlon CA, &ldquo;Current Recommendations for the Prophylaxis
and Treatment of Rabies,&rdquo;",
" <i>",
" Drugs",
" </i>",
" , 1998, 56(5):801-9.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6500/abstract-text/9829154/pubmed\" id=\"9829154\"
target=\"_blank\">",
" 9829154",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Lang J and Plotkin SA, &ldquo;Rabies Risk and Immunoprophylaxis in
Children,&rdquo;",
" <i>",
" Adv Pediatr Infect Dis",
" </i>",
" , 1997, 13:219-55.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6500/abstract-text/9544314/pubmed\" id=\"9544314\"
target=\"_blank\">",
" 9544314",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Strady A, Lang J, Lienard M, et al, &ldquo;Antibody Persistence Following
Pre-exposure Regimens of Cell-Culture Rabies Vaccines: 10-Year Follow-up and
Proposal for a New Booster Policy,&rdquo;",
" <i>",
" J Infect Dis",
" </i>",
" , 1998, 177(5):1290-5.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6500/abstract-text/9593014/pubmed\" id=\"9593014\"
target=\"_blank\">",
" 9593014",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 9848 Version 34.0",
" </div>",
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" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
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" Dosing: Adult",
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" <a class=\"outlineLink\" href=\"#F216783\">",
" Dosing: Pediatric",
" </a>",
" </li>",
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" Dosing: Geriatric",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216767\">",
" Dosage Forms: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216755\">",
" Generic Equivalent Available: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216770\">",
" Administration",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216768\">",
" Use",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216785\">",
" Adverse Reactions Significant",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216772\">",
" Contraindications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216759\">",
" Warnings/Precautions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F13299975\">",
" Metabolism/Transport Effects",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216763\">",
" Drug Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216765\">",
" Pregnancy Risk Factor",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F6801328\">",
" Pregnancy Implications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F16323774\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216774\">",
" International Brand Names",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F216758\">",
" Mechanism of Action",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9848\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
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" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9848|TAB\">",
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" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
title=\"Lexicomp clinical abbreviations\">",
" Lexicomp clinical abbreviations",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_patient\" href=\"UTD.htm?20/3/20531?
source=related_link\">",
" Rabies immune globulin (human): Patient drug information",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?40/29/41427?
source=related_link\">",
" Rabies immune globulin (human): Pediatric drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_22_6501="Teriparatide (recombinant human parathyroid hormone (1-34)):
Drug information";
var content_f6_22_6501=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
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" </sup>",
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" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"drugTitle\">",
" Teriparatide (recombinant human parathyroid hormone (1-34)): Drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?43/5/44116?source=see_link\">",
" see \"Teriparatide (recombinant human parathyroid hormone (1-34)): Patient
drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"block black-box-warn drugH1Div\" id=\"F5709064\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" ALERT: U.S. Boxed Warning",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" The FDA-approved labeling includes a boxed warning. See Warnings/Precautions
section for a concise summary of this information. For verbatim wording of the
boxed warning, consult the product labeling or",
" <a href=\"file://www.fda.gov\" target=\"_blank\">",
" www.fda.gov",
" </a>",
" .",
" </p>",
" </div>",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F225837\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Forteo&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F855044\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: Canada",
" </span>",
" <ul>",
" <li>",
" Forteo&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F225853\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacologic Category",
" </span>",
" <ul>",
" <li>",
" Parathyroid Hormone Analog",
" </li>",
" </ul>",
" </div>",
" <div class=\"block doa drugH1Div\" id=\"F225839\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Adult",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Osteoporosis:",
" </b>",
" SubQ: 20 mcg once daily;",
" <b>",
" Note:",
" </b>",
" Initial administration should occur under circumstances in which the patient
may sit or lie down, in the event of orthostasis.",
" </p>",
" </div>",
" <div class=\"block doe drugH1Div\" id=\"F3062230\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Geriatric",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Refer to adult dosing.",
" </p>",
" </div>",
" <div class=\"block dor drugH1Div\" id=\"F225840\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Renal Impairment",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No dosage adjustment required. Bioavailability and half-life increase with
Cl",
" <sub>",
" cr",
" </sub>",
" &lt;30 mL/minute. Use in severe renal impairment is contraindicated in the
Canadian labeling.",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F225815\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosage Forms: U.S.",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Injection, solution:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Forteo&reg;: 250 mcg/mL (2.4 mL) [delivers teriparatide 20 mcg/dose]",
" </p>",
" </div>",
" <div class=\"block foccan drugH1Div\" id=\"F12807316\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosage Forms: Canada",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Injection, solution:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Forteo&reg;: 250 mcg/mL (3 mL) [delivers teriparatide 20 mcg/dose]",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F225800\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Generic Equivalent Available: U.S.",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No",
" </p>",
" </div>",
" <div class=\"block meg drugH1Div\" id=\"F7874998\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Medication Guide",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" An FDA-approved patient medication guide, which is available with the product
information and at",
" <a href=\"file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088604.pdf\"
target=\"_blank\">",
" file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088604.pdf",
" </a>",
" , must be dispensed with this medication.",
" </p>",
" </div>",
" <div class=\"block adm drugH1Div\" id=\"F225818\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Administration",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Administer by subcutaneous injection into the thigh or abdominal wall.
Initial administration should occur under circumstances in which the patient may
sit or lie down, in the event of orthostasis.",
" <b>",
" Note:",
" </b>",
" The 3 mL prefilled pen (Canadian availability; not available in U.S.) must be
primed prior to each dose.",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F225817\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Treatment of osteoporosis in postmenopausal women at high risk of fracture;
treatment of primary or hypogonadal osteoporosis in men at high risk of fracture;
treatment of glucocorticoid-induced osteoporosis in men and women at high risk for
fracture",
" </p>",
" </div>",
" <div class=\"block mst drugH1Div\" id=\"F15255018\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Medication Safety Issues",
" </span>",
" <div class=\"collapsible\">",
" <span class=\"collapsible-title\">",
" Sound-alike/look-alike issues:",
" </span>",
" <div class=\"collapsible-wrap\">",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Forteo&reg; may be confused with Forfivo&trade; XL",
" </p>",
" </div>",
" </div>",
" </div>",
" <div class=\"block ars drugH1Div\" id=\"F225851\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Adverse Reactions Significant",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" &gt;10%: Endocrine &amp; metabolic: Hypercalcemia (transient increases noted
4-6 hours postdose [women 11%; men 6%])",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" 1% to 10%:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Cardiovascular: Orthostatic hypotension (5%; transient), chest pain (3%),
syncope (3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Central nervous system: Dizziness (8%), insomnia (4% to 5%), anxiety
(&le;4%), depression (4%), vertigo (4%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Dermatologic: Rash (5%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Endocrine &amp; metabolic: Hyperuricemia (3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Gastrointestinal: Nausea (9% to 14%), gastritis (&le;7%), dyspepsia (5%),
vomiting (3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Neuromuscular &amp; skeletal: Arthralgia (10%), weakness (9%), leg cramps
(3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Respiratory: Rhinitis (10%), pharyngitis (6%), dyspnea (4% to 6%), pneumonia
(4% to 6%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Miscellaneous: Antibodies to teriparatide (3% of women in long-term
treatment; hypersensitivity reactions or decreased efficacy were not associated in
preclinical trials), herpes zoster (&le;3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Postmarketing and/or case reports: Acute dyspnea, allergic reactions, edema
(facial/oral), hypercalcemia &gt;13 mg/dL, injection site reactions (bruising,
pain, swelling), muscle spasm, osteosarcoma, urticaria",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F225821\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Contraindications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hypersensitivity to teriparatide or any component of the formulation",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" Canadian labeling: Additional contraindications (not in U.S. labeling): Pre-
existing hypercalcemia; severe renal impairment; metabolic bone diseases other than
primary osteoporosis (including hyperparathyroidism and Paget&rsquo;s disease of
the bone); unexplained elevations of alkaline phosphatase; prior external beam or
implant radiation therapy involving the skeleton; bone metastases or history of
skeletal malignancies; pregnancy; breast-feeding mothers; pediatric patients or
young adults with open epiphysis",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F225804\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warnings/Precautions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Concerns related to adverse effects:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Orthostatic hypotension: May cause orthostatic hypotension; use with
caution in patients at risk of this effect or in those who would not tolerate
transient hypotensive episodes (cerebrovascular disease, cardiovascular disease,
hypovolemia, or concurrent medication use which may predispose to
hypotension/bradycardia). Transient orthostatic hypotension usually occurs within 4
hours of dosing and within the first several doses.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Osteosarcoma:",
" <b>",
" [U.S. Boxed Warning]: In animal studies, teriparatide has been associated
with an increase in osteosarcoma;",
" </b>",
" risk was dependent on both dose and duration. Avoid use in patients with an
increased risk of osteosarcoma (including Paget's disease, prior radiation,
unexplained elevation of alkaline phosphatase, or in patients with open epiphyses).
Do not use in patients with a history of skeletal metastases, hyperparathyroidism,
or pre-existing hypercalcemia. Exclude metabolic bone disease other than
osteoporosis prior to initiating therapy. Not for use in patients with metabolic
bone disease other than osteoporosis.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Disease-related concerns:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Cardiovascular disease: Use with caution in patients with
cardiovascular disease; limited data available concerning safety and efficacy.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Hepatic impairment: Use with caution in patients with hepatic
impairment; limited data available concerning safety and efficacy.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Renal impairment: Use with caution in patients with renal impairment;
limited data available concerning safety and efficacy. Use in severe renal
impairment is contraindicated in the Canadian labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Urolithiasis: Use with caution in patients with active or recent
urolithiasis.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Special populations:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Pediatrics: Safety and efficacy have not been established in
children.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Other warnings/precautions:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Appropriate use: Use of teriparatide for longer than 2 years is not
recommended.",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F13300117\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Metabolism/Transport Effects",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" None known.",
" </p>",
" </div>",
" <div class=\"block dri drugH1Div\" id=\"F6223234\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Drug Interactions",
" </span>",
" <br/>",
" <br/>",
" <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
" (For additional information:",
" <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
" Launch Lexi-Interact&trade; Drug Interactions Program",
" </a>",
" )",
" </div>",
" <div class=\"lexi\" id=\"lexiInteractImgB\">",
" <img border=\"0\" height=\"17\"
src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <p style=\"text-indent:0em;display:inline\">",
" There are no known significant interactions.",
" </p>",
" </div>",
" <div class=\"block foi drugH1Div\" id=\"F225834\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Ethanol/Nutrition/Herb Interactions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Ethanol: Excessive intake may increase risk of osteoporosis.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Herb/Nutraceutical: Ensure adequate calcium and vitamin D intake.",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F225810\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Risk Factor",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" C (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
" show table",
" </a>",
" )",
" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F225825\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Implications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Adverse events were observed in animal studies; the effect on human fetal
development has not been studied. Teriparatide is not indicated for use in pregnant
or premenopausal women.",
" </p>",
" </div>",
" <div class=\"block lac drugH1Div\" id=\"F225843\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Lactation",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Excretion in breast milk unknown/not recommended",
" </p>",
" </div>",
" <div class=\"block brc drugH1Div\" id=\"F225826\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Breast-Feeding Considerations",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Indicated for use in postmenopausal women. Studies have not been conducted to
determine excretion in breast milk. Not recommended for use in breast-feeding
women.",
" </p>",
" </div>",
" <div class=\"block fee drugH1Div\" id=\"F225824\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Solution",
" </b>",
" (Forteo Subcutaneous)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 600 mcg/2.4 mL (2.4 mL): $1431.48",
" </p>",
" </div>",
" <div class=\"block mop drugH1Div\" id=\"F225812\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Monitoring Parameters",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Serum calcium, serum phosphorus, uric acid; blood pressure; bone mineral
density",
" </p>",
" </div>",
" <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F225827\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" International Brand Names",
" </span>",
" <ul>",
" <li>",
" Forsteo (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, KP, NL,
NO, PT, RU, SE, TR);",
" </li>",
" <li>",
" Forteo (AR, AU, BR, CN, CO, CR, DO, GT, HK, HN, MX, MY, PA, PE, PH, SV, TH,
VE);",
" </li>",
" <li>",
" Human PTH (JP)",
" </li>",
" </ul>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F225803\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Mechanism of Action",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Teriparatide is a recombinant formulation of endogenous parathyroid hormone
(PTH), containing a 34-amino-acid sequence which is identical to the N-terminal
portion of this hormone. The pharmacologic activity of teriparatide, which is
similar to the physiologic activity of PTH, includes stimulating osteoblast
function, increasing gastrointestinal calcium absorption, and increasing renal
tubular reabsorption of calcium. Treatment with teriparatide results in increased
bone mineral density, bone mass, and strength. In postmenopausal women,
teriparatide has been shown to decrease osteoporosis-related fractures.",
" </p>",
" </div>",
" <div class=\"block phk drugH1Div\" id=\"F225820\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacodynamics/Kinetics",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Distribution: V",
" <sub>",
" d",
" </sub>",
" : ~0.12 L/kg",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Metabolism: Hepatic (nonspecific proteolysis)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Bioavailability: 95%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Half-life elimination: I.V.: 5 minutes; SubQ: ~1 hour",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Time to peak, serum: ~30 minutes",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Excretion: Urine (as metabolites)",
" </p>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <div class=\"reference\">",
" Body JJ, Gaich GA, Scheele WH, et al, &ldquo;A Randomized Double-blind Trial
to Compare the Efficacy of Teriparatide [Recombinant Human Parathyroid Hormone (1-
34)] With Alendronate in Postmenopausal Women With Osteoporosis,&rdquo;",
" <i>",
" J Clin Endocrinol Metab",
" </i>",
" , 2002, 87(10):4528-35.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6501/abstract-text/12364430/pubmed\" id=\"12364430\"
target=\"_blank\">",
" 12364430",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" National Osteoporosis Foundation, &ldquo;Clinician&rsquo;s Guide to
Prevention and Treatment of Osteoporosis,&rdquo; Washington, DC, 2010. Available at
file://www.nof.org/files/nof/public/content/file/344/upload/159.pdf",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Neer RM, Arnaud CD, Zanchetta JR, et al, &ldquo;Effect of Parathyroid
Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women With
Osteoporosis,&rdquo;",
" <i>",
" N Engl J Med",
" </i>",
" , 2001, 344(19):1434-41.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6501/abstract-text/11346808/pubmed\" id=\"11346808\"
target=\"_blank\">",
" 11346808",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Reeve, J, &ldquo;Recombinant Human Parathyroid Hormone,&rdquo;",
" <i>",
" BMJ",
" </i>",
" , 2002, 324(7335):435-6.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6501/abstract-text/11859030/pubmed\" id=\"11859030\"
target=\"_blank\">",
" 11859030",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Saag KG, Shane E, Boonen S, et al, &ldquo;Teriparatide or Alendronate in
Glucocorticoid-Induced Osteoporosis,&rdquo;",
" <i>",
" N Engl J Med",
" </i>",
" , 2007, 357(20):2028-39.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/22/6501/abstract-text/18003959/pubmed\" id=\"18003959\"
target=\"_blank\">",
" 18003959",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 10178 Version 35.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [1005-83.177.194.223-A277839E2F-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
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" <a href=\"#\" title=\"Collapse Topic Outline\">",
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" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5709064\">",
" ALERT: U.S. Boxed Warning",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225837\">",
" Brand Names: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F855044\">",
" Brand Names: Canada",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225853\">",
" Pharmacologic Category",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225839\">",
" Dosing: Adult",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F3062230\">",
" Dosing: Geriatric",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225840\">",
" Dosing: Renal Impairment",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225815\">",
" Dosage Forms: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F12807316\">",
" Dosage Forms: Canada",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225800\">",
" Generic Equivalent Available: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F7874998\">",
" Medication Guide",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225818\">",
" Administration",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225817\">",
" Use",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F15255018\">",
" Medication Safety Issues",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225851\">",
" Adverse Reactions Significant",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225821\">",
" Contraindications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225804\">",
" Warnings/Precautions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F13300117\">",
" Metabolism/Transport Effects",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F6223234\">",
" Drug Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225834\">",
" Ethanol/Nutrition/Herb Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225810\">",
" Pregnancy Risk Factor",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225825\">",
" Pregnancy Implications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225843\">",
" Lactation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225826\">",
" Breast-Feeding Considerations",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225824\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225812\">",
" Monitoring Parameters",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225827\">",
" International Brand Names",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225803\">",
" Mechanism of Action",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F225820\">",
" Pharmacodynamics/Kinetics",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/10178\"
rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
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var title_f6_22_6502="Bees, yellow jackets, hornets, and wasps: Avoidance";
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" <div id=\"topicTitle\">",
" Bees, yellow jackets, hornets, and wasps: Avoidance",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/22/6502/contributors\">",
" Authors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6502/contributors\">",
" Nancy L Breisch, PhD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6502/contributors\">",
" Albert Greene, PhD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/22/6502/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6502/contributors\">",
" David B Golden, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/22/6502/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6502/contributors\">",
" Elizabeth TePas, MD, MS",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/22/6502/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
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" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Jul 12, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;The stinging Hymenoptera are taxonomically divided into
three principal groups: ants, bees, and wasps (",
" <a class=\"graphic graphic_algorithm graphicRef80397 \" href=\"UTD.htm?
24/14/24815\">",
" algorithm 1",
" </a>",
" ). The majority of allergic reactions to stings are due to this order of
insects. This topic reviews avoidance of the flying Hymenoptera that include bees,
yellow jackets, hornets, and wasps.",
" </p>",
" <p>",
" The biology and identification of the flying Hymenoptera, as well as fire
ants, which are also members of the Hymenoptera order, are discussed separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?9/3/9271?
source=see_link\">",
" \"Bees, yellow jackets, hornets, and wasps: Biology and identification\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/36/7752?
source=see_link\">",
" \"Entomology and control of imported fire ants\"",
" </a>",
" .)",
" </p>",
" <p>",
" Diagnosis and management of stinging insect allergy is discussed separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?12/1/12313?
source=see_link\">",
" \"Bee, yellow jacket, wasp, and other Hymenoptera stings: Reaction types and
acute management\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?14/30/14824?
source=see_link\">",
" \"Diagnosis of Hymenoptera venom allergy\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/34/16936?
source=see_link\">",
" \"Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of
action\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/51/7994?
source=see_link\">",
" \"Stings of imported fire ants: Clinical manifestations, diagnosis, and
treatment\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" AVOIDANCE OF STINGS FROM INDIVIDUAL WORKERS",
" </span>",
" &nbsp;&mdash;&nbsp;The public often mistakenly thinks of bees and wasps as
inherently aggressive under any circumstances, due to the ease with which some
colonies are stimulated to attack in defense of their nest. In reality, individual
workers away from the nest tend to narrowly focus on foraging and typically ignore
humans, even when close to them. Stings are almost always provoked by firm,
accidental contact, such as stepping on a worker, taking the insect into the mouth
with food or drink, or",
" <span class=\"nowrap\">",
" pressing/striking",
" </span>",
" a bee or wasp with the hand. The risk of being stung is therefore elevated in
locations where large numbers of bees or wasps have congregated to feed,
particularly where humans are doing the same [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/1-4\">",
" 1-4",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" Personal behavior",
" </span>",
" &nbsp;&mdash;&nbsp;Preventive measures in locations such as picnic areas and
concession stands involve minimizing accidental contact with foragers. This
includes [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/4,5\">",
" 4,5",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Maintaining a high level of vigilance as to the presence of bees and wasps
in the immediate vicinity",
" </li>",
" <li>",
" Not walking with exposed feet",
" </li>",
" <li>",
" Exercising care with beverages",
" </li>",
" </ul>",
" </p>",
" <p>",
" Drinking directly out of cans or bottles presents the greatest risk, since
these containers are readily entered by inquisitive foragers that are subsequently
concealed from view. Tightly lidded cups with inserted straws are often recommended
as safer than open cups, but do not totally exclude entry by the smaller species.
Open cups or glasses that afford an unobstructed view of the liquid are probably
the safest option.",
" </p>",
" <p>",
" There are currently no effective repellent products for foraging bees or
wasps, despite advertising claims to the contrary. The most appropriate advice may
be to simply not eat or drink outdoors during the warm months, depending upon the
extent of a patient's concern [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/6\">",
" 6",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Wardrobe and cosmetics",
" </span>",
" &nbsp;&mdash;&nbsp;Public information distributed by the medical community
often contains advice concerning wardrobe and cosmetic selection to minimize the
chances of being stung, for example: \"Many stinging insects are foraging for food,
so don't look or smell like a flower - avoid brightly colored clothing and perfume
when outdoors\" [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/7\">",
" 7",
" </a>",
" ]. In fact, there is no empiric evidence that perfume or bright, floral-
colored clothing significantly increases a person's attractiveness to foraging
Hymenoptera or the risk of getting stung by them.",
" </p>",
" <p>",
" Orientation to flowers by honey bees is governed by a complex suite of
integrated factors that include floral colors, patterns, and shapes; specific
floral odors supplemented by multiple olfactory cues provided by the local
environment; and the recent foraging history of individual workers [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/8-10\">",
" 8-10",
" </a>",
" ]. A preconception of what a target item looks like and where it is found,
termed the \"search image\", is derived from the aggregate of specific visual
stimuli used by an organism to detect its food. Unlike humans, bees are most
sensitive to the short-wavelength end of the spectrum, particularly ultraviolet
light, followed by blue-violet and green. They are least sensitive to orange and
cannot perceive red [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/9,10\">",
" 9,10",
" </a>",
" ]. As a result, flowers that depend upon bees for pollination typically have
evolved distinctive ultraviolet patterns that are highly visible to the insects,
but are often not perceived by humans [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/10,11\">",
" 10,11",
" </a>",
" ]. The search image of foraging bees is therefore unlikely to be triggered by
a large patch of colored cloth that appears bright to humans, but has limited or no
biologic significance to Hymenoptera [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/6\">",
" 6",
" </a>",
" ].",
" </p>",
" <p>",
" In contrast to apparel, it would seem more likely that some cosmetic
fragrances might attract the attention of nearby foragers. Both honey bees and
certain vespine species collect carbohydrates from a wide array of natural and
manmade sources besides floral nectar, particularly fermenting fruit and sweet
beverages and foods [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/12,13\">",
" 12,13",
" </a>",
" ]. Orientation to these resources involves olfactory recognition of
distinctive volatile cues [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/13-15\">",
" 13-15",
" </a>",
" ]. Nevertheless, there are no published data demonstrating a significant
attractive effect of any cosmetic product for any Hymenoptera species.",
" </p>",
" <p>",
" An example of a different type of potential association between fragrances and
stinging risk is the alarm pheromone produced by the giant hornet of Japan, Vespa
mandarinia. Alarm pheromones are chemical compounds that are released by bees or
wasps to attract other colony members to the location to aid in defense. The giant
hornet of Japan has an alarm pheromone that incorporates alcohols and esters that
are also used in food flavorings and cosmetic fragrances [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/16\">",
" 16",
" </a>",
" ]. However, it is unknown whether or not any specific product incorporating
these chemicals elicits defensive behavior by this species.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Forager reduction",
" </span>",
" &nbsp;&mdash;&nbsp;Another approach to avoiding stings associated with
foraging bees and wasps involves implementing measures to reduce the number of
foragers.",
" </p>",
" <p>",
" One method is to minimize local sources of attraction [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/1,4,5\">",
" 1,4,5",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Tightly cover food and waste receptacles",
" </li>",
" <li>",
" Frequently clean surfaces of food residue",
" </li>",
" <li>",
" Frequently remove refuse, fallen fruit, and dog or other animal feces (since
the attendant flies are hunted by some wasp species)",
" </li>",
" <li>",
" Eliminate landscape plantings that attract large numbers of carbohydrate-
seeking Hymenoptera. This measure is generally justified only in extreme
circumstances. In many cases, Hymenoptera are not attracted to the flowers or fruit
on these plants, but to \"honeydew\", the sugar-rich excrement of sap-sucking
insects such as aphids, mealybugs, and scales.",
" </li>",
" </ul>",
" </p>",
" <p>",
" A more direct tactic is to attempt to reduce forager populations with the use
of baits, either by luring the insects into traps or as a means to deliver a
pesticide:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Numerous models of wasp traps are on the market [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/17,18\">",
" 17,18",
" </a>",
" ]. However, they tend to be swamped by the constantly replenishing colonies
within foraging range unless very large numbers of traps are deployed and
continually serviced. Thus, traps are of dubious value in protecting a given
location [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/18-20\">",
" 18-20",
" </a>",
" ].",
" </li>",
" <li>",
" Toxic baiting programs hold the greatest promise for success, but most
aspects of their methodology are still under development [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/15,21-23\">",
" 15,21-23",
" </a>",
" ]. Challenges that need to be solved to make this a viable approach include
affordability, insecticide efficacy, exclusion of non-target species, and
sustainability of bait attractiveness.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h1\">",
" AVOIDANCE OF STINGS FROM COLONIES",
" </span>",
" &nbsp;&mdash;&nbsp;Practical risk avoidance measures are limited. Maintaining
a continuous, effective level of vigilance for social wasp or bee colonies while
outdoors is beyond the capability of many people.",
" </p>",
" <p>",
" Group defensive behavior by a social wasp or bee colony may be elicited by
considerably more subtle stimuli than the pressure of direct contact needed to
provoke stinging from most individual foragers. Typically an abrupt movement of the
nest (often due to vibration of its immediate surroundings) will trigger defensive
behavior by a colony. However, in some cases, just nearby motion, the approach of a
dark object, or mammalian breath, is a sufficient stimulus [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/1,24-26\">",
" 1,24-26",
" </a>",
" ]. The consequences for the human or animal source of the disturbance are
usually far more severe than from an encounter with an individual forager. Many
species use an alarm pheromone to rapidly recruit workers for defense during an
emergency. Thus, large colonies are potentially capable of delivering hundreds, or
even thousands, of stings almost instantaneously [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/25,27\">",
" 25,27",
" </a>",
" ].",
" </p>",
" <p>",
" Arousal thresholds and intensity of aggressive response vary widely among
social Hymenoptera, and are dependent upon genetic lineage and a colony's age,
size, and history of disturbance [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/1,24,26,28\">",
" 1,24,26,28",
" </a>",
" ]. A colony that was previously aroused will often attack with far less
provocation than one that has never been disturbed. The major problem universally
posed by these insects is the cryptic nature of their nests, many of which are
totally concealed in protected cavities either above or below ground. Even large,
exposed nests in vegetation or attached to structures are typically obscured by
foliage, overhangs, or shadow [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/24\">",
" 24",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Colony control and avoidance",
" </span>",
" &nbsp;&mdash;&nbsp;Visible nests should be removed by a trained professional.
In addition, individuals with stinging insect allergy should avoid activities that
may disturb a colony, such as mowing the lawn or pruning a hedge.",
" </p>",
" <p>",
" Preventive measures normally involve killing the workers (or sometimes
capturing them, in the case of honey bees) if a social wasp or bee nest is observed
in an undesirable location. This activity should not be attempted by anyone other
than a licensed pest control professional who has received specialized training and
is equipped with clothing designed specifically to protect against stings, even
though insecticide products labeled for stinging insect control are readily
available to the general public [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/3,4\">",
" 3,4",
" </a>",
" ]. The process often requires extensive measures to protect the safety of
bystanders [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/29,30\">",
" 29,30",
" </a>",
" ]. The precise methodology of nest control operations is highly variable,
depending upon species and circumstances, and is beyond the scope of this topic
review.",
" </p>",
" <p>",
" An undiscovered, concealed bee or wasp nest is the most hazardous and may be
encountered virtually anywhere. The single greatest risk factor for multiple
stinging by a disturbed colony is simply being outdoors in a spot not frequented by
humans. This typically implies an area with vegetation. Thus, the more time spent
in natural locales (particularly off well-established paths), the higher the risk.
For people who live and work in developed locations, activities in parks, yards, or
gardens are most likely to bring them into accidental contact with a social bee or
wasp nest. Those activities producing vibration and disturbance to vegetation, such
as accompanying a dog or mowing, pruning, or string-trimming are most likely to
result in stinging [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/1,25\">",
" 1,25",
" </a>",
" ]. In particular, gasoline-powered lawn mowers have the distinction of being
perhaps the most efficient means for stimulating wasp or bee colonies to attack.
These machines are \"the perfect predator\" from the insects' point of view, since
they produce noise, vibration, odors, and heat [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/25\">",
" 25",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h2\">",
" Personal rescue actions",
" </span>",
" &nbsp;&mdash;&nbsp;Outdoor activities are either difficult to avoid or highly
pleasurable for many people, therefore the most useful advice often involves a few
common-sense guidelines for personal behavior once a nest is disturbed [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/25,31\">",
" 25,31",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Individuals should slowly walk away from the area without flailing the arms
if only a few bees or wasps are flying around them. Sudden motion often exacerbates
attack behavior and increases the chance of accidental contact.",
" </li>",
" <li>",
" Individuals should cover their mouth and nose and run from the area without
delay if many insects suddenly start to fly around them or if they are being stung.
Stinging insects tend to target the facial area, which can quickly produce panic
and disorientation in the victim.",
" </li>",
" <li>",
" If possible, persons under attack by bees or wasps should seek shelter in a
building or enclosed vehicle.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h2\">",
" Mitigating the severity of attacks",
" </span>",
" &nbsp;&mdash;&nbsp;Few readily-deployed measures that might mitigate the
intensity of social insect defensive reactions are available:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Attacking bees and wasps are strongly attracted to dark colors (one reason
why eyes, mouth, and nostrils are selectively targeted), so white or very light-
colored clothing that covers most of the body should confer some advantage [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/31,32\">",
" 31,32",
" </a>",
" ].",
" </li>",
" <li>",
" Mixed results have been reported on the efficacy of an aerosol spray of the
common insect repellent N,N-diethyl-m-toluamide (DEET) in decreasing the magnitude
of mass honey bee attacks [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/33,34\">",
" 33,34",
" </a>",
" ].",
" </li>",
" <li>",
" Smoke reduces defensive behavior in both honey bees and yellow jackets [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/32\">",
" 32",
" </a>",
" ], although this would seem to have limited practical value in an unexpected
confrontation.",
" </li>",
" <li>",
" Persons with outdoor occupations that present an elevated risk for
disturbing bee and wasp colonies have the option of carrying at least minimal
protective equipment with them (eg, a compact mesh veil to cover the head).
Firefighters in natural areas are urged to take refuge in a personal fire shelter
(a standard protective item made from aluminum foil, fiberglass, and woven silica)
in the case of severe stinging insect attack [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6502/abstract/31\">",
" 31",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Contrary to popular folklore, worker bees and wasps away from their nests
are not aggressive toward humans and have to be firmly touched before they will
sting. Personal protection therefore largely involves heightened awareness in areas
where these insects are abundant, particularly when eating or drinking. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Avoidance of stings from individual workers'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H3\">",
" 'Personal behavior'",
" </a>",
" above.)",
" </li>",
" <li>",
" There is currently no evidence that wearing perfume or bright, floral-
colored clothing attracts bees and wasps, or elevates sting risk, despite
widespread advice to the contrary. (See",
" <a class=\"local\" href=\"#H4\">",
" 'Wardrobe and cosmetics'",
" </a>",
" above.)",
" </li>",
" <li>",
" Sanitation measures that minimize food and food waste available to worker
bees and wasps tend to be more effective in reducing their numbers than other
methods. Toxic baiting techniques for area-wide abatement of foraging yellow
jackets are still largely in the experimental stage. Available traps for these
wasps typically do not capture sufficient workers to significantly reduce sting
risk. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Forager reduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" Preventing stings from colonies is more problematic than with individual
foragers, and depends mostly upon personal awareness when disturbing vegetation,
particularly when doing yard work. The most effective measure in mitigating the
severity of a mass attack is probably the wearing of white or light-colored
clothing while outdoors. (See",
" <a class=\"local\" href=\"#H6\">",
" 'Avoidance of stings from colonies'",
" </a>",
" above.)",
" </li>",
" <li>",
" Individuals should back slowly away from the area without making any sudden
movements if a few bees or wasps start flying around them. However, individuals
should cover their mouth and nose and run from the area and seek shelter in a
building or enclosed vehicle if large numbers of insects begin flying around them
or they are being stung. (See",
" <a class=\"local\" href=\"#H8\">",
" 'Personal rescue actions'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
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" Sackmann P, Rabinovich M, Corley JC. Successful removal of German
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" Schmidt JO, Boyer Hassen LV. When Africanized bees attack: what you and your
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" Winston ML. Killer bees: The Africanized honey bee in the Americas., Harvard
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" Breed MD, Guzm&aacute;n-Novoa E, Hunt GJ. Defensive behavior of honey bees:
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" Greene A. Born to gnaw. Pest Control Tech 2003; 31:49.",
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" Greene A. Sucking up stingers. Pest Control Tech 2004; 32:70.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6502/abstract/31\">",
" Vetter RS, Parker BT, Visscher PK. Can fire shelters protect firefighters
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6502/abstract/32\">",
" Visscher PK, Vetter RS. Smoke and target color effects on defensive behavior
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" Collins AM, Rubink WL, Cuadriello Aguilar JI, Hellmich RL II. Use of insect
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Entomol 1996; 89:608.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6502/abstract/34\">",
" Schmidt JO, Johnston AN, Ginter DL, Spangler HG. Olfactory stimulation of
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Entomol 2003; 40:275.",
" </a>",
" </li>",
" </ol>",
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" TOPIC OUTLINE",
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" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H10\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" AVOIDANCE OF STINGS FROM INDIVIDUAL WORKERS",
" </a>",
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" <a class=\"outlineLink\" href=\"#H3\">",
" Personal behavior",
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" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
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" <h1>",
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" Stings of imported fire ants: Clinical manifestations, diagnosis, and
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var title_f6_22_6503="Prognostic molecular profiles of breast cancer";
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" Prognostic molecular profiles of breast cancer",
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" Author",
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6/22/6503/contributors\">",
" Lisa A Carey, MD",
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href=\"UTD.htm?6/22/6503/contributors\">",
" Section Editor",
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6/22/6503/contributors\">",
" Daniel F Hayes, MD",
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6/22/6503/contributors\">",
" Don S Dizon, MD, FACP",
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" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Breast cancer is a heterogeneous and phenotypically diverse
disease. It is composed of several biologic subtypes that have distinct behaviors
and responses to therapy. This heterogeneity was first noted over 100 years ago
with the identification that simple removal of the ovaries was therapeutic in some
breast cancer patients, but not others. Breast cancer characterization (profiling)
has significantly advanced since the turn of the millennium due to the development
of sophisticated technologies, such as gene expression arrays, which permit
simultaneous measurement of thousands of genes to create a molecular portrait of
the tumor.",
" </p>",
" <p>",
" The emergence of genomic techniques and the ability to simultaneously measure
the expression of thousands of genes have led to the identification of biology-
based prognostic profiles, several of which have been validated and are in clinical
use. The development of prognostic profiles has been particularly useful in guiding
decision-making about adjuvant therapy along with well-established clinical
prognostic factors (eg, patient age, comorbidity, tumor size, grade, and nodal
status) [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/1,2\">",
" 1,2",
" </a>",
" ]. These molecular prognostic profiles can augment but do not replace classic
clinical factors.",
" </p>",
" <p>",
" Molecular prognostic signatures in breast cancer will be reviewed here. Breast
cancer subtypes, which have also been identified through gene expression profiling,
other prognostic and predictive markers used for breast cancer, and an overview of
gene expression profiling are discussed separately.",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/21/41302?
source=see_link\">",
" \"Molecular intrinsic subtypes of breast cancer\"",
" </a>",
" .)",
" </li>",
" <li>",
" (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/28/43465?
source=see_link\">",
" \"Measurement of prognostic factors in breast cancer\"",
" </a>",
" .)",
" </li>",
" <li>",
" (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/47/39674?
source=see_link\">",
" \"Overview of gene expression profiling, proteomics, and microRNA profiling
in clinical oncology\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H1237831259\">",
" <span class=\"h1\">",
" PROGNOSTIC VERSUS PREDICTIVE FACTORS",
" </span>",
" &nbsp;&mdash;&nbsp;By definition, a",
" <strong>",
" prognostic",
" </strong>",
" factor is capable of providing information on clinical outcome at the time of
diagnosis, independent of therapy. Such markers are usually indicators of growth,
invasion, and metastatic potential [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/3,4\">",
" 3,4",
" </a>",
" ]. In contrast, a",
" <strong>",
" predictive",
" </strong>",
" factor is capable of providing information on the likelihood of response to a
given therapeutic modality. Such markers are either within the target of the
treatment or serve as modulators or epiphenomena related to expression",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" function of the target. Although they can be separately classified, several
factors in breast cancer are both prognostic and predictive, including expression
of the estrogen receptor (ER) and the presence of overexpression of the human
epidermal growth factor-2 (HER2) receptor. As discussed below, some evidence
suggests that molecular profiles can also provide prognostic and predictive
information.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1237831274\">",
" <span class=\"h1\">",
" MOLECULAR PROFILES IN BREAST CANCER",
" </span>",
" &nbsp;&mdash;&nbsp;The three most commonly used molecular prognostic profiles
are the Recurrence Score (RS), derived from Oncotype DX, the Amsterdam 70-gene
profile (Mammaprint), and the Risk of Recurrence score (derived from PAM50). These
are described in more detail below.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027181923\">",
" <span class=\"h2\">",
" Criteria for evaluation of molecular profiles",
" </span>",
" &nbsp;&mdash;&nbsp;In evaluating any molecular signature, it is important to
consider several criteria:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Was the signature created from a dataset that is independent from the
validation signature?",
" </li>",
" <li>",
" Was the signature validated in large, multicenter, prospectively annotated
datasets?",
" </li>",
" <li>",
" What information does the signature provide, and what population is it",
" <span class=\"nowrap\">",
" appropriate/validated",
" </span>",
" for?",
" </li>",
" <li>",
" What population or application should it be used in? Where should it not be
used?",
" </li>",
" <li>",
" How much does the signature reflect commonly measured prognostic variables
(eg, hormone status, stage, or grade) or does it provide truly independent
information?",
" </li>",
" </ul>",
" </p>",
" <p>",
" The ability to better detect distant (rather than all) recurrences and early
(rather than late) recurrences are limitations of molecular profiles in use
clinically, because these estimates are a function of the dataset from which they
are derived and the methodology used to derive them. Because molecular profiles
have been derived from younger patients in general (ie, age &lt;65), a profile for
distant metastases within a five-year time frame in young patients is likely to
predict exactly that. It is likely to be less predictive in older patients.
Therefore, caution is needed when extrapolating to patient populations other than
those studied.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" Recurrence score",
" </span>",
" &nbsp;&mdash;&nbsp;The 21-gene recurrence score (RS, Oncotype Dx) is among the
best-validated prognostic assays. It also appears to predict response to systemic
chemotherapy. It is the most widely used in women with node-negative, estrogen
receptor (ER)-positive breast cancer, which is consistent with guidelines put forth
by the American Society of Clinical Oncology (ASCO) [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/5\">",
" 5",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182678\">",
" <span class=\"h3\">",
" Development of the RS",
" </span>",
" &nbsp;&mdash;&nbsp;The RS was developed by identifying the 250 most promising
candidate genes described in the literature. Investigators then used a reverse
transcription polymerase chain reaction (RT-PCR)-based method for generating
quantitative expression levels of these genes in fixed tissue from 447 patients
collected from three datasets. A mathematical formula that includes 16 genes (plus
five reference genes) was then generated to optimize prediction of distant relapse
despite",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
" tamoxifen",
" </a>",
" therapy. The sum of this calculation is known as the RS.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182685\">",
" <span class=\"h3\">",
" Validation",
" </span>",
" &nbsp;&mdash;&nbsp;The RS was validated in an independent dataset derived from
668 samples collected in the",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
" tamoxifen",
" </a>",
" -treated arm of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-
14 trial, a prospective randomized clinical trial examining the benefit of adjuvant
tamoxifen in hormone receptor-positive, node-negative breast cancer [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/6\">",
" 6",
" </a>",
" ]. Although this population had a generally good prognosis, the rate of
distant recurrence at 10 years was 7, 14, and 31 percent for patients with a low
(RS &lt;18), intermediate (RS 18 to 30), or high score (RS &gt;30) respectively.",
" </p>",
" <p>",
" Further analysis showed that for women on",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
" tamoxifen",
" </a>",
" , the RS was also predictive of locoregional and distant recurrence [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/7\">",
" 7",
" </a>",
" ]. Similar findings have been reported with aromatase inhibitors in
postmenopausal women [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/8\">",
" 8",
" </a>",
" ], suggesting that the RS identifies relative endocrine insensitivity as a
general phenomenon.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182725\">",
" <span class=\"h3\">",
" Predicting benefit from chemotherapy",
" </span>",
" &nbsp;&mdash;&nbsp;Multiple studies suggest that a high RS predicts patients
who will benefit from chemotherapy in the context of either pathologically negative
[",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/9-11\">",
" 9-11",
" </a>",
" ] or positive node involvement [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/8,10,12\">",
" 8,10,12",
" </a>",
" ]. This is illustrated in the following examples:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" In an analysis of patients with pathologically node-negative breast cancer
treated in NSABP B-20, the addition of CMF (",
" <a class=\"drug drug_general\" href=\"UTD.htm?9/20/9546?source=see_link\">",
" cyclophosphamide",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/38/24170?
source=see_link\">",
" methotrexate",
" </a>",
" , plus",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/32/33280?
source=see_link\">",
" fluorouracil",
" </a>",
" ) to",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
source=see_link\">",
" tamoxifen",
" </a>",
" resulted in a higher rate of distant disease free survival at 10 years among
patients with a high RS compared to treatment with tamoxifen alone (88 versus 60
percent, respectively; relative risk [RR] 0.26, 95% CI 0.13-0.53) [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/9\">",
" 9",
" </a>",
" ]. However, there was little evidence of a benefit with the addition of CMF
among those with a low RS (96 versus 97 percent; RR 1.31, 95% CI 0.46-3.78) or an
intermediate RS (90 versus 91 percent; RR 0.61, 95% CI 0.24-1.59).",
" <br/>",
" <br/>",
" Although it has been argued that the value of the RS can be estimated with
improvements in pathologic grading and quantitative hormone receptor scoring, this
study suggests that may not be true. Even with central laboratory grading, 19
percent of high-grade tumors had a low RS and 5 percent of low-grade tumors had a
high RS.",
" </li>",
" <li>",
" A separate study examined a subset of 367 tumors from postmenopausal women
with pathologically node-positive, hormone receptor-positive breast cancer treated
on Southwest Oncology Group (SWOG)-8814 who had been randomly assigned to",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
source=see_link\">",
" tamoxifen",
" </a>",
" alone or six cycles of CAF (",
" <a class=\"drug drug_general\" href=\"UTD.htm?9/20/9546?source=see_link\">",
" cyclophosphamide",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?35/37/36440?
source=see_link\">",
" doxorubicin",
" </a>",
" , and",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/32/33280?
source=see_link\">",
" fluorouracil",
" </a>",
" ) chemotherapy followed by tamoxifen [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/10\">",
" 10",
" </a>",
" ]. Compared to tamoxifen alone, the addition of CAF among women with a high
RS resulted in improvements in 10-year disease-free survival (55 versus 43 percent,
respectively; hazard rate [HR] 0.59, 95% CI 0.35-1.01) and overall survival (73
versus 54 percent, respectively; HR 0.56, 95% CI 0.31-1.02). These results were not
seen among women with a low or intermediate RS. &nbsp;",
" </li>",
" </ul>",
" </p>",
" <p>",
" The combined prognostic and predictive ability of RS, albeit limited, is the
reason that the RS is incorporated into adjuvant decision-making for node-negative
disease, as suggested by the American Society of Clinical Oncology (ASCO), the
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for
breast cancer, and the St Gallen International Expert Consensus [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/13,14\">",
" 13,14",
" </a>",
" ]. While it appears that the RS is helpful to determine those patients least
likely to benefit from the addition of chemotherapy, two issues remain
unresolved:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" To date, it is not clear at which RS cut-off chemotherapy should or should
not be administered. The recently completed",
" <a class=\"external\" href=\"file://clinicaltrials.gov/show/NCT00310180\">",
" TAILORx trial",
" </a>",
" will hopefully provide better data to inform the role of the RS in
identifying those node-negative patients who may and those who may not benefit from
chemotherapy [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/15\">",
" 15",
" </a>",
" ]. In this trial, women with an RS between 11 and 25 were randomly assigned
treatment with either endocrine therapy versus chemotherapy followed by endocrine
therapy.",
" </li>",
" <li>",
" Although the data from the SWOG study discussed above suggests a role for
the RS in patients with pathologically involved lymph nodes, we await the results
from prospective studies to better inform this application of the RS. The",
" <a class=\"external\" href=\"file://clinicaltrials.gov/show/NCT01272037\">",
" Southwest Oncology Group S1007 RxPONDER trial",
" </a>",
" , which utilizes the RS to assign hormone receptor-positive, HER2-negative,
node-positive patients to standard endocrine therapy with or without adjuvant
chemotherapy, is ongoing [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/16\">",
" 16",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Amsterdam 70-gene profile",
" </span>",
" &nbsp;&mdash;&nbsp;The Amsterdam 70-gene prognostic profile (Mammaprint) was
one of the first gene expression array-based marketed for prognostic purposes.
Although it was originally approved for use with unfixed, frozen tissue, it has now
been adapted for use with formalin-fixed, paraffin-embedded tissue. Unlike Oncotype
DX, it can be used to determine the prognosis in patients with breast cancer
regardless of hormone receptor-status and in patients with human epidermal growth
factor 2 (HER2) positive disease. However, it does not provide predictive
information on the utility of adjuvant therapy in patients.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182740\">",
" <span class=\"h3\">",
" Development of the 70-gene profile",
" </span>",
" &nbsp;&mdash;&nbsp;The 70-gene-profile was developed using a supervised DNA
microarray analysis of gene expression arrays on frozen tissue from 98 primary
breast tumors [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/17\">",
" 17",
" </a>",
" ]. A mathematical model is used to calculate a score that stratifies patients
as having a breast cancer with an associated poor-prognosis or good-prognosis.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182747\">",
" <span class=\"h3\">",
" Validation",
" </span>",
" &nbsp;&mdash;&nbsp;The 70-gene prognostic profile has been validated in
multiple studies [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/18-20\">",
" 18-20",
" </a>",
" ]. As examples:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" One study involved patients (age &lt;53 at diagnosis) with T1 to T2 node-
negative (n = 151) or node-positive (n = 144) breast cancer followed for nearly
seven years [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/18\">",
" 18",
" </a>",
" ]. The 10 year survival rates were 55 and 95 percent with the poor- and
good-prognosis gene signatures, respectively. The poor-prognosis signature was
significantly associated with an increased risk of distant metastases at 10 years
(49 versus 15 percent, hazard ratio [HR] 5.1, 95% CI 2.9 to 9.0).",
" </li>",
" <li>",
" A subsequent study was performed using data from 302 women under age 60 with
node-negative T1 to T2 tumors. Patients were treated without adjuvant systemic
chemotherapy and were followed for over 10 years [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/19\">",
" 19",
" </a>",
" ]. The 70-gene signature did better in predicting outcomes than clinical
factors (assessed using Adjuvant! Online), including time to distant metastasis (HR
2.13) and overall survival (HR 2.63), but not disease-free survival (HR 1.36). The
10 year overall survival rate was 70 versus 90 percent among women in the poor- or
good-prognosis signature group, respectively.",
" </li>",
" <li>",
" A separate study evaluated the role of the 70-gene signature in women with a
T1 breast cancer (size &le;2 cm) and reported that a poor-prognosis signature was
associated with lower breast cancer specific survival at 10 years compared to those
with a good-prognosis signature (72 versus 91 percent, respectively; HR for
mortality, 3.25, 95% CI 1.92-5.51) [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/21\">",
" 21",
" </a>",
" ]. The identification of a low risk group by prognosis signature was
independent of nodal status, tumor grade, ER and HER2 status.",
" </li>",
" </ul>",
" </p>",
" <p>",
" The clinical utility of the 70-gene profile will come from a large
international study, the",
" <a class=\"external\" href=\"file://clinicaltrials.gov/show/NCT00433589\">",
" Microarray in Node-Negative Disease May Avoid Chemotherapy (MINDACT) trial",
" </a>",
" , in which women with node negative breast cancer undergo clinical risk
assessment (using Adjuvant! Online and the 70-gene signature) [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/22\">",
" 22",
" </a>",
" ]. Patients with discordant clinical and genomic predictions are randomly
assigned to receive or not receive adjuvant chemotherapy. This trial has completed
accrual, and we await results to be presented.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182187\">",
" <span class=\"h2\">",
" PAM50 Risk of Recurrence Score",
" </span>",
" &nbsp;&mdash;&nbsp;The Predictor Analysis of Microarray 50 (PAM50) is a 50-
gene test that characterizes an individual tumor by intrinsic subtype [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/23\">",
" 23",
" </a>",
" ]. Results from the PAM50 are used to generate the risk of recurrence (ROR)
score, which can stratify patients with estrogen receptor-positive disease into
high, medium, and low subsets. The test can be performed on formalin-fixed
paraffin-embedded tissue. While not available for use in the US, it is available in
the European Union.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182762\">",
" <span class=\"h3\">",
" Development of the ROR score",
" </span>",
" &nbsp;&mdash;&nbsp;The PAM50 was developed using microarray and quantitative
RT-PCR data from a set of almost 190 prototype samples [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/23\">",
" 23",
" </a>",
" ]. In the initial testing set that included over 700 samples, a continuous
score was developed comprised of the intrinsic subtype (defined by the PAM50) and
tumor size, called the ROR score. The ROR was significantly predictive of prognosis
among patients with node-negative breast cancer [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/23\">",
" 23",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H1027182769\">",
" <span class=\"h3\">",
" Validation",
" </span>",
" &nbsp;&mdash;&nbsp;The PAM50 and ROR score has been subsequently validated in
several studies [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/24-27\">",
" 24-27",
" </a>",
" ]. Using data from two separate trials, the ROR score and PAM50 added
prognostic information beyond what could be assessed by clinical factors [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/26,27\">",
" 26,27",
" </a>",
" ]. In one study, the ROR outperformed the RS in its ability to stratify
patients with hormone receptor-positive, node-negative breast cancer into the high
rather than intermediate risk group [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/26\">",
" 26",
" </a>",
" ], suggesting the ROR may be a better prognostic indicator than the RS among
this population.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1644710771\">",
" <span class=\"h2\">",
" Other genomic signatures",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h3\">",
" 76-gene signature",
" </span>",
" &nbsp;&mdash;&nbsp;The",
" <span class=\"nowrap\">",
" Rotterdam/Veridex",
" </span>",
" 76-gene prognostic signature was developed in a test set of 115 node-negative
primary breast cancers from women who did not receive adjuvant therapy and had been
followed for more than eight years [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/28\">",
" 28",
" </a>",
" ]. Recognizing the genetic heterogeneity of breast cancer, separate prognostic
gene sets were developed for ER-negative (comprised of 16 genes) and ER-positive
(comprised of 60 genes) disease.",
" </p>",
" <p>",
" The 76 prognostic gene signature was validated in an independent set of 171
tumors, demonstrating 93 percent sensitivity and 48 percent specificity. It also
predicted distant metastasis-free survival independent of clinical variables.
Subsequent studies have validates the prognostic ability of this signature for
relapse free survival, particularly among patients with ER-positive disease [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/29,30\">",
" 29,30",
" </a>",
" ]. Further studies are required to validate this test prior to its use in
clinical practice.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1644710909\">",
" <span class=\"h3\">",
" Breast cancer index (BCI)",
" </span>",
" &nbsp;&mdash;&nbsp;The BCI is a combination of two profiles, the HOXB13-to-
IL17BR expression ratio (H:I ratio) and the Molecular Grade Index (MGI). Using
genome-wide microarray analysis, three differentially expressed genes were
identified: the antiapoptotic homeobox B13 (HOXB13, overexpressed in women who
took",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
" tamoxifen",
" </a>",
" and then recurred) and both interleukin 17B receptor (IL17BR) and EST AI240933
(overexpressed in women who took tamoxifen regardless of whether they recurred or
not) [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/31\">",
" 31",
" </a>",
" ]. Compared to clinical prognostic factors (eg, age, tumor size, tumor grade,
and lymph node status), the H:I ratio was significantly and independently
correlated with outcome (odds ratio [OR] 7.3, 95% CI 2.1-26).",
" </p>",
" <p>",
" Subsequent studies have validated the BCI as an accurate predictor of
endocrine responsiveness [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/32\">",
" 32",
" </a>",
" ] and prognosis [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6503/abstract/32,33\">",
" 32,33",
" </a>",
" ]. Given the emerging role of extended adjuvant therapy, efforts to identify
those patients more likely to benefit is of great potential value. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?19/40/20106?
source=see_link&amp;anchor=H38114838#H38114838\">",
" \"Adjuvant endocrine therapy for hormone receptor-positive breast cancer\",
section on 'Duration of endocrine treatment'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h1\">",
" SUMMARY",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Gene expression profiling is the simultaneous analysis of expression of
large numbers of genes. It has been used to develop breast cancer molecular
signatures. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" Molecular signatures offer the potential for use in clinical practice for
prognostic stratification and treatment selection for patients with breast cancer,
particularly if they are hormone receptor-positive. These molecular prognostic
profiles augment, but do not replace classic clinical factors. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" The most validated signatures in breast cancer include the 21-gene
recurrence score (RS, Oncotype Dx), the Amsterdam 70-gene profile, and the PAM50
Risk of Recurrence (ROR) score. All of these techniques can be performed on
formalin-fixed paraffin-embedded tissue. (See",
" <a class=\"local\" href=\"#H1237831274\">",
" 'Molecular profiles in breast cancer'",
" </a>",
" above.)",
" </li>",
" <li>",
" Despite the ability of these signatures to inform prognosis, none provide
insight into the optimal choice of chemotherapy regimen, if indicated. (See",
" <a class=\"local\" href=\"#H1237831259\">",
" 'Prognostic versus predictive factors'",
" </a>",
" above.)",
" </li>",
" <li>",
" We support obtaining the RS in patients with hormone receptor-positive,
HER2-negative, pathologically node-negative breast cancer in whom chemotherapy
added to endocrine therapy is considered. It is not clear what additional (or
alternative) advantages other genomic profiles offer at this time. We await results
of ongoing clinical trials to inform the roles of other signatures in the
management of newly diagnosed breast cancer. (See",
" <a class=\"local\" href=\"#H3\">",
" 'Recurrence score'",
" </a>",
" above.)",
" </li>",
" <li>",
" The Amsterdam 70-gene profile is a reasonable alternative to the RS for
informing the prognosis of patients with newly diagnosed breast cancer. However,
there are insufficient data about the clinical utility of this tool in decision-
making about chemotherapy benefit for patients with ER-positive disease. It does
not provide value in recommendations for systemic treatment for patients with ER-
negative disease. (See",
" <a class=\"local\" href=\"#H4\">",
" 'Amsterdam 70-gene profile'",
" </a>",
" above.)",
" </li>",
" <li>",
" The PAM50 ROR is a reasonable alternative to the RS to assign patients with
hormone receptor-positive disease into different prognostic groups. However, like
the Amsterdam 70-gene profile, there are insufficient data regarding the clinical
utility of this tool in determining the role of chemotherapy for these patients.
(See",
" <a class=\"local\" href=\"#H1027182187\">",
" 'PAM50 Risk of Recurrence Score'",
" </a>",
" above.)",
" </li>",
" <li>",
" A number of other signatures are under development, including the two-gene
signature (HOX13:IL17BR), which may prove useful in identifying endocrine
sensitivity and late relapse. (See",
" <a class=\"local\" href=\"#H1644710771\">",
" 'Other genomic signatures'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/18\">",
" van de Vijver MJ, He YD, van't Veer LJ, et al. A gene-expression signature
as a predictor of survival in breast cancer. N Engl J Med 2002; 347:1999.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/19\">",
" Buyse M, Loi S, van't Veer L, et al. Validation and clinical utility of a
70-gene prognostic signature for women with node-negative breast cancer. J Natl
Cancer Inst 2006; 98:1183.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/20\">",
" Mook S, Schmidt MK, Weigelt B, et al. The 70-gene prognosis signature
predicts early metastasis in breast cancer patients between 55 and 70 years of age.
Ann Oncol 2010; 21:717.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/21\">",
" Mook S, Knauer M, Bueno-de-Mesquita JM, et al. Metastatic potential of T1
breast cancer can be predicted by the 70-gene MammaPrint signature. Ann Surg Oncol
2010; 17:1406.",
" </a>",
" </li>",
" <li>",
" EORTC Trial 10041 (BIG 3-04) - MINDACT (Microarray In Node-negative and 1 to
3 positive lymph node Disease may Avoid ChemoTherapy). A prospective randomized
study comparing the 70-gene signature with the common clinical-pathological
criteria in selecting patients for adjuvant chemotherapy in breast cancer with 0-3
positive nodes.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/23\">",
" Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast
cancer based on intrinsic subtypes. J Clin Oncol 2009; 27:1160.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/24\">",
" Nielsen TO, Parker JS, Leung S, et al. A comparison of PAM50 intrinsic
subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-
treated estrogen receptor-positive breast cancer. Clin Cancer Res 2010; 16:5222.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/25\">",
" Chia SK, Bramwell VH, Tu D, et al. A 50-gene intrinsic subtype classifier
for prognosis and prediction of benefit from adjuvant tamoxifen. Clin Cancer Res
2012; 18:4465.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/26\">",
" Dowsett M, Lopez-Knowles E, Sidhu K. Comparison of PAM50 risk of recurrence
(ROR) score with oncotypeDx and IHC4 for predicting residual risk of RFS and
distant RFS after endocrine therapy: A TransATAC study. Cancer Res 2011;
71:Abstract nr S4/5.",
" </a>",
" </li>",
" <li>",
" Gnant M, Filipits M, B Mlineritsch B, et al. Clinical validation of the PAM50
risk of recurrence (ROR) score for predicting residual risk of distant-recurrence
(DR) after endocrine therapy in postmenopausal women with ER+ early breast cancer
(EBC): An ABCSG study. Cancer Res 2012; 72: Abstract nr S4/3.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/28\">",
" Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict
distant metastasis of lymph-node-negative primary breast cancer. Lancet 2005;
365:671.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/29\">",
" Foekens JA, Atkins D, Zhang Y, et al. Multicenter validation of a gene
expression-based prognostic signature in lymph node-negative primary breast cancer.
J Clin Oncol 2006; 24:1665.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/30\">",
" Desmedt C, Piette F, Loi S, et al. Strong time dependence of the 76-gene
prognostic signature for node-negative breast cancer patients in the TRANSBIG
multicenter independent validation series. Clin Cancer Res 2007; 13:3207.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/31\">",
" Ma XJ, Wang Z, Ryan PD, et al. A two-gene expression ratio predicts clinical
outcome in breast cancer patients treated with tamoxifen. Cancer Cell 2004;
5:607.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/22/6503/abstract/32\">",
" Jansen MP, Sieuwerts AM, Look MP, et al. HOXB13-to-IL17BR expression ratio
is related with tumor aggressiveness and response to tamoxifen of recurrent breast
cancer: a retrospective study. J Clin Oncol 2007; 25:662.",
" </a>",
" </li>",
" <li>",
" Sgroi DC, Sestak I, Cuzick J, et al. Comparative performance of breast cancer
Index (BCI) vs. Oncotype Dx and IHC4 in the prediction of late recurrence in
hormonal receptor-positive lymph node-negative breast cancer patients: A TransATAC
Study. Cancer Res 2012; 72 (24 Suppl); Abstract nr S1-9.",
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" PROGNOSTIC VERSUS PREDICTIVE FACTORS",
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" - Development of the 70-gene profile",
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" - Validation",
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" Other genomic signatures",
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" - 76-gene signature",
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" - Breast cancer index (BCI)",
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" REFERENCES",
" </a>",
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" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
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" </a>",
" </li>",
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source=related_link\">",
" Measurement of prognostic factors in breast cancer",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/21/41302?
source=related_link\">",
" Molecular intrinsic subtypes of breast cancer",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/47/39674?
source=related_link\">",
" Overview of gene expression profiling, proteomics, and microRNA profiling in
clinical oncology",
" </a>",
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" </div>",
" <div class=\"lgnd\">",
" Lichenoid interface dermatitis resembling that of idiopathic lichen planus.",
" <br/>",
" (A) Compact hyperorthokeratosis, thickened stratum granulosum and irregular
acanthosis of the epidermis together with a superficial lichenoid lymphocytic
infiltrate (hematoxylin-eosin, x100).",
" <br/>",
" (B and C) Higher magnification with necrotic keratinocytes up to the mid-
epidermal layers (hematoxylin-eosin, x200).",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_22_6504=[""].join("\n");
var outline_f6_22_6504=null;
var title_f6_22_6505="Coronary artery bypass graft surgery after acute ST elevation
myocardial infarction";
var content_f6_22_6505=[" <noscript>",
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" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Coronary artery bypass graft surgery after acute ST elevation myocardial
infarction",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/22/6505/contributors\">",
" Authors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6505/contributors\">",
" Oz M Shapira, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6505/contributors\">",
" John A Bittl, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/22/6505/contributors\">",
" Section Editors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6505/contributors\">",
" Gabriel S Aldea, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6505/contributors\">",
" Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6505/contributors\">",
" Donald Cutlip, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/22/6505/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/22/6505/contributors\">",
" Gordon M Saperia, MD, FACC",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/22/6505/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
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" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Jan 3, 2013.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;In patients with acute ST-elevation myocardial infarction
(STEMI), prompt restoration of myocardial blood flow is essential to optimize
myocardial salvage and decrease mortality. This is particularly important in the
first few hours after symptom onset, when the amount of myocardium salvageable by
reperfusion is greatest. Coronary artery reperfusion, if performed in a timely
manner, improves clinical outcomes compared to no reperfusion in nearly all groups
of patients with an acute ST elevation myocardial infarction (STEMI). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?15/46/16106?
source=see_link&amp;anchor=H4#H4\">",
" \"Primary percutaneous coronary intervention in acute ST elevation myocardial
infarction: Determinants of outcome\", section on 'Time from hospital arrival
(door-to-balloon time) on outcomes'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?1/43/1721?
source=see_link&amp;anchor=H69239847#H69239847\">",
" \"Fibrinolytic therapy in acute ST elevation myocardial infarction:
Initiation of therapy\", section on 'Timing'",
" </a>",
" .)",
" </p>",
" <p>",
" Both primary percutaneous coronary intervention (PCI) and fibrinolysis can
restore blood flow in an acutely occluded coronary artery in a much shorter time
than can coronary artery bypass graft surgery (CABG) and these procedures are
preferred to CABG in most cases. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/31/37369?
source=see_link\">",
" \"Selecting a reperfusion strategy for acute ST elevation myocardial
infarction\"",
" </a>",
" .)",
" </p>",
" <p>",
" This topic will address the indications, optimal timing, technical
considerations, and outcomes of urgent or emergent CABG in patients with acute
STEMI. The role of CABG in patients with non-ST elevation MI or unstable angina is
discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/1/29722?
source=see_link\">",
" \"Coronary arteriography and revascularization for unstable angina or non-ST
elevation acute myocardial infarction\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" INDICATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;In all studies of percutaneous coronary intervention (PCI)
or fibrinolysis, outcomes improve as the time from symptom onset to reperfusion
decreases. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?15/46/16106?
source=see_link&amp;anchor=H4#H4\">",
" \"Primary percutaneous coronary intervention in acute ST elevation myocardial
infarction: Determinants of outcome\", section on 'Time from hospital arrival
(door-to-balloon time) on outcomes'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?1/43/1721?
source=see_link&amp;anchor=H69239847#H69239847\">",
" \"Fibrinolytic therapy in acute ST elevation myocardial infarction:
Initiation of therapy\", section on 'Timing'",
" </a>",
" .)",
" </p>",
" <p>",
" In most cases, PCI or fibrinolysis can usually restore flow to the ischemic
myocardium more quickly than CABG, largely attributable to delays in getting the
patient to the operating room and the time it takes to complete the bypass surgical
procedure. Thus, CABG is uncommonly used as the reperfusion strategy of choice in
STEMI; it is estimated that CABG is performed in 5 percent or less of cases [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/1,2\">",
" 1,2",
" </a>",
" ].",
" </p>",
" <p>",
" CABG may be considered for the following subgroups of patients with STEMI.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" After unsuccessful or complicated PCI",
" </span>",
" &nbsp;&mdash;&nbsp;In most acute STEMI cases, the site of occlusion
responsible for the MI can be identified and successfully opened with PCI and
stenting. When successful, this leads to an improvement in clinical and
electrocardiographic signs of ischemia. In a small minority of cases, either the
culprit lesion cannot be identified or reperfusion cannot be reestablished. In such
cases, patients with ongoing ischemia may benefit from",
" <span class=\"nowrap\">",
" urgent/emergent",
" </span>",
" CABG in an effort to minimize myocardial damage and decrease in-hospital
morbidity and mortality.",
" </p>",
" <p>",
" Increased interventional experience and advances in technology have led to a
decline in the incidence of acute complications of PCI (irrespective of whether it
is in the setting of STEMI or not) to the range of 2 to 4 percent. Examples of
complications for which urgent CABG might be indicated include failed stent
deployment, extensive coronary artery dissection, perforation of a coronary artery
leading to pericardial tamponade, or recurrent acute closure. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/48/38666?
source=see_link&amp;anchor=H22#H22\">",
" \"Periprocedural complications of percutaneous coronary intervention\",
section on 'Emergency CABG for failed PCI'",
" </a>",
" .)",
" </p>",
" <p>",
" Patients with either unsuccessful or complicated PCI who have ongoing ischemia
and anatomy suitable for CABG should be referred for consideration of CABG as
opposed to a strategy of medical therapy only. The rationale includes: older
studies demonstrating acceptable surgical mortality after CABG in patients with
failed balloon angioplasty [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/3-6\">",
" 3-6",
" </a>",
" ]; small observational studies that have shown benefit from CABG after PCI in
patients with cardiogenic shock [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/7\">",
" 7",
" </a>",
" ]; and evidence from all studies of patients who are reperfused with either
fibrinolytic therapy or primary PCI in which outcomes are uniformly better than
with medical therapy alone. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?15/46/16106?
source=see_link&amp;anchor=H4#H4\">",
" \"Primary percutaneous coronary intervention in acute ST elevation myocardial
infarction: Determinants of outcome\", section on 'Time from hospital arrival
(door-to-balloon time) on outcomes'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?1/43/1721?
source=see_link&amp;anchor=H69239847#H69239847\">",
" \"Fibrinolytic therapy in acute ST elevation myocardial infarction:
Initiation of therapy\", section on 'Timing'",
" </a>",
" .)",
" </p>",
" <p>",
" The risks and benefits should be discussed among members of a
multidisciplinary team and with the patient and family. Factors favoring emergent
CABG include a large amount of ischemic myocardium, good general health, bypassable
vessels, and the ability to perform surgery within six hours of the PCI. The
presence of life-threatening ventricular arrhythmia should also drive the decision
for emergent CABG. (See",
" <a class=\"local\" href=\"#H358599859\">",
" 'Life threatening ventricular arrhythmias'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Mechanical complications of acute MI",
" </span>",
" &nbsp;&mdash;&nbsp;Mechanical complications of acute MI include rupture of the
left ventricular free wall or interventricular septum and acute mitral
regurgitation. Medical treatment alone results in close to 100 percent mortality in
these patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/8\">",
" 8",
" </a>",
" ]. Most of these patients will require emergency cardiac surgical repair of
the mechanical defect; CABG will be performed at that time. The approach to these
patients is discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/19/39225?
source=see_link\">",
" \"Mechanical complications of acute myocardial infarction\"",
" </a>",
" .)",
" </p>",
" <p>",
" We prefer immediate CABG, as opposed to PCI of the infarct related artery
followed by CABG and repair of the mechanical defect since termination of the
ischemia often does not lessen the adverse hemodynamic impact of the mechanical
defect, which may cause death. However, in some patients it may be appropriate to
initially reperfuse the patient with PCI and then have the patient undergo cardiac
surgery. For example, a patient with an acutely occluded (culprit) lesion in the
circumflex coronary artery, significant mitral regurgitation, and severe disease in
the left anterior descending and right coronary arteries (LAD and RCA) might
benefit from acute PCI of the circumflex and then CABG to the LAD and RCA with
repair of the mitral valve.",
" </p>",
" <p>",
" In all cases in which a mechanical defect has been identified, we recommend
immediate consultation between the interventional cardiologist and the
cardiothoracic surgeon. Other members of a multidisciplinary team should be
involved as necessary.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h2\">",
" As the primary reperfusion strategy",
" </span>",
" &nbsp;&mdash;&nbsp;Most patients with acute STEMI should receive either PCI or
fibrinolysis as the primary reperfusion strategy. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Indications'",
" </a>",
" above.) Studies of patients treated with either fibrinolysis or percutaneous
coronary intervention (PCI) have demonstrated that outcomes improve as the time to
reperfusion decreases.",
" </p>",
" <p>",
" In stable patients with left main or severe three vessel coronary artery
disease, CABG is often preferred to PCI (",
" <a class=\"graphic graphic_table graphicRef61364 \" href=\"UTD.htm?
43/4/44107\">",
" table 1",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/38/27240?
source=see_link&amp;anchor=H19#H19\">",
" \"Bypass surgery versus percutaneous intervention in the management of stable
angina pectoris: Recommendations\", section on 'Summary and recommendations'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/20/4426?
source=see_link&amp;anchor=H29#H29\">",
" \"Management of left main coronary artery disease\", section on 'Summary and
recommendations'",
" </a>",
" .)",
" </p>",
" <p>",
" There are no randomized trials or large, well-conducted observational studies
that have compared PCI to CABG in patients with left main or severe multivessel
disease in the setting of an acute MI. Our experience is that PCI can be performed
successfully and without major complication in the majority of cases. The decision
of whether to perform PCI or CABG as the primary reperfusion strategy in patients
with left main coronary artery disease or severe multivessel disease who are
unstable or who have ongoing ischemia is complex and should be individualized.
Management should involve cardiothoracic surgeons and interventional cardiologists
on a multidisciplinary team. The discussion should include deciding on the primary
reperfusion strategy and subsequent steps after &ldquo;culprit lesion&rdquo;
intervention if PCI is performed, as well as what will be done if initial catheter
based therapy fails.",
" </p>",
" <p>",
" We believe it is reasonable to perform PCI of a culprit unprotected left main
coronary artery if distal flow is abnormal and PCI can be performed more rapidly
and safely than CABG. This recommendation is consistent with that made in the 2011
American College of Cardiology",
" <span class=\"nowrap\">",
" Foundation/American",
" </span>",
" Heart",
" <span class=\"nowrap\">",
" Association/Society",
" </span>",
" of Cardiovascular angiography and Intervention PCI guideline [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/9,10\">",
" 9,10",
" </a>",
" ].",
" </p>",
" <p>",
" Patients who might benefit from CABG as the primary reperfusion strategy
include those who are no longer showing signs of acute ischemia (patients who have
stabilized) and have coronary anatomy at the time of coronary angiography that
suggests a benefit from CABG as opposed to PCI. Patients with left main or severe
multivessel coronary disease, particularly with depressed left ventricular systolic
function or those with diabetes are examples. If the patient is stable without
signs or symptoms of ongoing ischemia either clinically or by electrocardiogram,
CABG should be strongly considered as the primary reperfusion strategy in these
patients. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/38/27240?
source=see_link&amp;anchor=H19#H19\">",
" \"Bypass surgery versus percutaneous intervention in the management of stable
angina pectoris: Recommendations\", section on 'Summary and recommendations'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H259318985\">",
" <span class=\"h2\">",
" Late presentation or recurrent ischemia",
" </span>",
" &nbsp;&mdash;&nbsp;Some patients with STEMI present late (after 12 hours) and
are asymptomatic at the time of presentation; thus, urgent intervention is not
necessary. Subsequently, some of these individuals develop recurrent or inducible
angina or have reinfarction and require revascularization with either PCI or CABG.
We suggest using recommendations made for patients with stable coronary artery
disease as a guide for who should be referred for CABG and who for PCI. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/38/27240?
source=see_link&amp;anchor=H19#H19\">",
" \"Bypass surgery versus percutaneous intervention in the management of stable
angina pectoris: Recommendations\", section on 'Summary and recommendations'",
" </a>",
" .)",
" </p>",
" <p>",
" A few patients with STEMI who have received successful primary PCI develop
recurrent angina due to ischemia in a territory not reperfused at the time of PCI.
Many of these patients should be referred for repeat revascularization with either
PCI or CABG. For patients with multivessel disease who fall into this category
within the first 48 hours after STEMI, we agree with the 2011 American College of
Cardiology",
" <span class=\"nowrap\">",
" Foundation/American",
" </span>",
" Heart Association CABG guideline that states that urgent CABG is reasonable
compared to a delayed strategy [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/11\">",
" 11",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H2860987\">",
" <span class=\"h2\">",
" Cardiogenic shock",
" </span>",
" &nbsp;&mdash;&nbsp;Cardiogenic shock occurs in 6 to 7 percent of patients with
acute MI (excluding patients with mechanical complications). This complication
signifies loss of at least 40 percent of the left ventricular contractile mass.
Mortality with medical treatment of cardiogenic shock in acute MI approaches 80
percent. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?15/60/16329?
source=see_link\">",
" \"Clinical manifestations and diagnosis of cardiogenic shock in acute
myocardial infarction\"",
" </a>",
" .)",
" </p>",
" <p>",
" Cardiogenic shock occurs most often in patients with left main or severe three
vessel coronary artery disease, but can occur in patients with one- or two-vessel
disease. Although the limited evidence suggests similar outcomes, we prefer PCI to
CABG, irrespective of the extent of disease, if it can be performed in a timely
manner by a skilled team and if a mechanical complication of STEMI is not present.
The full discussion of the use of CABG in such patients is presented separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/37/35418?
source=see_link&amp;anchor=H36#H36\">",
" \"Prognosis and treatment of cardiogenic shock complicating acute myocardial
infarction\", section on 'Coronary artery bypass surgery'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2860937\">",
" <span class=\"h2\">",
" After failed fibrinolysis",
" </span>",
" &nbsp;&mdash;&nbsp;CABG is employed infrequently for revascularization after
failed fibrinolysis. PCI is preferred in this setting because of increased risks of
perioperative mortality and major hemorrhage with CABG, especially if the interval
between administration of the fibrinolytic agent and surgery is short. In an
analysis from the TIMI II study, 390 patients underwent CABG after fibrinolytic
treatment [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/12\">",
" 12",
" </a>",
" ]. Patients undergoing surgery within 24 hours of study, compared to those
undergoing later surgery, had higher rates of perioperative mortality (17 versus 4
percent) and major hemorrhage (74 versus 51 percent). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/27/8634?
source=see_link\">",
" \"Management of failed fibrinolysis (thrombolysis) or threatened reocclusion
in acute ST elevation myocardial infarction\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H358599859\">",
" <span class=\"h2\">",
" Life threatening ventricular arrhythmias",
" </span>",
" &nbsp;&mdash;&nbsp;Life-threatening ventricular arrhythmias occurring in the
setting of acute MI are triggered by ischemic myocardium or the combination of
ischemic myocardium plus scar formed from prior events. They are associated with
worse in-hospital mortality. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/10/30890?
source=see_link\">",
" \"Clinical features and treatment of ventricular arrhythmias during acute
myocardial infarction\"",
" </a>",
" .)",
" </p>",
" <p>",
" There are no randomized trials or important observational studies that
evaluated the optimal management strategy in these patients. Small series have
included patients with life-threatening ventricular arrhythmia in the setting of
acute MI [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/13,14\">",
" 13,14",
" </a>",
" ]. These studies suggest that operative and long-term mortality (approximately
7 and 15 percent, respectively) are reasonable with urgent CABG and that the
incidence of sudden death is reduced compared to no CABG.",
" </p>",
" <p>",
" As life-threatening ventricular arrhythmias often represent ongoing ischemia
in the setting of STEMI, our approach to revascularization is similar to the broad
population of patients with STEMI for whom we prefer PCI to CABG. We agree with
recommendations made in the 2011 American College of Cardiology",
" <span class=\"nowrap\">",
" Foundation/American",
" </span>",
" Heart Association CABG guideline, which states that urgent CABG is a
reasonable approach for patients with ongoing ischemia who will not undergo
emergent revascularization with PCI and who have left main stenosis greater than or
equal to 50 percent and or 3-vessel coronary artery disease [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/11\">",
" 11",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h1\">",
" TIMING",
" </span>",
" &nbsp;&mdash;&nbsp;For those patients in whom CABG will be performed, the
optimal timing depends on the indication. Ongoing ischemia, cardiogenic shock, PCI
failure, and mechanical complications are indications for emergency operation.",
" </p>",
" <p>",
" The optimal timing in more stable patients with indications for CABG is
unclear, with some older studies showing increased mortality when CABG was
performed in the first 12 to 24 hours after acute MI [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/12,15-19\">",
" 12,15-19",
" </a>",
" ] and others not [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/20-25\">",
" 20-25",
" </a>",
" ].",
" <br/>",
" </p>",
" <p>",
" We feel that CABG can be performed safely in patients with post-MI angina
based upon the patient's clinical status. In our view, patients presenting within
six hours after onset of symptoms should be operated emergently to maximize
myocardial salvage. The goal should be to complete bypass within 12 hours of
symptom onset.",
" </p>",
" <p>",
" Patients who present later than six hours after onset of symptoms when
myocardial necrosis has reached its peak should probably be delayed for three to
four days to decrease mortality and morbidity, including bleeding complications [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/1,26\">",
" 1,26",
" </a>",
" ].",
" </p>",
" <p>",
" For patients with recurrent or inducible ischemia or reinfraction,
particularly those with multivessel disease, CABG within 48 hours is a reasonable
strategy compared to more delayed revascularization.",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h1\">",
" TECHNICAL CONSIDERATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Several technical issues need to be considered in patients
undergoing CABG after acute STEMI.",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h2\">",
" Minimizing ischemic time",
" </span>",
" &nbsp;&mdash;&nbsp;An expeditious operation to shorten the interval during
which the patient is actively ischemic or hemodynamically unstable is a critical
component of the overall strategy aimed at reducing myocardial injury and systemic
organ dysfunction. Thus, patients who are continuously ischemic, hemodynamically
unstable, or having recurrent life-threatening arrhythmias should be stabilized and
transferred rapidly to the operating room. Resuscitation should continue en-route
to surgery, and unnecessary delays should be avoided. Aggressive use of
pharmacologic agents and the intraaortic balloon pump is essential to achieve
stabilization. Percutaneous bypass may be used in some patients as part of
resuscitation in the catheterization laboratory. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?15/34/15911?
source=see_link\">",
" \"Circulatory assist devices: Cardiopulmonary assist device and short-term
left ventricular assist devices\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h2\">",
" Intraaortic balloon pump",
" </span>",
" &nbsp;&mdash;&nbsp;The intraaortic balloon pump (IABP) can be an extremely
important adjunct to surgical treatment in patients with acute MI and mechanical
complications. For other patients, such as those with cardiogenic shock, the role
of a preoperative IABP is less clear. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/37/35418?
source=see_link&amp;anchor=H42#H42\">",
" \"Prognosis and treatment of cardiogenic shock complicating acute myocardial
infarction\", section on 'Summary and Recommendations'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/36/13896?
source=see_link\">",
" \"Intraaortic balloon pump counterpulsation\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h2\">",
" Type of graft",
" </span>",
" &nbsp;&mdash;&nbsp;The choice of bypass conduit is dictated by the patient's
condition.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" In the stable patient, arterial revascularization (particularly the left
internal mammary artery to the left anterior descending coronary artery) should be
used because of its superior short and long-term clinical results. Even in urgent
or emergency situation, aggressive use of arterial conduits should be pursued if
the patient can be stabilized. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/2/37930?
source=see_link&amp;anchor=H12#H12\">",
" \"Long-term outcome after coronary artery bypass graft surgery\", section
on 'LIMA plus another arterial graft'",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p>",
" In the unstable patient, venous conduits are preferred. This affords a more
expeditious revascularization and an opportunity to directly deliver cardioplegia,
to control reperfusion to the acutely ischemic area, and to avoid postoperative
vasospasm in patients who are usually on varying amounts of vasopressors [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/27,28\">",
" 27,28",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H259318725\">",
" <span class=\"h2\">",
" Minimally invasive CABG",
" </span>",
" &nbsp;&mdash;&nbsp;We believe that both on- and off-pump CABG are acceptable
techniques for patients with STEMI. An early report of 57 patients with acute MI
minimally invasive (off-pump) CABG without cardiopulmonary bypass suggested that
this procedure is associated with relatively low risk [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/29\">",
" 29",
" </a>",
" ]. In another trial, 128 patients within 48 hours of symptom onset were
randomly assigned to either on-pump or off-pump CABG [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/30\">",
" 30",
" </a>",
" ]. In-hospital mortality was significantly better in the off-pump group (1.6
versus 7.7 percent). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/10/37031?
source=see_link\">",
" \"Off-pump and minimally invasive direct coronary artery bypass graft
surgery: Outcomes\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H259318798\">",
" <span class=\"h2\">",
" Hybrid procedure",
" </span>",
" &nbsp;&mdash;&nbsp;An alternative approach to CABG in high-risk groups of
patients with STEMI is a hybrid operation. A subset of patients with suitable
anatomy may benefit from a minimally-invasive off-pump CABG of a left internal
mammary to the left anterior descending coronary artery in conjunction with PCI to
other significantly diseased coronary arteries. In select groups of patients, this
can be achieved during the same procedure performed in a hybrid operating room. In
other patients, the revascularization procedure can be staged. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?43/16/44296?
source=see_link&amp;anchor=H113901358#H113901358\">",
" \"Minimally invasive coronary artery bypass graft surgery: Definitions and
technical issues\", section on 'Hybrid procedures'",
" </a>",
" .) &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H16\">",
" <span class=\"h1\">",
" OUTCOMES AFTER CABG",
" </span>",
" &nbsp;&mdash;&nbsp;Numerous observational studies published between the mid-
1970s and the mid-1990s reported early and late outcomes after CABG for STEMI.
Hospital mortality was less than 10 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/1,12,17-19,21-27,31-
57\">",
" 1,12,17-19,21-27,31-57",
" </a>",
" ] and long-term freedom from angina and survival were improved compared to
medical therapy [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/12,18,19,21-23,27,33-
37,39-47,49,51,54,55\">",
" 12,18,19,21-23,27,33-37,39-47,49,51,54,55",
" </a>",
" ].",
" </p>",
" <p>",
" However, the applicability of the results of these studies to patients treated
since the introduction of PCI and the use of aggressive antithrombotic and statin
therapy is limited. Observational studies that have evaluated in-hospital or 30-day
mortality since 2000 have reported rates ranging between 1.7 and 22 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/1,2,58,59\">",
" 1,2,58,59",
" </a>",
" ]. The variation in mortality is likely explained by differences in patient
selection and severity of illness.",
" </p>",
" <p class=\"headingAnchor\" id=\"H526663924\">",
" <span class=\"h1\">",
" RECOMMENDATIONS OF OTHERS",
" </span>",
" &nbsp;&mdash;&nbsp;Recommendations for the use of CABG in patients with STEMI
are available from the American College of Cardiology",
" <span class=\"nowrap\">",
" Foundation/American",
" </span>",
" Heart Association and the European Society of Cardiology [",
" <a class=\"abstract\" href=\"UTD.htm?6/22/6505/abstract/11,60\">",
" 11,60",
" </a>",
" ]. Our recommendations are generally consistent with those made by these
organizations.",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" <sup>",
" th",
" </sup>",
" to 6",
" <sup>",
" th",
" </sup>",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" <sup>",
" th",
" </sup>",
" to 12",
" <sup>",
" th",
" </sup>",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Beyond the Basics topic (see",
" <a class=\"medical medical_patient\" href=\"UTD.htm?30/62/31717?
source=see_link\">",
" \"Patient information: Coronary artery bypass graft surgery (Beyond the
Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H22\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" One of the most important determinants of long-term outcome after ST-
elevation myocardial infarction (STEMI) is the speed with which blood flow is
restored to the ischemic myocardium. Under most circumstances this can be
accomplished more quickly with either primary percutaneous coronary intervention
(PCI) or fibrinolysis than with coronary artery bypass graft surgery (CABG).
Therefore, in patients with coronary anatomy suitable for surgery, the role of CABG
after acute MI is probably limited to those with cardiogenic shock, unsuccessful or
complicated primary PCI, mechanical complications, or those with a late
presentation (after 12 hours) or early recurrent ischemia. STEMI patients who are
not candidates for fibrinolysis or primary PCI should also be considered for CABG.
(See",
" <a class=\"local\" href=\"#H2\">",
" 'Indications'",
" </a>",
" above.):",
" </li>",
" <li>",
" For those patients in whom CABG will be performed, the optimal timing
depends on the indication. Ongoing ischemia, cardiogenic shock, PCI failure, and
mechanical complications are indications for emergency operation. The optimal
timing in more stable patients with indications for CABG is unclear; the decision
on timing should be made by a multidisciplinary team. (See",
" <a class=\"local\" href=\"#H9\">",
" 'Timing'",
" </a>",
" above.)",
" <br/>",
" <br/>",
" Patients who present later than six hours after onset of symptoms when
myocardial necrosis has reached its peak should probably be delayed for three to
four days to decrease mortality and morbidity, including bleeding complications.",
" <br/>",
" <br/>",
" For patients with recurrent or inducible ischemia or reinfarction,
particularly those with multivessel disease, CABG within 48 hours is a reasonable
strategy compared to more delayed revascularization.",
" </li>",
" <li>",
" Life-threatening ventricular arrhythmias occurring in the setting of acute
STEMI are associated with a significant increase in in-hospital mortality. Their
presence does not alter any of our recommendations below.",
" </li>",
" <li>",
" The following are our recommendations for the use of CABG (or percutaneous
coronary intervention) in patients with acute STEMI:",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" For patients with STEMI, outcomes improve as the time from symptom onset to
reperfusion decreases. In most cases, reperfusion can be achieved more quickly with
fibrinolysis or primary percutaneous coronary intervention (PCI) than with CABG.
Thus, for most patients, fibrinolysis or PCI is preferred to CABG. This preference
for PCI includes patients with one or two vessel disease who have cardiogenic
shock, but are without mechanical complications, as the restoration of myocardial
blood flow with PCI of the infarct related artery may take only minutes after
diagnostic coronary angiography has been performed. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Indications'",
" </a>",
" above.)",
" </li>",
" <li>",
" For patients with left main (as the culprit lesion) or three vessel coronary
artery disease, with or without cardiogenic shock, who do not have mechanical
complications (such as acute mitral regurgitation or rupture of either the
ventricular septal or free walls), we suggest immediate PCI rather than CABG (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). CABG is a reasonable alternative to PCI when it can be performed more
rapidly than PCI. (See",
" <a class=\"local\" href=\"#H2860987\">",
" 'Cardiogenic shock'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H8\">",
" 'As the primary reperfusion strategy'",
" </a>",
" above.)",
" </li>",
" <li>",
" For patients with unsuccessful or complicated PCI with evidence of ongoing
ischemia and in whom the coronary anatomy is suitable for CABG, we recommend
emergency CABG rather than medical therapy (",
" <a class=\"grade\" href=\"._grade_2?title=Grade 1B\">",
" Grade 1B",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H5\">",
" 'After unsuccessful or complicated PCI'",
" </a>",
" above.)",
" </li>",
" <li>",
" For most patients with hemodynamically significant mechanical complications,
we recommended immediate CABG and attempt at repair of the mechanical defect rather
than a strategy of PCI followed by cardiac surgery (",
" <a class=\"grade\" href=\"._grade_2?title=Grade 1B\">",
" Grade 1B",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H7\">",
" 'Mechanical complications of acute MI'",
" </a>",
" above.)",
" <br/>",
" <br/>",
" For some patients with ischemic mitral regurgitation, primary PCI with
hemodynamic support may reasonably preferred to CABG.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H99780884\">",
" <span class=\"h1\">",
" ACKNOWLEDGMENT",
" </span>",
" &nbsp;&mdash;&nbsp;The UpToDate editorial staff would&nbsp;like to thank Dr.
Richard J. Shemin for his contributions as an author to previous versions of this
topic review.",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
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" <div id=\"topicVersionRevision\">",
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angina pectoris: Recommendations",
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source=related_link\">",
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left ventricular assist devices",
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source=related_link\">",
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myocardial infarction",
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source=related_link\">",
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myocardial infarction",
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source=related_link\">",
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" </a>",
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" Fibrinolytic therapy in acute ST elevation myocardial infarction: Initiation
of therapy",
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source=related_link\">",
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" Long-term outcome after coronary artery bypass graft surgery",
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technical issues",
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" Off-pump and minimally invasive direct coronary artery bypass graft surgery:
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" </div>",
" <div class=\"lgnd\">",
" Reticulated white plaques and erosions are present on the buccal mucosa. The
findings resemble oral lichen planus.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Oral chronic graft-versus-host disease",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" Multiple white plaques are present on the tongue.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Oral chronic graft-versus-host disease",
" </div>",
" <div class=\"cntnt\" style=\"width: 324px; height: 432px; background-image:
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" </div>",
" <div class=\"lgnd\">",
" Multiple erosions are present on the tongue.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
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var title_f6_22_6507="P-glycoprotein drugs";
var content_f6_22_6507=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
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title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=EM
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" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
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" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Inhibitors of P-glycoprotein",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td>",
" Amiodarone",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Bepridil",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Clarithromycin",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Cyclosporin",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Diltiazem",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Erythromycin",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Itraconazole",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Ketoconazole",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Propafenone",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Quinidine",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Ritonavir",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Verapamil",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" The drugs listed above cause elevations in serum digoxin concentrations.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_22_6507=[""].join("\n");
var outline_f6_22_6507=null;
var title_f6_22_6508="Nasal challenge protocol";
var content_f6_22_6508=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=ALLRG
%2F67707&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=6\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=ALLRG
%2F67707&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=6\" onclick=\"\"
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" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Nasal ketorolac and oral aspirin challenge protocol*",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1\">",
" Time",
" </td>",
" <td class=\"subtitle1\">",
" Dose of intranasal ketorolac (in sprays) or oral aspirin (in mg)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle2_left\" colspan=\"2\">",
" Day 1",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 8 am",
" </td>",
" <td>",
" 1 spray (1 in 1 nostril)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 8:30 am",
" </td>",
" <td>",
" 2 sprays (1 in each nostril)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 9 am",
" </td>",
" <td>",
" 4 sprays (2 in each nostril)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 9:30 am",
" </td>",
" <td>",
" 6 sprays&bull; (3 in each nostril)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 10:30 am",
" </td>",
" <td>",
" 60 mg of aspirin",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 12 noon",
" </td>",
" <td>",
" 60 mg of aspirin",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 1:30 pm",
" </td>",
" <td>",
" Instructions and discharge",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle2_left\" colspan=\"2\">",
" Day 2",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 8 am",
" </td>",
" <td>",
" 150 mg",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 11 am",
" </td>",
" <td>",
" 325 mg",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" 2 pm",
" </td>",
" <td>",
" Instructions and discharge",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" * Clinical and objective evaluation performed every 30 minutes and as
needed.",
" <br>",
" <span class=\"bullet\">",
" &bull;",
" </span>",
" Provoking dose is repeated; symptoms are treated as indicated.",
" </br>",
" </div>",
" <div class=\"reference\">",
" Original figure modified for this publication. Lee RU, White AA, Ding D, et
al. Use of intranasal ketorolac and modified oral aspirin challenge for
desensitization of aspirin-exacerbated respiratory disease. Ann Allergy Asthma
Immunol 2010; 105:130. Illustration used with the permission of Elsevier Inc. All
rights reserved.",
" </div>",
" </div>",
" </div>",
" </div>",
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var title_f6_22_6509="Methanol metabolism";
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" &copy;2013 UpToDate",
" <sup>",
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" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" * Blocked by ethanol and fomepizole.",
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var title_f6_22_6510="Unconjugated bilirubin no anemia child";
var content_f6_22_6510=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
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" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
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" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
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" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Approach to the child with unconjugated hyperbilirubinemia who does not have
anemia or hemolysis",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Mandl KD. Jaundice-Unconjugated
Hyperbilirubinemia. In: Textbook of Pediatric Emergency Medicine, Fleisher GR,
Ludwig S, Henretig FM (Eds), Lippincott Williams &amp; Wilkins, Philadelphia
2006.&nbsp;Copyright &copy; 2006 Lippincott Williams &amp; Wilkins.",
" </div>",
" <div class=\"contractual\">",
" <br/>",
" <a href=\"file://www.lww.com\">",
" file://www.lww.com",
" </a>",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
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var outline_f6_22_6510=null;
var title_f6_22_6511="Vibrio on TCBS agar";
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" <sup>",
" &reg;",
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" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
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" </div>",
" <div class=\"lgnd\">",
" Vibrio species can be selectively recovered from stool by culture on
thiosulfate-citrate-bile salts-sucrose (TCBS) agar. On this medium, V.
parahaemolyticus usually produces a green colony and V. cholerae a yellow colony
(indicative of the fermentation of sucrose).",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Harriet Provine.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_22_6511=[""].join("\n");
var outline_f6_22_6511=null;

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