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    Caricato da

    Carlos Hernández
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    34t3rrw

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    34t3rrw

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    36 visualizzazioni206 pagine

    1

    Caricato da

    Carlos Hernández
    34t3rrw

    Copyright:

    © All Rights Reserved
    Scarica in formato TXT, PDF, TXT o leggi online su Scribd
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    " </div>",
    " <div class=\"lgnd\">",
    " This close up view from a plain radiograph shows an older stress fracture
    (Torg type 2) of the fifth metatarsal diaphysis. Note the widened fracture line
    (white arrow), extension of the fracture to the opposite cortex, intramedullary
    sclerosis, and significant periosteal new bone (causing lateral bulge of cortex).
    This stress fracture clearly lies distal to the intrametatarsal joint. There is
    great risk of nonunion with such diaphyseal stress fractures.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Robert L Hatch, MD, MPH.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var outline_f6_0_6146=null;
    var title_f6_0_6147="Scapular manipulation for shoulder reduction";
    var content_f6_0_6147=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=EM
    %2F57540&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>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=EM
    %2F57540&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",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " Scapular manipulation for reduction of anterior shoulder dislocation",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " The patient sits upright and leans the unaffected shoulder against the
    stretcher. The physician stands behind the patient and palpates the tip of the
    scapula with his thumbs and directs a force medially. The assistant stands in front
    of the patient and provides gentle downward traction on the humerus as shown. The
    patient is encouraged to relax the shoulder as much as possible.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Scott C Sherman, MD.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f6_0_6147=[""].join("\n");
    var outline_f6_0_6147=null;
    var title_f6_0_6148="Colon and rectal cancer";
    var content_f6_0_6148=[" <h1 id=\"patTopicTitle\">",
    " Patient information: Colon and rectal cancer (Beyond the Basics)",
    " </h1>",
    " <div id=\"patTopicContributors\">",
    " <div class=\"rcTop\">",
    " <div>",
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    " <tr>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?6/0/6148/contributors\">",
    " Authors",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6148/contributors\" id=\"au1734\">",
    " Miguel A Rodriguez-Bigas, MD",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6148/contributors\" id=\"au1707\">",
    " Axel Grothey, MD",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?6/0/6148/contributors\">",
    " Section Editors",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6148/contributors\" id=\"se1234\">",
    " Richard M Goldberg, MD",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6148/contributors\" id=\"se4549\">",
    " Kenneth K Tanabe, MD",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?6/0/6148/contributors\">",
    " Deputy Editor",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6148/contributors\" id=\"de5563\">",
    " Diane MF Savarese, MD",
    " </a>",
    " </td>",
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    " <div>",
    " </div>",
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    Topic\">",
    " Find",
    " </a>",
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    title=\"Print This Topic\">",
    " Print",
    " </a>",
    " <script src=\"file://w.sharethis.com/button/sharethis.js#publisher=357881b8-
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    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " COLORECTAL CANCER OVERVIEW",
    " </span>",
    " </p>",
    " <p>",
    " Colon and rectal cancer are cancers that involve the lowest part of the
    digestive system: the large intestine and the rectum (",
    " <a class=\"graphic graphic_figure graphicRef58531 \" href=\"UTD.htm?
    12/60/13250\">",
    " figure 1",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " Tests that monitor or screen for colorectal cancer are important tools in
    finding colon and rectal cancer at an early stage. Screening tests are described
    separately. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?7/23/7541?
    source=see_link\">",
    " \"Patient information: Colon and rectal cancer screening (Beyond the
    Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " This article has facts about the signs and symptoms, diagnosis, and treatment
    of early stage colon and rectal cancer. More information about colon and rectal
    cancer is available by subscription. (See",
    " <a class=\"local\" href=\"#H10049748\">",
    " 'Professional level information'",
    " </a>",
    " below.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " COLORECTAL CANCER SYMPTOMS",
    " </span>",
    " </p>",
    " <p>",
    " The most common symptoms of colon and rectal cancer include:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Stomach pain",
    " </li>",
    " <li>",
    " Change in bowel habits (constipation or diarrhea)",
    " </li>",
    " <li>",
    " Blood in the bowel movements",
    " </li>",
    " <li>",
    " Feeling weak or tired",
    " </li>",
    " <li>",
    " Low iron level (iron deficiency anemia)",
    " </li>",
    " <li>",
    " Black or dark-colored stools",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " COLORECTAL CANCER DIAGNOSIS",
    " </span>",
    " </p>",
    " <p>",
    " Your doctor or nurse may be concerned that you could have colon or rectal
    cancer if you have one or more of the above symptoms. In this case, a colonoscopy
    is often used to look inside the rectum and large intestine. Cancers growing within
    the large intestine and rectum can be seen during a colonoscopy, and a biopsy
    (removal of a piece of tissue for examination) can be done, confirming the presence
    of a cancer. Colonoscopy is described in a separate article. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?9/30/9698?
    source=see_link\">",
    " \"Patient information: Colonoscopy (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H4\">",
    " <span class=\"h2\">",
    " Staging",
    " </span>",
    " &nbsp;&mdash;&nbsp;Once a colorectal cancer is diagnosed, the next step is to
    determine its stage. Staging is a system used to describe the aggressiveness and
    spread of a cancer. The stage of a colorectal cancer is assigned based on:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Whether there are signs of cancer spread on a physical exam, CT scan, or
    MRI of the abdomen and pelvis, chest X-ray, or other imaging tests.",
    " </li>",
    " <li>",
    " The appearance of the cancer specimen when viewed under the microscope,
    after it has been removed with surgery.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Colorectal cancer stages range from stage I (cancer has invaded into but not
    through the entire wall of the intestine), to stage IV (the cancer has spread to
    distant organs, such as the liver). Treatment depends on disease stage.",
    " </p>",
    " <p>",
    " Earlier stages of disease (stages I through III) are referred to as localized
    colorectal cancers and generally treated with surgery, with or without
    chemotherapy. (See",
    " <a class=\"local\" href=\"#H9\">",
    " 'Who needs chemotherapy?'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " Stage IV cancer is called advanced colorectal cancer and is generally treated
    with chemotherapy; some patients may benefit from surgery. The following sections
    will discuss treatment for localized colon and rectal cancer. Treatment of stage IV
    disease is covered elsewhere. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?39/22/40293?
    source=see_link\">",
    " \"Patient information: Colorectal cancer treatment; metastatic cancer
    (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h1\">",
    " COLON CANCER TREATMENT",
    " </span>",
    " </p>",
    " <p>",
    " The treatment of colon cancer usually involves surgery, and it may also
    involve chemotherapy; radiation therapy is only rarely needed.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H6\">",
    " <span class=\"h2\">",
    " Surgery",
    " </span>",
    " &nbsp;&mdash;&nbsp;The initial treatment of colon cancer usually involves
    surgery. (See",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?37/9/38034?
    source=see_link\">",
    " \"Patient information: Colectomy (The Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " During the surgery, the cancerous part of the colon and surrounding tissues
    are removed. The lymph nodes (round organs that serve as filters for blood from the
    intestines) within this surrounding tissue are examined under a microscope to
    determine if the cancer has spread beyond the colon.",
    " </p>",
    " <p>",
    " In most people, the two ends of the colon can be reconnected immediately
    after the cancerous part has been removed. If this can be done, it means that you
    will continue to have bowel movements normally, through your rectum and anus.",
    " </p>",
    " <p>",
    " In other cases, the colon cannot be reconnected during the initial surgery.
    This can happen if the surgeon feels there is a high risk of infection, or if the
    tissues are inflamed and need time to heal. If this occurs, the surgeon will sew
    the colon to an opening in the skin on the abdomen. The opening is called a
    colostomy (",
    " <a class=\"graphic graphic_figure graphicRef57774 \" href=\"UTD.htm?
    6/7/6256\">",
    " figure 2",
    " </a>",
    " ). You will wear a bag over the colostomy to collect bowel movements.",
    " </p>",
    " <p>",
    " The colostomy is usually temporary. The two ends of the colon can often be
    reconnected after a few months, sometimes after chemotherapy is completed. In other
    cases, you will need the colostomy permanently.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H7\">",
    " <span class=\"h3\">",
    " Life with a colostomy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Having a colostomy will change how your body looks, which
    can be hard to accept. However, with education and support, it is possible to lead
    an active life with a colostomy. A team effort, which includes the colorectal
    surgeon, oncologist, and an enterostomal therapy (ET) nurse, is valuable in
    learning about the surgery and also in the care and recovery required after the
    procedure. The United Ostomy Associations of America is also a good source of
    information and support (",
    " <a class=\"external\" href=\"file://www.uoaa.org/\">",
    " www.uoaa.org",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?11/38/11875?
    source=see_link\">",
    " \"Patient information: Colostomy care (The Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H8\">",
    " <span class=\"h2\">",
    " Chemotherapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Chemotherapy is a treatment given to slow or stop the
    growth of cancer cells. Even after a colon cancer has been completely removed with
    surgery, cancer cells can remain in the body, increasing the risk of the cancer
    coming back (called a relapse or recurrence). In some people, chemotherapy can
    eliminate these cancer cells and increase the chance of cure. This type of
    chemotherapy is called \"adjuvant\", which means that it is given after a curative
    surgery (at which time all the tumor was removed).",
    " </p>",
    " <p>",
    " Most treatments involve a combination of several chemotherapy drugs, which
    are given in a specific order on specific days. Most of the drugs are given into
    the vein (intravenous, IV), but sometimes a single drug will be recommended, which
    can be given in pill form. Regardless of the specific type of regimen, most
    adjuvant treatment regimens for colon cancer last about six months.",
    " </p>",
    " <p>",
    " Your healthcare provider can describe which chemotherapy drugs will be
    needed, how long treatment will last, and what side effects are expected from your
    treatment.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H9\">",
    " <span class=\"h3\">",
    " Who needs chemotherapy?",
    " </span>",
    " &nbsp;&mdash;&nbsp;Chemotherapy is recommended for most people with stage III
    colon cancer (spread to the lymph nodes) and some people with stage II colon cancer
    (involvement of the whole thickness of the bowel wall but without involvement of
    the lymph nodes). Chemotherapy is not usually recommended for people with stage I
    colon cancer (cancer within the bowel wall but not all the way through it).",
    " </p>",
    " <p>",
    " Before you begin chemotherapy, it is important to discuss the potential risks
    and benefits of treatment with your doctor.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " In some cases, the benefits of chemotherapy (better chance of survival)
    clearly outweigh the possible risks (chemotherapy side effects like diarrhea,
    vomiting, hair loss, nerve damage, or more serious risks). Not everyone will have
    all of these side effects.",
    " </li>",
    " <li>",
    " In other cases, the small benefit of chemotherapy is not worth the risks.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " A Web-based tool called Adjuvant! Online can help you and your healthcare
    provider estimate the risk of cancer recurrence and the potential benefits of
    chemotherapy [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6148/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h1\">",
    " RECTAL CANCER TREATMENT",
    " </span>",
    " </p>",
    " <p>",
    " The majority of rectal cancers are treated with a combination of surgery,
    radiation therapy, and chemotherapy; as with colon cancers, treatment is chosen
    based upon disease stage.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Stage I rectal cancer &mdash; Surgery alone may cure the cancer.",
    " </li>",
    " <li>",
    " Stage II and III &mdash; Chemotherapy and radiation therapy are typically
    recommended along with surgery; sometimes, the chemotherapy and radiation are given
    before surgery (referred to as neoadjuvant chemoradiotherapy), with additional
    chemotherapy given after surgery.",
    " </li>",
    " <li>",
    " Stage IV &mdash; Predominantly treated with chemotherapy, with or without
    surgery. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?39/22/40293?
    source=see_link\">",
    " \"Patient information: Colorectal cancer treatment; metastatic cancer
    (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H11\">",
    " <span class=\"h2\">",
    " Neoadjuvant chemoradiotherapy and radiotherapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;A combination of chemotherapy and radiation therapy may be
    recommended before surgery for patients with rectal cancer; this is called
    neoadjuvant chemoradiotherapy. This treatment can shrink the tumor before it is
    removed, reduces the risk that the cancer will come back, and may reduce the
    chances that you will need a permanent colostomy. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/22/42346?
    source=see_link\">",
    " \"Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The two most common ways to take chemotherapy during radiation therapy are:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " A pump that fits into a pack you wear around your waist. The pump delivers
    the medicine (called 5-FU) into a port (an IV in your chest) continuously for about
    six weeks during radiation treatments.",
    " </li>",
    " <li>",
    " A daily dose of a pill called capecitabine. The pill is as effective as 5-
    FU given by pump and more convenient.",
    " </li>",
    " <li>",
    " Discuss all the potential risks and benefits of capecitabine with your
    doctor.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " In some cases, a short course of radiation therapy alone (typically five
    daily treatments) may be recommended prior to surgery instead of combined
    chemotherapy and radiation. This approach is more popular outside of the United
    States.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H12\">",
    " <span class=\"h2\">",
    " Surgery",
    " </span>",
    " &nbsp;&mdash;&nbsp;Surgery removes the cancerous part of the rectum and the
    associated lymph nodes. Sometimes this will require that the anus be removed along
    with the rectum. If the anus and rectum have to be removed, the surgeon will sew
    the remaining intestine to an opening in the skin on the abdomen. The opening is
    called a colostomy. You will wear a bag over the opening to collect bowel
    movements. (See",
    " <a class=\"local\" href=\"#H7\">",
    " 'Life with a colostomy'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " The type of surgery you have depends upon where your tumor is located and how
    far it has spread. Ask your surgeon to describe which surgery is right for you.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H13\">",
    " <span class=\"h2\">",
    " Treatment after surgery",
    " </span>",
    " &nbsp;&mdash;&nbsp;Postoperative (adjuvant) therapy is typically recommended
    after surgery. The type of treatment you have after surgery depends upon the stage
    of your cancer, as well as the treatment you had before surgery. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?4/51/4922?
    source=see_link\">",
    " \"Adjuvant therapy for resected rectal cancer\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " If your tumor is stage II or III, and you did not have chemotherapy and
    radiation therapy before surgery, you will probably have it after surgery. This is
    called adjuvant chemoradiotherapy (see",
    " <a class=\"local\" href=\"#H11\">",
    " 'Neoadjuvant chemoradiotherapy and radiotherapy'",
    " </a>",
    " above).",
    " </li>",
    " <li>",
    " If you had chemoradiotherapy or radiation therapy alone before surgery, you
    will probably need approximately four months of chemotherapy alone (without further
    radiation therapy) after surgery.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h1\">",
    " CLINICAL TRIALS",
    " </span>",
    " </p>",
    " <p>",
    " Progress in treating cancer requires that better treatments be identified
    through clinical trials, which are conducted all over the world. A clinical trial
    is a carefully controlled way to study the effectiveness of new treatments or new
    combinations of known therapies. Ask for more information about clinical trials or
    read about clinical trials at:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " <a class=\"external\" href=\"file://www.cancer.gov/clinicaltrials\">",
    " file://www.cancer.gov/clinicaltrials",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"external\" href=\"file://clinicaltrials.gov/\">",
    " file://clinicaltrials.gov/",
    " </a>",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h1\">",
    " FOLLOW-UP AFTER TREATMENT",
    " </span>",
    " </p>",
    " <p>",
    " After completing treatment for colorectal cancer, it is important to follow
    up with your healthcare team. You will need appointments on a regular basis for a
    few years to monitor for signs that the cancer has recurred. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/61/28634?
    source=see_link\">",
    " \"Surveillance after colorectal cancer resection\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Your follow-up schedule may differ slightly, but most people will have the
    following:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " A full colonoscopy is recommended before or after surgery to look for
    polyps or other cancers that were not seen previously. Colonoscopy is usually
    repeated one and four years after surgery, and every five years thereafter. If
    polyps or new cancers are found, this schedule may be adjusted.",
    " </li>",
    " <li>",
    " Visits with your healthcare provider are usually scheduled every three to
    four months for the first three years, every six months for two years, and then
    once per year. Most visits will include a discussion of how you are feeling and a
    physical examination. A blood test for a colorectal cancer tumor marker (CEA) may
    be done at each visit.",
    " </li>",
    " <li>",
    " A CT scan is usually recommended once per year for three years in people
    who have been treated for stage II or III colon cancer.",
    " </li>",
    " <li>",
    " For people who still have their anus after treatment for rectal cancer and
    who did not have radiation therapy, experts recommend a flexible
    proctosigmoidoscopy every six months for five years. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?41/12/42176?
    source=see_link\">",
    " \"Patient information: Flexible sigmoidoscopy (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h1\">",
    " COLORECTAL CANCER AND YOUR FAMILY",
    " </span>",
    " </p>",
    " <p>",
    " Having colon or rectal cancer means that your family may be at an increased
    risk of developing colorectal cancer. If you have one parent, brother, sister, or
    child with colorectal cancer or polyps at a young age (before the age of 60 years),
    or two relatives diagnosed at any age, you should begin screening for colon cancer
    earlier, typically at age 40, or 10 years younger than the earliest diagnosis in
    your family, whichever comes first. Colon cancer screening is discussed separately.
    (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?7/23/7541?
    source=see_link\">",
    " \"Patient information: Colon and rectal cancer screening (Beyond the
    Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Certain genetic conditions increase the risk of colon cancer. The most common
    conditions include Lynch syndrome or hereditary nonpolyposis colon cancer (HNPCC),
    and familial adenomatous polyposis (FAP). If you have a strong family history of
    colon cancer (two or more close relatives), talk to your doctor about the need for
    genetic counseling and possible genetic testing.",
    " </p>",
    " <p>",
    " Although the idea of genetic testing can be frightening, the results of
    genetic tests can help determine whether you and your family need further
    treatment, testing, or closer surveillance.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h1\">",
    " WHERE TO GET MORE INFORMATION",
    " </span>",
    " </p>",
    " <p>",
    " Your healthcare provider is the best source of information for questions and
    concerns related to your medical problem.",
    " </p>",
    " <p>",
    " This article will be updated as needed on our Web site (",
    " <a class=\"external\" href=\"file://www.uptodate.com/patients\">",
    " www.uptodate.com/patients",
    " </a>",
    " ). Related topics for patients, as well as selected articles written for
    healthcare professionals, are also available. Some of the most relevant are listed
    below.",
    " <br/>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H10049626\">",
    " <span class=\"h2\">",
    " Patient level information",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education
    materials.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H10049633\">",
    " <span class=\"h3\">",
    " The Basics",
    " </span>",
    " &nbsp;&mdash;&nbsp;The Basics patient education pieces 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.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?19/27/19890?
    source=see_link\">",
    " Patient information: Colon and rectal cancer (The Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?24/34/25123?
    source=see_link\">",
    " Patient information: Colon and rectal cancer screening (The Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?11/38/11875?
    source=see_link\">",
    " Patient information: Colostomy care (The Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?37/9/38034?
    source=see_link\">",
    " Patient information: Colectomy (The Basics)",
    " </a>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H10049648\">",
    " <span class=\"h3\">",
    " Beyond the Basics",
    " </span>",
    " &nbsp;&mdash;&nbsp;Beyond the Basics patient education pieces are longer,
    more sophisticated, and more detailed. These articles are best for patients who
    want in-depth information and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?7/23/7541?
    source=see_link\">",
    " Patient information: Colon and rectal cancer screening (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?9/30/9698?
    source=see_link\">",
    " Patient information: Colonoscopy (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?39/22/40293?
    source=see_link\">",
    " Patient information: Colorectal cancer treatment; metastatic cancer (Beyond
    the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?41/12/42176?
    source=see_link\">",
    " Patient information: Flexible sigmoidoscopy (Beyond the Basics)",
    " </a>",
    " <br/>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H10049748\">",
    " <span class=\"h2\">",
    " Professional level information",
    " </span>",
    " &nbsp;&mdash;&nbsp;Professional level articles are designed to keep doctors
    and other health professionals up-to-date on the latest medical findings. These
    articles are thorough, long, and complex, and they contain multiple references to
    the research on which they are based. Professional level articles are best for
    people who are comfortable with a lot of medical terminology and who want to read
    the same materials their doctors are reading.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/25/42394?
    source=see_link\">",
    " Colorectal cancer: Epidemiology, risk factors, and protective factors",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/33/17946?
    source=see_link\">",
    " Clinical manifestations, diagnosis, and staging of colorectal cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/49/30489?
    source=see_link\">",
    " Overview of the management of primary colon cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?33/44/34506?
    source=see_link\">",
    " Adjuvant therapy for resected stage III (node-positive) colon cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/55/30586?
    source=see_link\">",
    " Adjuvant chemotherapy for resected stage II colon cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/51/11066?
    source=see_link\">",
    " Adjuvant therapy for resected colon cancer in elderly patients",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/15/38137?
    source=see_link\">",
    " Overview of surgical procedures for resectable primary rectal cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/22/42346?
    source=see_link\">",
    " Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?4/51/4922?
    source=see_link\">",
    " Adjuvant therapy for resected rectal cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/61/28634?
    source=see_link\">",
    " Surveillance after colorectal cancer resection",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?16/39/17016?
    source=see_link\">",
    " Clinical manifestations and diagnosis of familial adenomatous polyposis",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/59/19386?
    source=see_link\">",
    " Clinical features and diagnosis of Lynch syndrome (hereditary nonpolyposis
    colorectal cancer)",
    " </a>",
    " <br/>",
    " <br/>",
    " The following organizations also provide reliable health information.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " National Cancer Institute",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;1-800-4-CANCER",
    " <br/>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.nci.nih.gov/\">",
    " www.nci.nih.gov",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " American Society of Clinical Oncology",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.cancer.net/portal/site/patient\">",
    " www.cancer.net/portal/site/patient",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " National Comprehensive Cancer Network",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.nccn.com/\">",
    " www.nccn.com",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " National Library of Medicine",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\"
    href=\"file://www.nlm.nih.gov/medlineplus/healthtopics.html\">",
    " www.nlm.nih.gov/medlineplus/healthtopics.html",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " \"Colon Cancer Can Run in the Family\". Berk T, Macrae, F (Eds). Available
    at",
    " <a class=\"external\" href=\"file://www.insight-
    group.org/links/CRCbook/\">",
    " www.insight-group.org/links/CRCbook/",
    " </a>",
    " .",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H19\">",
    " <span class=\"h2\">",
    " Patient support",
    " </span>",
    " &nbsp;&mdash;&nbsp;There are a number of online forums where patients can
    find information and support from other people with similar conditions.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " <a class=\"external\" href=\"file://about.com/\">",
    " About.com",
    " </a>",
    " Cancer Forum",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://cancer.about.com/forum\">",
    " file://cancer.about.com/forum",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6148/abstract/2-5\">",
    " 2-5",
    " </a>",
    " ]",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"literatureReviewDate\">",
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    " <ol id=\"reference\">",
    " <li>",
    " Adjuvant! Online program for colon cancer available online at
    www.adjuvantonline.com (Accessed on September 21, 2011).",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6148/abstract/2\">",
    " Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal
    cancer surgery. J Natl Cancer Inst 2001; 93:583.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6148/abstract/3\">",
    " Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA. Lymph node evaluation
    and survival after curative resection of colon cancer: systematic review. J Natl
    Cancer Inst 2007; 99:433.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6148/abstract/4\">",
    " Benson AB 3rd, Schrag D, Somerfield MR, et al. American Society of Clinical
    Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin
    Oncol 2004; 22:3408.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6148/abstract/5\">",
    " Figueredo A, Coombes ME, Mukherjee S. Adjuvant therapy for completely
    resected stage II colon cancer. Cochrane Database Syst Rev 2008; :CD005390.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
    " </div>",
    " <!-- patTopicMiddle -->",
    "</div>"].join("\n");
    var script_f6_0_6148=[""].join("\n");
    var outline_f6_0_6148=[" <div class=\"patTopicFancyTop\">",
    " <div class=\"rcTop\">",
    " <div>",
    " </div>",
    " </div>",
    " <div class=\"rcContent\">",
    " <p>",
    " Contents of this article",
    " </p>",
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    " <div class=\"patTopicFancySpacer\">",
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    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a href=\"#H1\">",
    " COLORECTAL CANCER OVERVIEW",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H2\">",
    " COLORECTAL CANCER SYMPTOMS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H3\">",
    " COLORECTAL CANCER DIAGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H5\">",
    " COLON CANCER TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H10\">",
    " RECTAL CANCER TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H14\">",
    " CLINICAL TRIALS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H15\">",
    " FOLLOW-UP AFTER TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H16\">",
    " COLORECTAL CANCER AND YOUR FAMILY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H17\">",
    " WHERE TO GET MORE INFORMATION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " GRAPHICS",
    " </h1>",
    " <div id=\"relatedGraphics\">",
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    " FIGURES",
    " </li>",
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    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?12/60/13250\"
    title=\"figure 1\">",
    " Diagram colon rectum PI",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?6/7/6256\"
    title=\"figure 2\">",
    " Colostomy PI",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>"].join("\n");
    var title_f6_0_6149="Megestrol acetate: Pediatric drug information";
    var content_f6_0_6149=[" <noscript>",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Megestrol acetate: Pediatric 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_general\" href=\"UTD.htm?32/55/33653?source=see_link\">",
    " see \"Megestrol acetate: Drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?12/37/12885?source=see_link\">",
    " see \"Megestrol acetate: 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=\"list ubnlist drugH1Div drugBrandNames\" id=\"F192314\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Megace&reg;;",
    " </li>",
    " <li>",
    " Megace&reg; ES",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F192315\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Apo-Megestrol&reg;;",
    " </li>",
    " <li>",
    " Megace&reg;;",
    " </li>",
    " <li>",
    " Megace&reg; OS;",
    " </li>",
    " <li>",
    " Nu-Megestrol",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list_set htclist drugH1Div drugBrandNames\" id=\"F1060125\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Therapeutic Category",
    " </span>",
    " <ul>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Antineoplastic Agent, Miscellaneous",
    " </span>",
    " </li>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Progestin",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block dos drugH1Div\" id=\"F1060118\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Usual",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/55/33653?
    source=see_link\">",
    " see \"Megestrol acetate: Drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Oral:",
    " <b>",
    " Note:",
    " </b>",
    " Megace&reg; ES is not equivalent mg per mg with other megestrol formulations
    (625 mg Megace&reg; ES is equivalent to 800 mg megestrol tablets or suspension).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Appetite stimulant in cachexia: Titrate dosage to response; decrease dose if
    weight gain is excessive:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children: Limited data has been reported in cachectic children with cystic
    fibrosis, HIV, and solid tumors: Megestrol (tablets or 40 mg/mL suspension): 7.5-10
    mg/kg/day in 1-4 divided doses; not to exceed 800 mg/day or 15 mg/kg/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Adolescents and Adults:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Megestrol (tablets or 40 mg/mL suspension): 800 mg/day in 1-4 divided doses;
    titrate dose to response; doses between 400-800 mg/day have been clinically
    effective",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Megace&reg; ES: 625 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Breast carcinoma: Female Adults: Megestrol (tablets or 40 mg/mL suspension):
    40 mg 4 times/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Endometrial carcinoma: Female Adults: Megestrol (tablets or 40 mg/mL
    suspension): 40-320 mg/day in divided doses; not to exceed 800 mg/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Uterine bleeding: Female Adults: Megestrol (tablets or 40 mg/mL suspension):
    40 mg 2-4 times/day",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F192294\"
    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;\">",
    " Suspension, oral, as acetate: 40 mg/mL (10 mL, 20 mL, 237 mL, 240 mL, 473 mL,
    480 mL)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Megace&reg;: 40 mg/mL (240 mL) [contains ethanol 0.06%, sodium benzoate;
    lemon-lime flavor]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Megace&reg; ES: 125 mg/mL (150 mL) [contains ethanol 0.06%, sodium benzoate;
    lemon-lime flavor]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Tablet, oral, as acetate: 20 mg, 40 mg",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F192278\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Yes: Excludes Megace&reg; ES",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F1060128\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hazardous agent; use appropriate precautions for handling and disposal",
    " <a href=\"file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf\"
    target=\"_blank\">",
    " (NIOSH, 2012)",
    " </a>",
    " .",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Oral: Shake oral suspension well before administering; administer without
    regard to food",
    " </p>",
    " </div>",
    " <div class=\"block sta drugH1Div\" id=\"F1060121\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Stability",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Store tablets and oral suspension at room temperature; protect from heat",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F1060127\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Appetite stimulation and promotion of weight gain in cachexia (particularly
    in HIV patients) which is unresponsive to nutritional supplementation; palliative
    treatment of breast and endometrial carcinomas",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F192337\"
    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;\">",
    " Megace&reg; may be confused with Reglan&reg;",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Megestrol may be confused with mesalamine",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " BEERS Criteria medication:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " This drug may be potentially inappropriate for use in geriatric patients
    (Quality of evidence - moderate; Strength of recommendation - strong).",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"block arm drugH1Div\" id=\"F192335\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Cardiovascular: Cardiomyopathy, chest pain, edema, heart failure,
    hypertension, palpitation, peripheral edema",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Central nervous system: Abnormal thinking, confusion, depression, fever,
    headache, hypoesthesia, insomnia, lethargy, malaise, mood changes, pain, seizure",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Dermatologic: Alopecia, pruritus, rash, vesiculobullous rash",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Endocrine &amp; metabolic: Adrenal insufficiency, amenorrhea, breakthrough
    bleeding, breast tenderness increased, cervical erosion and secretions (changes),
    Cushing's syndrome, diabetes, glucose intolerance, gynecomastia, hot flashes, HPA
    axis suppression, hypercalcemia, hyperglycemia, menstrual flow changes, spotting,
    vaginal bleeding pattern changes",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia,
    flatulence, nausea, salivation increased, weight gain (not attributed to edema or
    fluid retention), xerostomia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Genitourinary: Impotence, libido decreased, urinary frequency, urinary
    incontinence, urinary tract infection",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hematologic: Anemia, leukopenia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hepatic: Cholestatic jaundice, hepatomegaly, hepatotoxicity, LDH increased",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Carpal tunnel syndrome, neuropathy,
    paresthesia, weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Ocular: Amblyopia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Renal: Albuminuria",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Respiratory: Cough, dyspnea, hyperpnea, pharyngitis, pneumonia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Miscellaneous: Diaphoresis, herpes infection, infection, moniliasis, tumor
    flare",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Rare but important or life-threatening: Thromboembolic phenomena (including
    deep vein thrombosis, pulmonary embolism, thrombophlebitis)",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F1060132\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to megestrol or any component; pregnancy (known or
    suspected); concomitant use with dofetilide",
    " </p>",
    " </div>",
    " <div class=\"block pre drugH1Div\" id=\"F1060117\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Precautions",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Use with caution in patients with history of thromboembolic disease; use
    caution in patients with diabetes mellitus as increased insulin requirements have
    been reported in association with megestrol use",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F1060116\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hazardous agent; use appropriate precautions for handling and disposal",
    " <a href=\"file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf\"
    target=\"_blank\">",
    " (NIOSH, 2012)",
    " </a>",
    " . May cause fetal harm when administered during pregnancy; women of
    childbearing age should use appropriate contraceptive measures. May suppress HPA
    axis during chronic administration; acute adrenal insufficiency may occur with
    abrupt withdrawal after long-term use or with stress; withdrawal or discontinuation
    of megestrol should be done carefully. Consider providing exogenous glucocorticoids
    during periods of stress or severe infection.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
    " Oral suspensions contain sodium benzoate; benzoic acid (benzoate) is a
    metabolite of benzyl alcohol; large amounts of benzyl alcohol (&ge;99 mg/kg/day)
    have been associated with a potentially fatal toxicity (&ldquo;gasping
    syndrome&rdquo;) in neonates;",
    " <i>",
    " in vitro",
    " </i>",
    " and animal studies have shown that benzoate, a metabolite of benzyl alcohol,
    displaces bilirubin from protein-binding sites; avoid use of products containing
    sodium benzoate in neonates. Megestrol may inhibit the elimination of dofetilide
    resulting in increased dofetilide plasma concentrations and potential serious
    ventricular arrhythmias associated with QT interval prolongation; concomitant use
    with dofetilide is not recommended. Megestrol may reduce indinavir serum levels
    resulting in a need for increase in indinavir dose.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F13299657\"
    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=\"F192287\"
    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;\">",
    " Aminoglutethimide: May increase the metabolism of Progestins. Management:
    Progestin-containing contraceptives are not recommended; consider the use of
    alternative, nonhormonal contraceptives.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dofetilide: Megestrol may increase the serum concentration of Dofetilide.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the
    adverse/toxic effect of Progestins.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block foi drugH1Div\" id=\"F2104108\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Food Interactions",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " A high fat meal significantly increases plasma levels; avoid herbs with
    progestogenic properties (eg, bloodroot, chasteberry, damiana, oregano, and yucca)
    as they may enhance the adverse/toxic effects of megestrol",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F192290\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " D (tablet) / X (suspension) (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F4627707\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Adverse effects were demonstrated in animal studies. Use during pregnancy is
    contraindicated (suspension).",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F1060124\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Monitor for signs of thromboembolic phenomena and adrenal axis suppression",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Appetite stimulation: Weight, caloric intake, basal cortisol level",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Antineoplastic: Tumor response",
    " </p>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F1060115\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " A synthetic progestin with antiestrogenic properties which disrupt the
    estrogen receptor cycle. Megestrol interferes with the normal estrogen cycle and
    results in a lower LH titer. It may also have a direct effect on the endometrium.
    As an antineoplastic progestin, it is thought to act through an antileutenizing
    effect mediated via the pituitary. The exact mechanism for appetite stimulation has
    not been determined but is postulated to be due in part to a direct effect on the
    hypothalamus.",
    " </p>",
    " </div>",
    " <div class=\"block phd drugH1Div\" id=\"F1060130\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Onset of action:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Antineoplastic: 2 months of continuous therapy",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Weight gain: 2-4 weeks",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F1060131\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacokinetics (Adult data unless noted)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Absorption: Well absorbed",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Metabolism: In the liver",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Half-life: Adults: 10-120 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Time to peak serum concentration:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Tablet: 2-3 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Suspension: 3-5 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Elimination: In urine (57% to 78%) and feces (8% to 30%) within 10 days",
    " </p>",
    " </div>",
    " <div class=\"block pai drugH1Div\" id=\"F1060123\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Patient Information",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?12/37/12885?
    source=see_link\">",
    " see \"Megestrol acetate: Patient drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Follow dosage schedule and do not take more than prescribed. May cause
    photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin
    rash, redness, or itching); avoid exposure to sunlight and artificial light sources
    (sunlamps, tanning booth/bed); wear protective clothing, wide-brimmed hats,
    sunglasses, and lip sunscreen (SPF &ge;15); use a sunscreen [broad-spectrum
    sunscreen or physical sunscreen (preferred) or sunblock with SPF &ge;15]; contact
    physician if reaction occurs. May cause dry mouth. Report absent or altered menses,
    abdominal pain, vaginal itching, irritation, or discharge; report warmth, redness,
    or swelling of extremities, sudden onset of difficulty breathing, severe headache,
    or change in vision. May cause fetal harm particularly in the first 4 months of
    pregnancy; use appropriate contraception.",
    " </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\">",
    " Eubanks V, Koppersmith N, Wooldridge N, et al, &ldquo;Effects of Megestrol
    Acetate on Weight Gain, Body Composition, and Pulmonary Function in Patients With
    Cystic Fibrosis,&rdquo;",
    " <i>",
    " J Pediatr",
    " </i>",
    " , 2002, 140(4):439-44.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?6/0/6149/abstract-text/12006958 /pubmed\"
    id=\"12006958 \" target=\"_blank\">",
    " 12006958",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Nasr SZ, Hurwitz ME, Brown RW, et al, &ldquo;Treatment of Anorexia and
    Weight Loss With Megestrol Acetate in Patients With Cystic Fibrosis,&rdquo;",
    " <i>",
    " Pediatr Pulmonol",
    " </i>",
    " , 1999, 28(5):380-2.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?6/0/6149/abstract-text/10536070/pubmed\" id=\"10536070\"
    target=\"_blank\">",
    " 10536070",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " National Institute for Occupational Safety and Health (NIOSH), \"NIOSH List
    of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012.\"
    Available at",
    " <a href=\"file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf\"
    target=\"_blank\">",
    " file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf",
    " </a>",
    " . Accessed January 21, 2013.",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Stockheim JA, Daaboul JJ, Yogev R, et al, &ldquo;Adrenal Suppression in
    Children With the Human Immunodeficiency Virus Treated With Megestrol
    Acetate,&rdquo;",
    " <i>",
    " J Pediatr",
    " </i>",
    " , 1999, 134(3):368-70.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?6/0/6149/abstract-text/ 10064680 /pubmed\" id=\" 10064680
    \" target=\"_blank\">",
    " 10064680",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Tchekmedyian NS, Hickman M, and Heber D, &ldquo;Treatment of Anorexia and
    Weight Loss With Megestrol Acetate in Patients With Cancer or Acquired
    Immunodeficiency Syndrome,&rdquo;",
    " <i>",
    " Semin Oncol",
    " </i>",
    " , 1991, 18(1 Suppl 2):35-42.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?6/0/6149/abstract-text/1992535 /pubmed\" id=\"1992535 \"
    target=\"_blank\">",
    " 1992535",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 12578 Version 34.0",
    " </div>",
    " </div>",
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    " <div id=\"supportFooter\">",
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    "</div>"].join("\n");
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    var outline_f6_0_6149=[" <div id=\"toggleOutline\">",
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    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F192314\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F192315\">",
    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060125\">",
    " Therapeutic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060118\">",
    " Dosing: Usual",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F192294\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F192278\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060128\">",
    " Administration",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060121\">",
    " Stability",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060127\">",
    " Use",
    " </a>",
    " </li>",
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    " <a class=\"outlineLink\" href=\"#F192337\">",
    " Medication Safety Issues",
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    " <a class=\"outlineLink\" href=\"#F192335\">",
    " Adverse Reactions",
    " </a>",
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    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060132\">",
    " Contraindications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060117\">",
    " Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060116\">",
    " Warnings",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13299657\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F192287\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F2104108\">",
    " Food Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F192290\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F4627707\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060124\">",
    " Monitoring Parameters",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060115\">",
    " Mechanism of Action",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060130\">",
    " Pharmacodynamics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060131\">",
    " Pharmacokinetics (Adult data unless noted)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1060123\">",
    " Patient Information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_PED/12578\"
    rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
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    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
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    " </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",
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    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/55/33653?
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    " Megestrol acetate: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?12/37/12885?
    source=related_link\">",
    " Megestrol acetate: Patient drug information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f6_0_6150="Management of bronchiectasis in children without cystic
    fibrosis";
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    " <div id=\"topicContent\">",
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    " Management of bronchiectasis in children without cystic fibrosis",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?6/0/6150/contributors\">",
    " Authors",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6150/contributors\">",
    " Khoulood Fakhoury, MD",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6150/contributors\">",
    " Adaobi Kanu, MD",
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    href=\"UTD.htm?6/0/6150/contributors\">",
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    6/0/6150/contributors\">",
    " George B Mallory, MD",
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    href=\"UTD.htm?6/0/6150/contributors\">",
    " Deputy Editor",
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    6/0/6150/contributors\">",
    " Alison G Hoppin, MD",
    " </a>",
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    " Disclosures",
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    " All topics are updated as new evidence becomes available and our",
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    " peer review process",
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    " is complete.",
    " </span>",
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    " <span class=\"emphasis\">",
    " Literature review current through:",
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    " Oct 2013.",
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    " This topic last updated:",
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    " Apr 8, 2013.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Bronchiectasis is a structural abnormality characterized by
    abnormal dilation and distortion of the bronchial tree, resulting in chronic
    obstructive lung disease. This condition is typically the end result of a variety
    of pathophysiologic processes that render the bronchial walls weakened, easily
    collapsible, chronically inflamed, and plugged with mucus secretions. Associated
    findings include atelectasis, emphysema, fibrosis, and hypertrophy of the bronchial
    vasculature.",
    " </p>",
    " <p>",
    " In developed nations, cystic fibrosis (CF) is the most common cause of
    bronchiectasis in children. The management of CF-related bronchiectasis is
    discussed in detail in separate topic reviews. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39274?
    source=see_link\">",
    " \"Cystic fibrosis: Overview of the treatment of lung disease\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/22/41322?
    source=see_link\">",
    " \"Cystic fibrosis: Antibiotic therapy for lung disease\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Bronchiectasis can be caused by a variety of disease processes other than CF,
    most of which include some combination of bronchial obstruction and infection (",
    " <a class=\"graphic graphic_table graphicRef87712 \" href=\"UTD.htm?
    26/62/27630\">",
    " table 1",
    " </a>",
    " ). The types of disorders that cause bronchiectasis vary among populations and
    age groups. Infections and acquired causes of bronchiectasis are more common in
    adults and in developing nations, whereas congenital anomalies of the bronchi or
    immune system are more prominent in children and in industrialized nations.",
    " </p>",
    " <p>",
    " This topic review will describe the management and prevention of non-CF-
    related bronchiectasis in children. The causes, clinical manifestations, and
    diagnosis of non-CF-related bronchiectasis in children, and the treatment of
    bronchiectasis in adults are discussed elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/43/16057?
    source=see_link\">",
    " \"Causes of bronchiectasis in children\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/39/44662?
    source=see_link\">",
    " \"Clinical manifestations and evaluation of bronchiectasis in children\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=see_link\">",
    " \"Treatment of bronchiectasis in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " MEDICAL TREATMENT",
    " </span>",
    " &nbsp;&mdash;&nbsp;Management of bronchiectasis is aimed at treating the
    underlying cause (eg, removal of an airway foreign body, or treatment of aspiration
    or humoral immunodeficiency), improving mucociliary clearance, treating and
    preventing infection, and controlling inflammation.",
    " </p>",
    " <p>",
    " General treatment strategies for children with non-CF-related bronchiectasis
    are often extrapolated from studies in patients with CF or adults with
    bronchiectasis. This approach has some limitations, because the pathogenesis of
    bronchiectasis and pathogens seen in these populations can differ. Thus, optimal
    management depends upon the underlying cause of bronchiectasis and on individual
    patient characteristics, such as sputum cultures and the response to initial
    therapy. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39274?
    source=see_link\">",
    " \"Cystic fibrosis: Overview of the treatment of lung disease\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=see_link\">",
    " \"Treatment of bronchiectasis in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Management approaches include the following:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Antibiotic therapy",
    " </li>",
    " <li>",
    " Chest physiotherapy",
    " </li>",
    " <li>",
    " Mucolytic agents and airway hydration",
    " </li>",
    " <li>",
    " Bronchodilators",
    " </li>",
    " <li>",
    " Anti-inflammatory drugs",
    " </li>",
    " <li>",
    " Immunization",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Antibiotic therapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Acute respiratory exacerbations in patients with non-CF-
    related bronchiectasis are treated similarly to those in patients with CF. The
    choice of antibiotics is usually based upon sputum culture results; in young
    children who are unable to produce sputum, cultures can be obtained from a throat
    swab inserted deeply into the posterior pharynx to induce a cough. One study in
    children with newly diagnosed non-CF-related bronchiectasis in Australia suggests
    that Haemophilus influenzae is a common causative organism: at the time of
    diagnosis, H. influenzae was detected in 47 percent of specimens obtained by
    bronchoalveolar lavage (BAL), while P. aeruginosa was found in just 6 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " For outpatient treatment of acute exacerbations, most patients are given oral
    antibiotics for 10 to 14 days [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/2\">",
    " 2",
    " </a>",
    " ]. Intravenous antibiotics are reserved for severe exacerbations or
    exacerbations responding poorly to outpatient therapy. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/22/41322?
    source=see_link&amp;anchor=H3#H3\">",
    " \"Cystic fibrosis: Antibiotic therapy for lung disease\", section on
    'Treatment of acute pulmonary exacerbations'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Inhaled aminoglycosides are administered chronically for patients with
    persistent Pseudomonas aeruginosa infection, similar to the approach for patients
    with CF. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/22/41322?
    source=see_link&amp;anchor=H17#H17\">",
    " \"Cystic fibrosis: Antibiotic therapy for lung disease\", section on 'Inhaled
    tobramycin'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " There are no data to guide the chronic use of antibiotics for children with
    non-CF-related bronchiectasis. In our practice, we use long-term antibiotics for
    patients with frequent acute exacerbations (eg, three or more exacerbations
    annually) or those with progressive deterioration of lung function. The antibiotic
    is tailored to sputum cultures and sensitivities, rather than chosen empirically,
    and administered for cycles of two weeks, alternating with two weeks without
    antibiotics. Although antibiotics may decrease certain microbial infections, the
    emergence of antibiotic-resistant organisms is a risk, as has been demonstrated in
    populations with CF [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/3,4\">",
    " 3,4",
    " </a>",
    " ]. Therefore, this method should be used judiciously for a defined time
    period, with clinical reevaluation.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Chest physiotherapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Bronchopulmonary hygiene is routinely performed to improve
    mucociliary clearance. A variety of techniques are used, including postural
    drainage and percussion, breathing and coughing techniques, airway oscillating
    devices, external percussion vests, and intrapulmonary percussive ventilation.
    Based upon studies in patients with cystic fibrosis, none of these techniques
    appears superior to others, although there are differences in convenience,
    compliance, and cost. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39274?
    source=see_link&amp;anchor=H9#H9\">",
    " \"Cystic fibrosis: Overview of the treatment of lung disease\", section on
    'Chest physiotherapy'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " Mucolytic agents and airway hydration",
    " </span>",
    " &nbsp;&mdash;&nbsp;There are limited data to guide the use of mucolytic agents
    in non-CF-related bronchiectasis.",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?25/35/26163?
    source=see_link\">",
    " DNase",
    " </a>",
    " is recommended for treatment of many children with CF. However, one study in
    adults with idiopathic bronchiectasis reported potentially harmful effects of DNase
    (pulmozyme) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/5\">",
    " 5",
    " </a>",
    " ]. As a result, DNase it is not routinely recommended for the management of
    non-CF-related bronchiectasis. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39274?
    source=see_link&amp;anchor=H5#H5\">",
    " \"Cystic fibrosis: Overview of the treatment of lung disease\", section on
    'Inhaled DNase I (dornase alfa)'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=see_link\">",
    " \"Treatment of bronchiectasis in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Airway hydrating treatments (ie, hypertonic saline or",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?42/60/43975?
    source=see_link\">",
    " mannitol",
    " </a>",
    " ) have not been sufficiently studied in adults or children with non-CF-related
    bronchiectasis to warrant their routine use [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Bronchodilators",
    " </span>",
    " &nbsp;&mdash;&nbsp;Bronchodilator treatment may be appropriate in some
    children with bronchiectasis, but has not been studied rigorously. Bronchodilators
    relieve airway obstruction and may facilitate mucus clearance. A response to
    bronchodilators during pulmonary function testing can be used to identify patients
    who may benefit from bronchodilator therapy.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Antiinflammatory drugs",
    " </span>",
    " &nbsp;&mdash;&nbsp;Chronic treatment with",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/48/7946?source=see_link\">",
    " ibuprofen",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?34/15/35056?
    source=see_link\">",
    " azithromycin",
    " </a>",
    " are used for a subgroup of patients with CF-related bronchiectasis, but there
    is insufficient information to support their use in patients without CF.",
    " </p>",
    " <p>",
    " Chronic use of inhaled glucocorticoids is sometimes suggested for adult
    patients with bronchiectasis, but this practice is based upon limited evidence.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=see_link\">",
    " \"Treatment of bronchiectasis in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Due to lack of studies in children, we do not suggest inhaled glucocorticoids
    as routine therapy in children with non-CF-related bronchiectasis. However, for
    patients with bronchiectasis and asthma, inhaled corticosteroids have greater
    clinical benefit, and this treatment should be used depending on asthma severity
    and control.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Immunization",
    " </span>",
    " &nbsp;&mdash;&nbsp;For children with bronchiectasis, immunizations should be
    brought up to date and rigorously maintained. Maintenance of influenza and
    pneumococcal vaccinations are recommended. Live viral vaccines may not be
    appropriate for patients with some forms of immunodeficiency. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/14/7402?
    source=see_link&amp;anchor=H13#H13\">",
    " \"Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children\",
    section on 'Indications'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/56/39818?
    source=see_link&amp;anchor=H2#H2\">",
    " \"Standard immunizations for children and adolescents\", section on
    'Overview'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h1\">",
    " COMPLICATIONS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Preventing malnutrition is important in the management of
    bronchiectasis. In children with CF, malnutrition is associated with poor survival
    [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/7\">",
    " 7",
    " </a>",
    " ], and aggressive nutritional rehabilitation improves lung function [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/8,9\">",
    " 8,9",
    " </a>",
    " ]. In patients with CF, some of the nutritional risks are caused by pancreatic
    insufficiency. It is also important to monitor and maintain nutritional status in
    patients with non-CF bronchiectasis, as for children with any chronic illness.
    Interventions to improve nutrition may include nutritional counseling to increase
    calories and nutrition quality, and liquid nutritional supplements taken by mouth
    or gastrostomy tube. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/24/15754?
    source=see_link\">",
    " \"Cystic fibrosis: Nutritional issues\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Hemoptysis is uncommon in pediatric patients with bronchiectasis. Massive
    hemoptysis, variably defined as greater than 200 ml blood loss in a 24 hour period,
    or recurrent bleeding of more than 100 mL daily for several days [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/10\">",
    " 10",
    " </a>",
    " ], represents a substantial risk and calls for prompt intervention.
    Resuscitative measures should be aimed at providing adequate oxygenation and
    restoring intravascular volume. Management is similar to that for patients with
    other causes of hemoptysis, and may include embolization or surgery. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39274?
    source=see_link&amp;anchor=H34#H34\">",
    " \"Cystic fibrosis: Overview of the treatment of lung disease\", section on
    'Hemoptysis'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/0/37896?
    source=see_link\">",
    " \"Hemoptysis in children\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Other rare complications of bronchiectasis include pneumothorax, empyema, and
    cor pulmonale [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h1\">",
    " SURGERY",
    " </span>",
    " &nbsp;&mdash;&nbsp;Surgery is typically indicated in patients with localized
    bronchiectasis that results in severe symptoms, such as failure to thrive,
    recurrent infection, or severe hemoptysis [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/2,11\">",
    " 2,11",
    " </a>",
    " ]. Less commonly, surgery is used for patients with generalized bronchiectasis
    but localized and resectable complications, such as a nidus of infection or source
    of hemorrhage. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=see_link\">",
    " \"Treatment of bronchiectasis in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " In a 10-year followup of 84 pediatric patients undergoing resection for
    bronchiectasis, 39 percent had no significant symptoms or residual bronchiectasis,
    and 36 percent had marked reduction in symptoms but residual disease on
    radiographic study. Complications occurred in 11 percent of patients and included
    atelectasis, pneumothorax, chylothorax, bronchopulmonary fistula, and respiratory
    failure [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6150/abstract/12\">",
    " 12",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Lung transplantation is a procedure of last resort for patients with
    bronchiectasis. Most long-term studies have been done in patients with CF. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=see_link&amp;anchor=H19#H19\">",
    " \"Treatment of bronchiectasis in adults\", section on 'Lung
    transplantation'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39274?
    source=see_link&amp;anchor=H26#H26\">",
    " \"Cystic fibrosis: Overview of the treatment of lung disease\", section on
    'Lung transplantation'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h1\">",
    " PREVENTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The following measures prevent or reduce the severity of
    respiratory infections, and thereby reduce the risk for developing
    bronchiectasis:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Preventing tobacco smoke exposure (see",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/58/41895?
    source=see_link\">",
    " \"Control of secondhand smoke exposure\"",
    " </a>",
    " )",
    " </li>",
    " <li>",
    " Ensuring completion of vaccination series, particularly the pneumococcal and
    influenza vaccines (see",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/56/39818?
    source=see_link&amp;anchor=H2#H2\">",
    " \"Standard immunizations for children and adolescents\", section on
    'Overview'",
    " </a>",
    " )",
    " </li>",
    " <li>",
    " Aggressively treating respiratory infections, including suspected persistent
    bacterial bronchitis (PBB); identification and treatment of the underlying cause
    for recurrent pneumonias or other respiratory infections, including retained
    foreign bodies (see",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/47/30458?
    source=see_link\">",
    " \"Approach to the child with recurrent infections\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </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>",
    " Basics topic (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?39/57/40850?
    source=see_link\">",
    " \"Patient information: Bronchiectasis in children (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Bronchiectasis is characterized by abnormal dilation and distortion of the
    bronchial tree, resulting in chronic obstructive lung disease. This condition is
    the end result of a variety of pathophysiologic processes, usually a combination of
    infection and impaired airway drainage or obstruction. Important causes of
    bronchiectasis in children include cystic fibrosis, chronic aspiration, infection
    (with or without underlying immunodeficiency), foreign body aspiration, and
    congenital pulmonary defects (",
    " <a class=\"graphic graphic_table graphicRef87712 \" href=\"UTD.htm?
    26/62/27630\">",
    " table 1",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/43/16057?
    source=see_link\">",
    " \"Causes of bronchiectasis in children\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Management strategies for bronchiectasis in children depend on the
    underlying cause of bronchiectasis and individual patient characteristics. These
    approaches are similar to those used for adult patients with bronchiectasis. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'Medical treatment'",
    " </a>",
    " above and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=see_link\">",
    " \"Treatment of bronchiectasis in adults\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " For most pediatric patients with non-CF-related bronchiectasis, we suggest
    systemic antibiotics to treat acute exacerbations (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). We also suggest routine chest physiotherapy (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'Antibiotic therapy'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H4\">",
    " 'Chest physiotherapy'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " For those with persistent Pseudomonas aeruginosa infection, we suggest
    chronic treatment with inhaled aminoglycosides (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'Antibiotic therapy'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " For patients with frequent acute exacerbations or progressive deterioration
    of lung function, we suggest treatment with long-term antibiotics (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). The antibiotics are tailored to sputum cultures and sensitivities, rather
    than chosen empirically, and the patient is reevaluated periodically (see",
    " <a class=\"local\" href=\"#H3\">",
    " 'Antibiotic therapy'",
    " </a>",
    " above).",
    " </li>",
    " <li>",
    " For children with non-CF-related bronchiectasis we suggest NOT treating
    with",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?25/35/26163?
    source=see_link\">",
    " DNase",
    " </a>",
    " &nbsp;(",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). Although DNase is recommended for children with CF, it is not effective
    in adults with non-CF-related bronchiectasis, and may even be harmful. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Mucolytic agents and airway hydration'",
    " </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>",
    " <ol id=\"reference\">",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/1\">",
    " Kapur N, Grimwood K, Masters IB, et al. Lower airway microbiology and
    cellularity in children with newly diagnosed non-CF bronchiectasis. Pediatr
    Pulmonol 2012; 47:300.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/2\">",
    " Sethi GR, Batra V. Bronchiectasis: causes and management. Indian J Pediatr
    2000; 67:133.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/3\">",
    " Smyth AR, Walters S. Prophylactic anti-staphylococcal antibiotics for cystic
    fibrosis. Cochrane Database Syst Rev 2012; 12:CD001912.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/4\">",
    " Hill RL, Kearns AM, Nash J, et al. Linezolid-resistant ST36 methicillin-
    resistant Staphylococcus aureus associated with prolonged linezolid treatment in
    two paediatric cystic fibrosis patients. J Antimicrob Chemother 2010; 65:442.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/5\">",
    " O'Donnell AE, Barker AF, Ilowite JS, Fick RB. Treatment of idiopathic
    bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group.
    Chest 1998; 113:1329.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/6\">",
    " Redding GJ. Bronchiectasis in children. Pediatr Clin North Am 2009;
    56:157.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/7\">",
    " Sharma R, Florea VG, Bolger AP, et al. Wasting as an independent predictor
    of mortality in patients with cystic fibrosis. Thorax 2001; 56:746.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/8\">",
    " Shepherd RW, Holt TL, Thomas BJ, et al. Nutritional rehabilitation in cystic
    fibrosis: controlled studies of effects on nutritional growth retardation, body
    protein turnover, and course of pulmonary disease. J Pediatr 1986; 109:788.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/9\">",
    " Marchand V, Baker SS, Stark TJ, Baker RD. Randomized, double-blind, placebo-
    controlled pilot trial of megestrol acetate in malnourished children with cystic
    fibrosis. J Pediatr Gastroenterol Nutr 2000; 31:264.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/10\">",
    " Jean-Baptiste E. Clinical assessment and management of massive hemoptysis.
    Crit Care Med 2000; 28:1642.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/11\">",
    " Lewiston NJ. Bronchiectasis in childhood. Pediatr Clin North Am 1984;
    31:865.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6150/abstract/12\">",
    " Wilson JF, Decker AM. The surgical management of childhood bronchiectasis. A
    review of 96 consecutive pulmonary resections in children with nontuberculous
    bronchiectasis. Ann Surg 1982; 195:354.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 6355 Version 5.0",
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    var script_f6_0_6150=[""].join("\n");
    var outline_f6_0_6150=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
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    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H12\" 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\">",
    " MEDICAL TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " Antibiotic therapy",
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    " Chest physiotherapy",
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    " COMPLICATIONS",
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    " <a class=\"outlineLink\" href=\"#H10\">",
    " SURGERY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " PREVENTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"PEDS/6355\" rel=\"outline_link\">",
    " GRAPHICS",
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    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?26/62/27630\" title=\"table
    1\">",
    " Causes and evaluation of bronchiectasis in children",
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    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/47/30458?
    source=related_link\">",
    " Approach to the child with recurrent infections",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/43/16057?
    source=related_link\">",
    " Causes of bronchiectasis in children",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/39/44662?
    source=related_link\">",
    " Clinical manifestations and evaluation of bronchiectasis in children",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/58/41895?
    source=related_link\">",
    " Control of secondhand smoke exposure",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/22/41322?
    source=related_link\">",
    " Cystic fibrosis: Antibiotic therapy for lung disease",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/24/15754?
    source=related_link\">",
    " Cystic fibrosis: Nutritional issues",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39274?
    source=related_link\">",
    " Cystic fibrosis: Overview of the treatment of lung disease",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/0/37896?
    source=related_link\">",
    " Hemoptysis in children",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?39/57/40850?
    source=related_link\">",
    " Patient information: Bronchiectasis in children (The Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/14/7402?
    source=related_link\">",
    " Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/56/39818?
    source=related_link\">",
    " Standard immunizations for children and adolescents",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/11/38073?
    source=related_link\">",
    " Treatment of bronchiectasis in adults",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f6_0_6151="Chlorpropamide: Drug information";
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Chlorpropamide: 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?39/5/40020?source=see_link\">",
    " see \"Chlorpropamide: 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=\"list cbnlist drugH1Div drugBrandNames\" id=\"F150611\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Apo-Chlorpropamide&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F150648\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacologic Category",
    " </span>",
    " <ul>",
    " <li>",
    " Antidiabetic Agent, Sulfonylurea",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block doa drugH1Div\" id=\"F150615\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Adult",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Type 2 diabetes: Oral: The dosage of chlorpropamide is variable and should be
    individualized based upon the patient's response",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <i>",
    " Initial dose:",
    " </i>",
    " 250 mg daily in mild-to-moderate diabetes in middle-aged, stable diabetic
    patients",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <i>",
    " Titration:",
    " </i>",
    " After 5-7 days of initiation, subsequent daily dosages may be increased or
    decreased by 50-125 mg at 3- to 5-day intervals",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <i>",
    " Maintenance dose:",
    " </i>",
    " 100-250 mg daily; severe patients with diabetes may require 500 mg daily;
    avoid doses &gt;750 mg daily",
    " </p>",
    " </div>",
    " <div class=\"block doe drugH1Div\" id=\"F150616\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Geriatric",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Refer to adult dosing. Reduce initial dose to 100-125 mg/day in older
    patients; after 5-7 days of initiation, subsequent daily dosages may be increased
    or decreased by 50-125 mg at 3- to 5-day intervals (slower upward titration may be
    appropriate in older patients)",
    " </p>",
    " </div>",
    " <div class=\"block dor drugH1Div\" id=\"F150617\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Renal Impairment",
    " </span>",
    " <p style=\"text-indent:0em;margin-left:0em;margin-top:0em;text-
    align:justify;display:inline\">",
    " No specific dosage adjustment provided in manufacturer&rsquo;s labeling;
    conservative initial and maintenance doses are recommended.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Alternate recommendations (Aronoff, 2007):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &gt;50 mL/minute: Reduce dose by 50%.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;50 mL/minute: Avoid use.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hemodialysis: Avoid use.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Peritoneal dialysis: Avoid use.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Continuous renal replacement therapy (CRRT): Avoid use.",
    " </p>",
    " </div>",
    " <div class=\"block doh drugH1Div\" id=\"F150618\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Hepatic Impairment",
    " </span>",
    " <p style=\"text-indent:0em;margin-left:0em;text-
    align:justify;display:inline\">",
    " No specific dosage adjustment provided in manufacturer&rsquo;s labeling;
    conservative initial and maintenance doses are recommended in patients with liver
    impairment since chlorpropamide undergoes extensive hepatic metabolism.",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F150589\"
    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;\">",
    " Tablet, oral: 100 mg, 250 mg",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F150574\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Yes",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F9460444\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Administer once daily with breakfast. Daily dose may be divided to reduce GI
    upset. Patients that are NPO or require decreased caloric intake may need doses
    held to avoid hypoglycemia.",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F150592\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Management of blood sugar in type 2 diabetes mellitus (noninsulin dependent,
    NIDDM) as an adjunct to diet and exercise to lower blood glucose",
    " </p>",
    " </div>",
    " <div class=\"block usu drugH1Div\" id=\"F150644\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use - Unlabeled",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Central (neurogenic) diabetes insipidus",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F150653\"
    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;\">",
    " ChlorproPAMIDE may be confused with chlorproMAZINE",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Diabinese may be confused with DiaBeta&reg;, Diamox&reg;",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " High alert medication:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " The Institute for Safe Medication Practices (ISMP) includes this medication
    among its list of drugs which have a heightened risk of causing significant patient
    harm when used in error.",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " BEERS Criteria medication:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " This drug may be potentially inappropriate for use in geriatric patients
    (Quality of evidence - high; Strength of recommendation - strong).",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"block ars drugH1Div\" id=\"F150646\"
    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 always defined.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Central nervous system: Dizziness, headache",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Dermatologic: Pruritus (&lt;3%), maculopapular eruptions (&le;1%), urticaria
    (&le;1%), erythema multiforme, exfoliative dermatitis, photosensitivity",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Endocrine &amp; metabolic: Disulfiram-like reactions, hypoglycemia, SIADH",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Gastrointestinal: Nausea (&lt;5%), anorexia (&lt;2%), diarrhea (&lt;2%),
    hunger (&lt;2%), vomiting (&lt;2%), proctocolitis (&lt;1%), weight gain",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hematologic: Agranulocytosis, aplastic anemia, eosinophilia, hemolytic
    anemia, leukopenia, pancytopenia, porphyria cutanea tarda, thrombocytopenia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hepatic: Cholestatic jaundice, hepatic porphyria, hepatitis, liver failure",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F150595\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to chlorpropamide or any component of the formulation; type
    1 diabetes mellitus (insulin dependent, IDDM); diabetic ketoacidosis (with or
    without coma)",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F150578\"
    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; Cardiovascular mortality: Product labeling states oral hypoglycemic
    drugs may be associated with an increased cardiovascular mortality as compared to
    treatment with diet alone or diet plus insulin. Data to support this association
    are limited, and several studies, including a large prospective trial (UKPDS, 1998)
    have not supported an association.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hypoglycemia: All sulfonylurea drugs are capable of producing severe
    hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is
    deficient, after severe or prolonged exercise, when ethanol is ingested, or when
    more than one glucose-lowering drug is used. It is also more likely in elderly
    patients, malnourished patients and in patients with impaired renal or hepatic
    function; use with caution. Autonomic neuropathy, advanced age, and concomitant use
    of beta-blockers or other sympatholytic agents may impair the patient&rsquo;s
    ability to recognize the signs and symptoms of hypoglycemia; use with caution.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Sulfonamide allergy: Chemical similarities are present among
    sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop
    diuretics (except ethacrynic acid). Use with caution in patients with sulfonylurea
    or sulfonamide allergy; a risk of cross-reaction exists in patients with allergy to
    any of these compounds; avoid use when previous reaction has been severe.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Disease-related issues:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with
    G6PD deficiency may be at an increased risk of sulfonylurea-induced hemolytic
    anemia; however, cases have also been described in patients without G6PD deficiency
    during postmarketing surveillance. Use with caution and consider a nonsulfonylurea
    alternative in patients with G6PD deficiency.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Stress-related states: It may be necessary to discontinue therapy and
    administer insulin if the patient is exposed to stress (fever, trauma, infection,
    surgery).",
    " </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; Elderly: Avoid use in this age group due to prolonged half-
    life/hypoglycemia and risk of causing SIADH (Beers Criteria).",
    " </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; Long half-life: Patients should be properly instructed in the early
    detection and treatment of hypoglycemia; long half-life may complicate recovery
    from excess effects.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Secondary failure: Loss of efficacy may be observed following
    prolonged use as a result of the progression of type 2 diabetes mellitus which
    results in continued beta cell destruction. In patients who were previously
    responding to sulfonylurea therapy, consider additional factors which may be
    contributing to decreased efficacy (eg, inappropriate dose, nonadherence to diet
    and exercise regimen). If no contributing factors can be identified, consider
    discontinuing use of the sulfonylurea due to secondary failure of treatment.
    Additional antidiabetic therapy (eg, insulin) will be required.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F150643\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " <b>",
    " Substrate",
    " </b>",
    " of CYP2C9 (major);",
    " <b>",
    " Note:",
    " </b>",
    " Assignment of Major/Minor substrate status based on clinically relevant drug
    interaction potential",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F150583\"
    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;\">",
    " Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of
    Alcohol (Ethyl). A flushing reaction may occur.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Allopurinol: May increase the serum concentration of ChlorproPAMIDE.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Beta-Blockers: May enhance the hypoglycemic effect of Sulfonylureas.
    Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and
    penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear
    to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers
    are probably associated with lower risk than systemic agents.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Levobunolol; Metipranolol.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Chloramphenicol: May decrease the metabolism of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cimetidine: May increase the serum concentration of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of
    Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis
    suppression has led to episodes of acute adrenal crisis, which may manifest as
    enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic
    agent use.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Corticosteroids (Systemic): May diminish the hypoglycemic effect of
    Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis
    suppression has led to episodes of acute adrenal crisis, which may manifest as
    enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic
    agent use.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cyclic Antidepressants: May enhance the hypoglycemic effect of
    Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates.
    Management: Consider an alternative for one of the interacting drugs. Some
    combinations may be specifically contraindicated. Consult appropriate manufacturer
    labeling.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9
    Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9
    Substrates.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fibric Acid Derivatives: May enhance the hypoglycemic effect of
    Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fluconazole: May increase the serum concentration of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " GLP-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas.
    Management: Consider sulfonylurea dose reductions when used in combination with
    GLP-1 agonists.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of
    Hypoglycemic Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Hypoglycemic Agents: May enhance the adverse/toxic effect of other
    Hypoglycemic Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Loop Diuretics: May diminish the hypoglycemic effect of Hypoglycemic
    Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic
    effect of Antidiabetic Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " MAO Inhibitors: May enhance the hypoglycemic effect of Hypoglycemic Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Mifepristone: May increase the serum concentration of CYP2C9 Substrates.
    Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor
    closely for adverse effects, during and in the 2 weeks following mifepristone
    treatment.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9
    Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of
    Porfimer.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Probenecid: May decrease the protein binding of Sulfonylureas. Probenecid may
    increase the serum concentration of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Quinolone Antibiotics: May enhance the hypoglycemic effect of Sulfonylureas.
    This appears to be particularly concerning early in the course of combination
    therapy. Quinolone Antibiotics may diminish the hypoglycemic effect of
    Sulfonylureas. With longer-term combination, there is a greater risk of
    hyperglycemia.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ranitidine: May increase the serum concentration of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Rifampin: May increase the metabolism of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Salicylates: May enhance the hypoglycemic effect of Hypoglycemic Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect
    of Hypoglycemic Agents. Selective Serotonin Reuptake Inhibitors may increase the
    serum concentration of Hypoglycemic Agents. Management: Consider increased
    monitoring of glycemic control with concomitant use of a hypoglycemic agent and an
    SSRI. Dosage adjustments of the hypoglycemic agent may be necessary upon SSRI
    initiation or discontinuation.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Sulfonamide Derivatives: May enhance the hypoglycemic effect of
    Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic
    Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vitamin K Antagonists (eg, warfarin): Sulfonylureas may enhance the
    anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance
    the hypoglycemic effect of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Voriconazole: May increase the serum concentration of Sulfonylureas.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block foi drugH1Div\" id=\"F150607\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Ethanol/Nutrition/Herb Interactions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ethanol: Avoid ethanol (possible disulfiram-like reaction).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Herb/Nutraceutical: Herbs with hypoglycemic properties may enhance the
    hypoglycemic effect of chlorpropamide. This includes alfalfa, aloe, bilberry,
    bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger,
    ginseng (American), gymnema, marshmallow, stinging nettle",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F150584\"
    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=\"F150598\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Animal reproduction studies have not been conducted; therefore, the
    manufacturer classifies chlorpropamide as pregnancy category C. Chlorpropamide
    crosses the placenta and measurable serum concentrations can be found in infants
    exposed",
    " <i>",
    " in utero",
    " </i>",
    " . Teratogenic effects have been associated with chlorpropamide use in some
    studies; however, it is unknown if this is related to the medication or
    uncontrolled diabetes. Nonteratogenic adverse effects (eg, severe neonatal
    hypoglycemia, increased perinatal mortality) have also been associated with
    maternal chlorpropamide use. Maternal hyperglycemia can be associated with adverse
    effects in the fetus, including macrosomia, neonatal hyperglycemia, and
    hyperbilirubinemia; the risk of congenital malformations is increased when the Hb
    A",
    " <sub>",
    " 1c",
    " </sub>",
    " is above the normal range. Diabetes can also be associated with adverse
    effects in the mother. Poorly-treated diabetes may cause end-organ damage that may
    in turn negatively affect obstetric outcomes. Physiologic glucose levels should be
    maintained prior to and during pregnancy to decrease the risk of adverse events in
    the mother and the fetus. Until additional safety and efficacy data are obtained,
    the use of oral agents is generally not recommended as routine management of GDM or
    type 2 diabetes mellitus during pregnancy. The manufacturer recommends if
    chlorpropamide is used during pregnancy, it should be discontinued at least 1 month
    before the expected delivery date. Insulin is the drug of choice for the control of
    diabetes mellitus during pregnancy.",
    " </p>",
    " </div>",
    " <div class=\"block lac drugH1Div\" id=\"F150619\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Lactation",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Enters breast milk/not recommended",
    " </p>",
    " </div>",
    " <div class=\"block brc drugH1Div\" id=\"F5651827\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Breast-Feeding Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Chlorpropamide is found in breast milk. Breast-feeding is not recommended by
    the manufacturer. Potentially, hypoglycemia may occur in a nursing infant exposed
    to a sulfonylurea via breast milk.",
    " </p>",
    " </div>",
    " <div class=\"block dic drugH1Div\" id=\"F150599\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dietary Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " May cause GI upset; take with food.",
    " </p>",
    " </div>",
    " <div class=\"block fee drugH1Div\" id=\"F150597\"
    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>",
    " Tablets",
    " </b>",
    " (ChlorproPAMIDE Oral)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 100 mg (100): $58.16",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 250 mg (100): $122.90",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F150587\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Blood glucose, Hgb A",
    " <sub>",
    " 1c",
    " </sub>",
    " ; monitor for signs and symptoms of hypoglycemia (fatigue, sweating, numbness
    of extremities)",
    " </p>",
    " </div>",
    " <div class=\"block rer drugH1Div\" id=\"F150590\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Reference Range",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Recommendations for glycemic control in nonpregnant adults with diabetes
    (ADA, 2012):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hb A",
    " <sub>",
    " 1c",
    " </sub>",
    " : &lt;7% (a more aggressive [&lt;6.5%] or less aggressive [&lt;8%] Hb A",
    " <sub>",
    " 1c",
    " </sub>",
    " goal may be targeted based on patient-specific characteristics)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Preprandial capillary plasma glucose: 70-130 mg/dL",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Peak postprandial capillary blood glucose: &lt;180 mg/dL",
    " </p>",
    " </div>",
    " <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F150600\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " International Brand Names",
    " </span>",
    " <ul>",
    " <li>",
    " Abemide (JP, TW);",
    " </li>",
    " <li>",
    " Adiaben (HR);",
    " </li>",
    " <li>",
    " Anti-D (SG);",
    " </li>",
    " <li>",
    " Arodoc C (JP);",
    " </li>",
    " <li>",
    " Bioglumin (ES);",
    " </li>",
    " <li>",
    " Chlormide (JP);",
    " </li>",
    " <li>",
    " Chlorpropamid (PL);",
    " </li>",
    " <li>",
    " Copamide (IN);",
    " </li>",
    " <li>",
    " Dabinese (VE);",
    " </li>",
    " <li>",
    " Diabemide (BF, BJ, CI, ET, GH, GM, GN, IT, KE, LR, MA, ML, MR, MU, MW, NE,
    NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);",
    " </li>",
    " <li>",
    " Diabenese (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CO, CR, CY, DO, EG, ET, GB,
    GH, GM, GN, GR, GT, GY, HN, IL, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR,
    MU, MW, MX, NE, NG, NI, NL, OM, PA, PR, PT, QA, SA, SC, SD, SL, SN, SR, SV, SY, TN,
    TT, TZ, UG, YE, ZA, ZM, ZW);",
    " </li>",
    " <li>",
    " Diabet (ES);",
    " </li>",
    " <li>",
    " Diabezin (TW);",
    " </li>",
    " <li>",
    " Diabines (SE);",
    " </li>",
    " <li>",
    " Diabinese (AR, AU, BE, BR, CH, CN, EC, ES, HK, HR, ID, IE, KP, LU, NO, PE,
    PH, PK, PL, TH, TR, UY);",
    " </li>",
    " <li>",
    " Diabitex (BB, BM, BS, BZ, GY, JM, NL, SR, TT, ZA);",
    " </li>",
    " <li>",
    " Dibecon (TH);",
    " </li>",
    " <li>",
    " Glicoben (BR);",
    " </li>",
    " <li>",
    " Glycemin (TH);",
    " </li>",
    " <li>",
    " Hypomide (ZA);",
    " </li>",
    " <li>",
    " Insogen (MX);",
    " </li>",
    " <li>",
    " Litangen (TW);",
    " </li>",
    " <li>",
    " Meldian (HR);",
    " </li>",
    " <li>",
    " Mellitos C (JP);",
    " </li>",
    " <li>",
    " Propamide (MY, SG);",
    " </li>",
    " <li>",
    " Trane (AR)",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F150577\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Stimulates insulin release from the pancreatic beta cells; reduces glucose
    output from the liver; insulin sensitivity is increased at peripheral target
    sites",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F150594\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics/Kinetics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Onset of action: 1 hour",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Peak effect: 3-6 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Duration: 24 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Absorption: Rapid",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Distribution: V",
    " <sub>",
    " d",
    " </sub>",
    " : 0.13-0.23 L/kg (Arrigoni, 1987)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Protein binding: 90%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Metabolism: Extensively hepatic (~80%), primarily via CYP2C9; forms
    metabolites",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Half-life elimination: ~36 hours; prolonged in elderly or with renal
    impairment",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " End-stage renal disease: 50-200 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Time to peak, serum: 2-4 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Excretion: Urine (unchanged drug and as hydroxylated or hydrolyzed
    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\">",
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    " &ldquo;A Study of the Effects of Hypoglycemia Agents on Vascular
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    " Canadian Diabetes Association Clinical Practice Guidelines Expert Committee,
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    " &ldquo;Effect of Intensive Blood-Glucose Control With Metformin on
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    " , 1999, 33(1):119-24.",
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    " ]",
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    " </div>",
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    " <div class=\"reference\">",
    " Kirkman M, Briscoe VJ, Clark N, et al, \"Diabetes in Older Adults: A
    Consensus Report,\"",
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    " , 2012; doi: 10.1111/jgs.12035.",
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    " 23106132",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Klamann A, Sarfert P, Launhardt V, et al, &ldquo;Myocardial Infarction in
    Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With
    Sulfonylureas (Glibenclamide),",
    " <i>",
    " Eur Heart J",
    " </i>",
    " , 2000, 21(3):220-9.",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Meinert CL, Knatterud GL, Prout TE, et al, &ldquo;A Study of the Effects of
    Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset
    Diabetes. II. Mortality Results,&rdquo;",
    " <i>",
    " Diabetes",
    " </i>",
    " , 1970, 19:789-830.",
    " <span class=\"pubmed-id\">",
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    target=\"_blank\">",
    " 4926376",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " O'Keefe JH, Blackstone EH, Sergeant P, et al, &ldquo;The Optimal Mode of
    Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing
    Coronary Angioplasty and Coronary Bypass Surgery,&rdquo;",
    " <i>",
    " Eur Heart J",
    " </i>",
    " , 1998, 19(11):1696-703.",
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    " 9857923",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Qaseem A, Humphrey LL, Sweet DE, et al,&ldquo;Oral Pharmacologic Treatment
    of Type 2 Diabetes Mellitus: A Clinical Practice Guideline from the American
    College of Physicians,&rdquo;",
    " <i>",
    " Ann Intern Med",
    " </i>",
    " , 2012, 156(3):218-31.",
    " <span class=\"pubmed-id\">",
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    target=\"_blank\">",
    " 22312141",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " UK Prospective Diabetes Study (UKPDS) Group, &ldquo;Intensive Blood-Glucose
    Control With Sulphonylureas or Insulin Compared With Conventional Treatment and
    Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33),&rdquo;",
    " <i>",
    " Lancet",
    " </i>",
    " , 1998, 352(9131):837-53.",
    " <span class=\"pubmed-id\">",
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    target=\"_blank\">",
    " 9742976",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Verbalis JG, &ldquo;Diabetes Insipidus,&rdquo;",
    " <i>",
    " Rev Endocr Metab Disord",
    " </i>",
    " , 2003, 4(2):177-85.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
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    target=\"_blank\">",
    " 12766546",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
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    " Topic 9253 Version 41.0",
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    " TOPIC OUTLINE",
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    " <ul>",
    " <li class=\"plainItem\">",
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    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F150648\">",
    " Pharmacologic Category",
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    " <li class=\"plainItem\">",
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    " Dosing: Adult",
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    " Dosing: Geriatric",
    " </a>",
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    " Pricing: U.S. (Medi-Span&reg;)",
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    " Monitoring Parameters",
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    " REFERENCES",
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    " </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>",
    " Oct 16, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H18524881\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;A fistula is an abnormal communication between two
    epithelialized surfaces. An enterocutaneous fistula (ECF) is a communication
    between the bowel lumen and the skin. An exposed or enteroatmospheric fistula
    refers to drainage of intestinal contents from an open abdomen with no overlying
    soft tissue.",
    " </p>",
    " <p>",
    " Enteric fistulas represent difficult clinical complications, with significant
    morbidity and mortality. This topic review will focus on the management of external
    gastrointestinal enterocutaneous and enteroatmospheric fistulas. Internal fistulas
    and other types of fistulas are discussed elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?32/11/32951?
    source=see_link\">",
    " \"Rectovaginal, anovaginal, and colovesical fistulas\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/47/44792?
    source=see_link\">",
    " \"Urogenital tract fistulas in women\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/40/26246?
    source=see_link\">",
    " \"Perianal abscess: Clinical manifestations, diagnosis, treatment\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/52/42819?
    source=see_link\">",
    " \"Acute diverticulitis complicated by fistula formation\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/14/28903?
    source=see_link\">",
    " \"Clinical features, diagnosis, and prevention of pancreatic fistulas\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H1480967\">",
    " <span class=\"h1\">",
    " PRESENTATION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The most common presentation of an enteric fistula is in a
    postoperative patient with abdominal distension and tenderness, a low grade fever,
    and failure to recover normally from abdominal surgery. A wound infection is
    recognized and drained 7 to 10 days after surgery, followed by the appearance of
    enteric contents in the surgical wound [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/1\">",
    " 1",
    " </a>",
    " ]. Preoperative factors that increase the likelihood of the development of a
    fistula include malnutrition, infection, and emergency procedures. Spontaneous
    fistula formation is most common in inflammatory bowel disease, malignancy, or
    following radiation therapy [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18116253\">",
    " <span class=\"h1\">",
    " CLASSIFICATION OF ENTERIC FISTULAS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Enteric fistulas are classified as enterocutaneous or
    enteroatmospheric (exposed) fistulas.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322734\">",
    " <span class=\"h2\">",
    " Enterocutaneous fistulas",
    " </span>",
    " &nbsp;&mdash;&nbsp;Enterocutaneous fistulas are classified with regard to
    anatomy, etiology, physiology [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/3\">",
    " 3",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The anatomic classification of enteric fistulas is based upon the segment of
    bowel from which it originates (ie, gastrocutaneous, colocutaneous).",
    " </li>",
    " <li>",
    " The etiologic classification is based upon the underlying disease process
    (ie, postoperative, trauma, foreign body, Crohn&rsquo;s disease, diverticulitis,
    tuberculosis, malignancy) (",
    " <a class=\"graphic graphic_table graphicRef76953 \" href=\"UTD.htm?
    24/44/25291\">",
    " table 1",
    " </a>",
    " ). Most fistulas are the result of bowel injury during surgery, a leak from
    a bowel anastomosis, or erosion of mesh into adjacent bowel [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/1\">",
    " 1",
    " </a>",
    " ]. Approximately 20 to 40 percent of all enterocutaneous fistulas result
    from Crohn&rsquo;s disease [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/4,5\">",
    " 4,5",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/0/20490?
    source=see_link&amp;anchor=H12689057#H12689057\">",
    " \"Clinical manifestations, diagnosis and prognosis of Crohn's disease in
    adults\", section on 'Fistulas'",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " The physiologic classification is based on the volume of fistula output.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"hyphen-block\">",
    " <li>",
    " A low output fistula drains less than 200",
    " <span class=\"nowrap\">",
    " mL/day.",
    " </span>",
    " </li>",
    " <li>",
    " A moderate output fistula drains between 200 and 500",
    " <span class=\"nowrap\">",
    " mL/day.",
    " </span>",
    " </li>",
    " <li>",
    " A high output fistula drains more than 500",
    " <span class=\"nowrap\">",
    " mL/day.",
    " </span>",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322742\">",
    " <span class=\"h2\">",
    " Enteroatmospheric (exposed) fistulas",
    " </span>",
    " &nbsp;&mdash;&nbsp;Enteroatmospheric or exposed fistulas occur in the midst of
    an open abdomen with no overlying soft tissue (",
    " <a class=\"graphic graphic_picture graphicRef58058 \" href=\"UTD.htm?
    14/50/15140\">",
    " picture 1",
    " </a>",
    " ). These fistulas occur when the abdomen is left open after trauma or
    emergency surgery and are classified on the basis of the surrounding abdominal
    wound [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/6\">",
    " 6",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " A deep exposed fistula is characterized by uncontrolled infection and drains
    intestinal content directly into the peritoneal cavity, causing peritonitis.",
    " </li>",
    " <li>",
    " A superficial exposed fistula drains atop the granulating wound of a frozen
    abdomen (densely adherent intestines and other abdominal organs, also called fused
    visceral block) with an obliterated peritoneal cavity, and primarily represents a
    wound management and nutritional support problem.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18524895\">",
    " <span class=\"h1\">",
    " MANAGEMENT OF ENTEROCUTANEOUS FISTULAS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Initial treatment of an enterocutaneous fistula focuses on
    the correction of fluid and electrolyte imbalance, abscess drainage and treatment
    of infection, correction of malnutrition, and meticulous fistula control and skin
    care (",
    " <a class=\"graphic graphic_table graphicRef57027 \" href=\"UTD.htm?
    23/19/23868\">",
    " table 2",
    " </a>",
    " ). Approximately one-third of enterocutaneous fistulas will heal spontaneously
    with these measures within five to six weeks [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/7\">",
    " 7",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Patients who do not respond to conservative measures should be referred to a
    center capable of providing complex multidisciplinary care [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/8\">",
    " 8",
    " </a>",
    " ]. Treatment of enteric fistulas in specialized centers of excellence improves
    outcomes and decreases the mortality rate [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/4,9,10\">",
    " 4,9,10",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Spontaneous fistula closure rates vary depending upon the cause and volume of
    the fistula and the presence of well-vascularized soft tissue over the fistula (",
    " <a class=\"graphic graphic_table graphicRef76451 \" href=\"UTD.htm?
    29/48/30476\">",
    " table 3",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/11-21\">",
    " 11-21",
    " </a>",
    " ]. Distal obstruction, a short epithelialized fistula tract, infection, and
    malignancy are barriers to spontaneous closure [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/22\">",
    " 22",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H320290\">",
    " <span class=\"h2\">",
    " Fluid and electrolyte imbalance",
    " </span>",
    " &nbsp;&mdash;&nbsp;Aggressive correction of hypovolemia should occur in the
    first few hours of treatment. Measurement of electrolytes in the fistula fluid
    helps to guide proper replacement. Hypokalemia is the most common electrolyte
    abnormality. Ongoing fluid losses from high output upper gastrointestinal fistulas
    should be replaced with isotonic saline and potassium supplementation with serial
    measurements of serum electrolytes. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?13/20/13639?
    source=see_link\">",
    " \"Treatment of severe hypovolemia or hypovolemic shock in adults\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/2/9258?
    source=see_link\">",
    " \"Clinical manifestations and treatment of hypokalemia\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Duodenal or pancreatic fistulas may require bicarbonate replacement because of
    the development of metabolic acidosis. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/20/23878?
    source=see_link\">",
    " \"Treatment of pancreatic fistulas\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?30/44/31432?
    source=see_link&amp;anchor=H15#H15\">",
    " \"Approach to the adult with metabolic acidosis\", section on 'Treatment'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H320484\">",
    " <span class=\"h2\">",
    " Abscess drainage and treatment of infection",
    " </span>",
    " &nbsp;&mdash;&nbsp;Enterocutaneous fistulas are often associated with intra-
    abdominal infection, which can present as a contained abscess or peritonitis.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Peritonitis is a surgical emergency requiring laparotomy. Laparotomy for
    source control most often requires exteriorization of the fistula or proximal
    diversion. Rarely, an early fistula can be resected or closed primarily.",
    " </li>",
    " <li>",
    " Contained abscesses are amenable to percutaneous computed tomography (CT) or
    ultrasound (US) guided drainage [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/23\">",
    " 23",
    " </a>",
    " ]. A CT scan with oral contrast is useful to demonstrate the anatomy of the
    fistula, associated intra-abdominal abscesses, and areas of distal obstruction as
    well as directing percutaneous drainage procedures. Percutaneous abscess drainage
    with radiologic guidance is often possible to control and treat infection
    associated with fistula formation.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Drainage is usually performed through the anterior abdominal wall. However,
    abscesses deep in the pelvis or obscured by other organs may be accessed with a
    variety of approaches, including transgastric, transrectal, transvaginal, and
    transgluteal [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/24\">",
    " 24",
    " </a>",
    " ]. The drainage catheter is usually left in place until drainage is less than
    10 mL in 24 hours; this may take as long as 30 days. Catheter fistulograms during
    this period can show persistent communication between fistula and bowel, and permit
    assessment of resolution of the abscess cavity. Surgical intervention is needed if
    improvement does not occur.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H320386\">",
    " <span class=\"h2\">",
    " Nutrition",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients with a fistula should not be allowed to eat (NPO
    [nil per os]) during the initial stage of treatment. Nutritional support should be
    initiated slowly after correction of fluid, electrolyte, and vitamin deficits [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/25,26\">",
    " 25,26",
    " </a>",
    " ]. Baseline requirements for carbohydrates, fat, and protein increase with
    high output fistulas from 20",
    " <span class=\"nowrap\">",
    " kcal/kg",
    " </span>",
    " per day of carbohydrates and fat and 0.8",
    " <span class=\"nowrap\">",
    " g/kg",
    " </span>",
    " per day of protein to 30",
    " <span class=\"nowrap\">",
    " kcal/kg",
    " </span>",
    " and 1.5 to 2.5",
    " <span class=\"nowrap\">",
    " g/kg",
    " </span>",
    " per day, respectively. Enteral feedings are preferable because of the positive
    effects on immunologic and hormonal gut function, but are often impractical because
    of feeding intolerance, lack of access to the gastrointestinal tract, or high
    output fistula losses [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/27\">",
    " 27",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?13/32/13831?
    source=see_link\">",
    " \"Nutrition support in critically ill patients: An overview\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H1480975\">",
    " <span class=\"h2\">",
    " Fistulogram",
    " </span>",
    " &nbsp;&mdash;&nbsp;In the absence of sepsis, a fistulogram should be performed
    by the radiologist and surgeon working together to determine the origin of the
    fistula, document intestinal continuity, and ascertain the presence of distal
    obstruction [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/1,23,28\">",
    " 1,23,28",
    " </a>",
    " ]. A fistulogram is performed by injecting a water soluble contrast agent into
    the cutaneous opening. Following complete visualization of the tract, angiographic
    catheters and guide wires can be used under fluoroscopic guidance to outline any
    associated pockets or cavities [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/23\">",
    " 23",
    " </a>",
    " ]. &nbsp;",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18524911\">",
    " <span class=\"h2\">",
    " Fistula control and skin care",
    " </span>",
    " &nbsp;&mdash;&nbsp;A sump or pouch should be placed around the fistula. The
    adjacent skin must be protected with DuoDERM or other skin protectants. Skin
    protection creams and effluent collection bags must be tailored to the unique
    characteristics of each fistula, but the principles are similar to those used in
    the care of a colostomy or ileostomy [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/29\">",
    " 29",
    " </a>",
    " ]. The assistance of a skilled enterostomal therapist is helpful. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?2/10/2218?
    source=see_link\">",
    " \"Management of patients with a colostomy or ileostomy\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Vacuum-assisted wound management can be used to control the intestinal
    spillage and may accelerate fistula closure by promoting wound healing [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/30,31\">",
    " 30,31",
    " </a>",
    " ]. A study of vacuum-assisted wound management of 179 fistulas in 91 patients
    reported spontaneous closure in 40 percent within 90 days and 85 percent of the
    remaining fistulas closed following surgery [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/32\">",
    " 32",
    " </a>",
    " ]. The mortality rate was 16 percent (",
    " <a class=\"graphic graphic_picture graphicRef63582 \" href=\"UTD.htm?
    32/15/33016\">",
    " picture 2",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/41/26264?
    source=see_link\">",
    " \"Negative pressure wound therapy\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Fistula output can be reduced with somatostatin and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/7/43128?source=see_link\">",
    " octreotide",
    " </a>",
    " , a somatostatin analogue. However, these drugs are costly and there is no
    evidence that they improve the rate of fistula closure [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/33,34\">",
    " 33,34",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18524932\">",
    " <span class=\"h2\">",
    " Surgery",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients who have failed five to six weeks of nonoperative
    management will likely need surgery. However, surgery should not be undertaken for
    another few months to avoid bowel injury. The presence of an enterocutaneous
    fistula is usually associated with a phase of dense adhesions, termed
    &ldquo;obliterative peritonitis,&rdquo; making early surgery a hazardous
    undertaking [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/15,35\">",
    " 15,35",
    " </a>",
    " ]. Obliterative peritonitis may resolve as early as six weeks in a closed
    abdomen, but may persist for 6 to 12 months in a patient with an open abdomen.",
    " </p>",
    " <p>",
    " The goal of surgery for an enterocutaneous fistula is to reestablish the
    continuity of the intestinal tract and to achieve a tension-free closure of the
    abdomen with well-vascularized soft tissue. Before consideration of definitive
    repair of fistulas which fail to close spontaneously, patients should be
    nutritionally replete, free of infection, and have supple soft tissues adjacent to
    the fistula.",
    " </p>",
    " <p>",
    " Resection of a chronic enterocutaneous fistula requires careful planning,
    meticulous dissection to mobilize the entire intestinal tract, and resection of the
    segment of bowel that is the source of the fistula. Closure of large abdominal wall
    defects may require more complicated hernia repair techniques. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?42/49/43801?
    source=see_link\">",
    " \"Overview of abdominal hernias\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/34/32294?
    source=see_link\">",
    " \"Principles of component separation technique for complex abdominal wall
    defects and hernias\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The incision should be chosen to try and avoid adhesions and bowel loops
    adherent to the abdominal wall at the site of prior incisions. A new incision or
    extension of the previous incision in a cephalad direction will allow entry into
    a \"virgin\" area. Adhesions are then lysed and taken down from the abdominal
    wall.",
    " </p>",
    " <p>",
    " The adhesions are often dense and the dissection should be slow and careful.
    Expert surgeons recommend working laterally and delivering the bowel and adhesions
    from the side where they are more likely to be free [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/1\">",
    " 1",
    " </a>",
    " ]. Several techniques can be used to facilitate the dissection of dense
    adhesions. We inject isotonic saline into areas of dense adhesions. Others have
    reported placing an antibiotic soaked (",
    " <a class=\"drug drug_general\" href=\"UTD.htm?4/2/4136?source=see_link\">",
    " cefazolin",
    " </a>",
    " or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?39/10/40102?source=see_link\">",
    " kanamycin",
    " </a>",
    " ) sponge on areas of difficult adhesions [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/1\">",
    " 1",
    " </a>",
    " ]. Both methods help to reveal the plane between bowel loops.",
    " </p>",
    " <p>",
    " After resection of the affected bowel, a gastrostomy tube and feeding
    jejunostomy should be placed. &nbsp;",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H1481392\">",
    " <span class=\"h3\">",
    " Duodenal fistulas",
    " </span>",
    " &nbsp;&mdash;&nbsp;Duodenal fistulas are managed differently from other
    enteric fistulas [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/2\">",
    " 2",
    " </a>",
    " ]. Duodenal fistulas result from sphincterotomies, perforated duodenal ulcers,
    or gastrectomy. The majority of duodenal fistulas will heal with nonoperative
    management. Those that fail to heal are best treated with gastrojejunostomy rather
    than resection, which would require pancreaticoduodenectomy.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18524939\">",
    " <span class=\"h1\">",
    " MANAGEMENT OF ENTEROATMOSPHERIC FISTULAS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Enteroatmospheric (exposed) fistulas will",
    " <strong>",
    " not",
    " </strong>",
    " heal spontaneously because of the absence of overlying soft tissue.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18524947\">",
    " <span class=\"h2\">",
    " Prevention",
    " </span>",
    " &nbsp;&mdash;&nbsp;Enteroatmospheric fistulas can be prevented by coverage of
    exposed bowel with omentum or other biologic dressings during open abdomen
    management [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/36,37\">",
    " 36,37",
    " </a>",
    " ]. Negative pressure wound sponges and gauze dressings should",
    " <strong>",
    " not",
    " </strong>",
    " be applied directly to exposed bowel, particularly if there is an exposed
    suture line. Access to the wound should be limited to one or two highly experienced
    providers to reduce the risk of iatrogenic bowel injury.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322894\">",
    " <span class=\"h2\">",
    " Superficial enteroatmospheric fistulas",
    " </span>",
    " &nbsp;&mdash;&nbsp;A superficial enteroatmospheric fistula results in spillage
    of intestinal contents onto the granulation tissue covering a frozen abdomen (fused
    visceral block). Direct suture closure of small &ldquo;bud&rdquo; fistulas is
    sometimes possible. In other cases autogenous skin grafts [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/38\">",
    " 38",
    " </a>",
    " ] or acellular lumen dermal matrix [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/39\">",
    " 39",
    " </a>",
    " ] will be required.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322677\">",
    " <span class=\"h2\">",
    " Deep enteroatmospheric fistulas",
    " </span>",
    " &nbsp;&mdash;&nbsp;While a superficial enteroatmospheric fistula is primarily
    a wound management problem, a deep fistula typically results in peritonitis and
    critical illness. Referral to a center capable of providing complex
    multidisciplinary care is prudent in these difficult patients [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/8\">",
    " 8",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322712\">",
    " <span class=\"h3\">",
    " Nutrition",
    " </span>",
    " &nbsp;&mdash;&nbsp;Nutritional support is essential to reverse the catabolic
    effects of a deep exposed fistula. The ongoing peritonitis, large open abdominal
    wound, and protein losses from the gastrointestinal tract often require a
    combination of enteral and parenteral nutrition to deliver sufficient nutrients and
    replace essential elements. In general, the higher the fistula output, the greater
    the catabolic effect.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322597\">",
    " <span class=\"h3\">",
    " Source control",
    " </span>",
    " &nbsp;&mdash;&nbsp;The main goal in management of enteroatmospheric fistulas
    is to control the enteric contents at the source of the fistula. Exteriorization or
    proximal diversion of the fistula may be impossible because of massive edema and
    foreshortening of the mesentery.",
    " </p>",
    " <p>",
    " The &ldquo;floating stoma&rdquo; is one option to achieve source control in
    this situation [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/40\">",
    " 40",
    " </a>",
    " ]. To create a floating stoma, the hole in the gut is sutured to a similarly
    sized hole in a plastic sheet used as a temporary abdominal closure. A colostomy
    bag is then applied over the &ldquo;floating stoma&rdquo; controlling the fistula
    drainage until the wound granulates.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18524954\">",
    " <span class=\"h3\">",
    " Negative pressure wound therapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Negative pressure wound therapy, also called vacuum-
    assisted wound closure, has been widely applied to the management of
    enteroatmospheric fistulas [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/41\">",
    " 41",
    " </a>",
    " ]. This approach minimizes dressing changes and protects the surrounding
    skin.",
    " </p>",
    " <p>",
    " The negative pressure wound therapy is useful for a patient with an
    established fistula. For these patients, a preferred technique is to intubate the
    fistula and bring the tube out through the hole in the sponge of the vacuum-
    assisted dressing (",
    " <a class=\"graphic graphic_figure graphicRef50588 \" href=\"UTD.htm?
    23/21/23889\">",
    " figure 1",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/6\">",
    " 6",
    " </a>",
    " ]. Most of the drainage is collected in the tubes.",
    " </p>",
    " <p>",
    " However, caution must be used in applying a vacuum assisted dressing to
    exposed bowel without a fistula because this can lead to formation of a new fistula
    [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/42,43\">",
    " 42,43",
    " </a>",
    " ]. &nbsp;(See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/41/26264?
    source=see_link&amp;anchor=H18#H18\">",
    " \"Negative pressure wound therapy\", section on 'Open abdomen'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322837\">",
    " <span class=\"h3\">",
    " Skin grafts",
    " </span>",
    " &nbsp;&mdash;&nbsp;In most cases, an enteroatmospheric fistula is treated as a
    stoma and autologous skin grafts are applied to the surrounding granulation tissue.
    After the grafts heal, a variety of creative stoma management solutions can be
    adapted to the specific requirements of each fistula.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18524982\">",
    " <span class=\"h2\">",
    " Surgical closure",
    " </span>",
    " &nbsp;&mdash;&nbsp;Surgical closure of an enteroatmospheric fistula and
    abdominal wall reconstruction should",
    " <strong>",
    " not",
    " </strong>",
    " be considered until the skin graft is supple and can be pinched between the
    thumb and index, which signifies the existence of a plane between the graft and
    underlying bowel.",
    " </p>",
    " <p>",
    " In most cases, a two-team approach is employed. A general surgery team
    performs the visceral dissection and fistula resection followed by a reconstruction
    team to close the abdomen. A careful preoperative assessment of the available
    tissue for reconstruction is important.",
    " </p>",
    " <p>",
    " The component separation technique is an excellent reconstructive option if
    the rectus abdominis muscle is intact [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/44\">",
    " 44",
    " </a>",
    " ]. Defects of up to 10 cm in the upper abdomen, 20 cm in the mid-abdomen, and
    8 cm in the lower abdomen can be closed with this technique. A variety of other
    pedicled or free flaps with microvascular reconstruction are available for use
    depending on the nature of the defect, available soft tissue components, and
    patient comorbidities. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/34/32294?
    source=see_link\">",
    " \"Principles of component separation technique for complex abdominal wall
    defects and hernias\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Biologic material such as acellular human [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/45\">",
    " 45",
    " </a>",
    " ] or porcine [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/46\">",
    " 46",
    " </a>",
    " ] dermal matrix can be used to close defects, although there appears to be a
    high incidence of late hernia formation with the use of these materials [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/47,48\">",
    " 47,48",
    " </a>",
    " ]. As an example, a study of 10 patients with large abdominal defects showed
    that 100 percent of patients had successful defect closure with acellular human
    dermal matrix, but all patients developed significant laxity or hernias by one year
    of follow up [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/47\">",
    " 47",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?11/33/11799?
    source=see_link\">",
    " \"Reconstructive materials used in surgery: Classification and host
    response\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H1481384\">",
    " <span class=\"h1\">",
    " OUTCOMES",
    " </span>",
    " &nbsp;&mdash;&nbsp;With modern management strategies, most modern series
    report a mortality of 10 to 20 percent (",
    " <a class=\"graphic graphic_table graphicRef54412 \" href=\"UTD.htm?
    6/36/6731\">",
    " table 4",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6152/abstract/1,2,4,9,21\">",
    " 1,2,4,9,21",
    " </a>",
    " ].",
    " </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>",
    " Basics topics (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?4/50/4897?
    source=see_link\">",
    " \"Patient information: Enterocutaneous fistula (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H322535\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " An enterocutaneous fistula is a communication between the bowel lumen and
    the skin. An enteroatmospheric or exposed fistula refers to drainage of intestinal
    contents from an open abdomen with no overlying soft tissue. (See",
    " <a class=\"local\" href=\"#H18524881\">",
    " 'Introduction'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Initial treatment of an enterocutaneous fistula focuses on correction of
    fluid and electrolyte imbalance, abscess drainage and treatment of infection,
    correction of malnutrition, and meticulous fistula control and skin care.
    Approximately one-third of enterocutaneous fistulas heal spontaneously with these
    measures. Patients who do not respond to conservative measures should be referred
    to a center capable of providing complex multidisciplinary care. (See",
    " <a class=\"local\" href=\"#H18524895\">",
    " 'Management of enterocutaneous fistulas'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The goal of surgery for an enterocutaneous fistula is to reestablish the
    continuity of the intestinal tract to achieve a tension-free closure of the abdomen
    with well-vascularized soft tissue. Before consideration of definitive repair of
    fistulas that fail to close spontaneously, patients should be nutritionally
    replete, free of infection, and have supple soft tissues adjacent to the fistula.
    Resection of a chronic enterocutaneous fistula is a complex life-threatening
    operation that requires careful planning, meticulous dissection to mobilize the
    entire intestinal tract, and resection of the segment of bowel serving as the
    source of the fistula. (See",
    " <a class=\"local\" href=\"#H18524932\">",
    " 'Surgery'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Enteroatmospheric fistulas will not heal spontaneously because of the
    absence of overlying soft tissue. The main goal in management of enteroatmospheric
    fistulas is to control the enteric contents at the source of the fistula. &nbsp;In
    most cases, a fistula is treated as a stoma and autologous skin grafts are applied
    to the surrounding granulation tissue. Surgical closure of an enteroatmospheric
    fistula and abdominal wall reconstruction should",
    " <strong>",
    " not",
    " </strong>",
    " be considered until the skin graft is supple and can be pinched between the
    thumb and index, which signifies the existence of a plane between the graft and
    underlying bowel. (See",
    " <a class=\"local\" href=\"#H18524939\">",
    " 'Management of enteroatmospheric fistulas'",
    " </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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    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6152/abstract/45\">",
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6152/abstract/47\">",
    " de Moya MA, Dunham M, Inaba K, et al. Long-term outcome of acellular dermal
    matrix when used for large traumatic open abdomen. J Trauma 2008; 65:349.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?6/0/6152/abstract/48\">",
    " Jin J, Rosen MJ, Blatnik J, et al. Use of acellular dermal matrix for
    complicated ventral hernia repair: does technique affect outcomes? J Am Coll Surg
    2007; 205:654.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
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    " Topic 15157 Version 7.0",
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    var script_f6_0_6152=[""].join("\n");
    var outline_f6_0_6152=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
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    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H322535\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H18524881\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1480967\">",
    " PRESENTATION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H18116253\">",
    " CLASSIFICATION OF ENTERIC FISTULAS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H322734\">",
    " Enterocutaneous fistulas",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H322742\">",
    " Enteroatmospheric (exposed) fistulas",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H18524895\">",
    " MANAGEMENT OF ENTEROCUTANEOUS FISTULAS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H320290\">",
    " Fluid and electrolyte imbalance",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H320484\">",
    " Abscess drainage and treatment of infection",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H320386\">",
    " Nutrition",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H1480975\">",
    " Fistulogram",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18524911\">",
    " Fistula control and skin care",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18524932\">",
    " Surgery",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H1481392\">",
    " - Duodenal fistulas",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H18524939\">",
    " MANAGEMENT OF ENTEROATMOSPHERIC FISTULAS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18524947\">",
    " Prevention",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H322894\">",
    " Superficial enteroatmospheric fistulas",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H322677\">",
    " Deep enteroatmospheric fistulas",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H322712\">",
    " - Nutrition",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H322597\">",
    " - Source control",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H18524954\">",
    " - Negative pressure wound therapy",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H322837\">",
    " - Skin grafts",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18524982\">",
    " Surgical closure",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1481384\">",
    " OUTCOMES",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H322535\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15157\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15157|FIG\">",
    " <a href=\"#\" title=\"FIGURES\">",
    " FIGURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?23/21/23889\"
    title=\"figure 1\">",
    " Negative pressure wound therapy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15157|PIC\">",
    " <a href=\"#\" title=\"PICTURES\">",
    " PICTURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?14/50/15140\"
    title=\"picture 1\">",
    " Enteroatmospheric fistula",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?32/15/33016\"
    title=\"picture 2\">",
    " Negative pressure wound dressing in situ",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15157|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?24/44/25291\" title=\"table
    1\">",
    " Causes of enterocutaneous fistulae",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/19/23868\" title=\"table
    2\">",
    " Phases of management for enterocutaneous fistulae",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?29/48/30476\" title=\"table
    3\">",
    " Predictors of spontaneous closure of enterocutaneous fistulas",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?6/36/6731\" title=\"table
    4\">",
    " Mortality of gastrointestinal-cutaneous fistulae",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
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    " </div>"].join("\n");
    var title_f6_0_6153="Physiology of parturition";
    var content_f6_0_6153=[" <noscript>",
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    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Physiology of parturition",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
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    " Author",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6153/contributors\">",
    " Errol R Norwitz, MD, PhD",
    " </a>",
    " <br/>",
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    href=\"UTD.htm?6/0/6153/contributors\">",
    " Section Editor",
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    6/0/6153/contributors\">",
    " Charles J Lockwood, MD",
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    href=\"UTD.htm?6/0/6153/contributors\">",
    " Deputy Editor",
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    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    6/0/6153/contributors\">",
    " Vanessa A Barss, MD",
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    " Literature review current through:",
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    " This topic last updated:",
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    " Oct 9, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Labor is a physiological event involving a sequential,
    integrated set of changes within the myometrium, decidua, and uterine cervix that
    occur gradually over a period of days to weeks. Biochemical connective tissue
    changes in the uterine cervix appear to precede uterine contractions and cervical
    dilation, and all of these events usually occur before rupture of the fetal
    membranes.",
    " </p>",
    " <p>",
    " Labor is characterized by an increase in myometrial activity or, more
    precisely, a change in the myometrial contractility pattern from \"contractures\"
    (long-lasting, low frequency activity) to \"contractions\" (high intensity, high
    frequency activity) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/1\">",
    " 1",
    " </a>",
    " ], resulting in effacement and dilatation of the uterine cervix.",
    " </p>",
    " <p>",
    " Labor is a clinical diagnosis, classically defined by the triad of regular
    painful uterine contractions, progressive cervical effacement and dilatation, and
    show (bloody discharge). Cervical dilatation in the absence of uterine contractions
    is seen most commonly in the second trimester and is suggestive of cervical
    insufficiency. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?4/22/4457?
    source=see_link\">",
    " \"Cervical insufficiency\"",
    " </a>",
    " .) Similarly, the presence of uterine contractions in the absence of cervical
    change does not meet criteria for the diagnosis of labor. Such contractions are
    often attributed to \"false labor\" or uterine irritability.",
    " </p>",
    " <p>",
    " Labor and delivery are not passive processes by which uterine contractions
    push a rigid object through a fixed aperture. The ability of the fetus to
    successfully negotiate the pelvis during labor and delivery depends upon a complex
    interaction of three variables: power (uterine contractions), passenger (fetus),
    and passage (both bony pelvis and pelvic soft tissues). Although conventional
    wisdom dictates that powerful contractions are more likely to be associated with a
    successful outcome, there are no data to support this conclusion. Furthermore,
    precipitous labor probably results from low resistance of the pelvic soft tissues
    (the cervix in the first stage of labor and the muscles of the pelvic floor in the
    second stage) rather than from high myometrial activity [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " LABOR AT TERM",
    " </span>",
    " &nbsp;&mdash;&nbsp;The mean duration of human singleton pregnancy is 280 days
    (40 weeks) from the first day of the last menstrual period. A term pregnancy is
    defined as the period from 259 to 293 days after the first day of the last
    menstrual period (37 to 41 and",
    " <span class=\"nowrap\">",
    " 6/7th",
    " </span>",
    " weeks).",
    " </p>",
    " <p>",
    " Term labor may be regarded physiologically as a release from the inhibitory
    effects of pregnancy on the myometrium, rather than as an active process mediated
    by uterine stimulants. As an example, strips of myometrium obtained from a
    quiescent uterus at term and placed in an isotonic water bath will contract
    vigorously and spontaneously without added stimuli [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/3,4\">",
    " 3,4",
    " </a>",
    " ]. Nevertheless, both inhibitory and stimulatory mechanisms likely play a role
    in uterine activity.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " PHYSIOLOGICAL PHASES OF MYOMETRIAL ACTIVITY",
    " </span>",
    " &nbsp;&mdash;&nbsp;The regulation of uterine activity during pregnancy can be
    divided into four distinct physiologic phases [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/5,6\">",
    " 5,6",
    " </a>",
    " ]:",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Phase 0: inhibitors active",
    " </span>",
    " &nbsp;&mdash;&nbsp;Throughout most of pregnancy the uterus is maintained in a
    state of functional quiescence through the action of various putative inhibitors
    including, but not limited to:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Progesterone",
    " </li>",
    " <li>",
    " Prostacyclin (prostaglandin I-2)",
    " </li>",
    " <li>",
    " Relaxin",
    " </li>",
    " <li>",
    " Parathyroid hormone-related peptide",
    " </li>",
    " <li>",
    " Nitric oxide",
    " </li>",
    " <li>",
    " Calcitonin gene-related peptide",
    " </li>",
    " <li>",
    " Adrenomedullin",
    " </li>",
    " <li>",
    " Vasoactive intestinal peptide.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " Phase 1: myometrial activation",
    " </span>",
    " &nbsp;&mdash;&nbsp;As term approaches the uterus becomes activated in response
    to uterotropins, such as estrogen. This phase is characterized by increased
    expression of a series of contraction-associated proteins (CAPs) (including
    myometrial receptors for prostaglandins and oxytocin), activation of specific ion
    channels, and an increase in connexin-43 (a key component of gap junctions). An
    increase in gap junction formation between adjacent myometrial cells leads to
    electrical synchrony within the myometrium and allows for effective coordination of
    contractions.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Phase 2: stimulatory phase",
    " </span>",
    " &nbsp;&mdash;&nbsp;Following activation, the \"primed\" uterus can be
    stimulated to contract by the action of uterotonic agonists, such as the
    stimulatory prostaglandins E2 and F2 alpha and oxytocin.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Phase 3: involution",
    " </span>",
    " &nbsp;&mdash;&nbsp;Involution of the uterus after delivery occurs during phase
    3 and is mediated primarily by oxytocin.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Parturition cascade",
    " </span>",
    " &nbsp;&mdash;&nbsp;It is likely that a \"parturition cascade\" exists at term
    which removes the mechanisms maintaining uterine quiescence and recruits factors
    promoting uterine activity [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/2,7,8\">",
    " 2,7,8",
    " </a>",
    " ]. Given its teleological importance, such a cascade would likely have
    multiple redundant loops to ensure a fail-safe system of securing pregnancy success
    (and thus preserving the species). In such a model, each element is connected to
    the next in a sequential fashion, and many of the elements demonstrate positive
    feed-forward characteristics typical of a cascade mechanism.",
    " </p>",
    " <p>",
    " The sequential recruitment of signals that serve to augment the labor process
    suggest that it may not be possible to single out any one signaling mechanism as
    being responsible for the initiation of labor. Therefore, it is prudent to describe
    such mechanisms as being responsible for \"promoting\", rather than \"initiating\",
    the process of labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/9\">",
    " 9",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h1\">",
    " THE ROLE OF THE FETUS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Considerable evidence suggests that in most viviparous
    animals the fetus controls the timing of onset of labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/10-12\">",
    " 10-12",
    " </a>",
    " ]. During the Hippocratic period, the fetus was thought to be positioned head
    down at term so it could kick its legs up against the fundus of the uterus, thereby
    propelling itself through the birth canal. While we have moved away from this
    simple and mechanical view of labor, the factors responsible for the initiation and
    maintenance of labor at term are not well defined. Initial investigations focused
    on endocrine events, such as changes in the profile of circulating hormone levels
    in the maternal and fetal circulations. Subsequent studies have concentrated on the
    dynamic biochemical dialogue between the fetus and mother",
    " <span class=\"nowrap\">",
    " (paracrine/autocrine",
    " </span>",
    " events) in an attempt to understand the molecular mechanisms that regulate
    such interactions. The genetic regulation of the molecular events that occur during
    parturition are also being investigated [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/13\">",
    " 13",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The hypothesis that the fetus is in control of the timing of labor was
    elegantly demonstrated in domestic ruminants [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/14-18\">",
    " 14-18",
    " </a>",
    " ]. As an example, parturition in sheep is initiated by a sharp rise in fetal
    adrenal cortisol secretion related to increased fetal concentrations of and
    responsiveness to corticotropin&nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/16\">",
    " 16",
    " </a>",
    " ]. Cortisol acts on placental enzymes active in the biosynthesis of estrogens
    from progesterone to augment secretion of estrogen and decrease progesterone
    production. The resulting increase in the ratio of estrogen to progesterone
    stimulates placental release of prostaglandin F2 alpha, which enhances the
    myometrial response to oxytocin and stimulates contractions.",
    " </p>",
    " <p>",
    " However, the human placenta lacks the glucocorticoid-inducible",
    " <span class=\"nowrap\">",
    " 17-alpha-hydroxylase/17,20-lyase",
    " </span>",
    " enzyme that is essential to this process [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/12,19,20\">",
    " 12,19,20",
    " </a>",
    " ]. Therefore, activation of the hypothalamic-pituitary-adrenal axis in humans
    likely results in a different mechanism for initiation of labor (see",
    " <a class=\"local\" href=\"#H14\">",
    " 'Estrogen'",
    " </a>",
    " below).",
    " </p>",
    " <p>",
    " A role for the fetal genotype in the initiation of labor was suggested by
    horse-donkey crossbreeding experiments that resulted in a gestational length
    intermediate between that of horses (340 days) and that of donkeys (365 days) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/12,19\">",
    " 12,19",
    " </a>",
    " ]. This concept holds true whether pregnancy is maintained by the
    fetoplacental unit (as in the sheep and human) or by extrauterine tissues (as in
    the mouse and goat) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/15\">",
    " 15",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The slow progress in our understanding of the biochemical mechanisms involved
    in the process of labor in humans reflects, in large part, the difficulty in
    extrapolating from the endocrine-control mechanisms in various animals to the",
    " <span class=\"nowrap\">",
    " paracrine/autocrine",
    " </span>",
    " mechanisms of human parturition, processes that preclude direct
    investigation.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h1\">",
    " MYOMETRIAL ACTIVATION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Regardless of whether the trigger originates within or
    outside the fetus, the final common pathway for labor ends in the maternal tissues
    of the uterus and is characterized by the development of regular phasic uterine
    contractions. As in other smooth muscles, myometrial contractions are mediated
    through ATP-dependent binding of myosin to actin. This interaction is dependent
    upon the phosphorylation of myosin light chain by a",
    " <span class=\"nowrap\">",
    " calcium/calmodulin-dependent",
    " </span>",
    " enzyme, myosin light chain kinase. The availability of free intracellular
    calcium is thus a key modulator of myometrial contractility.",
    " </p>",
    " <p>",
    " GTP-binding proteins (G-proteins) play a pivotal role in myometrial
    contractility by coupling cell membrane receptors to effector enzymes and ion
    channels. As an example, activation of beta-adrenergic",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " PGE2 receptors promote myometrial relaxation via the",
    " <span class=\"nowrap\">",
    " Gas/adenyl",
    " </span>",
    " <span class=\"nowrap\">",
    " cyclase/cAMP",
    " </span>",
    " signal transduction pathway [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/3,21\">",
    " 3,21",
    " </a>",
    " ]. Oxytocin receptors, on the other hand, couple to",
    " <span class=\"nowrap\">",
    " Gaq/Gai/phospholipase",
    " </span>",
    " C pathways leading to an increase in inositol-1,4,5-trisphosphate (which
    releases calcium from the sarcoplasmic reticulum) and 1,2-diacylglycerol (which
    activates protein kinase C) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/22\">",
    " 22",
    " </a>",
    " ]. The end result is an increase in intracellular calcium and myometrial
    contractions [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/22,23\">",
    " 22,23",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Pregnancy affects not only cell surface receptor concentrations, but also the
    concentrations and coupling of the various G-proteins. Gaq and Gai are expressed at
    similar levels in nonpregnant and pregnant myometrium, both before and after the
    onset of labor. By comparison, Gas levels are higher in pregnant as compared with
    nonpregnant myometrium [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/24\">",
    " 24",
    " </a>",
    " ], and levels have been shown to decrease before labor, both at term and
    preterm [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/25\">",
    " 25",
    " </a>",
    " ]. It has been suggested, therefore, that labor results from a down-regulation
    of pathways that favor uterine quiescence leading to a relative dominance of
    stimulatory pathways that increase intracellular calcium bioavailability and
    promote myometrial contractility [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/3\">",
    " 3",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Other myometrial factors (eg, mechanotransduction via stretching or
    shortening) which could affect initiation, frequency, or strength of contractions
    are under investigation [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/26,27\">",
    " 26,27",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " In contrast to vascular smooth muscle, myometrial cells have sparse
    innervation, which is further reduced during pregnancy [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/28\">",
    " 28",
    " </a>",
    " ]. The regulation of the contractile mechanism of the uterus is therefore
    largely humoral",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " dependent upon intrinsic factors within myometrial cells. A number of hormones
    have been implicated in this regard. Some of these are discussed below.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h1\">",
    " HORMONES INVOLVED IN THE PARTURITIONAL CASCADE",
    " </span>",
    " &nbsp;&mdash;&nbsp;Comprehensive analyses of each of the individual",
    " <span class=\"nowrap\">",
    " paracrine/autocrine",
    " </span>",
    " pathways involved in the process of labor have been reviewed in detailed
    elsewhere&nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/2,5-9,15,19\">",
    " 2,5-9,15,19",
    " </a>",
    " ]. A few of the hormones implicated in this process are discussed below.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Prostaglandins",
    " </span>",
    " &nbsp;&mdash;&nbsp;Prostaglandins are predominantly",
    " <span class=\"nowrap\">",
    " paracrine/autocrine",
    " </span>",
    " hormones (ie, they act locally at their site of production on contiguous
    cells). An increase in uterine prostaglandin biosynthesis is a consistent element
    in the transition into labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/29\">",
    " 29",
    " </a>",
    " ], and is probably common to all species [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/30\">",
    " 30",
    " </a>",
    " ]. It seems likely that hormonal factors controlling the final pathway for the
    onset of labor in women, both at term and preterm, is an increased synthesis of
    prostaglandins of the E and F series within the uterine compartment, predominantly
    from the decidua and fetal membranes. The evidence can be summarized as follows:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Human uterine tissues are selectively enriched with arachidonic acid, the
    obligate precursor of prostaglandin biosynthesis.",
    " </li>",
    " <li>",
    " Concentrations of prostaglandins in amniotic fluid and in maternal plasma
    and urine are increased during parturition [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/29,31,32\">",
    " 29,31,32",
    " </a>",
    " ]. Moreover, prostaglandin levels appear to rise prior to the onset of
    myometrial concentrations suggesting that they are a cause, rather than a
    consequence, of labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/33\">",
    " 33",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " The intraamniotic, intravenous, or vaginal administration of exogenous
    prostaglandins can initiate labor at any stage of gestation and in all species [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/34\">",
    " 34",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Prostaglandins have been implicated in the three events most temporally
    related to the onset of labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/4,35\">",
    " 4,35",
    " </a>",
    " ]: the onset of synchronous uterine contractions, cervical ripening, and the
    increase in myometrial sensitivity to oxytocin due to an increase in myometrial gap
    junction formation",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " oxytocin receptor concentrations.",
    " </li>",
    " <li>",
    " Inhibitors of prostaglandin synthesis (including cyclooxygenase inhibitors
    such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?35/50/36649?
    source=see_link\">",
    " indomethacin",
    " </a>",
    " ) are capable of suppressing myometrial contractility both in vitro and in
    vivo, and of prolonging the length of gestation [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/4,36,37\">",
    " 4,36,37",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Taken together, these data affirm the critical role of prostaglandins,
    especially PGF2 alpha, in the initiation of labor. It appears that withdrawal of
    fetal-paracrine support of the quiescent uterus leads to decidual activation,
    followed by PGF2 alpha release and subsequent spontaneous labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/32\">",
    " 32",
    " </a>",
    " ]. PGE2 appears to play a more important role in cervical ripening (a
    remodeling process in which collagen is degraded leading to softening of the
    cervix) and rupture of the fetal membranes than in uterine contractility [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/29\">",
    " 29",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h2\">",
    " Progesterone",
    " </span>",
    " &nbsp;&mdash;&nbsp;Administration of a progesterone receptor antagonist [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/38,39\">",
    " 38,39",
    " </a>",
    " ] or removal of the corpus luteum [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/40\">",
    " 40",
    " </a>",
    " ] readily induces abortion in early pregnancy (before 7 weeks of gestation),
    suggesting that progesterone is necessary for early pregnancy maintenance.
    Administration of exogenous progesterone after early lutectomy prevents abortion,
    further supporting the hypothesis that ovarian progesterone production is essential
    in maintenance of early pregnancy. Placental progesterone production becomes
    important between 7 and 9 weeks, and the placenta is the dominant source of
    progesterone thereafter.",
    " </p>",
    " <p>",
    " However, the role of progesterone in late pregnancy is not as well defined [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/41\">",
    " 41",
    " </a>",
    " ]. Progesterone withdrawal does not occur in all women before labor, and mean
    circulating progesterone levels during labor are similar to those measured one week
    prior [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/42\">",
    " 42",
    " </a>",
    " ]. Moreover, the administration of progesterone late in pregnancy does not
    delay the onset of labor in primates [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/43\">",
    " 43",
    " </a>",
    " ], and progesterone receptor antagonists are not capable of inducing labor at
    term (although they may promote cervical ripening) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/44,45\">",
    " 44,45",
    " </a>",
    " ]. Finally, pregnancies complicated by maternal hypobetalipoproteinemia (LDL
    deficiency with very low levels of progesterone) culminate in spontaneous labor at
    term without incident [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/46\">",
    " 46",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " These data suggest that progesterone withdrawal is not a prerequisite for
    labor in humans. This is in contrast to most mammalian species in which
    progesterone withdrawal is an essential component of parturition [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/47\">",
    " 47",
    " </a>",
    " ]. However, circulating hormone concentrations do not necessarily reflect
    activity at the tissue level. The onset of labor in women may be preceded by a
    physiologic withdrawal of progesterone activity (\"functional progesterone
    withdrawal\") at the level of the uterus [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/47\">",
    " 47",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " On the other hand, there is increasing evidence that supplemental progesterone
    administration &nbsp;reduces the rate of preterm birth in high risk women. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?11/45/11994?
    source=see_link&amp;anchor=H4#H4\">",
    " \"Prevention of spontaneous preterm birth\", section on 'Supplemental
    progesterone'",
    " </a>",
    " .) Further investigation is needed to confirm the effectiveness of
    progesterone supplementation and to understand its mechanism of action. It has not
    been studied as a tocolytic for active preterm labor.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h2\">",
    " Estrogen",
    " </span>",
    " &nbsp;&mdash;&nbsp;The placenta is the primary source of estrogen biosynthesis
    during pregnancy. Estrogens do not themselves cause myometrial contractions, and
    maternal administration of estradiol to rhesus macaques from 130 days of gestation
    has no effect on length of pregnancy [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/48\">",
    " 48",
    " </a>",
    " ]. Instead, estrogens act by upregulating myometrial gap junctions [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/49\">",
    " 49",
    " </a>",
    " ] and uterotonic receptors (including L-type calcium channels and oxytocin
    receptors) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/50\">",
    " 50",
    " </a>",
    " ], thereby enhancing the capacity of the myometrium to generate
    contractions.",
    " </p>",
    " <p>",
    " Longitudinal measurements of circulating estrogen concentrations prior to the
    onset of labor show an increase in all primate species [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/51\">",
    " 51",
    " </a>",
    " ]. Because the primate placenta is an incomplete steroidogenic organ,
    placental estrogen synthesis has an obligate need for C-19 steroid precursors (it
    cannot synthesize estrogen from progesterone) [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/2,7\">",
    " 2,7",
    " </a>",
    " ]. The fetal adrenal provides an abundant C19 estrogen precursor
    (dehydroepiandrostenedione) directly from its intermediate (fetal) zone. In the
    rhesus monkey, continuous infusion of C19 precursor (androstenedione) leads to
    preterm delivery [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/52-54\">",
    " 52-54",
    " </a>",
    " ]. This effect is blocked by concurrent infusion of an aromatase inhibitor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/54\">",
    " 54",
    " </a>",
    " ], demonstrating that conversion to estrogen is important in promoting
    contractions. A similar effect has been shown using a continuous intraamniotic
    infusion of estrogen [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/48\">",
    " 48",
    " </a>",
    " ]. However, systemic infusion of estrogen failed to induce delivery [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/48\">",
    " 48",
    " </a>",
    " ], suggesting that the action of estrogen is likely",
    " <span class=\"nowrap\">",
    " paracrine/autocrine.",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h2\">",
    " Oxytocin",
    " </span>",
    " &nbsp;&mdash;&nbsp;Oxytocin is a peptide hormone synthesized in the
    hypothalamus and released from the posterior pituitary in a pulsatile fashion. Its
    biologic half-life is approximately three to four minutes, but appears shorter when
    higher doses are infused. Oxytocin is inactivated in the liver and kidney, although
    during pregnancy it is primarily degraded by placental oxytocinase. The evidence in
    support of a role for oxytocin in parturition can be summarized briefly as
    follows:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Oxytocin is the most potent endogenous uterotonic agent, and is capable of
    stimulating uterine contractions at intravenous infusion rates of 1 to 2",
    " <span class=\"nowrap\">",
    " mU/min",
    " </span>",
    " at term [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/55,56\">",
    " 55,56",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " The frequency and amplitude of oxytocin-induced uterine contractions are
    identical to those occurring during spontaneous labor.",
    " </li>",
    " <li>",
    " More than 100",
    " <span class=\"nowrap\">",
    " mU/min",
    " </span>",
    " oxytocin is needed to elicit uterine contractions in nonpregnant women,
    while 16",
    " <span class=\"nowrap\">",
    " mU/",
    " </span>",
    " min is sufficient to elicit contractions at 20 weeks of gestation, 2 to 3",
    " <span class=\"nowrap\">",
    " mU/min",
    " </span>",
    " at 32 weeks, and 1",
    " <span class=\"nowrap\">",
    " mU/min",
    " </span>",
    " at term [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/55\">",
    " 55",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Uterine contractions can be induced by electrical stimulation of the
    posterior pituitary gland or by nipple stimulation, presumably by increasing
    oxytocin concentrations in the blood.",
    " </li>",
    " <li>",
    " Oxytocin analogues that act as competitive antagonists of endogenous
    oxytocin effectively inhibit labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/57\">",
    " 57",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Circulating levels of oxytocin do not change significantly during pregnancy or
    prior to the onset of labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/55,56\">",
    " 55,56",
    " </a>",
    " ]. However, myometrial oxytocin receptor concentrations increase approximately
    100 to 200-fold during pregnancy, reaching a maximum during early labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/55,56,58,59\">",
    " 55,56,58,59",
    " </a>",
    " ]. This rise in receptor concentration accounts for the increased sensitivity
    of the myometrium to circulating levels of oxytocin during the second half of
    pregnancy.",
    " </p>",
    " <p>",
    " Specific high-affinity oxytocin receptors have also been isolated apart from
    the myometrium in the human amnion and decidua parietalis, but not decidua vera [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/50,55\">",
    " 50,55",
    " </a>",
    " ]. Neither amnion nor decidual cells are contractile, and the action of
    oxytocin on these tissues is uncertain. Oxytocin may play a dual role in the
    mechanism of parturition [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/55,58\">",
    " 55,58",
    " </a>",
    " ]: it may act directly through oxytocin receptor-mediated and nonreceptor,
    voltage-mediated calcium channels to affect intracellular biochemical pathways and
    promote uterine contractions or it may act indirectly through stimulation of
    amniotic and decidual prostaglandin production. Induction of labor at term is
    successful only when the oxytocin infusion is associated with an increase in PGF2
    alpha production, in spite of apparently adequate uterine contractions [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/50\">",
    " 50",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Studies examining fetal pituitary oxytocin production, the umbilical
    arteriovenous difference in plasma oxytocin concentration, amniotic fluid oxytocin
    levels, and fetal urinary oxytocin output demonstrate conclusively that the fetus
    secretes oxytocin into the maternal circulation [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/55,60\">",
    " 55,60",
    " </a>",
    " ]. Furthermore, the calculated oxytocin secretion rates from the fetus suggest
    an increase from a baseline of 1",
    " <span class=\"nowrap\">",
    " mU/min",
    " </span>",
    " prior to labor to approximately 3",
    " <span class=\"nowrap\">",
    " mU/min",
    " </span>",
    " after spontaneous labor [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/60\">",
    " 60",
    " </a>",
    " ]. The latter is similar to the dose of oxytocin normally administered to
    women to induce labor at term (2 to 8",
    " <span class=\"nowrap\">",
    " mU/min).",
    " </span>",
    " Although maternal serum oxytocin levels are not increased prior to the onset
    of labor or during the first stage of labor, oxytocin derived from the fetus and
    possibly from local decidual and other uterine sources could act on myometrial
    oxytocin receptors in a",
    " <span class=\"nowrap\">",
    " paracrine/",
    " </span>",
    " autocrine fashion to initiate and maintain effective uterine contractions.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?30/37/31322?
    source=see_link\">",
    " \"Principles of labor induction\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " It is unlikely that oxytocin provides the trigger for the initiation of labor,
    but the release of oxytocin during labor results in more forceful uterine
    contractions and undoubtedly facilitates delivery of the fetus and placenta. The
    existence of the so-called Ferguson reflex (release of maternal oxytocin from the
    posterior pituitary in response to distention of the cervix",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " vagina) remains controversial [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/61\">",
    " 61",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h2\">",
    " Hypothalamic-pituitary-adrenal factors",
    " </span>",
    " &nbsp;&mdash;&nbsp;The final common pathway for initiation of labor appears to
    be activation of the fetal hypothalamic-pituitary-adrenal axis, which is probably a
    common pathway for all species.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h3\">",
    " Corticotropin releasing hormone",
    " </span>",
    " &nbsp;&mdash;&nbsp;Activation of the fetal hypothalamic-pituitary-adrenal axis
    during the latter part of pregnancy results in release of large amounts of fetal
    cortisol [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/62,63\">",
    " 62,63",
    " </a>",
    " ]. Glucocorticoids (including cortisol) are potent stimulants of placental
    corticotropin releasing hormone (CRH) production, in contrast to their negative
    effect on hypothalamic CRH production &nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/64\">",
    " 64",
    " </a>",
    " ]. Inflammatory cytokines, catecholamines, acetylcholine, and oxytocin also
    increase placental CRH secretion [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/6\">",
    " 6",
    " </a>",
    " ], while progesterone and nitric oxide (NO) decrease placental CRH release.
    Circulating maternal plasma CRH levels increase progressively throughout the latter
    half of pregnancy, with a dramatic increase in the final six to eight weeks before
    delivery [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/62,63\">",
    " 62,63",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " During pregnancy, CRH bioactivity (as measured by its ability to promote ACTH
    release from the pituitary and to stimulate decidual PGE2 production) is decreased
    due to an increase in high-affinity CRH-binding protein (CRH-BP). However, in the
    last three to five weeks of gestation, CRH-BP concentrations fall, resulting in a
    rapid rise in circulating free CRH [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/65,66\">",
    " 65,66",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Women with an early rapid rise in plasma CRH tend to deliver earlier and those
    with a slow rise tend to deliver later, suggesting that production of CRH is an
    important factor in the timing of delivery. This hypothesis has been termed
    the \"placental clock\" [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/67\">",
    " 67",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " CRH has no direct inotropic action on human myometrium, but the increase in
    placental CRH at term is thought to have multiple actions on the uterus [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/68\">",
    " 68",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " It is secreted back into the fetal compartment where it can act to drive
    pituitary ACTH release, thereby providing a positive feed-forward loop for labor",
    " </li>",
    " <li>",
    " It may act locally within the placenta to promote fetoplacental
    vasodilatation [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/69\">",
    " 69",
    " </a>",
    " ]",
    " </li>",
    " <li>",
    " It can directly and preferentially stimulate DHEA-S secretion in fetal
    adrenal cortical cells via a protein kinase system [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/70,71\">",
    " 70,71",
    " </a>",
    " ]",
    " </li>",
    " <li>",
    " It exerts effects on the uterus and cervix by upregulation of the nitric
    oxide pathway and by augmenting estrogen effects on these tissues [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/72\">",
    " 72",
    " </a>",
    " ]",
    " </li>",
    " <li>",
    " It enhances prostaglandin production in the amnion, chorion and decidua",
    " </li>",
    " <li>",
    " It primes the myometrium and potentiates the effects of oxytocin [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/73\">",
    " 73",
    " </a>",
    " ]",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h3\">",
    " Glucocorticoids",
    " </span>",
    " &nbsp;&mdash;&nbsp;These hormones have several actions that can also help
    prepare the uterus for labor.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Glucocorticoids act directly to upregulate prostaglandin production in fetal
    membranes at term [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/6,74\">",
    " 6,74",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Cortisol appears to stimulate expression of placental (but not hypothalamic)
    CRH in vitro [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/64\">",
    " 64",
    " </a>",
    " ]. Studies demonstrating an increase in circulating CRH concentrations (as
    well as a decrease in ACTH and cortisol levels) in women receiving antepartum
    glucocorticoids to promote fetal lung maturation suggest that this mechanism may
    also be operative in vivo [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/75,76\">",
    " 75,76",
    " </a>",
    " ]. In addition, measurement of elevated maternal plasma CRH levels between
    28 and 30 weeks of gestation may predict women at increased risk of preterm
    delivery [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/77\">",
    " 77",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " In addition, cortisol enhances amnionic cyclooxygenase to enhance
    prostaglandin synthesis and inhibits chorionic prostaglandin dehydrogenase
    activity, thereby preventing prostaglandin metabolism [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/6,68\">",
    " 6,68",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Taken together, these data suggest the gradual increase in fetal pituitary-
    adrenal activity over the last few weeks of gestation may have a role in the
    initiation of labor at term. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/40/32393?
    source=see_link\">",
    " \"Pathogenesis of spontaneous preterm birth\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <span class=\"h2\">",
    " Other",
    " </span>",
    " &nbsp;&mdash;&nbsp;Various neuropeptides and hormones can affect myometrial
    contractility. The concentration of some of these agents changes in maternal serum
    during pregnancy suggesting that they might act in an endocrine fashion, while
    others are produced locally within myometrial smooth muscle cells and act in an",
    " <span class=\"nowrap\">",
    " autocrine/paracrine",
    " </span>",
    " manner. However, their role in the initiation and maintenance of labor at term
    remains controversial. Some of these factors are illustrated below:",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H20\">",
    " <span class=\"h3\">",
    " Parathyroid hormone-related peptide",
    " </span>",
    " &nbsp;&mdash;&nbsp;Parathyroid hormone-related peptide is a potent smooth
    muscle relaxant capable of inhibiting oxytocin-induced contractions in baboons [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/78\">",
    " 78",
    " </a>",
    " ]. It is unclear whether it has a physiologically important role in
    maintaining uterine quiescence prior to the onset of labor.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H21\">",
    " <span class=\"h3\">",
    " Luteinizing hormone/human chorionic gonadotropin",
    " </span>",
    " &nbsp;&mdash;&nbsp;Luteinizing",
    " <span class=\"nowrap\">",
    " hormone/human",
    " </span>",
    " chorionic gonadotropin may be important for maintaining uterine quiescence,
    especially in the first half of pregnancy. Human chorionic gonadotropin decreases
    gap junction formation in strips of myometrium in vitro, leading to a decrease in
    contraction frequency and intensity [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/79\">",
    " 79",
    " </a>",
    " ]. This effect is likely mediated through the adenyl cyclase signal
    transduction system resulting in an increase in intracellular cAMP, which favors
    uterine relaxation.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22\">",
    " <span class=\"h3\">",
    " Relaxin",
    " </span>",
    " &nbsp;&mdash;&nbsp;Relaxin is a member of the insulin-like growth factor
    family of proteins. Plasma levels are highest at 8 to 12 weeks of gestation and
    thereafter decline to low levels, which persist until term [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/80\">",
    " 80",
    " </a>",
    " ]. The primary source of relaxin is thought to be the corpus luteum.",
    " </p>",
    " <p>",
    " Relaxin appears to act indirectly to promote myometrial relaxation by
    stimulating myometrial prostacyclin production. This effect can be negated by
    inhibitors of prostaglandin synthesis. Relaxin also has been implicated in cervical
    ripening",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " rupture of the fetal membranes, but this remains controversial [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/81\">",
    " 81",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H23\">",
    " <span class=\"h3\">",
    " Cytokines",
    " </span>",
    " &nbsp;&mdash;&nbsp;Cytokines have long been implicated in the pathophysiology
    of preterm labor associated with intraamniotic infection [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/82\">",
    " 82",
    " </a>",
    " ]. These agents may also be a component of the process of normal term labor
    [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/83-85\">",
    " 83-85",
    " </a>",
    " ]. Proinflammatory mediator levels (IL-1, IL-6, TNF-alpha) appear to increase
    in the maternal peripheral circulation before the onset of spontaneous term labor
    [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/86\">",
    " 86",
    " </a>",
    " ]. The developing fetus may produce physical and hormonal signals that
    stimulate macrophage migration to the uterus, with release of cytokines and
    activation of inflammatory transcription factors.",
    " </p>",
    " <p>",
    " Concentrations of interleukin (IL) -8 (but not IL-2 or tumor necrosis factor
    alpha) in human myometrium, decidua, and fetal membranes are increased during labor
    [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/83\">",
    " 83",
    " </a>",
    " ]. IL-8 is a potent chemotactic cytokine acting primarily on neutrophils. It
    may cause an increase in collagenase enzyme activity leading to cervical ripening",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " spontaneous rupture of membranes. Moreover, cytokines and eicosanoids appear
    to interact and to accelerate each other's production in a cascade-like fashion,
    resulting in further increases in prostaglandin production [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/87\">",
    " 87",
    " </a>",
    " ]. It has also been proposed that the increased inflammatory response promotes
    uterine contractility via direct activation of contractile genes (eg, COX-2,
    oxytocin receptor, connexin)",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " impairment of the capacity of progesterone to mediate uterine quiescence [",
    " <a class=\"abstract\" href=\"UTD.htm?6/0/6153/abstract/88\">",
    " 88",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H24\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Human labor at term is a multifactorial physiological event involving an
    integrated set of changes within the maternal tissues of the uterus (myometrium,
    decidua, and uterine cervix) which occur gradually over a period of days to
    weeks.",
    " </li>",
    " <li>",
    " Such changes include, but are not limited to, an increase in prostaglandin
    synthesis and release within the uterus, an increase in myometrial gap junction
    formation, and up-regulation of myometrial oxytocin receptors (uterine
    activation).",
    " </li>",
    " <li>",
    " Once the myometrium and cervix are prepared, endocrine",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " <span class=\"nowrap\">",
    " paracrine/autocrine",
    " </span>",
    " factors from the fetoplacental unit bring about a switch in the pattern of
    myometrial activity from irregular contractures to regular contractions (uterine
    stimulation).",
    " </li>",
    " <li>",
    " The fetus appears to control the initiation of labor by coordinating the
    switch in myometrial activity via placental steroid hormone production, mechanical
    distension of the uterus, and by secretion of neurohypophyseal hormones and other
    stimulators of prostaglandin synthesis.",
    " </li>",
    " <li>",
    " Labor is a clinical diagnosis based upon regular painful uterine
    contractions, progressive cervical effacement and dilatation, and a show (bloody
    discharge).",
    " </li>",
    " <li>",
    " The ability of the fetus to successfully negotiate the pelvis during labor
    and delivery is dependent on the complex interaction of three variables: the
    powers, the passenger, and the passage.",
    " </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>",
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    " </a>",
    " </li>",
    " </ol>",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H24\" 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\">",
    " LABOR AT TERM",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " PHYSIOLOGICAL PHASES OF MYOMETRIAL ACTIVITY",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Phase 0: inhibitors active",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " Phase 1: myometrial activation",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " Phase 2: stimulatory phase",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " Phase 3: involution",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Parturition cascade",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " THE ROLE OF THE FETUS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " MYOMETRIAL ACTIVATION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " HORMONES INVOLVED IN THE PARTURITIONAL CASCADE",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " Prostaglandins",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " Progesterone",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " Estrogen",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " Oxytocin",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " Hypothalamic-pituitary-adrenal factors",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " - Corticotropin releasing hormone",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " - Glucocorticoids",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H19\">",
    " Other",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H20\">",
    " - Parathyroid hormone-related peptide",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H21\">",
    " - Luteinizing hormone/human chorionic gonadotropin",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H22\">",
    " - Relaxin",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H23\">",
    " - Cytokines",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H24\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?4/22/4457?
    source=related_link\">",
    " Cervical insufficiency",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/40/32393?
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    " <li class=\"plainItem\">",
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    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f6_0_6154="Pulsus paradoxus mechanism";
    var content_f6_0_6154=[" <div id=\"graphicsToolbar\">",
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    " &copy;2013 UpToDate",
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    " &reg;",
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    u/8A47RcDwjTvi5BaahqNw9hcvFcujRpvHyYXBH4nmp4fi7ANcuLxrK48l4EjEfmDhgSSfSvcB8B/hyP+YD
    N/wCDK7/+O0f8KH+HOf8AkAS/
    +DK7/wDjtFwPK/BPjJPFfxo8F+TbyW8cUlx8rPkMfslxzj8a+oq4Xw38JvBfhvW7TVtG0mWDULTcYZGvriU
    JuQofleQr91mHI713VID/2Q==);\">",
    " </div>",
    " <div class=\"lgnd\">",
    " Doppler echocardiogram in a patient with cardiac tamponade. Note the
    inspiratory increase of tricuspid flow velocities (A) and the expiratory increase
    of mitral (B) and aortic (C) flow velocities.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced from: Hoit BD. Imaging the pericardium. Cardiol Clin 1990; 8:594.
    Illustration used with the permission of Elsevier Inc. All rights reserved.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f6_0_6154=[""].join("\n");
    var outline_f6_0_6154=null;
    var title_f6_0_6155="Standard PD solution";
    var content_f6_0_6155=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=NEPH
    %2F78759&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=NEPH
    %2F78759&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=6\" 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",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Standard peritoneal dialysis solution",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td>",
    " Volume (liters)",
    " </td>",
    " <td>",
    " 0.25, 0.5, 1.0, 1.5, 2.5, 3.0, 5.0, 6.0",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Sodium (mEq/L)",
    " </td>",
    " <td>",
    " 132",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Potassium (mEq/L)",
    " </td>",
    " <td>",
    " 0-2, mostly 0",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Glucose (g/dL)",
    " </td>",
    " <td>",
    " 1.5, 2.5, 4.0, 25",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Calcium (mEq/L)",
    " </td>",
    " <td>",
    " 2.5-3.5",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Magnesium (mEq/L)",
    " </td>",
    " <td>",
    " 0.5-1.5",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lactate (mEq/L)",
    " </td>",
    " <td>",
    " 35-40",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Dinesh Chatoth, MD.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f6_0_6155=[""].join("\n");
    var outline_f6_0_6155=null;
    var title_f6_0_6156="Causes of acquired goiter in children";
    var content_f6_0_6156=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=ENDO
    %2F77604&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=9\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=ENDO
    %2F77604&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=9\" 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",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Causes of acquired goiter in children",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"sublist1_start\">",
    " Inflammatory causes",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Chronic autoimmune (Hashimoto's) thyroiditis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Subacute granulomatous thyroiditis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Acute suppurative thyroiditis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Colloid goiter",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Iodine-deficiency goiter",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1_start\">",
    " Ingestion of goitrogens",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Iodine",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Lithium carbonate",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Foodstuffs (cassava, millet)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1_start\">",
    " Thyroid infiltrative disease",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Histiocytosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Cystinosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1_start\">",
    " Toxic goiter",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Graves' disease",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Autonomously functioning thyroid adenoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Activating mutations of the TSH receptor",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Activating mutations of the G protein alpha subunit",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1_start\">",
    " Thyroid cysts",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Thyroglossal duct cysts",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Thyroid adenomas",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1_start\">",
    " Thyroid carcinoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Papillary carcinoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Follicular carcinoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist1\">",
    " Medullary carcinoma",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f6_0_6156=[""].join("\n");
    var outline_f6_0_6156=null;
    var title_f6_0_6157="Spinal cord disorders";
    var content_f6_0_6157=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=NEURO
    %2F50336&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>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=NEURO
    %2F50336&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",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Important causes of spinal cord dysfunction*",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " &nbsp;",
    " </td>",
    " <td class=\"subtitle1\">",
    " Age",
    " </td>",
    " <td class=\"subtitle1\">",
    " Course",
    " </td>",
    " <td class=\"subtitle1\">",
    " Clinical features",
    " </td>",
    " <td class=\"subtitle1\">",
    " Diagnosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Cervical spondylotic myelopathy",
    " </td>",
    " <td>",
    " Usually &gt;60 years",
    " </td>",
    " <td>",
    " Progressive or stepwise course",
    " </td>",
    " <td>",
    " Moderate-severe cases demonstrate gait and leg spasticity and amyotrophy
    of hand or arms",
    " </td>",
    " <td>",
    " MRI cervical spine",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Transverse myelitis",
    " </td>",
    " <td>",
    " Children, young adults",
    " </td>",
    " <td>",
    " Subacute",
    " </td>",
    " <td>",
    " Segmental cord syndrome",
    " </td>",
    " <td>",
    " MRI and CSF",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Viral myelitis",
    " </td>",
    " <td>",
    " Any age",
    " </td>",
    " <td>",
    " Acute-subacute",
    " </td>",
    " <td>",
    " Pure motor syndrome or Segmental cord syndrome",
    " </td>",
    " <td>",
    " MRI and CSF",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Epidural abscess",
    " </td>",
    " <td>",
    " Any age",
    " </td>",
    " <td>",
    " Subacute; may worsen abruptly",
    " </td>",
    " <td>",
    " Segmental cord syndrome",
    " </td>",
    " <td>",
    " MRI",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Infarction",
    " </td>",
    " <td>",
    " Usually &gt;60 years",
    " </td>",
    " <td>",
    " Abrupt onset",
    " </td>",
    " <td>",
    " Anterior cord syndrome",
    " </td>",
    " <td>",
    " MRI with diffusion weighted sequences",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Vascular malformation",
    " </td>",
    " <td>",
    " <p>",
    " &gt;40 years (dural fistula)",
    " </p>",
    " <p>",
    " 20's (intramedullary AVM)",
    " </p>",
    " </td>",
    " <td>",
    " Acute and/or stepwise",
    " </td>",
    " <td>",
    " Radicuomyelopathy",
    " </td>",
    " <td>",
    " MRI, spinal angiography",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Subacute combined degeneration",
    " </td>",
    " <td>",
    " Any age",
    " </td>",
    " <td>",
    " Slowly progressive",
    " </td>",
    " <td>",
    " Dorsal cord syndrome",
    " </td>",
    " <td>",
    " Vitamin B12 levels",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Radiation",
    " </td>",
    " <td>",
    " Any age",
    " </td>",
    " <td>",
    " Slowly progressive; beginning 6-12 months after radiation therapy",
    " </td>",
    " <td>",
    " Segmental cord syndrome or Ventral cord syndrome",
    " </td>",
    " <td>",
    " MRI, clinical history",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Syringomyelia",
    " </td>",
    " <td>",
    " Children, young adults",
    " </td>",
    " <td>",
    " Slowly progressive",
    " </td>",
    " <td>",
    " Central cord syndrome",
    " </td>",
    " <td>",
    " MRI",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Epidural metastasis",
    " </td>",
    " <td>",
    " Usually &gt;50 years",
    " </td>",
    " <td>",
    " Subacute, may worsen abruptly",
    " </td>",
    " <td>",
    " Segmental cord syndrome",
    " </td>",
    " <td>",
    " MRI",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Intramedullary tumor",
    " </td>",
    " <td>",
    " Young adults",
    " </td>",
    " <td>",
    " Slowly progressive",
    " </td>",
    " <td>",
    " Central cord syndrome",
    " </td>",
    " <td>",
    " MRI with gadolinium enhancement",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " ALS",
    " </td>",
    " <td>",
    " Usually &gt;60 years",
    " </td>",
    " <td>",
    " Slowly progressive",
    " </td>",
    " <td>",
    " Pure motor syndrome",
    " </td>",
    " <td>",
    " Electromyography",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " MRI: magnetic resonance imaging; CSF: cerebrospinal fluid; AVM: arteriovenous
    malformation; ALS: amyotrophic lateral sclerosis.",
    " <br>",
    " * This is a partial list of causes. Please see topic \"Disorders affecting
    the spinal cord\" for a more complete differential diagnosis.",
    " </br>",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var outline_f6_0_6157=null;
    var title_f6_0_6158="Average annual fracture rate";
    var content_f6_0_6158=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=ENDO
    %2F58577&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
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    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=ENDO
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    " Print",
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    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
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    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 529px\">",
    " <div class=\"ttl\">",
    " Annual fracture rate in men and women",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " Average annual fracture incidence rate per 10,000 men and women in Leicester,
    United Kingdom. The rate begins to increase in women after age 44 years as they
    enter menopause and in men after age 74 years.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: Donaldson LJ, Cook A, Thomson RG. Incidence
    of fractures in a geographically defined population.&nbsp;J Epidemiol Community
    Health 1990; 44:241.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var title_f6_0_6159="Complete rectal prolapse";
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
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    " <a class=\"etacLink\" href=\"#\">",
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    " </div>",
    " <div class=\"lgnd\">",
    " The everted rectal wall appears as a tubular mass made up of several
    concentric mucosal folds.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from Nelson, H, Dozois, R. Prolapse of the rectum.
    In: Sabiston Review of Surgery, 3rd ed, Townsend, CM, Sabiston, DC, WB Saunders,
    Philadelphia, 2001. p.978. Copyright &copy; 2001 Mayo Foundation for Medical
    Education and Research",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f6_0_6159=[""].join("\n");
    var outline_f6_0_6159=null;

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