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  • 47

    Diunggah oleh

    Carlos Hernández
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    47

    Diunggah oleh

    Carlos Hernández

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    var title_f0_47_752="Cystic hygroma MRI I";

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    " &copy;2013 UpToDate",
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    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
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    " Cystic hygroma in left axillary region",
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    " </div>",
    " <div class=\"lgnd\">",
    " Spin-echo, T2-weighted MR sequence shows high signal mass in the left axilla,
    which corresponds to the cyst seen on the CT scan.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Paul Stark, MD.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_752=[""].join("\n");
    var outline_f0_47_752=null;
    var title_f0_47_753="Rx asymptomatic chron severe MR";
    var content_f0_47_753=[" <div id=\"graphicsToolbar\">",
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
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    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=CARD%2F58148%7ECARD
    %2F81099&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
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    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " ACC/AHA Guidelines: Management strategy for asymptomatic patients with chronic
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    IlfuIpvuItnkiCAAA7);\">",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " LVEF: left ventricular ejection fraction; LVESD: left vendricular end-
    systolic dimension; AF: atrial fibrillation. Pulmonary hypertension is defined as
    pulmonary artery systolic pressure &gt;50 mmHg at rest or &gt;60 mmHg with
    exercise.",
    " <br>",
    " * Mitral valve repair may be performed in asymptomatic patients with normal
    left ventricular function if performed by an experienced surgical team and the
    likelihood of successful MV repair is greater than 90 percent.",
    " <br>",
    " <br>",
    " The 2012 European Society of Cardiology valvular heart disease guidelines
    recommend a similar management strategy. The key difference is&nbsp;that the LVESD
    cut-off used is &ge;45 mm in the ESC guidelines (versus &ge;40 mm in the ACC/AHA
    guidelines). In addition, the ESC guidelines state that&nbsp;mitral valve repair
    should be considered&nbsp;in asymptomatic patients without atrial fibrillation or
    pulmonary hypertension only&nbsp;if there is a high likelihood of durable repair at
    a low surgical risk and there is a flail leaflet and LVESD &ge;40mm. They also
    indicate that valve repair may be considered if left atrial volume is &ge;60 ML/m",
    " <sup>",
    " 2",
    " </sup>",
    " BSA and sinus rhythm is present&nbsp;",
    " <strong>",
    " or",
    " </strong>",
    " pulmonary hypertension on exercise (pulmonary artery systolic pressure
    &ge;60 mmHg). Authors/Task Force Members, Vahanian A, Alfieri O, et al. Guidelines
    on the management of valvular heart disease (version 2012): The Joint Task Force on
    the Management of Valvular Heart Disease of the European Society of Cardiology
    (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J
    2012; 33:2451.",
    " </br>",
    " </br>",
    " </br>",
    " </div>",
    " <div class=\"reference\">",
    " <br>",
    " Adapted from Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006
    Guidelines for the management of patients with valvular heart disease. A report of
    the American College of Cardiology / American Heart Association Task Force on
    Practice Guidelines (Writing committee to revise the 1998 guidelines for the
    management of patients with valvular heart disease). J Am Coll Cardiol 2006;
    48:e1.",
    " <br>",
    " <br/>",
    " </br>",
    " </br>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " ACC/AHA guidelines: Management strategy for symptomatic patients with chronic
    severe mitral regurgitation (MR)",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " LVEF: left ventricular ejection fraction; LVESD: left ventricular end-
    systolic dimension.",
    " <br>",
    " <br>",
    " The 2012 European Society of Cardiology (ESC) valvular heart disease
    guidelines recommend a similar management strategy. The key difference&nbsp;is that
    the ESC guidelines classify symptomatic patients by LVEF &gt;30 percent only
    (without any LVESD criterion). In addition, the ESC guidelines recommend valve
    surgery in patients with an LVEF &le;30 percent only if&nbsp;they are refractory to
    medical therapy and durable valve repair is likely and there is low comorbidity.
    Patients with LVEF &le; 30 percent&nbsp;who have refractory heart failure and who
    are not eligible for durable repair should receive extended HF treatment. Task
    Force Members, Vahanian A, Alfieri O, et al. Guidelines on the management of
    valvular heart disease (version 2012): The Joint Task Force on the Management of
    Valvular Heart Disease of the European Society of Cardiology (ESC) and the European
    Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2012; 33:2451.",
    " </br>",
    " </br>",
    " </div>",
    " <div class=\"reference\">",
    " Adapted from Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006
    Guidelines for the management of patients with valvular heart disease. A report of
    the American College of Cardiology / American Heart Association Task Force on
    Practice Guidelines (Writing committee to revise the 1998 guidelines for the
    management of patients with valvular heart disease). J Am Coll Cardiol 2006;
    48:e1.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    var title_f0_47_754="Transthoracic v transesophageal";
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
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    " <a href=\"?imageKey=CARD
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    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
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    " Email",
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    " <div class=\"graphic\">",
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    " <div class=\"ttl\">",
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    ,
    " </div>",
    " <div class=\"lgnd\">",
    " The apical four-chamber view from a transthoracic echocardiogram demonstrates
    only subtle changes in the posterior leaftlet of the mitral valve (arrow). However,
    the transesophageal echocardiogram (panel B) shows that the posterior leaflet of
    the mitral valve (pML) is both flail and attached to a vegetation. The anterior
    leaflet, which had a bright density on transthoracic echocardiography (red arrow),
    is normally postitioned and of normal thickness; the bright density is seen on the
    transesophageal echocardiogram to be the rough edge of the valve where the chordae
    attach (red arrow).",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_754=[""].join("\n");
    var outline_f0_47_754=null;
    var title_f0_47_755="Painful menstrual periods (dysmenorrhea)";
    var content_f0_47_755=[" <h1 id=\"patTopicTitle\">",
    " Patient information: Painful menstrual periods (dysmenorrhea) (Beyond the
    Basics)",
    " </h1>",
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    " <div class=\"rcTop\">",
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    " <table>",
    " <tr>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/47/755/contributors\">",
    " Authors",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/47/755/contributors\" id=\"au6153\">",
    " Roger P Smith, MD",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/47/755/contributors\" id=\"au6181\">",
    " Andrew M Kaunitz, MD",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/47/755/contributors\">",
    " Section Editor",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/47/755/contributors\" id=\"se4464\">",
    " Robert L Barbieri, MD",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/47/755/contributors\">",
    " Deputy Editor",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/47/755/contributors\" id=\"de1930\">",
    " Sandy J Falk, MD",
    " </a>",
    " </td>",
    " </tr>",
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    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " </p>",
    " <p>",
    " Painful menstruation, also known as dysmenorrhea, is one of the most common
    women&rsquo;s problems. Most women begin having dysmenorrhea during adolescence,
    usually within four to five years of the first menstrual period. Painful periods
    become less common as women age.",
    " </p>",
    " <p>",
    " This topic review discusses the causes, symptoms diagnosis, and treatment of
    dysmenorrhea in women who do not have an underlying cause for their pain (eg,
    endometriosis, fibroids, bowel or bladder disease, etc). Separate topic reviews
    discuss the management of these problems. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?25/63/26611?
    source=see_link\">",
    " \"Patient information: Endometriosis (Beyond the Basics)\"",
    " </a>",
    " and",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?20/20/20804?
    source=see_link\">",
    " \"Patient information: Uterine fibroids (Beyond the Basics)\"",
    " </a>",
    " and",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?31/55/32627?
    source=see_link\">",
    " \"Patient information: Chronic pelvic pain in women (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " CAUSE OF DYSMENORRHEA",
    " </span>",
    " </p>",
    " <p>",
    " Prostaglandins are chemicals that are formed in the lining of the uterus
    during menstruation. These prostaglandins cause muscle contractions in the uterus,
    which cause pain and decrease blood flow and oxygen to the uterus. Similar to labor
    pains, these contractions can cause significant pain and discomfort. Prostaglandins
    may also contribute to the nausea and diarrhea that some women experience.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " DYSMENORRHEA SYMPTOMS",
    " </span>",
    " </p>",
    " <p>",
    " The pain of dysmenorrhea is crampy and usually located in lower abdomen above
    the pubic bone (the suprapubic region); some women also have severe pain in the
    back or thighs. The pain usually begins just before or as menstrual bleeding
    begins, and gradually diminishes over one to three days. Pain usually occurs
    intermittently, ranging from mild to disabling.",
    " </p>",
    " <p>",
    " Other symptoms that may accompany cramping include nausea, diarrhea,
    dizziness, fatigue, headache, or a flu-like feeling.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h1\">",
    " DYSMENORRHEA DIAGNOSIS",
    " </span>",
    " </p>",
    " <p>",
    " The diagnosis of dysmenorrhea is based upon a woman's medical history and
    physical examination.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H5\">",
    " <span class=\"h2\">",
    " Physical examination",
    " </span>",
    " &nbsp;&mdash;&nbsp;Women with dysmenorrhea should have a complete abdominal
    and pelvic examination. During the examination, the healthcare provider will
    observe and feel the size and shape of the vagina, cervix, uterus, and ovaries. An
    internal pelvic examination may not be necessary in adolescent girls.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H6\">",
    " <span class=\"h2\">",
    " Other tests",
    " </span>",
    " &nbsp;&mdash;&nbsp;In some women, pelvic ultrasound (performed vaginally if
    possible) can be useful in determining if conditions such as uterine fibroids,
    adenomyosis, or endometriosis are present. &nbsp;",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h1\">",
    " DYSMENORRHEA TREATMENT",
    " </span>",
    " </p>",
    " <p>",
    " There are a number of treatments available for women with dysmenorrhea.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H8\">",
    " <span class=\"h2\">",
    " Non-steroidal antiinflammatory drugs (NSAIDs)",
    " </span>",
    " &nbsp;&mdash;&nbsp;NSAIDs are a class of medications that are very effective
    in reducing pain associated with dysmenorrhea. Some NSAIDs are available without a
    prescription while others require a prescription; prescription NSAIDs are probably
    no more effective than non-prescription NSAIDs as long as an adequate dose is
    taken.",
    " </p>",
    " <p>",
    " NSAIDs are most effective if they are started as soon as bleeding or other
    menstrual symptoms begins, and then taken on a regular schedule for two to three
    days.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H9\">",
    " <span class=\"h2\">",
    " Birth control pills",
    " </span>",
    " &nbsp;&mdash;&nbsp;Birth control pills and other forms of hormonal birth
    control (eg, patch, vaginal ring, injection, hormone-releasing intrauterine device,
    contraceptive implant) also represent effective treatments for women with
    dysmenorrhea. These treatments work by thinning the lining of the uterus, where
    prostaglandins are formed, thereby decreasing the uterine contractions and
    menstrual bleeding that contribute to pain and cramping. As discussed below, women
    may choose to use NSAIDs and hormonal contraceptives simultaneously to control
    dysmenorrhea.",
    " </p>",
    " <p>",
    " Obviously, hormonal methods of birth control do not make sense for women who
    are trying to become pregnant. However, women who are not actively trying to become
    pregnant usually have significantly less dysmenorrhea after using a hormonal birth
    control treatment for two to three months, even if the woman does not need to
    prevent pregnancy (eg, if the woman is not sexually active or if she or her partner
    has had a sterilization procedure). (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?21/32/22021?
    source=see_link\">",
    " \"Patient information: Hormonal methods of birth control (Beyond the
    Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Traditionally, hormonal birth control treatments (pills, patch, ring) are
    taken so that the woman has monthly bleeding. However, women who prefer",
    " <strong>",
    " NOT",
    " </strong>",
    " to have bleeding each month and those who wish to minimize dysmenorrhea can
    use these contraceptives continuously to avoid or minimize pain associated with the
    menstrual period. Taking the treatment continuously means the following:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Women who take a birth control pill would take one \"active\" pill per day
    for 21 or 24 days (depending upon the brand of pill), and then open a new pack of
    pills and do the same. This can be done indefinitely, although many women stop
    taking their pill for several days every 9 to 12 weeks; most women will have some
    menstrual bleeding during this time.",
    " </li>",
    " <li>",
    " Women who use the patch (Ortho Evra&reg;) would apply a new patch once per
    week for 9 to 12 weeks, and then use no patch for several days; most women will
    have some menstrual bleeding during this time.",
    " </li>",
    " <li>",
    " Women who use the vaginal ring (Nuvaring&reg;) would insert a new ring
    every three to four weeks for 9 to 12 weeks, and then use no ring for several days;
    most women will have some menstrual bleeding during this time.",
    " </li>",
    " <li>",
    " Women who use injections of medroxyprogesterone acetate (Depo-Provera&reg;)
    are given one injection every 12 weeks. Most women have some intermittent spotting
    or bleeding for the first few months; this usually decreases with time. Most women
    who use Depo-Provera&reg; have unpredictable spotting and bleeding initially;
    however, after women have received four or more injections (one year or more of
    use), most have little to no bleeding.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Women who take a hormonal birth control treatment continuously often have
    intermittent light bleeding or spotting, especially during the first two to three
    months of treatment; this usually declines with time. When bleeding occurs, it is
    usually lighter and associated with less severe cramping compared to before the
    treatment.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H10\">",
    " <span class=\"h2\">",
    " Intrauterine device (IUD)",
    " </span>",
    " &nbsp;&mdash;&nbsp;The intrauterine device that contains the hormone
    levonorgestrel (Mirena&reg;) can reduce dysmenorrhea by as much as 50 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/1\">",
    " 1",
    " </a>",
    " ]. In contrast, non-hormonal IUDs, such as those that contain copper, can
    have no effect or even worsen dysmenorrhea. The levonorgestrel IUD is discussed in
    detail in a separate topic review. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?4/16/4355?
    source=see_link\">",
    " \"Patient information: Long-term methods of birth control (Beyond the
    Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H11\">",
    " <span class=\"h2\">",
    " Non-pharmacologic treatments",
    " </span>",
    " &nbsp;&mdash;&nbsp;Treatments that do not require the use of a medication can
    also help to reduce the pain of dysmenorrhea. In some cases, these treatments are
    not as effective as medications, although they can be combined with a medication to
    increase the pain-relief benefit.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H12\">",
    " <span class=\"h3\">",
    " Heat",
    " </span>",
    " &nbsp;&mdash;&nbsp;Applying heat to the lower abdomen with a heating pad, hot
    water bottle, or self-heating patch can significantly reduce pain, often as well as
    treatment with an NSAID. It is important to avoid burning the skin with a heating
    pad or hot water bottle that is too hot; a temperature of approximately 104&ordm;F
    (40&ordm;C) is recommended. The heat can be applied as often as it is needed. Using
    heat in addition to ibuprofen may speed the relief of pain [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H13\">",
    " <span class=\"h3\">",
    " Dietary, vitamin, and herbal treatments",
    " </span>",
    " &nbsp;&mdash;&nbsp;A variety of dietary and vitamin therapies have been
    studied for the relief of dysmenorrhea [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/3\">",
    " 3",
    " </a>",
    " ]. However, the studies involved a small number of women and do not provide
    sufficient data regarding safety or efficacy. We do not recommend dietary, vitamin,
    or herbal remedies for dysmenorrhea.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H14\">",
    " <span class=\"h3\">",
    " Exercise",
    " </span>",
    " &nbsp;&mdash;&nbsp;Exercise seems to reduce menstrual symptoms, including
    pain, in some studies [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/4\">",
    " 4",
    " </a>",
    " ]. Exercise has a number of benefits, so it is reasonable to try exercising
    to reduce painful periods. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?7/42/7844?
    source=see_link\">",
    " \"Patient information: Exercise (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H15\">",
    " <span class=\"h3\">",
    " Complementary or alternative medicine",
    " </span>",
    " &nbsp;&mdash;&nbsp;There is some evidence that complementary medicine
    practices such as yoga or acupuncture are effective in reducing painful periods [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/5\">",
    " 5",
    " </a>",
    " ]. However, further study is needed to confirm the safety and efficacy of
    these treatments. Further information about complementary and alternative medicine
    is available from the National Center for Complementary and Alternative Medicine
    (",
    " <a class=\"external\" href=\"file://nccam.nih.gov/\">",
    " file://nccam.nih.gov/",
    " </a>",
    " ).",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H16\">",
    " <span class=\"h2\">",
    " Transcutaneous electrical nerve stimulation",
    " </span>",
    " &nbsp;&mdash;&nbsp;Transcutaneous electrical nerve stimulation (TENS) is a
    treatment that involves the use of electrode patches, which are applied to the skin
    near the area of pain. TENS has been used to treat pain caused by many conditions,
    and may help to reduce dysmenorrhea in some women.",
    " </p>",
    " <p>",
    " The patient wears a small battery pack on a belt, which generates a mild
    electrical current that passes to the electrodes. The electrical current is
    believed to stimulate the release of chemicals that block or reduce painful nerve
    impulses.",
    " </p>",
    " <p>",
    " An analysis of several studies showed that TENS does not relieve pain as well
    as medications, although it may be a useful alternative for women who cannot or
    prefer not to take pain-relieving medications [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H17\">",
    " <span class=\"h2\">",
    " Surgical options",
    " </span>",
    " &nbsp;&mdash;&nbsp;At least two surgical procedures have been developed to
    treat dysmenorrhea. Both of these surgeries involve cutting or destroying the
    uterine nerves, which prevents the transmission of pain signals. However, no
    surgery has been shown to provide long-term relief of pain and surgery may be
    associated with complications. This may be related to regrowth of nerves or pain
    signals being transferred by alternate routes [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/7\">",
    " 7",
    " </a>",
    " ]. As a result, surgical treatments for dysmenorrhea are not generally
    recommended.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h1\">",
    " IF THE INITIAL DYSMENORRHEA TREATMENT FAILS",
    " </span>",
    " </p>",
    " <p>",
    " The most effective treatments for dysmenorrhea include NSAIDs",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " hormonal birth control treatments. If one of these treatments does not
    sufficiently relieve pain within two to three months, another treatment may be
    offered. As an example, if a woman tries NSAIDs but does not improve or cannot
    tolerate the treatment, a hormonal birth control treatment may be recommended
    instead of or in addition to the NSAID (or vice versa).",
    " </p>",
    " <p>",
    " If neither NSAIDs nor a hormonal birth control treatment adequately improve
    pain, the next step depends upon the woman's age, symptoms, and other medical
    conditions. The options include:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Diagnostic laparoscopy may be recommended to determine if endometriosis, or
    another condition, could be causing the pain. Usually performed in an operating
    room under general anesthesia, laparoscopy is a minimally invasive surgery that
    uses small incisions and a thin telescope with a camera to determine if there are
    signs of endometriosis or other abnormalities on or near the uterus, ovaries, or
    other areas inside the pelvis.",
    " </li>",
    " <li>",
    " Assume the pain is caused by endometriosis and treat with a gonadotropin-
    releasing hormone (GnRH) agonist, such as nafarelin (Synarel&reg;) or leuprolide
    (Lupron&reg;). If dysmenorrhea improves within two to three months of starting
    treatment, it was probably caused by endometriosis.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " These options are discussed in full detail in a separate topic review. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?25/63/26611?
    source=see_link\">",
    " \"Patient information: Endometriosis (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <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=\"H191\">",
    " <span class=\"h2\">",
    " Patient level information",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education
    materials.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H11170351\">",
    " <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?5/8/5251?
    source=see_link\">",
    " Patient information: Endometriosis (The Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?25/13/25810?
    source=see_link\">",
    " Patient information: Uterine adenomyosis (The Basics)",
    " </a>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H11170359\">",
    " <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?25/63/26611?
    source=see_link\">",
    " Patient information: Endometriosis (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?20/20/20804?
    source=see_link\">",
    " Patient information: Uterine fibroids (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?31/55/32627?
    source=see_link\">",
    " Patient information: Chronic pelvic pain in women (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?21/32/22021?
    source=see_link\">",
    " Patient information: Hormonal methods of birth control (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?4/16/4355?
    source=see_link\">",
    " Patient information: Long-term methods of birth control (Beyond the
    Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?7/42/7844?
    source=see_link\">",
    " Patient information: Exercise (Beyond the Basics)",
    " </a>",
    " <br/>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H21\">",
    " <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?38/60/39879?
    source=see_link\">",
    " Primary dysmenorrhea in adult women: Clinical features and diagnosis",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?30/25/31125?
    source=see_link\">",
    " Primary dysmenorrhea in adolescents",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/36/28233?
    source=see_link\">",
    " Treatment of primary dysmenorrhea in adult women",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/35/27191?
    source=see_link\">",
    " Uterine adenomyosis",
    " </a>",
    " <br/>",
    " <br/>",
    " The following organizations also provide reliable health information.",
    " </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/ency/article/003150.htm\">",
    " www.nlm.nih.gov/medlineplus/ency/article/003150.htm",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The American College of Obstetricians and Gynecologists",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.acog.org/for_patients\">",
    " www.acog.org/For_Patients",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/755/abstract/1-7\">",
    " 1-7",
    " </a>",
    " ]",
    " </p>",
    " </div>",
    " </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 31, 2012.",
    " </div>",
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    " <div id=\"disclaimer\">",
    " The content on the UpToDate website is not intended nor recommended as a
    substitute",
    "for medical advice, diagnosis, or treatment. Always seek the advice of your own
    physician or",
    "other qualified health care professional regarding any medical questions or
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    " <a href=\"/home/terms-use\" target=\"_blank\">",
    " UpToDate Terms of Use",
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    " &copy;2013 UpToDate, Inc.",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <div id=\"patTopicRefHeader\">",
    " <div id=\"patTopicRefHeaderHeader\">",
    " References",
    " </div>",
    " <div id=\"patTopicRefHeaderTop\">",
    " <a href=\"#top\">",
    " <img alt=\"\" src=\"./../images/top_arrow.myextg\">",
    " Top",
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    " </a>",
    " </div>",
    " </div>",
    " <ol id=\"reference\">",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/755/abstract/1\">",
    " Baldaszti E, Wimmer-Puchinger B, L&ouml;schke K. Acceptability of the long-
    term contraceptive levonorgestrel-releasing intrauterine system (Mirena): a 3-year
    follow-up study. Contraception 2003; 67:87.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/755/abstract/2\">",
    " Akin MD, Weingand KW, Hengehold DA, et al. Continuous low-level topical heat
    in the treatment of dysmenorrhea. Obstet Gynecol 2001; 97:343.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/755/abstract/3\">",
    " Proctor ML, Murphy PA. Herbal and dietary therapies for primary and
    secondary dysmenorrhoea. Cochrane Database Syst Rev 2001; :CD002124.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/755/abstract/4\">",
    " Golomb LM, Solidum AA, Warren MP. Primary dysmenorrhea and physical
    activity. Med Sci Sports Exerc 1998; 30:906.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/755/abstract/5\">",
    " Helms JM. Acupuncture for the management of primary dysmenorrhea. Obstet
    Gynecol 1987; 69:51.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/755/abstract/6\">",
    " Proctor ML, Smith CA, Farquhar CM, Stones RW. Transcutaneous electrical
    nerve stimulation and acupuncture for primary dysmenorrhoea. Cochrane Database Syst
    Rev 2002; :CD002123.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/755/abstract/7\">",
    " Proctor ML, Latthe PM, Farquhar CM, et al. Surgical interruption of pelvic
    nerve pathways for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev
    2005; :CD001896.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
    " </div>",
    " <!-- patTopicMiddle -->",
    "</div>"].join("\n");
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    " <div class=\"rcTop\">",
    " <div>",
    " </div>",
    " </div>",
    " <div class=\"rcContent\">",
    " <p>",
    " Contents of this article",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"patTopicFancySpacer\">",
    " </div>",
    " <div class=\"patTopicOutline\">",
    " <div class=\"rcbBottom\">",
    " <div class=\"rcbLeft\">",
    " <div class=\"rcbRight\">",
    " <div class=\"rcbBottomLeft\">",
    " <div class=\"rcbBottomRight rcbBottomRightBottomOnly\">",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H2\">",
    " CAUSE OF DYSMENORRHEA",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H3\">",
    " DYSMENORRHEA SYMPTOMS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H4\">",
    " DYSMENORRHEA DIAGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H7\">",
    " DYSMENORRHEA TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H18\">",
    " IF THE INITIAL DYSMENORRHEA TREATMENT FAILS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H19\">",
    " WHERE TO GET MORE INFORMATION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_47_756="Erythromycin (topical): Patient drug information";
    var content_f0_47_756=[" <noscript>",
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    " <div id=\"disclaimer\">",
    " The content on the UpToDate website is not intended nor recommended as a
    substitute",
    "for medical advice, diagnosis, or treatment. Always seek the advice of your own
    physician or",
    "other qualified health care professional regarding any medical questions or
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    " UpToDate Terms of Use",
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    " &copy;2013 UpToDate, Inc.",
    " </div>",
    " <div id=\"drugTitle\">",
    " Erythromycin (topical): Patient drug information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
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    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
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    " <div id=\"topicText\">",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/28/31171?source=see_link\">",
    " see \"Erythromycin (topical): Drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?30/6/30818?
    source=see_link\">",
    " see \"Erythromycin (topical): Pediatric drug information\"",
    " </a>",
    " )",
    " </p>",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F8086237\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Akne-mycin&reg;;",
    " </li>",
    " <li>",
    " Ery",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F8086238\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Sans Acne&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yya-os drugH1Div\" id=\"F10031046\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What is this drug used for?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2691693",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " It is used to treat pimples (acne).",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt coi-os drugH1Div\" id=\"F10031045\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What do I need to tell my doctor before I take this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2702046",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If you have an allergy to erythromycin or any other part of this drug.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2705171",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If you are allergic to any drugs, foods, or other substances. Tell your
    doctor about the allergy and what signs you had, like rash; hives; itching;
    shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or
    any other signs.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yye-os drugH1Div\" id=\"F10031050\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What are some things I need to know or do while I take this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699677",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Keep a list of all your drugs (prescription, natural products, vitamins,
    OTC) with you. Give this list to your doctor.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696717",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Check all drugs you are taking with your doctor. This drug may not mix well
    with some other drugs.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2697641",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Tell your doctor if you are pregnant or plan on getting pregnant. You will
    need to talk about the benefits and risks of using this drug while you are
    pregnant.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2697636",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Tell your doctor if you are breast-feeding. You will need to talk about any
    risks to your baby.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyf-os drugH1Div\" id=\"F10031051\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What are some side effects of this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698029",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Dry skin.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698344",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Skin irritation.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698191",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Itching.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyh-os drugH1Div\" id=\"F10031053\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What are some side effects that I need to call my doctor about right away?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698721",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If you think there has been an overdose, call 1-800-222-1222 (the American
    Association of Poison Control Centers), your local poison control center
    (file://www.aapcc.org), or emergency room (ER) right away.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699066",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Signs of an allergic reaction, like rash; hives; itching; red, swollen,
    blistered, or peeling skin with or without fever; wheezing; tightness in the chest
    or throat; trouble breathing or talking; unusual hoarseness; or swelling of the
    mouth, face, lips, tongue, or throat.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699049",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Very bad skin irritation.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698603",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Any rash.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698977",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Side effect or health problem is not better or you are feeling worse.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyc-os drugH1Div\" id=\"F10031048\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " How is this drug best taken?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2694772",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Do not take this drug by mouth. Use on your skin only. Keep out of your
    mouth, nose, and eyes (may burn).",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696257",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Wash your hands before and after use.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696242",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Wash and rinse affected skin with warm water, then pat dry.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyd-os drugH1Div\" id=\"F10031049\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What do I do if I miss a dose?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696441",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Put on a missed dose as soon as you think about it.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696496",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If it is close to the time for your next dose, skip the missed dose and go
    back to your normal time.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696452",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Do not put on 2 doses or extra doses.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyi-os drugH1Div\" id=\"F10031054\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " How do I store and/or throw out this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699336",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Store at room temperature.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699301",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Protect skin solution and gel from heat.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyj-os drugH1Div\" id=\"F10031055\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " General drug facts",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699675",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If your symptoms or health problems do not get better or if they become
    worse, call your doctor.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699673",
    " </span>",
    " </span>",
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    " </div>",
    " <div class=\"lgnd\">",
    " Green or green-reddish leaves grow in groups of three and have smooth, fine-
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    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
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    " </div>",
    " </div>",
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    var outline_f0_47_757=null;
    var title_f0_47_758="Pathogenesis osteomyelitis children";
    var content_f0_47_758=[" <div id=\"graphicsToolbar\">",
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
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    " <a href=\"?imageKey=PEDS
    %2F65719&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=PEDS
    %2F65719&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: 506px\">",
    " <div class=\"ttl\">",
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    CiiigAooooAKKKKACiiigD//Z);\">",
    " </div>",
    " <div class=\"lgnd\">",
    " (A) During an episode of bacteremia, bacteria are deposited in the metaphysis
    from the metaphyseal vessels (nutrient artery and vein).",
    " <br/>",
    " (B) A focus of infection develops in the metaphysis, which leads to cellulitis
    in the bone marrow.",
    " <br/>",
    " (C) Exudate under pressure is forced laterally through the Haversian systems
    and Volkmann canals and into the cortex of the bone, where it can lift or rupture
    through the periosteum.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_758=[""].join("\n");
    var outline_f0_47_758=null;
    var title_f0_47_759="Metoclopramide: Pediatric drug information";
    var content_f0_47_759=[" <noscript>",
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    " <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
    " <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
    src=\"./../images/logoWKH.myextg\" width=\"175\">",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Metoclopramide: 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?0/13/216?source=see_link\">",
    " see \"Metoclopramide: Drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?33/45/34517?source=see_link\">",
    " see \"Metoclopramide: Patient drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"block black-box-warn drugH1Div\" id=\"F8117624\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " ALERT: U.S. Boxed Warning",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " The FDA-approved labeling includes a boxed warning. See Warnings/Precautions
    section for a concise summary of this information. For verbatim wording of the
    boxed warning, consult the product labeling or",
    " <a href=\"file://www.fda.gov\" target=\"_blank\">",
    " www.fda.gov",
    " </a>",
    " .",
    " </p>",
    " </div>",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F195600\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Metozolv&trade; ODT;",
    " </li>",
    " <li>",
    " Reglan&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F195601\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Apo-Metoclop&reg;;",
    " </li>",
    " <li>",
    " Metoclopramide Hydrochloride Injection;",
    " </li>",
    " <li>",
    " Metoclopramide Omega;",
    " </li>",
    " <li>",
    " Nu-Metoclopramide;",
    " </li>",
    " <li>",
    " PMS-Metoclopramide",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list_set htclist drugH1Div drugBrandNames\" id=\"F1060336\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Therapeutic Category",
    " </span>",
    " <ul>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Antiemetic",
    " </span>",
    " </li>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Gastrointestinal Agent, Prokinetic",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block don drugH1Div\" id=\"F11443886\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Neonatal",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " GERD: Oral, I.M., I.V.: 0.1-0.15 mg/kg/dose every 6 hours; avoid doses
    &gt;0.15 mg/kg due to increased potential for adverse effects caused by excessive
    serum concentrations (Kearns, 1998)",
    " </p>",
    " </div>",
    " <div class=\"block dos drugH1Div\" id=\"F1060329\"
    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?0/13/216?source=see_link\">",
    " see \"Metoclopramide: Drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Intubation of small intestine to facilitate radiographic examination of upper
    GI tract: I.V.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " &lt;6 years: 0.1 mg/kg as a single dose",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " 6-14 years: 2.5-5 mg as a single dose",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children &gt;14 years and Adults: 10 mg as a single dose",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Gastroesophageal reflux: Oral, I.M., I.V.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Infants and Children: 0.4-0.8 mg/kg/day in 4 divided doses",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Adults: 10-15 mg 4 times/day; single doses of 20 mg are occasionally needed
    prior to provoking situations. Treatment &gt;12 weeks has not been evaluated and is
    not recommended.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Postoperative nausea and vomiting: I.V.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children &le;14 years: 0.1-0.2 mg/kg/dose (maximum dose: 10 mg/dose); repeat
    every 6-8 hours as needed",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children &gt;14 years and Adults: 10 mg; repeat every 6-8 hours as needed",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Antiemetic",
    " <b>",
    " (chemotherapy-induced emesis)",
    " </b>",
    " : Oral, I.V.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children and Adults: 1-2 mg/kg/dose every 2-4 hours (maximum: 5 doses/day);
    pretreatment with diphenhydramine will decrease risk of extrapyramidal reactions to
    this dosage",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Diabetic gastroparesis: Adults: Oral, I.V.: 10 mg before each meal and at
    bedtime for 2-8 weeks",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Dosing adjustment in renal impairment:",
    " </b>",
    " Children and Adults:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " 40-50 mL/minute: Administer 75% of recommended dose",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " 10-40 mL/minute: Administer 50% of recommended dose",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;10 mL/minute: Administer 25% to 50% of recommended dose",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F195570\"
    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. [DSC] = Discontinued product",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, solution [preservative free]: 5 mg/mL (2 mL)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Reglan&reg;: 5 mg/mL (2 mL [DSC], 10 mL [DSC], 30 mL [DSC])",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Solution, oral: 5 mg/5 mL (0.9 mL, 10 mL, 473 mL)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Tablet, oral: 5 mg, 10 mg",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Reglan&reg;: 5 mg",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Reglan&reg;: 10 mg [scored]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Tablet, orally disintegrating, oral:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Metozolv&trade; ODT: 5 mg, 10 mg [mint flavor]",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F195554\"
    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 oral-disintegrating tablet",
    " </p>",
    " </div>",
    " <div class=\"block meg drugH1Div\" id=\"F8083407\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Medication Guide",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " An FDA-approved patient medication guide, which is available with the product
    information and as follows, must be dispensed with this medication:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Metoclopramide oral solution:",
    " <a href=\"file://www.fda.gov/downloads/Drugs/DrugSafety/UCM244086.pdf\"
    target=\"_blank\">",
    " file://www.fda.gov/downloads/Drugs/DrugSafety/UCM244086.pdf",
    " </a>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Metozolv&trade; ODT:",
    " <a
    href=\"file://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022246s000lbl.pdf\"
    target=\"_blank\">",
    " file://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022246s000lbl.pdf",
    " </a>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Reglan&reg; injection:",
    " <a href=\"file://www.fda.gov/downloads/Drugs/DrugSafety/UCM176362.pdf\"
    target=\"_blank\">",
    " file://www.fda.gov/downloads/Drugs/DrugSafety/UCM176362.pdf",
    " </a>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Reglan&reg; tablet:
    file://www.alavenpharm.com/downloads/ReglanTablets_MedicationGuide.pdf",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F1060340\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Oral: Administer 30 minutes before meals and at bedtime",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Parenteral: Dilute to 0.2 mg/mL (maximum concentration: 5 mg/mL) and infuse
    over 15-30 minutes (maximum rate of infusion: 5 mg/minute); higher doses (&gt;10
    mg) to be diluted in 50 mL of compatible solution (preferably NS) and administered
    over at least 15 minutes; rapid I.V. administration is associated with a transient
    but intense feeling of anxiety and restlessness, followed by drowsiness",
    " </p>",
    " </div>",
    " <div class=\"block scp drugH1Div\" id=\"F195662\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Compatibility",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Stable in D",
    " <sub>",
    " 5",
    " </sub>",
    " <sup>",
    " 1",
    " </sup>",
    " /",
    " <sub>",
    " 2",
    " </sub>",
    " NS, D",
    " <sub>",
    " 5",
    " </sub>",
    " W, mannitol 20%, LR, NS.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Y-site administration: Compatible:",
    " </b>",
    " Acyclovir, aldesleukin, amifostine, aztreonam, bivalirudin, bleomycin,
    caffeine citrate, ciprofloxacin, cisatracurium, cladribine, cyclophosphamide,
    cytarabine, dexmedetomidine, diltiazem, docetaxel, doripenem, doxapram,
    doxorubicin, droperidol, etoposide phosphate, famotidine, fenoldopam, fentanyl,
    filgrastim, fluconazole, fludarabine, fluorouracil, foscarnet, gallium nitrate,
    gemcitabine, granisetron, heparin, hetastarch in lactate electrolyte injection
    (Hextend&reg;), hydromorphone, idarubicin, leucovorin calcium, levofloxacin,
    linezolid, melphalan, meperidine, meropenem, methadone, methotrexate, mitomycin,
    morphine, ondansetron, oxaliplatin, paclitaxel, palonosetron, pemetrexed,
    piperacillin/tazobactam, quinupristin/dalfopristin, remifentanil, sargramostim,
    sufentanil, tacrolimus, telavancin, teniposide, thiotepa, tigecycline, topotecan,
    vinblastine, vincristine, vinorelbine, zidovudine.",
    " <b>",
    " Incompatible:",
    " </b>",
    " Allopurinol, amphotericin B cholesteryl sulfate complex, amsacrine, cefepime,
    doxorubicin liposome, furosemide, pantoprazole.",
    " <b>",
    " Variable (consult detailed reference):",
    " </b>",
    " Cisplatin, dexamethasone sodium phosphate, haloperidol, midazolam,
    propofol.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Compatibility in syringe: Compatible:",
    " </b>",
    " Aminophylline, ascorbic acid injection, atropine, benztropine, bleomycin,
    butorphanol, caffeine citrate, chlorpromazine, cisplatin, cyclophosphamide,
    cytarabine, dexamethasone sodium phosphate, dimenhydrinate, diphenhydramine,
    doxorubicin, droperidol, fentanyl, fentanyl with meperidine, fluorouracil, heparin,
    hydromorphone, hydroxyzine, insulin (regular), leucovorin calcium, lidocaine,
    magnesium sulfate, meperidine, methotrimeprazine, methylprednisolone sodium
    succinate, midazolam, mitomycin, morphine, ondansetron, pentazocine,
    prochlorperazine edisylate, promethazine, ranitidine, scopolamine, sufentanil,
    vinblastine, vincristine.",
    " <b>",
    " Incompatible:",
    " </b>",
    " Ampicillin, calcium gluconate, chloramphenicol, furosemide, pantoprazole,
    penicillin G potassium, sodium bicarbonate.",
    " <b>",
    " Variable (consult detailed reference):",
    " </b>",
    " Methotrexate.",
    " </p>",
    " </div>",
    " <div class=\"block sta drugH1Div\" id=\"F1060332\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Stability",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Protect from light; stable for 48 hours at room temperature when admixed with
    ascorbic acid, cimetidine (in NS only), cytarabine, dexamethasone sodium phosphate,
    diphenhydramine, doxorubicin, heparin, benztropine, dexamethasone hydrochloride,
    hydrocortisone sodium phosphate, lidocaine, magnesium sulfate, mannitol, potassium
    acetate, potassium chloride, and potassium phosphate; stable for 24 hours at room
    temperature when admixed with clindamycin (in NS only) and cyclophosphamide;
    incompatible with cephalothin, chloramphenicol, and sodium bicarbonate",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F1060339\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Treatment of gastroesophageal reflux; prevention of nausea and vomiting
    associated with chemotherapy; prevention of postoperative nausea and vomiting;
    facilitates intubation of the small intestine and symptomatic treatment of diabetic
    gastroparesis (FDA approved in adults)",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F195664\"
    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;\">",
    " Metoclopramide may be confused with metolazone, metoprolol, metroNIDAZOLE",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Reglan&reg; may be confused with Megace&reg;, Regonol&reg;, Renagel&reg;",
    " </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=\"F195661\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cardiovascular: AV block, bradycardia, HF, fluid retention, flushing
    (following high I.V. doses), hyper-/hypotension, supraventricular tachycardia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Central nervous system: Acute dystonic reactions (dose and age related),
    akathisia, confusion, depression, dizziness, drowsiness (dose related), fatigue,
    hallucinations (rare), headache, insomnia, lassitude, neuroleptic malignant
    syndrome (rare), Parkinsonian-like symptoms, restlessness, seizure, somnolence,
    suicidal ideation, tardive dyskinesia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dermatologic: Angioneurotic edema (rare), rash, urticaria",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Endocrine &amp; metabolic: Amenorrhea, galactorrhea, gynecomastia,
    hyperprolactinemia, impotence",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Gastrointestinal: Diarrhea, nausea, vomiting",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Genitourinary: Incontinence, urinary frequency",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Hematologic: Agranulocytosis, leukopenia, neutropenia, porphyria",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Hepatic: Hepatotoxicity (rare)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ocular: Visual disturbance",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Respiratory: Bronchospasm, laryngeal edema (rare), laryngospasm (rare)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Miscellaneous: Allergic reactions, methemoglobinemia, sulfhemoglobinemia",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F1060344\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to metoclopramide or any component; GI obstruction,
    pheochromocytoma, history of seizure disorder or patients receiving drugs likely to
    cause extrapyramidal reactions",
    " </p>",
    " </div>",
    " <div class=\"block pre drugH1Div\" id=\"F1060328\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Precautions",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Use with caution and reduce dosage in patients with renal impairment,
    hypertension, or depression; transient increases in plasma aldosterone may occur
    which could result in fluid retention or volume overload. Patients with CHF or
    cirrhosis of the liver may be at increased risk for development of fluid retention
    and volume overload. Use with caution in these patients and discontinue therapy if
    symptoms of excessive body fluids occurs. Abrupt discontinuation may (rarely)
    result in withdrawal symptoms (dizziness, headache, nervousness).",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F1060327\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " May cause tardive dyskinesia, which is often irreversible",
    " <b>",
    " [U.S. Boxed Warning]",
    " </b>",
    " ; duration of treatment and total cumulative dose are associated with an
    increased risk. Therapy durations &gt;12 weeks should be avoided (except in rare
    cases following risk:benefit assessment). Risk appears to be increased in the
    elderly, women, and diabetics; however, it is not possible to predict which
    patients will develop tardive dyskinesia. Therapy should be discontinued in any
    patient if signs or symptoms appear.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
    " Extrapyramidal symptoms (EPS) may occur, most frequently in children and
    young adults (&lt;30 years of age); generally manifested as acute dystonic
    reactions within the initial 24-48 hours of use; risk of these reactions is
    increased with I.V. administration of higher doses.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
    " Pseudoparkinsonism (eg, bradykinesia, tremor, rigidity) may also occur
    (usually within first 6 months of therapy) and is generally reversible following
    discontinuation. Rare reports of neuroleptic malignant syndrome; patients with
    NADH-cytochrome b5 reductase deficiency are at increased risk for developing
    methemoglobinemia and/or sulfhemoglobinemia. Neonates have prolonged clearance of
    metoclopramide which may lead to increased serum concentrations. In addition,
    neonates may have decreased NADH-cytochrome b5 reductase activity. Both conditions
    increase the risk of developing methemoglobinemia.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
    " Some products 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 displaces bilirubin from protein
    binding sites; avoid use of sodium benzoate containing products in neonates.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F195649\"
    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 CYP1A2 (minor), CYP2D6 (minor);",
    " <b>",
    " Note:",
    " </b>",
    " Assignment of Major/Minor substrate status based on clinically relevant drug
    interaction potential;",
    " <b>",
    " Inhibits",
    " </b>",
    " CYP2D6 (weak)",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F195563\"
    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;\">",
    " Anti-Parkinson's Agents (Dopamine Agonist): Metoclopramide may diminish the
    therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Antipsychotics: Metoclopramide may enhance the adverse/toxic effect of
    Antipsychotics.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CycloSPORINE (Systemic): Metoclopramide may increase the absorption of
    CycloSPORINE (Systemic).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Droperidol: May enhance the adverse/toxic effect of Metoclopramide.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Metyrosine: May enhance the adverse/toxic effect of Metoclopramide.
    Management: Seek alternatives to this combination when possible. Monitor patients
    receiving metoclopramide with metyrosine for development of extrapyramidal
    symptoms.",
    " <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 CYP2D6
    Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Posaconazole: Metoclopramide may decrease the serum concentration of
    Posaconazole.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic
    effect of Prilocaine. Combinations of these agents may increase the likelihood of
    significant methemoglobinemia. Management: Monitor patients for signs of
    methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination
    with other agents associated with development of methemoglobinemia. Avoid
    lidocaine/prilocaine in infants receiving such agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Promethazine: Metoclopramide may enhance the adverse/toxic effect of
    Promethazine.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Quinagolide: Metoclopramide may diminish the therapeutic effect of
    Quinagolide.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Selective Serotonin Reuptake Inhibitors: Metoclopramide may enhance the
    adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek
    alternatives to this combination when possible. Monitor patients receiving
    metoclopramide with selective serotonin reuptake inhibitors for signs of
    extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Serotonin Modulators: May enhance the adverse/toxic effect of Metoclopramide.
    This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic
    malignant syndrome.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tetrabenazine: Metoclopramide may enhance the adverse/toxic effect of
    Tetrabenazine.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tricyclic Antidepressants: Metoclopramide may enhance the adverse/toxic
    effect of Tricyclic Antidepressants. Management: Seek alternatives to this
    combination when possible. Monitor patients receiving metoclopramide with tricyclic
    antidepressants for signs of extrapyramidal symptoms, neuroleptic malignant
    syndrome, and serotonin syndrome.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Trimetazidine: Metoclopramide may enhance the adverse/toxic effect of
    Trimetazidine. Specifically, the risk of extrapyramidal symptoms may be enhanced.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Venlafaxine: Metoclopramide may enhance the adverse/toxic effect of
    Venlafaxine. Specifically, the risk of serotonin syndrome may be increased.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F195566\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " B (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F195581\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Teratogenic effects were not observed in animal studies; however, there are
    no adequate and well-controlled studies in pregnant women. Crosses the placenta;
    available evidence suggests safe use during pregnancy.",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F1060335\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Renal function; blood pressure and heart rate (when rapid I.V. administration
    is used)",
    " </p>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F1060326\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Potent dopamine receptor antagonist; blocks dopamine receptors in
    chemoreceptor trigger zone of the CNS, preventing emesis; accelerates gastric
    emptying and intestinal transit time without stimulating gastric, biliary, or
    pancreatic secretions",
    " </p>",
    " </div>",
    " <div class=\"block phd drugH1Div\" id=\"F1060342\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Onset of action:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Oral: Within 30-60 minutes",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " I.M.: Within 10-15 minutes",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " I.V.: Within 1-3 minutes",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Duration: Therapeutic effects persist for 1-2 hours, regardless of route
    administered",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F1060343\"
    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: Oral: Rapid",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Distribution: V",
    " <sub>",
    " d",
    " </sub>",
    " : 3.5 L/kg; crosses the placenta; appears in breast milk; breast milk to
    plasma ratio: 0.5-4.06",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Protein binding: ~30%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Bioavailability: Oral: 80 &plusmn; 15.5%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Half-life: Normal renal function:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Adults: 5-6 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children: ~4 hours (half-life and clearance may be dose-dependent)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Elimination: Primarily in the urine (~85%) and feces",
    " </p>",
    " </div>",
    " <div class=\"block pai drugH1Div\" id=\"F1060334\"
    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?33/45/34517?
    source=see_link\">",
    " see \"Metoclopramide: Patient drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " May cause drowsiness and impair ability to perform activities requiring
    mental alertness or physical coordination",
    " </p>",
    " </div>",
    " <div class=\"block adi drugH1Div\" id=\"F7788728\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Additional Information",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " In February 2009, the U.S. Food and Drug Administration (FDA) notified
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    movements of the body). Current labeling warns of the risk, but the warning will
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    and continued spontaneous reports of tardive dyskinesia to the FDA. The majority of
    reports are associated with higher doses, long-term use (&gt;3 months), and use in
    the elderly, particularly older women. Metoclopramide-induced tardive dyskinesia
    symptoms include impaired movement of the fingers, lip smacking, rapid eye
    movements or blinking, and tongue protrusion. These symptoms are rarely reversible
    following discontinuation of metoclopramide and treatment is not available at this
    time. The FDA is also requiring manufacturers to provide a medication guide to
    patients discussing the risk of tardive dyskinesia. Additional information can be
    found at",
    " <a
    href=\"file://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMed
    icalProducts/ucm106942.htm\" target=\"_blank\">",
    "
    file://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalPro
    ducts/ucm106942.htm",
    " </a>",
    " .",
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    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " Chicella MF, Batres LA, Heesters MS, et al, \"Prokinetic Drug Therapy in
    Children: A Review of Current Options,\"",
    " <i>",
    " Ann Pharmacother",
    " </i>",
    " , 2005, 39(4):706-11.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/47/759/abstract-text/15755792/pubmed\" id=\"15755792\"
    target=\"_blank\">",
    " 15755792",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Kearns GL, van den Anker JN, Reed MD, et al, \"Pharmacokinetics of
    Metoclopramide in Neonates,\"",
    " <i>",
    " J Clin Pharmacol",
    " </i>",
    " , 1998, 38(2):122-8.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/47/759/abstract-text/9549642/pubmed\" id=\"9549642\"
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    " 9549642",
    " </a>",
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    var title_f0_47_760="Management of gynecomastia";
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    " Management of gynecomastia",
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    " Author",
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    0/47/760/contributors\">",
    " Glenn D Braunstein, MD",
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    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Gynecomastia, a benign proliferation of the glandular
    tissue of the male breast, is caused by an increase in the ratio of estrogen to
    androgen activity. It is categorized as physiologic (occurring normally during
    infancy, puberty, and older age), or pathologic (due to drugs or disorders such as
    androgen deficiency, testicular tumors, hyperthyroidism, and chronic kidney
    disease). In adult men, 50 percent of cases of gynecomastia are due to persistent
    pubertal gynecomastia or medications, and an additional 25 percent are idiopathic
    (",
    " <a class=\"graphic graphic_table graphicRef53468 \" href=\"UTD.htm?
    41/21/42331\">",
    " table 1",
    " </a>",
    " )&nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/1,2\">",
    " 1,2",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " True gynecomastia should be differentiated from pseudogynecomastia, which
    refers to fat deposition without glandular proliferation. Gynecomastia must also be
    differentiated from breast carcinoma, which is far less common.",
    " </p>",
    " <p>",
    " The management of gynecomastia will be reviewed here. The epidemiology,
    pathogenesis, causes, and evaluation of gynecomastia are discussed separately.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/9/6294?
    source=see_link\">",
    " \"Epidemiology and pathogenesis of gynecomastia\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/47/27384?
    source=see_link\">",
    " \"Causes and evaluation of gynecomastia\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " GENERAL PRINCIPLES",
    " </span>",
    " &nbsp;&mdash;&nbsp;The management of gynecomastia depends upon its etiology,
    duration, severity, and presence or absence of tenderness. In many cases,
    gynecomastia resolves without therapy.",
    " </p>",
    " <p>",
    " The breast examination method used to determine the amount of glandular tissue
    present and to distinguish true gynecomastia from pseudogynecomastia is discussed
    separately (",
    " <a class=\"graphic graphic_figure graphicRef72334 \" href=\"UTD.htm?
    19/17/19730\">",
    " figure 1",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/47/27384?
    source=see_link&amp;anchor=H19#H19\">",
    " \"Causes and evaluation of gynecomastia\", section on 'Evaluation'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Spontaneous regression",
    " </span>",
    " &nbsp;&mdash;&nbsp;Gynecomastia of recent onset (less than six months) in both
    adolescents and adults will often regress spontaneously [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/3\">",
    " 3",
    " </a>",
    " ]. Thus, observation alone is a reasonable approach in most patients.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h3\">",
    " Pubertal gynecomastia",
    " </span>",
    " &nbsp;&mdash;&nbsp;Pubertal gynecomastia, a benign, physiologic process, is
    common in adolescent boys, often developing between ages 10 and 12 years, with a
    peak prevalence of 65 percent between ages 13 and 14, followed by regression in 85
    to 90 percent within six months to two years. Its persistence beyond age 17 is
    uncommon (",
    " <a class=\"graphic graphic_figure graphicRef64368 \" href=\"UTD.htm?
    23/42/24238\">",
    " figure 2",
    " </a>",
    " ).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h3\">",
    " Adults",
    " </span>",
    " &nbsp;&mdash;&nbsp;Regression of gynecomastia is also common in adults. In one
    report, regression of breast tissue occurred in 85 percent of adult men with
    gynecomastia due to various causes [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/3\">",
    " 3",
    " </a>",
    " ]. In contrast, in therapeutic trials, complete spontaneous regression in men
    receiving placebo or no therapy is much less frequent. (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Drug therapy'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " Pain is usually not severe. Varying degrees of tenderness and nipple
    sensitivity with rubbing against a shirt are more common than pain, and if severe,
    these symptoms may be indications for earlier therapeutic intervention, even though
    these symptoms are usually self-limited as fibrotic changes occur after 6 to 12
    months. (See",
    " <a class=\"local\" href=\"#H6\">",
    " 'Duration of gynecomastia'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " In men with gynecomastia due to medication or an underlying treatable disorder
    such as hypogonadism or hyperthyroidism, observation with follow-up breast
    examinations is a reasonable approach once the medication is stopped",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " the underlying disease has been treated.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Duration of gynecomastia",
    " </span>",
    " &nbsp;&mdash;&nbsp;A major factor that should influence the initial approach
    is the duration of gynecomastia. Histologic studies show that the glandular changes
    in the breast are the same regardless of etiology, and that the extent of glandular
    proliferation depends upon the intensity and duration of the stimulation. The
    histologic picture changes over time with ductal hyperplasia and periductal
    inflammation in the early stages (first six months). During this time period,
    gynecomastia is the most symptomatic and also most treatable. Later fibrosis and
    disappearance of the inflammatory reaction is found at 12 or more months (",
    " <a class=\"graphic graphic_picture graphicRef57619 graphicRef62060 \"
    href=\"UTD.htm?6/19/6458\">",
    " picture 1A-B",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/9/6294?
    source=see_link&amp;anchor=H9#H9\">",
    " \"Epidemiology and pathogenesis of gynecomastia\", section on 'Histology'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " It is unlikely that any medical therapy will result in significant regression
    in the late fibrotic stage. As a result, medical therapies, if used, should be
    tried early in the course.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Avoidance of offending drugs",
    " </span>",
    " &nbsp;&mdash;&nbsp;The simplest method to prevent or manage gynecomastia is to
    avoid or discontinue those drugs that cause it (",
    " <a class=\"graphic graphic_table graphicRef71421 \" href=\"UTD.htm?
    20/35/21053\">",
    " table 2",
    " </a>",
    " ). The risk associated with these drugs is variable. Gynecomastia will occur
    in approximately 10 percent of men receiving 25 mg per day of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?17/22/17767?source=see_link\">",
    " spironolactone",
    " </a>",
    " &nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/4\">",
    " 4",
    " </a>",
    " ], and in over 50 percent of those receiving antiandrogens for advanced
    prostate cancer (see",
    " <a class=\"local\" href=\"#H16\">",
    " 'Prostate cancer'",
    " </a>",
    " below).",
    " </p>",
    " <p>",
    " The breast enlargement that is seen in men with HIV receiving highly active
    antiretroviral therapy (HAART) is usually pseudogynecomastia due to lipodystrophy.
    Cases of true gynecomastia have also been described and are thought to be due to
    coexisting hypogonadism or medications, specifically nucleoside reverse
    transcriptase inhibitors such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " efavirenz",
    " </a>",
    " . In case reports, the gynecomastia resolved when efavirenz was discontinued
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/5,6\">",
    " 5,6",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/47/27384?
    source=see_link&amp;anchor=H6#H6\">",
    " \"Causes and evaluation of gynecomastia\", section on 'HAART'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/43/26298?
    source=see_link\">",
    " \"Epidemiology, clinical manifestations, and diagnosis of HIV-associated
    lipodystrophy\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/36/44617?
    source=see_link\">",
    " \"Treatment of HIV-associated lipodystrophy\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The incidence of gynecomastia differs within the same class of drugs:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The calcium channel blockers,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/18/9514?source=see_link\">",
    " verapamil",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?12/5/12377?
    source=see_link\">",
    " nifedipine",
    " </a>",
    " , have the highest frequencies of gynecomastia and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?12/16/12554?
    source=see_link\">",
    " diltiazem",
    " </a>",
    " the lowest [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Among H2-receptor blockers, the incidence of gynecomastia is highest with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?2/54/2921?source=see_link\">",
    " cimetidine",
    " </a>",
    " and lower with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?41/56/42888?
    source=see_link\">",
    " ranitidine",
    " </a>",
    " . Among the proton-pump inhibitors, the frequency with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/62/26601?
    source=see_link\">",
    " omeprazole",
    " </a>",
    " is higher than with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?3/14/3305?source=see_link\">",
    " lansoprazole",
    " </a>",
    " &nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/7\">",
    " 7",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Aldosterone antagonists, the frequency of gynecomastia is highest with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?17/22/17767?
    source=see_link\">",
    " spironolactone",
    " </a>",
    " , but much lower with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?4/58/5031?source=see_link\">",
    " eplerenone",
    " </a>",
    " , which is a much more selective aldosterone antagonist [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/8\">",
    " 8",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/47/27384?
    source=see_link\">",
    " \"Causes and evaluation of gynecomastia\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/54/28521?
    source=see_link\">",
    " \"Use of aldosterone antagonists in heart failure\"",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Breast cancer risk",
    " </span>",
    " &nbsp;&mdash;&nbsp;Men with gynecomastia due to Klinefelter's syndrome are at
    increased risk for breast cancer. Although routine mammography is not currently
    recommended, yearly breast exams should be done. A mammogram should be performed
    for any nipple discharge, palpable masses, or visual abnormalities that are not
    consistent with simple gynecomastia (",
    " <a class=\"graphic graphic_figure graphicRef72334 \" href=\"UTD.htm?
    19/17/19730\">",
    " figure 1",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/47/27384?
    source=see_link\">",
    " \"Causes and evaluation of gynecomastia\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h1\">",
    " TREATMENT",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h2\">",
    " Observation only",
    " </span>",
    " &nbsp;&mdash;&nbsp;As noted above, gynecomastia often regresses spontaneously,
    so observation alone is the initial step for most adolescents, and also for most
    men, after stopping offending medications",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " treating any underlying disorders. (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'Spontaneous regression'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " However, a trial of medical therapy is reasonable in the occasional boy with
    severe breast enlargement that is true gynecomastia and that is causing substantial
    pain, tenderness,",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " embarrassment. (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Drug therapy'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " Potential indications for early therapy include severe breast enlargement,
    pain, tenderness, and embarrassment that interferes with the patient's normal daily
    activities. Intervention may also be needed in patients with persistent
    gynecomastia, including those with pubertal gynecomastia that persists into later
    adolescence or early adulthood.",
    " </p>",
    " <p>",
    " Treatment options include drug therapy and surgical removal of breast
    glandular tissue [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/9,10\">",
    " 9,10",
    " </a>",
    " ]. Medical therapy may be effective in the early, active phase of
    gynecomastia, but not in the late fibrotic stage. In contrast, surgery is typically
    performed when the fibrotic stage has been reached. (See",
    " <a class=\"local\" href=\"#H6\">",
    " 'Duration of gynecomastia'",
    " </a>",
    " above.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Drug therapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Three types of medications have been tried, but clinical
    trial data are limited for each: androgens, selective estrogen receptor modulators,
    and aromatase inhibitors. None induce complete regression of gynecomastia, but may
    induce partial regression and relief of tenderness. None have been approved by the
    FDA for the treatment of gynecomastia.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h3\">",
    " Androgens",
    " </span>",
    " &nbsp;&mdash;&nbsp;Testosterone replacement in hypogonadal men often improves
    gynecomastia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/9,11,12\">",
    " 9,11,12",
    " </a>",
    " ], but there is no rationale for its use in eugonadal men, in whom it may
    actually worsen the gynecomastia due to aromatization of the testosterone to
    estradiol.",
    " </p>",
    " <p>",
    " The nonaromatizable androgen, dihydrotestosterone (DHT), has been reported to
    be effective for gynecomastia in uncontrolled studies [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/13,14\">",
    " 13,14",
    " </a>",
    " ] and has been approved for this use in some countries but not the United
    States.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h3\">",
    " Selective estrogen receptor modulators",
    " </span>",
    " &nbsp;&mdash;&nbsp;Although clinical trial data are limited, the selective
    estrogen receptor modulators (SERMs)",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
    " tamoxifen",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/15/6390?source=see_link\">",
    " raloxifene",
    " </a>",
    " appear to decrease breast volume in adolescents and adults with gynecomastia.
    However, complete breast regression is usually not achieved with this approach.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Pubertal gynecomastia &mdash; A retrospective review evaluated patients with
    persistent pubertal gynecomastia who received either",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/15/6390?source=see_link\">",
    " raloxifene",
    " </a>",
    " (60",
    " <span class=\"nowrap\">",
    " mg/day,",
    " </span>",
    " n = 10) or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
    source=see_link\">",
    " tamoxifen",
    " </a>",
    " (10 to 20",
    " <span class=\"nowrap\">",
    " mg/day,",
    " </span>",
    " n = 15) for three to nine months [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/15\">",
    " 15",
    " </a>",
    " ]. Approximately 90 percent of patients in both groups reported a decrease
    in gynecomastia, but more patients treated with raloxifene experienced a &ge;50
    percent reduction in the breast glandular tissue (86 versus 41 percent). Only 3 of
    the 10 patients in the raloxifene group and 1 of 15 patients in the tamoxifen group
    had complete resolution of the gynecomastia in both breasts. Forty percent of the
    patients in each group were not satisfied with the results and underwent surgical
    removal of the tissue. No conclusions can be drawn about the efficacy of the drugs
    compared to no treatment or placebo.",
    " <br/>",
    " <br/>",
    " SERM therapy is usually used for pubertal boys with severe gynecomastia,
    which is often associated with tenderness. However, the degree of breast
    enlargement and symptoms that trigger treatment are dependent upon the perception
    of boys and their parents. The typical doses used are the same as in the few
    studies described above (tamoxifen 10 to 20",
    " <span class=\"nowrap\">",
    " mg/day,",
    " </span>",
    " raloxifene 60",
    " <span class=\"nowrap\">",
    " mg/day).",
    " </span>",
    " </li>",
    " <li>",
    " Gynecomastia in adults &mdash; In two trials that included 16 men with
    gynecomastia who were randomly assigned to receive",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
    source=see_link\">",
    " tamoxifen",
    " </a>",
    " (10 mg twice daily) or placebo, there was a statistically significant
    reduction in tenderness and breast size with tamoxifen but no patient experienced
    complete remission [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/16,17\">",
    " 16,17",
    " </a>",
    " ]. Side effects were minimal in these trials, although epigastric distress
    and nausea have sometimes been noted.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " In summary, although SERMs do not result in complete regression of breast
    tissue, they may be effective for patients with painful gynecomastia. We use SERMs
    for men with severe gynecomastia (usually cosmetically bothersome) that is tender
    or painful (usually present for 6 to 12 months or less), prior to considering
    surgery. We typically use",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
    " tamoxifen",
    " </a>",
    " since it is the best studied of the SERMs and is reasonably well-tolerated.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h3\">",
    " Aromatase inhibitors",
    " </span>",
    " &nbsp;&mdash;&nbsp;Aromatase inhibitors block estrogen biosynthesis, and
    should theoretically be effective for gynecomastia by decreasing the estrogen to
    androgen ratio [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/18\">",
    " 18",
    " </a>",
    " ]. However, clinical trials to date have not demonstrated an important
    clinical benefit of these drugs for gynecomastia, in either adolescents or men with
    prostate cancer. The reason for this is unknown. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/9/6294?
    source=see_link&amp;anchor=H8#H8\">",
    " \"Epidemiology and pathogenesis of gynecomastia\", section on 'Imbalance
    between estrogen and androgen'",
    " </a>",
    " and",
    " <a class=\"local\" href=\"#H16\">",
    " 'Prostate cancer'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " The best data on aromatase inhibitors come from a double-blind, placebo
    controlled trial of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?21/49/22294?source=see_link\">",
    " anastrozole",
    " </a>",
    " (1 mg daily for six months) in 80 boys with pubertal gynecomastia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/19\">",
    " 19",
    " </a>",
    " ]. The percentage of patients with a significant reduction in breast volume
    (defined as &gt;50 percent by ultrasound)",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " with relief of tenderness was similar in the anastrozole and placebo groups.",
    " </p>",
    " <p>",
    " Based upon the available data, we do not suggest using aromatase inhibitors in
    boys with pubertal gynecomastia. Their use in men with prostate cancer undergoing
    antiandrogen therapy is discussed below. (See",
    " <a class=\"local\" href=\"#H26\">",
    " 'Prostate cancer patients'",
    " </a>",
    " below.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h2\">",
    " Surgery",
    " </span>",
    " &nbsp;&mdash;&nbsp;Surgical therapy should be considered for patients whose
    gynecomastia does not regress spontaneously or with medical therapy, is causing
    considerable discomfort or psychological distress, or is long-standing (greater
    than 12 months) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/10,20\">",
    " 10,20",
    " </a>",
    " ]. However, for adolescents, surgery is generally not recommended until adult
    testicular size is attained, as there may be regrowth of the breast tissue if the
    surgery is performed before puberty is substantially completed.",
    " </p>",
    " <p>",
    " The extent of surgery depends upon the severity of the breast enlargement and
    whether there is also excess adipose tissue present. Many patients are treated with
    a combination of direct surgical excision of the glandular tissue and liposuction
    through a periareolar incision of any coexisting adipose tissue [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/10,20,21\">",
    " 10,20,21",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " More extensive cosmetic surgery, including skin excision, is required for
    patients with marked gynecomastia or who develop excessive sagging of the breast
    tissue, as occurs with weight loss [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/20,22,23\">",
    " 20,22,23",
    " </a>",
    " ]. A transverse ellipse of excessive skin, fat, and glandular tissue is
    excised and the nipple-areola complex is removed as a full thickness graft and
    replaced in the appropriate anatomic position following removal of the redundant
    tissue [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/22\">",
    " 22",
    " </a>",
    " ]. Alternatively, the nipple-areola complex may remain attached to the
    surrounding dermis and blood supply and be rotated upward into its proper position
    after the excessive tissue is excised.",
    " </p>",
    " <p>",
    " Potential complications of surgical therapy for gynecomastia include sloughing
    of tissue due to compromise of the blood supply, contour irregularity, hematoma or
    seroma formation, and numbness of the nipple-areolar area [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/10,21-25\">",
    " 10,21-25",
    " </a>",
    " ]. However, when surgery is performed by an experienced cosmetic surgeon,
    complication rates are low, as illustrated in a series of 107 men with gynecomastia
    treated in one center [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/21\">",
    " 21",
    " </a>",
    " ]. Only one patient had a postoperative complication (dehiscence of the
    surgical wound). All but 2 of the 107 patients were considered to have a
    satisfactory cosmetic result (excellent in 94, good in 11).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h1\">",
    " PROSTATE CANCER",
    " </span>",
    " &nbsp;&mdash;&nbsp;Gynecomastia is common in men with prostate cancer
    undergoing androgen deprivation therapy. The prevalence of gynecomastia is
    approximately 15 percent in men treated with gonadotropin-releasing hormone (GnRH)
    agonists combined with an antiandrogen. The risk of gynecomastia is reduced with
    total androgen blockade with a GnRH analogue and an antiandrogen [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/26\">",
    " 26",
    " </a>",
    " ]. However, the prevalence is as high as 75 percent when antiandrogen
    monotherapy is used [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/27-29\">",
    " 27-29",
    " </a>",
    " ]. Much higher doses of antiandrogens are used for monotherapy (eg,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/2/30758?source=see_link\">",
    " bicalutamide",
    " </a>",
    " 150 mg versus 50 mg if combined with a GnRH agonist). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/12/10442?
    source=see_link&amp;anchor=H16#H16\">",
    " \"Overview of the treatment of disseminated prostate cancer\", section on
    'Side effects of ADT'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Both drug therapy and radiotherapy (RT) have limited benefit once gynecomastia
    is established in this setting; as a result, prevention of breast development is
    the goal of therapy. Strategies that have been used for prevention include
    pharmacologic therapy (antiestrogens or aromatase inhibitors) or radiotherapy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/26,30,31\">",
    " 26,30,31",
    " </a>",
    " ]. Data supports use of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
    " Tamoxifen",
    " </a>",
    " over RT, although RT is probably easier and there is no risk of tamoxifen
    altering the effectiveness of the antiandrogen. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?21/30/21993?
    source=see_link\">",
    " \"Side effects of androgen deprivation therapy\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h2\">",
    " Tamoxifen",
    " </span>",
    " &nbsp;&mdash;&nbsp;The SERM",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
    " tamoxifen",
    " </a>",
    " is effective for preventing antiandrogen-associated gynecomastia, as
    illustrated in three trials of men with prostate cancer receiving high dose (150",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/2/30758?source=see_link\">",
    " bicalutamide",
    " </a>",
    " alone or with tamoxifen (10 to 20",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/31-33\">",
    " 31-33",
    " </a>",
    " ]. Gynecomastia occurred in 86 of 124 patients (69 percent) treated with
    bicalutamide alone compared to 11 of 122 patients (9 percent) treated with
    bicalutamide combined with tamoxifen. Tamoxifen must be continued for the duration
    of antiandrogen therapy, as its effect does not persist after it is discontinued
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/34\">",
    " 34",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h2\">",
    " Anastrozole",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?21/49/22294?source=see_link\">",
    " Anastrozole",
    " </a>",
    " reduces the incidence of antiandrogen-associated gynecomastia, but is less
    effective than",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
    " tamoxifen",
    " </a>",
    " . This was illustrated in a trial of 88 men with prostate cancer who were
    randomly assigned to",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/2/30758?source=see_link\">",
    " bicalutamide",
    " </a>",
    " alone, or bicalutamide plus either anastrozole (1",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " or tamoxifen (20",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " for 48 weeks [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/33\">",
    " 33",
    " </a>",
    " ]. Gynecomastia developed in 73, 51, and 10 percent of men receiving
    bicalutamide alone, bicalutamide with anastrozole, or bicalutamide with tamoxifen,
    respectively.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <span class=\"h2\">",
    " Radiotherapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Prophylactic radiotherapy prevents antiandrogen-associated
    gynecomastia in some, but not all, men [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/30\">",
    " 30",
    " </a>",
    " ]. In four trials of prophylactic low-dose bilateral breast radiotherapy (10
    to 15 Gy in either one fraction or over three days), gynecomastia occurred in 155
    of 215 patients (72 percent) treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/2/30758?source=see_link\">",
    " bicalutamide",
    " </a>",
    " alone compared to 105 of 322 patients (33 percent) treated with bicalutamide
    plus radiotherapy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/31,32,35,36\">",
    " 31,32,35,36",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Treatment of established gynecomastia with higher radiation doses (eg, 20 Gy
    in five fractions) may improve pain, but is less effective at reducing the volume
    of tissue [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/37\">",
    " 37",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H20\">",
    " <span class=\"h2\">",
    " Tamoxifen versus RT",
    " </span>",
    " &nbsp;&mdash;&nbsp;Concomitant therapy with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?source=see_link\">",
    " tamoxifen",
    " </a>",
    " may be more effective than prophylactic radiotherapy for preventing
    gynecomastia in men receiving high dose",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/2/30758?source=see_link\">",
    " bicalutamide",
    " </a>",
    " monotherapy (150",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " after radical prostatectomy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/31,32\">",
    " 31,32",
    " </a>",
    " ]. In one trial of 102 men, gynecomastia developed in 68, 8, and 34 percent of
    patients receiving bicalutamide alone, bicalutamide combined with tamoxifen (10",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " or prophylactic radiotherapy, respectively [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/31\">",
    " 31",
    " </a>",
    " ]. Although antiandrogen therapy may be more effective than prophylactic
    radiation in this setting (antiandrogen monotherapy), it needs to be continued for
    the duration of antiandrogen therapy, and therefore, may be less convenient for
    some patients.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H21\">",
    " <span class=\"h2\">",
    " Surgical intervention",
    " </span>",
    " &nbsp;&mdash;&nbsp;Surgical prophylaxis of gynecomastia has been described,
    but surgery (subcutaneous mastectomy, liposuction) is most often considered for
    established disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/760/abstract/28\">",
    " 28",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H15\">",
    " 'Surgery'",
    " </a>",
    " above.)",
    " </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?43/30/44513?
    source=see_link\">",
    " \"Patient information: When men develop breasts (gynecomastia) (The
    Basics)\"",
    " </a>",
    " )",
    " </li>",
    " <li>",
    " Beyond the Basics topics (see",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?40/47/41713?
    source=see_link\">",
    " \"Patient information: Gynecomastia (breast enlargement in men) (Beyond the
    Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H23\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The management of gynecomastia depends upon a number of
    factors, including its etiology, duration, severity, and presence or absence of
    tenderness. When gynecomastia persists beyond 12 months, the breast glandular
    tissue has typically become fibrotic, and medical therapy is unlikely to be
    effective. (See",
    " <a class=\"local\" href=\"#H6\">",
    " 'Duration of gynecomastia'",
    " </a>",
    " above.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H24\">",
    " <span class=\"h2\">",
    " Adolescents",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " For most adolescents with gynecomastia, we recommend observation only with
    reevaluation in three to six months, because most will experience spontaneous
    regression (",
    " <a class=\"grade\" href=\"._grade_2?title=Grade 1B\">",
    " Grade 1B",
    " </a>",
    " ).",
    " </li>",
    " <li>",
    " For boys with severe breast enlargement that is confirmed to be glandular
    tissue and is causing substantial tenderness",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " embarrassment, we suggest a brief trial (three months) of a SERM (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). We currently use",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
    source=see_link\">",
    " tamoxifen",
    " </a>",
    " (10 mg twice daily) because there is inadequate experience with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/15/6390?source=see_link\">",
    " raloxifene",
    " </a>",
    " in this population. Patients and parents should be told that these drugs are
    not approved for this purpose.",
    " </li>",
    " <li>",
    " We suggest not using aromatase inhibitors, because they do not appear to be
    effective (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ).",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H25\">",
    " <span class=\"h2\">",
    " Men",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " For most men with gynecomastia, we suggest initial observation only with
    follow-up reevaluation (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ), especially in men with drug-induced gynecomastia or men with an
    underlying treatable disorder such as hypogonadism or hyperthyroidism, once the
    drug has been stopped",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " the underlying disorder has been treated.",
    " </li>",
    " <li>",
    " For men in whom no cause can be identified and the gynecomastia is tender
    and persists more than three months, we suggest a brief trial (three to six months)
    of a SERM for relief of tenderness (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). We currently use",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
    source=see_link\">",
    " tamoxifen",
    " </a>",
    " (10 mg twice daily) because there is inadequate experience with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/15/6390?source=see_link\">",
    " raloxifene",
    " </a>",
    " . Patients should be told that SERMs are not approved for this purpose. We
    suggest not using aromatase inhibitors, as they do not appear to be effective (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ).",
    " </li>",
    " <li>",
    " In men with persistent gynecomastia (&gt;one to two years) that the patient
    finds troubling psychologically, we suggest surgery, because the breast tissue has
    probably become fibrotic and unresponsive to drug therapy (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ).",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H26\">",
    " <span class=\"h3\">",
    " Prostate cancer patients",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " For prevention of gynecomastia in men with advanced prostate cancer
    undergoing high dose antiandrogen monotherapy, we suggest",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
    source=see_link\">",
    " tamoxifen",
    " </a>",
    " therapy to reduce the risk of developing gynecomastia (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ). Prophylactic radiation is a reasonable alternative for men who value the
    convenience of a short-term radiation intervention over the inconvenience and
    possible side effects of a daily medication.",
    " </li>",
    " <li>",
    " We suggest not using aromatase inhibitors for prevention, because they do
    not appear to be effective in this setting (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ).",
    " </li>",
    " <li>",
    " For men who have already developed gynecomastia on antiandrogen therapy, we
    suggest",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/27/33208?
    source=see_link\">",
    " tamoxifen",
    " </a>",
    " therapy (if it is of recent onset, and likely to be in its proliferative
    phase) (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ).",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
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    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/3\">",
    " TREVES N. Gynecomastia; the origins of mammary swelling in the male: an
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    " Dobs AS, Meikle AW, Arver S, et al. Pharmacokinetics, efficacy, and safety
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    " </a>",
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    " Kuhn JM, Roca R, Laudat MH, et al. Studies on the treatment of idiopathic
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/15\">",
    " Lawrence SE, Faught KA, Vethamuthu J, Lawson ML. Beneficial effects of
    raloxifene and tamoxifen in the treatment of pubertal gynecomastia. J Pediatr 2004;
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    " Parker LN, Gray DR, Lai MK, Levin ER. Treatment of gynecomastia with
    tamoxifen: a double-blind crossover study. Metabolism 1986; 35:705.",
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    " McDermott MT, Hofeldt FD, Kidd GS. Tamoxifen therapy for painful idiopathic
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    " Braunstein GD. Aromatase and gynecomastia. Endocr Relat Cancer 1999;
    6:315.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/19\">",
    " Plourde PV, Reiter EO, Jou HC, et al. Safety and efficacy of anastrozole for
    the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-
    controlled trial. J Clin Endocrinol Metab 2004; 89:4428.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/20\">",
    " Cordova A, Moschella F. Algorithm for clinical evaluation and surgical
    treatment of gynaecomastia. J Plast Reconstr Aesthet Surg 2008; 61:41.",
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    " Gioffr&egrave; Florio MA, Alfio AR, Fam&agrave; F, et al. [Evaluation of
    complications and long-term results after surgery for gynaecomastia]. Chir Ital
    2004; 56:113.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/22\">",
    " El-Khatib HA. A single stage liposuction and dermopexy for grade 3b and
    grade 4 pseudogynecomastia after massive weight loss: an observational study. Int J
    Surg 2007; 5:155.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/23\">",
    " Tashkandi M, Al-Qattan MM, Hassanain JM, et al. The surgical management of
    high-grade gynecomastia. Ann Plast Surg 2004; 53:17.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/24\">",
    " Steele SR, Martin MJ, Place RJ. Gynecomastia: complications of the
    subcutaneous mastectomy. Am Surg 2002; 68:210.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/25\">",
    " Mentz HA, Ruiz-Razura A, Newall G, et al. Correction of gynecomastia through
    a single puncture incision. Aesthetic Plast Surg 2007; 31:244.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/26\">",
    " Di Lorenzo G, Autorino R, Perdon&agrave; S, De Placido S. Management of
    gynaecomastia in patients with prostate cancer: a systematic review. Lancet Oncol
    2005; 6:972.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/27\">",
    " Chang A, Yeap B, Davis T, et al. Double-blind, randomized study of primary
    hormonal treatment of stage D2 prostate carcinoma: flutamide versus
    diethylstilbestrol. J Clin Oncol 1996; 14:2250.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/28\">",
    " Dobs A, Darkes MJ. Incidence and management of gynecomastia in men treated
    for prostate cancer. J Urol 2005; 174:1737.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/29\">",
    " Schr&ouml;der FH, Collette L, de Reijke TM, Whelan P. Prostate cancer
    treated by anti-androgens: is sexual function preserved? EORTC Genitourinary Group.
    European Organization for Research and Treatment of Cancer. Br J Cancer 2000;
    82:283.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/30\">",
    " Dicker AP. The safety and tolerability of low-dose irradiation for the
    management of gynaecomastia caused by antiandrogen monotherapy. Lancet Oncol 2003;
    4:30.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/31\">",
    " Di Lorenzo G, Perdon&agrave; S, De Placido S, et al. Gynecomastia and breast
    pain induced by adjuvant therapy with bicalutamide after radical prostatectomy in
    patients with prostate cancer: the role of tamoxifen and radiotherapy. J Urol 2005;
    174:2197.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/32\">",
    " Perdon&agrave; S, Autorino R, De Placido S, et al. Efficacy of tamoxifen and
    radiotherapy for prevention and treatment of gynaecomastia and breast pain caused
    by bicalutamide in prostate cancer: a randomised controlled trial. Lancet Oncol
    2005; 6:295.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/33\">",
    " Boccardo F, Rubagotti A, Battaglia M, et al. Evaluation of tamoxifen and
    anastrozole in the prevention of gynecomastia and breast pain induced by
    bicalutamide monotherapy of prostate cancer. J Clin Oncol 2005; 23:808.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/34\">",
    " Fradet Y, Egerdie B, Andersen M, et al. Tamoxifen as prophylaxis for
    prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg
    monotherapy in patients with prostate cancer: a randomised, placebo-controlled,
    dose-response study. Eur Urol 2007; 52:106.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/35\">",
    " Tyrrell CJ, Payne H, Tammela TL, et al. Prophylactic breast irradiation with
    a single dose of electron beam radiotherapy (10 Gy) significantly reduces the
    incidence of bicalutamide-induced gynecomastia. Int J Radiat Oncol Biol Phys 2004;
    60:476.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/36\">",
    " Widmark A, Foss&aring; SD, Lundmo P, et al. Does prophylactic breast
    irradiation prevent antiandrogen-induced gynecomastia? Evaluation of 253 patients
    in the randomized Scandinavian trial SPCG-7/SFUO-3. Urology 2003; 61:145.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/760/abstract/37\">",
    " Chou JL, Easley JD, Feldmeier JJ, et al. Effective radiotherapy in
    palliating mammalgia associated with gynecomastia after DES therapy. Int J Radiat
    Oncol Biol Phys 1988; 15:749.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
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    " Topic 7467 Version 5.0",
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    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H23\" 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\">",
    " GENERAL PRINCIPLES",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " Spontaneous regression",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " - Pubertal gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " - Adults",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " Duration of gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " Avoidance of offending drugs",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Breast cancer risk",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " Observation only",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " Drug therapy",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " - Androgens",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " - Selective estrogen receptor modulators",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " - Aromatase inhibitors",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " Surgery",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " PROSTATE CANCER",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " Tamoxifen",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " Anastrozole",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H19\">",
    " Radiotherapy",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H20\">",
    " Tamoxifen versus RT",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H21\">",
    " Surgical intervention",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H23\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H24\">",
    " Adolescents",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H25\">",
    " Men",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H26\">",
    " - Prostate cancer patients",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"ENDO/7467\" 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=\"ENDO/7467|FIG\">",
    " <a href=\"#\" title=\"FIGURES\">",
    " FIGURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?19/17/19730\"
    title=\"figure 1\">",
    " Exam for gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?23/42/24238\"
    title=\"figure 2\">",
    " Prevalence of gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"ENDO/7467|PIC\">",
    " <a href=\"#\" title=\"PICTURES\">",
    " PICTURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?11/33/11793\"
    title=\"picture 1A\">",
    " Normal breast histology",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?28/9/28824\"
    title=\"picture 1B\">",
    " Florid stage of gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"ENDO/7467|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?41/21/42331\" title=\"table
    1\">",
    " Causes of gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?20/35/21053\" title=\"table
    2\">",
    " Drugs and gynecomastia",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/47/27384?
    source=related_link\">",
    " Causes and evaluation of gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/9/6294?
    source=related_link\">",
    " Epidemiology and pathogenesis of gynecomastia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/43/26298?
    source=related_link\">",
    " Epidemiology, clinical manifestations, and diagnosis of HIV-associated
    lipodystrophy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/12/10442?
    source=related_link\">",
    " Overview of the treatment of disseminated prostate cancer",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?40/47/41713?
    source=related_link\">",
    " Patient information: Gynecomastia (breast enlargement in men) (Beyond the
    Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?43/30/44513?
    source=related_link\">",
    " Patient information: When men develop breasts (gynecomastia) (The Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?21/30/21993?
    source=related_link\">",
    " Side effects of androgen deprivation therapy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/36/44617?
    source=related_link\">",
    " Treatment of HIV-associated lipodystrophy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/54/28521?
    source=related_link\">",
    " Use of aldosterone antagonists in heart failure",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_47_761="Gentamicin (systemic): Drug information";
    var content_f0_47_761=[" <noscript>",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Gentamicin (systemic): 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?18/8/18564?source=see_link\">",
    " see \"Gentamicin (systemic): Patient drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/63/8185?source=see_link\">",
    " see \"Gentamicin (systemic): Pediatric drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"block black-box-warn drugH1Div\" id=\"F8107079\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " ALERT: U.S. Boxed Warning",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " The FDA-approved labeling includes a boxed warning. See Warnings/Precautions
    section for a concise summary of this information. For verbatim wording of the
    boxed warning, consult the product labeling or",
    " <a href=\"file://www.fda.gov\" target=\"_blank\">",
    " www.fda.gov",
    " </a>",
    " .",
    " </p>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F8107109\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Gentamicin Injection, USP",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F8107344\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacologic Category",
    " </span>",
    " <ul>",
    " <li>",
    " Antibiotic, Aminoglycoside",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block doa drugH1Div\" id=\"F8107267\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Adult",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Individualization is",
    " <b>",
    " critical",
    " </b>",
    " because of the low therapeutic index.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be
    more accurate than dosing on the basis of total body weight (TBW).",
    " </b>",
    " In morbid obesity, dosage requirement may best be estimated using a dosing
    weight of IBW + 0.4 (TBW - IBW).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Initial and periodic plasma drug levels (eg, peak and trough with
    conventional dosing) should be determined, particularly in critically-ill patients
    with serious infections or in disease states known to significantly alter
    aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <b>",
    " Usual dosage ranges:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " I.M., I.V.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Conventional: 1-2.5 mg/kg/dose every 8-12 hours; to ensure adequate peak
    concentrations early in therapy, higher initial dosage may be considered in
    selected patients when extracellular water is increased (edema, septic shock,
    postsurgical, or trauma)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Once daily: 4-7 mg/kg/dose once daily; some clinicians recommend this
    approach for all patients with normal renal function; this dose is at least as
    efficacious with similar, if not less, toxicity than conventional dosing",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Intrathecal: 4-8 mg/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;\">",
    " <b>",
    " Indication-specific dosing:",
    " </b>",
    " I.M., I.V.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Brucellosis:",
    " </b>",
    " 240 mg (I.M.) daily or 5 mg/kg (I.V.) daily for 7 days; either regimen
    recommended in combination with doxycycline",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Cholangitis:",
    " </b>",
    " 4-6 mg/kg once daily with ampicillin",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Diverticulitis (complicated):",
    " </b>",
    " 1.5-2 mg/kg every 8 hours (with ampicillin and metronidazole)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <b>",
    " Endocarditis:",
    " </b>",
    " Treatment: 3 mg/kg/day in 1-3 divided doses",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Meningitis",
    " </b>",
    " <b>",
    " <i>",
    " Enterococcus",
    " </i>",
    " </b>",
    " <b>",
    " sp or",
    " </b>",
    " <b>",
    " <i>",
    " Pseudomonas aeruginosa:",
    " </i>",
    " </b>",
    " I.V.: Loading dose 2 mg/kg, then 1.7 mg/kg/dose every 8 hours (administered
    with another bacteriocidal drug)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Pelvic inflammatory disease:",
    " </b>",
    " Loading dose: 2 mg/kg, then 1.5 mg/kg every 8 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Alternate therapy: 4.5 mg/kg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Plague (",
    " </b>",
    " <b>",
    " <i>",
    " Yersinia pestis",
    " </i>",
    " </b>",
    " <b>",
    " ):",
    " </b>",
    " Treatment: 5 mg/kg/day, followed by postexposure prophylaxis with
    doxycycline",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Pneumonia, hospital- or ventilator-associated:",
    " </b>",
    " 7 mg/kg/day (with antipseudomonal beta-lactam or carbapenem)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <b>",
    " Synergy (for gram-positive infections):",
    " </b>",
    " 3 mg/kg/day in 1-3 divided doses (with ampicillin)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Tularemia:",
    " </b>",
    " 5 mg/kg/day divided every 8 hours for 1-2 weeks",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Urinary tract infection:",
    " </b>",
    " 1.5 mg/kg/dose every 8 hours",
    " </p>",
    " </div>",
    " <div class=\"block dop drugH1Div\" id=\"F8107266\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Pediatric",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/63/8185?
    source=see_link\">",
    " see \"Gentamicin (systemic): Pediatric drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Individualization is",
    " <b>",
    " critical",
    " </b>",
    " because of the low therapeutic index.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be
    more accurate than dosing on the basis of total body weight (TBW).",
    " </b>",
    " In morbid obesity, dosage requirement may best be estimated using a dosing
    weight of IBW + 0.4 (TBW - IBW).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Initial and periodic plasma drug levels (eg, peak and trough with
    conventional dosing) should be determined, particularly in critically-ill patients
    with serious infections or in disease states known to significantly alter
    aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Usual dosage ranges:",
    " </b>",
    " I.M., I.V.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Infants and Children &lt;5 years: 2.5 mg/kg/dose every 8 hours*",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children &ge;5 years: 2-2.5 mg/kg/dose every 8 hours*",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " *",
    " <b>",
    " Note:",
    " </b>",
    " Higher individual doses and/or more frequent intervals (eg, every 6 hours)
    may be required in selected clinical situations (cystic fibrosis) or serum levels
    document the need.",
    " </p>",
    " </div>",
    " <div class=\"block doe drugH1Div\" id=\"F8107268\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Geriatric",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Refer to adult dosing.",
    " </p>",
    " </div>",
    " <div class=\"block dor drugH1Div\" id=\"F8107269\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Renal Impairment",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Conventional dosing:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &ge;60 mL/minute: Administer every 8 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " 40-60 mL/minute: Administer every 12 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " 20-40 mL/minute: Administer every 24 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;20 mL/minute: Loading dose, then monitor levels",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " High-dose therapy: Interval may be extended (eg, every 48 hours) in patients
    with moderate renal impairment (Cl",
    " <sub>",
    " cr",
    " </sub>",
    " 30-59 mL/minute) and/or adjusted based on serum level determinations.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis
    days) (Heintz, 2009): Dialyzable (~50%; variable; dependent on filter, duration,
    and type of IHD):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Loading dose of 2-3 mg/kg loading dose followed by:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Mild UTI or synergy: 1 mg/kg every 48-72 hours; consider redosing for pre-HD
    or post-HD concentrations &lt;1 mg/L",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Moderate-to-severe UTI: 1-1.5 mg/kg every 48-72 hours; consider redosing for
    pre-HD concentrations &lt;1.5-2 mg/L or post-HD concentrations &lt;1 mg/L",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Systemic gram-negative rod infection: 1.5-2 mg/kg every 48-72 hours; consider
    redosing for pre-HD concentrations &lt;3-5 mg/L or post-HD concentrations &lt;2
    mg/L",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <b>",
    " Note:",
    " </b>",
    " Dosing dependent on the assumption of 3 times/week, complete IHD sessions.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Peritoneal dialysis (PD):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Administration via PD fluid:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Gram-positive infection (eg, synergy): 3-4 mg/L (3-4 mcg/mL) of PD fluid",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Gram-negative infection: 4-8 mg/L (4-8 mcg/mL) of PD fluid",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Administration via I.V., I.M. route during PD: Dose as for Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;10 mL/minute and follow levels",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005):
    Drug clearance is highly dependent on the method of renal replacement, filter type,
    and flow rate. Appropriate dosing requires close monitoring of pharmacologic
    response, signs of adverse reactions due to drug accumulation, as well as drug
    concentrations in relation to target trough (if appropriate). The following are
    general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2
    L/hour and minimal residual renal function) and should not supersede clinical
    judgment:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " CVVH/CVVHD/CVVHDF: Loading dose of 2-3 mg/kg followed by:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Mild UTI or synergy: 1 mg/kg every 24-36 hours (redose when concentration
    &lt;1 mg/L)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Moderate-to-severe UTI: 1-1.5 mg/kg every 24-36 hours (redose when
    concentration &lt;1.5-2 mg/L)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Systemic gram-negative infection: 1.5-2.5 mg/kg every 24-48 hours (redose
    when concentration &lt;3-5 mg/L)",
    " </p>",
    " </div>",
    " <div class=\"block doh drugH1Div\" id=\"F8107270\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Hepatic Impairment",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Monitor plasma concentrations.",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F8107316\"
    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. [DSC] = Discontinued product",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Infusion, premixed in NS: 60 mg (50 mL, 100 mL [DSC]); 80 mg (50 mL, 100 mL);
    100 mg (50 mL, 100 mL); 120 mg (100 mL)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, solution: 40 mg/mL (2 mL, 20 mL)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, solution [pediatric]: 10 mg/mL (2 mL [DSC])",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, solution [pediatric, preservative free]: 10 mg/mL (2 mL)",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F8107117\"
    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=\"F8107276\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " I.M.: Administer by deep I.M. route if possible. Slower absorption and lower
    peak concentrations, probably due to poor circulation in the atrophic muscle, may
    occur following I.M. injection; in paralyzed patients, suggest I.V. route.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been
    shown to inactivate aminoglycosides",
    " <i>",
    " in vitro",
    " </i>",
    " . This has been observed to a greater extent with tobramycin and gentamicin,
    while amikacin has shown greater stability against inactivation. Concurrent use of
    these agents may pose a risk of reduced antibacterial efficacy",
    " <i>",
    " in vivo",
    " </i>",
    " , particularly in the setting of profound renal impairment. However,
    definitive clinical evidence is lacking. If combination penicillin/aminoglycoside
    therapy is desired in a patient with renal dysfunction, separation of doses (if
    feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical
    response should be considered.",
    " </p>",
    " </div>",
    " <div class=\"block scp drugH1Div\" id=\"F8107219\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Compatibility",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Stable in dextran 40, D",
    " <sub>",
    " 5",
    " </sub>",
    " W, D",
    " <sub>",
    " 10",
    " </sub>",
    " W, mannitol 20%, LR, NS;",
    " <b>",
    " incompatible",
    " </b>",
    " with fat emulsion 10%;",
    " <b>",
    " variable stability (consult detailed reference)",
    " </b>",
    " in peritoneal dialysis solution.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Y-site administration: Compatible:",
    " </b>",
    " Acyclovir, aldesleukin, alprostadil, amifostine, amiodarone, amsacrine,
    anidulafungin, atracurium, aztreonam, bivalirudin, caffeine citrate, caspofungin,
    cefepime, ceftazidime, ciprofloxacin, cisatracurium, cyclophosphamide,
    cyclosporine, cytarabine, daptomycin, dexmedetomidine, diltiazem, docetaxel,
    doripenem, doxapram, doxorubicin liposome, enalaprilat, esmolol, etoposide
    phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, foscarnet,
    gemcitabine, granisetron, hetastarch in lactate electrolyte injection
    (Hextend&reg;), hydromorphone, IL-2, insulin (regular), labetalol, levofloxacin,
    linezolid, lorazepam, magnesium sulfate, melphalan, meperidine, meropenem,
    midazolam, milrinone, morphine, multivitamins, nicardipine, ondansetron, oxytocin,
    paclitaxel, palonosetron, pancuronium, piperacillin/tazobactam, potassium chloride,
    remifentanil, sargramostim, tacrolimus, telavancin, teniposide, theophylline,
    thiotepa, tigecycline, vasopressin, vecuronium, vinorelbine, vitamin B complex with
    C, zidovudine.",
    " <b>",
    " Incompatible:",
    " </b>",
    " Allopurinol, amphotericin B cholesteryl sulfate complex, azithromycin,
    drotrecogin alfa, furosemide, hetastarch in NS, idarubicin, indomethacin,
    iodipamide meglumine, pemetrexed, propofol, warfarin.",
    " <b>",
    " Variable (consult detailed reference):",
    " </b>",
    " Filgrastim, heparin, pantoprazole, phenytoin.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Compatibility in syringe: Compatible:",
    " </b>",
    " Caffeine citrate, clindamycin, dimenhydrinate, iohexol, iopamidol,
    iothalamate meglumine 60%, penicillin G sodium.",
    " <b>",
    " Incompatible:",
    " </b>",
    " Ampicillin, cloxacillin, heparin, pantoprazole.",
    " <b>",
    " Variable (consult detailed reference):",
    " </b>",
    " Ioxaglate meglumine 39.3% and ioxaglate sodium 19.6%.",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F8107118\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Treatment of susceptible bacterial infections, normally gram-negative
    organisms, including",
    " <i>",
    " Pseudomonas",
    " </i>",
    " ,",
    " <i>",
    " Proteus",
    " </i>",
    " ,",
    " <i>",
    " Serratia",
    " </i>",
    " , and gram-positive",
    " <i>",
    " Staphylococcus",
    " </i>",
    " ; treatment of bone infections, respiratory tract infections, skin and soft
    tissue infections, as well as abdominal and urinary tract infections, and
    septicemia; treatment of infective endocarditis",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F8107082\"
    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;\">",
    " Gentamicin may be confused with gentian violet, kanamycin, vancomycin",
    " </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
    (intrathecal administration) among its list of drug classes which have a heightened
    risk of causing significant patient harm when used in error.",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"block ars drugH1Div\" id=\"F8107170\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions Significant",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Frequency not defined.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Cardiovascular: Edema, hyper/hypotension",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Central nervous system: Ataxia, confusion, depression, dizziness, drowsiness,
    encephalopathy, fever, headache, lethargy, pseudomotor cerebri, seizures, vertigo",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Dermatologic: Alopecia, erythema, itching, purpura, rash, urticaria",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Endocrine &amp; metabolic: Hypocalcemia, hypokalemia, hypomagnesemia,
    hyponatremia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Gastrointestinal: Anorexia, appetite decreased,",
    " <i>",
    " C. difficile",
    " </i>",
    " -associated diarrhea, enterocolitis, nausea, salivation increased,
    splenomegaly, stomatitis, vomiting, weight loss",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hematologic: Agranulocytosis, anemia, eosinophilia, granulocytopenia,
    leukopenia, reticulocytes increased/decreased, thrombocytopenia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hepatic: Hepatomegaly, LFTs increased",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Local: Injection site reactions, pain at injection site,
    phlebitis/thrombophlebitis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Arthralgia, gait instability, muscle cramps,
    muscle twitching, muscle weakness, myasthenia gravis-like syndrome, numbness,
    paresthesia, peripheral neuropathy, tremor, weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Ocular: Visual disturbances",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Otic: Hearing impairment, hearing loss (associated with persistently
    increased serum concentrations; early toxicity usually affects high-pitched sound),
    tinnitus",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Renal: BUN increased, casts (hyaline, granular) in urine, creatinine
    clearance decreased, distal tubular dysfunction, Fanconi-like syndrome (high dose,
    prolonged course) (infants and adults), oliguria, renal failure (high trough serum
    concentrations), polyuria, proteinuria, serum creatinine increased, tubular
    necrosis, urine specific gravity decreased",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Respiratory: Dyspnea, laryngeal edema, pulmonary fibrosis, respiratory
    depression",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Miscellaneous: Allergic reaction, anaphylaxis, anaphylactoid reactions",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F8107166\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to gentamicin or other aminoglycosides",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F8107167\"
    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; Nephrotoxicity:",
    " <b>",
    " [U.S. Boxed Warning]: May cause nephrotoxicity;",
    " </b>",
    " usual risk factors include pre-existing renal impairment, concomitant
    nephrotoxic medications, advanced age and dehydration. Discontinue treatment if
    signs of nephrotoxicity occur; renal damage is usually reversible.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Neuromuscular blockade and respiratory paralysis: May cause
    neuromuscular blockade and respiratory paralysis; especially when given soon after
    anesthesia or muscle relaxants.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Neurotoxicity:",
    " <b>",
    " [U.S. Boxed Warning]: May cause neurotoxicity;",
    " </b>",
    " usual risk factors include pre-existing renal impairment, concomitant
    neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is
    proportional to the amount of drug given and the duration of treatment. Tinnitus or
    vertigo may be indications of vestibular injury and impending bilateral
    irreversible damage. Discontinue treatment if signs of ototoxicity occur.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Superinfection: Prolonged use may result in fungal or bacterial
    superinfection, including",
    " <i>",
    " C. difficile",
    " </i>",
    " -associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been
    observed &gt;2 months postantibiotic treatment.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Disease-related concerns:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hearing impairment: Use with caution in patients with pre-existing
    vertigo, tinnitus, or hearing loss.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hypocalcemia: Use with caution in patients with hypocalcemia.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Neuromuscular disorders: Use with caution in patients with
    neuromuscular disorders, including myasthenia gravis.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Renal impairment: Use with caution in patients with pre-existing renal
    insufficiency; dosage modification required.",
    " </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-term use: Not intended for long-term therapy due to toxic hazards
    associated with extended administration.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F13299397\"
    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=\"F8107194\"
    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;\">",
    " AbobotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking
    effect of AbobotulinumtoxinA.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Agalsidase Alfa: Gentamicin (Systemic) may diminish the therapeutic effect of
    Agalsidase Alfa.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Agalsidase Beta: Gentamicin (Systemic) may diminish the therapeutic effect of
    Agalsidase Beta.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " BCG: Antibiotics may diminish the therapeutic effect of BCG.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic
    effect of Bisphosphonate Derivatives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Capreomycin: May enhance the neuromuscular-blocking effect of
    Aminoglycosides.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin.
    Especially with higher doses of carboplatin.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cephalosporins (2nd Generation): May enhance the nephrotoxic effect of
    Aminoglycosides.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cephalosporins (3rd Generation): May enhance the nephrotoxic effect of
    Aminoglycosides.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cephalosporins (4th Generation): May enhance the nephrotoxic effect of
    Aminoglycosides.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CISplatin: May enhance the nephrotoxic effect of Aminoglycosides.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of
    Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of
    Colistimethate.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect
    of CycloSPORINE (Systemic).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of
    Gallium Nitrate.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides.
    Specifically, nephrotoxicity and ototoxicity.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory
    depressant effect of Neuromuscular-Blocking Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of
    Aminoglycosides. Data only in premature infants.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking
    effect of OnabotulinumtoxinA.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Penicillins: May decrease the serum concentration of Aminoglycosides.
    Primarily associated with extended spectrum penicillins, and patients with renal
    dysfunction.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Nafcillin; Oxacillin;
    Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine;
    Penicillin V Potassium.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking
    effect of RimabotulinumtoxinB.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium
    Picosulfate. Management: Consider using an alternative product for bowel cleansing
    prior to a colonoscopy in patients who have recently used or are concurrently using
    an antibiotic.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid
    Vaccine. Only the live attenuated Ty21a strain is affected. Management:
    Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in
    patients being treated with systemic antibacterial agents. Use of this vaccine
    should be postponed until at least 24 hours after cessation of antibacterial
    agents.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F8107119\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " D (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F8107120\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Gentamicin crosses the placenta and produces detectable serum levels in the
    fetus. Renal toxicity has been described in two case reports following first
    trimester exposure. There are several reports of total irreversible bilateral
    congenital deafness in children whose mothers received streptomycin during
    pregnancy; therefore, the manufacturer classifies gentamicin as pregnancy category
    D. Although ototoxicity has not been reported following maternal use of gentamicin,
    a potential for harm exists.",
    " <b>",
    " [U.S. Boxed Warning]: Aminoglycosides may cause fetal harm if administered
    to a pregnant woman.",
    " </b>",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Due to pregnancy induced physiologic changes, some pharmacokinetic parameters
    of gentamicin may be altered. Pregnant women have an average-to-larger volume of
    distribution which may result in lower serum peak levels than for the same dose in
    nonpregnant women. Serum half-life is also shorter.",
    " </p>",
    " </div>",
    " <div class=\"block lac drugH1Div\" id=\"F8107122\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Lactation",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Enters breast milk/use caution (AAP rates &ldquo;compatible&rdquo;; AAP 2001
    update pending)",
    " </p>",
    " </div>",
    " <div class=\"block brc drugH1Div\" id=\"F8107165\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Breast-Feeding Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Gentamicin is excreted into breast milk; however, it is not well absorbed
    when taken orally. This limited oral absorption may minimize exposure to the
    nursing infant. Nondose-related effects could include modification of bowel
    flora.",
    " </p>",
    " </div>",
    " <div class=\"block dic drugH1Div\" id=\"F8107275\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dietary Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Calcium, magnesium, potassium: Renal wasting may cause hypocalcemia,
    hypomagnesemia, and/or hypokalemia.",
    " </p>",
    " </div>",
    " <div class=\"block fee drugH1Div\" id=\"F8107318\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Solution",
    " </b>",
    " (Gentamicin Sulfate Injection)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 10 mg/mL (2 mL): $3.78",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 40 mg/mL (2 mL): $1.26",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Solution",
    " </b>",
    " (Gentamicin Sulfate Intravenous)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 10 mg/mL (8 mL): $1.79",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F8107280\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Urinalysis, urine output, BUN, serum creatinine, plasma gentamicin levels (as
    appropriate to dosing method). Levels are typically obtained after the third dose
    in conventional dosing. Hearing should be tested before, during, and after
    treatment; particularly in those at risk for ototoxicity or who will be receiving
    prolonged therapy (&gt;2 weeks)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Some penicillin derivatives may accelerate the degradation of
    aminoglycosides",
    " <i>",
    " in vitro",
    " </i>",
    " . This may be clinically-significant for certain penicillin (ticarcillin,
    piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin)
    combination therapy in patients with significant renal impairment. Close monitoring
    of aminoglycoside levels is warranted.",
    " </p>",
    " </div>",
    " <div class=\"block rer drugH1Div\" id=\"F8107222\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Reference Range",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Timing of serum samples: Draw peak 30 minutes after 30-minute infusion has
    been completed or 1 hour after I.M. injection; draw trough immediately before next
    dose",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Therapeutic levels:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Peak:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Serious infections: 6-8 mcg/mL (12-17 micromole/L)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Life-threatening infections: 8-10 mcg/mL (17-21 micromole/L)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Urinary tract infections: 4-6 mcg/mL",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Synergy against gram-positive organisms: 3-5 mcg/mL",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Trough:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Serious infections: 0.5-1 mcg/mL",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Life-threatening infections: 1-2 mcg/mL",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " The American Thoracic Society (ATS) recommends trough levels of &lt;1 mcg/mL
    for patients with hospital-acquired pneumonia.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Obtain drug levels after the third dose unless renal dysfunction/toxicity
    suspected",
    " </p>",
    " </div>",
    " <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F12707701\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " International Brand Names",
    " </span>",
    " <ul>",
    " <li>",
    " Agentam (PH);",
    " </li>",
    " <li>",
    " Alcomicin (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW,
    LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG,
    YE, ZM, ZW);",
    " </li>",
    " <li>",
    " Apigent (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);",
    " </li>",
    " <li>",
    " Azupel (PY);",
    " </li>",
    " <li>",
    " Bactiderm (PH);",
    " </li>",
    " <li>",
    " Biogaracin (IN);",
    " </li>",
    " <li>",
    " Cidomycin (AE, BH, CY, EG, GB, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE,
    ZA);",
    " </li>",
    " <li>",
    " Diakarmon (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW,
    LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG,
    YE, ZM, ZW);",
    " </li>",
    " <li>",
    " Epigent (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);",
    " </li>",
    " <li>",
    " Ethigent (ID);",
    " </li>",
    " <li>",
    " Garamicin (TH);",
    " </li>",
    " <li>",
    " Garamicina (BR, CO, CR, DO, GT, HN, NI, PA, SV);",
    " </li>",
    " <li>",
    " Garamycin (AE, BH, CH, CY, EG, HK, ID, IN, IQ, IR, JO, KW, LB, LY, MY, NO,
    OM, PL, QA, RU, SA, SG, SY, TR, TW, YE);",
    " </li>",
    " <li>",
    " Garasent (MY, SG);",
    " </li>",
    " <li>",
    " Genacin (PK);",
    " </li>",
    " <li>",
    " Genbexil (EC);",
    " </li>",
    " <li>",
    " Gensumycin (FI, NO, SE);",
    " </li>",
    " <li>",
    " Gentabiotic (PE);",
    " </li>",
    " <li>",
    " Gentac (TW);",
    " </li>",
    " <li>",
    " Gentalline (FR);",
    " </li>",
    " <li>",
    " Gentalyn (CN, IT, PE, VE);",
    " </li>",
    " <li>",
    " Gentamen (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);",
    " </li>",
    " <li>",
    " Gentamina (AR);",
    " </li>",
    " <li>",
    " Gentarad (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);",
    " </li>",
    " <li>",
    " Gentasporin (IN);",
    " </li>",
    " <li>",
    " Gentawin (TH);",
    " </li>",
    " <li>",
    " Genticin (GB, IE);",
    " </li>",
    " <li>",
    " Genticyn (IN);",
    " </li>",
    " <li>",
    " Hexamycin (DK);",
    " </li>",
    " <li>",
    " Lyramycin (IN);",
    " </li>",
    " <li>",
    " Miramycin (HK, SG, TH);",
    " </li>",
    " <li>",
    " Mycin (PH);",
    " </li>",
    " <li>",
    " Nelgen (PH);",
    " </li>",
    " <li>",
    " Obogen (PH);",
    " </li>",
    " <li>",
    " Ocugenta (KP);",
    " </li>",
    " <li>",
    " Qutacin (TW);",
    " </li>",
    " <li>",
    " Rigaminol (PE);",
    " </li>",
    " <li>",
    " Rocy Gen (PH);",
    " </li>",
    " <li>",
    " Rovixida (AR);",
    " </li>",
    " <li>",
    " Rupegen (AR);",
    " </li>",
    " <li>",
    " Servigenta (MY);",
    " </li>",
    " <li>",
    " Tangyn (PH);",
    " </li>",
    " <li>",
    " Timact (ID)",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F8107220\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Interferes with bacterial protein synthesis by binding to 30S and 50S
    ribosomal subunits resulting in a defective bacterial cell membrane",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F8107223\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics/Kinetics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Absorption:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Intramuscular: Rapid and complete",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Oral: None",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Distribution: Primarily into extracellular fluid (highly hydrophilic); high
    concentration in the renal cortex; minimal penetration to ocular tissues via I.V.
    route",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " V",
    " <sub>",
    " d",
    " </sub>",
    " : Increased by edema, ascites, fluid overload; decreased with dehydration",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Neonates: 0.4-0.6 L/kg",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children: 0.3-0.35 L/kg",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Adults: 0.2-0.3 L/kg",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Relative diffusion from blood into CSF: Minimal even with inflammation",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " CSF:blood level ratio: Normal meninges: Nil; Inflamed meninges: 10% to 30%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Protein binding: &lt;30%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Half-life elimination:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Infants: &lt;1 week: 3-11.5 hours; 1 week to 6 months: 3-3.5 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Adults: 1.5-3 hours; End-stage renal disease: 36-70 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Time to peak, serum: I.M.: 30-90 minutes; I.V.: 30 minutes after 30-minute
    infusion",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Excretion: Urine (as unchanged drug)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Clearance: Directly related to renal function",
    " </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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    " </ol>",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107079\">",
    " ALERT: U.S. Boxed Warning",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107109\">",
    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107344\">",
    " Pharmacologic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107267\">",
    " Dosing: Adult",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107266\">",
    " Dosing: Pediatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107268\">",
    " Dosing: Geriatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107269\">",
    " Dosing: Renal Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107270\">",
    " Dosing: Hepatic Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107316\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107117\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107276\">",
    " Administration",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107219\">",
    " Compatibility",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107118\">",
    " Use",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107082\">",
    " Medication Safety Issues",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107170\">",
    " Adverse Reactions Significant",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107166\">",
    " Contraindications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107167\">",
    " Warnings/Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13299397\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107194\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107119\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107120\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107122\">",
    " Lactation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107165\">",
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    " Dietary Considerations",
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    " <a class=\"outlineLink\" href=\"#F8107318\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107280\">",
    " Monitoring Parameters",
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    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107220\">",
    " Mechanism of Action",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8107223\">",
    " Pharmacodynamics/Kinetics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9142\" rel=\"outline_link\">",
    " GRAPHICS",
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    var title_f0_47_762="Epidemiology, pathogenesis, clinical manifestations and
    diagnosis of Waldenström macroglobulinemia";
    var content_f0_47_762=[" <noscript>",
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    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Epidemiology, pathogenesis, clinical manifestations and diagnosis of
    Waldenstr&ouml;m macroglobulinemia",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
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    " Author",
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    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/47/762/contributors\">",
    " S Vincent Rajkumar, MD",
    " </a>",
    " <br/>",
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    href=\"UTD.htm?0/47/762/contributors\">",
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    " <br/>",
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    0/47/762/contributors\">",
    " Stanley L Schrier, MD",
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    0/47/762/contributors\">",
    " Robert A Kyle, MD",
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    " Rebecca F Connor, MD",
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    " Literature review current through:",
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    " Oct 2013.",
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    " This topic last updated:",
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    " Sep 13, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H6575411\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The term &ldquo;macroglobulinemia&rdquo; refers to the
    production of excess IgM monoclonal protein that occurs in certain clonal
    lymphoproliferative disorders and plasma cell dyscrasias. This broad definition
    includes patients with monoclonal gammopathy of undetermined significance of the
    IgM type (IgM MGUS), smoldering Waldenstr&ouml;m macroglobulinemia (SWM),
    Waldenstr&ouml;m macroglobulinemia (WM), and a number of related disorders in which
    an IgM monoclonal protein is detected, such as chronic lymphocytic leukemia (CLL),
    a number of lymphoma variants, and primary (AL) amyloidosis.",
    " </p>",
    " <p>",
    " WM is a distinct clinicopathologic entity demonstrating lymphoplasmacytic
    lymphoma (LPL) in the bone marrow with an IgM monoclonal gammopathy in the blood.
    Patients may present with symptoms related to the infiltration of the hematopoietic
    tissues or the effects of monoclonal IgM in the blood.",
    " </p>",
    " <p>",
    " This topic review will limit discussion to the clinical manifestations and
    diagnosis of WM. The pathologic features of lymphoplasmacytic lymphoma and the
    prognosis and treatment of WM are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/47/37626?
    source=see_link\">",
    " \"Treatment and prognosis of Waldenstr&ouml;m macroglobulinemia\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/61/38872?
    source=see_link\">",
    " \"Clinical manifestations, pathologic features, and diagnosis of
    lymphoplasmacytic lymphoma\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/60/4041?
    source=see_link&amp;anchor=H22391020#H22391020\">",
    " \"Clinical course and management of monoclonal gammopathy of undetermined
    significance\", section on 'IgM MGUS'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " EPIDEMIOLOGY",
    " </span>",
    " &nbsp;&mdash;&nbsp;WM is a rare disorder with an incidence of approximately
    three per million people per year with 1400 new cases diagnosed in the United
    States each year [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/1,2\">",
    " 1,2",
    " </a>",
    " ]. The median age at diagnosis is 64 years; less than 1 percent of patients
    are under 40 years of age, and approximately 60 percent are males [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/3\">",
    " 3",
    " </a>",
    " ]. WM is much more common in Caucasians than in other ethnic groups [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/4\">",
    " 4",
    " </a>",
    " ]. Specifically, it is uncommon in Blacks and those of Mexican descent who
    make up approximately 5 percent of cases [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The majority of patients with the histopathologic finding of lymphoplasmacytic
    lymphoma (LPL) have a circulating monoclonal IgM consistent with the diagnosis of
    WM. In the past, LPL and WM have been arbitrarily differentiated from each other
    based on the level of the monoclonal IgM protein. Currently, the preferred
    terminology in cases of LPL with circulating monoclonal IgM is WM, rather than
    lymphoplasmacytic lymphoma, regardless of the size of the monoclonal IgM protein.
    (See",
    " <a class=\"local\" href=\"#H21\">",
    " 'Diagnosis'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " Although WM appears to be a sporadic disease in the majority of cases, a
    familial predisposition is present in up to 20 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/5-13\">",
    " 5-13",
    " </a>",
    " ]. The nature and course of disease for patients with a family history appears
    to be similar to that of sporadic cases [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/12\">",
    " 12",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Since there are no proven preventative approaches, there is no role for
    screening asymptomatic relatives at this time. The largest population-based study
    evaluated 24,609 first-degree relatives of 2749 patients with WM or LPL and 8279
    controls [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/10\">",
    " 10",
    " </a>",
    " ]. First-degree relatives of patients with WM or LPL had a 20-fold increased
    risk of developing",
    " <span class=\"nowrap\">",
    " WM/LPL.",
    " </span>",
    " They also had an increased risk of developing non-Hodgkin lymphoma, chronic
    lymphocytic leukemia, and MGUS (relative risks of 3, 3, and 5, respectively). No
    association was found for multiple myeloma or Hodgkin lymphoma.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " ETIOLOGY",
    " </span>",
    " &nbsp;&mdash;&nbsp;The etiology of WM is unknown. No obvious causative or
    predisposing factor has been identified. In a case-control study of 65 cases of WM
    compared with 213 hospital controls, no differences in sociodemographic factors,
    prior medical conditions, medication use, alcohol consumption, employment in any
    particular industry or occupation, specific occupational exposures (including
    radiation), or familial cancer history were found [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/14\">",
    " 14",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " However, larger studies have suggested an association with chronic immune
    stimulation and autoimmune disorders [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/12,15-17\">",
    " 12,15-17",
    " </a>",
    " ]. As an example, a retrospective report of users of United States Veterans
    Affairs health care facilities from 1997 to 2004, reported that hepatitis C virus
    infection conferred a threefold higher risk of WM (adjusted hazard ratio 2.8, 95%
    CI 2.0-3.8) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/15\">",
    " 15",
    " </a>",
    " ]. Another study suggested a possible association with exposure to farming,
    pesticides, and wood dust, but not for solvents, hair dye, or asbestos [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/12\">",
    " 12",
    " </a>",
    " ]. More studies are needed to determine if there is a causal relationship
    between these host and environmental factors and WM.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h1\">",
    " PATHOGENESIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Both somatic mutations and chromosomal abnormalities have
    been identified in the malignant B cells of WM, although cytogenetic abnormalities
    based on metaphase analysis or abnormal DNA content are typically not seen until WM
    has transformed to a more aggressive disease. The pattern of somatic mutations
    suggests selection by antigenic stimulation at a relatively late stage of B-cell
    differentiation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/18-20\">",
    " 18-20",
    " </a>",
    " ], such as a post-germinal center IgM memory B cell that has undergone somatic
    hypermutation but has failed to undergo isotype class switching (",
    " <a class=\"graphic graphic_table graphicRef54590 \" href=\"UTD.htm?
    39/8/40076\">",
    " table 1",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/21,22\">",
    " 21,22",
    " </a>",
    " ]. Further discussion of the pathogenesis of the underlying malignant clone,
    lymphoplasmacytic lymphoma, is presented separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/61/38872?
    source=see_link&amp;anchor=H198194648#H198194648\">",
    " \"Clinical manifestations, pathologic features, and diagnosis of
    lymphoplasmacytic lymphoma\", section on 'Pathogenesis'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " This population of clonal B cells results in the production of abnormal
    monoclonal IgM. This monoclonal IgM may manifest itself clinically via several
    mechanisms, either in the setting of clinical WM, or in a patient who only has IgM
    MGUS:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The IgM can act as an autoantibody directed against myelin-associated
    glycoprotein or other nerve components resulting in neuropathy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/23,24\">",
    " 23,24",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H8\">",
    " 'Neuropathy'",
    " </a>",
    " below.)",
    " </li>",
    " <li>",
    " The IgM may be directed against antigens on the patient's own red blood
    cells resulting in a Coombs positive autoimmune cold hemolytic anemia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/25\">",
    " 25",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H15\">",
    " 'Complete blood count'",
    " </a>",
    " below.)",
    " </li>",
    " <li>",
    " Amorphous material consisting of the monoclonal IgM protein may be deposited
    in the extracellular space of the kidneys, gastrointestinal tract, or skin. (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Kidney involvement'",
    " </a>",
    " below and",
    " <a class=\"local\" href=\"#H12\">",
    " 'Gastrointestinal symptoms'",
    " </a>",
    " below and",
    " <a class=\"local\" href=\"#H13\">",
    " 'Other'",
    " </a>",
    " below.)",
    " </li>",
    " <li>",
    " The IgM protein may precipitate out of the serum in cold temperatures
    resulting in symptoms of cryoglobulinemia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/26,27\">",
    " 26,27",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H10\">",
    " 'Cryoglobulinemia'",
    " </a>",
    " below.)",
    " </li>",
    " <li>",
    " The pentameric configuration of IgM molecules increases serum viscosity
    thereby slowing the passage of blood through capillaries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/28\">",
    " 28",
    " </a>",
    " ]. IgM levels high enough to cause hyperviscosity syndrome almost always
    denote underlying WM rather than IgM MGUS. (See",
    " <a class=\"local\" href=\"#H7\">",
    " 'Hyperviscosity syndrome'",
    " </a>",
    " below.)",
    " </li>",
    " <li>",
    " In patients with WM, the malignant B cells may directly infiltrate the
    hematopoietic tissues resulting in cytopenias (eg, anemia, thrombocytopenia,
    neutropenia), lymphadenopathy, hepatomegaly,",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " splenomegaly. (See",
    " <a class=\"local\" href=\"#H6\">",
    " 'Overview'",
    " </a>",
    " below.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h1\">",
    " CLINICAL PRESENTATION",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Overview",
    " </span>",
    " &nbsp;&mdash;&nbsp;During the course of their disease, patients with WM can
    develop symptoms related to infiltration of hematopoietic tissues (eg, anemia,
    lymphadenopathy, hepatosplenomegaly)",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " symptoms related to the IgM monoclonal protein in their blood (eg,
    hyperviscosity, peripheral neuropathy) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/29,30\">",
    " 29,30",
    " </a>",
    " ]. Most patients with WM present with non-specific constitutional symptoms,
    but up to one-quarter of patients may be asymptomatic at diagnosis. The most common
    presenting features include weakness, fatigue, weight loss, and chronic oozing of
    blood from the nose or gums. Recurrent infections may also occur due to a relative
    decrease in other immunoglobulins.",
    " </p>",
    " <p>",
    " As an example, a series of 217 patients with WM reported the following
    symptoms and physical findings at presentation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/3\">",
    " 3",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Constitutional \"B\" symptoms &mdash; 23 percent",
    " </li>",
    " <li>",
    " Bleeding &mdash; 23 percent",
    " </li>",
    " <li>",
    " Neurologic symptoms &mdash; 22 percent",
    " </li>",
    " <li>",
    " Symptoms secondary to hyperviscosity &mdash; 31 percent",
    " </li>",
    " <li>",
    " Lymphadenopathy &mdash; 25 percent",
    " </li>",
    " <li>",
    " Hepatomegaly &mdash; 24 percent",
    " </li>",
    " <li>",
    " Splenomegaly &mdash; 19 percent",
    " </li>",
    " <li>",
    " Funduscopic abnormalities &mdash; 34 percent",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " No osteolytic bone lesions were found at presentation in this series and
    involvement of the lung, kidney, gut, and skin were each seen in approximately 4
    percent of patients. Cold agglutinins were present in 5 percent of patients, but
    only 1.5 percent had symptoms attributable to cold agglutinins.",
    " </p>",
    " <p>",
    " Tissues may be involved in WM through infiltration with malignant cells or via
    deposition of IgM or amyloid fibrils. The following sections describe involvement
    of specific organs in more detail.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Hyperviscosity syndrome",
    " </span>",
    " &nbsp;&mdash;&nbsp;Symptoms related to hyperviscosity are present in up to 30
    percent of patients, producing neurologic complaints such as blurring or loss of
    vision, headache, vertigo, nystagmus, dizziness, tinnitus, sudden deafness,
    diplopia, or ataxia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/3\">",
    " 3",
    " </a>",
    " ]. Marked hyperviscosity can rarely lead to confusion, dementia, disturbances
    of consciousness, stroke, or coma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/31,32\">",
    " 31,32",
    " </a>",
    " ]. When accompanied by anemia, hyperviscosity and the associated plasma volume
    expansion may precipitate or aggravate heart failure [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/33\">",
    " 33",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Clinical manifestations are rarely attributable to hyperviscosity if serum
    viscosity is &lt;4 centipoises (CP, normal value &le;1.8 CP). Although the
    correlation between serum viscosity and clinical manifestations is not precise,
    symptoms often begin when serum viscosity is &gt;4 CP, and most patients are
    symptomatic when serum viscosity is &gt;6 CP. As an example, in a compilation of
    two different series, zero, 67, and 75 percent of patients had symptoms of
    hyperviscosity when the serum viscosity was less than 3, greater than 4, and
    greater than 5 CP, respectively [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/34\">",
    " 34",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H19\">",
    " 'Serum viscosity'",
    " </a>",
    " below.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Neuropathy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Approximately 20 percent of patients may present with
    symptoms of neuropathy at the time of diagnosis. The most frequent neurologic
    abnormality is a distal, symmetric, and slowly progressive sensorimotor peripheral
    neuropathy causing paresthesias and weakness [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/23,24,35,36\">",
    " 23,24,35,36",
    " </a>",
    " ]. The lower extremities are usually more involved than the upper extremities.
    Anti-myelin-associated glycoprotein (MAG) activity is found in about one-half of
    these patients, but there is no correlation between these antibodies and the
    severity of symptoms [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/23\">",
    " 23",
    " </a>",
    " ]. Other autoantibodies of uncertain pathogenetic significance have also been
    described, including those directed against GM1 ganglioside and asialo-GM1
    ganglioside [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/24\">",
    " 24",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Other neurologic manifestations can occur but are less common. These include
    cranial nerve palsies, mononeuropathy, mononeuritis multiplex, multifocal
    leukoencephalopathy, and sudden deafness. Infiltration of the meninges by
    plasmacytoid lymphocytes is rare [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/37\">",
    " 37",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Physical examination and electromyography (EMG) may be helpful in
    differentiating between neuropathy due to WM, multiple myeloma (MM), or MGUS from
    that due to other causes such as amyloid or POEMS syndrome. As mentioned above, the
    neuropathy in WM, MM, and MGUS is usually demyelinating with sensory involvement
    more common than motor involvement. In contrast, the neuropathy in amyloid is
    usually axonal and the neuropathy in POEMS syndrome, while also demyelinating, more
    commonly involves the motor neurons. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/14/35049?
    source=see_link&amp;anchor=H5#H5\">",
    " \"POEMS syndrome\", section on 'Peripheral neuropathy and CNS involvement'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/12/7369?
    source=see_link&amp;anchor=H9#H9\">",
    " \"Overview of polyneuropathy\", section on 'Diagnostic evaluation'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Among patients with a peripheral neuropathy, sural nerve biopsy may reveal
    myelin degeneration, cellular infiltration of the nerve, or IgM deposits on the
    myelin sheath. However, it is impossible to determine whether the presence of IgM
    in the biopsy specimen is a causative factor or whether it represents passive
    deposition of IgM in an already damaged nerve [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/23,38\">",
    " 23,38",
    " </a>",
    " ]. Amyloid deposition in the nerve may be responsible for the sensorimotor
    peripheral neuropathy in some patients. Amyloid may be investigated using Congo red
    staining of a subcutaneous fat pad aspirate or bone marrow biopsy. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/27/37304?
    source=see_link&amp;anchor=H5#H5\">",
    " \"Paraneoplastic syndromes affecting peripheral nerve and muscle\", section
    on 'Association with plasma cell dyscrasias'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " Funduscopic abnormalities",
    " </span>",
    " &nbsp;&mdash;&nbsp;Funduscopic abnormalities were noted in 34 percent of
    patients in one series [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/3\">",
    " 3",
    " </a>",
    " ]. A classic finding in WM associated with hyperviscosity is the presence of
    dilated, segmented, and tortuous retinal veins, giving a \"sausage link\"
    appearance (",
    " <a class=\"graphic graphic_picture graphicRef50216 \" href=\"UTD.htm?
    20/45/21215\">",
    " picture 1",
    " </a>",
    " ). Other retinal lesions, including hemorrhages, exudates, and papilledema may
    be impressive, and central retinal vein thrombosis can occur. Funduscopic
    examination is indicated for patients with suspected hyperviscosity related
    symptoms.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h2\">",
    " Cryoglobulinemia",
    " </span>",
    " &nbsp;&mdash;&nbsp;Approximately 10 percent of macroglobulins in WM
    precipitate in the cold (cryoglobulins), but are rarely responsible for cold
    hypersensitivity. However, if the cryoglobulin precipitates at temperatures greater
    than 22&ordm;C, serious symptoms can occur and may include Raynaud phenomenon,
    urticaria, purpura, acral cyanosis,",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " tissue necrosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/26,27\">",
    " 26,27",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?33/15/34040?
    source=see_link\">",
    " \"Clinical manifestations and diagnosis of the mixed cryoglobulinemia
    syndrome (essential mixed cryoglobulinemia)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Kidney involvement",
    " </span>",
    " &nbsp;&mdash;&nbsp;Renal insufficiency is unusual in WM. Despite this,
    deposits of IgM in the glomerular basement membrane may be prominent and
    infiltration of lymphocytes or plasmacytoid cells can occur [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/39,40\">",
    " 39,40",
    " </a>",
    " ]. Urinary monoclonal light chains (Bence Jones protein) can be detected by
    immunofixation in 70 percent of patients, but the quantity is much less than in
    multiple myeloma and cast nephropathy does not occur [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/39\">",
    " 39",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/1/22551?
    source=see_link\">",
    " \"Pathogenesis and diagnosis of myeloma cast nephropathy (myeloma kidney)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Nephrotic syndrome is rare and, when present, is usually caused by
    amyloidosis. Immune-mediated glomerulonephritis, which is typically due to IgM
    deposition or cryoglobulinemia, and nonamyloid nephrotic syndrome (with a minimal
    change-like picture), have been described [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/40,41\">",
    " 40,41",
    " </a>",
    " ]. A renal biopsy may be needed in patients who have recent unexplained renal
    dysfunction. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/62/35815?
    source=see_link\">",
    " \"Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and
    heavy chain deposition diseases\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/15/7418?
    source=see_link\">",
    " \"Clinical presentation, laboratory manifestations, and diagnosis of
    immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Gastrointestinal symptoms",
    " </span>",
    " &nbsp;&mdash;&nbsp;The monoclonal IgM protein may rarely be deposited as
    extracellular amorphous material in the lamina propria of the gastrointestinal
    tract and produce severe malabsorption with diarrhea and steatorrhea [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/42,43\">",
    " 42,43",
    " </a>",
    " ]. Lymphangiectasia is seen on intestinal biopsy in some cases. Patients may
    also develop protein-losing enteropathy and be at increased risk of thrombosis due
    to the enteric loss of anticoagulant proteins. Possible contributing factors
    include the infiltration by malignant cells, amyloid deposition, or increased
    viscosity of the interstitial fluid due to high concentrations of IgM [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/43\">",
    " 43",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/50/3881?
    source=see_link\">",
    " \"Protein-losing gastroenteropathy\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h2\">",
    " Other",
    " </span>",
    " &nbsp;&mdash;&nbsp;Other clinical presentations, such as lytic bone lesions,
    pulmonary involvement, and skin lesions are uncommon.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " In contrast to multiple myeloma, bone pain is rare in WM. Fewer than 5
    percent of patients with otherwise classical WM have lytic bone lesions. When
    present, these patients are usually classified as having IgM multiple myeloma,
    rather than WM [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/44\">",
    " 44",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Pulmonary involvement is rarely a prominent feature of WM. It is manifested
    by cough and dyspnea and the presence of a pleural effusion, diffuse pulmonary
    infiltrates, or an isolated mass. These pulmonary manifestations often respond to
    alkylating agents or irradiation.",
    " </li>",
    " <li>",
    " Skin lesions are uncommon, occurring in approximately 3 percent of patients
    at presentation. More commonly, the skin may show dependent purpura secondary to
    abnormalities in platelet function and hyperviscosity.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Lymphoplasmacytoid cells may infiltrate the dermis and produce macular or
    papulonodular lesions. Multiple flesh-colored pruritic papules on extensor surfaces
    may be present and are secondary to deposition of IgM reacting with epidermal
    basement membrane proteins [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/45-47\">",
    " 45-47",
    " </a>",
    " ]. The presence of an IgM monoclonal protein and erythematous urticarial skin
    vasculitis (Schnitzler's syndrome) has been described [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/48\">",
    " 48",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?21/18/21802?
    source=see_link&amp;anchor=H20#H20\">",
    " \"Cutaneous manifestations of internal malignancy\", section on
    'Vasculitis'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h1\">",
    " LABORATORY FINDINGS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Approximately 25 percent of patients with WM will be
    asymptomatic when a diagnosis is made. These patients may be brought to attention
    based upon abnormal laboratory tests performed for other reasons.",
    " </p>",
    " <p>",
    " As an example, a series of 217 patients with WM reported the following
    laboratory abnormalities at presentation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/3\">",
    " 3",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Anemia &mdash; 38 percent",
    " </li>",
    " <li>",
    " Neutropenia (absolute neutrophil count",
    " <span class=\"nowrap\">",
    " &le;1000/microL)",
    " </span>",
    " &mdash; 4 percent",
    " </li>",
    " <li>",
    " Thrombocytopenia (platelet count",
    " <span class=\"nowrap\">",
    " &le;50,000/microL)",
    " </span>",
    " &mdash; 2 percent",
    " </li>",
    " <li>",
    " Elevated lactate dehydrogenase (LDH) &mdash; 11 percent",
    " </li>",
    " <li>",
    " Elevated beta-2 microglobulin level &mdash; 54 percent",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The erythrocyte sedimentation rate is usually greatly increased but may be
    normal. Further evaluation of a patient suspected of having WM includes a bone
    marrow aspiration with biopsy and serum protein electrophoresis (SPEP).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h2\">",
    " Complete blood count",
    " </span>",
    " &nbsp;&mdash;&nbsp;Anemia can be seen in approximately 40 percent of patients
    with newly diagnosed WM. A moderate to severe degree of anemia is found in about 80
    percent of patients with symptomatic WM, and the peripheral blood smear typically
    shows striking rouleaux formation (",
    " <a class=\"graphic graphic_picture graphicRef74369 \" href=\"UTD.htm?
    27/33/28183\">",
    " picture 2",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " The genesis of anemia is multifactorial, and includes:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Inadequate red cell synthesis",
    " </li>",
    " <li>",
    " Blood loss",
    " </li>",
    " <li>",
    " Decreased erythrocyte survival, which may rarely be due to an autoimmune
    hemolytic anemia",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The hemoglobin and hematocrit levels are often spuriously lower than expected
    from the reduction in red cell mass because of an increase in plasma volume. In one
    series, the Coombs test was positive in 10 percent of patients, but only 3 percent
    developed significant hemolysis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/3\">",
    " 3",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Lymphocytosis and monocytosis are also common findings in WM. Leukopenia and
    thrombocytopenia (due to marrow infiltration) may be present initially but the
    platelet count is rarely less than",
    " <span class=\"nowrap\">",
    " 50,000/microL.",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h2\">",
    " Platelet function and blood coagulation",
    " </span>",
    " &nbsp;&mdash;&nbsp;A clinically important bleeding diathesis is common in WM
    and is secondary to hyperviscosity, and an interference with clotting factor and
    platelet function. While chronic oozing of blood from the nose or gums is common,
    bleeding may occur from the gastrointestinal tract during",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " after surgery [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/3\">",
    " 3",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The most frequent laboratory abnormality related to coagulation is
    prolongation of the thrombin time, a reflection of the inhibition of fibrin
    polymerization by the IgM paraprotein [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/49\">",
    " 49",
    " </a>",
    " ]. Alterations in platelet function, probably due to an interaction between
    the IgM paraprotein and platelet surface membrane glycoproteins, can result in
    prolongation of the bleeding time, impaired clot retraction, defective in vivo
    platelet aggregation, and decreased in vitro platelet adhesion [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/50\">",
    " 50",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/59/23482?
    source=see_link\">",
    " \"Platelet function testing\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Routine studies to test bleeding and clotting function are not necessary in WM
    in the absence of clinical bleeding. In patients who have clinical bleeding,
    unexplained by hyperviscosity, the evaluation should include prothrombin time,
    partial thromboplastin time, thrombin time, and factor X activity.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h2\">",
    " Bone marrow examination",
    " </span>",
    " &nbsp;&mdash;&nbsp;A bone marrow aspirate and biopsy demonstrating
    lymphoplasmacytic lymphoma is an essential component of the diagnosis of WM. While
    the bone marrow aspirate is frequently hypocellular, the biopsy specimen is usually
    hypercellular and extensively infiltrated with lymphoid and plasmacytoid cells (",
    " <a class=\"graphic graphic_picture graphicRef66365 \" href=\"UTD.htm?
    28/2/28708\">",
    " picture 3",
    " </a>",
    " ). Intranuclear vacuoles containing IgM monoclonal protein (Dutcher bodies)
    within the malignant cells of WM are common (",
    " <a class=\"graphic graphic_picture graphicRef67576 \" href=\"UTD.htm?
    17/54/18272\">",
    " picture 4",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " Details on the morphologic, immunophenotypic, and genetic abnormalities seen
    in lymphoplasmacytic lymphoma are presented separately (",
    " <a class=\"graphic graphic_table graphicRef69760 \" href=\"UTD.htm?
    3/16/3341\">",
    " table 2",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/61/38872?
    source=see_link\">",
    " \"Clinical manifestations, pathologic features, and diagnosis of
    lymphoplasmacytic lymphoma\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h2\">",
    " Serum protein electrophoresis",
    " </span>",
    " &nbsp;&mdash;&nbsp;The detection of a monoclonal IgM protein in the serum is a
    key diagnostic criterion for WM. Serum protein electrophoresis (SPEP) reveals a
    sharp, narrow spike or dense band of monoclonal IgM, usually migrating in the gamma
    area (",
    " <a class=\"graphic graphic_figure graphicRef61928 \" href=\"UTD.htm?
    34/2/34862\">",
    " figure 1",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/58/10154?
    source=see_link&amp;anchor=H10#H10\">",
    " \"Recognition of monoclonal proteins\", section on 'Monoclonal gammopathy'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " While SPEP is a good screening test for monoclonal protein, additional
    studies, usually serum immunofixation, must be performed in order to confirm the
    presence of a monoclonal protein and to determine its type. The quantitative IgM
    level obtained by nephelometry may be 2 or 3",
    " <span class=\"nowrap\">",
    " g/dL",
    " </span>",
    " more than that found in the serum protein electrophoretic spike [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/51\">",
    " 51",
    " </a>",
    " ]. Consequently, the method used to measure the serum protein abnormality must
    be consistent during diagnosis and follow-up. Immunodiffusion methods should not be
    used in WM (or multiple myeloma), because this technique is inaccurate with IgA and
    IgM [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/52\">",
    " 52",
    " </a>",
    " ]. In the setting of cryoglobulins or cold agglutinins, the sample should be
    warmed prior to quantitation of the monoclonal protein in order to minimize
    interference by these entities.",
    " </p>",
    " <p>",
    " In each individual case, immunoperoxidase staining detects either kappa or
    lambda light chains, but not both. Seventy-five percent of the IgM proteins are of
    the kappa light chain type. Reciprocal reductions in the concentrations of IgG and
    IgA are often present, but are not as profound as in multiple myeloma.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <span class=\"h2\">",
    " Serum viscosity",
    " </span>",
    " &nbsp;&mdash;&nbsp;Serum viscosity should be performed in any patient with a
    monoclonal gammopathy and signs and symptoms suggesting the hyperviscosity
    syndrome. Serum viscosity should also be determined whenever the monoclonal IgM
    protein spike is &gt;4",
    " <span class=\"nowrap\">",
    " g/dL.",
    " </span>",
    " (See",
    " <a class=\"local\" href=\"#H7\">",
    " 'Hyperviscosity syndrome'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " The relationship between serum viscosity and IgM protein concentration is
    nonlinear. Thus, with low serum IgM concentrations, an increase of 1 to 2",
    " <span class=\"nowrap\">",
    " g/dL",
    " </span>",
    " produces only a small increase in serum viscosity, but with IgM levels of 4 to
    5",
    " <span class=\"nowrap\">",
    " g/dL,",
    " </span>",
    " an increment of 1 to 2",
    " <span class=\"nowrap\">",
    " g/dL",
    " </span>",
    " greatly increases viscosity.",
    " </p>",
    " <p>",
    " The normal value for serum viscosity is 1.8 centipoise (CP), but
    hyperviscosity symptoms are rarely present unless the viscosity is &gt;4 CP. Many
    laboratories report viscosity in relative terms (eg, relative to distilled water or
    saline) rather than in absolute terms (ie, CP). Because relative and absolute
    viscosities of plasma are similar, these two units can be used interchangeably.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/58/10154?
    source=see_link&amp;anchor=H2213249#H2213249\">",
    " \"Recognition of monoclonal proteins\", section on 'Serum viscosity'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H180513910\">",
    " <span class=\"h2\">",
    " Serum free light chain assay",
    " </span>",
    " &nbsp;&mdash;&nbsp;The serum free light chain (FLC) assay measures serum kappa
    and lambda light chain levels, which can then be expressed as a FLC kappa to lambda
    ratio. Patients without proliferative disorders of plasma cells or B-lymphocytes
    have normal FLC ratios [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/53\">",
    " 53",
    " </a>",
    " ]. In comparison, patients with plasma cell disorders will have greater than
    expected proportions of kappa or lambda light chains resulting in an abnormal
    ratio. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/58/10154?
    source=see_link&amp;anchor=H2212928#H2212928\">",
    " \"Recognition of monoclonal proteins\", section on 'Serum free light
    chains'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " There is a paucity of data regarding serum FLC assays in patients with WM.
    While initial studies suggest that FLC levels correlate with other markers of tumor
    burden [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/54-56\">",
    " 54-56",
    " </a>",
    " ], the role of FLC assays in the diagnosis and determination of treatment
    response need further clarification in prospective trials.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H20\">",
    " <span class=\"h2\">",
    " Laboratory artifacts",
    " </span>",
    " &nbsp;&mdash;&nbsp;Circulating monoclonal protein may interfere with one or
    more laboratory tests performed on liquid-based automated analyzers, either by
    precipitating during the analysis, or by virtue of specific binding properties. The
    most common artifacts are a low value for HDL cholesterol, a high value for
    bilirubin, as well as altered measurement of inorganic phosphate. Other examples
    include interference with measurement of LDL cholesterol, C-reactive protein,
    antistreptolysin-O, creatinine, glucose, urea nitrogen, iron, and inorganic
    calcium. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/58/10154?
    source=see_link&amp;anchor=H5#H5\">",
    " \"Recognition of monoclonal proteins\", section on 'Interference with
    laboratory tests'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H21\">",
    " <span class=\"h1\">",
    " DIAGNOSIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The diagnosis of WM is made based upon an evaluation of a
    bone marrow biopsy specimen, analysis of the serum protein components, and
    consideration of the clinical scenario [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/57-59\">",
    " 57-59",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " To make a diagnosis of WM, the following criteria must be met [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/58\">",
    " 58",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " An IgM monoclonal gammopathy (of any size) must be present in the serum.",
    " </li>",
    " <li>",
    " Ten percent or more of the bone marrow biopsy sample must demonstrate
    infiltration by small lymphocytes that exhibit plasmacytoid or plasma cell
    differentiation (lymphoplasmacytic features or lymphoplasmacytic lymphoma) with an
    intertrabecular pattern.",
    " </li>",
    " <li>",
    " This infiltrate should express a typical immunophenotype (eg, surface
    IgM+,",
    " <span class=\"nowrap\">",
    " CD5+/-,",
    " </span>",
    " CD10-, CD19+, CD20+, CD22+, CD23-, CD25+, CD27+, FMC7+, CD103-, CD138-). The
    plasmacytic component will be CD138+, CD38+ and CD45- or dim.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Variations from the typical immunophenotype may occur, but the goal is to
    satisfactorily exclude other lymphoproliferative disorders, including chronic
    lymphocytic leukemia and mantle cell lymphoma. Details on the morphologic,
    immunophenotypic, and genetic abnormalities seen in lymphoplasmacytic lymphoma are
    presented separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/61/38872?
    source=see_link\">",
    " \"Clinical manifestations, pathologic features, and diagnosis of
    lymphoplasmacytic lymphoma\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22\">",
    " <span class=\"h1\">",
    " DIFFERENTIAL DIAGNOSIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;WM must be differentiated from other monoclonal
    gammopathies and lymphomas. Specifically, WM must be differentiated from IgM
    monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma,
    chronic lymphocytic leukemia, and mantle cell lymphoma (",
    " <a class=\"graphic graphic_table graphicRef69760 \" href=\"UTD.htm?
    3/16/3341\">",
    " table 2",
    " </a>",
    " and",
    " <a class=\"graphic graphic_table graphicRef82116 \" href=\"UTD.htm?
    31/39/32380\">",
    " table 3",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " In addition, WM can transform into a more aggressive disease akin to Richter's
    transformation, typically with elevated serum lactate dehydrogenase levels,
    chromosomal abnormalities, aneuploid DNA content, immunoblastic morphology, and
    poor response to therapy. This subject is discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?5/19/5433?
    source=see_link\">",
    " \"Pathobiology and treatment of histologic transformation in the indolent
    non-Hodgkin lymphomas\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H23\">",
    " <span class=\"h2\">",
    " IgM monoclonal gammopathy of undetermined significance",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients with IgM MGUS are diagnosed based upon the
    following criteria:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Serum IgM concentration &lt;3.0",
    " <span class=\"nowrap\">",
    " g/dL",
    " </span>",
    " </li>",
    " <li>",
    " The absence of anemia, hepatosplenomegaly, lymphadenopathy, and systemic
    symptoms",
    " </li>",
    " <li>",
    " Minimal or no lymphoplasmacytic infiltration of the bone marrow; overall
    marrow involvement by such cells should be &lt;10 percent.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " This subject is discussed in depth separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/60/4041?
    source=see_link&amp;anchor=H22391020#H22391020\">",
    " \"Clinical course and management of monoclonal gammopathy of undetermined
    significance\", section on 'IgM MGUS'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H24\">",
    " <span class=\"h2\">",
    " Smoldering Waldenstr&ouml;m macroglobulinemia",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients who meet criteria for WM but do not have any
    clinical symptoms and lack evidence of anemia, hepatosplenomegaly, lymphadenopathy,
    or hyperviscosity are considered to have smoldering Waldenstr&ouml;m
    macroglobulinemia. These patients do not require therapy but need to be monitored
    for disease progression. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/47/37626?
    source=see_link&amp;anchor=H3#H3\">",
    " \"Treatment and prognosis of Waldenstr&ouml;m macroglobulinemia\", section on
    'Asymptomatic patients'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H25\">",
    " <span class=\"h2\">",
    " Multiple myeloma",
    " </span>",
    " &nbsp;&mdash;&nbsp;Classical multiple myeloma with an IgM paraprotein is
    extremely rare, comprising only 0.5 percent of the Mayo Clinic series. Often, the
    lymphoplasmacytic lymphoma seen in the bone marrow of patients with WM can be
    distinguished from plasma cells seen in the bone marrow of patients with multiple
    myeloma by the absence of CD56 and the presence of a substantial small lymphocytic
    component that expresses a clonal surface immunoglobulin.",
    " </p>",
    " <p>",
    " In difficult cases, one may have to rely on the differences in clinical
    presentation to exclude multiple myeloma. For example, a diagnosis of IgM multiple
    myeloma is preferred over a diagnosis of WM if bone lesions are present. Symptoms
    of hyperviscosity, and the presence of lymphadenopathy",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " splenomegaly favor a diagnosis of WM. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/13/35034?
    source=see_link&amp;anchor=H11#H11\">",
    " \"Clinical features, laboratory manifestations, and diagnosis of multiple
    myeloma\", section on 'Monoclonal proteins'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Chromosomal abnormalities may also be of help in making this distinction.
    While most cases of MM have an abnormal DNA content, WM will typically have a
    diploid DNA content, unless it has transformed to Richter&rsquo;s syndrome.
    Patients with multiple myeloma and t(11;14) may have lymphoplasmacytic or small
    mature plasma cell morphology, along with CD20 expression. The t(11;14)
    translocation is not seen in WM, and its presence suggests IgM myeloma. In one
    study, this translocation was seen in seven of eight patients with IgM myeloma and
    in none of 74 patients with WM [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/60\">",
    " 60",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/23/10618?
    source=see_link&amp;anchor=H9#H9\">",
    " \"Staging and prognostic studies in multiple myeloma\", section on
    'Fluorescent in situ hybridization (FISH)'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H26\">",
    " <span class=\"h2\">",
    " Chronic lymphocytic leukemia",
    " </span>",
    " &nbsp;&mdash;&nbsp;Polyclonal increases in gamma globulins can be seen in up
    to 15 percent of patients with chronic lymphocytic leukemia (CLL). CLL can be
    easily differentiated from WM by its immunophenotype.",
    " </p>",
    " <p>",
    " In contrast to WM, the abnormal B-cells in CLL are CD5 positive, CD23
    positive, and FMC7 negative. Gene expression profiling studies of WM cells reveal a
    phenotype more akin to chronic lymphocytic leukemia than multiple myeloma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/61\">",
    " 61",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/38/35431?
    source=see_link\">",
    " \"Pathologic features, diagnosis, and differential diagnosis of chronic
    lymphocytic leukemia\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H27\">",
    " <span class=\"h2\">",
    " Mantle cell lymphoma",
    " </span>",
    " &nbsp;&mdash;&nbsp;In contrast to WM and other indolent non-Hodgkin lymphomas,
    nuclear staining for cyclin D1 (bcl-1) is present in more than 70 percent of cases
    of mantle cell lymphoma (MCL). Most MCLs also have t(11;14)(q13;q32), a
    translocation seen in some cases of multiple myeloma, but not in WM. In MCL, the
    clonal cells are characteristically CD5 positive, CD23 negative. In contrast, in WM
    the clonal population is typically C5 negative and CD23 negative. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/29/30169?
    source=see_link&amp;anchor=H7#H7\">",
    " \"Clinical manifestations, pathologic features, and diagnosis of mantle cell
    lymphoma\", section on 'Cyclin D1'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H28\">",
    " <span class=\"h2\">",
    " Amyloidosis",
    " </span>",
    " &nbsp;&mdash;&nbsp;On occasion, patients may have both WM and an IgM-related
    systemic amyloidosis. The clinical presentation in primary (AL) amyloidosis depends
    on the number and nature of the organs affected and may include nephrotic syndrome,
    restrictive cardiomyopathy, peripheral neuropathy, hepatomegaly, macroglossia, or
    purpura. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/15/7418?
    source=see_link&amp;anchor=H143177#H143177\">",
    " \"Clinical presentation, laboratory manifestations, and diagnosis of
    immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)\", section on
    'Clinical presentation'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " One series described 50 patients with an IgM monoclonal protein and systemic
    amyloidosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/62\">",
    " 62",
    " </a>",
    " ]. Six (12 percent) had a serum IgM protein concentration &gt;3",
    " <span class=\"nowrap\">",
    " g/dL.",
    " </span>",
    " The majority had an increase of lymphocytes and plasma cells in the bone
    marrow. In the eight patients in whom it was studied, the amyloid deposits
    consisted of a monoclonal immunoglobulin light chain, indicating that the
    amyloidosis was of the primary (AL) type. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/15/7418?
    source=see_link\">",
    " \"Clinical presentation, laboratory manifestations, and diagnosis of
    immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " A retrospective French collection of patients with IgM-related systemic AL
    amyloidosis has been reported; 53 of the 64 patients (83 percent) had a prior
    diagnosis of either WM or lymphoplasmacytic non-Hodgkin lymphoma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/47/762/abstract/63\">",
    " 63",
    " </a>",
    " ]. The median elapsed time between diagnosis of the IgM-related disorder and
    amyloidosis was 8 months (range: 0 to 192 months). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/15/7418?
    source=see_link&amp;anchor=H1664740#H1664740\">",
    " \"Clinical presentation, laboratory manifestations, and diagnosis of
    immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)\", section on
    'IgM-associated AL amyloidosis'",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H29\">",
    " <span class=\"h1\">",
    " SUMMARY",
    " </span>",
    " &nbsp;&mdash;&nbsp;Waldenstr&ouml;m macroglobulinemia (WM) is a rare
    clinicopathologic entity demonstrating 10 percent or greater infiltration of the
    bone marrow by clonal lymphoplasmacytic cells and a monoclonal IgM gammopathy in
    the blood. Patients usually present in their seventh decade with symptoms related
    to the infiltration of the hematopoietic tissues or the effects of monoclonal IgM
    in the blood. (See",
    " <a class=\"local\" href=\"#H6575411\">",
    " 'Introduction'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H2\">",
    " 'Epidemiology'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " WM most commonly presents with pallor, oronasal bleeding, systemic
    complaints (eg, weakness, fatigue, weight loss, fever, night sweats) and
    organomegaly (eg, enlarged lymph nodes, spleen,",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " liver). In contrast to patients with multiple myeloma, involvement of the
    bone or kidneys is uncommon. (See",
    " <a class=\"local\" href=\"#H6\">",
    " 'Overview'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " An important presentation includes central nervous system signs and symptoms
    due to the hyperviscosity syndrome (eg, blurring or loss of vision, headache,
    ataxia, dementia, stroke, or coma). This may be severe enough to constitute a
    medical emergency, requiring urgent plasmapheresis. (See",
    " <a class=\"local\" href=\"#H7\">",
    " 'Hyperviscosity syndrome'",
    " </a>",
    " above and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/47/37626?
    source=see_link&amp;anchor=H7#H7\">",
    " \"Treatment and prognosis of Waldenstr&ouml;m macroglobulinemia\", section
    on 'Emergent management of hyperviscosity'",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " A classic finding in WM associated with hyperviscosity is the presence of
    dilated, segmented, and tortuous retinal veins, giving a \"sausage link\"
    appearance (",
    " <a class=\"graphic graphic_picture graphicRef50216 \" href=\"UTD.htm?
    20/45/21215\">",
    " picture 1",
    " </a>",
    " ). (See",
    " <a class=\"local\" href=\"#H9\">",
    " 'Funduscopic abnormalities'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Another major presentation is that of neurologic symptoms such as
    paresthesias and weakness. Other neurologic complaints may include cranial nerve
    palsies and sudden deafness. (See",
    " <a class=\"local\" href=\"#H8\">",
    " 'Neuropathy'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Patients with WM who are asymptomatic are considered to have smoldering WM
    (SWM).",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The diagnosis of WM is made when the following two criteria are met (see",
    " <a class=\"local\" href=\"#H21\">",
    " 'Diagnosis'",
    " </a>",
    " above):",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Presence of an IgM monoclonal paraprotein on serum immunofixation. (See",
    " <a class=\"local\" href=\"#H18\">",
    " 'Serum protein electrophoresis'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Ten percent or more of the bone marrow biopsy sample must demonstrate
    infiltration by small lymphocytes that exhibit plasmacytoid or plasma cell
    differentiation (lymphoplasmacytic features or lymphoplasmacytic lymphoma) with an
    intertrabecular pattern. This infiltrate should express a typical immunophenotype
    (eg, surface IgM+,",
    " <span class=\"nowrap\">",
    " CD5+/-,",
    " </span>",
    " CD10-, CD19+, CD20+, CD22+, CD23-, CD25+, CD27+, FMC7+, CD103-, CD138-).
    (See",
    " <a class=\"local\" href=\"#H17\">",
    " 'Bone marrow examination'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The differential diagnosis includes other monoclonal gammopathies and
    lymphomas. Specifically, WM must be differentiated from IgM monoclonal gammopathy
    of undetermined significance (MGUS), multiple myeloma, chronic lymphocytic
    leukemia, and mantle cell lymphoma. (See",
    " <a class=\"local\" href=\"#H22\">",
    " 'Differential diagnosis'",
    " </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>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/30\">",
    " Dimopoulos MA, Panayiotidis P, Moulopoulos LA, et al. Waldenstr&ouml;m's
    macroglobulinemia: clinical features, complications, and management. J Clin Oncol
    2000; 18:214.",
    " </a>",
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    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/31\">",
    " Pavy MD, Murphy PL, Virella G. Paraprotein-induced hyperviscosity. A
    reversible cause of stroke. Postgrad Med 1980; 68:109.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/32\">",
    " Mueller J, Hotson JR, Langston JW. Hyperviscosity-induced dementia.
    Neurology 1983; 33:101.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/33\">",
    " Bloch KJ, Maki DG. Hyperviscosity syndromes associated with immunoglobulin
    abnormalities. Semin Hematol 1973; 10:113.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/34\">",
    " Crawford J, Cox EB, Cohen HJ. Evaluation of hyperviscosity in monoclonal
    gammopathies. Am J Med 1985; 79:13.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/35\">",
    " Rudnicki SA, Harik SI, Dhodapkar M, et al. Nervous system dysfunction in
    Waldenstr&ouml;m's macroglobulinemia: response to treatment. Neurology 1998;
    51:1210.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/36\">",
    " Baehring JM, Hochberg EP, Raje N, et al. Neurological manifestations of
    Waldenstr&ouml;m macroglobulinemia. Nat Clin Pract Neurol 2008; 4:547.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/37\">",
    " Richards AI. Response of meningeal Waldenstr&ouml;m's macroglobulinemia to
    2-chlorodeoxyadenosine. J Clin Oncol 1995; 13:2476.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/38\">",
    " Dalakas MC, Flaum MA, Rick M, et al. Treatment of polyneuropathy in
    Waldenstr&ouml;m's macroglobulinemia: role of paraproteinemia and immunologic
    studies. Neurology 1983; 33:1406.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/39\">",
    " Morel-Maroger L, Basch A, Danon F, et al. Pathology of the kidney in
    Waldenstr&ouml;m's macroglobulinemia. Study of sixteen cases. N Engl J Med 1970;
    283:123.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/40\">",
    " Veltman GA, van Veen S, Kluin-Nelemans JC, et al. Renal disease in
    Waldenstr&ouml;m's macroglobulinaemia. Nephrol Dial Transplant 1997; 12:1256.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/41\">",
    " Lindstr&ouml;m FD, Hed J, Enestr&ouml;m S. Renal pathology of
    Waldenstr&ouml;m's macroglobulinaemia with monoclonal antiglomerular antibodies and
    nephrotic syndrome. Clin Exp Immunol 1980; 41:196.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/42\">",
    " Veloso FT, Fraga J, Saleiro JV. Macroglobulinemia and small intestinal
    disease. A case report with review of the literature. J Clin Gastroenterol 1988;
    10:546.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/43\">",
    " Pratz KW, Dingli D, Smyrk TC, Lust JA. Intestinal lymphangiectasia with
    protein-losing enteropathy in Waldenstrom macroglobulinemia. Medicine (Baltimore)
    2007; 86:210.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/44\">",
    " Takahashi K, Yamamura F, Motoyama H. IgM myeloma--its distinction from
    Waldenstr&ouml;m's macroglobulinemia. Acta Pathol Jpn 1986; 36:1553.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/45\">",
    " Cobb MW, Domloge-Hultsch N, Frame JN, Yancey KB. Waldenstr&ouml;m
    macroglobulinemia with an IgM-kappa antiepidermal basement membrane zone antibody.
    Arch Dermatol 1992; 128:372.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/46\">",
    " Lowe L, Fitzpatrick JE, Huff JC, et al. Cutaneous macroglobulinosis. A case
    report with unique ultrastructural findings. Arch Dermatol 1992; 128:377.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/47\">",
    " Gressier L, Hotz C, Leli&egrave;vre JD, et al. Cutaneous macroglobulinosis:
    a report of 2 cases. Arch Dermatol 2010; 146:165.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/48\">",
    " Schnitzler L, Schubert B, Boasson M, et al. Urticaire chronique,
    l&eacute;sions osseuses, macroglobulin&eacute;mie IgM: Maladie de Waldenstrom?
    Bulletin de la Societe Francaise Dermatologica Sypholologie 1974; 81:363.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/49\">",
    " Coleman M, Vigliano EM, Weksler ME, Nachman RL. Inhibition of fibrin monomer
    polymerization by lambda myeloma globulins. Blood 1972; 39:210.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/50\">",
    " Penny R, Castaldi PA, Whitsed HM. Inflammation and haemostasis in
    paraproteinaemias. Br J Haematol 1971; 20:35.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/51\">",
    " Riches PG, Sheldon J, Smith AM, Hobbs JR. Overestimation of monoclonal
    immunoglobulin by immunochemical methods. Ann Clin Biochem 1991; 28 ( Pt 3):253.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/52\">",
    " Virella G, Fundenberg HH. Comparison of immunoglobulin determinations in
    pathological sera by radial immunodiffusion and laser nephelometry. Clin Chem 1977;
    23:1925.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/53\">",
    " Katzmann JA, Abraham RS, Dispenzieri A, et al. Diagnostic performance of
    quantitative kappa and lambda free light chain assays in clinical practice. Clin
    Chem 2005; 51:878.",
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/54\">",
    " Itzykson R, Le Garff-Tavernier M, Katsahian S, et al. Serum-free light chain
    elevation is associated with a shorter time to treatment in Waldenstrom's
    macroglobulinemia. Haematologica 2008; 93:793.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/55\">",
    " Leleu X, Moreau AS, Weller E, et al. Serum immunoglobulin free light chain
    correlates with tumor burden markers in Waldenstrom macroglobulinemia. Leuk
    Lymphoma 2008; 49:1104.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/56\">",
    " Leleu X, Xie W, Bagshaw M, et al. The role of serum immunoglobulin free
    light chain in response and progression in waldenstrom macroglobulinemia. Clin
    Cancer Res 2011; 17:3013.",
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    " </li>",
    " <li>",
    " Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization
    Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon
    2008.",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/58\">",
    " Owen RG, Treon SP, Al-Katib A, et al. Clinicopathological definition of
    Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second
    International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol 2003;
    30:110.",
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    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/59\">",
    " Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and
    management of Waldenstrom's macroglobulinemia. J Clin Oncol 2005; 23:1564.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/60\">",
    " Avet-Loiseau H, Garand R, Lod&eacute; L, et al. Translocation t(11;14)
    (q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants.
    Blood 2003; 101:1570.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/61\">",
    " Chng WJ, Schop RF, Price-Troska T, et al. Gene-expression profiling of
    Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic
    lymphocytic leukemia than multiple myeloma. Blood 2006; 108:2755.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/62\">",
    " Gertz MA, Kyle RA, Noel P. Primary systemic amyloidosis: a rare complication
    of immunoglobulin M monoclonal gammopathies and Waldenstr&ouml;m's
    macroglobulinemia. J Clin Oncol 1993; 11:914.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/47/762/abstract/63\">",
    " Terrier B, Jaccard A, Harousseau JL, et al. The clinical spectrum of IgM-
    related amyloidosis: a French nationwide retrospective study of 72 patients.
    Medicine (Baltimore) 2008; 87:99.",
    " </a>",
    " </li>",
    " </ol>",
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    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H29\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H6575411\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " EPIDEMIOLOGY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " ETIOLOGY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " PATHOGENESIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " CLINICAL PRESENTATION",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " Overview",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " Hyperviscosity syndrome",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Neuropathy",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " Funduscopic abnormalities",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " Cryoglobulinemia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " Kidney involvement",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " Gastrointestinal symptoms",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " Other",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " LABORATORY FINDINGS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " Complete blood count",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " Platelet function and blood coagulation",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " Bone marrow examination",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " Serum protein electrophoresis",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H19\">",
    " Serum viscosity",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H180513910\">",
    " Serum free light chain assay",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H20\">",
    " Laboratory artifacts",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H21\">",
    " DIAGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H22\">",
    " DIFFERENTIAL DIAGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H23\">",
    " IgM monoclonal gammopathy of undetermined significance",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H24\">",
    " Smoldering Waldenstr&ouml;m macroglobulinemia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H25\">",
    " Multiple myeloma",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H26\">",
    " Chronic lymphocytic leukemia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H27\">",
    " Mantle cell lymphoma",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H28\">",
    " Amyloidosis",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H29\">",
    " SUMMARY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"HEME/6657\" 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=\"HEME/6657|FIG\">",
    " <a href=\"#\" title=\"FIGURES\">",
    " FIGURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?34/2/34862\"
    title=\"figure 1\">",
    " SPEP in WM",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"HEME/6657|PIC\">",
    " <a href=\"#\" title=\"PICTURES\">",
    " PICTURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?20/45/21215\"
    title=\"picture 1\">",
    " Retinopathy in WM",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?27/33/28183\"
    title=\"picture 2\">",
    " Rouleaux in myeloma",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?28/2/28708\"
    title=\"picture 3\">",
    " Lymphoplasmacytic cells in WM",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?17/54/18272\"
    title=\"picture 4\">",
    " Dutcher body",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"HEME/6657|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?39/8/40076\" title=\"table
    1\">",
    " Immunoglobulin genes in B cells",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?3/16/3341\" title=\"table
    2\">",
    " Ddx LPL path",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?31/39/32380\" title=\"table
    3\">",
    " DDx WM",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
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    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/62/35815?
    source=related_link\">",
    " Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and
    heavy chain deposition diseases",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/38/35431?
    source=related_link\">",
    " Pathologic features, diagnosis, and differential diagnosis of chronic
    lymphocytic leukemia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/59/23482?
    source=related_link\">",
    " Platelet function testing",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/50/3881?
    source=related_link\">",
    " Protein-losing gastroenteropathy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/58/10154?
    source=related_link\">",
    " Recognition of monoclonal proteins",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/23/10618?
    source=related_link\">",
    " Staging and prognostic studies in multiple myeloma",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/47/37626?
    source=related_link\">",
    " Treatment and prognosis of Waldenstr&ouml;m macroglobulinemia",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_47_763="Abnormal pressure SOD";
    var content_f0_47_763=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=GAST
    %2F65380&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=GAST
    %2F65380&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\">",
    " Abnormal pressure profile of sphincter of Oddi measured at common bile duct
    and pancreatic duct",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td>",
    " Basal pressure (mmHg)",
    " </td>",
    " <td>",
    " &gt;40",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Phasic contractions (mmHg)",
    " </td>",
    " <td>",
    " &gt;350",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Frequency (per minute)",
    " </td>",
    " <td>",
    " &gt;7",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Retrograde sequence (percent)",
    " </td>",
    " <td>",
    " &gt;50",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_763=[""].join("\n");
    var outline_f0_47_763=null;
    var title_f0_47_764="Burns epi deaths";
    var content_f0_47_764=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=SURG
    %2F50206&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=7\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=SURG
    %2F50206&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=7\" 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\">",
    " Estimated deaths from fire-related burn injuries* in 2004, by World Health
    Organization region",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tr>",
    " <td class=\"subtitle1\">",
    " &nbsp;",
    " </td>",
    " <td class=\"subtitle1\">",
    " Africa",
    " </td>",
    " <td class=\"subtitle1\">",
    " The Americas",
    " </td>",
    " <td class=\"subtitle1\">",
    " EMR&bull;",
    " </td>",
    " <td class=\"subtitle1\">",
    " Europe",
    " </td>",
    " <td class=\"subtitle1\">",
    " SEAR&Delta;",
    " </td>",
    " <td class=\"subtitle1\">",
    " WPR&loz;",
    " </td>",
    " <td class=\"subtitle1\">",
    " World",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Population (000)",
    " </td>",
    " <td>",
    " 737,536",
    " </td>",
    " <td>",
    " 874,380",
    " </td>",
    " <td>",
    " 519,688",
    " </td>",
    " <td>",
    " 883,311",
    " </td>",
    " <td>",
    " 1,671,904",
    " </td>",
    " <td>",
    " 1,738,457",
    " </td>",
    " <td>",
    " 6,436,826",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Burn deaths (000)",
    " </td>",
    " <td>",
    " 48",
    " </td>",
    " <td>",
    " 8",
    " </td>",
    " <td>",
    " 29",
    " </td>",
    " <td>",
    " 23",
    " </td>",
    " <td>",
    " 186",
    " </td>",
    " <td>",
    " 16",
    " </td>",
    " <td>",
    " 310",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Percent of deaths&sect;",
    " </td>",
    " <td>",
    " 6.51",
    " </td>",
    " <td>",
    " 0.91",
    " </td>",
    " <td>",
    " 5.58",
    " </td>",
    " <td>",
    " 2.60",
    " </td>",
    " <td>",
    " 1.11",
    " </td>",
    " <td>",
    " 0.92",
    " </td>",
    " <td>",
    " 0.53",
    " </td>",
    " </tr>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " * Burns covering 20 percent or more of total body surface area.",
    " <br>",
    " &bull; Eastern Mediterranean region.",
    " <br>",
    " &Delta; South-East Asia region.",
    " <br>",
    " &loz; Western Pacific region.",
    " <br>",
    " &sect; Percent of all deaths attributed to burn injuries.",
    " </br>",
    " </br>",
    " </br>",
    " </br>",
    " </div>",
    " <div class=\"reference\">",
    " Data from: World Health Organization. Disease and injury estimates for 2004.
    Morbidity and Mortality. Deaths. Summary: Deaths (000s) by cause, in WHO regions,
    estimates for 2004.
    www.who.int/healthinfo/global_burden_disease/estimates_regional/en/index.html.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_764=[""].join("\n");
    var outline_f0_47_764=null;
    var title_f0_47_765="Conditions increasing ischemia";
    var content_f0_47_765=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=CARD
    %2F53315&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=CARD
    %2F53315&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\">",
    " Conditions provoking or exacerbating ischemia",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\" class=\"container\">",
    " <tr>",
    " <td class=\"container\">",
    " <table cellspacing=\"0\">",
    " <tr>",
    " <td class=\"subtitle1_single\">",
    " Increased oxygen demand",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle2_single\">",
    " Non-cardiac",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Hyperthermia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Hyperthyroidism",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Sympathomimetic toxicity (eg, cocaine use)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Hypertension",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Anxiety",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Arteriovenous fistulae",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle2_single\">",
    " Cardiac",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Hypertrophic cardiomyopathy",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Aortic stenosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Dilated cardiomyopathy",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2_start\">",
    " Tachycardia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Ventricular",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Supraventricular",
    " </td>",
    " </tr>",
    " </table>",
    " </td>",
    " <td class=\"container\">",
    " <table cellspacing=\"0\">",
    " <tr>",
    " <td class=\"subtitle1_single\">",
    " Decreased oxygen supply",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle2_single\">",
    " Non-cardiac",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Anemia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2_start\">",
    " Hypoxemia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Pneumonia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Asthma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Chronic obstructive pulmonary disease",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Pulmonary hypertension",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Interstitial pulmonary fibrosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Obstructive sleep apnea",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Sickle cell disease",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Sympathomimetic toxicity (eg, cocaine use)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2_start\">",
    " Hyperviscosity",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Polycythemia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Leukemia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Thrombocytosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"sublist2\">",
    " Hypergammaglobulinemia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle2_single\">",
    " Cardiac",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Aortic stenosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Hypertrophic cardiomyopathy",
    " </td>",
    " </tr>",
    " </table>",
    " </td>",
    " </tr>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: ACC/AHA/ACP Guidelines for the Management of
    Patients with Chronic Stable Angina. J Am Coll Cardiol 1999; 33:2092. Copyright
    &copy;1999 American College of Cardiology.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_765=[""].join("\n");
    var outline_f0_47_765=null;
    var title_f0_47_766="Dietary counseling tips";
    var content_f0_47_766=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PEDS
    %2F80182&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=5\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
    %2F80182&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=5\" 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\">",
    " Tips for dietary counseling in children",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " Challenge",
    " </td>",
    " <td class=\"subtitle1\">",
    " Possible solutions",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"4\">",
    " Family has little or no structure to dietary patterns (few family meals,
    meals are not eaten at the table, television on during meals, etc...)",
    " </td>",
    " <td>",
    " Encourage family to eat meals together.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Emphasize scheduling of meals and snacks.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Avoid skipping meals.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Limit meal-time distractions (eg, television).",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"2\">",
    " Child is motivated by sports and activity, but has little interest in
    making dietary changes",
    " </td>",
    " <td>",
    " Emphasize physical activity as primary goal; frame dietary recommendations
    as tools to be stronger and improve athletic performance.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Discuss energy in versus energy out; emphasize the importance of achieving
    proper balance between nutrition and activity.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"3\">",
    " Family frequently eats meals away from home",
    " </td>",
    " <td>",
    " Identify barriers that prevent families from eating at home more often.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide meal-planning resources, initially using recipes that are familiar
    to them; begin the process of cooking more at home using these recipes.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Assess the type of restaurant, usual selections, and discuss
    alternatives.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"2\">",
    " Large portion sizes",
    " </td>",
    " <td>",
    " Emphasize structured (pre-planned and timed) meals and snacks.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide tools and education to help child learn to pay attention to bodily
    cues for hunger and fullness.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"3\">",
    " Fast eating pace",
    " </td>",
    " <td>",
    " Emphasize that eating slowly is important in recognizing fullness.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide family with strategies to slow down eating pace.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Discuss \"mindful eating\" and encourage all family members to practice
    slow, mindful eating.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"2\">",
    " Poor dietary quality (lack of fruits/vegetables and whole grains,
    consumption of whole milk, etc...)",
    " </td>",
    " <td>",
    " Provide education about food groups, discussing the importance of each
    food group as part of the daily diet.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " One approach is to discuss the concept of a \"balanced plate,\" focusing
    on supplying ample vegetables, fruits and fiber (approximately 1/4 plate each for
    vegetables, grains, fruits, and protein). Guidance available at",
    " <a href=\"file://www.choosemyplate.gov/\" target=\"_blank\">",
    " www.choosemyplate.gov",
    " </a>",
    " .",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"2\">",
    " Lacks nutritional knowledge (no label reading, does not make shopping
    list, etc...)",
    " </td>",
    " <td>",
    " Assess family's level of nutritional knowledge, and start by helping them
    set small goals, such as balancing their plates or providing a variety of foods.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " When the family is ready, increase goals gradually by discussing which
    foods should be eaten most often, which foods should be eaten sparingly, and
    teaching the family how to read food labels.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"2\">",
    " Excessive refined grains (white bread) and simple carbohydrates (sugars)",
    " </td>",
    " <td>",
    " Emphasize the importance of including fiber in the diet as a means of
    decreasing hunger and feeling full after eating.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Explain that whole grains are digested and absorbed at a slower rate than
    refined gains and sugars, resulting in a more stable blood sugar which reduces
    hunger and is healthier.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"2\">",
    " High-fat dairy intake",
    " </td>",
    " <td>",
    " Compare nutritional information in high fat dairy products to low fat
    dairy products.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Discuss types of fat: which fats are healthier, and which fats should be
    avoided (ie, trans fats and saturated fats).",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"4\">",
    " Skipping meals",
    " </td>",
    " <td>",
    " Emphasize the importance of eating three regularly-scheduled meals a day
    to have a healthy weight and metabolism.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Explain that meal-skipping can lead to increased hunger and excessive
    eating later.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Start by establishing a small goal to eat just one food group at the time
    that they would usually skip a meal.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Increase goal gradually by introducing other food groups as the child is
    ready; encouraging them to achieve a balanced meal.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"3\">",
    " Excessive snacking",
    " </td>",
    " <td>",
    " Set a snack schedule between meals to encourage less grazing.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Outline several choices for healthy snacks.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Emphasize the importance of eating a single portion of food from two
    different food groups to encourage fullness until the next meal.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"3\">",
    " High intake of sugar-sweetened beverages",
    " </td>",
    " <td>",
    " Discuss empty calories from sugar-containing beverages (which include 100
    percent fruit juice).",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Estimate the number of calories that the child is currently taking from
    beverages.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Suggest low-sugar alternatives for family to try.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"4\">",
    " Low fruit and vegetable intake",
    " </td>",
    " <td>",
    " Provide education regarding serving sizes of vegetables and fruits.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Discuss the importance of fiber from vegetables and fruits.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Have the family try new vegetables and fruits to increase variety.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide quick and easy recipes or products.",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"5\">",
    " Picky eating",
    " </td>",
    " <td>",
    " Introduce child to new foods gradually.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide the same foods for each family member; no \"special orders.\"",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Eat meals and snacks together as a family.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Structure meals and snacks.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Encourage, but do not pressure child to eat a specific food. Continue to
    offer the same food on multiple occasions.",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_766=[""].join("\n");
    var outline_f0_47_766=null;
    var title_f0_47_767="Xray of distal clavicle fracture Type II";
    var content_f0_47_767=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=EM
    %2F57129&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
    %2F57129&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\">",
    " Xray of distal clavicle fracture: Type II",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " This plain radiograph shows a type II fracture of the distal third of the
    clavicle, with characteristic upward displacement of the proximal fragment.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Robert L Hatch, MD, MPH.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_47_767=[""].join("\n");
    var outline_f0_47_767=null;

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