pearls 2

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=90 BGCOLOR="#006699" TEXT="#080000" background="0862c5c3.jpg"> <div> <FONT SIZE="5" COLOR="#FFCC66" FACE="Arial" ><B>USMLE PEARLS</B></FONT><B>    </B><B> |     </B><A HREF="index.htm" TARGET="_top" TITLE="USMLE PEARLS"><U><B>home</B></U></A></div> <div> <A HREF="id18.htm" TARGET="_top" TITLE="pearls 1"><U>pearls 1</U></A>   |   <B>pearls 2</B>   |   <A HREF="id34.htm" TARGET="_top" TITLE="pearls3"><U>pearls3</U></A>   |   <A HREF="id37.htm" TARGET="_top" TITLE="pearls 5"><U>pearls 5</U></A>   |   <A HREF="id38.htm" TARGET="_top" TITLE="pearls4"><U>pearls4</U></A>   |   <A HREF="id36.htm" TARGET="_top" TITLE="photo"><U>photo</U></A>   |   <A HREF="id30.htm" TARGET="_top" TITLE="pth"><U>pth</U></A>   |   <A HREF="id35.htm" TARGET="_top" TITLE="cardiac disease in pregnancy"><U>cardiac disease in pregnancy</U></A>   |   <A HREF="id32.htm" 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TARGET="_top" TITLE="Treatments for Coagulation Disorders in"><U>Treatments for  Coagulation Disorders in Pregnancy </U></A>   |   <A HREF="id26.htm" TARGET="_top" TITLE="Friedrieichs Ataxia"><U>Friedrieich's Ataxia</U></A>   |   <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U>Contact Me</U></A></div> <div> </div> </td> </tr><tr> <td valign="top" width=210 BGCOLOR="#000033" TEXT="#F7F7FF"> <div> <A HREF="id18.htm" TARGET="_top" TITLE="pearls 1"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pearls 1</B></U></A></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pearls 2</B></div> <div> <A HREF="id34.htm" TARGET="_top" TITLE="pearls3"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pearls3</B></U></A></div> <div> <A HREF="id37.htm" TARGET="_top" TITLE="pearls 5"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pearls 5</B></U></A></div> <div> <A HREF="id38.htm" TARGET="_top" TITLE="pearls4"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pearls4</B></U></A></div> <div> <A HREF="id36.htm" TARGET="_top" TITLE="photo"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">photo</B></U></A></div> <div> <A HREF="id30.htm" TARGET="_top" TITLE="pth"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pth</B></U></A></div> <div> <A HREF="id35.htm" TARGET="_top" TITLE="cardiac disease in pregnancy"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cardiac disease in pregnancy</B></U></A></div> <div> <A HREF="id32.htm" TARGET="_top" TITLE="Features of chromosomal defects "><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Features of chromosomal defects </B></U></A></div> <div> <A HREF="id29.htm" TARGET="_top" TITLE="Ultrasound of Fetal Biometrics and Growt"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ultrasound of Fetal Biometrics and Growth</B></U></A></div> <div> <A HREF="id28.htm" TARGET="_top" TITLE="FEMALE MASS"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FEMALE MASS</B></U></A></div> <div> <A HREF="id19.htm" TARGET="_top" TITLE=" testicular feminization syndrome "><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> testicular feminization syndrome </B></U></A></div> <div> <A HREF="id27.htm" TARGET="_top" TITLE="GENYCOMASTIA"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">GENYCOMASTIA</B></U></A></div> <div> <A HREF="id20.htm" TARGET="_top" TITLE="FSH"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FSH</B></U></A></div> <div> <A HREF="id21.htm" TARGET="_top" TITLE="Fragile X Syndrome"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fragile X Syndrome</B></U></A></div> <div> <A HREF="id22.htm" TARGET="_top" TITLE="Mental Retardation "><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mental Retardation </B></U></A></div> <div> <A HREF="id23.htm" TARGET="_top" TITLE="Substance Abuse"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Substance Abuse</B></U></A></div> <div> <A HREF="id24.htm" TARGET="_top" TITLE="Infertility"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Infertility</B></U></A></div> <div> <A HREF="id25.htm" TARGET="_top" TITLE="Treatments for Coagulation Disorders in"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Treatments for  Coagulation Disorders in Pregnancy </B></U></A></div> <div> <A HREF="id26.htm" TARGET="_top" TITLE="Friedrieichs Ataxia"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Friedrieich's Ataxia</B></U></A></div> <div> <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U><B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Contact Me</B></U></A></div> <bR> <div> <B>Mini Incision</B></div> <bR> <div> Unlike traditional or open surgery, a Vesica sling procedure requires only a small incision in the lower abdomen. </div> <bR> <div> <B>Pubic bone with anchor and sutures in place</B></div> <bR> <div> <B>Intra-Abdominal View</B></div> <div> Sling in place, supporting urethra bladder neck and sphincter, like a "hammock" </div> <bR> <div> <B>Crossection View</B></div> <div> Sling in place</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="565" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="279"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="279" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="279"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="279" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 76 WIDTH="279"><div> <B>Before Sling</B></div> <div> The bladder neck is in a dropped position allowing for involuntary leakage of urine due to any downward pressure.</div> </tD> <tD VALIGN=TOP WIDTH="279"><div> <B>After Sling</B></div> <div> The bladder neck and urethra are properly lifted and returned to their normal position.</div> </tD> </tR> </TABLE></div> <div> Correction of Hypermobility</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="565" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 16 WIDTH="279"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="279" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=TOP WIDTH="279"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="279" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 76 WIDTH="279"><div> <B>Before Sling</B></div> <div> The sphincter function is deficient allowing for involuntary leakage due to any downward pressure.</div> </tD> <tD VALIGN=TOP WIDTH="279"><div> <B>After Sling</B></div> <div> Using a sling made of your own vaginal tissue or a synthetic, the sphincter is moved into a closed position.</div> </tD> </tR> </TABLE></div> <div> Correction of ISD</div> <bR> </td> <td valign="top" height=390 BGCOLOR="#FFFFFF" TEXT="#080000" background="08596173.png"> <div> <I>pearls 2</I></div> <div>  <div align="center"><table cellspacing="0" cellpadding="3" border="1"> <tr><td align="center"><a href="http://www.bravenet.com/" target="_top"> <img src="http://images.bravenet.com/pub/sitering/main.gif" width="134" height="61" alt="Bravenet SiteRing" border="0" /></a></td> <td align="center"><font face="Arial,Helvetica" size="2"> <b>The sinoe medical association SiteRing</b><br /> <br />This site owned by<br /> <a href="mailto:sinoe@earthlink.net" target="_top">danil hammoudi.md</A> </font></td></tr> <tr><td colspan="2" align="center"> <a href="http://pub33.bravenet.com/sitering/nav.php?usernum=2787914458&action=prev&siteid=" target="_top"><img src="http://images.bravenet.com/pub/sitering/prev.gif" width="69" height="25" 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href="http://www.bravenet.com/" target="_top">SiteRing by Bravenet.com</a></font> </div>  <IMG SRC="08d649b0.png" border=0 width="356" height="155" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="08e45b40.png" border=0 width="325" height="436" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="08fa0e60.png" border=0 width="416" height="230" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In women, which of the following are the leading causes of cancer death in the United States in descending order</B></div> <div> <B>Lung, breast, colorectal</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The leading causes of cancer death in the United States in women in descending order are </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lung, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">breast,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> colorectal, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ovarian, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and uterine cancer. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The increased rate of lung cancer is associated with the increased rate of smoking by American women.</B></div> <div> <B>====================================================================================================================</B></div> <div> <B><U>urinary stress incontinence</U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Voiding Flow Rate</B></div> <bR> <div> Increased [<6 times per day]</div> <div> normal<B> postvoid </B>residual volume</div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Residual Volume</B></div> <bR> <div>  Decreased </div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Bladder Compliance</B></div> <bR> <div> Increased</div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pelvic examination</B></div> <div> possible cystocele , rectocele, uterine prolapse</div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">q tips test</B></div> <div> >35 degree change</div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033663300.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">OFFICE ASSESSMENT OF </B><B>STRESS</B><B> </B><B>URINARY</B><B> </B><B>INCONTINENCE</B></div> <div> <B>Urinalysis, Postvoiding Residual Volume, and </B><B>Stress</B><B> Test</B></div> <bR> <div> <B>Residual urine may increase due to outlet obstruction or reduced bladder contractility, resulting in overflow </B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B>incontinence</B></FONT><B>. </B></div> <div> <B>A residual volume less than 50 ml is considered normal, over 200 ml is considered inadequate emptying.</B></div> <div> <B> Overflow </B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B>incontinence</B></FONT><B> is most common among institutionalized elderly wo</B><B>me</B><B>n.</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Genuine urinary stress incontinence is characterized by a loss of the urethral/vesicle angle when increases in intra-abdomina/intravesicale pressure fail to be transmitted to the urethra.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> No change occurs in voiding flow rate, residual urine, or bladder compliance. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> </B><B>Stress</B><B> </B><B>Incontinence</B><B> is defined as the</B><B><U> escape of small amounts of urine during "</U></B><B><U>stress</U></B><B><U>"</U></B><B> </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">activity, such as laughing, coughing, sports, and the like.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Escape of urine during '</B><B>stress</B><B>' is due to weakness of pelvic support.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This weakness is often, but not always, associated with childbirth.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A feeling of "something falling out" or prolapse, may also be associated with leaking urine. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> continence depends on strong bladder and pelvic support.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> </B><B>stress</B><B> </B><B>incontinence</B><B> occurs </B></div> <div> <B>when the urethral sphincter or pelvic muscle cannot adequately support the bladder,.</B><B> </B><B>in the absence of any detrusor contraction</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This allows the bladder to slip down into the pelvic cavity and place pressure on the urethra,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> the duct that carries urine from the bladder to outside the body. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">As a result, body movements, such as exercising, coughing or sneezing, can place additional pressure on the bladder causing it to leak. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although it can affect anyone,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> it is a common condition among women who have gone through childbirth or menopause</B></div> <div> In these cases, a surgical procedure, known as bladder neck suspension, alleviates the pressure placed on the urethra by elevating the neck of the bladder. Although effective, the traditional "open" procedure requires a large incision and a long, painful recovery. </div> <bR> <div> Using laparoscopic techniques, surgeons can now perform the same procedure through 3 to 5 tiny openings.</div> <bR> <div> <IMG SRC="08a7c790.png" border=0 width="124" height="121" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="08b83830.png" border=0 width="131" height="131" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="08c58950.jpg" border=0 width="600" height="405" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"><IMG SRC="089a6a60.jpg" border=0 width="422" height="422" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09097bb0.png" border=0 width="151" height="187" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09196ab0.png" border=0 width="150" height="171" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09296ab0.png" border=0 width="150" height="171" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09364790.png" border=0 width="100" height="121" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09464790.png" border=0 width="100" height="121" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09578720.png" border=0 width="120" height="114" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="096a5ae0.png" border=0 width="165" height="174" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="097a5aa0.png" border=0 width="165" height="170" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09864500.png" border=0 width="100" height="80" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="09964500.png" border=0 width="100" height="80" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <TABLE BORDER="2" CELLPADDING="2" CELLSPACING="1" WIDTH="1015" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#000066 > <tR> <tD VALIGN=TOP HEIGHT= 227 WIDTH="1003"><div> There are several types of urinary incontinence:</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stress</B><B> </B><B>incontinence</B><B> (SUI)</B> Presents clinically as the involuntary loss of urine during coughing, sneezing, laughing or other physical activities that increase intra-abdominal pressure. This occurs primarily in women, and can occur in men especially after prostate or other pelvic surgery.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urge </B><B>Incontinence</B><B> (UI</B>) The symptom of UI is the involuntary loss of urine associated with a strong desire to void (urgency). This can be associated with neurologic disorders, it can also be present in individuals who appear to be neurologically normal. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Overflow </B><B>incontinence</B><B> (OI)</B> Involuntary loss of urine associated with over distension of the bladder is termed overflow incontinence. This type of incontinence may have a variety of presentations, including frequent or constant dribbling or urge or stress incontinence. It is very commonly associated with an enlarged prostate.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mixed </B><B>Incontinence</B><B> (MI)</B> It is not unusual for patients to present with a combination of urge and stress incontinence.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Functional </B><B>Incontinence</B><B> (FI)</B> Urine loss which is caused by factors outside the lower urinary tract; such as chronic impairment due to physical or cognitive functioning or both.</div> <bR> </tD> </tR> </TABLE></B></div> <div> <B>The Burch Procedure - What is It?</B></div> <div> During the Burch procedure, the lower bladder is supported by suturing the vagina to the pelvic ligaments. </div> <div> This corrects the weakness so that during a '<FONT SIZE="3" COLOR="#800000" FACE="Arial Narrow" >stress</FONT>' activity,</div> <div>  the bladder does not move down and allow urine to escape.</div> <div> <B>The Burch Procedure - Who Is a Candidate for It?</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Any woman who has frequent <FONT SIZE="3" COLOR="#800000" FACE="Arial Narrow" >urinary</FONT> leakage occurring with coughing, sneezing, laughing, sporting activities, and the like. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Any woman who experiences recurrence due to failure of previous surgery to correct <FONT SIZE="3" COLOR="#800000" FACE="Arial Narrow" >urinary</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial Narrow" >stress</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial Narrow" >incontinence</FONT>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Women with "mixed" <FONT SIZE="3" COLOR="#800000" FACE="Arial Narrow" >urinary</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial Narrow" >incontinence</FONT>, who will also require medication and exercise in addition to the Burch procedure</div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000008000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">urinary</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT><B>incontinence</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B>?</B></FONT></div> <div> <B>Loss of bladder control is not a disease, but rather a sign that a problem exists.</B></div> <div> <B> There are 4 basic forms of </B><B>urinary</B><B> </B><B>incontinence</B><B>:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>stress</B><B>,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> urge, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">overflow </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and reflex. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are caused by a number of possible conditions or disorders that affect the </B><B>urinary</B><B> system.</B></div> <bR> <bR> <div> <B><U>Pathophysiology </U></B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Detrusor Instability (Urge Incontinence) is characterized by spontaneous, uninhibited bladder contractions or spasms. The disorder is usually idiopathic, and it is most common in older, post-menopausal women. Detrusor instability is the most common type of incontinence,</B></div> <bR> <div> <B><U>Overflow Incontinence </U></B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Overflow incontinence is caused by overdistention of the bladder. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dribbling is especially common; </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">however, urgency and stress symptoms may </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The bladder may become distended as a result of detrusor inadequacy (as in diabetes) or because of physical obstruction urinary incontinence, urine leakage, urine leak (prostate hyperplasia in men).</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A large cystocele may </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Iatrogenic Incontinence. The most urinary incontinence, overactive bladder, urine leakage, urine leak common causes are use of antipsychotics, antihistamines, antidepressants, decongestants, diuretics, sedative-hypnotics, and antihypertensives (alpha-blockers).</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other causes of incontinence include loss of intrinsic urethral tone, detrusor muscle hypotonicity, delirium, urinary tract infection, overactive bladder psychiatric disorders, endocrine disorders, and stool impaction incontinence </B></div> <bR> <div> <B>Types of Urinary Incontinence </B></div> <div> <B>Type of urinary incontinence, urine leakage, urine leak, incontenence Incontinence Symptoms Mechanism Common Causes </B></div> <div> <B>Detrusor instability (urge incontinence) Urgency (strong desire to void) Uninhibited detrusor contractions Not caused by any neurologic deficit </B></div> <div> <B>Stress Incontinence Involuntary loss of urine during coughing, sneezing, lifting Intrinsic sphincter deficiency. Hypermobility of bladder neck, altered angle between urethra and bladder base Obstetrical trauma, neurologic lesion,</B></div> <div> <B>pelvic muscle relaxation</B></div> <div> <B> </B></div> <div> <B>Overflow Incontinence Dribbling, urgency, stress Acontractile or underactive detrusor; outlet obstruction Diabetes, drugs, fecal impaction.</B></div> <div> <B>In men: prostate disease</B></div> <bR> <div> <B>In women: anti-incontinence surgery, cystocele</B></div> <div> <B> </B></div> <bR> <div> <B>Clinical Evaluation and Treatment of Incontinence </B></div> <bR> <div> <B>The characteristics of the incontinence Urinary incontinence, urine leakage, urine leak is assessed (on way to bathroom, without </B></div> <bR> <div> <FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B> </B></FONT><B>Many urologists classify </B><B>stress</B><B> </B><B>incontinence</B><B> by a three-category system: </B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Type I</U></B><B> is </B><B>stress</B><B> </B><B>incontinence</B><B> in which the bladder neck and urethra are open and slightly hypermobile (too moveable), and the urethra descends (moves down) less than 2 cm during </B><B>stress</B><B> (that is, the angle of the urethra is nearly unchanged). Type I patients also have little or no sign of </B><B>cystocele</B><B>. </B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Type II</U></B><B> refers to </B><B>stress</B><B> </B><B>incontinence</B><B> in which the bladder neck and urethra are closed and very hypermobile, and the urethra descends more than 2 cm during </B><B>stress</B><B> that is, the angle of the urethra is increased. Type II patients also may have cystocele; if the cystocele is inside the vagina, the classification is Type IIA; if the cystocele is outside the vagina, the classification is Type IIB. </B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Type III</U></B><B>, or intrinsic sphincter deficiency, refers to severe </B><B>stress</B><B> </B><B>incontinence</B><B> in which urethral position and support are not factors, but the urethral sphincter is very weak. Type III patients often have undergone a previous, failed surgical procedure. </B></div> <bR> <div> <FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B> </B></FONT><B>Classification of </B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B>urinary</B></FONT><B> </B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B>incontinence</B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stress</B><B> </B><B>incontinence</B><B> is characterized by involuntary loss of urine occurring with increases in intra-abdominal pressure.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Women complain of </B><B>urinary</B><B> leakage with cough, exercise, laughing, and Valsalva maneuver. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stress</B><B> </B><B>incontinence</B><B> is caused by urethral hypermobility or intrinsic sphincter deficiency</B><FONT SIZE="3" COLOR="#990000" FACE="Arial" ><B>. </B></FONT></div> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urethral hypermobility, the most common cause of </B><B>stress</B><B> </B><B>incontinence</B><B>, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">occurs when there is loss of the anatomic support of the bladder neck. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This damage to the bladder neck supports may be the result of vaginal delivery or tissue atrophy, resulting from advancing age and estrogen withdrawal.</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Intrinsic sphincter deficiency is caused by decreased urethral resting tone. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stress</B><B> </B><B>incontinence</B><B> can occur with advanced pelvic prolapse.</B></div> <bR> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Detrusor instability (</B><B> </B><B>urge </B><B>incontinence</B><B>) </B><B>is defined as the involuntary loss of urine associated with a sudden and strong desire to void (urgency).</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Spontaneous uninhibited detrusor overactivity results in detrusor contractions. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Patients with this condition complain of an inability to control voiding and experience a sudden urgency to void, which is sometimes unsuppressible.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These patients report</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>urinary</B><B> frequency (>7 times/day), </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nocturia (>1 time/night), </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">enuresis, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and pelvic pain. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although detrusor instability is most often</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> iatrogenic,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> secondary causes include </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">urinary</B><B> tract infection,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> anti-</B><B>incontinence</B><B> surgery,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> bladder stones </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">or foreign bodies,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> and bladder cancer. </B></div> <div> <B>Another cause is</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> intrinsic urethral sphincter weakness such as that from </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">myelomeningocele, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">epispadias, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">prostatectomy, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">trauma, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">radiation, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">or sacral cord lesion. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"><IMG SRC="09af5090.png" border=0 width="245" height="265" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B><A HREF="http://www.homedr.com/int.html" TARGET="_top" TITLE="http://www.homedr.com/int.html"><U><B><IMG SRC="09bb40b0.jpg" border=0 width="180" height="267" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></U></A></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <TABLE BORDER="2" CELLPADDING="2" CELLSPACING="1" WIDTH="898" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#FFFF00 > <tR> <tD VALIGN=TOP HEIGHT= 918 WIDTH="886"><div> <I><B><U>Stress</U></B></I><I><B><U> </U></B></I><I><B><U>Incontinence</U></B></I><B><U> </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">is leakage of urine during physical movement, such as coughing, sneezing, bending, or exercising.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This is the most common form of </B><B>incontinence</B><B> in women and can occur at any age.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Usually not much urine is lost, and this type of </B><B>incontinence</B><B> may result from weakened pelvic floor muscles resulting from pregnancy and childbirth</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Hormonal changes of menopause and in the week before the menstrual period may be a factor in </B><B>stress</B><B> </B><B>incontinence</B><B>.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>Stress</B><B> </B><B>incontinence</B><B> is treatable.</B></div> <bR> <bR> <div> <B><U> </U></B><I><B><U>Urge </U></B></I><I><B><U>Incontinence</U></B></I><B><U> </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">occurs when there is a strong urge to urinate, but the urine cannot be held back.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Urge </B><B>incontinence</B><B> may be triggered by coughing, the sound of running water, or after drinking small amounts of water. Urine loss may occur during sleep.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This type of </B><B>incontinence</B><B> is usually caused by strong, inappropriate bladder contractions.</B> </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A variation of urge </B><B>incontinence</B><B> is reflex </B><B>incontinence</B><B>, when urine the bladder contracts and empties of urine without the sense of urgency. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Overactive nerves controlling the bladder may be at fault.</B></div> <bR> <bR> <bR> <div> <I><B><U>Overflow </U></B></I><I><B><U>incontinence</U></B></I></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <FONT SIZE="3" COLOR="#000066" FACE="Arial" ><B>occurs when the nerve supply to the bladder is impaired. </B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The bladder is overfilled and leaks urine. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This can be caused by delaying the need to urinate, by diabetes, spinal injuries, weak bladder muscles, or other diseases or disorders.</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <I><B><U>Continuous </U></B></I><I><B><U>incontinence</U></B></I><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">is rare. Urine leaks more or less constantly with no urge to urinate. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This may be caused by congenital abnormalities, pelvic surgery or advanced cancer within the pelvis.</B> </div> <bR> <bR> <div> <I><B><U>Mixed </U></B></I><I><B><U>incontinence</U></B></I><B><U> </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">usually refers to the occurrence of </B><B>stress</B><B> and urge </B><B>incontinence</B><B> together.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Other combinations are also called mixed </B><B>incontinence</B><B>, but this combination is the most common.</B></div> <bR> <bR> <div> <B><U> </U></B><I><B><U>Functional </U></B></I><I><B><U>Incontinence</U></B></I><B><U> </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">occurs when the </B><B>urinary</B><B> tract is functioning normally, but a person has a disability that prevents him from reaching the toilet in time. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This can be a physical obstacle such as a wheelchair, or a disorder with thinking and planning ahead, such as Alzheimer's.</B></div> <bR> <bR> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT><I><B><U>Transient </U></B></I><I><B><U>incontinence</U></B></I></div> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" ><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </FONT><B>refers to temporary </B><B>incontinence</B><B>. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Medications, </B><B>urinary</B><B> tract infections, and even constipation can cause transient </B><B>incontinence</B><FONT SIZE="3" COLOR="#000066" FACE="AvantGarde Bk BT" ><B>.</B></FONT><B> </B></div> <bR> </tD> </tR> </TABLE></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="541" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#FF0000 > <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#000000 HEIGHT= 20 ><NOBR><div> <B>Reversible Causes and Risk Factors for </B><B>Urinary</B><B> </B><B>Incontinence</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#000099 HEIGHT= 227 WIDTH="295"><div> <B>• Immobility/chronic degenerative disease</B></div> <div> <B>• Impaired cognition</B></div> <div> <B>• Medications</B></div> <div> <B>• Morbid obesity</B></div> <div> <B>• Diuretics</B></div> <div> <B>• Smoking</B></div> <div> <B>• Fecal impaction</B></div> <div> <B>• Delirium</B></div> <div> <B>• Low fluid intake</B></div> </tD> <tD VALIGN=CENTER WIDTH="231"><div> <B>• Environmental barriers</B></div> <div> <B>• High-impact physical activities</B></div> <div> <B>• Diabetes</B></div> <div> <B>• Stroke</B></div> <div> <B>• Estrogen deprivation</B></div> <div> <B>• Pelvic muscle weakness</B></div> <div> <B>• Childhood nocturnal enuresis</B></div> <div> <B>• Race</B></div> <div> <B>• Pregnancy/vaginal delivery/episiotomy</B></div> </tD> </tR> </TABLE></B></div> <div> <I><B><U>Risk Factors Associated with </U></B></I><I><B><U>Incontinence</U></B></I></div> <div> <B>Immobility/chronic generative disease</B></div> <div> <B>• Impaired cognition</B></div> <div> <B>• Medications, including diuretics</B></div> <div> <B>• Morbid obesity</B></div> <div> <B>• Smoking</B></div> <div> <B>• Fecal impaction</B></div> <div> <B>• Delirium</B></div> <div> <B>• Low fluid intake</B></div> <div> <B>• Environmental barriers</B></div> <div> <B>• High-impact physical activities</B></div> <div> <B>• Diabetes</B></div> <div> <B>• Stroke</B></div> <div> <B>• Estrogen depletion</B></div> <div> <B>• Pelvic muscle weakness</B></div> <div> <B>• Childhood nocturnal enuresis</B></div> <div> <B>• Race</B></div> <div> <B>• Pregnancy/vaginal delivery/episiotomy</B></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="481" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#FF0000 > <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#000099 HEIGHT= 20 WIDTH="469"><div> <B>Medications Causing </B><B>Incontinence</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#000099 HEIGHT= 151 ><NOBR><div> <B>Enalapril</B></div> <div> <B>Benztropine</B><B> </B></div> <div> <B>Trihexyphenidyl</B></div> <div> <B>Benzodiazepines </B></div> <div> <B>Cisapride</B></div> <div> <B>Furosemide</B></div> <div> <B>Hydrochlorothiazide </B></div> <div> <B>Alcohol</B></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#000099 WIDTH="233"><div> <B>Hyoscyamine</B></div> <div> <B>Oxybutynin</B></div> <div> <B>Prazosin</B></div> <div> <B>Terazosin</B></div> <div> <B>Thioridazine</B></div> <div> <B>Chlorpromazine</B></div> <div> <B>Haloperidol</B></div> <div> <B>Clozapine</B></div> </tD> </tR> </TABLE></B></div> <bR> <bR> <bR> <div> <B>Identification and Management of Reversible Conditions That Cause or Contribute to </B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B>Urinary</B></FONT><B> </B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B>Incontinence</B></FONT></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="1044" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#000066 > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="505"><div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Condition</B></div> </tD> <tD VALIGN=CENTER WIDTH="524"><div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Management</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 823 WIDTH="505"><div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Conditions Affecting the Lower </B><B>Urinary</B><B> Tract</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> tract infection</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(symptomatic with frequency, urgency, dysuria, etc)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atrophic vaginitis/urethritis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pregnancy/vaginal delivery/episiotomy</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stool impaction</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Drug Side Effects*</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diuretics</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polyuria, frequency, and urgency</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Caffeine</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Aggravation or precipitation of </B><B>urinary</B><B> </B><B>incontinence</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Anticholinergic agents</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> retention, overflow </B><B>incontinence</B><B>, impaction</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Psychotropic agents</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Antidepressants: anticholinergic actions, sedation</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Antipsychotics: anticholinergic actions, sedation,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rigidity, and immobility</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sedatives/hypnotics/central nervous system</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">depressants: sedation, delirium, immobility,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">muscle relaxation</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Narcotic analgesics</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> retention, fecal impaction, sedation, delirium</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">"</B><FONT SIZE="3" COLOR="#FFFF00" FACE="Arial" ><B>-Adrenergic blockers</B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urethral relaxation</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">"</B><FONT SIZE="3" COLOR="#FFFF00" FACE="Arial" ><B>-Adrenergic agonists</B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> retention (present in many cold and diet over-the-counter preparations)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">$</B><FONT SIZE="3" COLOR="#FFFF00" FACE="Arial" ><B>-Adrenergic agonists</B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> retention</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Calcium channel blockers</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary</B><B> retention</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Alcohol</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polyuria, frequency, urgency, sedation, delirium,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">immobility</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Increased Urine Production</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Metabolic (hyperglycemia, hypercalcemia)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Excess fluid intake</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Volume overload</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Increased Urine Production</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Venous insufficiency with edema</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Congestive heart failure</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Impaired Ability or Willingness to Reach a Toilet</B><B> </B><B>Delirium</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Chronic illness, injury, or restraint that</B><B> </B><B>interferes with mobility</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Psychologic </B></div> </tD> <tD VALIGN=CENTER WIDTH="524"><div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Antimicrobial therapy</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Oral or topical estrogen</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Behavioral intervention; avoid surgical therapy postpartum as condition may be self-limiting</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Disimpaction; appropriate use of stool softeners, bulk-forming agents, and laxatives if necessary; implement high-fiber intake, adequate mobility, and fluid intake</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With all medications, discontinue or change therapy, as clinically possible; dosage reduction or modification (eg, flexible scheduling of rapid-acting diuretics) also may help</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Better control of diabetes mellitus; therapy for hypercalcemia</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">depends on underlying cause</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Reduction in intake of diuretic fluids (eg, caffeinated beverages)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Support stocking, leg elevation, sodium restriction, diuretic therapy</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Medical therapy</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diagnosis and treatment of underlying cause(s) of acute confusional state</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Regular toileting, use of toilet substitutes, environmental alterations (eg, bedside commode, urinal)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Remove restraints if possible; appropriate pharmacologic or</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nonpharmacologic treatment or both</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 HEIGHT= 19 WIDTH="1032"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="1032" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <B>*</B> Many side effects are seen with over-the-counter drugs, the use of which may not be reported by some patients.</div> <bR> <div> <B><U>Clinical evaluation of </U></B><B><U>urinary</U></B><B><U> </U></B><B><U>incontinence</U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Duration, characteristics, and severity</B><B> of the </B><B>incontinence</B><B>, precipitating factors and reversible causes should be assessed. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dysuria, urgency, pelvic pain, dyspareunia, constipation, fecal </B><B>incontinence</B><B>, pelvic prolapse, or abnormal vaginal discharge should be sought. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A history of </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">diabetes,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> thyroid disease, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">spinal cord injury, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cerebral vascular accidents,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> urethral sphincter damage, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">or fistula conditions should be excluded.</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Estrogen status</B><B> should be determined because</B><FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B><U> </U></B></FONT></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypoestrogenism can </U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">contribute to recurrent cystitis</U></B><FONT SIZE="3" COLOR="#990000" FACE="Arial" ><B>, </B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">detrusor instability, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and </B><B>stress</B><B> </B><B>incontinence</B><B>. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Patients should be questioned about recurrent </B><B>urinary</B><B> tract infections, kidney stones, bladder pain, or hematuria.</B></div> <bR> <bR> <bR> <div> <B><U>Physical examination</U></B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neurologic examination.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>Normal sensation in the perineal and the back of the leg confirms intact sensory enervation of the lower </B><B>urinary</B><B> tract. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sacral reflex activity is tested via the anal reflex-stroking the skin with a cotton swab adjacent to the anus causes reflex contraction of the external anal sphincter.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Pelvic floor muscle tone can be assessed by voluntary contraction of the anal sphincter and vagina during a bimanual exam. </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pelvic exam</B><B> should be performed to assess</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> the external genitalia, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">perineal sensation, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">presence of pelvic organ prolapse (cystocele, enterocele, rectocele, uterine prolapse), </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">estrogen status, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and pelvic muscle strength. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A bimanual exam with rectovaginal exam should be done to rule out pelvic masses.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Observation of urine loss</B><B> while the patient has a full bladder can be performed by having the patient cough vigorously in the standing position. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If instantaneous leakage occurs with cough, </B><B>stress</B><B> </B><B>urinary</B><B> </B><B>incontinence</B><B> is likely while detrusor instability (urge </B><B>incontinence</B><B>) is suggested by delayed or sustained leakage.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urethral hypermobility</B><B> due to loss of bladder neck support can be assessed using a cotton swab test. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A sterile, lubricated cotton swab is inserted transurethrally into the bladder and then withdrawn slowly until resistance is felt, then the patient is then asked to cough or perform a Valsalva maneuver. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A 30</B><FONT SIZE="3" COLOR="#990000" FACE="WP MathA" ><B></B></FONT><B> deflection indicates urethral hypermobility.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Post-void residual</B><B> is useful to rule out overflow </B><B>incontinence</B><B> and incomplete bladder emptying, and a urinalysis and/or urine culture to rule out </B><B>urinary</B><B> tract infection. After a normal void, a post-void residual urine volume is determined using a catheterization or bladder scan. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A post-void residual should be less than below 100 cc.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cystometry</B><B> is used to measure the pressure volume relationship of the bladder as it distends.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Complex cystometry uses specialized equipment with pressure catheters to record bladder pressures. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Simple cystometry can readily be performed in the office with a red rubber catheter, a syringe, and sterile water.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinalysis or urine culture</B><B> should be obtained. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Creatinine BUN, glucose, and calcium are recommended if compromised renal function is suspected or if polyuria is present. </B></div> <bR> <div> <B><U>Simple Urodynamic Testing</U></B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Simple cystometry demonstrates the activity of the detru-sor muscle.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Single-channel (bladder only) and dual-chan-nel (bladder and abdominal) cystometrography techniques are used.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This test does not require specific urogynecologic equipment.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Simple manometric systems can suffice. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Three important aspects of bladder function can be assessed by this simple test </B></div> <bR> <div> <B>• Compliance: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The upper graph shows increased filling </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">without increased pressure,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> which is characteristic of normal compliance. </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The lower graph shows increasing pressure with increasing volume, indicating an abnormality of compliance.</B></div> <bR> <div> <B>• Detrusor activity.' The upper graph shows no spontaneous detrusor activity, whereas the middle graph shows abnormal phasic pressure changes during filling.</B></div> <div> <B>• Sensation: This is reportedby the patient at the various volume levels.</B></div> <bR> <div> <B>Treatment of </B><B>urinary</B><B> </B><B>incontinence</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Detrusor instability (urge </B><B>incontinence</B><B>)</B><B> is treated with bladder retraining and pharmacologic therapy.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stress</B><B> </B><B>incontinence</B><B> is treated with Kegel exercises, pharmacotherapy, biofeedback, electrical stimulation, medical devices, or surgery.</B></div> <bR> <bR> <div> <B>Behavioral modification</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Detrusor instability (urge </B><B>incontinence</B><B>) may respond to dietary restriction of caffeine, alcohol, chocolate, and spicy food, as these can all cause bladder irritation. Scheduled toileting should be offered to incontinent patients. Bladder training (timed voiding) helps to progressively distend the bladder and allows the patient to regain control over voiding patterns. The patient is instructed to void at pre-assigned times during the waking hours. The initial voiding interval is set at less than the current voiding interval and is gradually increased.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Kegel's exercise</B><B>. Pelvic muscle exercises are used in </B><B>stress</B><B> </B><B>urinary</B><B> </B><B>incontinence</B><B> and detrusor instability (urge </B><B>incontinence</B><B>). A typical regimen of pelvic floor exercises is based on sets of contractions of the levator muscles performed 2-4 times daily. This regimen results in a 60-70% improvement in their symptoms.</B></div> <bR> <div> <B>Kegel Exercises</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pelvic muscle exercises (Kegel exercises) help improve </B><B>urinary</B><B> control in 40-75% of patients. The patient performs the exercise by contracting the pubococcygeus muscle, thus improving the tone of the voluntary external urethral musculature. Exercises are indicated in patients with either </B><B>stress</B><B> or urge </B><B>incontinence</B><B>. The success of pelvic muscle exercises depends on the patient's ability to identify the correct muscles for the exercise and her commitment to performing the exercises. Simple written or verbal instructions may be insufficient to teach patients how to perform pelvic muscle exercises properly.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The correct method can be taught during a routine pelvic examination. While the examiner identifies the muscle by direct palpation, the patient is asked to contract the muscle, and verbal feedback can be provided to ensure appropriate performance of the exercise. Those women who are unable to isolate their pelvic muscles or who cannot contract these muscles may need biofeedback or electrical stimulation.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Patients should be instructed to perform 10-20 lO-second pelvic floor contractions three or more times per day. A minimum of 30 contractions per day for at least 6 weeks is usually required to achieve a detectable beneficial effect. Older women may need a longer training period. These exercises should be performed indefinitely to prevent recurrence of </B><B>incontinence</B><B>.</B></div> <bR> <div> <B>Electrical Stimulation</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Electrical stimulation with a transvaginal probe reduces detrusor overactivity in approximately 50% of affected women. Like timed voiding and muscle training, this treatment is free of systemic side effects. The main drawback is the cost of rental or purchase, which may be an out-of-pocket expense for many patients. Several devices approved by the Food and Drug Administration are available, and treatment can be home based or, less commonly, office based.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Typically, a transvaginal probe is used once or twice daily for 15-20 minutes. Symptom relief generally occurs within 6-8 weeks and may persist with reduced stimulation (eg, three times weekly). Women with pacemakers should avoid this therapy unless other options are not available.</div> <bR> <bR> <div> <B>Vaginal and Urethral Devices</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">An increasing selection of vaginal and urethral devices are available in North America. This appears to be the fastest-growing type of incontinence therapy. Pessaries that are modified for incontinence (Fig. 14) provide additional suburethral pressure and are safe and reasonably effective. A bladder support prosthesis is significantly more expensive and more cumbersome to fit than a pessary. No published study compares the efficacy rates of these two medical devices; therefore, the less expensive, simpler technique is preferred as an initial intervention.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">External urethral barriers are becoming increasingly available. These options range from patches that fit over the urethral meatus to small suction cups that limit urine loss. Each of these barriers have aspects of efficacy, cost, comfort, and side effects (eg, infection, skin irritation, urethral prolapse) to be considered. More experience is needed before recommendations can be clear.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Internal urethral barriers are available, but they have the distinct disadvantage of causing urinary tract infections and hematuria. Although effective in preventing urine loss, the devices are less than optimal because of these side effects. Nonetheless, equipped with this knowledge, a patient may select these devices to avoid or postpone surgery.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Intrinsic urethral sphincter dysfunction has been treated by periurethral bulking injections to improve urethral coaptation. Injections have been used in women with a well-supported but poorly functioning intrinsic urethra; short-term cure rates approach 70-90%. Periurethral collagen injections are not indicated in women with urethral hypermobility because cure rates are only 20-25% in this group of women. These methods are probably best used by physicians who specialize in the treatment of incontinence.</div> <bR> <div> <B>Pharmacotherapy</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pharmacotherapy is used for detrusor instability (urge </B><B>incontinence</B><B>) and </B><B>stress</B><B> </B><B>urinary</B><B> </B><B>incontinence</B><B>. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Oxybutynin (Ditropan) </B><B>is the agent of choice (2.5-5 mg PO tid-qid). Start patients on 2.5 mg po bid and then titrate up based on symptoms. The primary side effects of anticholinergic medications include dry mouth, constipation, blurred vision, change in mental status, and nausea. These medications are contraindicated in patients with narrow angle glaucoma. Other anticholinergic agents, including propantheline, dicyclomine, and flavoxate, may be used in patients with a poor response to oxybutynin.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tolterodine (Detrol)</B><B> is a bladder selective anticholinergic agent that is associated with improved symptoms and reduced side effects.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Imipramine (Tofranil)</B><B> has been shown to be effective in the treatment of both </B><B>stress</B><B> and detrusor instability (urge </B><B>incontinence</B><B>). Dosage is 25-100 mg daily. Side effects include orthostatic hypertension and dry mouth.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Alpha-adrenergic agonists,</B><B> phenylpropanolamine (PPA) and pseudoephedrine are useful in the treatment of </B><B>stress</B><B> </B><B>incontinence</B><B>. Dosage for PPA is 25-100 mg PO in a sustained release form (bid) and for pseudoephedrine, 15-30 mg PO tid.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Estrogen replacement</B><B>, either oral or vaginal, should be used as an adjunctive agent for postmenopausal women with </B><B>stress</B><B> </B><B>urinary</B><B> </B><B>incontinence</B><B>. The combination of an alpha-agonist and estrogen have a synergistic effect. Progestin should be added in patients who have a uterus.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="591" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=4 BGCOLOR=#000000 HEIGHT= 20 ><NOBR><div> <B>Pharmacologic Agents for the Treatment of </B><B>Urinary</B><B> </B><B>Incontinence</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 20 WIDTH="140"><div> <B>Medication</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>Dosage</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> <B>Mechanism of Action</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Indication</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 39 WIDTH="140"><div> <B>Oxybutynin ( Ditropan)</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>2.5 mg bid-5 mg tid</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> <B>Anticholinergic/Spasmolytic</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Detrusor instability</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 58 WIDTH="140"><div> <B>Hyoscyamine ( Levsin, Cystospaz)</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>0.15 mg tid-qid</B><B> </B></div> <div> <B>0.375 mg bid-tid (extended release)</B></div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> <B>Anticholinergic</B></div> </tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Detrusor instability</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 39 WIDTH="140"><div> <B>Flavoxilate ( Urispas)</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> <B>100-200 mg tid-qid</B></div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> <B>Anticholinergic/Spasmolytic</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Detrusor instability</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 39 WIDTH="140"><div> <B>Tolterodine ( Detrol)</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>2 mg bid</B></div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> <B>Anticholinergic</B></div> </tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Detrusor instability</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 58 WIDTH="140"><div> <B>Propantheline bromide</B><B> </B></div> <div> <B>( Pro-Banthine)</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>7.5 mg tid</B></div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> <B>Anticholinergic</B></div> </tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Detrusor instability</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 39 WIDTH="140"><div> <B>Phenylpropanolamine ( Entex)</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>5 mg bid</B></div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> <B>Alpha-adrenergic stimulation</B></div> </tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Stress</B><B> </B><B>incontinence</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 39 WIDTH="140"><div> <B>Pseudoephedrine ( Sudafed)</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>60 mg qid</B></div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> <B>Alpha-adrenergic stimulation</B></div> </tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Stress</B><B> </B><B>incontinence</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 77 WIDTH="140"><div> <B>Imipramine ( Tofranil)</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> <B>25-75 mg daily</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="163"><div> <B>Anticholinergic and alpha-adrenergic stimulation</B></div> </tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Detrusor instability</B><B> </B></div> <div> <B>Stress</B><B> </B><B>incontinence</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 77 WIDTH="140"><div> <B>Estrogen ( Premarin)</B></div> </tD> <tD VALIGN=CENTER WIDTH="140"><div> <B>0.625 mg po or vaginally, daily</B></div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> <B>Beneficial effects on urethral mucosa and sphincter</B></div> </tD> <tD VALIGN=CENTER WIDTH="123"><div> <B>Detrusor instability</B><B> </B></div> <div> <B>Stress</B><B> </B><B>incontinence</B></div> </tD> </tR> </TABLE></B></div> <bR> <div>  <A NAME="rtftoc10"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="4" COLOR="#000099" FACE="Arial" >Medications which can affect Continence</FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b7011899000000.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diuretics</B> - can result in brisk filling of bladder </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b7011899000000.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Anticholinergics</B> - impair detrusor contraction </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b7011899000000.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sedative/hypnotics</B> - can produce confusion </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b7011899000000.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Narcotics</B> - impair detrusor contraction </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b7011899000000.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Alpha-adrenergic agonists</B> - increase tone of internal sphincter </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b7011899000000.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Alpha-adrenergic antagonists</B> - decrease tone of internal sphincter </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b7011899000000.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Calcium channel blockers</B> - decrease detrusor contraction </div> <bR> <bR> <div> <B>Surgical correction</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Surgery is used primarily in the treatment of </B><B>stress</B><B> </B><B>urinary</B><B> </B><B>incontinence</B><B> due to urethral hypermobility or intrinsic sphincter deficiency. Urethral hypermobility is corrected with retropubic urethropexy, transvaginal needle suspension, or a suburethral sling. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Retropubic urethropexy: </B><B>vaginal tissue underneath the urethra is suspended to the pubic symphysis (</B><B> </B><B>Marshall-Marchetti-Krantz urethropexy) or Cooper's ligament (</B><B> </B><B>Burch colposuspension). The transvaginal needle suspension procedure is performed via the vaginal route with a small abdominal incision. The success rates for the retropubic urethropexy, transvaginal needle suspension, and suburethral sling are 80%, 70%, and 85%, respectively.</B></div> <div> <B>Intrinsic sphincter deficiency can be managed with a suburethral sling or periurethral </B><FONT SIZE="3" COLOR="#000000" FACE="Arial" >collagen injections</FONT></div> <bR> <bR> <bR> <div> ====================================================================================================================</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Maternal megaloblastic anemia and fetal congenital malformations due to folic acid deficiency can occur as rare complications of anticonvulsant therapy,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> specifically treatment with phenytoin (Dilantin). </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f099000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Phenytoin, , can diminish absorption of folate, resulting in macrocytosis, </B></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="337" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP COLSPAN=2 HEIGHT= 39 ><NOBR><div> <B>Brand Name(s):</B></div> <div> <B>Di-Phen, Dilantin, Diphenylan, Phenytex </B></div> </NOBR></tD> </tR> </TABLE></div> <bR> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="1065" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" BGCOLOR=#FF0000 > <tR> <tD VALIGN=CENTER COLSPAN=5 HEIGHT= 19 WIDTH="1053"><div> <B>Side Effects</B><B> </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 245 WIDTH="374"><div> <B><U>Serious</U></B><B><U> </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fever, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">sore</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> throat, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">swollen glands, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">point-like rash on the skin or mucous membranes,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> blistering or peeling, mouth sores or bleeding gums, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">easy bruising, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pallor, weakness, confusion, or seizures may be a sign of a potentially fatal blood disorder or other </B><B>complication</B><B>.</B></div> </tD> <tD VALIGN=CENTER WIDTH="1"><bR> <bR> </tD> <tD VALIGN=CENTER WIDTH="403"><div> <B><U>Common</U></B><B><U> </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sedation, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lethargy,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> nervousness, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dizziness,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> thickened gums,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> excessive growth of body and facial hair. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">High doses may cause abnormal movements of the eyes,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> mouth, tongue, or limbs. Prolonged use may cause mild nerve impairment in the arms or legs.</B><FONT SIZE="3" COLOR="#FFFF00" FACE="Arial" ><B> </B></FONT></div> </tD> <tD VALIGN=CENTER WIDTH="0"><bR> <bR> </tD> <tD VALIGN=CENTER WIDTH="271"><div> <B><U>Less Common</U></B><B><U> </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Constipation, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">acne, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mild skin rash, incoordination. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There are numerous additional possible side effects; </B></div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="152" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" BGCOLOR=#FFFF00 > <tR> <tD VALIGN=CENTER HEIGHT= 19 ><NOBR><div> <B>Precautions</B> </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 118 WIDTH="148"><div> <B><U>Over 60</U></B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B> </B></FONT></div> <div> <B><U>Driving and Hazardous Work</U></B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B> </B></FONT></div> <div> <B><U>Alcohol</U></B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B> </B></FONT></div> <div> <B><U>Pregnancy</U></B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B> </B></FONT></div> <div> <B><U>Breast Feeding</U></B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B> </B></FONT></div> <div> <B><U>Infants and Children</U></B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" ><B> </B></FONT></div> <div> <B><U>Special Concerns</U></B><FONT SIZE="1" COLOR="#000000" FACE="Verdana" > </FONT></div> </tD> </tR> </TABLE></div> <bR> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" > <A NAME="pregna"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></FONT><B>Pregnancy</B><B> </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Anticonvulsants are associated with an increased risk of birth defects.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, seizures during pregnancy can also increase the risks to the unborn child.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. </B><B><U>Folate supplementation is recommended beginning 1 to 2 months before conception and throughout pregnancy</U></B></div> <bR> <div> <B>Pathophysiology: </B><B>Mechanism of Action: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> blocks voltage-sensitive sodium channels in neurons. T</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">his action leads to a delay in neuronal electrical recovery.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>Phenytoin</B><B>’s inhibitory effect is dependent on the voltage and frequency of firing of the neuron by selectively blocking those neurons that are firing at high frequency. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> prevents the electrical spread of a focus of irritable tissue from entering normal tissue. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> administration has been associated with toxic effects. </B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</U></B><B><U> toxicity depends on the route of administration, duration, exposure and dosage.</U></B><FONT SIZE="3" COLOR="#6633CC" FACE="Arial" ><B> </B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The route of administration is the most important determinant of toxicity. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> may be given via the oral or intravenous route.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, fos</B><B>phenytoin</B><B> may be administered intramuscularly.</B></div> <div> <B>Pharmacokinetics: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> is a weak acid and has erratic GI absorption. </B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Following ingestion, </U></B><B><U>phenytoin</U></B><B><U> precipitates in the stomach's acid environment. </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This fact is particularly important in the setting of an intentional overdose.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Peak blood levels occur three to 12 hours following a single dose ingestion. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The parenteral form of </B><B>phenytoin</B><B> is dissolved in 40% propylene glycol and 10% ethanol and adjusted to a pH of 12 with the addition of sodium hydroxide to maintain solubility.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>Phenytoin</B><B> administered intravenously at a rate greater than 50 mg/min may cause hypotension and arrhythmias. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These </B><B>complication</B><B>s are believed to be secondary to the diluent, propylene glycol. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Extravasation of the solution may cause skin irritation or phlebitis. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> has a volume of distribution of 0.6 L/kg and is extensively bound to plasma proteins (90%).</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Blood levels of </B><B>phenytoin</B><B> reflect only total serum concentration of the drug. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Only the free, unbound </B><B>phenytoin</B><B> has biological activity. </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Patients predisposed to elevated free </B><B>phenytoin</B><B> levels include</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> neonates, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">the elderly </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and patients with uremia, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypoalbuminemia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">or hyperbilirubinemia. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These patients may exhibit signs of toxicity when drug levels are within the therapeutic range </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Certain medications can interfere with </B><B>phenytoin</B><B> levels. </B></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0cc000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hepatic microsomal enzymes primarily metabolize </B></I><I><B>Phenytoin</B></I><I><B>.</B></I></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Much of the drug is excreted in the bile as an inactive metabolite, which is then reabsorbed from the intestinal tract and ultimately excreted in the urine</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Less than 5% of </B><B>phenytoin</B><B> is excreted unchanged in the urine.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Individuals with impaired metabolic or excretory pathways may exhibit early signs of toxicity. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> metabolism is dose-dependent. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Elimination follows first order kinetics (fixed percentage of drug metabolized during a per unit time) at the low drug concentrations and zero-order kinetics (fixed amount of drug metabolized per unit time) at higher drug concentrations. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This change in kinetics reflects the saturation of metabolic pathways. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0cc336600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, very small increments in dosage may result in side effects.</B></div> <div> <B>Physical: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phenytoin</B><B> may cause a febrile reaction, hypotension (during intravenous infusion) or bradycardia.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mouth: Gingival hyperplasia (chronic use - most common adverse effect [20%])</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neurologic:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hyper- or hyporeflexia</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Abnormal gait (bradykinesia, truncal ataxia)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Respiratory Distress </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Encephalopathy </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Meningeal irritation with pleocytosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tremor (intention) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Irritability or Agitation </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Confusion </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hallucinations</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mental status varies from completely normal to the extremes of stupor and coma, particularly if there are co-ingestants</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Peripheral neuropathy (chronic use) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Priapism </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Urinary incontinence</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Choreoathetoid movements </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dysarthria </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dysphagia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Seizures (rare) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Death (rare)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Eyes:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nystagmus (horizontal, vertical) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ophthalmoplegia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diplopia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Miosis or mydriasis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypersensitivity Reactions: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fever, rash and lymphadenopathy are commonly seen together. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Systemic lupus erythematosus(SLE) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polyarteritis </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polymyositis </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Eosinophilia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Megaloblastic anemia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pseudolymphoma </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lymphadenopathy</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vascular: Phlebitis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Skin:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hirsutism </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Acne </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Rashes </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Rash can be mild, morbilliform, scarlatinoid or as severe as Stevens-Johnson syndrome.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Jaundice </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Facial or periorbital edema </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Erythema multiforma (EM) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Toxic epidermal necrolysis (TEN)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">GI/Abdomen:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Right upper quadrant tenderness </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hepatomegaly </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Splenomegaly </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nausea </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vomiting </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hepatitis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fetal hydantoin syndrome </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(</B><FONT SIZE="3" COLOR="#000066" FACE="Arial" ><B>broad nasal bridge, </B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">wide fontanelle,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> low hairline, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cleft lip/palate,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> epicanthal folds, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">short neck, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">microcephaly,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> low-set ears, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">small or absent nails, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dislocated hip,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> hypoplasia of distal phalanges,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> impaired growth,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> congenital heart defects) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Metabolic: Osteomalacia and hypothyroidism (chronic toxicity) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypotension, bradycardia, myocardial depression, ventricular fibrillation, asystole and tissue necrosis have all been associated with the IV formulation.</B></div> <bR> <div> <B>Lab Studies: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Serum </B><B>Phenytoin</B><B> Level:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The therapeutic range is 10-20 mcg/ml. Plasma levels (mcg/ml) have an association with acute neurological symptoms.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Free </B><B>phenytoin</B><B> levels range from 1.0-2.0 mcg/ml, and correlate well with clinical evidence of toxicity (ie, those with decreased protein binding may have signs and symptoms of toxicity despite a normal total </B><B>phenytoin</B><B> level; however, their free </B><B>phenytoin</B><B> level will be elevated).</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Less than 10 - rare</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">10 to 20 - occasional mild nystagmus</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">20 to 30 - nystagmus</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">30 to 40 - ataxia, slurred speech, nausea, vomiting</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">40 to 50 - lethargy, confusion</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Greater than 50 - coma, seizures</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the intentional overdose setting, immediately check a dextrose stick in any patient with altered mental status.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Aspirin and acetaminophen levels</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HCG (in women of childbearing years)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">+/- Ethanol level (for multiple ingestions, altered mental status)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">+/- Electrolytes (for questionable clinical presentation, elderly, multiple medical problems)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">+/- Liver function tests (for suspected hepatotoxicity or to determine patient baseline)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Chronic Toxicity:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Complete blood count (CBC) (anemia, eosinophilia, atypical lymphocytosis, pancytopenia)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Liver function tests (LFTs) (hepatotoxicity)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Electrolytes (hyperglycemia, hyperosmolar nonketotic coma)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Drug Interactions:</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When physicians prescribe other medications in combination with </B><B>phenytoin</B><B>, they must be very alert to the possibility of inadvertent toxicity or decreased efficacy of the antiepileptic medication. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066009900.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Numerous interactions between </B><B>phenytoin</B><B> and other medications are known to exist. </B></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000660000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Increases serum levels of </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000660000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">toxic metabolites of acetaminophen, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000660000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">oral anticoagulants </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000660000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and primidone (eg,phenobarbital). </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Decreases serum levels of </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">amiodarone, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">carbamazepine, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">contraceptives, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">corticosteroids, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cyclosporine, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">disopyramide, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">doxycycline, f</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">urosemide, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">levodopa, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">methadone,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> mexiletine, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">quinidine, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">theophylline </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and valproic acid. </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Serum levels are increased by </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">amiodarone, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">chloramphenicol,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cimetidine, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">disulfiram, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ethosuximide, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fluconazole,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> isoniazid, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">oral anticoagulants, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">phenylbutazone, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">sulfonamides, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">trimethoprim </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000bf00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and valproic acid. </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Serum levels are decreased by </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">antineoplastic drugs, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">calcium, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">diazepam,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> diazoxide, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ethanol (chronic),</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> folic acid, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">phenobarbital, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rifampin, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">sucralfate</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> and theophylline. </B></I></div> <bR> <div> <I><B>====================================================================================================================</B></I></div> <div> <B>Which of the following histologic findings is most characteristic of the endometrium of a 13-year-old girl whose menarche began 1 year ago and who has been bleeding irregularly for the past 3 months</B></div> <div> <B><U>Tubular endometrial glands with many mitoses</U></B></div> <bR> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The description of this young woman, in the beginning of her reproductive life,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> is characteristic of anovulation with unopposed estrogen. </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The expected finding would be a proliferative histologic picture; </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">therefore tubular endometrial glands with many mitoses would be the correct finding in this case. </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There will not be evidence of ovulation (serrated endometrial glands with inspissated secretions; , </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">endometrial carcinoma (back-to-back endometrial glands with prominent nuclei, hyperchronism and loss of cellular polarity; , </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">or pregnancy (decidual reaction forming around endometrial arterioles;</B></I></div> <bR> <div> <I><B>====================================================================================================================</B></I></div> <bR> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dysmaturity syndrome occurs in 20%-30% of post-term pregnancies </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and is characterized by </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">aging of the placenta, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">"dehydration" of the fetoplacental unit,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> and meconium staining in utero.</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Oligohydramnios is frequently seen.</B></I></div> <bR> <div> <I><B>====================================================================================================================</B></I></div> <bR> <div> <I><B><U> </U></B></I><FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><I><B><U>Beckwith-Wiedemann syndrome </U></B></I></FONT></div> <div> <I>: </I><FONT SIZE="3" COLOR="#333333" FACE="Arial" ><I><B>exomphalos-macroglossia- gigantism: neo-natal hypoglycaemia, visceromegaly, hemihypertrophy </B></I></FONT></div> <div> <B>SYNONYMS: </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Beckwith <FONT SIZE="3" COLOR="#800000" FACE="Arial" >syndrome</FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Wiedemann II <FONT SIZE="3" COLOR="#800000" FACE="Arial" >syndrome</FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Exomphalos-macroglossia-gigantism <FONT SIZE="3" COLOR="#800000" FACE="Arial" >syndrome</FONT> </div> <bR> <bR> <bR> <div> <I><B>refers to </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">macrosomic fetuses </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> hypoglycemia [hyperinsulinism]</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f0ff006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> macroglossia. </B></I></div> <div> The classic triad of<B> macrosomia, omphalocele, and macroglossia characterizes it. </B></div> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >S</FONT><B>ynonym: Exomphalos-macroglossia-gigantism </B><B>syndrome</B></div> <div> <B>[see also belw the details]</B></div> <div> <B>Macroglossia</B> (enlarged tongue) </div> <div> Although always larger than usual for an infant, the size of the tongue can vary from child to child, as can it's effects on the child's ability to eat, breathe, or speak. Therapy may be required, and in more severe cases, corrective surgery may be necessary. Most children seem to "grow into their tongues," and thus do not require <U>tongue reduction surgery</U>. The enlargement is usually not apparent by 6-8 years of age. </div> <div> <B>Abdominal Wall Defects</B> </div> <div> <I>-Omphalocele</I>: a defect in the abdominal wall, near the umbilical cord, which allows intestines and possibly other abdominal organs to protrude into a covering membrane (sac). This usually requires surgical intervention soon after birth. </div> <div> <I>-Umbilical Hernia</I>: a hernia in the area of the navel, which may or may not require surgery. </div> <div> <I>-Diastasis Recti</I>: weak or separated abdominal muscles, which can give a pot-belly appearance. </div> <div> <B>Increased Growth</B> </div> <div> <I>-Birth Weight and Length</I>: usually above average. </div> <div> <I>-Visceramegaly</I>: enlarged abdominal organs, particularly kidneys, liver, and pancreas. </div> <div> <I><U>-Hemihypertrophy</U></I>: enlargement of one part of the body. Usually all or part of one side of the body is affected, but there are some cases where parts of both sides of the body are involved. Sometimes hemihypertrophy is not present at birth but becomes apparent later in childhood. </div> <div> <B>Typical facial features</B> </div> <div> <I>-Earlobe creases</I>: or pits behind the upper ear. </div> <div> <I>-Prominent occiput</I>: enlarged back of the skull. </div> <div> <I>-Nevus Flammeus</I>: a strawberry mark commonly found on the forehead and eyelids. This is sometimes called a "stork bite," and usually disappears in early childhood. </div> <bR> <div> Prenatal ultrasound has been occasionally helpful in the diagnosis of BWS when certain characteristics are present. An omphalocele is the most easily detected. Other characteristics that may cause suspicion of BWS include enlarged abdominal circumference, enlarged kidneys, enlarged placenta, increased amniotic fluid, protruding tongue or when a larger than expected fetus is present. Currently there is no definitive blood test for BWS, although an elevated Alpha-fetoprotein (AFP) level in the presence of an omphalocele may help in the diagnosis. Research is now being done to identify and isolate the gene responsible for the Beckwith-Wiedemann Syndrome. Hopefully, a prenatal test for the gene will soon follow</div> <bR> <bR> <div> <B><U>Etiology</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" >: </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sporadic in most cases,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Beckwith-Wiedemann syndrome has an <B>autosomal dominant inheritance</B>, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">with incomplete penetrance and variable expressivity.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Rearrangements involving chromosome<B> 11p15</B> region seems to be the mutation responsible for this disorder </div> <div> <B><U>Diagnosis:</U></B><FONT SIZE="3" COLOR="#000033" FACE="Arial" > </FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The detection of macrosomia, omphalocele , and macroglossia associated with normal karyotype makes the diagnosis of Beckwith-Wiedmann </B><B>syndrome</B><B>. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other features occurring in variable incidence include</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B>nephromegaly, </B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hepatomegaly, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">polyhydramnios, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ear lobe creases, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">diaphragmatic hernia</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> and cardiac defects</B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pancreatic cell hyperplasia</U></B><FONT SIZE="3" COLOR="#000033" FACE="Arial" ><B> may affect 30 to 50 % of the patients, causing hyperinsulinism and neonatal hypoglycemia on the second or third day of life</B></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A fairly typical finding also is a small ear-lobe groove</B></div> <bR> <bR> <div> <B><U>Genetic anomalies: </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Structural anomalies of the chromosome including paternal isodisomy of the 11p15.5 region, isodisomy of 11q and uniparental disomy may be detected by cytogenetic studies.</B></div> <bR> <div> <I><B><U>Differential diagnosis:</U></B></I><B> </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Down's </B><B>syndrome</B><B> must be excluded by chromosomal analysis due to the occurrence of macroglosia in both conditions.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Diabetic fetopathy is another cause of macrosomia, and thus a differential diagnosis.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Normal levels of maternal glucose exclude this possibility. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Zellweger's </B><B>syndrome</B><B> can also combine </B><B><U>liver and kidney enlargement</U></B><B>, and may be diagnosed prenatally by measuring fatty acid concentration and activity of marker enzymes</B></div> <bR> <div> <B><U>Complications:</U></B><B> </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Untreated neonatal hypoglycemia is an important complication and may result in further cerebral dysfunction, such as seizures, mild to moderate mental retardation, or neonatal death in more severe cases</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Macroglosia can cause variable complications ranging from feeding difficulties to airway obstruction and death</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Long term complications includes high risk for abdominal tumors, in particular Wilm's tumor, hepatoblastoma, neuroblastoma, and adrenal cortical carcinoma 3</B><FONT SIZE="1" COLOR="#000033" FACE="Arial" ><B>,11</B></FONT><B>. </B></div> <bR> <div> <B><U>Prognosis:</U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neonatal mortality rate is approximately 21%, caused mainly by congestive heart failure</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Among those who survive, the prognosis is in general favorable, depending on the severity of the associated anomalies and long term complications.</B></div> <bR> <div> <B><U>Management:</U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> When diagnosed before viability, termination can be offered. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">After viability, sonographic evaluation of fetal growth is suggested. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When macrosomia is suspected, c-section may be offered due to the risk of shoulder dystocia.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Delivery in a tertiary center is recommended for early abdominal wall defect repair and treatment of the hypoglycemia. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sonograghic screening for abdominal tumors each trimester is recommended during the first 6 years of life9</B></div> <div> <I><B><U><IMG SRC="09c938a0.png" border=0 width="147" height="138" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></I></div> <bR> <div> <I><B><U> <TABLE BORDER="2" CELLPADDING="2" CELLSPACING="1" WIDTH="532" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#000099 > <tR> <tD VALIGN=TOP HEIGHT= 113 ><NOBR><div> <B>Beckwith-Wiedemann</B><B> </B><B>syndrome</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">big tongue </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">organomegaly (liver, kidneys, pancreas, heart) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">omphalocele, umbilical hernia or diastasis recti </B></div> <bR> </NOBR></tD> </tR> </TABLE></U></B></I></div> <bR> <bR> <div> <I><B><U>Wilms tumor</U></B></I></div> <div> <I><B>nephroblastoma </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">3rd most common kiddie tumor (most common abd tumor) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">arises from embryonal renal tissue (</B></I><I><B>nephroblastomatosis</B></I><I><B>) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">large </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">only 10% are calcified </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">4-10% bilateral </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mets --> lungs, para-aortic nodes </B></I></div> <div> <I><B>associated with: </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">aniridia</B></I><I><B> </B></I></div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Beckwith-Wiedemann syndrome</U></B></I><I><B><U> </U></B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hemihypertrophy</B></I><I><B> </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Drash </B></I><I><B>syndrome</B></I><I><B> </B></I></div> <bR> <div> <I><B>CLINICAL FEATURES:</B></I></div> <div> <I><B>1. Neonatal Manifestations</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dysmorphic features (see below) and neonatal somatic gigantism </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">apnea, cyanosis, seizures, feeding difficulties due to macro-glossia </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypoglycemia </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">tends to be intractable, severe, and persist for months </B></I></div> <div> <I><B>2. Clinical Features</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Feature(%)</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">macroglossia (98%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nephromegaly (97%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">splenomegaly (82%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">midface hypoplasia (81%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cryptorchidism (81%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">omphalocele (76%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hepatomegaly (73%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">prominent occiput (72%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ear anomalies - creases, pits (66%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">facial nevusflammeus (62%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">neonatal hypoglycemia (61%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">polyhydramios (51%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">umbilical hernia (49%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cardiac defects (34%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hemihypertrophy (33%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">diastasis recti (33%) </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">others: MR,microcephaly, tall stature </B></I></div> <div> <I><B>3. Complications</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">neoplastic transformation (see above) </B></I></div> <div> <I><B>INVESTIGATIONS:</B></I></div> <div> <I><B>1. Serum</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">neonatal polycythemia </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypoglycemia with hyperinsulinemia </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">moniter alpha fetoprotein and abdominal U/S q6m till age 6 years to screen for hepatoblastoma and Wilms tumor, respectively </B></I></div> <div> <I><B>2. Imaging Studies</B></I></div> <div> <I><B>1. Skeletal X-Rays</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">advanced bone age </B></I></div> <div> <I><B>MANAGEMENT:</B></I></div> <div> <I><B>1. Supportive</B></I></div> <div> <I><B>1. Multidisciplinary Approach</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paediatrics, Surgery, Speech Therapy </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">feeding difficulties - use large, soft nipple </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">upper airway obstruction - place on side and stomach </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">stabilization of omphalocele </B></I></div> <div> <I><B>2. Hypoglycemia</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">steroids for 1-4 months </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">glucose infusions </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">see file on "Hypoglycemia" </B></I></div> <div> <I><B>2. Surgery</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">omphalocele repair </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">orthognathic and orthodontic </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? role of partial glossectomy </B></I></div> <bR> <div> <I><B> <TABLE BORDER="2" CELLPADDING="2" CELLSPACING="1" WIDTH="475" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#000066 > <tR> <tD VALIGN=TOP HEIGHT= 624 WIDTH="463"><div> <B>Genetic Defect</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">the gene for insulin-like growth factor II is found within the 11pter-p15.4 region and may be responsible for: </B></div> <div> <B>1. Cellular Hyperplasia</B></div> <div> <B>1. Pancreatic</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pancreatic islet hyperplasia (nesidioblastosis) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">relative hyperinsulinemia -> neonatal hypo-glycemia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">microcephaly and retarded brain development may occur independent of hypoglycemia </B></div> <div> <B>2. Visceromegaly</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nephromegaly, hepatomegaly, and splenomegaly during embryogenesis may predispose to certain developmental defects -> anomalies of intestinal rotation and fixation, omphalocele, diaphragmatic eventration, renal medullary dysplasia </B></div> <div> <B>3. Gonads</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">gonadal interstitial cell hyperplasia (in males) </B></div> <div> <B>4. Pituitary</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">amphophil hyperplasia </B></div> <div> <B>2. Neoplastic Transformation</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">in 5% - adrenocortical carcinoma, Wilms' tumor </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rare - carcinoid tumor, embryonal rhabdomyosarcoma, fibroma, glioma, gonadoblastoma, hepato-blastoma, myxoma, retinoblastoma </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000ffff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Note: the genes for rhabdomyosarcoma, adrenocortical carcinoma and Wilms' tumor are also on chromosome 11 </B></div> <bR> </tD> </tR> </TABLE></B></I></div> <bR> <bR> <div> <I><B><U>more info just for your knowledge:</U></B></I></div> <div> <B>Genomic imprinting</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Expression of an allele depends on its parental origin </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Disease can occur if the normally expressed allele is absent or mutated: </div> <div> Deletion </div> <div> Uniparental disomy - (2 copies from 1 parent) </div> <div> Chromosome rearrangment </div> <div> Mutation which leads to loss of expression </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mechanism appears to operate at transcriptional level and involves DNA methylation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Clustering of imprinted genes suggests possible signal which can act on several genes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Imprint changes as required - tissue specific differences, variation during development, when passing from parent to child. </div> <div> <B>Genes involved in BWS</B> </div> <div> Imprinted gene cluster at 11p15.5 contains at least 3 genes: </div> <div> IGF-2 - insulin like growth factor 2 - Promotes embryonic growth - <B>PATERNAL</B> Expression only (most tissues- biallelic in adult liver) </div> <div> H19 - tumour suppressor RNA - <B>MATERNAL</B> expression only </div> <div> P57<FONT SIZE="1" COLOR="#000000" FACE="Arial" >kip2 </FONT>- product (KIP2) is a growth inhibitor -<B> MATERNAL</B> expression (leaky paternal expression) </div> <div> <B>Coregulation of IGF 2 and H19 in mice</B> - </div> <div> Expression of these genes essentially the same during development (time, tissues) </div> <div> Expression of maternal IGF 2 (biallelic expression) can occur due to deletion of active maternal H19 </div> <div> <B>Proposed mechanism</B> - competition between their promoters for a set of <B>enhancers </B>(enhancers positively stimulate transcription. Their function does not critically depend on precise position or orientation) </div> <bR> <div> <B>Involvement of IGF 2 and H19 in BWS</B> </div> <div> Most cases due to biallelic expression of IGF2 </div> <div> 20% BWS due to paternal UPD </div> <div> 5 - 10% BWS, Wilms tumour - hypermethylation of maternal H19 associated with biallelic expression of IGF 2</div> <div> <B>Alteration of imprinting in translocation families</B> </div> <div> Maternally transmitted translocations are associated with BWS. </div> <div> Two clusters </div> <div> 200-400Kb from IGF2 </div> <div> Several Mb from IGF2 </div> <div> Suggests that distant genes may have a deregulating effect. </div> <div> Translocation family D (Brown et al) has inversion with breakpoint 200-400Kb from IGF2. </div> <div> Found biallelic IGF2 expression and alteration of replication timing. </div> <div> H19 studies showed normal expression and methylation. <B>Therefore,</B> <B>biallelic expression can also occur through a H19 - independent pathway</B></div> <div> <B>Possible mechanisms for H19 independent biallelic IGF2 expression</B> </div> <div> Repressive chromatin structure normally on maternal chromosome established or maintained by elements centromeric of IGF2. (repressive chromatin structure does not extend to H19) </div> <div> Inversion removes a linked silencer (located at least 300Kb centromeric of the gene) </div> <div> Breakpoint interrupts a maternally expressed gene whose product is essential for silencing the maternal IGF2 eg a repressor which binds to maternal IGF2 </div> <div> <B>Involvement of p57</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>kip</B></FONT><B> in BWS and WT</B> </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">BWS</B> </div> <div> Several germline mutations have been identified which lead to a reduction in growth suppressive activity </div> <div> Probably accounts for <20% BWS cases </div> <div> Paternal UPD also leads to a down regulation of KIP2 expression </div> <div> KIP2 mRNA has been shown to be normal in at least one non UPD case </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">WT</B> </div> <div> No somatic coding mutations found. But full inactivation of H19 was detected</div> <bR> <div> <IMG SRC="09d44d40.png" border=0 width="324" height="212" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <IMG SRC="09f901d0.jpg" border=0 width="400" height="285" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <bR> <div> <I><B><U>================================================================</U></B></I></div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Meckel-Gruber syndrome</U></B></I><FONT SIZE="3" COLOR="#6600FF" FACE="Arial" ><I><B> is associated with a variety of anomalies, .</B></I></FONT></div> <bR> <bR> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">encephalocele</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">multiple renal cysts</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The triad of </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">occipital encephalocele,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> large polycystic kidneys </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and postaxial polydactyly characterizes MKS.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Associated abnormalities include </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">oral clefting, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">genital anomalies, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CNS malformations </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and fibrosis of the liver</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Pulmonary hypoplasia is the leading cause of death.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> With the advent of ultrasound, prenatal diagnosis is possible during the second trimester or late first trimester</B></div> <bR> <div> <B>Pathophysiology: </B><B>It has been suggested that a failure of mesodermal induction causes MKS.</B></div> <div> <B> The induction cascades of early morphogenesis involve numerous growth factors, homeo box genes and paired domain genes</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">T</B><FONT SIZE="3" COLOR="#000033" FACE="Arial" ><B>here is a predilection for the Finnish population where the birth incidence is 1 in 9000. </B></FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A GENETIC (recessive) syndrome that can be detected from the </B><B><U>18th week of pregnancy by Ultrasound &/or High AFP test results.</U></B><B> </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">(AFP: Alpha Fetal Protein Testing).</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Meckel Gruber Syndrome is the name given to a specific rare inherited lethal disorder. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This specific, rare, inherited lethal disorder/disease </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Meckel Gruber Syndrome is characterized by congenital (present at birth) deformations of the brain, resulting in mental retardation, cystic growths of the kidneys, and malformations of the hands and feet.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The children may also show</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> fibrous growths in the ducts of the liver, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">bone deformities of the arms and legs,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> a sloping forehead, cleft palate, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cardiac abnormalities, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and incomplete development of external and/or internal genitalia.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Symptoms vary among each case, however. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These symptoms invariably lead to death primarily due to lung and kidney failure.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Oligohydramnios resulting from dysplastic kidneys leads to fetal pulmonary hypoplasia. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Since the prognosis is grim, with death in utero or shortly after birth, prenatal diagnosis has led to therapeutic abortion of many affected fetuses. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Race: </B><B>Although the Finnish have the highest birth incidence, MKS affects all racial and ethnic backgrounds. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sex: </B><B>The male to female ratio is nearly equal, which is consistent with autosomal recessive inheritance. </B></div> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Approximately one-third are stillborn</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Two-thirds of infants survive for a maximum of 2 hours, 30 minutes</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Affected children rarely live more than four days after birth.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Isolated reports of longer survival: 5 months, 8 months, 13 months, 28 months, 3 years, 4 years</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fetal ultrasound will detect an occipital encephalocele and dysplastic kidneys if oligohydramnios is not present.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Newborns die shortly after birth from pulmonary hypoplasia. The most striking feature will be an occipital encephalocele. Also, polydactyly is easily seen. Postmortem examination of the kidneys will reveal marked cystic dysplasia.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pregnancy history should be reviewed for stillbirths or early neonatal deaths with findings of polycystic kidneys, occipital encephalocele and polydactyly. Also, the possibility of consanguinity should be addressed.</B></div> <div> <B><U>Physical: </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occipital encephalocele</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This consists of extrusion or herniation of rhombic roof elements, cerebellar vermis, caudal third ventricle and distended fourth ventricle through a widened posterior fontanelle. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occasionally, the medial occipital cortex is included in the sac formed by the dilated caudal third ventricle. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A dural sac covers the protruding central nervous system (CNS) structures.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polycystic kidneys</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cystic dysplasia of the kidneys is the most constant and characteristic feature of MKS. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Kidneys may be enlarged 10-20 times their normal size. Abnormal kidneys function poorly and cause oligohydramnios.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Postaxial polydactyly</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although all 4 extremities are usually affected, polydactyly is the most variable feature of the classic triad of major abnormalities. Some cases, however, do not exhibit polydactyly.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hepatic dysgenesis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A hepatic lesion is a consistent feature. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There is arrested development of the intrahepatic biliary system with varying degrees of reactive bile duct proliferation, bile duct dilatation, portal fibrosis and portal fibrous vascular obliteration.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Oral clefts</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cleft lip and cleft palate may also be present.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Genital anomalies</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Without chromosome analysis or gonadal histology, genital ambiguity secondary to external genital anomalies can cause confusion in sex assignment of the fetus or infant.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dandy-Walker malformation</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although an infrequent finding, 7 cases of Dandy-Walker malformation have been reported. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This complex dysembryogenesis includes a central cyst communicating with the fourth ventricle, agenesis of vermis and splaying of the cerebellar hemispheres. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hydrocephalus is usually present.</B></div> <div> <B><U>Causes: </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">MKS is an autosomal recessive disorder.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Since there is considerable phenotypic overlap with trisomy 13, it was postulated that the gene for MKS was on chromosome 13.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Analysis of polymorphic DNA markers from 5 Finnish families, however, assigned the MKS locus to chromosome 17q21-q24, telomeric to the homeo box B (HOXB) region. Disruption of the same HOXB genes in mice lead to malformations that resemble MKS. However, this locus has been excluded as a causative locus for MKS.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A subset of Middle Eastern and Northern African families with MKS did not show linkage to chromosome 17q. A second locus (MKS2) has been mapped to 11q13, demonstrating the clinical and genetic heterogeneity of MKS.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Final identification of the MKS locus is underway.</B></div> <bR> <bR> <div> <B><U>Diagnosis Of MG-S</U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There currently is no reliable test for Meckel Gruber Syndrome. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A prenatal ultrasound at 14 weeks may reveal symptoms of MG-S, however reliable detection cannot be achieved until approx. 18 weeks. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Checking cells taken from the fluid surrounding the developing fetus, a process known as amniocentesis, may also reveal elevated levels of </B><I><B>alpha fetoprotein</B></I><B>, a protein which is a marker of abnormal fetal spinal development.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A doctor may request consent to perform an autopsy and to take blood from affected individuals and their parents. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A chromosomal analysis may be completed to rule out other causes. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These tests are especially important to determine the chances for the parents of having another affected child and may help scientists to develop a reliable test for the disease in the future. Anyone with a previous pregnancy affected by MG-S should consult their doctor about planning for future pregnancies.</B></div> <div> <B><U>Lab Studies: </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Chromosome analysis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Chromosome analysis is essential for ruling out trisomy 13, which MKS mimics. Trisomy 13 carries a 1% recurrence risk as opposed to 25% for MKS. Linkage or mutation analysis is not yet available. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If anomalies are detected early in the first trimester, chorionic villus sampling (CVS) can be performed at 10-12 weeks gestation or later in pregnancy if oligohydramnios does not permit amniocentesis. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amniocentesis is performed after 14 weeks gestation if an adequate fluid pocket is present.</B></div> <div> <B><U>Imaging Studies: </U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Prenatal sonography</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is currently the best method available to diagnose MKS. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Second trimester is the usual time of diagnosis; however, with a skilled operator, first trimester diagnosis may be possible for both high-risk and low-risk families. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diagnosis in the second trimester becomes more difficult when oligohydramnios secondary to poor renal output impairs visualization. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occipital encephalocele is easily visualized beginning in late first trimester. Part of the brain and meninges will protrude through the skull defect. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Large, cystic echogenic kidneys are a consistent ultrasonographic finding, although oligohydramnios can obscure detection of renal dysplasia. Second trimester detection of polydactyly may be possible with experienced sonographers even if the finding is not present.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Magnetic resonance imaging (MRI)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">MRI is a valuable complement to ultrasound in assessing fetal anomalies in the presence of severe oligohydramnios. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">MRI can detect renal size and occipital defects such as encephaloceles.</B></div> <bR> <div> <B><U>Histologic Findings:</U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>Failure of the metanephric duct and renal blastema to interact appears to be the primary renal abnormality.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The kidneys, therefore, show little corticomedullary differentiation and the nephrons are severely deficient, causing enlargement of the kidneys.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Thin-walled cysts appear throughout the parenchyma. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hepatic lesions can be considered one of the hidden abnormalities of MKS since they are visible only during postmortem examination</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. An arrest of development occurs at the stage of bilaminar plates, which atrophy during normal development.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In MKS, the plates do not atrophy and prevent reorganization by the remaining biliary cells to form tubular ducts.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f033000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The resultant fibrosis can be so severe as to occlude portal veins.</B></div> <bR> <div> <B><U>Technical Information</U></B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">MG-S is inherited in an autosomal recessive manner. This means that the condition does not appear unless the person inherits the disorder from each parent.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Parents of affected children are known as carriers, since they carry one copy of the affected gene, but they also carry one copy of the normal gene. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">As a result, they do not show the symptoms or are mildly affected by the disease. If a child inherits both affected genes, then they will exhibit the symptoms of Meckel Gruber Syndrome. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">To diagram a family, with both parents being carriers of the gene: </B></div> <div> <I><B>Father</B></I><B>: Aa</B></div> <div> <I><B>Mother</B></I><B>: Aa </B></div> <div> <I><B>Child 1</B></I><B>: AA (Non-Carrier)</B></div> <div> <I><B>Child 2</B></I><B>: Aa (Carrier)</B></div> <div> <I><B>Child 3</B></I><B>: Aa (Carrier)</B></div> <div> <I><B>Child 4</B></I><B>: aa (Meckel-Gruber Syndrome)</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The risks are the same with EACH pregnancy</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Recent discoveries have linked a gene thought to cause Meckel Gruber Syndrome to the long arm of chromosome 17 (17q22-q23) in Finnish families. Another gene region, on the long arm of chromosome 11 (11q13), has been implicated in cases from individuals in the Middle East and North Africa.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f066000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Overall, it is likely that a number of different genetic problems may lead to the disease</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B>.</B></FONT></div> <div> <B> <TABLE BORDER="2" CELLPADDING="2" CELLSPACING="1" WIDTH="923" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" BGCOLOR=#262626 > <tR> <tD VALIGN=TOP HEIGHT= 599 ><NOBR><div> <B>Features Listed For </B><B>MECKEL-GRUBER</B><B> </B><B>SYNDROME</B><B> (DYSENCEPHALIA SPLANCHNOCYSTICA) </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Abnormal liver (including function) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Anal atresia/stenosis </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Biliary atresia/stenosis </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cardiac situs inversus/dextrocardia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cerebellar abnormalities (structural) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cerebral atrophy/myelin abnormality </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cleft palate </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cleft upper lip (non-midline) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Club foot/hindfoot, varus </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Coloboma of iris </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Congenital cardiac anomaly, unspecified </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dandy-Walker malformation </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Holoprosencephaly/arhinencephaly </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypospadias </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lobulated tongue (including hamartomata) </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lung hypoplasia/agenesis </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microcephaly </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microphthalmia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Multiple renal cysts </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neonatal teeth </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pancreas (exocrine), general abnormalities </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polydactyly of toes </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polydactyly/bifid thumb/pollex </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polysplenia </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Post-axial polydactyly of fingers </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Posterior encephalocele/meningocele </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pre-axial polydactyly of fingers </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pulmonary segmentation defects </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0ffff0000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stature/length short, prenatal onset </B></div> <bR> </NOBR></tD> </tR> </TABLE></B></div> <bR> <div> <B><U>polydactyly</U></B></div> <bR> <bR> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ellis-van Creveld</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Laurence-Moon-Biedle </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">trisomy 13-15 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">simple polydactyly </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Carpenter <FONT SIZE="3" COLOR="#800000" FACE="Arial" >syndrome</FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Meckel-Gruber<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>syndrome<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <bR> <div> <B>=====================================================================================================================</B></div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Immaturity syndrome </U></B></I><I><B><U> and small-for-gestational-age syndrome </U></B></I><FONT SIZE="3" COLOR="#6600FF" FACE="Arial" ><I><B> are spurious distractors.</B></I></FONT></div> <bR> <div> <B>====================================================================================================================</B></div> <div> <B><U>Clinical characteristics of prematurity/</U></B><B><U>dysmaturity</U></B><B><U> </U></B></div> <div> <B>1. Low birth weight. </B></div> <div> <B>2. Small frame - may appear thin with poor muscle development.</B></div> <div> <B>3. Periarticular laxity. </B></div> <div> <B>4. Usually flexor laxity but occasional contracture. </B></div> <div> <B>5. Usually hypotonia - occasional hypertonia. </B></div> <div> <B>6. High compliance to chest wall - soft ribcage. </B></div> <div> <B>7. Low compliance to lungs - stiff lungs - respiratory distress secondary to fatigue. </B></div> <div> <B>8. General muscle weakness - delayed time to standing. </B></div> <div> <B>9. Short, silky hair coat. </B></div> <div> <B>10. Domed forehead.</B></div> <div> <B>11. Floppy ears - poor ear cartilage development. </B></div> <div> <B>12. Weak suckle. </B></div> <div> <B>13. Poor thermoregulation. </B></div> <div> <B>14. GI tract dysfunction.</B></div> <div> <B>15. Delayed maturation of renal function - low urine output.</B></div> <div> <B>16. Entropion with secondary corneal ulcers. </B></div> <div> <B>17. Poor glucose regulation.</B></div> <bR> <bR> <div> <B><U>Clinical characteristics of postmaturity </U></B></div> <div> 1<FONT SIZE="3" COLOR="#000033" FACE="Arial" ><B>. Normal to high birth weight.</B></FONT></div> <div> <B>2. Large frame but thin with muscle wasting. </B></div> <div> <B>3. Often flexor contraction - occasionally flexor laxity. </B></div> <div> <B>4. Usually hypertonia - occasional hypotonia.</B></div> <div> <B>5. Delayed time to standing because of hyperreactive state and poor postural reflexes. </B></div> <div> <B>6. Long hair coat. </B></div> <div> <B>7. Fully erupted incisors.</B></div> <div> <B>8. Weak suckle. </B></div> <div> <B>9. Poor thermoregulation. </B></div> <div> <B>10. GI tract dysfunction.</B></div> <div> <B>11. Delayed maturation of renal function - low urine output.</B></div> <div> <B>12. Poor glucose regulation.</B></div> <bR> <div> Often hypoxic ischemia syndrome (HIS) and neonatal septicemia coexist with prematurity/dysmaturity/postmaturity. </div> <div> It can be exceedingly difficult to distinguish the signs from these syndromes and determine the relative severity or even presence of each.</div> <bR> <bR> <div> <I><B>Causes</B></I></div> <div> <I><B>1. Placental problems: </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">twins,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> placentitis, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">premature placental separation.</B></I></div> <div> <I><B>2. Fetal problems: </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fetal sepsis (Herpes virus, EVA, ehrlichiosis, other bacteria), </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fetal malformation,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> hydroallantois, </B></I></div> <div> <I><B>3. Maternal problems: </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">severe systemic disease,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> chronic debilitation. </B></I></div> <div> <I><B>4. Iatrogenic:</B></I></div> <div> <I><B>a. Early induction based on: </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">inaccurate breeding dates, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">misinterpreting late term colic as ineffective labor.</B></I></div> <div> <I><B>b. Early C-section because of catastrophic medical problem in mare: </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fatal colic, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fracture of major bone, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">progressive neurologic disease.</B></I></div> <div> <I><B>5. Idiopathic: most common cause.</B></I></div> <bR> </td> </tr></table></body>