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http://elliottcountyhighschool.com/
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Elliott County High School Alumni Elliott County Alumni Photos Class of 1979 Vanessa Mayse Unknown Grad Year Hugo Martin Unknown Grad Year April Kelly Class of 1997 Johnda Weaver What is this site ? Send messages to alumni View ECHS Alumni Profiles Share your memories Share photos with others Discuss past activities Register Now - It ' s Free ! Famous Alumni Add a Famous Alumni There are currently no Elliott County notable alumni listed . Be the first to add an ECHS famous alumni . Memorials Add a Memorial Create a Elliott County High School memorial for an individual alum that has passed away . There are currently no memorials for Elliott County alumni . Latest Alumni Listings View Complete List Add Your Name Class of 1969 Ella Oliver Class of 1989 Karen Dicket Class of 1976 Donna Ison Class of 1979 Vanessa Mayse Rocky Adkins Class of 2018 Jerry Eldridge Class of 1993 Sherry O ' Neal Deborah Atkins Class of 1998 Mickey Black Class of 2014 Shawn Carter Jonathan Whitt Class of 1976 John Green Hugo Martin Class of 2016 Isaac Fannin Class of 1981 Evelyn Padgett Whitney Tate Joanne Welch Stephanie Greene Class of 1980 Mark Green Class of 1978 Cathy Fannin April Birthdays Ben Stafford Curtis Kegley Register to Display Your Birthday Memories Add Your Memories Elliott County Alumni Merchandise Sale price : $ 19.99 Sale price : $ 26.99 Sale price : $ 29.99 Sale price : $ 59.99 Sale price : $ 49.99 Sale price : $ 36.99 View More ECHS Merchandise This site has been created for the former students of Elliott County HS located in Sandy Hook , Kentucky . We also encourage you to keep up to date on news and reconnect with Elliott County High School alumni . You can also find out what other graduates are doing now , share memories with other alumn , upload pictures from Elliott County and find other alumni Latest Updates from Elliott County High School Alumni Ella Oliver has someone searching for them . Karen Dicket has someone searching for them . Donna Ison Rocky Adkins Plus many more Most recent : 14 days ago added photos to their personal photo gallery registered as a ECHS Class of 1979 alumni updated her profile picture Most recent : February registered as a ECHS alumni updated his profile picture added photos to their personal photo gallery Most recent : July Curtis Elliott County Kegley ECHS Class of 1992 alumni 2017 April Kelly updated her ECHS alumni Most recent : 2017
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[
"Alumni",
"Elliott County High School",
"Vanessa Mayse"
] |
http://elliottlawsc.com/attorneys.html
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Stevens B Elliott BA University of South Carolina 1978 JD University of South Carolina School of Law 1981 steveelliottlawsccom B Reynolds Elliott BS Clemson University 2003 JD University of South Carolina School of Law 2008 reynoldselliottlawsccom
|
[
"University of South Carolina School of Law"
] |
http://elliscountyspca.org/index.html
|
Bring Home a Friend for Life Our mission is to provide every animal exceptional care and a loving home Adopt a Pet Adopt a Pet Interested in adopting from ECSPCA Missing Pets Get resources and help for finding lost pets Foster a Pet Interested in fostering with ECSPCA Volunteer Get information for volunteering at ECSPCA It all adds up Food and housing expenses along with the cost of medical attention for each animal at the ECSPCA shelter and shelter funds are limited but you can help Help us with just 5 monthly Your monthly donation of 5 or more will ensure that we have the resources we need to help every animal we receive Our goal is to have at least 100 generous donors signed up at 5 or more for a total of 500 in additional funds each month Sign up on our and your monthly contribution will go to work for shelter dogs and cats immediately Donations of supplies are always needed as well You can find a list of supplies needed on our Donations Page Donate Now Lost Pet Resources and Help Lost pets are held for a minimum of three full working days for an owner to claim so it is also important that you look for your lost pet immediately Walking through the shelter is the best way to verify whether or not your pet is there as you are the one who knows exactly what your pet looks like View Lost Pet Information ECSPCA Foster Program Foster homes fill an important need for underage puppies and kittens pets with medical issues moms and their babies pets needing more oneonone attention pets needing training and often just when a pet needs a break from the shelter or the shelter is too crowded Fostering helps the animals in need plus opens up a spot for another animal to be able to stay at the shelter Foster Program Information Ellis Scoop Quarterly Newsletter 2019 will bring a new edition to our shelter It will include upcoming offsite events updates fundraisers prizes to be won training tips and so much more Quarterly Newsletter
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[
"ECSPCA"
] |
http://elmers.com/about/faqs/van-yogi
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Elmer ' s FAQs ABOUT US deep roots why elmer ' s elmer ' s family of brands FAQs general how - to clean - up solutions DIY foam & display boards Ask Van & Yogi make your own slime kids in need foundation corporate responsibility careers contact us SITE USAGE privacy policy terms and conditions Ask the Elmer ’ s Glue Experts : Van & Yogi How durable is Elmer ' s ProBond Advanced ? ProBond Advanced delivers a heavy - duty strength and durability like a polyurethane glue without the foam residue that can ruin your project ' s finished appearance and quality . It is 100 % weatherproof and backed by a performance guarantee from the glue brand that DIY enthusiasts have trusted for generations . It ' s strong enough for tough outdoor weather conditions ! How long does a project need to be clamped for maximum bond ? While clamping is recommended when using most DIY adhesives , ProBond Advanced eliminates the need to monitor or " babysit " your project by giving you control of where the glue goes and where it stays when drying . Unlike polyurethane glues that can foam more than 200 percent during the drying process , ProBond Advanced has zero foam expansion . So , you wo n ' t have to check the bond throughout the drying process as you would normally when using a polyurethane glue . Once the glue has been applied , you can clamp and walk away . You should clamp your project for two hours or longer . For maximum hold , we recommend allowing the project to cure for 24 hours before handling Does the application method vary with the materials used ? ProBond Advanced was designed specifically for bonding porous surfaces , such as wood , concrete and drywall , to non - porous surfaces , such as metal , glass and ceramic . Porous surfaces will absorb some of the glue during the application . For best results , apply ProBond Advanced to both the porous and non - porous surface . Once you ' ve clamped the two materials , wipe away any excess wet glue with a wet cloth and move onto your other weekend projects while the glue dries . We recommend clamping for two hours or longer , and for maximum hold , allow the bond to cure for 24 hours before handling . If I am bonding metal to wood , on which surface should I apply the adhesive ? Able to work on almost any substrate , ProBond Advanced delivers a heavy - duty bond between porous ( wood , concrete , drywall ) and non - porous ( metal , glass , ceramic ) surfaces . So , a metal to wood application is an ideal use for ProBond Advanced . Porous surfaces , such as the wood being used in your project , will absorb a small bit of the glue . Therefore , we recommend applying ProBond Advanced to both the wood and metal , and clamping for two hours . For maximum bond , you should allow your project to cure for 24 hours before handling . I ' ve noticed that recycled glass bottles are being used as lamp shades in lighting projects . How can I use Elmer ' s ProBond Advanced to complete a project like this ? For a glass bottle lighting project , ProBond Advanced would work very well in adhering the bottles to a porous surface such as wood . However , please remember that ProBond Advanced is not heat - resistant , so we do n ' t recommend applying the glue to the actual light fixture or any place where it would be in direct contact with a heat source . ProBond Advanced was designed to bond mixed materials without the foam residue you get working with a polyurethane , making it an ideal adhesive for your upcycling projects . The nontoxic formula also makes it possible to work on projects safely whether you ' re indoors or outdoors . How long should the adhesive dry before being exposed to outdoor elements ? Outdoor projects require a bond that is strong enough to withstand the elements . ProBond Advanced delivers heavy - duty strength and a 100 % weatherproof bond you can trust for both your indoor or outdoor home projects , without any of the foam residue from a polyurethane glue . We recommend allowing the bond to dry on your outdoor projects for 24 hours or longer . For semi - porous or non - porous substrates , it may require several days for full strength . How much adhesive should be used per application ? Porous surfaces , like wood , concrete and drywall , absorb some of the glue , while non - porous surfaces , such as glass or metal will not absorb the glue . We recommend applying the glue liberally to both surfaces . The amount of glue should be enough to have squeezed out from the bond line when you press the two surfaces together . Once the project is clamped , clean up with a wet cloth is easy to wipe off any excess glue around the bond line . Leave your project clamped for two hours , and for maximum strength allow the project to cure for 24 hours before handling . Is special preparation required before painting the bond ? ProBond Advanced dries translucent , wo n ' t stain hands , and is washable when wet , making clean - up easy . We recommend clamping your project for two hours . Excess glue from around the bond line should be removed with a damp cloth . For maximum hold , allow the glue to cure for 24 hours before handling your project . Once the glue is dry , it can be painted to match any color , without additional preparation .
|
[
"Elmer ’s Glue Experts",
"ProBond Advanced",
"Van & Yogi"
] |
http://elohell.net/league-of-legends-counterpicks/syndra-counters
|
Home Counterpicks Syndra Syndra The Dark Sovereign Mid 6300 975 Transcendent Syndra ' s spells gain extra effects at their max rank . Dark Sphere - Deals 15 % bonus damage to champions . Force of Will - Increases the slowing duration by 33 % Scatter the Weak - Spell width increased by 50 % . Dark Sphere Active : Syndra conjures a Dark Sphere , dealing magic damage . The sphere remains for 6 seconds and can be manipulated by Syndra ' s other abilities . Transcendent Bonus : Deals 15 % bonus damage against champions Range : 800 Cooldown : 4 seconds Cost : 40 / 50 / 60 / 70 / 80 mana Magic Damage : 70 / 110 / 150 / 190 / 230 ( + 0.6 ability power ) Magic Damage to Champions ( Rank 5 ) : 264.5 ( + 0.69 per ability power ) Force of Will Active : On Syndra ' s first cast , she grabs a target Dark Sphere or enemy minion . Force of Will can be activated a second time to throw the Dark Sphere or enemy minion . Enemies hit by the thrown object take magic damage and are slowed for 1.5 seconds . Transcendent Bonus : Slow duration is increased to 2 seconds . Range : 925 Cost : 60 / 70 / 80 / 90 / 100 mana Cooldown : 12 / 11 / 10 / 9 / 8 seconds Magic Damage : 80 / 120 / 160 / Scatter the Weak Active : Syndra knocks back enemies and Dark Spheres , dealing magic damage to enemies that collide with the Dark Spheres . Dark Spheres that are knocked back stun all enemies in their path for 1.5 seconds . Transcendent Bonus : Spell width increased by 50 % Cost : 50 mana Range : 700 Missile Speed : 2,500 Magic Damage : 70 / 115 / 160 / 205 / 250 ( + 0.4 ability power ) Cooldown : 18 / 16.5 / 15 / 13.5 / 12 seconds Missile Speed : 2500 Unleashed Power Active : Syndra draws upon her full cataclysmic power , harnessing all Dark Spheres to deal magic damage to an enemy champion . Range : 675 - 750 Cost : 100 mana Magic Damage per Sphere : 90 / 135 / 180 ( + 0.2 ability power ) Cooldown : 100 / 90 / 80 seconds Minimum Magic Damage : 270 / 405 / 540 ( + 0.6 ability power ) Damage with 6 Spheres : 560 / 810 / 1080 ( + 1.2 per ability power ) Damage with 7 Spheres : 630 / 975 / 1260 ( + Health Points 380 Mana 250 Damage 51 Attack Range 550 Armor 15 IP Cost 6300 Health Regen 5.5 Mana Regen 6.9 Attack Speed 0.625 Movement Speed 330 Magic Resistance 30 1 lvl Guides Counterpicks Syndra Strong Against Katarina 28 13 0 comments Annie 20 3 0 comments Lux 20 11 Orianna 14 2 Cassiopeia 12 2 Heimerdinger 16 11 Twisted Fate 6 0 Ahri 12 17 Fizz 10 19 Yasuo 3 0 Syndra Weak Against Zed LeBlanc 17 Fizz 19 10 Ahri Talon 8 1 Heimerdinger 16 Katarina 13 28 Kassadin 6 Lux Azir Syndra Synergy Singed 1 Maokai Sion Lee Sin Nunu Taric Zac Blitzcrank Ads
|
[
"Syndra"
] |
http://elpaso.ttuhsc.edu/bcc/
|
Texas Tech Physicians of El Paso Breast Care Center Home About Us Survivorship Program Contact Us Breast Care Center The Texas Tech Physicians of El Paso Breast Care Center is a nationally accredited breast center accredited by the National Accreditation Program for Breast Centers NAPBC The NAPBC is a program administered by the American College of Surgeons Accreditation by the NAPBC is only given to those centers that have voluntarily committed to providing the highest level of quality breast care and that undergo a rigorous evaluation process and review of their performance Read more at wwwnapbcbreastorg Mission Survivorship Program
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[
"Breast Care Center"
] |
http://elps.org/
|
Patience A comic opera July 12 - 14 Learn More ! ELPs History The Empire Lyric Players , commonly referred to as ELPs , was organized in 1958 by Holy Family High School graduates and has been a constant presence in the Denver Community Theater scene since . Their first . . . Read more » Volunteer Every ELPs show is made possible by an army ( or a British Navy if you prefer ) of people who love Theater , their fellow ELPers , and most of all Gilbert and Sullivan . Some people prefer to contribute to . . . Read more » Videos and Photos
|
[
"Patience",
"ELP"
] |
http://elrinconcitopaisatwo.com/
|
El Rinconcito Paisa 2 El Rinconcito Paisa 2 Quality freshness and friendly service is what you can expect with every visit at El Rinconcito Paisa We offer a great selection of Paisa style breakfast including Omelette Rinconcito made with beef mushrooms onions tomatoes bacon potato and chocolate Delight in our delicately wrapped tamales with yellow rice and chicken pork and carrots If youre looking for great home cooking try one of our House Specialties including Ox tail soup beef trip soup or our rinconcito paisa platter with fried port skin Spanish sausage blood sausage beef French fries and corn cake We are open daily from 11 am Call
|
[
"El Rinconcito Paisa",
"Paisa style breakfast",
"Omelette Rinconcito"
] |
http://elsword.wikia.com/wiki/How_to_Repair_Equipment
|
How to Repair Equipment You can also do this at the weaponssmith shop
|
[
"Repair Equipment"
] |
http://elte.prompt.hu/sites/default/files/tananyagok/IntroductionToPracticalBiochemistry/ch05s03.html
|
53 Centrifugation When an object attached to a rope is whirled around one can feel that the rope must be pulled inward towards the centre of the rotation in order to keep the object on the orbit This force prevents the object from getting away and move with a constant speed along a straight tangential line The inward force with which one has to pull the rope is called the centripetal force One can also define the outward force the centrifugal force by which the object pulls the rope This force is equal in magnitude to the centripetal force but has the F c is a virtual socalled fictional force emerging due to the inertia of the object Yet because it leads to a simpler mathematical formalism equations describing the processes when solutions are centrifuged use the F c force According to the wellknown Newton equation 51 Upon centrifugation acceleration equals the product of the radius of the orbit and the square of the angular velocity 52 The fictive centrifugal accelerating force in vacuum is therefore 53 The product of the radius and the square of the angular velocity equals the centrifugal accelerating potential Traditionally and perhaps somewhat misleadingly the magnitude of this potential is compared to the Earths gravitational accelerating potential g and has been expressed in g units The reason is quite simple Earths gravitational potential similarly to the accelerating potential provided by centrifugation can also sediment particles dispersed in solution This type of quantitation shows how many times centrifugation is more effective to sediment particles compared to the gravitational effect of Earth In the fastest laboratory ultracentrifuges the applied accelerating potential can exceed 1 000 000 g When solutions are centrifuged the particles are not in vacuum but in a solvent having a given density massvolume Importantly the centrifugal force acts not only on the particles but on the solvent too If the density of the particle equals the density of the solvent the particle will not move relative to the solvent and its velocity along the radius will be zero If the density of the particle exceeds that of the solvent the particle sediments sinks ie it moves outwards along the radius while the displaced solvent molecules move inwards In the opposite case when the density In order to provide a simple mathematical description of this phenomenon the buoyancy factor has been defined as follows 54 The numerator of the fraction contains the density of the medium solvent while the denominator contains the density of the particle Introduction of the buoyancy factor leads to the following equation 55 This equation clearly shows that upon centrifugation the force acting on a given particle is a function of the mass of the particle the relative density of the particle compared to that of the medium the angular velocity of the rotation and the distance of the particle from the centre of the rotation ie from the spindle of the centrifuge The first two of these parameters namely the mass and the density are characteristic of the particle and differences in these parameters can allow for the physical separation of different types of particles As we will see there are two major types of centrifugationbased separation techniques In one technique called differential centrifugation the separation is based on both particle mass and density In the case of the other called equilibrium densitygradient centrifugation the separation is based strictly on the density of the particles As soon as the particles are accelerated by the centrifugal force and start moving towards the spindle a dragging force F d called friction is exerted on them by the medium This force which has a direction opposite to the direction of the particle movement is proportional to the velocity of the particle At the typically very low speed of the sedimentation process the F d force is a linear function of the velocity The ratio of the force and the velocity is defined as the frictional coefficient f The value of f is a function of the viscosity of the medium and of the size and shape of the particle as described below by Stokes law 56 In this equation r denotes the Stokes radius If the particle is spherical this equals the radius of the particle If the particle is not spherical r a virtual value denotes the radius of a spherical particle that has identical diffusion properties as the nonspherical particle in question and µ denotes viscosity of the medium Note that the value of the frictional coefficient is proportional to the radius of the particle The larger the particle the higher dragging force is exerted on it by the medium In the course of centrifugation the velocity of each particle is increasing due to the accelerating force F c However as the velocity increases the dragging force also increases Therefore the velocity of each particle can increase to a given value where the value of the dragging force F d reaches the value of the accelerating F c value The magnitude of the two opposing forces becomes equal in a very short time 57 Once the magnitude of the two opposing forces becomes equal the resultant force becomes zero Therefore the particle will move with a constant velocity characteristic to that particle at the given accelerating potential and medium A similar phenomenon is described in Chapter 7 on electrophoresis There the accelerating force is proportional to the charge instead of the mass of the particle but the friction force and the phenomenon of two opposing forces leading to a characteristic particle velocity is analogous Substituting F c into the previous equation leads to the following equation 58 If the above equation is rearranged by dividing particle velocity with the centrifugal acceleration potential the resulting equation will lead to a useful parameter This is the sedimentation coefficient its unit of measure is one over seconds which is usually expressed in Svedberg units This coefficient describes the sedimentation propensity of the particle It provides the characteristic sedimentation velocity of a particle triggered by a unit level of accelerating potential 59 The numerator of the equation contains all parameters that favour sedimentation The higher the mass and relative density compared to the medium of the particle the higher its sedimentation velocity will be when unit accelerating potential is applied The mass of the particle of a given density of course is linearly proportional to its volume In other words the mass is a linear function of the cube of the particle radius The denominator contains the parameter that negatively influences sedimentation speed The larger the frictional coefficient the lower velocity will be triggered by unit level acceleration potential As we have If two particles have identical density the larger particle will sediment faster and the ratio of the velocities will follow a square law with respect to the ratio of the particle radii This relationship provides the basis for the socalled differential centrifugation methods 531 Differential centrifugation cell fractionation based primarily on particle size The density of the various organelles differs on a smaller scale than their size Therefore while both size and density affect sedimentation velocity their size difference dominates when organelles are separated by centrifugation In the procedure of differential centrifugation cell constituents are separated from each other by their Svedberg value Several consecutive centrifugation steps are applied in the order of increasing accelerating potential Each individual centrifugation step relies on the different sedimentation speed of the different cell constituents at the given acceleration potential At a properly chosen acceleration potential almost 100 of the largest component will sediment in the time span of the centrifugation The sedimented organelles form a pellet at the bottom of the centrifuge tube The potential should be set so that in the same period of time only a small Figure 51 Differential centrifugation In the course of differential centrifugation consecutive centrifugation steps are applied The consecutive centrifugation steps follow each other in the order of increasing centrifugal acceleration potential During the first centrifugation only the largest andor heaviest cell constituents sediment in the time frame of the centrifugation Typically only nuclei and undisrupted whole cells form the pellet The supernatant of the first centrifugation step is further centrifuged in the consecutive step at higher acceleration potential and typically for a longer period of time Following this scheme ever smaller andor lowerdensity cell constituents can be sedimented The disrupted cell homogenate is centrifuged first at a relatively low accelerating potential of 500 g for 10 minutes Under these conditions only particles having the highest Svedberg value intact cells and nuclei will form the pellet All other cell constituents will sediment at a much lower rate and remain in the homogenate The supernatant of the first centrifugation is transferred into an empty centrifugation tube and is subjected to another centrifugation step now at a significantly higher accelerating potential of 10000 g and for 20 minutes These conditions favour sedimentation of mitochondria lysosomes and peroxisomes having lower Svedberg values g ribosomes and large proteins can also be sedimented 532 Equilibrium densitygradient centrifugation fractionation based on density In the previous section we introduced the method of differential centrifugation For simplicity we stated that the constituents of the sample were separated in a medium of homogeneous density This first approximation has didactical advantages as it makes the basic principle of differential centrifugation easier to comprehend Nevertheless it is sometimes advantageous to use a very shallow density gradient in the medium during differential centrifugation This is done only to suppress convectional flows in the medium that could unsettle and mix layers of already separated cell constituents The essence of equilibrium densitygradient centrifugation is principally different In this case a rather steep density gradient is created in the mediumin such a manner that the density of the medium gradually increases towards the bottom of the centrifuge tube This is achieved by using a very highdensity additive for example caesium chloride CsCl The density gradient is created as follows When the centrifuge tube is filled with the medium a high concentration CsCl solution is added first Subsequently in the process of filling the tube the concentration of CsCl is gradually decreased resulting in a CsCl gradient and as Figure 52 Equilibrium densitygradient centrifugation In the course of equilibrium densitygradient centrifugation a concentration gradient of a high density compound such as caesium chloride is generated The compound should not react with the biological sample The concentration gradient of this special additive creates a density gradient in the centrifuge tube The density gradually increases toward the bottom of the centrifuge tube The sample is layered on the lowdensity top of this gradient As the centrifugation begins each compound of the sample starts to sediment By doing so the compounds travel through layers of increasing density As soon as a compound In the course of centrifugation particles start to sediment moving towards the bottom of the centrifuge tube By doing so they travel through an increasing density medium Each particle sediments to a section of the medium where its own density equals the density of the medium At this section the buoyancy factor becomes zero and as a consequence the accelerating force acting on the particle also becomes zero The particle stops sedimenting If it moved further towards the bottom of the tube it would meet a higher density medium and a force opposing to its moving direction would be exerted Note that the two centrifugation approaches introduced above separate particles by partially different characteristics Consecutive combination of the two methods can lead to a more efficient separation than achieved by any of the methods alone Therefore to increase separation efficiency fractions generated by differential centrifugation can be subjected to a subsequent densitygradient centrifugation step to further separate individual components Figure 53
|
[
"cell fractionation"
] |
http://elviswomen.greggers.net/annmargret.htm
|
Main Pages and Lists Actresses A - G Actresses H - O Actresses P - Z Ann - Margret Viva Las Vegas , 1964 Full Name : Ann - Margret Olsson Smith Born : April 28 , 1941 , in Stockholm , Sweden . Husband ( s ) : Roger Smith ( 1967 - present ) Official Site : www . ann - margret . com Of all Elvis ' leading ladies , Ann - Margret will always be Number One . Not because she was the sexiest , or the best actress ( although she certainly qualifies on both counts ! ) , or because " Viva Las Vegas " was that great of a film ( but for an Elvis film , it ' s pretty good ! ) , but because the on - screen chemistry between them was NOT ACTING . It ' s probably why Viva Las Vegas is still one of the best - remembered of both Elvis ' and AM ' s films . Watching the film today , what comes across is two talented stars at the peak of their confidence , enjoying each other ' s company , and having fun ! And that ' s pretty much what was happening off - screen , too ! But do n ' t just take my word for it ; get it straight from the source ( Ann - Margret : My Story ) . Needless to say , when people think of actresses in Elvis films , Ann - Margret is almost always the first to come to mind . Although born in Stockholm , Ann - Margret Olsson was raised in the town of Valsjobyn , Sweden , a small mountain village . At the age of five , she and her mother joined her father in America . Growing up near Chicago , she was performing in a group by age 16 . She appeared on the Ted Mack Amateur Hour around that time singing " Them There Eyes " . At the age of 19 , she was discovered by George Burns in Las Vegas . She appeared on " The Jack Benny Show " , and was soon in the movies with " Pocketful of Miracles " . Her first important role came in 1963 with " Bye , Bye Birdie " , a musical about a rock star who is drafted into the army ( hmmm . . . ) . Viva Las Vegas immediately followed . As Rusty Martin , Ann - Margret sang " My Rival " , " Appreciation " , and duetted with Elvis on " The Lady Loves Me " . The duet " You ' re The Boss " was recorded for the film but not used . Since Ann - Margret was on the same record label as Elvis at the time ( RCA Victor ) , it ' s surprising that there was no soundtrack album released including both artists . ( Elvis only did this once : see Nancy Sinatra ) . However , nowadays , you can get the soundtrack which includes both the duets . According to AM ' s autobiography , she and Elvis hit it off almost immediately when they first met . They had a lot in common , both in their public images , and their private personalities . In fact , the very contrast between " wild in public " and " shy in person " was one of their most notable similarities . They shared a deep belief in God . They were both very close to their families . For both stars , their fame came overwhelmingly fast , and a tight - knit family was both a Although the British press reported them engaged , AM and Elvis soon went their separate ways . They remained friends afterwards , attending each other ' s concerts in Vegas , whenever they were in town . ( Ann - Margret and her husband Roger Smith were among the very few celebrities who attended Elvis ' funeral . ) In 1971 , she was nominated for Best Supporting Actress for " Carnal Knowledge " , and in 1975 for Best Actress for " Tommy " . Between theatrical films , TV movies , and her night club act , AM has kept herself quite busy . Among her most recent successes was a role as Cinderella in the fantasy mini - series 10th Kingdom , as well as an appearance in the film , Any Given Sunday , a notable guest role on the popular TV series Touched By An Angel , and an appearance with friend Burt Reynolds in The Final Hit . She also starred in the musical " The Best Little Whorehouse in Texas " , which was her first stage role ! Ann - Margret Links Fan Sites - When I first started this page , J.W. Smith ' s Ann - Margret page was the only other one out there ( and it ' s gone now ) . There are quite a few to browse , and all have something unique to offer ! These are sites that I visit on a regular basis just to see if they ' ve updated or added anything . . . I suggest you do the same . . . The Official Ann - Margret Site ! - Apparently it was Roger ' s idea to put up a website for AM ( well , after all , he IS her number one fan ! ) Check it out ! Film clips , photos , bio , fan club info and more ! The Unofficial Ann - Margret Page From Sweden ! - a nice site from AM ' s homeland ! Many ( constantly changing ! ) pages with photos , and a " Sound Clip of the Month " page , too ! Have a look ! ! Viva Ann - Margret - Another fan site ! some pretty unique photos here ! DRD ' s Ann - Margret Page - another fan page , this one ' s got a couple pages of photos , and a movie page , so far ! You go , Doug ! Other Links Ann - Margret - IMDB - Wikipedia Facebook : Ann - Margret TCM ' s Ann - Margret page Ann - Margret Pictures - FanPix Listen to Ann - Margret on last . fm Ann of a Thousand Knights : Ann - Margret Thanks the Soldiers - one of my favorite AM stories , and it ai n ' t no urban legend ! Fansource : Ann - Margret - news items , press photos , official fan club info , etc . Viva Las Vegas Photo Shoot Session - from the EPSS site . Loads more photos of AM and Elvis here than you ever thought existed ! Luis ' Ann - Margret Page - from the guy who brought us the excellent Debra Paget pages , so you know it ' s a great collection of photos ! Luis has 13 pages worth of AM photos here , plus a bunch of video clips ! Ann - Margret Books : Do your Ann - Margret research ! These are the AM books worth seeking out ! Ann - Margret : My Story , by Ann - Margret and Todd Gold - The autobiography ! Either the print version or the audio - book , you gotta get yourself a copy ! Ann Margret : A Dream Come True : A Photo Extravaganza and Memoir , by Neal Peters and David Smith . - Another must - have on every AM fan ' s list ! This coffee - table book is chock full o ' great photos ! Careless Love : The Unmaking of Elvis Presley , by Peter Guralnick - The second half of Peter ' s great two - volume biography of Elvis , this one covering the movie years and beyond . Print or Audio - book version . Elvis and Me , by Priscilla Presley and Sandra Harmon - Life with Elvis from Priscilla ' s view , including her take on Elvis ' relationship with Ann - Margret . Ann - Margret Music ! Buy Ann - Margret ' s music on CD , streaming or download MP3s Ann - Margret 1961 - 1966 The AM box - set ! Ann - Margret : The Definitive Collection Nice 2 - Disc Set ! The Essential Ann - Margret Another Great 2 - Disc Set ! The soundtrack ! Contains the duet version of " Today , Tomorrow , and Forever " or download from iTunes ! Ann - Margret Videos ! A&E Biography - Ann - Margret : Sugar & Spice " BIOGRAPHY tells the story of the still - vibrant star through extensive clips from her films , rare photographs and interviews with friends and confidantes . . .From teenage sensation to accolades , awards and respect , join BIOGRAPHY for the triumphant tale of Ann - Margret . " Search eBay for some Ann - Margret Stuff ! Ad ACTRESS ANN - MARGRET PIN UP - 8X10 PUBLICITY PHOTO ( BT026 ) $ 8.98 Free Shipping ANN MARGRET 8X10 CELEBRITY PHOTO PICTURE HOT SEXY 1 $ 7.99 Free Shipping ANN MARGRET 8X10 CELEBRITY PHOTO PICTURE HOT SEXY 3 $ 7.99 ANN MARGRET 8X10 CELEBRITY PHOTO PICTURE HOT SEXY 2 ELVIS PRESLEY & ANN - MARGRET ON THE SET OF " VIVA LAS VEGAS " - 8X10 PHOTO ( AB919 ) $ 8.98 ACTRESS ANN - MARGRET - 8X10 PUBLICITY PHOTO ( RT636 ) $ 9.98 HOT ANN MARGRET TAKING A STILL SHOT IN PINK & WHITE SEXY OUTFIT PUBLICITY PHOTO $ 8.69 Ann Margret by Photographer Harry Langdon with Embossed Stamp Photo 2M $ 5.99 ACTRESS ANN - MARGRET - 8X10 PUBLICITY PHOTO ( FB - 383 ) ACTRESS ANN - MARGRET - 8X10 PUBLICITY PHOTO ( RT637 ) $ 9.98 ELVIS PRESLEY ANN - MARGRET CANDID PHOTO - OnTheSet of the movie VIVA LAS VEGAS $ 7.49 ACTRESS ANN - MARGRET - 8X10 PUBLICITY PHOTO ( FB - 070 ) ELVIS PRESLEY AND ANN - MARGRET IN " VIVA LAS VEGAS " - 8X10 PUBLICITY PHOTO ( AB944 ) Ann - Margret - 8x10 Photo - 22 $ 16.99 Ann - Margret - 8x10 Photo - 15 $ 16.99 Ann - Margret - 8x10 Photo - 8 ANN MARGRET - " SONGS FROM THE SWINGER " / RCA VICTOR ' 66 $ 5.99 ACTRESS ANN - MARGRET PIN UP - 8X10 PUBLICITY PHOTO ( AZ519 ) Screen World 1964 Ann Margret Joan Crawford James Franciscus Elizabeth Taylor $ 25.00 Teen Screen Magazine - January 1963 - George Chakiris , Annette , Ann - Margret $ 3.00 ANN MARGRET & TUESDAY WELD " THE CINCINNATI KID " - 8X10 PUBLICITY PHOTO ( DA - 083 ) ACTRESS ANN MARGRET - 8X10 PUBLICITY PHOTO ( FB - 590 ) ELVIS PRESLEY & ANN - MARGRET IN " VIVA LAS VEGAS " - 8X10 PUBLICITY PHOTO ( DA - 182 ) ACTRESS ANN - MARGRET - 8X10 PUBLICITY PHOTO ( AB - 501 ) ACTRESS ANN MARGRET - 8X10 PUBLICITY PHOTO ( BB - 423 ) Elvis Presley And Ann Margret Face Of Face 8x10 Glossy Photo Print $ 4.00 ELVIS PRESLEY AND ANN - MARGRET IN " VIVA LAS VEGAS " - 8X10 PUBLICITY PHOTO ( AB920 ) ANN - MARGRET Vintage 35mm Slide LOT TRANSPARENCY PHOTO Slides AM3 $ 14.99 ELVIS PRESLEY & ANN - MARGRET ON THE SET OF " VIVA LAS VEGAS " - 8X10 PHOTO ( AB924 ) ELVIS PRESLEY AND ANN - MARGRET IN " VIVA LAS VEGAS " - 8X10 PUBLICITY PHOTO ( AB964 ) CLASSIC CELEBRITY ACTRESS ANN MARGRET SEXY IN A SWIM SUIT PUBLICITY PHOTO $ 7.64 Nice Signed Ann Margret 8X10 Color RP Photo SEXY w / coa Free Shipping $ 6.35 Ann Margret by Photographer Harry Langdon with Embossed Stamp Photo 101L Ann Margret Super Hot Wearing Her Sexy Body 8x10 Photo Picture Print $ 3.99 ACTRESS ANN - MARGRET PIN UP - 8X10 PUBLICITY PHOTO ( AZ522 ) Ann Margret Sensual Shirtless 8x10 Picture Celebrity Print $ 3.99 Shout It Out ! Leave Us Your Comments About Ann - Margret ! Main Page Main Menu of Wahinis List of Movies Video / Music Store Links Contact Greggers
|
[
"Ann-Margret",
"Viva Las Vegas"
] |
http://email.about.com/od/gmailtips/qt/et061206.htm
|
How To Email & Messaging How to Preview Gmail Attachments Without Leaving the Message You do n ' t have to download every attachment Getty Images by Heinz Tschabitscher Updated March 09 , 2019 You can , of course , download the attachments that are sent to your Gmail account , but you do n ' t have to Most file attachments can be previewed on the website so you can see the picture up - close , listen to the audio file , read the PDF ( even if it ' s multiple pages long ) , watch the video clip , etc . , and not have to save anything to your computer . This is extremely handy since some file attachments do n ' t really need to be saved . For example , if someone sends you a Word document that they want you to read over , you can just preview the attachment within the web browser and then reply to the email without ever having to download the file to your computer . Email attachments are also easily integrated into Google Drive . If you do n ' t want the attachment taking up space on your computer , you can save it directly to your Google account so it ' s stored online . This has the added benefit of letting you delete the email but still revisit the attachment whenever and wherever you want . Some file types can not be previewed in Gmail . This might include ISO files , RAR files , etc . How to Preview Gmail Attachments Online Place your mouse cursor over the attachment thumbnail . In Gmail , attachments are located at the bottom of the message just before the Reply and Forward options . Click anywhere on the attachment without clicking either of the two buttons . Clicking anything but the buttons will let you preview the attachment . You can now look at , read , watch , or listen to the attachment without downloading it . The close button is the back arrow at the top left of the preview screen . There are several other options while viewing the attachment , depending on the format it ' s in . You can zoom up , scroll through pages , save it to your Google Drive account , print it , download it to your computer , open it in a new window and see its details , such as the file extension and size . Large attachments may not preview in Gmail . If you find that you can not preview an image , document , or video , you ' ll be required to download it to open it . If you have different apps attached to your Google account , you can do other things too . For example , there ' s one app that lets you split PDF files . You could preview the PDF attachment on Gmail and then select that app to extract pages out of it . How to Download Gmail Attachments If you do n ' t want to open the attachment , but instantly download it instead : Hover your mouse over the attachment . Click the download arrow to choose where to save the attachment . Also remember what ' s written above in the previous section ; you can download the attachments while previewing it too . However , the steps here are for downloading the attachment immediately without having to preview it first . Save the Attachment to Your Google Drive Account The last option you have when dealing with Gmail attachments is to save the file directly to your Google Drive account . Put your mouse over the attachment to see the download button and one other button called Save to Drive Click that button to immediately copy the attachment to Google Drive for viewing later , emailing , sharing , etc . How to Save Inline Images in Gmail On occasion , you might get an email that has an image saved within the message but not as an attachment . These are in - line images that appear next to the text . You can download these kinds of image attachments too , two different ways : Right - click the picture and choose Save image as . It might be called something similar in a browser other than Chrome . The other way is to left click the picture so that it opens in the attachment preview screen like a normal attachment . Click the Download button icon ( the down arrow ) from the top right of the screen . Continue Reading
|
[
"Gmail Attachments"
] |
http://email.about.com/od/outlookexpressbeginners/qt/Send_a_File_as_an_Attachment_with_Windows_Live_Mail_WM_OE.htm
|
How To Email & Messaging Email a File as an Attachment in Windows Live Mail by Heinz Tschabitscher Updated April 30 , 2018 Using Windows Mail or Outlook Express , it is easy to send text messages to friends , colleagues , and strangers . You can even use fancy stationery or insert pictures in your messages But that ' s not all . You can also add any file to your emails and send it as an attachment to anybody equipped with an email address . Just ask before you send a large file Send a File as an Attachment with Windows Live Mail , Windows Mail or Outlook Express To send a file attached to an email with Windows Live Mail , Windows Mail or Outlook Express : Create a new message . Click the Attach button . Find and highlight the desired file in the Open or Insert Attachment dialog . You can highlight and attach multiple files at once by holding down the Ctrl key while you click on them with the mouse . Click Open Attach , whichever you see . Sending Multiple Files with Ease and Elegance If you want to send more than one file with an email , you can also pack them neatly into one ZIP archive . And if you have the folder containing the file you want to attach open in Windows Explorer , you can alternatively , but easily , attach it by drag - and - drop
|
[
"Email & Messaging",
"Windows Live Mail",
"Outlook Express"
] |
http://email.about.com/od/outlooktips/qt/Import_from_Google_Calendar_into_Outlook.htm
|
How To Email & Messaging Import From Google Calendar Into Outlook Transfer Your Calendar Events Easily Import Google Calendar Into Outlook . Hero Images / Getty Images by Heinz Tschabitscher Updated April 15 , 2019 You can view your Google Calendar alongside your Outlook calendar by subscribing to your own Google Calendar in Outlook . Alternatively , you can import events from Google Calendar into Outlook , but the two calendars will not sync following updates . These instructions apply to Outlook 2019 , Outlook 2016 , Outlook 2013 , and Outlook for Office 365 . Subscribe to Your Google Calendar Setting up an iCal subscription ensures that the copy of your Google Calendar in Outlook is current . Log in to your Google Calendar . Select My Calendars in the left pane . Point to the calendar you want to add to outlook . Select the three dots that appear to the right of the calendar name and then choose Settings Right - click the URL in the Integrate Calendar section and select Copy Open Outlook and go to the File tab . Select Account Settings > Account Settings Select the Internet Calendars tab . New Press Ctrl - V to paste the address you copied from your Google Calendar account . Type the name of the calendar in the Folder Name box and click OK Import Events From Google Calendar Into Outlook If you want events currently listed in your Google Calendar account without updates , you can import it into Outlook . Log into your Google Calendar account . Select the Settings icon in the upper - right corner and select Settings Import & Export in the left pane . Export and choose the Export button . A ZIP file will download to your computer . Go to the download and select Extract All Start Outlook and select the File Open & Export > Import / Export . The Import and Export Wizard will open . Choose Import an iCalendar ( .ics ) or vCalendar file , and then choose Next Browse to where you stored the extracted file . Select the one that ends with gmail . com and choose OK Import . Your Google Calendar events will appear in Outlook . Continue Reading
|
[
"Google Calendar",
"Import",
"Outlook"
] |
http://email.about.com/od/yahoomailtips/qt/et_sort_mailbox.htm
|
How To Email & Messaging How to Sort Messages in Yahoo ! Mail by Heinz Tschabitscher Updated October 02 , 2018 You can read emails in Yahoo ! Mail not only by date , but also sort by sender and subject , or group them by attachment and starred . As You Like It By default , Yahoo ! Mail displays the messages in a mailbox sorted by date . This , granted , is very useful most days and dates , sometimes , though , you may want to quickly find the big emails containing attachments , for example , or group messages from the same person . Luckily , you can sort mailboxes in Yahoo ! Mail by a number of criteria — and even group by conversation . Sort Messages in Yahoo ! Mail To sort a folder in Yahoo ! Mail : Click Sort by in the folder ' s toolbar . Select the desired sort order from the menu that has appeared . Unread Messages will put unread emails on top ; unread and read emails will each be sorted by date . Attachments put messages that contain files above those that do not ; the secondary sort order again is by date . Starred has emails you marked with a star on top ; starred and unscarred emails are sorted descending by date . Sender sorts by name ( then email address ) in the From : line . Subject will sort emails alphabetically ( A – Z ) by subject Yahoo ! Mail will disregard " Re : " , " Fwd : " and similar expressions at the beginning . Optionally , select Group by conversation to use the subject as a secondary sorting algorithm . Messages will be sorted by date , for example , but older messages will be grouped under the latest message with the same subject . Group by conversation is not available when you sort by subject or sender . Sort Messages in Yahoo ! Mail Basic To sort the emails in a folder in Yahoo ! Mail Basic : Open the folder you want to sort in Yahoo ! Mail Basic . Click the Sort By menu to open it . The menu will show the current sorting order , e.g . Date Select the desired criterion from the menu . Date will sort chronologically by date received . Sender sorts alphabetically by the email address in the From : line . Subject will sort alphabetically by Subject : line . Attachment sorts by whether an attachment is present ( but not by their number ) . Starred puts starred emails on top or bottom . Choose Descending Order for the latest messages on top or Z - A sorting or Ascending Order for sorting oldest to newest and A - Z . Note that alphabetical sorting may not put non - English characters where you would expect them . Click Apply Other Ways to Get to the Messages You Seek If you are looking for a specific message , in addition to sorting folders and scanning lists , you can also search for messages more precisely , of course , using a number of search criteria , or have Yahoo ! Mail return all a sender ' s messages quickly . ( Tested with Yahoo ! Mail and Yahoo ! Mail Basic in a desktop browser ) Continue Reading
|
[
"Yahoo ! Mail",
"Sort Messages",
"Group by conversation"
] |
http://embarcaderocenter.com/about/
|
About Spanning four blocks in the heart of downtown San Francisco Embarcadero Center is one of the largest mixeduse complexes in the Western United States Featuring a unique and award winning architectural design Embarcadero Center offers four buildings with luxury offices space hundreds of shops restaurants services and a stateoftheart multiplex cinema Embarcadero Center History In the 1950s city planner M Justin Herman spearheaded a plan to redevelop the San Francisco waterfront location where Embarcadero Center stands today Inspired to create a mixeduse city within a city David Rockefeller John Portman and TrammelCrow submitted the winning proposal to develop the 85 acre site Built in phases over 15 years development began in 1968 and concluded in 1983 During this time the vision for the four Embarcadero Center towers was brought to life Construction of each of the four buildings was completed over a ten year span between 1971 and 1981 Upon completion the towers immediately Embarcadero Center still holds this premiere position in the City and welcomes more than 16000 people each day Owned and operated by Boston Properties the four towers are the corporate headquarters for major companies and the setting for thriving retail and restaurant businesses An innovator for over 40 years Embarcadero Center is dedicated to energy efficiency and sustainability The entire complex has earned LEED certification and continues to provide welcoming surroundings for tenants and visitors while protecting and preserving the environment
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[
"Embarcadero Center",
"San Francisco",
"LEED certification"
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http://embassymetals.com/
|
NEXT GENERATION POWDERED METAL THE EMBASSY ADVANTAGE ENGINEERING EXPERTISE THE EMBASSY ADVANTAGE Growing bigger , smarter to serve you better Embassy Powdered Metals offers something unique in metal parts fabrication . Expanded facilities , a skilled team of experts extends our capacity to provide custom , cost - saving solutions to a wide range of industries . State - of - the - art green engineering expertise and a commitment to lean manufacturing processes help our growing list of customers discover the cost - effective advantages of superior engineered metal . Most important : we become a valued partner in your continued success . CAPABLE OF MORE Whether you need new PM products designed and produced , or you ’ re ramping up production of a proven part , we ’ ve got you covered . LEARN MORE ENGINEERING SOLUTIONS Embassy specializes in collaborating with customers to engineer metal parts that do more — meeting precise needs , applications , and specifications . LEARN MORE MASTERING ENGINEERED METALS Take a deep dive into how Embassy engineers improved performance , longer life , and enhanced cost effectiveness into every powdered metal part . Putting more into powdered metal , so you get more out of it . Let us show you how our unique combination of engineering expertise , production capabilities , and commitment to personalized solutions can make all the difference . CONTACT US WE ’ RE HIRING ! Join Our Dedicated Team At Embassy Powdered Metal , we believe that our greatest competitive advantage is our people . And there ’ s never been a more exciting time to join our team ! We are ISO Certified
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[
"Embassy Powdered Metals",
"manufacturing processes"
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http://embassysuites3.hilton.com/en/hotels/illinois/embassy-suites-by-hilton-chicago-downtown-CHIDWES/index.html
|
All At A Glance At Embassy Suites by Hilton Chicago Downtown , you ' re in the heart of downtown Chicago , Illinois , surrounded by shopping and entertainment venues . Located on State Street between Ohio and Ontario Streets , we ' re three blocks west of Michigan Avenue ' s Magnificent Mile , and convenient to the Loop , the financial district and popular attractions . A block away is the free seasonal Navy Pier trolley and subway , linking to local attractions and both Midway and O ' Hare airports . A great choice in Chicago hotels , this downtown all - suites property is convenient to Boeing , the Chicago Board of Trade , City Hall , IBM , Prudential Plaza and Willis Tower . Start the day with a free made - to - order breakfast . Relax in a two - room suite , complete with a separate lounge , refrigerator , microwave and WiFi access . Unwind with drinks * * and snacks at our complimentary Evening Reception . Sample Italian specialties at Osteria Via Stato and Pizzeria Via Stato . Maintain any exercise routine in the complimentary fitness center , and melt away stress in the indoor pool . Plan your meeting , wedding or special event for 300 guests at our Chicago hotel , downtown on State Street . In addition to our business center , we provide video conferencing , webcasting , and teleconferencing services . * * Service of alcohol subject to state and local laws . Must be of legal drinking age . Highlights Chicago downtown hotel located just one block from Free Navy Pier trolley ( seasonal ) and subway 3 blocks from Magnificent Mile ; walking distance to the Loop and popular attractions Free made - to - order breakfast and complimentary Evening Reception * * Suites include mini - refrigerator , microwave , coffeemaker and WiFi 11,000 sq . ft . of flexible Chicago event space , perfect for meetings , events and weddings What to do around here Our Embassy Suites Chicago Downtown hotel is located in the heart of Chicago , putting you close to many of the city ’ s main attractions . Downtown Chicago is great for walking , and there are options for shopping and dining in every direction . Cruise Michigan Avenue ’ s Magnificent Mile to find mid - range and high - end shops . One block west is Rush Street , known for its nightlife . Take the kids to Lincoln Park Zoo for a day of family fun . For a more cultural experience , visit the Chicago Museum Things to do Local Attractions Shop at mid - range and high - end stores , and find numerous dining and entertainment venues along Michigan Avenue ' s Magnificent Mile View some of the most notable contemporary art in the United States at the Chicago Museum of Contemporary Art Experience animals from reptiles to mammals at Lincoln Park Zoo . Do n ’ t forget to meet the new arrivals Listen to some of the world ’ s most renowned musicians at House of Blues For entertainment that attracts both locals and visitors , check out the nightlife on Rush Street , one block west of the Magnificent Mile Meetings & Events Need guest rooms or meeting space for your group , meeting or special event ? Book Now Parking Deal Savings Package Save with our Park and Stay promotion , a discount on paying for parking separately . View Offer Details American Girl Special Offers Celebrate being a girl with this downtown special , just 7 blocks from the American Girl Place ® . View More Details
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"Embassy Suites by Hilton",
"Chicago",
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http://embassysuites3.hilton.com/en/hotels/washington/embassy-suites-by-hilton-seattle-north-lynnwood-SEALWES/offers/index.htm
|
Skip brand navigation All Embassy Suites by Hilton Seattle North Lynnwood 20610 44th Ave West Lynnwood Washington 98036 USA TEL : + 1 - 425 - 775 - 2500 FAX : + 1 - 425 - 774 - 0485 skip form Arrival Open calendar Monday Departure Open calendar Monday Rooms Adults ( 18 + ) Children Use flexible dates Add special rate codes Check Rooms & Rates * Price Match Guarantee Skip secondary navigation Hotel Home Amenities & Services Maps & Directions Rooms & Suites Plan An Event Special Offers Dining Things To Do Not what you ' re looking for ? Find Nearby Hotels Find a Special Offer Arrival Wednesday Departure Wednesday Find Offers Share Print Special Offers Sort by : Compare this offer You can compare up to 4 offers Family Fun Package Wake up to breakfast for four and internet access when you book your next stay at participating hotels . More Details Book now Compare this offer You can compare up to 4 offers Honors Discount Advance Purchase Save big on your two - room suite when you book early . More Details Book now Book a Double Points Stay Without Thinking Twice Your next trip could be twice as rewarding with the 2X Points Package when you book your stay at any participating Embassy Suites Hotels . Sip Savor Stay Come check out our recent renovation ! Book By 31 Mar 2019 Stay Between 31 Oct 2018 and 31 Mar 2019 MAKE YOUR NEXT MEETING SIMPLY SUCCESSFUL With Meetings Simplified ™ , you get a comfortable meeting room , full - service catering and an LCD projector . Book By 15 Apr 2019 Request Pricing FROM 2 NIGHTS TO 2 WEEKS , WE ’ VE GOT YOU COVERED . Essential Extras Package Book the Essential Extras package for Premium Wi - Fi , late check - out and more . Make the most of your weekends . Now ’ s your chance to sleep in , eat well and leave late . A weekend away with us , and you ’ ll never see Saturday the same way . Military Family Rate Enjoy exclusive savings for active & retired military , veterans and their families on leisure stays . Relax , unwind and put your feet up — you ’ ve earned it . MAKE WEEKEND MEMORIES Compare
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"Embassy Suites",
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http://embeddedprogrammer.blogspot.com/2012/07/hacking-ov7670-camera-module-sccb-cheat.html
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Embedded Programmer Monday July 23 2012 Hacking the OV7670 camera module SCCB cheat sheet inside An indepth look of the OV7670 camera module The OV7670 is a low cost image sensor DSP that can operate at a maximum of 30 fps and 640 x 480 VGA resolutions equivalent to 03 Megapixels The captured image can be preprocessed by the DSP before sending it out This preprocessing can be configured via the Serial Camera Control Bus SCCB You can see the full datasheet here There are many camera modules that come with standard 01 spaced headers in eBay with prices under 10 Ill be using the one shown below it comes WITHOUT a FIFO buffer HARDWARE The camera module comes with a 9x2 header the pin diagram is shown below VDD GND SDIOC SDIOD VSYNC HREF PCLK XCLK D7 D6 D5 D4 D3 D2 D1 D0 RESET PWDN Now Ill cover the meaning of these pins Pin Type Description VDD Supply Power supply GND Supply Ground level SDIOC Input SCCB clock SDIOD InputOutput SCCB data VSYNC Output Vertical synchronization HREF Output Horizontal synchronization PCLK Output Pixel clock XCLK Input System clock D0D7 Output Video parallel output RESET Input Reset Active low PWDN Input Power down Active high A note about supply voltage and IO voltage As stated in the datasheet VDDA can range from 245V to 300V VDDC can range from 162V to 198V VDDIO can range from 17V to 300V You can hopefully see here sorry its buried among other files the schematic of the model Im using in this post As you can see U1 and U2 are LDO regulators one is a 28V regulator for VDDA and VDDIO and the other is a 18V regulator for VDDC The actual regulator that gets soldered on the module seems to vary between modules In conclusion for the same model Im using You can safely supply 33V 30V 36V to the OV7670 VDD I used this configuration You can safely use a maximum of 30V for the IO pins However the module IO pins will work at 28V A 5V supply for the OV7670 VDD might work try at your own risk it depends on the maximum input voltage of the LDO regulators your module has You can use 33V on the IO pins the internal IO protection diodes will clamp the IO voltage to 28V However this may degrade the OV7670 faster andor cause more power loss I used this configuration STRUCTURE OF AN IMAGE Before going into the signaling its necessary to understand how video and images are representend in digital format A video is a succession of frames a frame is a still image taken at an instant of time A frame is compromised of lines and a line is compromised of pixels A pixel is the smallest part of a digital image and it looks like a colored dot P0 P1 P2 P3 P4 L0 L1 L2 L3 L4 A 5x5 image For example the image above has 5 lines and each line has 5 pixels This means the image has a resolution of 5x5 pixels This image is monochrome there are also color image This color can be encoded in various formats in the next section well cover the most relevant formats for the OV7670 PIXEL FORMATS Monochrome In monochromes images each pixel is stored as 8 bits representing gray scale levels from 0 to 255 Where 0 is black 255 is white and the intermediate values are grays RGB Is a fact that any color can be decomposed in red green and blue light at different intensities This approach is known as the RGB color model Using this model each pixel must be stored as three intensities of these red green and blue lights RGB color model Image from wikipedia The most common format is RGB888 in this format each pixel is stored in 24 bits the red green and blue channels are stored in 8 bits each This means that the intensity of each light can go from 0 to 255 where 0 is the absence of light and 255 is the maximum intensity The formats used by the OV7670 are the RGB565 RGB555 and RGB444 The difference with the RGB888 format is the number of bits assigned to each channel For example in the RGB565 format the red channel is stored as 5 bits the green channel as 6 bits and the blue channel as 5 bits These formats take less memory when stored but in exchange sacrifice the number of colors available YCbCr YCbCr is a format in which a RGB color can be encoded The Y or luminance component is the amount of white light of a color and the Cb and Cr are the chroma components which respectly encode the blue and red levels relative to the luminance component Decomposition of an image into its Y Cb and Cr components Image from wikipedia As you can see the Y channel encodes the gray scale levels of the image Therefore the easiest way to get a monochrome image from the OV7670 is to extract the Y channel of the YCbCr format As the RGB format the YCbCr also stores each channel as 8 bits from 0 to 255 and we can convert from YCbCr to RGB using the following expression The OV7670 uses the YCbCr422 format this format is stored as follows Byte 0 Byte 1 Byte 2 Byte 3 Word 0 Cb0 Y0 Cr0 Y1 Word 1 Cb2 Y2 Cr2 Y3 Word 2 Cb4 Y4 Cr4 Y5 Data stored as words 4 bytes Or equivalently the data arrives in the following order N Byte 1st Cb0 2nd Y0 3rd Cr0 4th Y1 5th Cb2 6th Y2 7th Cr2 8th Y3 And the actual pixels are the following Pixel 0 Y0 Cb0 Cr0 Pixel 1 Y1 Cb0 Cr0 Pixel 2 Y2 Cb2 Cr2 Pixel 3 Y3 Cb2 Cr2 Pixel 4 Y4 Cb4 Cr4 Pixel 5 Y5 Cb4 Cr4 Notice each pixel is 3 byte long eg Y0 Cb0 and Cr0 as in the RGB format But in the YCbCr422 format the Cb and Cr channels are shared between two consecutive pixels eg pixels 0 and 1 share Cb0 and Cr0 Therefore two pixels are compressed into 4 bytes or 32 bits this means that in average each pixel is stored as 2 bytes or 16 bits From the example above 3 words 12 bytes store 6 pixels The extra advantage of YCbCr is that the Y channel is the grayscale image whereas in RGB youll need to average the 3 channels to get the grayscale image SIGNALING The OV7670 sends the data in a parallel synchronous format First of all to get any data out of the OV7670 is necessary to supply a clock signal on the XCLK pin According to the datasheet this clock must have a frequency between 10 and 48 MHz However I have successfully used a 8 MHz clock with some configuration via the SCCB If you are using a microcontroller that has clock output you can use that to clock the OV7670 these can generally output their inner system clock prescaled by some factor If your microcontroller doesnt have clock output capability but youre using an external crystal then you can connect the OSC_OUT pin to the OV7670 After a clock signal has been applied to the XCLK pin the OV7670 will start driving its VSYNC HREF and D0D7 pins Lets take a look at these signals Horizontal Synchronization First thing to notice the D0D7 must be sampled at the rising edge of the PCLK signal Number two D0D7 must be sampled only when HREF is high Also the rising edge of HREF signals the start of a line and the falling edge of HREF signals the end of the line All these bytes sampled when HREF was high correspond to the pixels in one line Note that one byte is not a pixel it depends on the format chosen By default the format is YCbCr422 this means that in average two bytes correspond to a pixel VGA timing The image above shows the signals for a VGA 640 x 480 frame During HSYNC high state we must capture 640 pixels equivalent to a line The 480 lines equivalent to a frame are captured during the low state of VSYNC This means that the falling edge of VSYNC signals the start of a frame and its rising edge signals the end of a frame That covers all the process of obtaining one frame the remaining question is how fast are frames sent By default the PCLK will have the same frequency of XCLK however prescalers and PPLs can be configured using the SCCB to produce a PCLK of different frequency A PCLK of 24 MHz will produce 30 fps a PCLK of 12 MHz will produce 15 fps and so on All this is independent of the format of the image VGA CIF QCIF etc SCCB Serial Camera Control Bus What makes the OV7670 so versatile is its inner DSP that can preprocess the image before its sent This DSP can be accessed via a SCCB interface This SCCB protocol is very similar to the I2C protocol You can see the SCCB specification here I couldnt get my STM32 microcontrollers I2C module to work with the OV7670s SCCB interface so I implemented a bit bang version of the SCCB specification This implementation is my peripheral library libstm32pp After making sure the SCCB is working we can tweak the OV7670 Changing the FPS To change the frames per second fps we need to change the frequency of PCLK And for that we need to modify the following registers via the SCCB Register Address Default Description CLKRC 0x11 0x80 Bit6 0 Apply prescaler on input clock 1 Use external clock directly Bit05 Clock prescaler Finternal clock Finput clock Bit05 1 Range 0 0000 to 1 1111 DBLV 0x6B 0x0A Bit76 PLL control 00 Bypass PLL 01 Input clock x4 10 Input clock x6 11 Input clock x8 Bit4 Regulator control 0 Enable internal regulator 1 Bypass internal regulator Now that you know the involved registers the process is straightforward For example say we have a 8 MHz input clock and we want a 24 MHz PCLK The only possible configuration is prescaler by 2 and PLL x6 CLKRC Bit6 must be 0 to enable prescaler CLKRC Bit05 must be 1 to enable prescaler by 2 DBLV Bit76 must be 10 to enable PLL x6 Pseudocode 1 2 3 4 5 6 7 8 9 10 11 unsigned char tmp Configuration for 30 FPS CLKRC register Prescaler 2 tmp readOV76700x11 writeOV76700x11 tmp 0b10000000 0b00000001 DBLV register PLL 6 tmp readOV76700x6B writeOV76700x6B tmp 0b00111111 0b10000000 Changing the frame formatresolution The OV7670 can use various frame formats VGA 640 x 480 QVGA 320 x 240 CIF 352 x 240 QCIF 176 x 144 Manual scaling By default the OV7670 uses the VGA format if you want to do image processing on a microcontroller with the OV7670 output this may be way too much data and you might want the QCIF format instead To change the format we need to modify the following registers Register Address Default Description COM3 0x0C 0x00 Bit6 0 Nothing 1 Swap the data MSB and LSB Bit5 On powedown 0 Tristate the output clock 1 Do not tristate the output clock Bit4 On powerdown 0 Tristate the output data 1 Do not tristate the output data Bit3 0 Disable scaling 1 Enable scaling Bit2 0 Disable downsampling cropping windowing 1 Enable downsampling cropping windowing COM7 0x12 0x00 Bit7 0 Nothing 1 Reset all the registers to default values Bit5 0 Nothing 1 Use CIF format Bit4 0 Nothing 1 Use QVGA format Bit3 0 Nothing 1 Use QCIF format Bit1 0 Disable color bar 1 Enable color bar Bit2 0 00 YUV 01 RGB 10 Bayer raw 11 Processed bayer raw Example say we want to use the QCIF format well need to enable the scaling and select the QCIF format COM3 Bit3 must be 1 to enable scaling COM7 Bit3 must be 1 to use the QCIF format Pseudocode 1 2 3 4 5 6 7 8 9 10 11 unsigned char tmp Configuration for QCIF format COM3 register Enable format scaling tmp readOV76700x0C writeOV76700x0C tmp 0b00001000 COM7 register Select QCIF format tmp readOV76700x12 writeOV76700x12 tmp 0b11000111 0b00001000 Ill add more possible configurations as I explore other features MY RESULTS I have tested my OV7670 module with a STM32F4 microcontroller This microcontroller comes with a Digital CaMera Interface DCMI and a Direct Memory Access DMA controller these two can capture the frames without the intervention of the processor I used an XCLK of 8 MHz but configured the OV7670 to output a PCLK of 24 MHz this means I was capturing 30 fps I used the QCIF format however I was receiving 174 x 144 pixels instead of 176 x 144 Color format was the default YCbCr422 One of every six frames was sent to a PC using a UART communication at 3 Mbps On the PC side I received the frames using a modded version of qSerialTerm only the Y channel gray scale version of the incoming frames was used The result is shown in the following image A ninja star servo horn captured by the OV7670 camera module Now you can use qSerialTerm to visualize images streamed through the Serial Port Check this post for more info TROUBLESHOOTING SCCB Make sure the SCCB is working properly the OV7670 will answer with an ACK after it has been address properly The 7 bit SCCBI2C address is 0x21 this translates to 0x42 for write address and 0x43 for read address For debugging purposes try reading some registers and check that they contain their default values eg reading the 0x01 register should return 0x80 Always read a register first modify the desired bits and then write it back to the OV7670 Image sensor Check wiring pin configuration and clock configuration Start only grabbing a snapshot only one frame this is from VSYNC falling edge to VSYNC rising edge Repeat this procedure multiple times and make sure the number of bytes per snapshot is constant Cover the camera lens and verify that the snapshot have the following information in bytes 128 0 128 0 128 0 128 0 ie every even byte should be 128 and every odd byte should be 0 This correspond to a pitch black image If the two previous experiments fail your uC might be too slow to grab the OV7670 stream either increase its clock speed or get a faster uC If you are using a DMA controller then give it high priority clock it as fast as possible andor dedicate it to this task If you are visualizing the grabbed snapshot in a PC for starters only use the luminance Y channel ie only use the even bytes of the snapshot On the PC assign R G B Y for each pixel At this point all the electricalsoftware part should be working The only remaining issue is the camera focus distance from the camera lens to the image sensor you will have to vary the camera focus by trial and error until you get a clear image Varying the camera focus UPDATE Check this post about 3 demos that involve the STM32F4 the OV7670 and qSerialTerm Full code available qSerialTerm displaying a frame sent by the STM32F4 and was captured by the OV7670 Posted by Jorge Aparicio at 438 PM Email This BlogThis Share to Twitter Labels Crossplatform Electronics Open Source Ubuntu Windows Subscribe to Post Comments Atom
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[
"Hacking",
"camera"
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http://embellishsalon.com/
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Stylists Services Gallery Welcome to Embellish Salon Located in Bayport Minnesota Embellish Salon serves clients from all across the Twin Cities metro area Embellish has an experienced group of stylists that keep up to date with the latest styles and trends Services See the services Embellish Salon offers Stylists Meet the experienced staff of Embellish Salon Photo Gallery Check out the work of the talented Embellish Staff
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"Salon",
"Embellish",
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http://embryo.asu.edu/pages/mesenchyme
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Mesenchyme By Kate MacCord Published : 2012 - 09 - 14 Keywords : Tissue Developmental mechanics Mesenchyme is a type of animal tissue comprised of loose cells embedded in a mesh of proteins and fluid , called the extracellular matrix . The loose , fluid nature of mesenchyme allows its cells to migrate easily and play a crucial role in the origin and development of morphological structures during the embryonic and fetal stages of animal life . Mesenchyme directly gives rise to most of the body ’ s connective tissues , from bones and cartilage to the lymphatic and circulatory systems . Furthermore , the interactions between mesenchyme and another tissue type , epithelium , help to form nearly every organ in the body . Although most derives from the middle embryological germ layer , the mesoderm , the outer germ layer known as the ectoderm also produces a small amount of from a specialized structure called the neural crest . Mesenchyme is generally a transitive tissue ; while crucial to morphogenesis during development , little can be found in adult organisms . The exception is mesenchymal stem cells , which are found in small quantities in bone marrow , fat , muscles , and the dental pulp of baby teeth . Mesenchyme forms early in embryonic life . As the primary germ layers develop during gastrulation , cell populations lose their adhesive properties and detach from sheets of connected cells , called epithelia . This process , known as an epithelial - mesenchymal transition , gives rise to the mesodermal layer of the embryo , and occurs many times throughout development of higher vertebrates . Epithelial - mesenchymal transitions play key roles in cellular proliferation and tissue repair , and are indicated in many pathological processes , including the development of excess fibrous connective tissue ( fibrosis ) and the spread of disease between organs ( metastasis ) . The reverse process , the mesenchymal - develop adhesive properties and arrange themselves into an organized sheet . This type of transition is also common during development , and is involved in kidney formation . The concept of has a long history , which has shaped our modern understanding of the tissue in many ways . In 1879 , Charles Sedgwick Minot , an anatomist based out of Harvard Medical School in Boston , Massachusetts , first described what he termed mesamoeboids , the cellular portion of what would soon come to be recognized as . Minot found these cells in the context of histological studies of mesoderm . He understood the loose , mobile cells of as primitive representatives of the , but did not consider these cells as a type of tissue . Two years after Minot ’ s recognition of mesamoeboids , Oscar and Richard Hertwig , two brothers and doctoral students of Ernst Haeckel at the University of Jena in Jena , Germany , coined the term mesenchyma in their publication Die Coelomtheorie . Versucheiner Erklärung des mittleren Keimblattes Coelom Theory : An attempt to explain the middle germ layer ) , and they used it to describe the type of tissue that was comprised of the amoeboid cells that Minot had portrayed . The Hertwig brothers established that originates from , and they situated this relationship in the broader context of the development of the coelom , a fluid - filled body cavity . Their Die Coelomtheorie also advanced the idea that the three germ layers maintain separate identities and develop distinct tissues and organs , a concept known as germ - layer theory . In 1888 , N . Katschenko suggested that found in the region of the head originated from the neural crest , an ectodermal derivative , effectively expanding the tissue ’ s origins beyond that of a single germ layer . Five years later , Harvard Medical School doctoral student Julia Platt , in Cambridge , Massachusetts , provided evidence based on her studies of Necturus maculosus embryos , a type of aquatic salamander , that the that developed into the skeletal elements of the branchial arches derived from ectoderm . Platt ’ s 1893 publication , “ Ectodermic Origin of the Cartilages of the Head , ” and her conclusions about the ectodermal origins of in the head region , and thus skeletal and cartilaginous tissues of the skull , went against the entrenched germ - layer theory and the mesodermal origins of advocated by the Hertwig brothers in their 1881 Die Coelomtheorie . Platt ’ s findings were rejected by many established embryologists who upheld the theory of integrity of the In the years following Platt ’ s publication , several other embryologists identified ectodermal origins for and its derivative skeletal elements in the head region of fish and birds . It was not until nearly thirty years after Platt ’ s initial publication that independent studies demonstrated a major ectodermal contribution to . In 1921 , while investigating the limits of in the formation of cerebral ganglia in Urodeles , commonly known as salamanders , Francis Landacre at the Ohio State University in Columbus , Ohio , showed the ectodermal origin of cranial . Landacre ’ s work was followed by other studies which further concluded an ectodermal component of . The idea that in the cranial region derived from was finally abrogated in the 1940s by the independent research of embryologists Sven Hörstadius at Uppsala University in Uppsala , Sweden , and Gavin de Beer at the University College in London , England . Soon after the debate over ectodermal ended , research on the role of during development erupted . By the 1960s , embryologists realized that , in combination with epithelium , played an essential role in the morphogenesis of many organs during embryonic and fetal development . Epithelio - mesenchymal interactions form nearly every organ of the body , from hair and sweat glands to the digestive tract , kidneys , and teeth . In 1969 , Edward Kollar and Grace Baird from the University of Chicago in Chicago , Illinois , designed a series of experiments to understand how and work together when cells differentiate , and how the two tissues combine to make embryonic structures . Their research drew on a long history of investigating tissue interactions during morphogenesis , and especially on the 1954 work of John Cairn at the University of Texas in Austin , Texas , and John Saunders , at Marquette University in Milwaukee , Wisconsin . Cairn and Saunders recognized that holds the inductive stimulus within interactions between . Using tooth development as a model system , Kollar and Baird provided evidence that drives both induction differentiation during epithelio - mesenchymal interactions , and is thus the tissue that confers structural specificity during these interactions , or determines what structure will form . Kollar and Baird published their findings in 1969 in “ The Influence of the Dental Papilla on the Development of Tooth Shape in Embryonic Mouse Tooth Germs , ” and in 1970 in “ Tissue Interactions in Embryonic Mouse Tooth Germs . ” Shortly before Kollar and Baird published their account of epithelio - mesenchymal interactions , Alexander Friedenstein discovered mesenchymal stem cells in mice Mus musculus ) . In publications from 1966 through 1987 , Friedenstein , in conjunction with his peers at the University of Moscow in Moscow , Russia , provided evidence from transplantation experiments that taken from bone marrow can differentiate into mesenchymal tissues , such as fat , bone , and cartilage . These cells came to be known as mesenchymal , and have subsequently been found in blood , cartilaginous , skeletal , and fatty tissues . Mesenchymal provide a reservoir of reserve cells that the body can use for normal or pathological tissue regeneration and repair . The abilities of mesenchymal to differentiate into different tissues , known as cell potency , has been a cause of debate in recent years , leading researchers to question whether these cells are truly multipotent , and can give rise to multiple cells types . The potential multipotency of mesenchymal , in conjunction with their presence in adult organisms , has made them an attractive alternative to embryonic stem cells for research on tissue regeneration . Current research on spreads across many biological fields . The focus of research , however , divides between two general interests : the role and expression of - specific genes during development , including pathological processes , and the locations and capabilities of mesenchymal . While some still investigate at the tissue level , the two current focuses reflect a trend towards the analysis and understanding of molecular - level mechanisms by which functions during development . Beginning with the definition by the Hertwig brothers , research has moved from anatomical investigations in developing embryos , to cellular contributions for organ formation and tissue level interactions , and now to the genetic mechanisms of development and tissue repair . There is historical continuity within research , but there remain vestiges of the controversy that surrounded this tissue in the late nineteenth century . In her 1893 article in which she introduced the biological community to the ectodermal origins of in the head region , Julia Platt also suggested a change in terminology . Mesenchyme of ectodermal origins she specified by the term mesectoderm , while mesodermal she called mesendoderm . The medical community , especially pathologists , still employs this distinction between mesenchymal sources , only referring to a tissue as if it is derived from . Pathologists maintain the distinction because the mesenchymal source determines the type and behavior of a disease . Meanwhile , developmental biologists tend to recognize by a single name , regardless of source . The study of has a long history , from ' s recognition within the framework of germ - layer theory , to controversy about ' s origins , to uncovering ' s roles in morphogenesis and its capacity to produce . This history is in part due to the fact that is crucial for embryonic growth and development , as well as maintenance of connective tissues in adulthood . The loose nature of cells within allows the tissue to move and to be molded . During embryogenesis gives rise to the body ’ s connective tissues , from cartilage and bone to fat , muscle , and the circulatory system . Meanwhile , nearly every organ forms through epithelio - mesenchymal interactions , in which provides both the inductive stimulus and determines the path of differentiation . Although little remains in the body during adulthood , the final remnants of this tissue , mesenchymal , allow connective tissues to repair and regenerate . Sources Cairns , John M , and John W . Saunders . “ The Influence of Embryonic Mesoderm on the Regional Specification of Epidermal Derivatives in the Chick . ” Journal of Experimental Zoology 127 ( 1954 ) : 221 – 48 . Friedenstein , Alexander , I . Piatetzky - Shapiro , and Klara Petrakova . “ Osteogenesis in Transplants of Bone Marrow Cells . ” Journal of Embryology and Experimental Morphology 16 ( 1966 ) : 381 – 90 . Gilbert , Scott . Developmental Biology 8th edition . Massachusetts : Sinauer , 2003 . Hall , Brian K . “ The Neural Crest and Neural Crest Cells : Discovery and Significance for Theories of Embryonic Organization . ” Journal of Biosciences 3 ( 2008 ) : 781 – 93 . Hertwig , Oscar , and Richard Hertwig . Die Coelomtheorie . Versucheiner Erklärung des mittleren Keimblattes [ Coelom Theory : An Attempt to Explain the Middle Germ Layer ] . Jena : Fischer , 1881 . http : / / books . google . com / books ? id = KOhOAAAAMAAJ&ots = x5r19l0yfu&dq = oscar % 20hertwig&pg = PP1 # v = onepage&q = oscar % 20hertwig&f = false ( Accessed September 14 , 2012 ) . Katschenko , N . “ Zur Entwicklungsgeschichte der Selachierembryos [ On the Develomental Hisotry of Selacian Embryos ] . ” Anatomischer Anzeiger [ Anatomical Gazette ] 3 ( 1888 ) : 445 – 67 . Kollar , Edward J . , and Grace R . Baird . “ The Influence of the Dental Papilla on the Development of Tooth Shape in Embryonic Mouse Tooth Germs . ” Journal of Embryology and Experimental Morphology 21 ( 1969 ) : 131 – 48 . Kollar , Edward J . , and Grace R . Baird . “ Tissue Interactions in Embryonic Mouse Tooth Germs : I . Reorganization of the Dental Epithelium during Tooth - Germ Reconstruction . ” Journal of Embryology and Experimental Morphology 24 ( 1970 ) : 159 – 70 . Kollar , Edward J . , and Grace R . Baird . “ Tissue Interactions in Embryonic Mouse Tooth Germs : II . The Inductive Role of the Dental Papilla . ” Journal of Embryology and Experimental Morphology 24 ( 1970 ) : 173 – 86 . Le Lièvre , Christiane , and Nicole Le Douarin . “ Mesenchymal Derivatives of the Neural Crest : Analysis of Chimaeric Quail and Chick Embryos . ” 34 ( 1975 ) : 125 – 54 . Minot , Charles Sedgwick . “ Preliminary Notice of Certain Laws of Histological Differentiation . ” Proceedings of the Boston Society of Natural History XX ( 1879 ) : 202 – 9 . Platt , Julia . “ Ectodermic Origin of the Cartilages of the Head . ” Anatomischer Anzeiger [ Anatomical Gazette ] 8 ( 1893 ) : 506 – 9 . How to cite MacCord , Kate , " Mesenchyme " . Embryo Project Encyclopedia ( 2012 - 09 - 14 ) . ISSN : 1940 - 5030 http : / / embryo . asu . edu / handle / 10776 / 3941 . Show full item record Publisher Arizona State University . School of Life Sciences . Center for Biology and Society . Embryo Project Encyclopedia . Rights © Arizona Board of Regents Licensed as Creative Commons Attribution - NonCommercial - Share Alike 3.0 Unported ( http : / / creativecommons . org / licenses / by - nc - sa / 3.0 / ) Last modified Wednesday , July 4 , 2018 - 04 : 40 Topic Processes Subject Mesoderm ; Mesenchyme ; Gastrulation ; Minot , Charles Sedgwick , 1852 - 1914 ; Haeckel , Ernst , 1834 - 1919 ; Stem cells ; Mesenchymal stem cells ; Embryological development ; Embryos ; Cell differentiation ; Concept Printer - friendly version Send by email PDF version
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[
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http://emedicine.medscape.com/article/1016198-clinical
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pediatrics : Surgery Voiding Dysfunction Clinical Presentation Updated : Oct 30 , 2017 Author : Christopher S Cooper , MD , FACS , FAAP ; Chief Editor : Marc Cendron , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication References History Pediatric lower urinary tract dysfunction encompasses a wide spectrum of syndromes . Voiding symptoms ( ie , urgency , frequency , incontinence ) may be transient , intermittent , or persistent . Transient voiding symptoms are commonly encountered due to urinary tract infection ( UTI ) or as a result of nonspecific urethritis or periurethral irritation due to vaginitis . Symptoms may also occur without a recognized explanation . A detailed voiding diary provides documentation of voiding habits , frequency of micturition , voided volumes , number and timing of incontinence episodes , and fluid intake . 12 Overactive bladder The hallmark symptom of overactive bladder ( OAB ) in children is urgency , and children with this symptom can be clinically diagnosed based on the definition by the International Children ’ s Continence Society . 13 A careful history usually reveals that the child has had ongoing urinary urgency . The children are commonly evaluated because of daytime urinary incontinence or UTI . Children with OAB may have a history of holding maneuvers , such as standing on tiptoes , crossing of the legs , or squatting with the heel pressed into the perineum . The clinician may find that OAB has been present in a patient since the child began developing daytime urinary control or that it arose in a child who previously had a normal voiding pattern . The appearance of OAB in a child who previously had daytime urinary control may occur after a UTI or may appear with no apparent triggering event . Dysfunctional voiding Dysfunction of the pelvic floor musculature ( dysfunctional voiding ) involves failure to relax the urethra and pelvic floor muscles with voiding . It is caused by involuntary contraction of the urethral sphincter or pelvic floor muscles during the voiding phase of the micturition cycle . This pattern of voiding incoordination in a child with a neurogenic bladder is called detrusor sphincter dyssynergia . Dysfunctional voiding symptoms vary from mild daytime frequency and postvoid dribbling to daytime and nighttime wetting , urgency , urge incontinence , pelvic holding maneuvers , and UTIs . In the most severe form , children with dysfunctional voiding resemble those with neurogenic bladder or anatomic bladder outlet obstruction . Children with this condition can have increased intravesical pressure upon voiding , incomplete bladder emptying , UTIs , persistent vesicoureteral reflux ( VUR ) , dilatation of the upper tract ( hydronephrosis ) , or , rarely , renal damage . Giggle incontinence Giggle incontinence is the occurrence of involuntary complete bladder evacuation induced by laughter . ( In some children , episodes of incontinence may occur with giggling , whereas in others , they are induced only by vigorous laughter . ) The etiology is unknown ; the condition is not a form of stress incontinence , nor is it due to weakness of the sphincter . Giggle incontinence typically appears in children aged 5 - 7 years . The problem can persist throughout the school years but usually improves or disappears with age . The child ’ s voiding pattern is The authors of one study found a high incidence of daytime voiding symptoms in patients in whom they diagnosed giggle incontinence . 11 The authors concluded that laughter induced unstable detrusor contractions in children susceptible to detrusor instability . Underactive bladder Underactive bladder syndrome describes children who void infrequently . The condition is diagnosed if a child voids three or fewer times in 24 hours or if he or she does not void for 12 hours . These children may also use abdominal straining to void . The pattern of infrequent voiding is clinically important . The detrusor muscle may be hypocontractile , and voiding may be accomplished by using increased intra - abdominal pressure ( abdominal straining ) as the driving force to expel urine . The diagnosis may be confirmed by means of a urodynamic study . The voiding pattern in underactive bladder may be a variant of normal . If the condition is identified , however , the voiding pattern should be treated with behavioral modification of the child ' s voiding regimen . Constipation When chronic constipation has been present in a child with a voiding disorder , it may be the primary cause of bladder dysfunction . There is a close association between fecal retention and OAB . In fact , the two conditions are so frequently associated that the term “ dysfunctional elimination syndrome ” has been introduced in the literature . The effects of constipation on bladder function may be related to the direct effect of retained fecal material distending the rectosigmoid colon , or it may be the result of shared neural input . Many children and families are reluctant to discuss stooling history . Often , neither the child nor the parent appears to have accurate information about stooling frequency or character . Indicators of constipation include the following : Infrequent passage of stools Small , hard stools or elongated , wide - bore stools Encopresis Palpable stool on abdominal examination Soiling in the underwear ( often misinterpreted as being due to improper or careless wiping ) Large quantities of stool in the colon , especially the rectosigmoid area on abdominal radiography Other factors that may result in daytime wetting Many children aged 3 - 5 years tend to delay urination because of intense concentration on playing or watching television . As a result , they occasionally have damp or soaked clothing . If the child ’ s voiding pattern is otherwise normal , this pattern of voiding dysfunction usually subsides when an increased effort is made toward scheduled voiding . One study of an initial trial of timed voiding reported that 45 % of patients had a significant improvement in the frequency of wetting . 14 Vaginal reflux of urine from voiding in a knees - closed position can cause dampness when the child assumes an upright posture after voiding or postvoid dribbling . Labial adhesions of the labia minora may cause daytime wetting as a result of the pooling of urine in the vagina . Treatment of the labial adhesions eliminates this cause of urinary incontinence . If incontinence is persistent and continually ongoing , an ectopic ureter should be suspected and should prompt evaluation by a urologist , who can often make the diagnosis on the basis of renal ultrasonography , voiding cystourethrography ( VCUG ) , and physical examination findings . The diagnosis of a neurogenic bladder is usually evident from the patient ' s history ; occasionally , occult neuropathic bladder dysfunction can be discovered based on evaluation for urinary symptoms . Daytime wetting in a previously continent child should prompt the clinician to consider the possibility of sexual abuse or other trauma . Physical Examination No notable findings are apparent upon physical examination of a child with voiding dysfunction ; however , a thorough examination should be performed to evaluate for other sources of voiding symptoms . Perform a careful physical examination to rule out an abnormality of the lumbosacral area that would suggest the presence of occult spinal dysraphism . Signs of this condition include a sacral dimple or tuft of hair , dermal vascular malformations , a small lipomeningocele , or absence of the gluteal cleft with flattened buttocks . The neurologic examination should include assessment of motor strength , deep tendon reflexes , perineal sensation , gait , and coordination . Carefully examine the patient ’ s genitalia to be certain that they are normal . Look for labial adhesions in girls and meatal stenosis in boys . In girls , the genitalia should be examined to evaluate for sexual abuse . One study reported that 6 % of a group of patients ( 89 % of whom was female ) evaluated for voiding dysfunction had a history of sexual abuse . 15 Rashes in the perineal or genital areas may indicate fungal infections that result from chronic wetness . Complications Children with daytime wetting have a higher rate of parent - reported psychological problems than do children who have no daytime wetting . This has been found to be the case in children as young as age 7 years . 16 Persistence of daytime wetting may markedly disrupt the social lives of older children . Daytime wetting can negatively affect self - esteem and is a major stressor in school - age children . In a study of 2000 children that looked at their perceptions of potential stressful events , wetting in school ranked behind only parental death and going blind . 17 Skin irritation and rashes may result from chronic wetness . Children should be monitored for skin breakdown . Topical antifungal therapy may also be initiated for those with tinea . Detrusor instability with pelvic holding maneuvers may foster recurrent UTIs or persistence of VUR . In a study by Avlan et al , the rates of VUR , UTI , and renal damage in patients with OAB plus dysfunctional voiding or with pure dysfunctional voiding were higher than in patients with OAB alone . 18 Other studies found VUR and recurrent UTIs in , respectively , 16 - 20 % and as many as 60 % of children with voiding dysfunction . 19 20 In rare cases , dilatation of the upper urinary tract ( hydronephrosis ) and kidney damage caused by recurrent infections may occur . The dilation of the upper tract is secondary to high storage pressures . This pressure can induce secondary reflux . The pressure and kidney infections cause kidney damage . A few children with functional voiding disorder have marked dysfunctional voiding ( ie , nonneurogenic bladder [ Hinman - Allen syndrome ] ) and may incur significant renal damage . Inappropriate contraction of the external urinary sphincter during voiding and subsequent elevation of the intravesical pressure is the typical pathology . Daytime or nighttime wetting , recurrent UTI , constipation , and increased postvoid residual urine volume in the absence of a neurologic lesion are the dominant clinical features . 21 Differential Diagnoses Sections Voiding Dysfunction Overview Presentation DDx Workup Treatment Medication References
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[
"Voiding Dysfunction",
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http://emedicine.medscape.com/article/1056742-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Dermatology Dermatofibroma Updated : Jun 04 , 2018 Author : Joseph C Pierson , MD ; Chief Editor : Dirk M Elston , MD more . . . Sections Overview Background Pathophysiology Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Questions & Answers Media Gallery References Background Dermatofibroma ( superficial benign fibrous histiocytoma ) is a common cutaneous nodule of unknown etiology that occurs more often in women . Dermatofibroma frequently develops on the extremities ( mostly the lower legs ) and is usually asymptomatic , although pruritus and tenderness can be present . It is actually the most common painful skin tumor . 1 A number of well - described , histologic subtypes of dermatofibroma have been reported . Removal of the tumor is usually not typically required unless diagnostic uncertainty exists or particularly troubling symptoms are present . This article discusses primarily cutaneous ( superficial ) dermatofibroma . Subcutaneous ( deep ) benign fibrous histiocytomas are also well documented and may have a more aggressive clinical course , as can tumors displaying cellular , aneurysmal ( hemosiderotic ) , and atypical histologic variants of dermatofibroma . In addition , benign fibrous histiocytomas are reported in bone , orbital , airway , gastrointestinal , splenic , genitourinary , and intracranial locations . Next : Pathophysiology What to Read Next on Medscape Sections Dermatofibroma Overview Pathophysiology Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Questions & Answers Media Gallery References Recommended Journal Article Teaching Benign Skin Lesions as a Strategy to Improve the Triage Amalgamated Dermoscopic Algorithm ( TADA ) Diseases & Conditions Targetoid Hemosiderotic Hemangioma
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[
"Dermatofibroma",
"skin tumor",
"Diseases"
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http://emedicine.medscape.com/article/1065086-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Dermatology Drug - Induced Lupus Erythematosus Updated : Jul 10 , 2018 Author : Catharine Lisa Kauffman , MD , FACP ; Chief Editor : Dirk M Elston , MD more . . . Sections Overview Background Pathophysiology Etiology Epidemiology Prognosis Show All Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery Tables References Background Drug - induced lupus erythematosus ( DILE ) is a variant of lupus erythematosus that resolves within days to months after withdrawal of the culprit drug in a patient with no underlying immune system dysfunction . DILE can arise months to years after exposure to drugs prescribed to treat various medical conditions ( eg , antihypertensives , antibiotics , anticonvulsants ) . The most common drugs that cause DILE are hydralazine , procainamide , quinidine , isoniazid , diltiazem , targeted immunotherapy , and minocycline ( see Etiology ) . 1 2 3 Drug - induced subacute cutaneous lupus erythematosus ( DISCLE ) is a DILE variant with predominant skin involvement , temporally related to drug exposure , and resolving after drug discontinuation . 4 It has been seen in association with hydrochlorothiazide , terbinafine , and leflunomide . 5 6 Care must be taken to correctly diagnose the symptoms of DILE and differentiate it from systemic lupus erythematosus ( SLE ) , and DILE should be recognized clinically and serologically for prompt intervention . Although both SLE and DILE are autoimmune disorders and can have similar clinical and laboratory features ( see the Table below ) , research suggests different mechanistic pathways ( see Pathophysiology ) . Guidelines for diagnosis and management of SLE have been established . 7 Although the pathogenesis of DILE is not completely understood , a genetic predisposition may play a role , as has been shown with certain drugs metabolized by acetylation , such as procainamide or hydralazine . 8 Table . Comparison of Findings Between Drug - Induced Lupus Erythematosus and Systemic Lupus Erythematosus ( Open Table in a new window ) Findings SLE DILE Clinical Average age of onset of 20 - 30 y Affects blacks more than whites Female - to - male ratio of 9 : 1 Average age of onset of 50 - 70 y Affects whites more than blacks Female - to - male ratio of 1 : 1 Laboratory Antihistone antibodies in 50 % Anti - dsDNA present in 80 % C3 / C4 levels decrease Cutaneous findings in > 75 % Raynaud phenomenon in 50 % Antinuclear antibodies in > 95 % Antihistone antibodies in > 95 % Anti - ssDNA present Anti - dsDNA rare C3 / C4 levels normal Cutaneous findings in ~ 25 % Raynaud phenomenon in 25 % Antinuclear antibodies in > 95 % Immunofluorescence Histopathology Direct immunofluorescence reveals granular deposition of IgG at dermoepidermal junction Lymphohistiocytic interface dermatitis Apoptosis basal vacuolization Same as SLE Same as SLE DILE = drug - induced lupus erythematosus , IgG = immunoglobulin G ; SLE = systemic lupus erythematosus . A large systematic review of 117 DISCLE cases demonstrated that white women made up the large majority of cases , and the mean age was 58 years . Antihypertensives and antifungals were most frequently the culprits . Time intervals between drug exposure and appearance of DISCLE varied and were drug - class dependent . Most cases resolved within weeks of drug withdrawal . No significant differences in the clinical , histopathological , or immunopathological features between DISCLE and idiopathic SCLE were detected . 9 Varying mechanisms leading to the formation of self - recognizing antibodies may explain the differential characteristics of drug effects in persons with DILE and those with SLE . For example , whereas some drugs can cause DILE , others may cause a flare of preexisting SLE . Drugs such as procainamide , chlorpromazine , and quinidine cause the production of antinuclear antibodies against the histone dimer H2A - H2B . Hydralazine forms antinuclear antibodies to H1 and the H3 - H4 complex . 10 Drugs that cause DILE usually take months to years before the associated symptoms occur , whereas flares of SLE due to drugs may occur within hours to days . Serositis may be prominent . 11 Most patients with DILE have 1 or more clinical symptoms of SLE , such as arthralgias , lymphadenopathy , rash , and fever , and have had no prior history of autoimmune disease . However , certain manifestations typical in persons with SLE are not usually observed in persons with DILE . No specific criteria establish the diagnosis of DILE , and excluding underlying autoimmune disease is not a simple process . DILE is typically diagnosed by a process of elimination to rule out SLE ( see Differentials ) . Symptoms of DILE usually clear within weeks of stopping the culprit drug . Generally , no other specific treatments are known . Low doses of systemic corticosteroids may be prescribed for short periods if the symptoms are severe ( see Treatment For patient education resources , see the Blood and Lymphatic System Center and the Arthritis Center , as well as Lupus ( Systemic Lupus Erythematosus ) and Drug Allergy Next : Pathophysiology Sections Drug - Induced Lupus Erythematosus Overview Epidemiology Prognosis Show All Presentation DDx Workup Medication Questions & Answers Media Gallery Tables References
|
[
"Drug-Induced Lupus Erythematosus",
"procainamide",
"genetic predisposition"
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http://emedicine.medscape.com/article/1070326-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Dermatology Eosinophilic Pustular Folliculitis Updated : Apr 03 , 2018 Author : Robert A Schwartz , MD , MPH ; Chief Editor : Dirk M Elston , MD more . . . Sections Overview Background Pathophysiology Etiology Epidemiology Prognosis Show All Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Background In 1965 , Ise and Ofuji described a 42 - year - old Japanese housewife with a possible follicular variant of subcorneal pustular dermatosis . 1 The patient had crops of follicular pustules on her back , face , chest , and upper arms representing histologic subcorneal pustulosis of the upper hair follicles as depicted below . The patient also had a leukocytosis of 14,100 white cells / µL , 8 % of which were eosinophils . In 1970 , Ofuji et al described 3 additional patients and proposed that this new entity be called eosinophilic pustular folliculitis ( EPF ) . 2 The use of the term folliculitis has been challenged for this disorder because hair follicles are not seen on the palms or the soles , which may be affected . Widespread hyperpigmented patches on the back and the arms in a patient with eosinophilic pustular folliculitis . Courtesy of Professor T . Nishikawa , Department of Dermatology , Keio University School of Medicine , Tokyo , Japan . View Media Gallery Three variants of this disorder have been described : classic eosinophilic pustular folliculitis ( as originally described by Ofuji ) , HIV - associated eosinophilic pustular folliculitis , and infantile eosinophilic pustular folliculitis . Some investigators prefer to consider these three distinct disorders . Of the three , the infantile variety is by far the least characterized . Because the exact nature of these conditions is unknown , whether these conditions are three interrelated forms of a single disease or three distinct dermatoses is unclear . These conditions share a common pathologic feature , namely a noninfectious eosinophilic infiltration of 3 Next : Pathophysiology What to Read Next on Medscape Related Conditions and Diseases HIV Infection and AIDS Pediatric HIV Infection Early Symptomatic HIV Infection Treatment Recommendations for HIV - Infected Patients With Co - infections Antiretroviral Therapy ( ART ) in Pregnant Women With HIV Infection Ocular Manifestations of HIV Infection News & Perspective FDA Clears New Drug - Sparing Option for HIV Infection Bacterial STIs Increase Among PrEP Users HIV - 1 Envelope Protein Opening Exposes Antibody Targets Tools Drug Interaction Checker Pill Identifier Calculators Formulary Slideshow Herpesviruses : Test Your Knowledge Most Popular Articles According to Dermatologists FDA Proposes Major Changes to Sunscreen Rules Management and Treatment of Psoriasis with Biologics Clinical Practice Guidelines ( 2019 ) New Guidelines Address Management and Treatment of Psoriasis Recent Developments in Lymph Node Surgery for Melanoma Atopic Dermatitis : The Skin Barrier and Beyond View More Sections Eosinophilic Pustular Folliculitis Overview Pathophysiology Etiology Epidemiology Prognosis Show All Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Recommended Diseases & Conditions HIV Infection and AIDS Diseases & Conditions Pediatric HIV Infection
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[
"Eosinophilic Pustular Folliculitis",
"Drugs & Diseases",
"Pathophysiology"
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http://emedicine.medscape.com/article/1076389-treatment
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Dentistry Tooth Discoloration Treatment & Management Updated : Sep 07 , 2015 Author : Dharti N Patel , DMD , FDS , RCSEd , FICOI ; Chief Editor : Dirk M Elston , MD more . . . Sections Overview Presentation Workup Treatment Medical Care Surgical Care Consultations Diet Activity Show All Follow - up Media Gallery Tables References Medical Care Dental treatment of tooth discoloration involves identifying the etiology and implementing therapy . Medical treatment also may be warranted , depending on the etiology of the tooth discoloration . Diet and habits : Extrinsic staining caused by foods , beverages , or habits ( eg , smoking , chewing tobacco ; see Causes and Pathophysiology ) is treated with a thorough dental prophylaxis and cessation of dietary or other contributory habits to prevent further staining . 25 Toothbrushing : Effective toothbrushing twice a day with a dentifrice helps to prevent extrinsic staining . Most dentifrices contain an abrasive , a detergent , and an antitartar agent . In addition , some dentifrices now contain tooth - whitening agents . Professional tooth cleaning : Some extrinsic stains may be removed with ultrasonic cleaning , rotary polishing with an abrasive prophylactic paste , or air - jet polishing with an abrasive powder . 26 However , these modalities can lead to enamel removal ; therefore , their repeated use is undesirable . 27 Enamel microabrasion : This technique involves the rotary application of a mixture of weak hydrochloric acid and silicon carbide particles in a water - soluble paste . 28 The resultant surface is smooth and has a glazed appearance . Enamel microabrasion is indicated for the removal of superficial intrinsic tooth discoloration , including that caused by fluorosis and decalcifications secondary to orthodontic brackets or bands . Enamel microabrasion may be used in conjunction with bleaching . Bleaching ( tooth whitening ) : Early bleaching techniques were developed almost a century ago , and all of the techniques involved a process of oxidation . Today , with proper patient selection , bleaching is a safe , easy , and inexpensive modality that is used to treat many types of tooth discoloration . Usually , bleaching is not indicated for the treatment of discoloration of the primary teeth . Bleaching includes 2 types of techniques : vital and nonvital . Vital bleaching Bleaching of vital teeth is indicated primarily for patients with generalized yellow , orange , or light brown extrinsic discoloration ( including chlorhexidine staining ) , although it may be helpful in ameliorating mild cases of tetracycline - induced intrinsic discoloration and fluorosis . Currently , the bleaching agents most commonly used are carbamide and hydrogen peroxide . 29 When applied in higher concentrations , the agents produce more significant bleaching than they do without these measures . In office " power " bleaching involves the use of a 15 - 40 % hydrogen peroxide solution and must be performed by a dental professional because careful isolation of the teeth is required to protect the soft tissues from the caustic effects of the bleaching agent . 30 The use of home bleaching systems is currently popular ; they may be used alone or in combination with in - office bleaching . The systems must be used under the careful supervision of dentists or dental hygienists . Patients apply a 10 - 22 % carbamide peroxide solution into a custom - made mouthguard . After repeated daily and / or nightly ( often while patients sleep ) applications for 2 - 6 weeks , the teeth are gradually bleached . The public is advised to avoid the use of home bleaching systems that are not approved by the Whitening strips , using a 5.3 % hydrogen peroxide – impregnated polyethylene strip , offer an at - home alternative to the above methods and can be recommended for maintaining already whitened teeth . 31 Whitening toothpastes , containing 1 % or less peroxide , are minimally effective . With darker stains , the best results are achieved by using a combination of office and home bleaching systems . Most patients also require periodic re - treatment . Clinicians should be aware of potential adverse reactions and contraindications for bleaching . Approximately two thirds of patients have short - term , minor tooth sensitivity to cold and / or gingival irritation . Tooth surfaces , particularly exposed roots or enamel surfaces with defects secondary to incomplete amelogenesis , are porous to the bleaching agent and are more likely to develop cold sensitivity . Gingival irritation usually is related to improper fitting of the custom - made mouthguard . Allergic reactions to the bleaching agent are exceedingly rare . No adverse reactions are documented in pregnant or breastfeeding women or in patients who smoke ; however , bleaching is not advised in these patients . Nonvital bleaching Nonvital bleaching is indicated for the treatment of teeth with discoloration secondary to pulpal degeneration . This technique involves placing a mixture of 30 % hydrogen peroxide and sodium perborate into the pulp chamber for as long as 1 week . 32 For nonvital bleaching , a tooth with an unrestored crown is ideal . Cervical external root resorption is a possible adverse sequela , especially in teeth that become pulpless before the patient is aged 25 years . Special intracanal barrier restoration helps to minimize this adverse reaction . Next : Surgical Care Sections Tooth Discoloration Overview Presentation Workup Treatment Surgical Care Consultations Diet Activity Show All Follow - up Media Gallery Tables References
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[
"Tooth Discoloration",
"etiology",
"Pathophysiology"
] |
http://emedicine.medscape.com/article/1104368-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Dermatology Carotenemia Updated : Apr 03 , 2018 Author : Robert A Schwartz , MD , MPH ; Chief Editor : Dirk M Elston , MD more . . . Sections Overview Pathophysiology Etiology Prognosis Patient History Physical Examination Differential Diagnosis Workup Dietary Treatment Show All References Overview Carotenemia is a clinical condition characterized by yellow pigmentation of the skin ( xanthoderma ) and increased beta - carotene levels in the blood . In most cases , the condition follows prolonged and excessive consumption of carotene - rich foods , such as carrots , squash , and sweet potatoes . Carotenemia is a common finding in children . The condition of carotenemia is harmless , but it can lead to a mistaken diagnosis of jaundice . Orangeness also may possess a significant symbolic significance . 1 See the image below . Carotenoderma visible on nasolabial folds of young child . Carotene is a lipochrome that normally adds yellow color to the skin . With elevated blood levels of carotene , the prominence of this yellowing is increased . Carotenemia may be particularly evident when the stratum corneum is thickened or when the subcutaneous fat is strongly represented . The condition is more easily appreciated in light - complexioned people , and may present chiefly as yellowing of the palms and the soles in more darkly pigmented individuals . Carotinemia was originally noted as xanthosis diabetica in 1904 by von Noorden , who observed it to be prominent in the nasolabial folds and on the palms and soles . 2 Causes Diet - induced carotenemia is observed most frequently in infants and young children . 3 Mothers may induce the condition by giving their infants large amounts of carrots in commercial infant food preparations . 4 In addition , vegetarians are more likely to develop carotenemia than nonvegetarians . The condition may also be associated with the ingestion of carotene - rich nutritional supplements . 5 Diseases , including hypothyroidism 6 diabetes mellitus 7 hepatic disorders anorexia nervosa , and renal diseases , may also give rise to carotenemia . 8 Next : Pathophysiology Sections Carotenemia Pathophysiology Etiology Prognosis Patient History Physical Examination Differential Diagnosis Workup Dietary Treatment Show All References Recommended Diseases & Conditions Vitamin Toxicity Diseases & Conditions Dermatologic Manifestations of Down Syndrome
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[
"Carotenemia",
"skin",
"jaundice"
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http://emedicine.medscape.com/article/1110595-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Dermatology Ectodermal Dysplasia Updated : Feb 11 , 2019 Author : Kara N Shah , MD , PhD ; Chief Editor : Dirk M Elston , MD more . . . Sections Overview Background Pathophysiology Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Medication Media Gallery References Background The ectodermal dysplasias ( EDs ) comprise a large , heterogeneous group of inherited disorders that are defined by primary defects in the development of 2 or more tissues derived from embryonic ectoderm . The tissues primarily involved are the skin and its appendages ( hair follicles , eccrine glands , sebaceous glands , and , nails ) and teeth . Although Thurnam published the first report of a patient with ectodermal dysplasia in 1848 , the term ectodermal dysplasia was not coined until 1929 by Weech . 1 The ectodermal dysplasias are congenital , diffuse , and nonprogressive . To date , more than 192 distinct disorders have been described . The most common ectodermal dysplasias are X - linked recessive hypohidrotic ectodermal dysplasia ( Christ - Siemens - Touraine syndrome ) , as shown in the image below , and hidrotic ectodermal dysplasia ( Clouston syndrome ) . A newborn boy with anhidrotic / hypohidrotic ectodermal dysplasia syndrome showing generalized fine scaling and a history of intermittent fever . View Media Gallery Current classification of ectodermal dysplasias is based on clinical features . Pure ectodermal dysplasias are manifested by defects in ectodermal structures alone , while ectodermal dysplasia syndromes are defined by the combination of ectodermal defects in association with other anomalies . Freire - Maia and Pinheiro proposed the first classification system of the ectodermal dysplasias in 1982 , 2 with additional updates in 1994 and 2001 . 3 4 Their original classification system stratified the ectodermal dysplasias into different subgroups according to the presence or absence of ( 1 ) hair anomalies or trichodysplasias , ( 2 ) dental abnormalities , ( 3 ) nail abnormalities or onychodysplasias , and ( 4 ) eccrine gland dysfunction or dyshidrosis . Overall , the ectodermal dysplasias were classified into either group A disorders , which were manifested by defects in at least 2 of the 4 classic ectodermal structures as defined above , with or without other defects , and group B disorders , which were manifested by a defect in one classic ectodermal structure ( 1 - 4 from above ) in combination with ( 5 ) a defect in one other ectodermal structure ( ie , ears , lips , dermatoglyphics ) . Eleven group A subgroups were defined , each with a distinct combination of 2 or more 5 This classification was revised in 2014 to include 163 defined ectodermal dysplasia syndromes . 6 With the recent identification of the causative genetic defect for a number of the ectodermal dysplasias , newer classification systems have been devised . In 2003 , Lamartine reclassified the ectodermal dysplasias into the following 4 functional groups based on the underlying pathophysiologic defect : ( 1 ) cell - to - cell communication and signaling , ( 2 ) adhesion , ( 3 ) development , and ( 4 ) other . 7 Similarly , in 2001 , Priolo and Laganà reclassified the ectodermal dysplasias into 2 main functional groups : ( 1 ) defects in developmental regulation / epithelial - mesenchymal interaction and ( 2 ) defects in cytoskeleton maintenance and cell stability . 8 Other classification systems categorize the ectodermal dysplasias based on defects in cell - cell communication and signaling , adhesion , transcription regulation , or development . 9 Several ectodermal dysplasia syndromes may manifest in association with midfacial defects , mainly cleft lip , cleft palate , or both . The 3 most commonly recognized entities are ( 1 ) ectodermal dysplasia , ectrodactyly , and clefting ( EEC ) syndrome 10 ; ( 2 ) Hay - Wells syndrome or ankyloblepharon , ectodermal dysplasia , and cleft lip / palate ( AEC ) syndrome ; and ( 3 ) Rapp - Hodgkin syndrome , all of which are caused by mutations in the TP63 gene . See the images below . Ectodermal dysplasia , ectrodactyly , and clefting syndrome . Light - colored hair and scalp and earlobe defects are observed . Cleft lip and palate results in a characteristic nasal contour . View Media Gallery Ectrodactyly observed in an individual with ectodermal dysplasia , ectrodactyly , and clefting syndrome . Typical cleft lip / palate and maxillary hyperplasia in a patient with Rapp - Hodgkin syndrome . Next : Pathophysiology Sections Ectodermal Dysplasia Overview Pathophysiology Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Medication Media Gallery References
|
[
"ectodermal dysplasias",
"embryonic ectoderm",
"hair follicles"
] |
http://emedicine.medscape.com/article/1175560-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Neurology Mercury Toxicity Updated : Nov 05 , 2018 Author : David A Olson , MD ; Chief Editor : Tarakad S Ramachandran , MBBS , MBA , MPH , FAAN , FACP , FAHA , FRCP , FRCPC , FRS , LRCP , MRCP , MRCS more . . . Sections Overview Background Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Background Mercury in any form is poisonous , with mercury toxicity most commonly affecting the neurologic , gastrointestinal ( GI ) and renal organ systems . Poisoning can result from mercury vapor inhalation , mercury ingestion , mercury injection , and absorption of mercury through the skin . ( See Etiology and Prognosis . ) Mercury has 3 forms : ( 1 ) elemental mercury , ( 2 ) inorganic salts , and ( 3 ) organic compounds . Perhaps the most deadly form of mercury is methylmercury . Only 2 – 10 % of the ingested mercury is absorbed from the gut , and ingested elemental mercury is not absorbed at all ; however , 90 % of any methylmercury ingested is absorbed into the bloodstream from the GI tract . ( See the images below . ) This is a 1 - view , abdominal , upright radiograph in a male patient who intentionally ingested 8 ounces of elemental mercury . Notice how the mercury outlines the large intestine from ascending to descending . Image courtesy of Fred P . Harchelroad , MD , and Ferdinando L . Mirarchi , DO . View Media Gallery Patient with intentional ingestion of mercury from blood pressure instrument . Note how mercury beads can be seen deposited in lung fields . Image courtesy of Shuchi Vyas , MD . View Media Gallery Organic mercury compounds , specifically methylmercury , are concentrated in the food chain . Fish from contaminated waters are the most common culprits . Industrial mercury pollution is often in the inorganic form , but aquatic organisms and vegetation in waterways such as rivers , lakes , and bays convert it to deadly methylmercury . Fish eat contaminated vegetation , and the mercury becomes biomagnified in the fish . Fish protein binds more than 90 % of the consumed methylmercury so tightly that even the most vigorous cooking methods ( eg , deep - frying , boiling , baking , For centuries , mercury was an essential part of many different medicines , such as diuretics , antibacterial agents , antiseptics , and laxatives . In the late 18th century , antisyphilitic agents contained mercury . It was during the 1800s that the phrase " mad as a hatter " was coined , owing to the effects of chronic mercury exposure in the hat - making industry , where the metal was used in the manufacturing process . In 1889 , Charcot , in his Clinical Lectures on Diseases of the Nervous System , attributed some rapid oscillatory tremors to mercury exposure . 1 In Wilson ' s classic textbook of neurology , published in 1940 , Wilson concurred with Charcot ' s attribution of tremors to mercury poisoning , but also described mercury - induced cognitive impairments , such as inattention , excitement , and hallucinosis . 2 In 1961 , researchers in Japan correlated elevated urinary mercury levels with the features of the previously mysterious Minamata disease . Before the etiology of Minamata disease was discovered , it plagued the residents around Minamata Bay in Japan with tremors , sensory loss , ataxia , and visual field constriction . ( See Presentation . ) 3 Minamata disease is an example of organic toxicity . In Minamata Bay , a factory discharged inorganic mercury into the water . The mercury was methylated by bacteria and subsequently ingested by fish . Local villagers ate the fish and began to exhibit signs of neurologic damage , such as visual loss , extremity numbness , hearing loss , and ataxia . Babies exposed to the methylmercury in utero were the most severely affected . Furthermore , because mercury was also discovered in the breast milk of the mothers , the babies ' exposure continued after birth . 4 On January 19 , 2013 , The Minamata Convention on Mercury was agreed upon at the fifth session of the Intergovernmental Negotiating Committee in Geneva , Switzerland . It is a global treaty to protect human health and the environment from the adverse effects of mercury . The major highlights of the convention included a ban on new mercury mines , the phase - out of existing ones , control measures on air emissions , and the international regulation of the informal sector for artisanal and small - scale gold mining . 4 Mercury is still found in many industries , including in battery , thermometer , and barometer manufacturing . Mercury can also be found in fungicides used in the agricultural industry . Before 1990 , paints contained mercury as an antimildew agent . In medicine , mercury is used in dental amalgams and various antiseptic agents . ( See Etiology and Prognosis . ) Mercury may also be contained in some cosmetics , such as skin - lightening products . One study measured international skin - lightening products for their mercury content , focusing on products available to US consumers either online or in stores . The products were screened for mercury content using a portable x - ray fluorescence spectrometer . Of the 549 products tested , 6 % contained mercury levels above 1000 ppm , and 45 % contained mercury levels that exceeded 10,000 ppm . Of lightening products purchased in the United States , 3.3 % were found to contain mercury 5 Complications Minamata disease has devastating neurologic consequences as a primary outcome of methyl mercury intoxication ; unfortunately , these are relatively resistant to treatment . Complications include the following ( see Presentation ) : Acute perioral and facial paresthesias Visual - field constriction Respiratory distress and nonspecific dermatitis Extremity numbness eventually appears , along with headache , fatigue , and tremor Ataxia and dysarthria can also be observed Severe poisoning eventually causes the patient to lie in a mute , semirigid posture that is broken only by episodes of crying or primitive reflexive movements . ( See Presentation . ) Babies exposed in utero are the most severely affected . They are affected by low birth weight , seizure disorders , profound developmental delay , incomplete visual loss ( including tunnel vision ) or total blindness , and hearing loss . Neurologic damage in the form of diffuse and widespread neuronal atrophy is most severe in patients exposed in utero . Long - term studies may indicate that even prenatal exposure at low concentrations can cause subtle , but detectable , decrements in the areas of motor function , language , and memory . Children so affected may have long - term stigmata , including motor impairment , visual loss , hearing loss , developmental delay , and seizure disorders . Several members of the Plenary Panel on Human Health in the 12th International Conference on Mercury as a Global Pollutant held in Korea in June 2015 wrote an excellent summary article on this meeting . 6 Next : Etiology Sections Mercury Toxicity Overview Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References
|
[
"Mercury Toxicity",
"renal organ systems .",
"elemental mercury ,"
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http://emedicine.medscape.com/article/1191370-medication
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Ophthalmology Viral Conjunctivitis ( Pink Eye ) Medication Updated : Sep 19 , 2018 Author : Ingrid U Scott , MD , MPH ; Chief Editor : Andrew A Dahl , MD , FACS more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers References Medication Summary The goals of pharmacotherapy are to reduce morbidity and prevent complications . Ocular Lubricants Class Summary These agents are used for symptomatic relief . Artificial tears ( Altalube , Gen Teal Tears , Bion Tears , Murine Tears , Natures Tears ) View full drug information Artificial tears act to stabilize and thicken precorneal tear film and prolong tear film breakup time , which occurs with dry eye states . Antihistamines Class Summary These agents are used to treat severe itching . Azelastine ophthalmic View full drug information Azelastine competes with histamine for the H1 receptor and inhibits the release of histamine and other mediators involved in the allergic response . Ketotifen , ophthalmic ( Alaway , Zaditor , Zyrtec Itchy Eye Drops ) Ketotifen is a relatively selective H1 receptor antagonist and inhibitor of histamine release from mast cells . OTC . Olopatadine ophthalmic ( Pataday , Patanol , Pazeo ) Olopatadine is a relatively selective H1 receptor antagonist and inhibitor of histamine release from mast cells . Corticosteroids Corticosteroids may be used for pseudomembranes and decreased vision and / or glare due to subepithelial infiltrates . They have anti - inflammatory properties and cause profound and varied metabolic effects . In addition , these agents modify the body ' s immune response to diverse stimuli . Extreme caution should be taken when using corticosteroids , as they may worsen an underlying HSV infection or induce dependency in the context of persistent EKC subepithelial infiltrates . Prednisolone ophthalmic ( AK - Pred , Pred Mild , Omnipred ) This agent decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability . Less potent ( eg , prednisolone 0.125 % , fluorometholone 0.1 % ) are usually sufficient to treat subepithelial infiltrates . The steroid must be tapered very carefully , often over months . Topical cyclosporine A emulsion ( Restasis , Allergan , Irvine CA ) may provide a viable steroid - sparing alternative for selected patients . Fluorometholone ( Flarex , FML , FML Forte ) Fluorometholone inhibits edema , fibrin deposition , capillary dilation , phagocytic migration , capillary proliferation , collagen deposition , and scar formation . It decreases inflammation and corneal neovascularization , suppresses migration of PMNs , and reverses capillary permeability . It is believed to act by inducing phospholipase A2 inhibitory proteins . Loteprednol ophthalmic ( Alrex , Lotemax ) Loteprednol etabonate decreases inflammation by suppressing migration of polymorphonuclear leukocytes ( PMNs ) and reversing increased capillary permeability . Immunosuppressant Agents Immunosuppressant agents are used as adjunctive or alternative treatment when steroid use is ineffective or requires minimization . Cyclosporine ophthalmic ( Restasis ) The exact mechanism of the immunosuppressive activity of cyclosporine is unknown , but preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of the cell cycle has been suggested . Antivirals These agents are used for the treatment of HSV infection . Trifluridine ( Viroptic ) Trifluridine is a pyrimidine ( thymidine ) analogue drug of choice in the United States for topical antiviral therapy for HSV infection . It inhibits viral replication by incorporating into viral deoxyribonucleic acid ( DNA ) in place of thymidine . It is prescribed initially 9 times per day until resolution of the epithelial keratitis , then QID for another week . If the patient has no response in 7 - 14 days , consider other treatments . Trifluridine requires refrigeration and contains the toxic preservative thimerosal . Ganciclovir ophthalmic ( Zirgan ) Ganciclovir is a selective antiviral activated only within infected cells by viral thymidine kinase . It is a viral DNA chain terminator and DNA polymerase inhibitor . It is available in gel formulation and is stable at room temperature . It is prescribed 5 times per day until resolution of the epithelial keratitis , then TID for an additional week . Acyclovir ( Zovirax ) This is a prodrug that inhibits viral replication ; it is activated by phosphorylation by virus - specific thymidine kinase . The recommended dosage for acute epithelial keratitis or stromal keratitis ranges from 200 mg PO BID to 400 mg PO TID . Some clinicians recommend the highest anti - zoster strength of 800 mg owing to the variability among patients in gastric absorption and the resultant variability and unpredictability of measurable serum concentrations . Valacyclovir ( Valtrex ) Valacyclovir is a prodrug that is rapidly converted to the active drug acyclovir . It produces a greater serum concentration of acyclovir with smaller oral dosing . Valacyclovir is more expensive than acyclovir but can be as effective with a more convenient dosing regimen . Famciclovir ( Famvir ) This agent is a prodrug that , when biotransformed into its active metabolite , penciclovir , may inhibit viral DNA synthesis / replication . It has been used successfully in the suppression of genital herpes . Its efficacy in HSV keratitis currently is under study . Antibiotics Therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting . Antibiotics are used to prevent superinfections . Ofloxacin ophthalmic ( Ocuflox ) Ofloxacin is a pyridine carboxylic acid derivative with broad - spectrum bactericidal effect . It inhibits bacterial growth by inhibiting DNA gyrase . It is indicated for superficial ocular infections of conjunctiva or cornea due to susceptible microorganisms . Trimethoprim / polymyxin B ophthalmic ( Polytrim Ophthalmic Solution ) This combination is used for ocular infection of the cornea or conjunctiva caused by susceptible microorganisms . Ciprofloxacin ophthalmic ( Ciloxan ) Ciprofloxacin has activity against Pseudomonas and Streptococcus species , methicillin - resistant Staphylococcus aureus ( MRSA ) , S epidermidis , and most gram - negative organisms ; it has no activity against anaerobes . Sulfacetamide ophthalmic ( Bleph 10 ) This agent interferes with bacterial growth by inhibiting bacterial folic acid synthesis by competitively antagonizing para - aminobenzoic acid . Questions Sections Viral Conjunctivitis ( Pink Eye ) Overview Presentation DDx Workup Treatment Medication Questions & Answers References
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[
"Viral Conjunctivitis",
"Medication",
"pharmacotherapy"
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http://emedicine.medscape.com/article/120497-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Endocrinology Toxic Nodular Goiter Updated : Oct 14 , 2016 Author : Philip R Orlander , MD ; Chief Editor : George T Griffing , MD more . . . Sections Overview Presentation DDx Workup Treatment Guidelines Medication Follow - up References Background A toxic nodular goiter ( TNG ) is a thyroid gland that contains autonomously functioning thyroid nodules , with resulting hyperthyroidism . There are distinct considerations if the patient has a single solitary toxic nodule ( see Solitary Thyroid Nodule ) . TNG , or Plummer ' s disease , was first described by Henry Plummer in 1913 . TNG is the second most common cause of hyperthyroidism in the Western world , after Graves disease . In elderly individuals and in areas of endemic iodine deficiency , TNG is the most common cause of hyperthyroidism . Pathophysiology Toxic nodular goiter ( TNG ) represents a spectrum of disease ranging from a single hyperfunctioning nodule ( toxic adenoma ) within a multinodular thyroid to a gland with multiple areas of hyperfunction . The natural history of a multinodular goiter involves variable growth of individual nodules ; this may progress to hemorrhage and degeneration , followed by healing and fibrosis . Calcification may be found in areas of previous hemorrhage . Some nodules may develop autonomous function . Autonomous hyperactivity is conferred by somatic mutations of the thyrotropin , or thyroid - stimulating hormone ( TSH ) , receptor 1 Autonomously functioning nodules may become toxic in 10 % of patients . Hyperthyroidism predominantly occurs when single nodules are larger than 2.5 cm in diameter . Signs and symptoms of TNG are similar to those of other types of hyperthyroidism . Epidemiology Frequency United States Toxic nodular goiter accounts for approximately 15 - 30 % of cases of hyperthyroidism in the United States , second only to Graves disease . International In areas of endemic iodine deficiency , toxic nodular goiter ( TNG ) accounts for approximately 58 % of cases of hyperthyroidism , 10 % of which are from solitary toxic nodules . Graves disease accounts for 40 % of cases of hyperthyroidism . In patients with underlying nontoxic multinodular goiter , initial iodine supplementation ( or iodinated contrast agents ) can lead to hyperthyroidism ( Jod - Basedow effect ) . Iodinated drugs , such as amiodarone , may also induce hyperthyroidism in patients with underlying nontoxic multinodular goiter . Roughly 3 % of patients treated with amiodarone in amiodarone - induced hyperthyroidism 2 Mortality / Morbidity Morbidity and mortality from toxic nodular goiter ( TNG ) may be divided into problems related to hyperthyroidism and problems related to growth of the nodules and gland . Local compression problems due to nodule growth , although unusual , include dyspnea , hoarseness , and dysphagia . Both TNG and Graves disease have increased mortality but for different reasons . 3 TNG is more common in elderly adults ; therefore , complications due to comorbidities , such as coronary artery disease , are significant in the management of hyperthyroidism . Sex Toxic nodular goiter occurs more commonly in women than in men . In women and men older than 40 years , the prevalence rate of palpable nodules is 5 - 7 % and 1 - 2 % , respectively . Age Most patients with toxic nodular goiter ( TNG ) are older than 50 years . Thyrotoxicosis often occurs in patients with a history of longstanding goiter . Toxicity occurs in a subset of patients who develop autonomous function . This toxicity usually peaks in the sixth and seventh decades of life , especially in persons with a family history of multinodular goiter or TNG , suggesting a genetic component . Clinical Presentation Sections Toxic Nodular Goiter Overview Presentation DDx Workup Treatment Guidelines Medication Follow - up References
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[
"Toxic Nodular Goiter",
"Henry Plummer"
] |
http://emedicine.medscape.com/article/1240789-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Orthopedic Surgery Triangular Fibrocartilage Complex Injuries Treatment & Management Updated : Nov 26 , 2018 Author : James R Verheyden , MD ; Chief Editor : Harris Gellman , MD more . . . Sections Overview Presentation Workup Treatment Media Gallery References Approach Considerations If a congruent reduction can not be achieved or if the dorsal instability is unstable in 30 ° of supination , then arthroscopic evaluation of the triangular fibrocartilage complex ( TFCC ) is recommended with repair as needed . Repairing TFCC tears is contraindicated in the presence of infection or degeneration . Palmer class 2 degenerative TFCC tears ( see Pathophysiology ) represent a pathologic progression of disease associated with ulnar impaction syndrome . Degeneration of the TFCC is found with repetitive pronation and axial grip loading in association with positive ulnar variance and impaction between the ulnar head and the proximal pole of the lunate . Treatment of degenerative TFCC tears associated with ulnar impaction syndrome consists of nonoperative treatment first with immobilization , avoidance of aggravating activities , and nonsteroidal anti - inflammatory drugs ( NSAIDs ) . Palmer class 2A and 2B lesions that fail to respond to conservative treatment are treated with gentle debridement . If the patient is ulnar - positive and symptomatic , a formal ulnar shortening is considered . An arthroscopic wafer is contraindicated , in that this would require resection of intact TFCC to perform the procedure or require performing the procedure entirely through the distal radioulnar joint ( DRUJ ) portals . The surgical indications for an arthroscopic wafer procedure are a Palmer class 2C or 2D lesion in a positive ulnar variance of not more than 2 mm without evidence of lunotriquetral ( LT ) instability . If LT instability is present , this is addressed with formal ulnar shortening in an attempt to tighten the ulnocarpal ligaments and decrease the motion between the lunate and triquetrum . For patients with a positive ulnar variance of more than 2 mm , formal ulnar shortening is performed . For patients with neutral or negative ulnar variance and a Palmer class 2C lesion , an arthroscopic debridement is performed . Palmer class 2E lesions respond unpredictably to arthroscopic debridement . They are usually treated with a salvage procedure such as a limited ulnar head resection , a Sauve - Kapandji procedure , or a Darrach procedure that addresses the DRUJ and lunotriquetral ( LT ) joint pathology . Medical Therapy Initial treatment of both symptomatic degenerative and traumatic TFCC tears is 8 - 12 weeks of conservative therapy consisting of the following : NSAIDs Immobilization in slight flexion and ulnar deviation in a short arm cast for 4 - 6 weeks , followed by removable wrist splints and physical therapy Initial treatment with long arm casting for 4 - 6 weeks for traumatic tears and 3 - 4 weeks of short arm casting for degenerative tears recommended by some The natural history of symptomatic tears , according to Osterman ' s study of 133 patients , 37 is as follows : Traumatic tears with neutral ulnar variance did not worsen over time , and one third of patients were asymptomatic at 9.5 years of follow - up In persons with traumatic tears with positive ulnar variance , two thirds of patients worsened over time both symptomatically and radiologically Over a 3 - year period , Lee et al treated 117 patients with TFCC tears who did not have DRUJ instability . 38 They found nonsurgical treatment to be moderately successful in treating these patients and recommended a minimum of 6 months nonsurgical treatment as the first - line treatment for this injury . Acute isolated TFCC disruption with dislocation or instability of distal radioulnar joint Isolated TFCC disruptions may be associated with DRUJ instability . These injuries are often associated with distal radius and forearm fractures . Forced hyperpronation usually results in dorsal dislocation . On physical examination , the ulnar head is prominent dorsally and the patient has limited forearm supination . Less commonly , volar dislocation results from forced supination . Dorsal skin dimpling is often observed , and pronation is limited . The volarly displaced ulnar head is often not felt because of the overlying soft tissues . When dislocation of the ulnar head is not present , subluxation and instability are more difficult to diagnose . Subluxation and instability of the DRUJ are assessed on physical examination by shucking the radius and ulna past each other to determine the amount of dorsal / palmar laxity . This should be performed in neutral , pronation , and supination and compared to the opposite side . The more common dorsal DRUJ instability is reduced with the forearm in supination . Palmar DRUJ instability is reduced with the forearm in pronation . If a congruent reduction can be achieved and the forearm is stable through a full range of motion , then the forearm is immobilized in a long arm cast in the position of stability for 4 - 6 weeks . With a dorsal dislocation , the preferred position of immobilization is in approximately 30 ° of supination for 4 weeks , followed by gradual reduction to neutral over the next 2 weeks . If a congruent reduction can not be achieved or if the dorsal instability is unstable in 30 ° of supination , then arthroscopic evaluation of the TFCC is recommended with repair as needed . Surgical Options If the DRUJ joint remains unstable , open reduction is required to remove interposed structures . When instability persists with forearm range of motion , supplemental Kirschner wire ( K - wire ) stabilization just proximal to the DRUJ is recommended for 4 - 6 weeks . Instability of the DRUJ is often associated with distal radius fractures and Galeazzi fracture - dislocations . Anatomic reduction of these fractures often stabilizes the joint . When fixation of these fractures does not stabilize the joint , stabilization can be obtained with either ( 1 ) long arm casting in a reduced position , open reduction , and TFCC repair or ( 2 ) supplemental K - wire fixation . Rettig and Raskin noted a high association with Galeazzi fractures within 7.5 cm of the midarticular surface of the distal radius and with DRUJ instability after open reduction and internal fixation ( ORIF ) of the radial shaft fracture . 39 In individuals with radial head fracture and tenderness over the DRUJ , every attempt should be made to preserve the radial head to prevent proximal migration of the radius . DRUJ disruption associated with a displaced radial head fracture and proximal migration of the radius is termed the Essex - Lopresti fracture . Geel and Palmer noted good results in 18 of 19 patients with radial head fracture and pain at the DRUJ who were treated with ORIF of the radial head . 40 Arthroscopic vs open repair In a study of 16 competitive athletes with wrist TFCC injuries from 2001 through 2005 , McAdams et al found that arthroscopic debridement or repair of TFCC injury provided pain relief and allowed patients to return to play . There was slower recovery in patients with concomitant ulnar - side wrist injuries . 41 Yao et al compared an all - arthroscopic TFCC repair technique with an outside - in technique in 10 matched pairs of fresh - frozen cadaveric wrists and found that the all - arthroscopic technique resulted in decreased operating time , reduced postoperative immobilizations , and decreased irritation from suture knots below the skin . 42 43 In a study of 75 patients with TFCC repair by arthroscopic or open technique between 1997 and 2006 , Anderson et al found that there was no statistical difference in clinical outcome between the two approaches to repair . They did note an increased rate of postoperative superficial ulnar pain in patients who underwent open repair ( 14 / 39 patients with open technique vs 8 / 36 patients with arthroscopy ) . Females had a higher rate of reoperation . 44 Reiter et al performed a retrospective study of 46 patients who underwent arthroscopic repair of Palmer class 1B tears to assess functional and subjective outcomes , as well as to determine whether clinical outcomes were related to ulnar length . Good - to - excellent results were achieved in 63 % of the patients , including increased range of motion and grip strength and pain relief . Neutral or positive ulnar variance was not a contraindication for repair and did not necessitate simultaneous ulnar shortening . 13 A systematic review by Andersson et al examined the outcomes of open and arthroscopic repair of TFCC injuries . 45 The primary outcome measure was the rate of postoperative DRUJ reinstability ; secondary outcome measures were range of motion ( ROM ) , grip strength , residual pain , functional wrist scores , complication rate , and reoperation rate . The two repair approaches yielded comparable results in terms of DRUJ reinstability and functional outcome scores . The evidence was insufficient to allow recommendation of one technique over the other in clinical practice . Operative Details Open repair Make a dorsal ulnar incision between the fourth and fifth extensor compartments . Carry the dissection down to the dorsal radioulnar ( DRU ) ligament . Reflect the DRU ligament and the periosteum over the lunate fossa . Place horizontal mattress sutures in the TFCC through drill holes placed in the dorsoulnar aspect of the distal radius . Wrist arthroscopy Indications for wrist arthroscopy include acute unstable tears , acute tears that fail to respond to conservative management , and chronic tears for which conservative management fails . 41 46 47 48 General arthroscopic principles are as follows : Debride to a stable smooth rim of tissue Maintain a 2 - mm peripheral rim Excise less than two thirds of the central portion of the TFCC Maintain the integrity of the DRU ligament , the palmar radioulnar ( PRU ) ligament , and the disk carpal ligaments Traumatic central tears ( Palmer class 1A ) Perform debridement as above . Traumatic ulnar - side tears ( Palmer class 1B ) with outside - in technique Debride the synovitis and the edges of the tear . 49 Make a 1 - cm incision just radial to the extensor carpi ulnaris ( ECU ) tendon . Open the radial aspect of the ECU tendon sheath for 1 cm . Retract the ECU palmarly . Under arthroscopic visualization , pass two needles through the capsule and across the tear using a meniscus mender or similar TFCC repair device . Use a wire loop passed through one needle to retrieve a 2 - 0 polydioxanone suture passed through the other needle . This creates a loop . Tie the suture over the dorsal wrist capsule , approximating the tear . From two to four sutures may be required . Reconstruct the ECU tendon as needed . Immobilize the wrist and elbow for 4 weeks in a splint or Muenster cast . Ulnar extrinsic ligament tears ( Palmer class 1C ) Perform a miniopen or arthroscopic repair using zone - specific cannulas . Stay between the ECU and the flexor carpi ulnaris ( FCU ) to avoid the neurovascular bundle . Traumatic radial - side tears ( Palmer class 1D ) Debride as with a Palmer class 1A tear , or repair as follows : Debride the edge of the sigmoid notch with a shaver down to bleeding bone Make drill holes through the distal radius with a K - wire passed percutaneously into the joint from the sigmoid notch across the distal radius Pass a 2 - 0 double - ended polydioxanone suture on long needles through the TFCC and into the drill holes Tie the suture on the surface of the radius through a small incision while protecting the superficial radial nerve Pin the DRU joint in neutral rotation with a single 0.062 - in . K - wire Immobilize the wrist and elbow for 8 weeks in a splint or Muenster cast Transosseous suture anchors can be used in place of drill holes Degenerative tears ( Palmer classes 2A and 2B ) Gently debride . If the patient is ulnar - positive and symptomatic , use open ulnar shortening . Degenerative tears ( Palmer class 2C ) Gently debride in patients who are ulnar - neutral or ulnar - negative . For patients who are ulnar - positive , consider the arthroscopic wafer procedure . Wnorowski demonstrated almost a 50 % unloading of the ulnar side of the wrist after excision of the central portion of the TFCC and resection of the radial two thirds of the width of the ulnar head to a depth of subchondral bone . 50 Patients with an arthroscopic wafer procedure may have a more prolonged postoperative course than those with open ulnar shortening . Degenerative tears ( Palmer class 2D ) Treatment is similar to that for Palmer class 2C tears . Carefully assess LT instability . If the LT joint is stable , perform debridement . If it is unstable , consider an open shortening osteotomy to unload the ulnar head and tighten the ulnar extrinsic ligaments . Then , consider an LT fusion or pinning or an LT ligament repair . 51 An arthroscopic wafer procedure is contraindicated , because it leads to more laxity in the ulnar extrinsic and LT ligaments . Degenerative tears ( Palmer class 2E ) Degenerative tears have an unpredictable response to arthroscopic debridement . These tears usually require a salvage operation . The DRUJ and the LT joint must be addressed . A limited ulnar head excision can be performed . The Sauve - Kapandji procedure involves radioulnar joint arthrodesis and proximal ulnar pseudarthrosis . The Darrach procedure is a resection of the distal end of the ulna . Ulnar - shortening osteotomy Consider ulnar - shortening osteotomy for patients with positive ulnar variance , patients in whom debridement fails , and patients who present with a delay in treatment of longer than 6 months . Advantages of an ulnar - shortening osteotomy are as follows : It is extra - articular It maintains the mechanical integrity of the DRUJ It maintains the origins and insertions of the ligamentous tissue and capsule forming the peripheral aspect of the TFCC ; it may result in tightening of the ulnocarpal complex , including the LT ligament , with shortening It is potentially less painful than an arthroscopic resection Postoperative Care After surgery , all patients are immobilized immediately . If debridement alone is performed , patients are placed in a bulky dressing and started on motion exercises at 5 - 7 days . All other patients are placed in a sugar - tong splint . Skin sutures are removed at 7 - 10 days . A Muenster - style cast is used for 2 weeks , followed by a short arm cast for 3 weeks for patients who have undergone TFCC repairs . Complications Complications include the following : Infection Stiffness Repair failure Wrist arthroscopy complications Continued pain Decreased strength Hardware failure Nonunion ( in cases of nonunion , perform an ulnar - shortening osteotomy ) Sections Triangular Fibrocartilage Complex Injuries Overview Presentation Workup Treatment Media Gallery References
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[
"Triangular",
"Fibrocartilage",
"Treatment"
] |
http://emedicine.medscape.com/article/1284026-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Plastic Surgery Orbital Floor Fractures ( Blowout ) Treatment & Management Updated : Mar 14 , 2018 Author : Adam J Cohen , MD ; Chief Editor : Deepak Narayan , MD , FRCS more . . . Sections Overview Workup Treatment Questions & Answers Media Gallery References Medical Therapy Medical treatment is warranted for patients for whom surgery is not indicated . This may include patients who present without significant enophthalmos ( 2 mm or more ) , a lack of marked hypo - ophthalmus , absence of an entrapped muscle or tissue , a fracture less than 50 % of the floor , or a lack of diplopia . The patient can be treated with oral antibiotics on an empiric basis due to the disruption of the integrity of the orbit in communication with the maxillary sinus . A short course of oral prednisone reduces edema of the orbit and muscle , allowing for a better assessment of enophthalmos or entrapment . Discourage nose blowing to avoid creating or worsening orbital emphysema . Nasal decongestants can be used if not contraindicated . Surgical Therapy The orbital floor can be accessed through a conjunctival approach , through cutaneous exposure , or through a transmaxillary approach . Access to this region allows for exploration and release of displaced or entrapped soft tissue , thereby correcting any extraocular motility disturbances . In addition , repair of the bony defect with removal or repositioning of bony fragments allows for restoration of the partition between the orbit and maxillary antrum , thereby preserving orbital volume and geometry and eliminating impingement of soft tissue structures . Transconjunctival approach The transconjunctival approach can be combined with a lateral canthotomy for exposure of the orbital floor ( see image below ) . Operative photo of fracture repair via transconjunctival approach . View Media Gallery Initiate this approach with a curvilinear incision approximately 3 mm below the tarsal plate parallel to lower lid punctum . Carry this surgical plane forward in a fashion posterior to the orbicularis oculi muscle and anterior to lower lid retractors and orbital septum . If placed too low , orbital fat prolapse likely compromises visibility of the fracture ; if placed too high , postoperative architectural distortion may ensue . Moving in a vector anterior to the septum , approach the orbital rim and overshoot it for several millimeters . Incise the periosteum at the medial aspect of the anterior border of the inferior orbital rim and carry it laterally . Then elevate the periosteum with a hand - over - hand technique using sharp periosteal elevators , starting nasally and moving temporally until adequate exposure is obtained . Preserve an anterior flap to be sutured at the conclusion of the procedure and remain cognizant of the location of the infraorbital groove and foramen that encase the infraorbital neurovascular bundle . The advantages of this approach include the absence of visible scars and reduced risk of lower eyelid retraction . Cutaneous approach The cutaneous approach commences with a skin - muscle flap elevation via an incision 2 - 3 mm below the lower lid margin . Carry this dissection anterior to the orbital septum until the orbital rim is exposed . Incise the periosteum and release it from its bony attachments as described in the transconjunctival approach . Of note is the downward sloping of the floor immediately posterior to the rim , which can result in breach of the septum during periosteal dissection . Transantral approach A transantral approach allows access to the orbital floor via the maxillary sinus . This approach may be especially useful when repairing a floor fracture of the trap door variety . Achieve exposure of the incision site with upper labial retraction exposing the buccal - gingival sulcus . Create a horizontal incision just inferior to the buccal - gingival sulcus so that a wide mucosal band is present . This wide band allows for imbrication of the wound , avoiding oral - antral fistulization . Use a periosteal elevator to strip the anterior maxillary wall of periosteum . The proximity of the infraorbital foramen should be kept in mind to minimize the risk of insult to the neurovascular bundle . Create a Caldwell - Luc antrostomy with an osteotome and mallet , followed by rongeurs to increase the diameter of the antrostomy , providing access to the orbital floor , medial wall , and ethmoid sinus complex . Strip the mucosa from the maxillary antrum and cauterize the remnants . Following repair of the fracture , attention to hemostasis is followed by closing the buccal - gingival mucosa with fast - absorbing suture material . This approach results in inferior orbital floor exposure and is not favored for floor fracture repair . Some authors have advocated an endoscopic transantral approach for improved visualization of fractures and to eliminate the need for eyelid incisions . 16 Other approaches Tessier described vertical osteotomy of an intact orbital rim for exposure of the orbital floor . This osteotomy is essentially 2 vertical osteotomies on either side of the infraorbital foramen conjoined by a horizontal osteotomy . Two osteotomies of the orbital floor originating at the inferior rim and extending past the infraorbital groove origins are created , allowing for removal of this segment , which can be replaced at the conclusion of surgery . Endoscopic - assisted approaches via a transmaxillary and transnasal route have been described . 17 18 19 20 Suzuki et al described a modified transnasal endoscopic approach designed to address problems with repairing anterior and lateral orbital floor fractures that have been encountered with previous transnasal endoscopic techniques . The modified approach involves going through the anterior space to the nasolacrimal duct , with surgeons removing the medial maxillary bone , shifting the lateral wall of the nose medially to provide greater access to the maxillary sinus , carefully removing bone fragments entrapping the orbital content , and correcting the periorbita ( orbital periosteum ) . 21 Implants Several types of implants are available for reconstructive use . The ideal implant should be easy to insert and manipulate , inert , not prone to infection or extrusion , easily anchored to surrounding structures , and reasonably priced . It should not rouse fibrous tissue formation . Most orbital floor defects can be repaired with synthetic implants composed of porous polyethylene , silicone , metallic rigid miniplates , Vicryl mesh , resorbable materials , or metallic mesh . Autogenous bone from the maxillary wall or the calvaria can be used , as can nasal septum or conchal cartilage . A study by Holtmann et al found better results with resorbable 0.15 - mm diameter polydioxanone foil than with titanium mesh in the repair of median orbital floor defects of 250 - 300 mm 2 in size . Using the foil , diplopia was reduced from 16 % of patients preoperatively to 4.9 % postoperatively . Fifty percent of patients who underwent reconstruction with titanium mesh reported foreign body sensations and a cold feeling in the operative region during weather changes , compared with just 4.7 % of patients reconstructed with the 0.15 - mm foil . 22 A retrospective study by Kronig et al indicated that good functional and aesthetic results can be achieved 1 year after the repair of pure orbital floor fractures with autogenous bone . In patients with both orbital floor and medial wall fractures , reconstruction of both walls resulted in an absence of enophthalmos , while in those in whom the medial wall was not reconstructed , 29 % still had enophthalmos after a year . 23 Preoperative Details Review and carefully document the patient ' s complete medical status and pertinent signs and symptoms pertaining to the injury . The procedure and the risks , benefits , and alternatives should be explained clearly and documented . The patient should be aware of the possibility of persistent , worsening , or new - onset diplopia , hypesthesia , and enophthalmos and of the risk of visual loss secondary to the procedure . Assess the patient ' s expectations to avoid a successful surgical outcome coupled with a poor outcome perceived by the patient . Clearly document visual acuity , degree of enophthalmos , pupillary and extraocular muscle function , and the amount of diplopia in all fields of gaze . Meticulous review of imaging is essential for planning the surgical approach and identifying surrounding structures that may serve as anchoring sites for an implant . Secure the appropriate implant several days prior to surgery . Intraoperative Details During the repair , periodically assess pupillary function . Assessing the pupil size prior to general anesthesia , after general anesthesia is induced , and after any periorbital injections containing epinephrine ( prior to manipulating the globe ) is worthwhile . Narcotics can cause pupillary constriction ( miosis ) , and epinephrine can cause pupillary dilation ( mydriasis ) . If not assessed before orbital content manipulation , the cause of a dilated pupil can be obscured when the pupil is checked . Perform a thorough exploration of fracture for bony fragments and occult fractures involving the medial wall . Inspection of soft tissue for necrosis is also necessary once freed from the fracture . Forced duction tests may be performed to confirm that tissues have been released completely . Following floor restoration , assess the fit and stability of the implant . Take special care to be sure the implant is not protruding , which can result in an aesthetically poor result , patient discomfort , and soft tissue breakdown , which can invite infection . If a titanium implant is used and anchored to the orbital , the implant may be covered with AlloDerm to reduce visibility . As for any surgical procedure , the surgeon should be made aware of the patient ' s overall status as monitored by the anesthesiologist . If extraocular muscle manipulation is forthcoming inform the anesthesia staff , so that bradycardia secondary to the oculocardiac reflex can be identified and communicated . The bradycardia should abate with release of the extraocular muscles . Postoperative Details Elevate the patient ' s head to 30 ° . Gently place gauze soaked in iced saline over the closed eyelids . Assess visual acuity and pupillary function every 15 minutes for the first hour and every 30 minutes until discharge . Nose blowing , strenuous activity , and straining should be avoided in the immediate postoperative period . Instruct the patient to use cool compresses for 48 hours , to finish all prescribed oral antibiotics , and to use analgesics sparingly . Postoperative oral steroids may help reduce swelling . Any change in visual acuity or increase in pain should prompt the patient to contact the surgeon immediately . Follow - up Follow - up examinations should assess and document visual acuity , pupillary and extraocular muscle function , neuralgia , and the amount of enophthalmos and diplopia . Complications As with any surgical procedure , bleeding , infection , and the need for additional surgery are risks . The possible loss of vision is the most ominous complication associated with floor repair . Residual or new - onset diplopia , neuralgia , and extraocular muscle dysfunction are potential complications . The patient should understand these risks completely , and no promises are to be made concerning resolution of any presurgical neuralgia . 24 Implant extrusion and residual enophthalmos are postoperative sequelae requiring additional surgery . Although the surgery may be a complete success in the eyes of the surgeon , the patient may view the outcome as unsatisfactory . To minimize this , the surgeon and patient should be in mutual agreement regarding the realistic outcome of the repair . Outcome and Prognosis Successful repair of orbital blowout fractures may be complicated by persistent problems . Neuralgia in the distribution of the infraorbital nerve may worsen after surgery . Improvement of this problem , if any , may take 6 months or more . More troubling is persistent diplopia . If isolated to extreme positions of gaze , it may go unnoticed or may not be bothersome to the patient . However , if the diplopia affects functional positions of gaze , corrective prisms can be tried . Ultimately , eye muscle surgery may be required to address this problem with repositioning of the extraocular muscles to allow for orthophoric fixation of images . A study by Su et al of 83 pediatric patients with orbital blowout fractures found that the length of time for postoperative recovery from diplopia was associated with age , with the younger patients taking longer to recover than the older ones . 25 Enophthalmos can worsen over time . Despite adequately repairing the fracture , atrophy of the orbital fat can occur , resulting in further enophthalmos . Future and Controversies The timing and indications for reconstruction of orbital floor fractures remain controversial . Early repair ( within the first 2 wk ) often is indicated when criteria discussed within this article are met . However , these are at best broad guidelines and not absolute criteria for management . Patients who demonstrate significant improvement without signs of entrapment can be treated conservatively . Delayed repair is also an option in select patients . Even after the fracture is repaired , further surgery may be needed for persistent diplopia . Questions Sections Orbital Floor Fractures ( Blowout ) Overview Workup Treatment Questions & Answers Media Gallery References
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[
"Orbital Floor Fractures",
"Medical treatment",
"enophthalmos"
] |
http://emedicine.medscape.com/article/1298345-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Plastic Surgery Vascular Ulcers Updated : Aug 02 , 2018 Author : Allen Gabriel , MD , FACS ; Chief Editor : Joseph A Molnar , MD , PhD , FACS more . . . Sections Overview Problem Epidemiology Etiology Pathophysiology Presentation Indications Contraindications Show All Workup Treatment Media Gallery References Problem Ulcers of the lower extremities , particularly in individuals older than 65 years , are a common cause for visits to the podiatrist , wound care specialist , primary care physician , vascular surgeon , or dermatologist . 1 The great majority of vascular ulcers are chronic or recurrent . They cause a considerable amount of morbidity among patients with peripheral vascular disease , including work incapacity . The care of chronic vascular ulcers places a significant burden on the patient and the health care system . Additionally , these nonhealing ulcers place the patient at much higher risk for lower extremity amputation 2 Next : Epidemiology What to Read Next on Medscape Related Conditions and Diseases Wound Care Pressure Injuries ( Pressure Ulcers ) and Wound Care Thermal Injury Management Initial Evaluation and Management of the Burn Patient Regional Anesthesia For Postoperative Pain Control Diabetic Ulcers News & Perspective Wound Management Preclinical and Clinical Studies of Hyaluronic Acid in Wound Care Advances in Wound Management Tools Drug Interaction Checker Pill Identifier Calculators Formulary Slideshow Gunshot Wounds : A Targeted Approach Most Popular Articles According to Plastic Surgeons Making Sense of Stem Cells and Fat Grafting in Plastic Surgery Implications of Aging in Plastic Surgery Analysis of the Popular Social Media for Plastic Surgeons FDA Warns ' Bad Actor ' Doc Over Illegal Marketing of Breast Device Prepectoral Breast Reconstruction : A Technical Algorithm View More Sections Vascular Ulcers Overview Epidemiology Etiology Pathophysiology Presentation Indications Contraindications Show All Workup Treatment Media Gallery References Recommended Wound Management Journal Article Advances in Wound Management
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[
"Vascular Ulcers",
"peripheral vascular disease"
] |
http://emedicine.medscape.com/article/136217-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Allergy & Immunology Immediate Hypersensitivity Reactions Updated : Feb 09 , 2015 Author : Becky Buelow , MD , MS ; Chief Editor : Michael A Kaliner , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Follow - up Tables References Background The immune system is an integral part of human protection against disease , but the normally protective immune mechanisms can sometimes cause detrimental reactions in the host . Such reactions are known as hypersensitivity reactions , and the study of these is termed immunopathology . The traditional classification for hypersensitivity reactions is that of Gell and Coombs and is currently the most commonly known classification system . 1 It divides the hypersensitivity reactions into the following 4 types : Type I reactions ( ie , immediate hypersensitivity reactions ) involve immunoglobulin E ( IgE ) – mediated release of histamine and other mediators from mast cells and basophils . 2 Examples include anaphylaxis and allergic rhinoconjunctivitis . Type II reactions ( ie , cytotoxic hypersensitivity reactions ) involve immunoglobulin G or immunoglobulin M antibodies bound to cell surface antigens , with subsequent complement fixation . An example is drug - induced hemolytic anemia . Type III reactions ( ie , immune - complex reactions ) involve circulating antigen - antibody immune complexes that deposit in postcapillary venules , with subsequent complement fixation . An example is serum sickness . Type IV reactions ( ie , delayed hypersensitivity reactions , cell - mediated immunity ) are mediated by T cells rather than by antibodies . An example is contact dermatitis from poison ivy or nickel allergy . Some authors believe this classification system may be too general and favor a more recent classification system proposed by Sell et al . 3 This system divides immunopathologic responses into the following 7 categories : Inactivation / activation antibody reactions Cytotoxic or cytolytic antibody reactions Immune - complex reactions Allergic reactions T - cell cytotoxic reactions Delayed hypersensitivity reactions Granulomatous reactions This system accounts for the fact that multiple components of the immune system can be involved in various types of hypersensitivity reactions . For example , T cells play an important role in the pathophysiology of allergic reactions ( see Pathophysiology ) . In addition , the term immediate hypersensitivity is somewhat of a misnomer because it does not account for the late - phase reaction or for the chronic allergic inflammation that often occurs with these types of reactions . Allergic reactions manifest clinically as anaphylaxis , allergic asthma , urticaria , angioedema , allergic rhinitis , some types of drug reactions , and atopic dermatitis . These reactions tend to be mediated by IgE , which differentiates them from non - IgE - mediated ( formerly called anaphylactoid ) reactions that involve IgE - independent mast cell and basophil degranulation . Such reactions can be caused by iodinated radiocontrast dye , opiates , or vancomycin and appear similar clinically to urticaria or even anaphylaxis . 4 5 Patients prone to IgE - mediated allergic reactions are said to be atopic . Atopy is the genetic predisposition to make IgE antibodies in response to allergen exposure . 6 The focus of this article is allergic reactions in general . Although some of the clinical manifestations listed previously are briefly mentioned , refer to the articles on these topics for more detail . For example , see Allergic and Environmental Asthma Anaphylaxis Food Allergies Rhinitis , Allergic ; and Urticaria Pathophysiology Immediate hypersensitivity reactions are mediated by IgE , but T and B cells play important roles in the development of these antibodies . CD4 + T - cells are divided into 3 broad classes : effector T - cells , memory T - cells , and T - regulatory ( Treg ) cells . Effector T - cells are further divided based on the cytokines they produce : TH1 , TH2 , and TH17 cells . TH1 cells produce interferon - gamma and interleukin ( IL ) - 2 , and promote a cell - mediated immune response . TH2 57 Memory T - cells rapidly differentiate into effector T - cells in secondary immune responses . CD4 + CD25 + FOXP3 + Treg cells are essential in peripheral tolerance and serve to suppress dysregulated immuneresponses . CD4 + CD25 + FOXP3 + Tregs inhibit TH2 cytokine production through the secretion and action of IL - 10 and TGF - beta . Proper function of CD4 + CD25 + FOXP3 + Treg cells has been shown to be important in the tolerance of allergens . 8 Abnormalities in the CD4 + CD25 + FOXP3 + Treg population may play a role in the development of allergic disease . The allergic reaction first requires sensitization to a specific allergen and occurs in genetically predisposed individuals . The allergen is either inhaled or ingested and is then processed by an antigen - presenting cell ( APC ) , such as a dendritic cell , macrophage , or B - cell . 7 8 The antigen - presenting cells then migrate to lymph nodes , where they prime naïve TH cells that bear receptors for the specific antigen . After antigen priming , naïve TH cells differentiate into TH1 , TH2 , or TH17 cells based upon antigen and cytokine signaling . In the case of allergen sensitization , the differentiation of naïve TH cells is skewed toward a TH2 phenotype . These allergen - primed TH2 cells then release IL - 4 , IL - 5 , IL - 9 , and IL - 13 . IL - 5 plays a role in eosinophil development , recruitment , and activation . IL - 9 plays a regulatory role in mast cells activation . IL - 4 and IL For this to occur , B cells must also bind to the allergen via allergen - specific receptors . They then internalize and process the antigen and present peptides from it , bound to the major histocompatibility class II molecules found on B - cell surfaces , to the antigen receptors on TH2 cells . The B cell must also bind to the TH2 cell and does so by binding the CD40 expressed on its surface to the CD40 ligand on the surface of the TH2 cell . IL - 4 and IL - 13 released by the TH2 cells Immediate hypersensitivity reactions . Sensitization phase of an immunoglobulin E – mediated allergic reaction . The antigen - specific IgE antibodies can then bind to high - affinity receptors located on the surfaces of mast cells and basophils . Reexposure to the antigen can then result in the antigen binding to and cross - linking the bound IgE antibodies on the mast cells and basophils . This causes the release and formation of chemical mediators from these cells . These mediators include preformed mediators , newly synthesized mediators , and cytokines . The major mediators and their functions are described as follows : 9 10 Preformed mediators See the list below : Histamine : This mediator acts on histamine 1 ( H1 ) and histamine 2 ( H2 ) receptors to cause contraction of smooth muscles of the airway and GI tract , increased vasopermeability and vasodilation , enhanced mucus production , pruritus , cutaneous vasodilation , and gastric acid secretion . Tryptase : Tryptase is a major protease released by mast cells . Its role is not completely understood , but it can cleave C3 , C3a , and C5 in addition to playing a role in airway remodeling . 11 Tryptase is found in all human mast cells but in few other cells and thus is a good marker of mast cell activation . Proteoglycans : Proteoglycans include heparin and chondroitin sulfate . The role of the latter is unknown ; heparin seems to be important in storing the preformed proteases and may play a role in the production of alpha - tryptase . Chemotactic factors : An eosinophilic chemotactic factor of anaphylaxis causes eosinophil chemotaxis ; an inflammatory factor of anaphylaxis results in neutrophil chemotaxis . Eosinophils release major basic protein and , together with the activity of neutrophils , can cause significant tissue damage in the later phases of allergic reactions . Newly formed mediators Arachidonic acid metabolites Leukotrienes - Produced via the lipoxygenase pathway : Leukotriene B4 - Neutrophil chemotaxis and activation , augmentation of vascular permeability Leukotrienes C4 and D4 - Potent bronchoconstrictors , increase vascular permeability , and cause arteriolar constriction Leukotriene E4 - Enhances bronchial responsiveness and increases vascular permeability Leukotrienes C4 , D4 , and E4 - Comprise what was previously known as the slow - reacting substance of anaphylaxis Cyclooxygenase products : Prostaglandin D2 - Produced mainly by mast cells ; bronchoconstrictor , peripheral vasodilator , coronary and pulmonary artery vasoconstrictor , platelet aggregation inhibitor , neutrophil chemoattractant , and enhancer of histamine release from basophils Prostaglandin F2 - alpha - Bronchoconstrictor , peripheral vasodilator , coronary vasoconstrictor , and platelet aggregation inhibitor Thromboxane A2 - Causes vasoconstriction , platelet aggregation , and bronchoconstriction Platelet - activating factor ( PAF ) : PAF is synthesized from membrane phospholipids via a different pathway from arachidonic acid . It aggregates platelets but is also a very potent mediator in allergic reactions . It increases vascular permeability , causes bronchoconstriction , and causes chemotaxis and degranulation of eosinophils and neutrophils . Adenosine : This is a bronchoconstrictor that also potentiates IgE - induced mast cell mediator release . Bradykinin : Kininogenase released from the mast cell can act on plasma kininogens to produce bradykinin . An additional ( or alternative ) route of kinin generation , involving activation of the contact system via factor XII by mast cell – released heparin , has been described . 12 13 Bradykinin increases vasopermeability , vasodilation , hypotension , smooth muscle contraction , pain , and activation of arachidonic acid metabolites . However , its role in IgE - mediated allergic reactions has not been clearly demonstrated . 4 Cytokines See the list below : IL - 4 : IL - 4 stimulates and maintains TH2 cell proliferation and switches B cells to IgE synthesis . IL - 5 : IL - 5 is key in the maturation , chemotaxis , activation , and survival of eosinophils . IL - 5 primes basophils for histamine and leukotriene release . IL - 6 : IL - 6 promotes mucus production . IL - 13 : IL - 13 has many of the same effects as IL - 4 . Tumor necrosis factor - alpha : Tumor necrosis factor - alpha is a pro - inflammatory cytokine which activates neutrophils and eosinophils and increases monocyte chemotaxis . 14 The collective biological activities of the aforementioned mediators can cause variable clinical responses depending on which organ systems are affected , as follows : Urticaria / angioedema : Release of the above mediators in the superficial layers of the skin can cause pruritic wheals with surrounding erythema . If deeper layers of the dermis and subcutaneous tissues are involved , angioedema results . Angioedema is swelling of the affected area ; it tends to be painful rather than pruritic . Allergic rhinitis : Release of the above mediators in the upper respiratory tract can result in sneezing , itching , nasal congestion , rhinorrhea , and itchy or watery eyes . Allergic asthma : Release of the above mediators in the lower respiratory tract can cause bronchoconstriction , mucus production , and inflammation of the airways , resulting in chest tightness , shortness of breath , and wheezing . Anaphylaxis : Systemic release of the above , resulting in symptoms in 2 or more organ systems , is considered anaphylaxis . In addition to the foregoing symptoms , the GI system can also be affected with nausea , abdominal cramping , bloating , and diarrhea . Systemic vasodilation and vasopermeability can result in significant hypotension and is referred to as anaphylactic shock . Anaphylactic shock is one of the two most common causes for death in anaphylaxis ; the other is throat swelling and asphyxiation . 10 Allergic reactions can occur as immediate reactions , late - phase reactions , or chronic allergic inflammation . Immediate or acute - phase reactions occur within seconds to minutes after allergen exposure . Some of the mediators released by mast cells and basophils cause eosinophil and neutrophil chemotaxis . Attracted eosinophils and resident lymphocytes are activated by mast cell mediators . These and other cells ( eg , monocytes , T cells ) are believed to cause the late - phase reactions that can occur hours after antigen exposure and after the signs or symptoms of the acute - phase reaction have resolved . The signs and symptoms of the late - phase reaction can include redness and swelling of the skin , nasal discharge , airway narrowing , sneezing , coughing , and wheezing . These effects can last a few hours and usually resolve within 24 - 72 hours . Finally , continuous or repeated exposure to an allergen ( eg , a cat - allergic patient who owns a cat ) can result in chronic allergic inflammation . Tissue from sites of chronic allergic inflammation contains eosinophils and T cells ( particularly TH2 cells ) . Eosinophils can release many mediators ( eg , major basic protein ) , which can cause tissue damage and thus increase inflammation . Collectively , this results in structural and functional changes to the affected tissue . Furthermore , a repeated allergen challenge can result in increased levels of antigen - specific IgE Epidemiology Frequency United States The prevalence of atopic diseases ( i.e. , asthma , allergic rhinitis , food allergy , and atopic dermatitis ) has increased since the year 2000 . Allergic rhinitis is the most prevalent allergic disease ; 6 it affects approximately 17 - 22 % or more of the population . 15 Asthma was estimated to affect approximately 25.7 million people in the United States in 2010 . Asthma prevalence increased from 7.3 % in 2001 to 8.4 % in 2010 . 16 Ninety percent of asthma cases in children are estimated to be allergic , compared with 50 - 70 % in adults . 15 Atopic dermatitis has increased in prevalence worldwide over the last decade . The prevalence of anaphylaxis may be as high as 2 % , with an increase in younger patients . 17 International Approximately 300 million people worldwide are estimated to have asthma . Prevalence rates vary around the world and are estimated to be from 3 - 38 % in children 18 and 2 - 12 % in adults . 19 The International Study of Asthma and Allergies in Childhood ( ISAAC ) is an epidemiological research program that was established in 1991 to evaluate asthma , eczema , and allergic rhinitis in children worldwide . The study is composed of 3 phases . Phase 1 used questionnaires designed to assess the prevalence and severity of asthma and allergic disease in defined populations in centers around the world . Most of this data was collected in the mid 1990s . Phase 2 was designed to assess possible etiological factors based on information gathered from Phase 1 . Phase 3 is a 20 Data from ISAAC show variations in the prevalence of allergic diseases between countries . ISAAC researchers found significant variability in the prevalence of allergic rhinoconjunctivitis in children from 56 countries . Rates varied from 1.4 - 39.7 % and , although sites varied , a general trend of increasing prevalence of allergic rhinoconjunctivitis was found over the 7 years between phases 1 and 3 . 21 Similar to other allergic diseases , the prevalence in atopic dermatitis varies widely between countries . Prevalence varies from 1.4 % in China to 21.8 % in Morocco , and prevalence is generally increasing . 21 Asthma , as with other atopic diseases , was previously increasing in prevalence . 22 23 Data from a study from England suggest that the prevalence of asthma , allergic rhinitis , and atopic dermatitis may be stabilizing . 24 Hospital admissions for anaphylaxis , however , have increased by 600 % over the past decade in England and by 400 % for food allergy . Admission rates for urticaria increased 100 % , and admission rates for angioedema increased 20 % , which suggests that these allergic diseases may be increasing in prevalence . Studies in Africa and Europe have shown a greater prevalence of reversible bronchospasm in urban populations than in rural populations . This difference was initially thought to be related to environmental pollution , but the results from studies of asthma prevalence before and after the unification of Germany contradict this theory . 25 The prevalence of asthma in East Germany prior to 1990 was lower than in West Germany , despite the fact that East Germany had more air pollution . Over the 10 years after unification , the prevalence of asthma in the former East Germany has increased and is now comparable with that of former West Germany . 25 In addition , children placed in day care and with older siblings have a lower likelihood of developing atopic disease . 26 These findings have led to the hygiene hypothesis , which proposes that early exposure to infectious agents or endotoxins helps direct the immune system toward a TH1 cell – predominant response that , in turn , inhibits the production of TH2 cells . A TH1 response does not lead to allergies , while a cleaner , more hygienic environment may lead to TH2 predominance and more allergies . 27 Mortality / Morbidity Mortality from allergic diseases occurs primarily from anaphylaxis and asthma , although deaths from asthma are relatively rare . Between 2007 - 2009 in the United States , the asthma death rate per 1,000 persons was 0.15 . 28 The death rate was 75 % higher for blacks compared to whites , 30 % higher for females compared to males , and nearly 7 times higher for adults than children . Approximately 500 people die annually from anaphylaxis in the United States . Allergic diseases are a significant cause of morbidity . In 2007 , $ 56 billion was spent on medical costs , lost school , and work days and early deaths due to asthma in the United States alone . 29 Children with untreated allergic rhinitis do worse on aptitude tests than their nonatopic peers . Race The reason for the differences in the prevalence of allergic diseases with respect to race are complex and not completely understood . In the US between 2008 - 2010 , multiracial individuals had the highest asthma prevalence at 14.1 % . 28 Next , blacks had a prevalence of 11.2 % , followed by American Indian / Alaska Native at 9.4 % , and whites at 7.7 % . Among the Hispanic population , the highest asthma prevalence rates were seen in persons of Puerto Rican ( 16.1 % ) and Mexican ( 5.4 % ) descents . Asthma prevalence was also higher in persons with a family income below the poverty level . Thus , it is likely that differences in allergic diseases among different racial or ethnic groups is multifactorial and includes genetic , environmental , and socioeconomic factors . Sex Some unexplained differences exist in the prevalence of allergic diseases between the sexes . Asthma is more prevalent in boys during the first decade of life ; after puberty , prevalence is higher in females . 9 The male - to - female ratio of children who have atopic disease is nearly 2 : 1 . Skin test reactivity in women can fluctuate with the menstrual cycle , but this is not clinically significant . Age In general , allergic rhinitis symptoms ( and skin test reactivity ) tend to wane with increasing age . Food allergies and subsequent anaphylaxis are more prevalent in children . Some children may outgrow their allergies to certain foods , or their reactions may diminish over time . However , anaphylaxis from food and other triggers is still a threat in adults . Some food allergies , such as allergy to shellfish , may last a lifetime . Childhood asthma is more prevalent in boys and can often resolve by adulthood . However , females tend to develop asthma later in life ( beginning in adolescence ) and can also have asthma that is more severe . Clinical Presentation
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[
"Immediate Hypersensitivity Reactions",
"immunoglobulin E",
"immunoglobulin G"
] |
http://emedicine.medscape.com/article/152083-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Cardiology Cardiac Tamponade Updated : Nov 28 , 2018 Author : Chakri Yarlagadda , MD , FACC , FSCAI , FASNC , CCDS ; Chief Editor : Terrence X O ' Brien , MD , MS , FACC more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Practice Essentials Cardiac tamponade is a clinical syndrome caused by the accumulation of fluid in the pericardial space , resulting in reduced ventricular filling and subsequent hemodynamic compromise . The condition is a medical emergency , the complications of which include pulmonary edema , shock , and death . Signs and symptoms Symptoms vary with the acuteness and underlying cause of the tamponade . Patients with acute tamponade may present with dyspnea , tachycardia , and tachypnea . Cold and clammy extremities from hypoperfusion are also observed in some patients . Other symptoms and signs may include the following : Elevated jugular venous pressure Pulsus paradoxus Chest pressure Decreased urine output Confusion Dysphoria See Clinical Presentation for more detail . Diagnosis Prompt diagnosis is key to reducing the mortality risk for patients with cardiac tamponade . Although echocardiography provides useful information , cardiac tamponade is a clinical diagnosis . Echocardiography can be used to visualize ventricular and atrial compression abnormalities as blood cycles through the heart . The following may be observed with 2 - dimensional ( 2 - D ) echocardiography : An echo - free space posterior and anterior to the left ventricle and behind the left atrium Early diastolic collapse of the right ventricular free wall Late diastolic compression / collapse of the right atrium Swinging of the heart in the pericardial sac Left ventricular pseudohypertrophy Inferior vena cava plethora with minimal or no collapse with inspiration A greater than 40 % relative inspiratory augmentation of blood flow across the tricuspid valve A greater than 25 % relative decrease in inspiratory flow across the mitral valve See Workup for more detail . Management Removal of pericardial fluid is the definitive therapy for tamponade and can be done using the following three methods : Emergency subxiphoid percutaneous drainage Pericardiocentesis ( with or without echocardiographic guidance ) Percutaneous balloon pericardiotomy The role of medication therapy in cardiac tamponade is limited . Treatment and Medication Background Cardiac tamponade is a clinical syndrome caused by the accumulation of fluid in the pericardial space , resulting in reduced ventricular filling and subsequent hemodynamic compromise . The condition is a medical emergency , the complications of which include pulmonary edema , shock , and death . ( See Pathophysiology Etiology , and Prognosis . ) The overall mortality risk depends on the speed of diagnosis , the treatment provided , and the underlying cause of the tamponade . Untreated , the condition is rapidly and universally fatal ( see the image below ) . ( See Presentation , and . ) This anteroposterior - view chest radiograph shows a massive , bottle - shaped heart and conspicuous absence of pulmonary vascular congestion . Reproduced with permission from Chest , 1996 : 109 : 825 . View Media Gallery Pathophysiology The pericardium , which is the membrane surrounding the heart , is composed of 2 layers . The thicker parietal pericardium is the outer fibrous layer ; the thinner visceral pericardium is the inner serous layer . The pericardial space normally contains 20 - 50mL of fluid . Reddy et al describe 3 phases of hemodynamic changes in tamponade , as follows 1 Phase I - The accumulation of pericardial fluid impairs relaxation and filling of the ventricles , requiring a higher filling pressure ; during this phase , the left and right ventricular filling pressures are higher than the intrapericardial pressure Phase II - With further fluid accumulation , the pericardial pressure increases above the ventricular filling pressure , resulting in reduced cardiac output ( see the Cardiac Output calculator ) Phase III - A further decrease in cardiac output occurs , which is due to the equilibration of pericardial and left ventricular ( LV ) filling pressures Pericardial effusions , which cause cardiac tamponade , can be serous , serosanguineous , hemorrhagic , or chylous . The underlying process for the development of tamponade is a marked reduction in diastolic filling , which results when transmural distending pressures become insufficient to overcome increased intrapericardial pressures . Tachycardia is the initial cardiac response to these changes to maintain the cardiac output . Systemic venous return is also altered during tamponade . Because the heart is compressed throughout the cardiac cycle due to the increased intrapericardial pressure , systemic venous return is impaired and right atrial and right ventricular collapse occurs . Because the pulmonary vascular bed is a vast and compliant circuit , blood preferentially accumulates in the venous circulation , at the expense of LV filling . This results in reduced cardiac output and venous return . The amount of pericardial fluid needed to impair diastolic filling of the heart depends on the rate of fluid accumulation and the compliance of the pericardium . Rapid accumulation of as little as 150mL of fluid can result in a marked increase in pericardial pressure and can severely impede cardiac output , 2 whereas 1000 mL of fluid may accumulate over a longer period without any significant effect on diastolic filling of the heart . This is due to adaptive stretching of the pericardium over time . A compliant pericardium can allow considerable fluid accumulation over a long time period without hemodynamic compromise . Etiology For all patients , malignant diseases are the most common cause of pericardial tamponade . Among etiologies for tamponade , Merce et al reported the following incidence rates : Malignant diseases - 30 - 60 % of cases Uremia - 10 - 15 % of cases Idiopathic pericarditis - 5 - 15 % Infectious diseases - 5 - 10 % Anticoagulation - 5 - 10 % Connective tissue diseases - 2 - 6 % Dressler or postpericardiotomy syndrome - 1 - 2 % Tamponade can occur as a result of any process that causes pericarditis . Pericarditis can result from the following 3 Human immunodeficiency virus ( HIV ) infection Infection - Viral , bacterial ( tuberculosis ) , fungal Drugs - Hydralazine , procainamide , isoniazid , minoxidil Postcoronary intervention - Ie , coronary dissection and perforation Acupuncture 4 Postcardiac percutaneous procedures - Including mitral valvuloplasty , atrial septal defect ( ASD ) closure , left atrial appendage occlusion Trauma to the chest Cardiovascular surgery - Postoperative pericarditis 5 Postmyocardial infarction - Free wall ventricular rupture , Dressler syndrome Connective tissue diseases - Systemic lupus erythematosus , rheumatoid arthritis , dermatomyositis Radiation therapy to the chest , radiofrequency ablation 6 Iatrogenic 7 - After sternal biopsy , transvenous pacemaker lead implantation , pericardiocentesis , or central line insertion Uremia Anticoagulation treatment Idiopathic pericarditis Complication of surgery at the esophagogastric junction - Eg , antireflux surgery Pneumopericardium - Due to mechanical ventilation or gastropericardial fistula Hypothyroidism Still disease Duchenne muscular dystrophy Type A aortic dissection Streptococcus constellatus infection ( very rare ; only 3 cases in the literature ) 8 In patients undergoing heart valve surgery , cardiac tamponade has been associated with any amount of pericardial effusion at the first postoperative transthoracic echocardiography as well as with mechanical valve replacement of the aortic or mitral valve . 9 Epidemiology Occurrence in the United States The incidence of cardiac tamponade is 2 cases per 10,000 population in the United States . Approximately 2 % of penetrating injuries are reported to result in cardiac tamponade . Sex - and age - related demographics In children , cardiac tamponade is more common in boys than in girls , with a male - to - female ratio of 7 : 3 . In adults , cardiac tamponade appears to be slightly more common in men than in women . A male - to - female ratio of 1.25 : 1 was observed at the author ' s referral center , based on the International Classification of Diseases ( ICD ) code 423.9 . However , a male - to - female ratio of 1.7 : 1 was observed at another level 1 trauma center . Cardiac tamponade related to trauma or HIV is more common in young adults , whereas tamponade due to malignancy and / or renal failure occurs more frequently in elderly individuals . Prognosis Cardiac tamponade is a medical emergency . The prognosis depends on prompt recognition and management of the condition and the underlying cause of the tamponade . Untreated , cardiac tamponade is rapidly and universally fatal . Haneya et al retrospectively ( 2005 - 2011 ) evaluated the impact of timing and indication of reexploration for bleeding or tamponade following cardiac surgery in 209 patients and found that reexploration was associated with higher rates of mortality and morbidity . 10 Multivariate analysis indicated it was the adverse effects of reexploration ( eg , blood loss , transfusion requirements ) rather than the procedure itself that were independent risk factors for death . Adverse outcomes were more likely in those whose reexploration was delayed and who suffered from cardiac tamponade . 10 In a separate study , Le et al indicated that following cardiac surgery , there is no advantage for the use of multiple mediastinal chest tubes over a single chest tube in preventing return to the operating room for bleeding or tamponade . 11 In addition to treatment for the tamponade , all patients should also receive treatment for the condition ’ s underlying cause in order to prevent recurrence . In a study of patients with cardiac tamponade , Cornily et al reported a 1 - year mortality rate of 76.5 % in patients whose tamponade was caused by malignant disease , compared with 13.3 % in patients with no malignant disease . The investigators also noted a median survival of 150 days in patients with malignant disease . 12 Clinical Presentation Sections Cardiac Tamponade Overview DDx Questions & Answers Media Gallery References
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[
"Cardiac Tamponade",
"clinical syndrome",
"Chest pressure"
] |
http://emedicine.medscape.com/article/161080-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Cardiology Pulseless Electrical Activity Treatment & Management Updated : Mar 27 , 2018 Author : Sandy N Shah , DO , MBA , FACC , FACP , FACOI ; Chief Editor : Jose M Dizon , MD more . . . Sections Overview Presentation DDx Workup Treatment Approach Considerations Pharmacologic Therapy Surgical Care Show All Guidelines Medication Questions & Answers References Approach Considerations Once reversible causes of pulseless electrical activity ( PEA ) are identified , they should be corrected immediately . This process may involve needle decompression of pneumothorax , pericardiocentesis for tamponade , volume infusion , correction of body temperature , administration of thrombolytics , or surgical embolectomy for pulmonary embolus . Consultations Once the cause of PEA is identified and the patient ' s condition is stabilized , consultation with appropriate services may be obtained . A cardiothoracic surgery consult may be appropriate for a pulmonary embolectomy in patients with a large pulmonary embolus . In patients with drug overdose , consultation with the toxicology department or the local poison center may be useful after restoration of hemodynamic stability . Transfer Some institutions may not have the capability to provide specialized care ( eg , cardiac surgery , pulmonary embolectomy ) . Once stabilized , patients in these centers may be transferred to tertiary care centers for definitive care . Prevention The following measures may prevent some cases of in - hospital PEA : Patients who have been on prolonged bed rest should receive deep venous thrombosis ( DVT ) prophylaxis . Patients who are on ventilators should be monitored carefully for the development of auto – positive - end - expiratory pressure ( PEEP ) . Hypovolemia should be treated aggressively , especially in patients with active bleeding . Next : Pharmacologic Therapy
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[
"PEA",
"pneumothorax",
"volume infusion"
] |
http://emedicine.medscape.com/article/1689966-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Genomic Medicine Breast Cancer and HER2 Overview of HER2 Breast Cancer Updated : Mar 14 , 2019 Author : Maurie Markman , MD , MS ; Chief Editor : Karl S Roth , MD more . . . Sections Practice Essentials Overview of HER2 Breast Cancer Testing for HER2 Adjuvant Therapy for HER2 - Positive Breast Cancer Treatment of HER2 - Positive Metastatic Breast Cancer Novel HER2 Receptor Agents Questions & Answers Show All References Practice Essentials ERBB2 is a transmembrane tyrosine kinase receptor and a member of the ErbB protein family ( ie , the epidermal growth factor receptor [ EGFR ] family ) . ERBB2 is most commonly known as HER2 and sometimes also as NEU . For this article , it will be referred to as HER2 . HER2 gene product is overexpressed in 18 - 20 % of invasive breast cancers . 1 The American Society of Clinical Oncology and the College of American Pathologists issued the following updated recommendations for HER2 testing in breast cancer 2 HER2 status should be determined in all patients with invasive breast cancer on the basis of 1 or more test results . HER2 - positive status is indicated by evidence of protein overexpression or gene amplification . When results are equivocal , reflex testing should be performed with an alternative assay , and repeat testing should be considered if results are discordant with other findings . Laboratories should be able to show high concordance with a validated HER2 test on a large and representative set of specimens , and testing must be performed in an accredited laboratory . Providers should recommend HER2 - targeted therapies if the patient ' s HER2 test result is positive and such treatment is clinically appropriate . Most experts do not recommend HER2 - targeted therapy if the HER2 test result is negative and there is no histopathologic discordance with HER2 testing . Delay the decision to recommend HER2 - targeted therapy if the HER2 test result is equivocal . Reflex testing should be done on the same specimen . These recommendations have also been adapted and studied in other countries , such as England , France , and Italy . 3 4 5 Testing for HER2 Testing for HER2 may be done by means of either immunohistochemistry ( IHC ) or fluorescence in situ hybridization ( FISH ) . The scoring method for HER2 expression on IHC is based on the cell membrane staining pattern and is as follows : 3 + : Positive HER2 expression - Uniform intense membrane staining of more than 30 % of invasive tumor cells . 2 + : Equivocal for HER2 protein expression - Complete membrane staining that is either nonuniform or weak in intensity but has circumferential distribution in at least 10 % of cells . 0 or 1 + : Negative for HER2 protein expression . HER2 test results must be reported as indeterminate if technical issues prevent one or both tests from being interpreted accurately . FISH has been used to establish HER2 status when IHC yields equivocal results , but it is now also being used alone for this purpose in an increasing number of centers . The interpretation for HER2 FISH testing ( HER2 - to - CEP17 ratio and gene copy number ) is as follows : Positive HER2 amplification : FISH ratio higher than 2.2 or HER2 gene copy greater than 6.0 . Equivocal amplification : FISH ratio of 1.8 - 2.2 or gene copy of 4.0 - 6.0 . Negative amplification : FISH ratio lower than 1.8 or gene copy less than 4.0 . Treatment of HER2 - positive breast cancer HER2 agents used in adjuvant therapy for HER2 - positive breast cancer include the following : Trastuzumab Neratinib , extended adjuvant therapy following trastuzumab - based therapy Lapatinib , particularly in combination with capecitabine Pertuzumab Agents used in the treatment of HER2 - positive metastatic breast cancer include the following : Trastuzumab ( in conjunction with other chemotherapy ) Ado - trastuzumab emtansine Lapatinib Pertuzumab Novel HER2 agents under evaluation include the following : Amrubicin Dasatinib HER2 chimeric receptor and TGF - beta dominant negative receptor expressing EBV - specific lymphocytes Overview of HER2 Breast Cancer ERBB2 is a transmembrane tyrosine kinase receptor and a member of the ErbB protein family , more commonly known as the epidermal growth factor receptor ( EGFR ) family . ERBB2 is most commonly known as HER2 and sometimes as also NEU . For this article , it will be referred to as HER2 . Activation of this class of cellular receptors is known to result in increased activity of a variety of molecular pathways associated with tumor growth and progression . HER2 gene product is overexpressed in 18 - 20 % of invasive breast cancers , which has both Before the routine use of trastuzumab ( Herceptin , a monoclonal antibody ) in adjuvant therapy , HER2 overexpression was associated with a more aggressive tumor phenotype and worse prognosis ( higher rate of recurrence and mortality ) , independent of other clinical features ( eg , age , stage , tumor grade ) , especially in patients who did not receive adjuvant chemotherapy . Additionally , HER2 status has been shown to be predictive for response to certain chemotherapeutic agents ( ie , doxorubicin [ Adriamycin ] ; and HER2 - targeted therapies trastuzumab , pertuzumab , and lapatinib [ Tykerb , a small - molecule oral tyrosine kinase inhibitor directed specifically to the HER2 receptor ] ) . Retrospectively analyzed results from clinical trials have shown that HER2 - positive patients benefit from anthracycline - based regimens secondary to the co - amplification of topoisomerase II with . Preliminary data also suggest that HER2 may predict response to and benefit from paclitaxel in the adjuvant setting . Go to Breast Cancer for complete information on this topic . Although several methods for HER2 testing have been developed , approximately 20 % of current HER2 testing may be inaccurate . Therefore , the American Society of Clinical Oncology ( ASCO ) and the College of American Pathologists ( CAP ) have recommended guidelines in HER2 testing to ensure accuracy . Breast cancer specimens should initially undergo HER2 testing by a validated immunohistochemistry ( IHC ) assay ( ie , HercepTest , Dako , Glostrup , Denmark ) for HER2 protein expression . 6 The scoring method for HER2 expression is based on the cell membrane staining pattern and is as follows : 3 + : Positive HER2 expression - Uniform intense membrane staining of more than 30 % of invasive tumor cells . 2 + : Equivocal for HER2 protein expression - Complete membrane staining that is either nonuniform or weak in intensity but has circumferential distribution in at least 10 % of cells . 0 or 1 + : Negative for HER2 protein expression . Breast cancer specimens with equivocal IHC should undergo validation using a gene amplification method , such as fluorescence in situ hybridization ( FISH ) . More centers are relying on FISH alone for determining HER2 status . In general , FISH testing is thought to be more reliable than IHC , but it is more expensive . Equivocal IHC results can be seen in 15 % of invasive breast cancers , whereas equivocal FISH results are seen in less than 3 % of invasive breast cancer specimens and those that had previously been considered positive . Discordant results ( IHC 3 + / FISH negative or IHC less than 3 + / FISH positive ) have been observed in approximately 4 % of specimens . Currently , no data support excluding this group from treatment with trastuzumab . Newer methodologies for establishing HER2 status , including reverse transcriptase – polymerase chain reaction ( RT - PCR ) and chromogenic in situ hybridization ( CISH ) , have not yet been validated . The interpretation for HER2 FISH testing ( HER2 / CEP17 ratio and gene copy number ) is given below : Positive amplification : FISH ratio is greater than 2.2 or gene copy is greater than 6.0 . Equivocal amplification : FISH ratio of 1.8 - 2.2 or gene copy of 4.0 - 6.0 . Negative amplification : FISH ratio is less than 1.8 or gene copy of less than 4.0 . Adjuvant Therapy for HER2 - Positive Breast Cancer Overexpression of HER2 occurs in approximately 20 % of breast cancers and was correlated with a more aggressive phenotype and worse prognosis before the development of HER2 - targeted therapies . The advent of trastuzumab , a monoclonal antibody ( mAb ) targeting the extracellular domain of the receptor , has changed the treatment paradigm for HER2 - positive breast cancer . Trastuzumab has a powerful synergism with a variety of chemotherapeutics , yet lacks the side effects ( with the notable exception of cardiotoxicity , which means it generally should not be given with anthracyclines ) . Results are available from studies ( HERA , FinHer , NSABP B - 31 , BCIRG006 , N9831 ) that have demonstrated that the inclusion of trastuzumab produces roughly a 50 % improvement in disease - free survival and 33 % improvement in overall survival , regardless of the chemotherapy regimen or sequence of trastuzumab delivery . These trials randomized 11,650 women with early - stage HER2 - positive breast cancer to trastuzumab versus non - trastuzumab - based adjuvant chemotherapy , and based on their results , trastuzumab was approved by the US Food and Drug Administration ( FDA Another study from the BCIRG006 further established that adjuvant trastuzumab for 1 year improved disease - free and overall survival among women with early - stage HER2 - positive breast cancer at 5 years , and found that a nonanthracycline regimen plus trastuzumab had a more favorable risk - benefit ratio than anthracycline - based regimens due to similar efficacy , fewer acute toxic effects , and lower risks of cardiotoxicity and leukemia . 7 Whether the combination of 2 anti - HER2 - targeted therapies with chemotherapy will prove beneficial in early - stage disease is currently being tested in the ongoing phase III ALTTO ( Adjuvant Lapatinib and / or Trastuzumab Treatment Options ) trial , as well as the similar Neo ALTTO ( Neoadjuvant Lapatinib and / or Trastuzumab Treatment Optimization ) trial . In February 2019 , the FDA approved trastuzumab / hyaluronidase ( Herceptin Hylecta ) in combination with chemotherapy for the treatment of select patients with HER2 - positive early breast cancer , in combination with paclitaxel in patients with metastatic HER2 - positive breast cancer as a frontline treatment , and alone for patients with metastatic disease who have received at least 1 prior chemotherapy regimen . This new SC formulation includes trastuzumab in combination with recombinant human hyaluronidase PH20 , an enzyme that allows a ready - to - use formulation for slow SC administration ( ie , given 8 Approval was based on two randomized trials , HannaH ( NCT00950300 ) and SafeHER ( NCT01566721 ) . In HannaH , patients with HER2 - positive operable or locally advanced breast cancer were randomized to receive 8 cycles of either SC trastuzumab or IV trastuzumab concurrently with chemotherapy , followed by surgery and continued therapy with either formulation of trastuzumab , for an additional 10 cycles . The endpoints for HannaH were pathologic complete response ( pCR ) and pharmacokinetics of both SC and IV trastuzumab . Pathological complete response was observed in 45.4 % of patients receiving Herceptin Hylecta 9 SafeHER was a prospective , two - cohort , nonrandomized , multinational , open - label trial assessing the overall safety and tolerability of SC trastuzumab with chemotherapy in patients with HER2 - positive breast cancer . SafeHER confirms safety and tolerability of adjuvant SC trastuzumab for HER2 - positive early breast cancer . 10 A study that evaluated the efficacy of lapatinib in HER2 - negative and HER2 - uncharacterized metastatic breast cancer concluded that although patients with HER2 - negative or HER2 - untested metastatic breast cancer did not experience benefit from the addition of lapatinib to paclitaxel , first - line therapy with paclitaxel - lapatinib significantly improved clinical outcomes in patients who were HER2 - positive . 11 Neratinib is an irreversible tyrosine - kinse inhibitor of EGFR , HER1 , HER2 , and HER4 . Dual blockade by antiangiogenic / HER2 agents ( eg , neratinib ) targeting HER and EGFR pathways produces greater inhibition of human breast cancer cell lines . In July 2017 , the FDA approved neratinib for extended adjuvant therapy for early stage HER2 positive breast cancer following adjuvant trastuzumab - based therapy . 12 The approval was based on the the phase 3 ExteNET trial , a multicenter , randomized , double - blind , placebo - controlled trial of neratinib following adjuvant trastuzumab treatment . After 2 years of follow - up , invasive disease - free survival ( iDFS ) was 94.2 % in patients treated with neratinib , compared with 91.9 % in those receiving placebo . 13 Baselga et al reported that adding pertuzumab to traditional therapy with trastuzumab and docetaxel improved disease - free survival time in patients with HER2 - positive metastatic breast cancer . 14 Pertuzumab gained approvals for neoadjuvant treatment in combination with trastuzumab and docetaxel for patients with HER2 - positive , locally advanced , inflammatory , or early stage breast cancer . 15 Based on the findings from the APHINITY trial , pertuzumab was also approved for the use in combination with trastuzumab and chemotherapy for adjuvant treatment of patients with HER2 - positive early breast cancer at high risk of recurrence . In the multicenter , double - blind , placebo - controlled study , 4804 patients with HER2 - positive early breast cancer were randomized to receive pertuzumab or placebo , in combination with adjuvant trastuzumab and chemotherapy . At a median follow - up of 45.4 months , 7.1 % patients in the pertuzumab group had developed invasive breast cancer , compared to 8.7 % patients in the placebo group . At 3 years , an estimated 94.1 % of patients in the pertuzumab group were free of invasive breast cancer , compared to 93.2 % of patients in the placebo group . 16 Treatment of HER2 - Positive Metastatic Breast Cancer In the metastatic setting , a pivotal phase III trial compared first - line chemotherapy ( doxorubicin / epirubicin and cyclophosphamide or paclitaxel ) plus trastuzumab versus chemotherapy alone in HER2 - positive patients . Trastuzumab plus chemotherapy was associated with a significant improvement in time to disease progression ( 7.4 mo vs 4.6 mo ) , objective response rate ( 50 % vs 32 % ) , and 1 - year survival ( 25.1 mo vs 20.3 mo ) compared with chemotherapy alone . 17 Additionally , there is evidence suggesting that up - front use of trastuzumab with chemotherapy , in women with advanced HER2 - positive breast cancer , prolongs life as compared with sequential administration , with trastuzumab reserved for the time of disease progression on an initial chemotherapy regimen . Based on these results , the FDA approved trastuzumab for first - line therapy in HER2 - positive metastatic breast cancer . However , the question of optimal duration of trastuzumab therapy remains unresolved . Clinical evidence to support continued trastuzumab treatment after initial progression has emerged . Retrospective studies have described a response to trastuzumab in multiple lines of therapy , and patients treated with more than 2 trastuzumab - containing regimens appear to have advantageous overall survival and TTP outcomes . Results from a prospective , randomized study of 112 patients with HER2 - positive metastatic breast cancer initially progressing on a trastuzumab - based therapy ( GBG - 26 / BIG 3 - 05 study ) showed that trastuzumab / capecitabine resulted in a longer progression - free survival ( 8.2 mo vs 5.6 mo ) and overall survival ( 25.5 mo vs 20.4 mo ) as compared with the capecitabine - only arm . 18 Objective response rates were also significantly improved in the combination arm ( 48.1 % ) versus capecitabine alone ( 27 % ) . Larger trials are currently ongoing to assess the activity of trastuzumab in multiple lines of treatment . Another agent used in the treatment of HER2 - positive metastatic breast cancer is lapatinib , a tyrosine kinase inhibitor ( TKI ) . Lapatinib was approved in 2007 for the treatment of metastatic breast cancer in HER2 - positive patients after progression on trastuzumab . This small molecule is known to block multiple epidermal growth factor receptors ( EGFRs ) , EGFR ( HER - 1 ) and HER2 , and is generally well tolerated , with the main toxicities being diarrhea , skin rash , fatigue , and nausea . An analysis of cardiac toxicity found that 1.6 % of patients exposed to lapatinib experienced a decline in left ventricular ejection fraction ( LVEF ) , with 0.2 % being symptomatic , lower than the comparable incidence observed with trastuzumab . 19 Preclinical data have indicated synergistic activity between lapatinib and trastuzumab , leading to a randomized study of this combination . A phase III trial involving 296 heavily pretreated , trastuzumab - refractory metastatic breast cancer patients randomized to treatment with lapatinib alone or lapatinib with trastuzumab reported combination therapy significantly improved progression - free survival ( 8.4 wks vs 12 wks ) compared with lapatinib alone . 20 There was a nonsignificant trend toward improved median overall survival . Diarrhea and rash were the most common side effects . An asymptomatic decline in LVEF was seen in 5 % of patients in the combination arm , compared with 2 % in the lapatinib - alone arm . In onestudy , 991 patients with HER2 - positive advanced breast cancer previously treated with trastuzumab and taxane were randomized to treatment with the antibody - drug conjugate trastuzumab emtansine or lapatinib plus capecitabine . Trastuzumab emtansine was shown to significantly prolong progression - free ( 9.6 months vs . 6.4 months ) and overall survival ( 30.9 months vs . 25.1 months ) compared with lapatinib plus capecitabine , and was associated with a better toxicity profile . 21 Baselga et al reported that adding pertuzumab to traditional therapy with trastuzumab and docetaxel improved disease - free survival time in patients with HER2 - positive metatstatic breast cancer . 14 For more information , see Novel HER2 Receptor Agents . See Breast Cancer Treatment Protocols for summarized information . Novel HER2 Receptor Agents Only 1 in 3 HER2 - positive metastatic breast cancer patients respond to single - agent trastuzumab , and most , if not all , eventually develop resistance . To overcome resistance , trastuzumab has been modified using a covalent linker to attach DM1 , a derivative of the microtubule destabilizer maytansine . Ado - trastuzumab ( Kadcyla ) was approved as a single agent for treatment of HER2 - positive , metastatic breast cancer in patients who have already undergone unsuccessful treatment with trastuzumab and a taxane , either separately or in combination . By exploiting trastuzumab to target the cytotoxic activity of DM1 to HER2 - overexpressing cells , ado - trastuzumab offers a novel mechanism for overcoming trastuzumab resistance . A phase I trial of every - 3 - week ado - trastuzumab demonstrated a clinical benefit rate of 53 % in metastatic breast cancer patients that had progressed on previous trastuzumab . Additionally , preliminary results from a phase II trial reported an objective response rate of 43 % . 22 Approval was based on results from EMILIA , an international phase III study comparing ado - trastuzumab to lapatinib plus capecitabine ( n = 991 ) . The study showed a significantly prolonged progression - free and overall survival with less toxicity than lapatinib plus capecitabine . 16 Since December 2017 , the FDA has approved 4 biosimilars of trastuzumab ( Herzuma , Ogivri , Ontruzant , Trazimera ) to treat HER2 - overexpressed breast cancer . All biosimilars of trastuzumab have demonstrated efficacies and safety outcomes similar to those of the standard trastuzumab . 23 24 25 26 Pertuzumab ( Perjeta ) , a humanized monoclonal antibody that blocks the activation of the HER2 receptor by hindering dimerization , was approved by the FDA in combination with trastuzumab and docetaxel . This novel therapy is targeted at HER2 - positive metastatic breast cancer patients previously not treated with hormone therapy or chemotherapy . Its future use in earlier stages is currently being investigated . FDA - approval of pertuzumab was based on results from the Clinical Evaluation of Pertuzumab and Trastuzumab ( CLEOPATRA ) trial . Pertuzumab elicits action at a different ligand binding site from trastuzumab to prevent HER2 dimerization . The combination of both HER2 receptor antibodies ( pertuzumab plus trastuzumab ) is superior to either agent alone . The trial compared first - line trastuzumab plus docetaxel ( plus placebo ) to trastuzumab plus docetaxel plus pertuzumab in HER2 - postive metastatic breast cancer . Results from the study showed an average increase in progression - free survival of 6.1 months The FDA approved pertuzumab for neoadjuvant treatment in combination with trastuzumab and docetaxel for patients with HER2 - positive , locally advanced , inflammatory , or early stage breast cancer ( either greater than 2 cm in diameter or node positive ) . Approval was based on a randomized trial that compared a number of regimens with and without pertuzumab in women with HER2 - positive breast cancer . In the trial , 39.3 % of patients treated with pertuzumab , trastuzumab , and docetaxel ( n = 107 ) achieved a pathologic complete response ( pCR ) , compared 15 Several ongoing phase I / II trials are investigating this TKI combination with trastuzumab , paclitaxel , or vinorelbine in patients with trastuzumab - refractory breast cancer . Other EGFR TKIs , such as gefitinib and erlotinib , have been studied in combination with trastuzumab and endocrine therapy with disappointing results .
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[
"Practice Essentials",
"Breast Cancer"
] |
http://emedicine.medscape.com/article/173594-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Gastroenterology Dumping Syndrome Updated : Oct 03 , 2017 Author : Rajan Kanth , MD ; Chief Editor : BS Anand , MD more . . . Sections Overview Presentation Workup Treatment Medication Questions & Answers References Background Anatomic structures of the stomach are divided into the cardia , fundus , body , and pylorus . The fundus serves as the reservoir for ingested meals , while the distal stomach churns and mixes with digestive enzymes and initiates the digestive process . Once the foods are processed , the pylorus releases the food in a controlled fashion downstream into the duodenum . The capacity of the stomach in adults is approximately 1.5 - 2 liters , and its location in the abdomen allows for considerable distensibility . Gastric motility is controlled by myogenic ( intrinsic ) , circulating hormonal , and neural activity ( gastric plexus , myenteric plexus , sympathetic and parasympathetic nerves ) . Alterations in thegastric anatomy after surgery or interference in its extrinsic innervation ( vagotomy ) may have profound effects on the gastric reservoir and pyloric sphincter mechanism and , in turn , alter gastric emptying . These effects , for convenience , have been termed postgastrectomy Postgastrectomy syndromes include small capacity , dumping syndrome , bile gastritis , afferent loop syndrome , efferent loop syndrome , anemia , and metabolic bone disease . Postgastrectomy syndromes are iatrogenic conditions that may arise from partial gastrectomies , independent of whether the gastric surgery was initially performed for peptic ulcer disease , cancer , or weight loss ( bariatric ) . The surgical procedures include Billroth - I , Billroth - II , and Roux - en - Y gastric bypass . 1 Hertz made the association between postprandial symptoms and gastroenterostomy in 1913 . 2 Hertz stated that the condition was due to " too rapid drainage of the stomach . " Wyllys et al first used the term " dumping " in 1922 after observing radiographically the presence of rapid gastric emptying in patients with vasomotor and GI symptoms . 3 Pathophysiology Dumping syndrome is the effect of altered gastric reservoir function , abnormal postoperative gastric motor function , and / or pyloric emptying mechanism . 4 5 See the image below . Pathophysiology of dumping syndrome . Clinically significant dumping syndrome occurs in approximately 10 % of patients after any type of gastric surgery and in up to 50 % of patients after laparoscopic Roux - en - Y gastric bypass . Dumping syndrome has characteristic alimentary and systemic manifestations . It is a frequent complication observed after a variety of gastric surgical procedures , such as vagotomy , pyloroplasty , gastrojejunostomy , and laparoscopic Nissan fundoplication . Dumping syndrome can be separated into early and late forms , depending on the occurrence of symptoms in relation to the time elapsed after a meal . Postprandially , the function of the body of the stomach is to store food and to allow the initial chemical digestion by acid and proteases before transferring food to the gastric antrum . In the antrum , high - amplitude contractions triturate the solids , reducing the particle size to 1 - 2 mm . Once solids have been reduced to this desired size , they are able to pass through the pylorus . An intact pylorus prevents the passage of larger particles into the duodenum . Gastric emptying is controlled by the fundic tone , antropyloric mechanisms , and Gastric resection reduces the fundic reservoir , thereby reducing the stomach ' s receptiveness ( accommodation ) to a meal . Vagotomy increases the gastric tone , similarly limiting accommodation . An operation in which the pylorus is removed , bypassed , or destroyed increases the rate of gastric emptying . Duodenal feedback inhibition of gastric emptying is lost after a bypass procedure , such as gastrojejunostomy . Accelerated gastric emptying of liquids is a characteristic feature and a critical step in the pathogenesis of dumping syndrome . Gastric mucosal function is altered by surgery , and acid and enzymatic The accommodation response and the phasic contractility of the stomach in response to distention are abolished after vagotomy or partial gastric resection . 6 This probably accounts for the immediate transfer of ingested contents into the duodenum . Early dumping syndrome and reflux gastritis are less frequent when segmented gastrectomy rather than distal gastrectomy is performed for early gastric cancer . 7 In persons with long segment Barrett esophagus treated with a truncal vagotomy , partial gastrectomy , and Roux - en - Y gastrojejunostomy , 41 % developed dumping within the first 6 months after surgery , but severe dumping is rare ( 5 % of cases ) . 8 The dumping syndrome occurs in 45 % of persons who are malnourished and who have had a partial or complete gastrectomy . 9 The late dumping syndrome is suspected in the person who has symptoms of hypoglycemia in the setting of previous gastric surgery , and this late dumping can be proven with an oral glucose tolerance test ( hyperinsulinemic hypoglycemia ) , as well as gastric emptying scintigraphy , which shows the abnormal pattern of initially delayed and then accelerated gastric emptying . 10 Early dumping Rapid emptying of gastric contents into the small intestine or colon may result in high amplitude propagated contractions and increased propulsive motility , thereby contributing to the diarrhea seen in persons with the dumping syndrome . 11 The emptying of liquids is fast relative to persons without distal gastrectomy with Billroth - I reconstruction . 12 Symptoms of early dumping syndrome occur 30 - 60 minutes after a meal . Symptoms are believed to result from accelerated gastric emptying of hyperosmolar contents into the small bowel . This leads to fluid shifts from the intravascular compartment into the bowel lumen , resulting in rapid small bowel distention and an increase in the frequency of bowel contractions . Rapid instillation of liquid meals into the small bowel has been shown to induce dumping symptoms in healthy individuals who have not had gastric surgery . Bowel distention may be responsible for GI symptoms , such as crampy abdominal This hypothesis has been questioned for several reasons . First , the severity of dumping is not reliably related to the volume of hypertonic solution ingested . Second , intravenous infusion sufficient to prevent the postprandial fall in plasma volume may not abolish the dumping symptoms . Furthermore , Kalser and Cohen measured intrajejunal osmolarity and glucose content using a continuous perfusion method . 13 They found that the degree of dilution of the hyperosmolar glucose in patients postgastrectomy was similar in symptomatic and asymptomatic subjects . Provocation with oral glucose in patients with early dumping generally provokes an increase in the heart rate . Although vasoconstriction is expected in a volume - contracted state , patients with dumping syndrome have vasodilation . 14 An increase in blood flow to the superior mesenteric artery has been described in patients with dumping syndrome . This peripheral and splanchnic vasodilatory response seems to be pivotal in the pathogenesis of dumping . In experimentally induced dumping in dogs , symptoms can be induced in a healthy animal by transfusion of portal vein blood . This led to the hypothesis that humoral factors may have an important role in the pathogenesis of dumping . Some evidence suggests that hyperosmolar small intestine content leads to serotonin release which , in turn , leads to mesenteric and peripheral vasodilation . It results in fluid shifts and hypotension in the early phase of dumping syndrome . The postprandial release of gut hormones , such as enteroglucagon , peptide YY , pancreatic polypeptide , vasoactive intestinal polypeptide , glucagonlike peptide - 1 ( GLP - 1 ) , and neurotensin , is higher in patients with dumping syndrome compared with asymptomatic patients after gastric surgery . Some or all of these peptides are likely to participate in the pathogenesis of dumping syndrome . Glucagon , GLP - 1 and glucose - dependent insulinotropic peptide ( GIP ) levels were higher in those with Roux - en - Y gastric bypass , as compared with those nonsurgical patients 15 The exaggerated postprandial GLP - 1 release contributes to the symptoms of early dumping by activating sympathetic outflow . 16 One of the effects of these hormones is the retardation of proximal GI motility and the inhibition of secretion . This function is called the ileal brake . Some authors have suggested that the accelerated release of these hormones is an attempt to activate the ileal brake , thereby delaying proximal transit time in response to rapid delivery of food to the distal small bowel . Late dumping Late dumping occurs 1 - 3 hours after a meal . The pathogenesis is thought to be related to the early development of hyperinsulinemic ( reactive ) hypoglycemia . 17 18 Rapid delivery of a meal to the small intestine results in an initial high concentration of carbohydrates in the proximal small bowel and rapid absorption of glucose . This is countered by a hyperinsulinemic response . The high insulin levels stay for longer period and are responsible for the subsequent hypoglycemia . Intrajejunal glucose induces a higher insulin release than does the intravenous infusion of glucose . 19 The serum glucose levels were the same in both experiments . This effect of enhanced insulin release after an enteral glucose load as compared to intravenous glucose administration is called the incretin effect . Two hormones are thought to play a pivotal role in the incretin effect . These are glucose - dependent insulinotropic peptide and GLP - 1 . In human studies , an increase in GLP - 1 response has been noted after an oral glucose challenge . An increased GLP - 1 response has been noted in patients after total gastrectomy , esophageal resection , and partial gastrectomy . Furthermore , a positive correlation was found between the rise in plasma GLP - 1 and insulin release . An exaggerated GLP - 1 response likely plays an important role in the hyperinsulinemia and hypoglycemia in patients with late dumping . The reason why some patients remain asymptomatic after gastric surgery whereas others develop severe symptoms remains elusive . Etiology Dumping can be separated into early and late forms depending on the occurrence of symptoms in relation to the time elapsed after a meal . Both forms occur because of the rapid delivery of large amounts of osmotically active solids and liquids to the duodenum . This is a direct result of alterations in the storage function of the stomach and / or pyloric emptying mechanism . The severity of dumping syndrome is proportional to the rate of gastric emptying . Postprandially , the stomach assumes its reservoir function to allow initial chemical digestion by acid and proteases before transferring food to the antrum . In the antrum , high - amplitude contractions triturate solids . Once solids have been reduced to 1 - 2 mm , they are able to empty through the pylorus . An intact pylorus has a separating function that prevents the passage of larger particles into the duodenum . Gastric emptying is controlled by fundic tone , antropyloric mechanisms , and duodenal Gastric resection can reduce the fundic reservoir , thereby reducing the receptiveness of the stomach to a meal . Similarly , vagotomy increases gastric tone , limiting accommodation . Any operation in which the pylorus is removed , bypassed , or destroyed increases the rate of gastric emptying . Duodenal feedback inhibition of gastric emptying is also lost after bypass of the duodenum with gastrojejunostomy . Accelerated early gastric emptying of liquids is a characteristic feature and a critical step in the pathogenesis of dumping syndrome . Gastric mucosal function is altered by surgery , and acid and enzymatic secretions are decreased . Also , hormonal secretions that sustain the gastric phase of digestion are adversely affected . Epidemiology The global incidence and severity of symptoms in dumping syndrome are related directly to the extent of gastric surgery . 5 20 21 United States data An estimated 20 - 50 % of all patients who have undergone gastric surgery have some symptoms of dumping . 21 However , only 1 - 5 % are reported to have severe disabling symptoms . The incidence of significant dumping has been reported to be 6 - 14 % in patients after truncal vagotomy and drainage and from 14 - 20 % after partial gastrectomy . The incidence of dumping syndrome after proximal gastric vagotomy without any drainage procedure is less than 2 % . Newer gastric operations , such as proximal gastric vagotomy ( which produces minimal disturbance of gastric emptying mechanisms ) , are associated with a much lower incidence of postgastrectomy syndromes . In the pediatric population , dumping syndrome is described almost exclusively in children who have undergone Nissen fundoplication . 22 Reductions in the need for elective gastric surgery have led to a decline in the frequency of postgastrectomy syndromes . A 10 - fold reduction has occurred in elective operations for peptic ulcer disease in the last 20 - 30 years . Although this trend preceded the advent of histamine - 2 receptor antagonists , these drugs and proton pump inhibitors have accelerated the decline . Helicobacter pylori treatment and eradication in patients with peptic ulcer disease have further decreased the need for surgery . Although the need for elective surgery for peptic ulcer disease has declined , the need for emergency surgery has remained the same over the last 20 years . Emergency surgery tends to be more mutilating to the stomach . This increases the incidence of more severe symptoms . Gastric surgery is also performed as part of the care of persons with a gastric malignancy , or as an approach to weight loss ( bariatric surgery ) . Bariatric surgery is the only satisfactory long - term treatment for severe obesity ( body mass index [ BMI ] 40 kg / m² or greater , or 35 kg / m² or greater with severe obesity - associated comorbidities , such as diabetes , obstructive sleep apnea , or debilitating degenerative arthritis ) . Even in specialized units , the mortality rate of bariatric surgery may be 1 % , 23 Some 80 % of the deaths that occur within a month of bariatric surgery arise from anastomotic leaks , pulmonary emboli , and respiratory failure . Other authors report that long - acting octreotide is as effective long term as subcutaneous octreotide , with superior symptom control as assessed by the Gastrointestinal Specific Quality of Life Index , better maintenance of body weight , and higher quality of life . 24 Pancreatic nesidioblastosis or pancreatic islet cell hyperplasia has been speculated to contribute to the sometimes disabling neurologic immune restoration inflammatory syndrome ( NIRIS ) . Resection of this hyperplasia - - and therefore removing the exaggerated insulin response - - has been proposed . Sex - related demographics A female preponderance exists in the incidence of postgastrectomy syndromes . Clinical Presentation Sections Dumping Syndrome Overview Presentation Workup Treatment Medication Questions & Answers References
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[
"Dumping Syndrome"
] |
http://emedicine.medscape.com/article/1799897-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Dentistry Management of Dental Trauma Updated : Jan 09 , 2019 Author : Neshe E Gampel , MD ; Chief Editor : Anil P Punjabi , MD , DDS more . . . Sections Practice Essentials Overview Anatomy Etiology Presentation Treatment Show All Media Gallery References Practice Essentials Dental trauma is relatively common and can occur secondary to falls , fights , sporting injuries , or motor vehicle accidents . Because many clinicians work in a community - based environment where there is no dentist on call for emergencies , they may find themselves forced to deal with acute dental injuries in such situations . A study sought to determine whether oral cavity cancers occurred more commonly at sites of dental trauma . The study concluded that oral cavity cancers occur predominantly at sites of potential dental and denture trauma , especially in nonsmokers without other risk factors . A key finding of this study was that the location where oral cavity cancers arise is different in smokers and nonsmokers . Recognizing teeth irritation as a potential carcinogen should have an impact on prevention and treatment strategies . 1 2 Prevention A position statement from the National Athletic Trainers ' Association ( NATA ) recommends that athletic trainers , coaches , and parents should motivate all athletes to wear mouthguards that are properly fitted during any sports activity with an increased risk of orofacial injury . 3 Clinical evaluation Initial evaluation of a patient with dental trauma should include the following : Full physical examination of the head , neck , and face Assessment of possible injuries to adjacent areas and structures ( eg , facial fractures or head and neck trauma ) Imaging modalities that may be considered include the following : CT of the head , neck , and maxillofacial bones Periapical radiography Panoramic radiography of the teeth See Overview for more detail . Management Treatment of dental trauma varies according to the type of injury involved : Fracture Avulsion Luxation ( tooth displacement ) Tetanus booster and antibiotics should be administered whenever a dental injury is at risk for infection . Arrangements should be made for prompt follow - up with a dentist or an oral and maxillofacial surgeon . Dental fractures may be classified as follows : Ellis class I ( superficial enamel only ) – No emergency care is required ; follow - up with a dentist is arranged as needed Ellis class II ( enamel and dentin , with sensitivity to temperature , air , and palpation ) – The exposed dentin is covered , preferably with dental cement ; the patient is referred to a dentist within 24 hours Ellis class III ( enamel , dentin , and pulp ; a dental emergency ) – The fracture is covered with dental cement ; patients receive urgent and immediate dental follow - up ; topical painkillers increase the risk of infection and thus should not be applied Root fractures – Extraction of the coronal segment is required ; if no more than one third of the root is involved , a dentist may be able to perform a root canal and salvage the tooth Principles of management for dental avulsions include the following : An adult tooth that is avulsed should be reimplanted in its socket as soon as possible If the tooth can not be reimplanted , it should be placed in a protective solution ; it should never be allowed to dry If the tooth has been dry for a significant period , it should be soaked in the appropriate solution ( which depends on the length of the dry period ) Some studies suggest that when a tooth has been out of the mouth for longer than 60 minutes , immediate reimplantation is not required , and a root canal of the tooth should be performed with the tooth outside the mouth before it is reimplanted After reimplantation , any other injuries are repaired In children with dental avulsions , primary teeth are never reimplanted , because reimplantation of a deciduous tooth can cause harm to the developing permanent tooth Luxations may be classified as follows : Concussion - Mild injury to the periodontal ligament , with some clinical tenderness but no movement of the tooth Subluxation - More significant injury to the periodontal ligament , with clinical tenderness and movement of the tooth Extrusion - Partial removal of a tooth from its socket Lateral luxation - Lateral displacement of a tooth at an angle , with possible fracture of the alveolar bone as well Intrusion - Impaction of a tooth into its socket in the fractured alveolar bone Treatment of luxations includes the following : Concussion and subluxation – A soft diet , administration of nonsteroidal anti - inflammatory drugs ( NSAIDs ) , and referral to a dentist ; subluxation is a more significant injury and is more often associated with pulpal necrosis Extrusion – Restoration of the tooth to its original position ; splinting Lateral luxation – Repositioning of the tooth , often made more difficult by a fractured alveolar bone ; splinting , done by a general practitioner only if the alveolar bone fracture is minimal and done by a dentist or an oral and maxillofacial surgeon if the fracture is more extensive Intrusion – Usually , the general practitioner can provide no emergency treatment ; referral to a dentist within 24 hours is indicated Associated injuries to the maxillofacial bones may be classified as follows : Le Fort I – Transverse fracture separating the body of the maxilla from the lower portion of the pterygoid plate and nasal septum Le Fort II – Pyramidal fracture of the central maxilla and palate ; facial tugging moves the nose but not the eyes Le Fort III ( ie , craniofacial disjunction ) – Facial skeleton completely separated from the skull , with the fracture extending through the frontozygomatic suture lines and through the orbit , the base of the nose , and the ethmoid ; on physical examination , the entire face shifts with tugging The image below depicts the Le Fort classification of maxillary fractures . Le Fort I , II , and III maxillary fractures . View Media Gallery Next : Overview Sections Management of Dental Trauma Anatomy Etiology Presentation Treatment Show All Media Gallery References
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[
"Dental Trauma",
"Luxation",
"Avulsion"
] |
http://emedicine.medscape.com/article/180234-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Gastroenterology Peritonitis and Abdominal Sepsis Updated : Jan 11 , 2017 Author : Brian J Daley , MD , MBA , FACS , FCCP , CNSC ; Chief Editor : Praveen K Roy , MD , AGAF more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery Tables References Background Peritonitis is defined as an inflammation of the serosal membrane that lines the abdominal cavity and the organs contained therein . The peritoneum , which is an otherwise sterile environment , reacts to various pathologic stimuli with a fairly uniform inflammatory response . Depending on the underlying pathology , the resultant peritonitis may be infectious or sterile ( ie , chemical or mechanical ) . Intra - abdominal sepsis is an inflammation of the peritoneum caused by pathogenic microorganisms and their products . 1 The inflammatory process may be localized ( abscess ) or diffuse in nature . ( See Pathophysiology . ) Peritonitis is most often caused by introduction of an infection into the otherwise sterile peritoneal environment through organ perforation , but it may also result from other irritants , such as foreign bodies , bile from a perforated gall bladder or a lacerated liver , or gastric acid from a perforated ulcer . Women also experience localized peritonitis from an infected fallopian tube or a ruptured ovarian cyst . Patients may present with an acute or insidious onset of symptoms , limited and mild disease , or systemic and severe disease with septic shock . ( See Etiology . ) Peritoneal infections are classified as primary ( ie , from hematogenous dissemination , usually in the setting of an immunocompromised state ) , secondary ( ie , related to a pathologic process in a visceral organ , such as perforation or trauma , including iatrogenic trauma ) , or tertiary ( ie , persistent or recurrent infection after adequate initial therapy ) . Primary peritonitis is most often spontaneous bacterial peritonitis ( SBP ) seen mostly inpatients with chronic liver disease . Secondary peritonitis is by far the most common form of peritonitis encountered in clinical practice . Tertiary peritonitis Clinical Presentation Infections of the peritoneum are further divided into generalized ( peritonitis ) and localized ( intra - abdominal abscess ) . This article focuses on the diagnosis and management of infectious peritonitis and abdominal abscesses . An abdominal abscess is seen in the image below . A 35 - year - old man with a history of Crohn disease presented with pain and swelling in the right abdomen . In figure A , a thickened loop of terminal ileum is evident adherent to the right anterior abdominal wall . In figure B , the right anterior abdominal wall is markedly thickened and edematous , with adjacent inflamed terminal ileum . In figure C , a right lower quadrant abdominal wall abscess and enteric fistula are observed and confirmed by the presence of enteral contrast in the abdominal wall . View Media Gallery The diagnosis of peritonitis is usually clinical . Diagnostic peritoneal lavage may be helpful in patients who do not have conclusive signs on physical examination or who can not provide an adequate history ; in addition , paracentesis should be performed in all patients who do not have an indwelling peritoneal catheter and are suspected of having SBP , because results of aerobic and anaerobic bacterial cultures , used in conjunction with the cell count , are useful in guiding therapy . ( See Workup The current approach to peritonitis and peritoneal abscesses targets correction of the underlying process , administration of systemic antibiotics , and supportive therapy to prevent or limit secondary complications due to organ system failure . ( See Treatment and Management and Medication Early control of the septic source is mandatory and can be achieved operatively and nonoperatively . Nonoperative interventions include percutaneous abscess drainage , as well as percutaneous and endoscopic stent placements . Operative management addresses the need to control the infectious source and to purge bacteria and toxins . The type and extent of surgery depends on the underlying disease process and the severity of intra - abdominal infection . Anatomy The peritoneum is the largest and most complex serous membrane in the body . It forms a closed sac ( ie , coelom ) by lining the interior surfaces of the abdominal wall ( anterior and lateral ) , by forming the boundary to the retroperitoneum ( posterior ) , by covering the extraperitoneal structures in the pelvis ( inferior ) , and by covering the undersurface of the diaphragm ( superior ) . This parietal layer of the peritoneum reflects onto the abdominal visceral organs to form the visceral peritoneum . It thereby creates a potential space between the The peritoneum consists of a single layer of flattened mesothelial cells over loose areolar tissue . The loose connective tissue layer contains a rich network of vascular and lymphatic capillaries , nerve endings , and immune - competent cells , particularly lymphocytes and macrophages . The peritoneal surface cells are joined by junctional complexes , thus forming a dialyzing membrane that allows passage of fluid and certain small solutes . Pinocytotic activity of the mesothelial cells and phagocytosis by macrophages allow for the clearance of macromolecules . Normally , the amount of peritoneal fluid present is less than 50 mL , and only small volumes are transferred across the considerable surface area in a steady state each day . The peritoneal fluid represents a plasma ultrafiltrate , with electrolyte and solute concentrations similar to that of neighboring interstitial spaces and a protein content of less than 30 g / L , mainly albumin . In addition , peritoneal fluid contains small numbers of desquamated mesothelial cells and various numbers and morphologies of migrating immune cells ( reference range is < 300 cells / μ L , predominantly The peritoneal cavity is divided incompletely into compartments by the mesenteric attachments and secondary retroperitonealization of certain visceral organs . A large peritoneal fold , the greater omentum , extends from the greater curvature of the stomach and the inferior aspect of the proximal duodenum downward over a variable distance to fold upon itself ( with fusion of the adjacent layers ) and ascends back to the taenia omentalis of the transverse colon . This peritoneal fold demonstrates a slightly different microscopic anatomy , with fenestrated surface epithelium and a large number of adipocytes , lymphocytes , and macrophages , The compartmentalization of the peritoneal cavity , in conjunction with the greater omentum , influences the localization and spread of peritoneal inflammation and infections . Pathophysiology In peritonitis caused by bacteria , the physiologic response is determined by several factors , including the virulence of the contaminant , the size of the inoculum , the immune status and overall health of the host ( eg , as indicated by the Acute Physiology and Chronic Health Evaluation II [ APACHE II ] score ) , and elements of the local environment , such as necrotic tissue , blood , or bile . 2 Intra - abdominal sepsis from a perforated viscus ( ie , secondary peritonitis or suppurative peritonitis ) results from direct spillage of luminal contents into the peritoneum ( eg , perforated peptic ulcer , diverticulitis , appendicitis , iatrogenic perforation ) . With the spillage of the contents , gram - negative and anaerobic bacteria , including common gut flora , such as Escherichia coli and Klebsiella pneumoniae , enter the peritoneal cavity . Endotoxins produced by gram - negative bacteria lead to the release of cytokines that induce cellular and humoral cascades , resulting in cellular damage , septic shock , and multiple organ dysfunction syndrome ( MODS ) . The mechanism for bacterial inoculation of ascites has been the subject of much debate since Harold Conn first recognized it in the 1960s . Enteric organisms have traditionally been isolated from more than 90 % of infected ascites fluid in spontaneous bacterial peritonitis ( SBP ) , suggesting that the GI tract is the source of bacterial contamination . The preponderance of enteric organisms , in combination with the presence of endotoxin in ascitic fluid and blood , once favored the argument that SBP was due to direct transmural migration of bacteria from an intestinal or hollow organ lumen , An alternative proposed mechanism for bacterial inoculation of ascites suggests a hematogenous source of the infecting organism in combination with an impaired immune defense system . Nonetheless , the exact mechanism of bacterial displacement from the GI tract into ascites fluid remains the source of much debate . A host of factors contributes to the formation of peritoneal inflammation and bacterial growth in the ascitic fluid . A key predisposing factor may be the intestinal bacterial overgrowth found in people with cirrhosis , mainly attributed to decreased intestinal transit time . Intestinal bacterial overgrowth , along with impaired phagocytic function , low serum and ascites complement levels , and decreased activity of the reticuloendothelial system , contributes to an increased number of microorganisms and decreased capacity to clear them from the bloodstream , resulting in their migration into and eventual proliferation within ascites fluid . Interestingly , adults with SBP typically have ascites , but most children with SBP do not have ascites . The reason for and mechanism behind this is the source of ongoing investigation . Fibrinolysis Alterations in fibrinolysis ( through increased plasminogen activator inhibitor activity ) and the production of fibrin exudates have an important role in peritonitis . The production of fibrin exudates is an important part of the host defense , but large numbers of bacteria may be sequestered within the fibrin matrix . This may retard systemic dissemination of intraperitoneal infection and may decrease early mortality rates from sepsis , but it also is integral to the development of residual infection and abscess formation . As the fibrin matrix matures , the bacteria within are protected from host clearance mechanisms . Whether fibrin ultimately results in containment or persistent infection may depend on the degree of peritoneal bacterial contamination . In animal studies of mixed bacterial peritonitis that examined the effects of systemic defibrinogenation and those of abdominal fibrin therapy , heavy peritoneal contamination uniformly led to severe peritonitis with early death ( < 48 h ) because of overwhelming sepsis . Bacterial load Bacterial load and the nature of the pathogen also play important roles . Some studies suggest that the number of bacteria present at the onset of abdominal infections is much higher than originally believed ( approximately 2 × 10 8 CFU / mL , much higher than the 5 × 10 5 CFU / mL inocula routinely used for in vitro susceptibility testing ) . This bacterial load may overwhelm the local host defense . Bacterial virulence Bacterial virulence factors 3 that interfere with phagocytosis and with neutrophil - mediated bacterial killing mediate the persistence of infections and abscess formation . Among these virulence factors are capsule formation , facultative anaerobic growth , adhesion capabilities , and succinic acid production . Synergy between certain bacterial and fungal organisms may also play an important role in impairing the host ' s defense . One such synergy may exist between Bacteroides fragilis and gram - negative bacteria , particularly E coli ( see the image below ) where co - inoculation significantly increases bacterial proliferation and abscess formation . Gram - negative Escherichia coli . View Media Gallery Enterococci Enterococci may be important in enhancing the severity and persistence of peritoneal infections . In animal models of peritonitis with E coli B fragilis , the systemic manifestations of the peritoneal infection and bacteremia rates were increased , as were bacterial concentrations in the peritoneal fluid and rate of abscess formation . Nevertheless , the role of Enterococcus organisms in uncomplicated intra - abdominal infections remains unclear . Antibiotics that lack specific activity against Enterococcus are often used successfully in the therapy of peritonitis , and the organism is not often recovered as a blood - borne pathogen in intra - abdominal sepsis . Fungi The role of fungi in the formation of intra - abdominal abscesses is not fully understood . Some authors suggest that bacteria and fungi exist as nonsynergistic parallel infections with incomplete competition , allowing the survival of all organisms . In this setting , treatment of the bacterial infection alone may lead to an overgrowth of fungi , which may contribute to increased morbidity . Abscess formation Abscess formation occurs when the host defense is unable to eliminate the infecting agent and attempts to control the spread of this agent by compartmentalization . This process is aided by a combination of factors that share a common feature , ie , impairment of phagocytotic killing . Most animal and human studies suggest that abscess formation occurs only in the presence of abscess - potentiating agents . Although the nature and spectrum of these factors have not been studied exhaustively , certain fiber analogues ( eg , bran ) and the contents of autoclaved stool have been identified as Cytokines The role of cytokines in the mediation of the body ' s immune response and their role in the development of the systemic inflammatory response syndrome ( SIRS ) and multiple organ failure ( MOF ) have been a major focus of research over the past decade . Comparatively few data exist about the magnitude of the intraperitoneal / abscess cytokine response and implications for the host . Existing data suggest that bacterial peritonitis is associated with an immense intraperitoneal compartmentalized cytokine response . Higher levels of certain cytokines ( ie , tumor necrosis factor - alpha [ TNF - Etiology The etiology of disease depends on the type , as well as location , of peritonitis , as follows : Primary peritonitis Secondary peritonitis Tertiary peritonitis Chemical peritonitis Peritoneal abscess Primary peritonitis Spontaneous bacterial peritonitis ( SBP ) is an acute bacterial infection of ascitic fluid . Contamination of the peritoneal cavity is thought to result from translocation of bacteria across the gut wall or mesenteric lymphatics and , less frequently , via hematogenous seeding in the presence of bacteremia . SBP can occur as a complication of any disease state that produces the clinical syndrome of ascites , such as heart failure and Budd - Chiari syndrome . Children with nephrosis or systemic lupus erythematosus who have ascites have a high risk of developing SBP . The highest risk of SBP , however is in patients with cirrhosis who are in a decompensated state . 4 In particular , decreased hepatic synthetic function with associated low total protein level , low complement levels , or prolonged prothrombin time ( PT ) is associated with maximum risk . Patients with low protein levels in ascitic fluid ( < 1 g / dL ) have a 10 - fold higher risk of developing SBP than those with a protein level greater than 1 g / dL . Approximately 10 - 30 % of patients with cirrhosis and ascites develop SBP . 5 The incidence rises to more than 40 % with ascitic fluid protein contents of less than 1 g / dL ( which occurs 15 % of patients ) , presumably because of decreased ascitic fluid opsonic activity . More than 90 % of cases of SBP are caused by a monomicrobial infection . The most common pathogens include gram - negative organisms ( eg , [ 40 % ] , K pneumoniae [ 7 % ] , Pseudomonas species , Proteus species , other gram - negative species [ 20 % ] ) and gram - positive organisms ( eg , Streptococcus pneumoniae [ 15 % ] , other Streptococcus species [ 15 % ] , and Staphylococcus species [ 3 % ] ) ( see Table 1 ) . However , some data suggest that the percentage of gram - positive infections may be increasing . 6 7 One study cites a 34.2 % incidence of streptococci , ranking in second position after Enterobacteriaceae . 7 Viridans group streptococci ( VBS ) accounted for 73.8 % of these streptococcal isolates . A single organism is noted in 92 % of cases , and 8 % of cases are polymicrobial . Anaerobic microorganisms are found in less than 5 % of cases , and multiple isolates are found in less than 10 % . Secondary peritonitis Common etiologic entities of secondary peritonitis ( SP ) include perforated appendicitis ; perforated gastric or duodenal ulcer ; perforated ( sigmoid ) colon caused by diverticulitis , volvulus , or cancer ; and strangulation of the small bowel ( see Table 1 ) . Necrotizing pancreatitis can also be associated with peritonitis in the case of infection of the necrotic tissue . The pathogens involved in SP differ in the proximal and distal GI tract . Gram - positive organisms predominate in the upper GI tract , with a shift toward gram - negative organisms in the upper GI tract in patients on long - term gastric acid suppressive therapy . Contamination from a distal small bowel or colon source initially may result in the release of several hundred bacterial species ( and fungi ) ; host defenses quickly eliminate most of these organisms . The resulting peritonitis is almost always polymicrobial , containing a mixture of aerobic and anaerobic bacteria with As many as 15 % of patients who have cirrhosis with ascites who were initially presumed to have SBP have SP . In many of these patients , clinical signs and symptoms alone are not sensitive or specific enough to reliably differentiate between the 2 entities . A thorough history , evaluation of the peritoneal fluid , and additional diagnostic tests are needed to do so ; a high index of suspicion is required . Table 1 . Common Causes of Secondary Peritonitis ( Open Table in a new window ) Source Regions Causes Esophagus Boerhaave syndrome Malignancy Trauma ( mostly penetrating ) Iatrogenic * Stomach Peptic ulcer perforation Malignancy ( eg , adenocarcinoma , lymphoma , gastrointestinal stromal tumor ) Trauma ( mostly penetrating ) Iatrogenic * Duodenum Peptic ulcer perforation Trauma ( blunt and penetrating ) Biliary tract Cholecystitis Stone perforation from gallbladder ( ie , gallstone ileus ) or common duct Malignancy Choledochal cyst ( rare ) Pancreas Pancreatitis ( eg , alcohol , drugs , gallstones ) Trauma ( blunt and penetrating ) Small bowel Ischemic bowel Incarcerated hernia ( internal and external ) Closed loop obstruction Crohn disease Malignancy ( rare ) Meckel diverticulum Large bowel and appendix Ischemic bowel Diverticulitis Ulcerative colitis and Crohn disease Appendicitis Colonic volvulus Iatrogenic Uterus , salpinx , and ovaries Pelvic inflammatory disease ( eg , salpingo - oophoritis , tubo - ovarian abscess , ovarian cyst ) Malignancy ( rare ) Trauma ( uncommon ) * Iatrogenic trauma to the upper GI tract , including the pancreas and biliary tract and colon , often results from endoscopic procedures ; anastomotic dehiscence and inadvertent bowel injury ( eg , mechanical , thermal ) are common causes of leak in the postoperative period . Common organisms cultured in secondary peritonitis are presented in Table 2 , below . 8 Table 2 . Microbial Flora of Secondary Peritonitis ( Open Table in a new window ) Type Organism Percentage Aerobic Gram negative Escherichia coli 60 % Enterobacter / Klebsiella 26 % Proteus 22 % Pseudomonas 8 % Gram positive Streptococci 28 % Enterococci 17 % Staphylococci 7 % Anaerobic Bacteroides 72 % Eubacteria 24 % Clostridia 17 % Peptostreptococci 14 % Peptococci 11 % Fungi Candida 2 % Other rare , nonsurgical causes of intra - abdominal sepsis include the following : Chlamydia peritonitis Tuberculosis peritonitis Acquired immunodeficiency syndrome ( AIDS ) - associated peritonitis The most common cause of postoperative peritonitis is anastomotic leak , with symptoms generally appearing around postoperative days 5 - 7 . After elective abdominal operations for noninfectious etiologies , the incidence of SP ( caused by anastomotic disruption , breakdown of enterotomy closures , or inadvertent bowel injury ) should be less than 2 % . Operations for inflammatory disease ( ie , appendicitis , diverticulitis , cholecystitis ) without perforation carry a risk of less than 10 % for the development of SP and peritoneal abscess . This risk may rise to greater than 50 % in gangrenous After operations for penetrating abdominal trauma , SP and abscess formation are observed in a small number of patients . Duodenal and pancreatic involvement , as well as colon perforation , gross peritoneal contamination , perioperative shock , and massive transfusion , are factors that increase the risk of infection in these cases . Peritonitis is also a frequent complication and significant limitation of peritoneal dialysis . 3 Peritonitis leads to increased hospitalization and mortality rates . Tertiary peritonitis Tertiary peritonitis ( see Table 3 , below ) develops more frequently in immunocompromised patients and in persons with significant preexisting comorbid conditions . Although rarely observed in uncomplicated peritoneal infections , the incidence of tertiary peritonitis in patients requiring ICU admission for severe abdominal infections may be as high as 50 - 74 % . Tuberculous peritonitis ( TP ) is rare in the United States ( < 2 % of all causes of peritonitis ) , but it continues to be a significant problem in developing countries and among patients with human immunodeficiency virus ( HIV ) infection . The presenting symptoms are often nonspecific and insidious in onset ( eg , low - grade fever , anorexia , weight loss ) . Many patients with TP have underlying cirrhosis . More than 95 % of patients with TP have evidence of ascites on imaging studies , and more than half of these patients In most cases , chest radiographic findings in patients with TP peritonitis are abnormal ; active pulmonary disease is uncommon ( < 30 % ) . Results on Gram stain of ascitic fluid are rarely positive , and culture results may be falsely negative in up to 80 % of patients . A peritoneal fluid protein level greater than 2.5 g / dL , a lactate dehydrogenase ( LDH ) level greater than 90 U / mL , or a predominantly mononuclear cell count of greater than 500 cells / μ L should raise suspicion of TP but have limited Table 3 . Microbiology of Primary , Secondary , and Tertiary Peritonitis Peritonitis ( Type ) Etiologic Organisms Antibiotic Therapy ( Suggested ) Class Type of Organism Primary Gram - negative ( 40 % ) K pneumoniae ( 7 % ) species ( 5 % ) species ( 5 % ) Streptococcus species ( 15 % ) Staphylococcus species ( 3 % ) Anaerobic species ( < 5 % ) Third - generation cephalosporin Secondary Gram - negative Enterobacter species Klebsiella species Second - generation cephalosporin Third - generation cephalosporin Penicillins with anaerobic activity Quinolones with anaerobic activity Quinolone and metronidazole Aminoglycoside and metronidazole Gram - positive Anaerobic Bacteroides fragilis Other Bacteroides Eubacterium Clostridium Anaerobic Tertiary Enterobacter Second - generation cephalosporin Penicillins with anaerobic activity Quinolones with anaerobic activity Quinolone and metronidazole Aminoglycoside and metronidazole Carbapenems Triazoles or amphotericin ( considered in fungal etiology ) ( Alter therapy based on culture results . ) Gram - positive Fungal Candida Chemical peritonitis Chemical ( sterile ) peritonitis may be caused by irritants such as bile , blood , barium , or other substances or by transmural inflammation of visceral organs ( eg , Crohn disease ) without bacterial inoculation of the peritoneal cavity . Clinical signs and symptoms are indistinguishable from those of SP or peritoneal abscess , and the diagnostic and therapeutic approach should be the same . 9 Peritoneal abscess Peritoneal abscess describes the formation of an infected fluid collection encapsulated by fibrinous exudate , omentum , and / or adjacent visceral organs . The overwhelming majority of abscesses occur subsequent to SP . Abscess formation may be a complication of surgery . The incidence of abscess formation after abdominal surgery is less than 1 - 2 % , even when the operation is performed for an acute inflammatory process . The risk of abscess increases to 10 - 30 % in cases of preoperative perforation of the hollow viscus , significant fecal contamination of the peritoneal cavity , bowel Epidemiology The overall incidence of peritoneal infection and abscess is difficult to establish and varies with the underlying abdominal disease processes . SBP occurs in both children and adults and is a well - known and ominous complication of cirrhosis . Of patients with cirrhosis who have SBP , 70 % are Child - Pugh class C . In these patients , the development of SBP is associated with a poor long - term prognosis . Once thought to occur only in those individuals with alcoholic cirrhosis , SBP is now known to affect patients with cirrhosis from any cause . In patients with ascites , the prevalence may be as high as 18 % . This number has grown from 8 % over the past 2 decades , most likely secondary to an increased awareness of SBP and heightened threshold to perform diagnostic paracentesis . Although the etiology and incidence of hepatic failure differ between children and adults , in those individuals with ascites , the incidence of SBP is roughly equal . Two peak ages for SBP are characteristic in children : one in the neonatal period and the other at age 5 years . Prognosis Over the past decade , the combination of better antibiotic therapy , more aggressive intensive care , and earlier diagnosis and therapy with a combination of operative and percutaneous techniques have led to a significant reduction in morbidity and mortality related to intra - abdominal sepsis . Spontaneous bacterial peritonitis The mortality rate in SBP may be as low as 5 % in patients who receive prompt diagnosis and treatment . However , in hospitalized patients , 1 - year mortality rates may range from 50 - 70 % . 10 This is usually secondary to the development of complications , such as gastrointestinal bleeding , renal dysfunction , and worsening liver failure . 11 Patients with concurrent renal insufficiency have been shown to be at a higher risk of mortality from SBP than those without concurrent renal insufficiency . Mortality from SBP may be decreasing among all subgroups of patients because of advances in its diagnosis and treatment . The overall mortality rate in patients with SBP may exceed 30 % if the diagnosis and treatment are delayed , but the mortality rate is less than 10 % in fairly well - compensated patients with early therapy . As many as 70 % of patients who survive an episode of SBP have a recurrent episode within 1 year , and in these patients , the mortality rate approaches 50 % . Some studies suggest that the recurrence rate of Secondary peritonitis and peritoneal abscess Uncomplicated SP and simple abscesses carry a mortality rate of less than 5 % , but this rate may increase to greater than 30 - 50 % in severe infections . The overall mortality rate related to intra - abdominal abscess formation is less than 10 - 20 % . Factors that independently predict worse outcomes include advanced age , malnutrition , presence of cancer , a high APACHE II score on presentation , preoperative organ dysfunction , the presence of complex abscesses , and failure to improve in less than 24 - 72 hours after adequate therapy . In severe intra - abdominal infections and peritonitis , the mortality rate may increase to greater than 30 - 50 % . The concurrent development of sepsis , SIRS , and MOF can increase the mortality rate to greater than 70 % , and , in these patients , more than 80 % of deaths occur with an active infection present . Soriano et al found that cirrhotic patients with SP who underwent surgical treatment tended to have a lower mortality rate than did those who received medical therapy only ( 53.8 % vs 81.8 % , respectively ) . 12 Among the surgically treated patients with SP , the survival rate was greater in those with the shortest time between diagnostic paracentesis and surgery . These researchers concluded that the prognosis of cirrhotic patients with SP could be improved via a low threshold of suspicion on the basis of Runyon ' s criteria and microbiologic data , prompt use of abdominal CT scanning , and early surgical evaluation . In comparison with patients with other forms of peritonitis , patients who develop tertiary peritonitis have significantly longer ICU and hospital stays , higher organ dysfunction scores , and higher mortality rates ( 50 - 70 % ) . Other factors affecting prognosis Several scoring systems ( eg , APACHE II , SIRS , multiple organ dysfunction syndrome [ MODS ] , Mannheim peritonitis index ) have been developed to assess the clinical prognosis of patients with peritonitis . Most of these scores rely on certain host criteria , systemic signs of sepsis , and complications related to organ failure . Although valuable for comparing patient cohorts and institutions , these scores have limited value in the specific day - to - day clinical decision - making process for any given patient . In general , the mortality rate is less than 5 The mortality rate without organ failure generally is less than 5 % but may rise to greater than 90 % with quadruple organ failure . A delay of more than 2 - 4 days in instituting either medical therapy or surgical therapy has been clearly associated with increased complication rates , the development of tertiary peritonitis , the need for reoperation , multiple organ system dysfunction , and death . Outcomes are worse in patients requiring emergent reoperations for persistent or recurrent infections ( 30 - 50 % increase in the mortality rate ) ; however , patients undergoing early planned second - look operations do not demonstrate this trend . Persistent infection , recovery of enterococci , and multidrug - resistant gram - negative organisms , as well as fungal infection , are related to worse outcomes and recurrent complications . Patients older than 65 years have a threefold increased risk of developing generalized peritonitis and sepsis from gangrenous or perforated appendicitis and perforated diverticulitis than younger patients and are 3 times more likely to die from these disease processes . Older patients with perforated diverticulitis are 3 times more likely than younger patients to have generalized rather than localized ( ie , pericolic , pelvic ) peritonitis . These findings are consistent with the hypothesis that the biologic features of peritonitis differ in elderly persons , who are more likely to present with an advanced or more severe process than Overall , studies suggest that host - related factors are more significant than the type and source of infection with regard to the prognosis in intra - abdominal infections . 13 Patient Education For patient education resources , Digestive Disorders Center as well as Abdominal Pain in Adults Appendicitis Diverticulosis and Diverticulitis Cirrhosis , and Sepsis ( Blood Infection ) Clinical Presentation Sections Peritonitis and Abdominal Sepsis Overview Presentation DDx Treatment Questions & Answers Media Gallery Tables References
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Gastroenterology Acute Pancreatitis Workup Updated : Mar 14 , 2019 Author : Jeffrey C F Tang , MD ; Chief Editor : BS Anand , MD more . . . Sections Overview Presentation DDx Workup Treatment Guidelines Medication Questions & Answers Media Gallery Tables References Approach Considerations Once a working diagnosis of acute pancreatitis is reached , laboratory tests are obtained to support the clinical impression . In addition to confirming the diagnosis , laboratory tests are helpful in determining the etiology and looking for complications . Although diagnostic imaging is unnecessary in most cases of pancreatitis , 20 visualization of inflammatory changes within the pancreas provides morphologic confirmation of the diagnosis . Obtain imaging tests when the diagnosis is in doubt , when severe pancreatitis is present , or when a given imaging study might provide specific information needed to answer a clinical question . Image - guided aspiration may be useful for differentiating infected from sterile necrosis and for draining fluid collections . Genetic testing for mutations associated with acute pancreatitis may be considered , even if effective treatments for these genetic conditions are lacking . In 2013 , the American College of Gastroenterology issued guidelines for the management of acute pancreatitis , including the following 21 Because acute pancreatitis can usually be diagnosed based on clinical symptoms and laboratory testing , contrast - enhanced computed tomography ( CT ) scanning and / or magnetic resonance imaging ( MRI ) of the pancreas should be performed only in the absence of clinical improvement or if the diagnosis is unclear Assessment of the patient ’ s hemodynamic status should occur immediately upon presentation , with resuscitative measures initiated as necessary Patients with systemic inflammatory response syndrome ( SIRS ) and / or organ failure should , if possible , be admitted to an intensive care unit ( ICU ) or an intermediary care setting All patients should receive aggressive hydration , unless this is precluded by cardiovascular and / or renal comorbidities ; aggressive intravenous ( IV ) hydration is most effective within the first 12 - 24 hours , with possibly little benefit derived from its administration after this point Within 24 hours of admission , patients with concurrent acute cholangitis should undergo endoscopic retrograde cholangiopancreatography ( ERCP ) ; in high - risk patients , the risk of severe post - ERCP pancreatitis should be reduced through the use of postprocedure rectal nonsteroidal anti - inflammatory drug ( NSAID ) suppositories and / or pancreatic duct stents The guidelines recommend against routinely using prophylactic antibiotics in cases of severe acute pancreatitis and / or sterile necrosis ; however , intervention in patients with infected necrosis may be delayed through the use of antibiotics that do not penetrate the necrotic tissue In mild cases of acute pancreatitis with no nausea and vomiting , oral feeding can be initiated immediately ; enteral nutrition should be used in severe cases to prevent infectious complications , and parenteral nutrition should be avoided Regardless of the lesion ' s size , location , and / or extension , intervention is not necessary for asymptomatic pancreatic and / or extrapancreatic necrosis and / or pseudocysts Surgical , radiologic , and / or endoscopic drainage in stable patients with infected necrosis should be postponed ( for 4 weeks if possible ) to permit a wall to develop around the necrosis As of 2015 , the American Gastroenterological Association recommends the following in the diagnosis and management of asymptomatic neoplastic pancreatic cysts 22 For asymptomatic mucinous cysts , a 2 - year interval is recommended for a cyst of any size undergoing surveillance , with surveillance being stopped after 5 years if there is no change . Perform surgery only if there is more than one concerning feature on MRI confirmed on endoscopic ultrasonography ( EUS ) and only in centers with high volumes of pancreatic surgery , and there should be no surveillance after surgery if there is no invasive cancer or dysplasia . The risk of malignant transformation of pancreatic cysts is approximately 0.24 % per year , and the risk of cancer in cysts without a significant change over a 5 - year period is likely to be lower . The small risk of malignant progression in stable cysts is likely outweighed by the costs of surveillance and the risks of surgery . Positive cytology on EUS - guided fine - needle aspiration ( FNA ) has the highest specificity for diagnosing malignancy ; if there is a combination of high - risk features on imaging , that is likely to increase the risk of malignancy even further . Similarly , if a cyst has both a solid component and a dilated pancreatic duct ( confirmed on both EUS and MRI ) , the specificity for malignancy is likely to be high even in the absence of positive cytology . There is lower immediate postoperative mortality , as well as long - term mortality , for patients who undergo surgery in high - volume pancreatic centers . It seems sensible to offer screening even after the cyst has been resected , provided the patients have not undergone total pancreatectomy . Surveillance should continue as long as the patient remains a good candidate for surgery . MRI every 2 years may be a reasonable approach for these patients . The clinician may elect to offer more frequent surveillance in the case of invasive cancer resection , particularly if there is concern that the lesion has not been fully resected . Laboratory Studies Amylase and lipase Serum amylase and lipase levels are typically elevated in persons with acute pancreatitis . However , these elevations may only indicate pancreastasis . In research studies , amylase or lipase levels at least 3 times above the reference range are generally considered diagnostic of acute pancreatitis . Serum amylase determinations are routinely available , but they are not specific for pancreatitis . Preferably , the amylase P level should be measured , which is somewhat more specific to pancreatic pathology . Elevations can occur in patients with small intestinal obstruction , mesenteric ischemia , tubo - ovarian disease , renal insufficiency , or macroamylasemia . Rarely , elevations may reflect parotitis . The serum half - life of amylase is short , and elevations generally return to the reference ranges within a few days . Lipase has a slightly longer half - life and its abnormalities may support the diagnosis if a delay occurs between the pain episode and the time the patient seeks medical attention . Elevated lipase levels are more specific to the pancreas than elevated amylase levels . Lipase levels remain high for 12 days . In patients with chronic pancreatitis ( usually caused by alcohol abuse ) , lipase levels may be elevated in the presence of a normal serum amylase level . The level of serum amylase or lipase does not indicate whether the disease is mild , moderate , or severe , and monitoring levels serially during the course of hospitalization does not offer insight into the prognosis . Liver - associated enzymes Determine alkaline phosphatase , total bilirubin , aspartate aminotransferase ( AST ) , and alanine aminotransferase ( ALT ) levels to search for evidence of gallstone pancreatitis . An ALT level higher than 150 U / L suggests gallstone pancreatitis and a more fulminant disease course . Serum electrolytes , BUN , creatinine , glucose , cholesterol , and triglycerides Obtain measurements for blood urea nitrogen ( BUN ) , creatinine , and electrolytes ; a great disturbance in the electrolyte balance is usually found , secondary to third spacing of fluids . Measure blood glucose level because it may be elevated from B - cell injury in the pancreas . Measure calcium , cholesterol , and triglyceride levels to search for an etiology of pancreatitis ( eg , hypercalcemia or hyperlipidemia ) or complications of pancreatitis ( eg , hypocalcemia resulting from saponification of fats in the retroperitoneum ) . However , be aware that baseline serum triglyceride levels can be falsely lowered during an episode of acute pancreatitis . Complete blood count and hematocrit A complete blood count ( CBC ) demonstrates leukocytosis ( white blood cell [ WBC ] count higher than 12,000 / µL ) with the differential being shifted toward the segmented polymorphonuclear ( PMN ) cells . Leukocytosis may represent inflammation or infection . Hemoconcentration at admission ( an admission hematocrit value greater than 47 % ) has been proposed as a sensitive measure of more severe disease . However , this has subsequently been shown to have value only as a negative predictor — that is , a lack of hemoconcentration effectively rules out severe disease . If blood transfusion is necessary , as in cases of hemorrhagic pancreatitis , obtain type and cross - match . C - reactive protein A C - reactive protein ( CRP ) value can be obtained 24 - 48 hours after presentation to provide some indication of prognosis . Higher levels have been shown to correlate with a propensity toward organ failure . A CRP value in double figures ( ie , ≥ 10 mg / dL ) strongly indicates severe pancreatitis . CRP is an acute - phase reactant that is not specific for pancreatitis . Other tests Evaluate arterial blood gases if a patient is dyspneic . Whether tachypnea is due to acute respiratory distress syndrome ( ARDS ) or diaphragmatic irritation must be determined . Lactic dehydrogenase ( LDH ) , BUN , and bicarbonate levels should be measured both at admission and at 48 hours in order to help determine the Ranson criteria for survival . Immunoglobulin G4 ( IgG4 ) levels can be checked to evaluate for autoimmune pancreatitis , especially in recurrent acute pancreatitis that is not explained by an obvious etiology . However , this test is not specific , because IgG4 levels can be elevated in as many as 10 % of patients with acute pancreatitis who do not have autoimmune pancreatitis . Trypsin and its precursor trypsinogen - 2 in both the urine and the peritoneal fluid have been evaluated as possible markers for acute pancreatitis ( especially post - ERCP pancreatitis ) but are not widely used . Trypsinogen activation peptide ( TAP ) is formed when trypsinogen is cleaved to form trypsin and can be measured commercially in the urine to diagnose acute pancreatitis and to help determine severity . Although not currently in use clinically , polymorphisms in the chemokine monocyte chemotactic protein 1 ( MCP - 1 ) gene may also predict severity . This is the first gene identified that plays a role strictly in predicting the severity of disease . Abdominal Radiography Abdominal radiographs have a limited role in acute pancreatitis . Kidneys - ureters - bladder ( KUB ) radiography with the patient in the upright position is primarily performed to detect free air in the abdomen , indicating a perforated viscus , as would be the case in a penetrating , perforated duodenal ulcer . In some cases , the inflammatory process may damage peripancreatic structures , resulting in a colon cut - off sign , a sentinel loop , or an ileus . The presence of calcifications within or around the pancreas may indicate chronic pancreatitis Ultrasonography Abdominal ultrasonography Ultrasonography of the abdomen is the most useful initial test in determining the etiology of pancreatitis and is the technique of choice for detecting gallstones . In the setting of acute pancreatitis , sensitivity is reduced to 70 % - 80 % . In addition , the ability to identify choledocholithiasis is limited . Although ultrasonography can be used as a screening test , it may not be specific if overlying gas shadows secondary to bowel distention are present . Ultrasonography can not measure the severity of disease . Endoscopic ultrasonography Endoscopic ultrasonography ( EUS ) is an endoscopic procedure that allows a high - frequency ultrasound transducer to be inserted into the gastrointestinal ( GI ) tract to visualize the pancreas and the biliary tract . This study allows a more detailed image to be obtained than with transcutaneous ultrasonography because the high - frequency transducer can be introduced directly adjacent to the pancreas . Its principal role in the evaluation of acute pancreatitis is the detection of microlithiasis and periampullary lesions not easily revealed by other methods . This modality should not be used to help identify chronic pancreatitis until several months after the episode of acute pancreatitis . In specialized centers with highly trained medical staff , a secretin - stimulated EUS study may reveal resistance to ductal outflow at the level of the papilla , as evidenced by dilatation of the pancreatic duct to a greater extent and longer duration than in a healthy population . This can be helpful in evaluating patients with recurrent idiopathic pancreatitis . Computed Tomography Scanning Abdominal computed tomography ( CT ) scanning is generally not indicated for patients with mild pancreatitis unless a pancreatic tumor is suspected ( usually in elderly patients ) . It is always indicated in patients with severe acute pancreatitis and is the imaging study of choice for assessing complications . Scans are seldom needed within the first 72 hours after symptom onset unless the diagnosis is uncertain , because inflammatory changes are often not radiographically present until this time . 23 Abdominal CT scans also provide prognostic information based on the following grading scale developed by Balthazar and colleagues 24 25 26 Grade A - Normal pancreas Grade B - Focal or diffuse gland enlargement Grade C - Intrinsic gland abnormality recognized by haziness on the scan Grade D - Single ill - defined collection or phlegmon Grade E - Two or more ill - defined collections or the presence of gas in or near the pancreas The chances of infection and death are virtually nil in grades A and B but steadily increase in grades C through E . Patients with grade E pancreatitis have a 50 % chance of developing an infection and a 15 % chance of dying . Dynamic spiral CT scanning is used to determine the presence and extent of pancreatic necrosis . After the administration of an oral agent to define bowel structures , a study of the upper abdomen is performed twice , before and after administration of an intravenous ( IV ) bolus of iodine contrast agent . For a healthy pancreas , density numbers are in the range of 30 - 40 Hounsfield units on an unenhanced study , increasing to 100 - 150 Hounsfield units on an enhanced study . When pancreatic necrosis is present , focal or diffuse areas of unenhanced parenchyma on the second study suggest pancreatic necrosis . Pancreatic necrosis for research purposes is defined as loss of enhancement in at least 30 % of the pancreatic parenchyma . Magnetic Resonance Cholangiopancreatography Magnetic resonance cholangiopancreatography ( MRCP ) has an emerging role in the diagnosis of suspected biliary and pancreatic duct obstruction in the setting of pancreatitis . Heavily T2 – weighted images provide a noninvasive image of the biliary and pancreatic ducts . 1 Although MRCP is not as sensitive as endoscopic retrograde cholangiopancreatography ( ERCP ) , it is safer , noninvasive , and fast , as well as provides images useful in guiding clinical care decisions . MRCP should be used if choledocholithiasis is suspected but there is concern that pancreatitis might worsen if ERCP is performed . Endoscopic Retrograde Cholangiopancreatography Endoscopic retrograde cholangiopancreatography ( ERCP ) is an endoscopic procedure used to evaluate the biliary and pancreatic ductal systems and is indicated in a subset of patients with acute pancreatitis ( see the image below ) . However , ERCP should be used with extreme caution in patients with acute pancreatitis and should never be used as a first - line diagnostic tool in this disease . 1 This procedure should be performed only in the following situations : The patient has severe acute pancreatitis that is believed , and is seen on other radiographic studies , to be secondary to choledocholithiasis The patient has biliary pancreatitis and is experiencing worsening jaundice and clinical deterioration despite maximal supportive therapy This patient with acute gallstone pancreatitis underwent endoscopic retrograde cholangiopancreatography . Cholangiogram shows no stones in common bile duct and multiple small stones in gallbladder . Pancreatogram shows narrowing of the pancreatic duct in area of genu , resulting from extrinsic compression of ductal system by inflammatory changes in the pancreas . View Media Gallery When combined with sphincterotomy and stone extraction , ERCP may reduce the length of hospital stay , the complication rate , and , possibly , mortality . In the case of biliary pancreatitis where a dilated obstructed common bile duct is diagnosed on the basis of the findings of computed tomography ( CT ) scanning or any other imaging modality and an elevated plasma bilirubin level ( > 5 mg / dL ) , ERCP with sphincterotomy is warranted within the first 72 hours . Biliary pancreatitis should always be treated eventually with a cholecystectomy after the process has subsided . Occasionally , ERCP with sphincter of Oddi manometry reveals sphincter of Oddi dysfunction ( SOD ) as the cause of recurrent idiopathic pancreatitis . Known risk factors for post - ERCP pancreatitis are summarized in table 1 , below . 27 28 Table 1 . Risk Factors for Post - ERCP Pancreatitis . ( Open Table in a new window ) Acute pancreatitis ( any ) or a history of post - ERCP pancreatitis Younger age Female sex Absence of bile duct stones More than 10 attempts to cannulate the papilla of Vater Pancreatic duct cannulation Contrast medium injection of the the pancreatic system Pancreatic sphincterotomy Sphincter of Oddi dysfunction In suspected SOD , especially SOD type 3 , the risk of procedure - induced pancreatitis can exceed 30 % . It is generally thought that the experience of the operator is a risk factor for post - ERCP pancreatitis . Although no difference was found between case volume of the endoscopist or center , high - volume centers treated a larger number of patients at high risk of pancreatitis and performed a significantly greater number of procedures . 28 Image - Guided Aspiration and Drainage Computed tomography ( CT ) - guided needle aspiration is used to differentiate infected necrosis from sterile necrosis in patients with severe necrotizing pancreatitis . The needle is placed into an area of low attenuation in or around the pancreas of a patient with fever and tachycardia or other signs of a systemic inflammatory response syndrome , generally following the first week of severe pancreatitis . The procedure may be repeated weekly if clinically indicated . The specimen should be delivered to the laboratory within an hour and interpreted promptly . The specimen should always be evaluated for Gram stain , culture , and sensitivity . If the Gram stain shows bacteria or fungi , surgical debridement of the infected necrosis is generally indicated . An exception would be if the patient can not tolerate surgery ; in that case , CT - guided catheter drainage may be more effective . Endoscopic ultrasonography ( EUS ) - guided needle aspiration can often be used to differentiate infected necrosis from sterile necrosis in the same manner as CT - guided needle aspiration . EUS can also be used to guide drainage of pancreatic and peripancreatic fluid collections that have complicated an episode of acute pancreatitis . 29 These procedures should only be carried out once the pseudocyst has had the opportunity to mature . A complete description of these procedures is beyond the scope of this article . Genetic Testing With the advent of molecular medicine , various genetic abnormalities have been identified with pancreatitis . Although effective treatments for these conditions have yet to be discovered , it is sometimes reasonable to begin testing for these mutations in patients with otherwise idiopathic pancreatitis , rather than subjecting the entire group to the risks of endoscopic sphincterotomy or stent placement for presumptive diagnosis of sphincter of Oddi dysfunction . As more is learned about molecular mechanisms and therapy , logical novel treatments may eventually be offered to these patients as part of clinical trials . Of course , as with any type of genetic testing , expert genetic counseling that addresses social , familial , insurance , and financial issues is essential for all persons before testing . In fact , it is the author ’ s policy not to perform any genetic testing unless patients are first counseled by a qualified genetic counselor . Hereditary pancreatitis has been associated with a mutation of cationic trypsinogen ( PRSS1 ) . At least 4 mutations have thus far been identified . These mutations appear to render the protein resistant to second - line proteolytic defense mechanisms . Patients with PRSS1 mutations typically develop their first episode of pancreatitis by the time they are in their mid teens . Most often , there is a strong family history of pancreatic disease ( eg , acute or chronic pancreatitis , pancreatic malignancy ) . It should be noted that - related pancreatitis is very rare . Some patients with idiopathic pancreatitis have atypical mutations in the CFTR gene , which follows an autosomal recessive pattern of inheritance . This is a fascinating advance in understanding the spectrum of cystic fibrosis , in which phenotypic expression depends on the degree to which the mutation affects the activity of the CFTR enzyme ’ s function . Relatively minor mutations that do not affect pulmonary function may influence chloride transport in the pancreas enough to predispose individuals to recurrent idiopathic pancreatitis . Mutations in the SPINK1 gene can predispose patients to acute pancreatitis . The SPINK1 protein blocks the active binding site of trypsin , rendering it inactive . However , approximately 1 in 100 persons in the United States are at least heterozygotes for SPINK1 . It is an autosomal recessive gene pattern of inheritance . Therefore , although mutations of the SPINK1 gene are not usually enough to cause pancreatitis , they are likely to be a cofactor responsible for pancreatitis in some individuals . Histologic Findings For practical purposes , the infinite spectrum of pancreatitis severity is usually subdivided into mild and severe categories as follows : Mild pancreatitis - The gland exhibits interstitial edema and an inflammatory infiltrate without hemorrhage or necrosis , usually with minimal or no organ dysfunction Severe pancreatitis - Extensive inflammation and necrosis of the pancreatic parenchyma are present , often associated with severe gland dysfunction and multiorgan system failure At surgery , peripancreatic fatty tissue is predominantly involved by necrosis , whereas the gland is usually less affected ; hence , the extent of pancreatic necrosis is commonly overestimated . In very severe cases , arterial thrombosis may lead to panlobular infarction , in which the gland becomes a hemorrhagic , necrotic , gangrenous mass . The natural history of fat necrosis depends on its location and extent ; small areas ( < 1 cm ) may resolve entirely , whereas large areas ( > 5 cm ) may liquefy within a fibrotic capsule . Staging Various strategies have been used to predict the severity and outcome of acute pancreatitis , including the Ranson , Acute Physiology and Chronic Health Evaluation ( APACHE ) II , Glasgow , and Imrie scoring systems . Each has advantages and disadvantages , and none is currently recognized as a criterion standard . For research purposes , the Atlanta classification of acute pancreatitis has been used to differentiate between severe and mild cases of acute pancreatitis . 2 According to this classification , patients are diagnosed with severe acute pancreatitis if they show the following : Evidence of organ failure ( eg , systolic blood pressure below 90 mm Hg , arterial partial pressure of oxygen [ P a O 2 ] 60 mm Hg or lower , serum creatinine level 2 mg / dL or higher , GI bleeding amounting to 500 mL or more in 24 hours ) Local complications ( eg , necrosis , abscess , pseudocyst ) Ranson score of 3 or higher or APACHE score of 8 or higher Ranson criteria Ranson used a series of different criteria for the severity of acute pancreatitis to formulate a scoring system that is still widely used . 30 Criteria present on admission include the following : Patient older than 55 years WBC count higher than 16,000 / µL Blood glucose level higher than 200 mg / dL Serum LDH level higher than 350 IU / L AST level higher than 250 IU / L Criteria developing during the first 48 hours include the following : Hematocrit fall of more than 10 % BUN level increase by more than 8 mg / dL Serum calcium level lower than 8 mg / dL P a O less than 60 mm Hg Base deficit higher than 4 mEq / L Estimated fluid sequestration higher than 6 L Each of the above criteria counts for 1 point toward the score . A Ranson score of 0 - 2 has a minimal mortality , and the patient is admitted to the regular ward for medical therapy and support . A Ranson score of 3 - 5 has a 10 % - % 20 % mortality rate , and the patient should be admitted to the intensive care unit ( ICU ) . A Ranson score higher than 5 after 48 hours has a mortality of more than 50 % and is associated with more systemic complications . Although the Ranson criteria are perhaps the best known scoring system , they have several drawbacks . First , 11 criteria are used , some of which are evaluated on day 1 and others on day 2 . The Ranson score is valid only at 48 hours after onset and not at any other time during the disease . Second , the threshold for an abnormal value depends on whether the pancreatitis is caused by alcohol or gallstones . Finally , the sensitivity is only 73 % and the specificity is 77 % for predicting mortality . BUN An elevated BUN level at admission has been associated with an increase in severe acute pancreatitis and / or death . This corresponds well with the APACHE II score . The rise in BUN is thought to be due to hemoconcentration , which is a surrogate marker for intravascular depletion . Intravascular depletion is thought to be a key mediator of the inflammatory response in acute pancreatitis . APACHE II The APACHE score has the advantage of being able to assess the patient at any point during the illness ; however , it is very cumbersome for routine clinical use . Attempts have been made to make this evaluation user friendly ( eg , with APACHE II , the Simplified Acute Physiology Score [ SAPS ] , and the Imrie score ) , but it remains cumbersome . The sensitivity is 77 % , and the specificity is 84 % . See the APACHE II Scoring System calculator . Biological markers The most widely available biological marker for staging acute pancreatitis is the hematocrit value . Admission hemoconcentration to a hematocrit value greater than 47 % had been reported as a sensitive predictor of pancreatic necrosis at admission . However , a subsequent study has revealed admission hematocrit to be useful only as a negative predictor for necrosis in patients without hemoconcentration . CRP , a nonspecific acute - phase reactant produced by the liver in response to interleukin ( IL ) – 6 , is a useful marker at 36 - 48 hours . A CRP level greater than 6 at 24 hours or greater than 7 at 48 hours is consistent with severe acute pancreatitis . The sensitivity of this test is 73 % , and the specificity is 71 % . IL - 6 levels begin to rise in the first several hours of pancreatitis , stimulating the release of CRP . Early studies of IL - 6 as a biological marker appear promising , indicating that this may be a reliable indicator of pancreatitis severity . However , this conclusion is not yet validated , and IL - 6 is not yet commercially available for clinical use in this setting . Several other blood tests show promise in predicting the severity of acute pancreatitis . These include trypsinogen activation peptide ( TAP ) , polymorphonuclear elastase , and phospholipase A . Like IL - 6 , they are generally not used in clinical practice and are more expensive than typically used tests . Some are only slightly better than using CRP . Genetic markers Polymorphisms in the chemokine monocyte chemotactic protein 1 ( MCP - 1 ) gene may play a role in predisposing patients to severe acute pancreatitis , although this marker is still under investigation and is not used clinically . Treatment & Management Sections Acute Pancreatitis Overview Presentation DDx Workup Treatment Guidelines Medication Questions & Answers Media Gallery Tables References
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[
"Acute Pancreatitis Workup"
] |
http://emedicine.medscape.com/article/1835801-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pediatrics : Developmental and Behavioral Articles Reading Learning Disorder Treatment & Management Updated : May 27 , 2016 Author : Eric R Crouch , MD ; Chief Editor : Caroly Pataki , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Follow - up References Medical Care Appropriate referrals to a special education ( SPED ) setting , specialized tutoring setting , or both can prove important for long - term progress and improved reading performance . Once the learning disorder of dyslexia or dyscalculia have been recognized and delineated , various methods of treatment should be used to assist the child ' s academic development . Remedial teachers , speech and language therapists , and occupational therapists can all be very valuable in the management of children with learning disorders and may also further refine the spectrum of clinical findings for the pediatrician . Remedial help Various treatments regarding ocular dominance , eye teaming , and scotopic sensitivity have been applied to children with reading disorders . Evidence - based clinical research over the past 30 years has determined many of these alternative treatments to be ineffective . The physiological basis of dyslexia is not materially impacted by treatments that do not address the underlying neuroanatomic dysfunction in the phonemic processing . The pediatric ophthalmologist and pediatric neurologist must explain to the parents that dyslexia is not a disorder of the visual system but rather is a disability in processing separate from the visual pathways to the occipital cortex and is based in neurophysiological maldevelopment of various regions of language development . Visual training , including eye muscle exercises , ocular pursuits , and training with or without bifocals does not benefit children with dyslexia , dyscalculia , or other learning disorders . Tinted lenses or Irlen lenses have also been unhelpful for children with dyslexia . Balance board training , crawling exercises , and perceptual training have also been ineffective for children with dyslexia and other learning disorders . Some of these controversial methods can even result in delayed diagnosis or delayed treatment for the affected child . Children with a concomitant diagnosis of ADHD or hyperactivity may benefit from pharmaceutical treatment . However , the parents should be cautioned to realize that such treatments , although they may improve behavior and attention , are not directly associated with improvements in academic performance . The child still requires specific treatments tailored to the management of the dyslexia . Children with associated psychiatric disorders , including depression , anxiety , aggression , or oppositional behavior , can be managed by the child psychiatrist . Many children with dyslexia can become depressed due to the psychosocial impact of being taught Consultations School consultations The 2004 IDEA requires public schools to provide free and appropriate evaluations and education for children with learning disabilities . Because as many as 20 % of all children may have phonologically based reading problems , not all children are evaluated by the school . If a parent or health care provider suspects a significant reading problem , the parent should make a formal request ( ie , a dated letter ) for evaluation to the school and request to develop an appropriate individual education plan ( IEP ) . With parental permission , a second letter from a health care provider requesting the evaluation often helps ; however , the parent must make the initial request . Although state and local school district regulations differ , most districts must comply with a request for evaluation within 60 school days . SPED services provided for a child with a reading disability typically include some time each day in a small group with a reading specialist . The child spends the remainder of the day in a standard classroom . In addition to SPED , many elementary schools also offer the Title I enhanced reading program , which is designed to address the reading needs of economically disadvantaged children . In schools that offer the Title I program , a parental request for those services is often the sole requirement . No formal assessment is required for participation in Title I , although assessment might help some children . In many school districts , all reading programs in kindergarten and first and second grades are administered through the Title I mechanism ; SPED is reserved for reading problems in the Intervention strategies Reading problems affect many children ; however , skillful early intervention at school or home can help ameliorate mild reading difficulties . The following strategies apply both to early intervention and to remedial work for an older child who reads poorly : Phonemic awareness tasks in kindergarten include rhyming , making discriminations between similar but different words , blending sounds into words , isolating sounds from words , and segmenting words . These tasks prepare the child for reading , and all have shown some effectiveness in research settings . Explicitly teaching children about segmenting and blending words has proven more effective in teaching reading than programs that do not explicitly teach those skills . In first grade , explicit instruction in how the most common sounds are spelled enhances both reading and spelling skills . Showing children how to sound out words and providing texts they can decode helps in practicing and retaining learned sound - spelling relationships . Some schools do not emphasize these processes . The only option for children in these schools is to find an appropriate reading tutor or after - school reading programs . Programs that use the Orton - Gillingham or Lindamood - Bell methods have some success teaching students with reading disorders . Both systems emphasize sound recognition and sound - symbol relationships as the basis for reading . Parents should evaluate private reading clinics and should also inquire about reading clinics offered by local colleges of education . Helpful software programs are also available to teach phonemic recognition ; programs such as Reader Rabbit or Blues Clues can be effective adjuncts to tutoring and classroom intervention . Medication Sections Reading Learning Disorder Overview Presentation DDx Workup Treatment Follow - up References Recommended Diseases & Conditions Mathematics Learning Disorder Sleep Disorders
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[
"Disorder Treatment",
"Management",
"SPED"
] |
http://emedicine.medscape.com/article/1839601-technique
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Clinical Procedures Fractional Flow Reserve Measurement Technique Updated : Oct 13 , 2016 Author : Eiman Jahangir , MD , FACC ; Chief Editor : Karlheinz Peter , MD , PhD more . . . Sections Overview Periprocedural Care Technique Approach Considerations Specific Approaches to FFR Measurement Complications Show All Medication Media Gallery References Approach Considerations Typically , conscious sedation is administered as part of the cardiac catheterization . Unless the patient is uncomfortable , no other anesthesia is required . The patient is placed in the supine position . To measure fractional flow reserve ( FFR ) , the operator crosses the coronary stenosis with an FFR - specific guide wire designed to record the coronary arterial pressure distal to the stenosis . The pressure transducer is located approximately 20 mm proximal to the distal tip of the wire , and it can be seen fluoroscopically . Once the transducer is distal to the stenosis , a hyperemic stimulus is administered by injection through the guide catheter , and the FFR is monitored for a significant change . To achieve maximum hyperemia , adenosine is typically used : a 15 - 30 µg bolus in the right coronary artery , a 20 - 40 µg bolus in the left coronary artery , or intravenous ( IV ) infusion for 3 - 4 minutes at 140 µg / kg / min . The mean arterial pressures from the pressure wire transducer and from the guide catheter are then An FFR value lower than 0.75 indicates a hemodynamically significant stenosis . An FFR value higher than 0.8 indicates a stenosis that is not hemodynamically significant . Values between 0.75 and 0.80 are indeterminate and should be considered in the context of patient ’ s clinical history to determine if revascularization is necessary . Next : Specific Approaches to FFR Measurement What to Read Next on Medscape Related Conditions and Diseases Lipid Management Guidelines Fast Five Quiz : Do You Know Current Guidelines for Lipid Management ? Tricyclic Antidepressant Toxicity in Pediatrics Fast Five Quiz : How Much Do You Know About Hypertriglyceridemia ? Fast Five Quiz : How Much Do You Know About Facilitating Healthy Weight Loss ? Fast Five Quiz : How Much Do You Know About Medical Factors That Help and Hinder Memory ? News & Perspective Tackling Residual Atherosclerotic Risk in Statin - Treated Adults : Focus on Emerging Drugs Lipid Management Suboptimal Despite High - Intensity Therapy AHA Issues First Cardio - Oncology Rehabilitation Statement Tools Drug Interaction Checker Pill Identifier Calculators Formulary Slideshow Cardiology Guidelines : 2017 Midyear Review Most Popular Articles According to Cardiologists Alcohol and the Electric Atrium : How Drinking Promotes AF ? Marijuana Edible Linked to Myocardial Infarction The Remarkable Story of a Wonder Drug , Which Now Comes to an End in the Primary Prevention Setting : Say Bye - bye to Aspirin ! A Morning Walk , Less Sitting Can Lower Blood Pressure for Hours New AHA / ACC CVD Primary Prevention Guideline View More Sections Fractional Flow Reserve Measurement Overview Periprocedural Care Technique Specific Approaches to FFR Measurement Complications Show All Medication Media Gallery References Recommended Diseases & Conditions Lipid Management Guidelines News Lipid Management Suboptimal Despite High - Intensity Therapy
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[
"fractional flow reserve",
"Measurement Technique"
] |
http://emedicine.medscape.com/article/185356-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Gastroenterology Small Intestinal Diverticulosis Treatment & Management Updated : Jun 26 , 2015 Author : Rohan C Clarke , MD ; Chief Editor : Julian Katz , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Follow - up References Medical Care Clinicians must maintain a high index of clinical awareness to avoid missing small intestinal diverticulosis . Therefore , any patient with unresolved symptoms , complications , or recurrent symptoms should be evaluated further . The general recommendation favors a conservative approach to the management of asymptomatic diverticula . These lesions are generally left alone unless they can be related to diseases . In certain locations , diverticula are associated with special complications . For example , periampullary diverticula can be associated with pancreatitis , cholangitis , or recurrent choledocholithiasis after cholecystectomy . Intraluminal diverticula are observed in the duodenum and can be complicated by intestinal obstruction and biliary and pancreatic diseases . A higher complication rate is associated with jejunoileal diverticulosis and , as such , may justify a less conservative approach to its management . Capsule endoscopy might be of value , if available , to identify the site of the bleeding . Push enteroscopy or double balloon enteroscopy should be used once a lesion amenable to therapeutic intervention has been identified . Inpatient treatment is indicated only in patients presenting with complications . The duration of such admission depends on the nature of the complication and the interventions rendered . Once inflammation / infection has resolved , endoscopic modalities may be employed to further evaluate and treat , if possible . Prehospital care Acute abdomen and obvious or occult gastrointestinal ( GI ) hemorrhage are the clinical scenarios that necessitate prehospital intervention . Vascular access , intravenous fluid , oxygen , and prompt transport to the hospital are all that is required in the field . Medical management Abdominal pain without clinical evidence of diverticulitis or intestinal obstruction requires no specific treatment . Patients benefit from the use of bulk - forming agents , such as fiber , bran , and cellulose products . Intractable pain associated with anemia and jejunal loop dilatation on radiograph should heighten concern for jejunal diverticulosis . When diverticula are secondary to small bowel dysmotility , no specific intervention is warranted , other than surgical if complications arise . For diverticulitis , patients often require hospitalization because preoperative diagnosis of small bowel diverticulitis is difficult . Initial interventions include the following : Bed rest Nothing by mouth and / or nasogastric suctioning IV fluid Broad - spectrum antibiotic coverage Surgical consultation : Urgent surgery rarely is indicated unless perforation , abscess , or neoplasm is suspected . Consultations Consultation with a general surgeon is indicated for all patients requiring surgical management . A gastroenterologist assists with diagnosis and follow - up strategy and performs both diagnostic and therapeutic endoscopy Diet and activity The role of diet is not clear . A high - fiber diet that improves bowel motility and is used in colonic diverticulosis may be beneficial . No restriction of activity is indicated . Management of complications The approach to management of complicated small bowel diverticula involves initiation of medical and supportive management . Surgical consultation must be performed promptly . GI bleeding and / or hemorrhage Note the following : Patient is treated with intravenous ( IV ) fluid and blood products as necessary . Diagnostic workup is usually completed in the intensive care setting . Most patients stop bleeding , allowing elective surgery . Mesenteric angiography with infusion of vasoconstrictors can be used in persistent hemorrhage . Laparotomy may be indicated as an emergency therapy for continuing bleeding or as elective treatment if bleeding responds to conservative management . Intestinal perforation Early surgery is the treatment of choice for patients with intestinal perforation . Fluid and electrolyte management as well as antibiotics are essential adjuncts . Intestinal obstruction Initial management of intestinal obstruction is similar to uncomplicated diverticulitis . Urgent surgical consultation is mandatory . Intestinal pseudoobstruction Cautious conservative management is indicated for intestinal psuedoobstruction while excluding mechanical obstruction . Fistula formation Fistula formation is a rare complication . Malabsorption Malabsorption is often a complication of bacterial overgrowth resulting from blind loop syndrome . It usually responds to antibiotics . Diverticula Preoperative diagnosis of diverticula is seldom made . This can present as intussusception , volvulus , or pseudoobstruction . Flatulence and bloating Flatulence and bloating are other complications of bacterial overgrowth , which usually responds to antibiotic therapy . Surgical Care Complications of small bowel diverticulosis , such as massive bleeding or diverticulitis with perforation , require surgery . Diagnosis is seldom made preoperatively . The aim is to control complications when present and / or to prevent future complications . Emergency surgery is indicated for severe diverticulitis , intestinal perforation , intestinal obstruction , and hemorrhage that continues after conservative management . Several operative procedures are available depending on the type of diverticulum , site , and nature of complications . Simple diverticulectomy is most commonly used for symptomatic diverticulum or bleeding diverticulum of the duodenum . The diverticulum is simply excised , and the bowel is closed longitudinally or transversely , ensuring minimal luminal stenosis . This procedure requires modification in cases involving a diverticulum that is embedded deep in the head of the pancreas or is associated with the ampulla of Vater , is perforated , or is intraluminal in location . It can be technically difficult in the presence of common duct obstruction . These patients benefit more from choledochoduodenostomy . Meckel diverticulum can also be removed by Intestinal resection and end - to - end anastomosis is the preferred approach to jejunoileal diverticulum , which tends to be multiple , irrespective of the type of complication . Enterotomy can be performed solely to remove enterolith of diverticular origin causing distal obstruction . Caveats of surgical management Perforated duodenal diverticulum requires a special approach . Simple excision and closure may be complicated by obstruction ; therefore , consider complete diversion of the bowel from the duodenum , then perform vagotomy , antrectomy , closure of the duodenal loop , and Billroth II anastomosis . Dysmotility alone without obstruction is not an indication for bowel resection because resection would not prevent propagation of motility disorder . Medication Sections Small Intestinal Diverticulosis Overview Presentation DDx Workup Treatment Follow - up References
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[
"Small Intestinal Diverticulosis",
"Treatment",
"Management"
] |
http://emedicine.medscape.com/article/186389-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Gastroenterology Hyperamylasemia Updated : Apr 01 , 2019 Author : Abraham Mathew , MD , MS ; Chief Editor : BS Anand , MD more . . . Sections Background Pathophysiology Etiology Laboratory Studies Special Concerns Show All References Background Amylase is a digestive enzyme that normally acts extracellularly to cleave starch into smaller carbohydrate groups and , finally , into monosaccharides , by hydrolysis of the internal alpha - 1 , 4 - glycoside bonds , which results in the production of maltose and oligosaccharides . Among healthy individuals , the pancreas and the salivary glands account for almost all the serum amylase , 40 % - 45 % from the pancreas and 55 % - 60 % from the salivary glands . Serum amylase is increased in at least 75 % of pancreatitis cases ; however , serum amylase can be normal , even in the face of massive pancreatic necrosis . The major limitation of using serum amylase measurement in diagnosing pancreatitis is the lack of specificity . 1 Next : Pathophysiology What to Read Next on Medscape Related Conditions and Diseases Gastric Volvulus Pancreatic Divisum Acute Pancreatitis Imaging Pancreatic Pseudoaneurysm Kidney - Pancreas Transplantation Pediatric Choledochal Cyst Surgery News & Perspective Obesity and Pancreatitis Periprocedural Hydration in the Prevention of Post - ERCP Pancreatitis Meta - analysis of Prophylactic Corticosteroid Use in Post - ERCP Pancreatitis Tools Drug Interaction Checker Pill Identifier Calculators Formulary Most Popular Articles According to Gastroenterologists Drug - Induced Liver Injury : 5 Things to Know Autoimmune Hepatitis Clinical Practice Guidelines ( 2019 ) High - Fat Diet Adversely Affects Gut Microbiota Facing Facts : Protective Masks Needed to Combat Endoscopy ' s High Risk for Contamination Ulcerative Colitis Clinical Practice Guidelines ( 2019 ) View More Sections Hyperamylasemia Pathophysiology Etiology Laboratory Studies Special Concerns Show All References Recommended Diseases & Conditions Pancreatic Divisum Procedures Gastric Volvulus
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[
"Hyperamylasemia",
"digestive enzyme",
"maltose"
] |
http://emedicine.medscape.com/article/187001-workup
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Gastroenterology Biliary Obstruction Workup Updated : Nov 07 , 2018 Author : Jennifer Lynn Bonheur , MD ; Chief Editor : Vinay Kumar Kapoor , MBBS , MS , FRCS , FAMS more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers References Laboratory Studies Serum bilirubin level Regardless of the cause of cholestasis , serum bilirubin values ( especially direct ) are usually elevated . However , the degree of hyperbilirubinemia can not help reliably distinguish between the causes of obstruction . Extrahepatic obstruction This is typically associated with considerable direct and indirect bilirubin elevation . However , in the early phases of obstruction and with incomplete or intermittent obstruction , serum bilirubin levels may only be mildly elevated . Initially , an increase in the conjugated bilirubin level occurs without affecting the unconjugated bilirubin level because obstruction of the CBD prevents excretion of already conjugated bilirubin into the duodenum . Conjugated bilirubin that does reach the intestine is deconjugated by intestinal bacteria . Unconjugated bilirubin , in contrast to the conjugated form , easily crosses the intestinal epithelial barrier into the blood . Intrahepatic obstruction Both conjugated and unconjugated bilirubin fractions may increase in varying proportions . The unconjugated fraction may be increased because of the inability of the damaged cells to conjugate normal amounts of unconjugated serum bilirubin . The increase of the conjugated fraction usually results from metabolic deficiency in the excretory mechanism caused by the inflammatory process of the disease . Alkaline phosphatase ( ALP ) level A membrane - bound enzyme localized to the bile canalicular pole of hepatocytes , ALP is markedly elevated in persons with biliary obstruction . However , high levels of this enzyme are not specific to cholestasis . To determine whether the enzyme is likely to be of hepatic origin , measure gamma - glutamyl transpeptidase ( GGT ) or 5 - prime - nucleotidase . These values tend to parallel the ALP levels in patients with liver disease . GGT is used most commonly . While it is part of the routine evaluation of biliary obstruction , the degree of Extrahepatic obstruction ALP levels are elevated in nearly 100 % of patients , except in some cases of incomplete or intermittent obstruction . Values are usually greater than 3 times the upper limit of the reference range , and in most typical cases , they exceed 5 times the upper limit . An elevation less than 3 times the upper limit is evidence against complete extrahepatic obstruction . Intrahepatic obstruction ALP levels are usually elevated , and they often are less than 3 times the upper limit of the normal reference range . However , 5 - 10 % of patients have a greater degree of elevation . Levels of serum transaminases Levels of these are usually only moderately elevated in patients with cholestasis but occasionally may be markedly increased , especially if cholangitis is present . Usually , serum aspartate aminotransferase ( AST ) levels are not elevated unless secondary acute parenchymal damage is present . When elevations occur , they are usually only mild to moderate ( < 10 times the upper reference limit ) . However , when extrahepatic obstruction occurs acutely , AST values may quickly rise to more than 10 times the normal value , and then they fall after approximately 72 hours . With time and progressive hepatocyte damage caused by distended biliary ductules , an elevation in AST levels may be observed . A 3 - fold or more increase Alanine aminotransferase ( ALT ) is predominantly found in the liver , and most elevations are due to intrahepatic disease . Although less specific to the liver , the AST level is also elevated in cases of intrahepatic cholestasis . ALT and AST levels are usually elevated to the same degree in patients with viral hepatitis and those with drug - induced liver damage . In association with alcoholic liver disease , cirrhosis , and metastatic lesions to the liver , the AST level is elevated more frequently than the ALT level . In general , AST levels are usually GGT levels These levels are elevated in patients with diseases of the liver , biliary tract , and pancreas when the biliary tract is obstructed . Levels parallel the levels of ALP and 5 - prime - nucleotidase in conditions associated with cholestasis . The extreme sensitivity of GGT , as opposed to ALP , limits its usefulness ; however , the level helps distinguish hepatobiliary disease as the cause of an isolated rise in ALP . Prothrombin time ( PT ) This may be prolonged because of malabsorption of vitamin K . Correction of the PT by parenteral administration of vitamin K may help distinguish hepatocellular failure from cholestasis . Little or no improvement occurs in patients with parenchymal liver disease . Hepatitis serology Because differentiating viral hepatitis from extrahepatic obstructive causes may be difficult , include serologic assays for acute viral hepatitis B and C in the investigation of all patients with cholestasis . Antimitochondrial antibody levels The presence of antimitochondrial antibodies , usually in high titers , is indicative of PBC . They are usually absent in patients with mechanical biliary obstruction or PSC . Urine bilirubin levels Urine bilirubin normally is absent . When it is present , only conjugated bilirubin is passed into the urine . This may be evidenced by dark - colored urine seen in patients with obstructive jaundice or jaundice due to hepatocellular injury . However , reagent strips are very sensitive to bilirubin , detecting as little as 0.05 mg / dL . Thus , urine bilirubin may be found even in the absence of hyperbilirubinemia or clinical jaundice . Imaging Studies Plain radiographs are of limited utility to help detect abnormalities in the biliary system . Frequently , calculi are not visualized because few are radiopaque . Ultrasonography ( US ) Ultrasonography is the least expensive , safest , and most sensitive technique for visualizing the biliary system , particularly the gallbladder . Current accuracy is close to 95 % . This is the procedure of choice for the initial evaluation of cholestasis and for helping differentiate extrahepatic from intrahepatic causes of jaundice . Extrahepatic obstruction is suggested by the presence of dilated intrahepatic bile ducts , but the presence of normal bile ducts does not exclude obstruction that may be new or intermittent . Visualization of the pancreas , kidney , and blood vessels is also possible . Ultrasonography is considered somewhat limited in its overall ability to help detect the specific cause and level of obstruction . US is not as useful for CBD stones ( bowel gas may obscure visualization of the CBD ) . The cystic duct is also poorly imaged . In addition , it is less useful diagnostically in individuals who are obese . Computed tomography ( CT ) scanning Traditional CT scanning Traditional CT scanning is usually considered more accurate than US for helping determine the specific cause and level of obstruction . In addition , it helps visualize liver structures more consistently than US . The addition of intravenous contrast helps differentiate and define vascular structures and the biliary tract . CT scanning has limited value in helping diagnose CBD stones because many of them are radiolucent and CT scanning can only image calcified stones . It is also less useful in the diagnosis of cholangitis because the findings that specifically suggest bile duct infection ( increased attenuation due to pus , bile duct wall thickening , and gas ) are seen infrequently . Lastly , CT scanning is expensive and involves exposure to radiation , both of which lessen the routine use CT scans compared to US examinations . Spiral CT scanning Spiral ( helical ) CT scanning improves biliary tract imaging by providing several overlapping images in a shorter time than traditional CT scanning and by improving resolution by reducing the presence of respiratory artifacts . CT cholangiography by the helical CT technique is used most often to image the biliary system and makes possible visualization of radiolucent stones and other biliary pathology . 8 Limitations of helical CT cholangiography include reactions to the contrast , which are becoming less frequent . Also , as serum bilirubin levels increase , the ability to visualize the biliary tree diminishes and the ability to fully delineate tumors decreases . Patients are required to hold their breath while images are acquired . Magnetic resonance cholangiopancreatography ( MRCP ) MRCP is a noninvasive way to visualize the hepatobiliary tree . It takes advantage of the fact that fluid ( eg , that found in the biliary tree ) is hyperintense on T2 - weighted images . The surrounding structures do not enhance and can be suppressed during image analysis . However , in its early stages , it was limited in its ability to detect nondilated bile ducts . The advent of rapid acquisition with relaxation enhancement ( RARE ) sequences and half - Fourier RARE ( also known as half - Fourier acquisition single - shot turbo spin Note the following : As with helical CT scanning , MRCP gives radiologists the ability to analyze source images and 2 - and 3 - dimensional projections . Although some techniques require patients to hold their breath for the highest quality images , the time required to complete the scan is decreasing as imaging techniques improve , and alternative procedures capture images between patient breaths . MRCP provides a sensitive noninvasive method of detecting biliary and pancreatic duct stones , strictures , or dilatations within the biliary system . It is also sensitive for helping detect cancer . MRCP combined with conventional MR imaging of the abdomen can also provide information about the surrounding structures ( eg , pseudocysts , masses ) . While ERCP and MRCP may be similarly effective in detecting malignant hilar and perihilar obstruction , MRCP has been shown to be better able to determine the extent and type of tumor as compared to ERCP . In addition , unlike ERCP , MRCP does not require contrast material to be injected to visualize the ductal system , thereby avoiding the morbidity associated with injected contrast . The limitations of MRCP include the contraindications to magnetic resonance imaging . Absolute contraindications include the presence of a cardiac pacemaker , cerebral aneurysm clips , ocular or cochlear implants , and ocular foreign bodies . Relative contraindications include the presence of cardiac prosthetic valves , neurostimulators , metal prostheses , and penile implants . Fluid stasis in the adjacent duodenum or in ascitic fluid may produce image artifacts on MRCP , making it difficult to clearly visualize the biliary tree . The risk of MRCP during pregnancy is not known . Although MRCP currently does not have the capability for the therapeutic applications of the more invasive ERCP , it can be useful for diagnostic purposes and poses less risk to the patient as compared to ERCP . Procedures Endoscopic retrograde cholangiopancreatography ( ERCP ) ERCP is an outpatient procedure that combines endoscopic and radiologic modalities to visualize both the biliary and pancreatic duct systems . Endoscopically , the ampulla of Vater is identified and cannulated . A contrast agent is injected into these ducts , and x - ray images are taken to evaluate their caliber , length , and course . It is especially useful for lesions distal to the bifurcation of the hepatic ducts . Besides being a diagnostic modality , ERCP has a therapeutic application because obstructions can potentially be relieved by the removal of stones , sphincterotomy , and the placement of stents and drains . The addition of cholangioscopy to the ERCP , by advancing a smaller " baby " scope through the endoscope into the common duct , allows for biopsies and brushings within the ducts and better identification of lesions seen on cholangiogram . ERCP has a limited capacity to image the biliary tree proximal to the site of obstruction . Also , it can not be performed if altered anatomy prevents endoscopic access to the ampulla ( eg , Roux loop ) . Complications of this technique include pancreatitis , perforation , biliary peritonitis , sepsis , hemorrhage , and adverse effects from the dye and the drug used to relax the duodenum . The risk of any complication is less than 10 % . Severe complications occur in less than 1 % . The sensitivity and specificity of ERCP are 89 - 98 % and 89 - 100 % , respectively . ERCP is still considered the criterion standard for imaging the biliary system , particularly if therapeutic intervention is planned . Percutaneous transhepatic cholangiogram ( PTC ) PTC is performed by a radiologist using fluoroscopic guidance . 9 The liver is punctured to enter the peripheral intrahepatic bile duct system . An iodine - based contrast medium is injected into the biliary system and flows through the ducts . Obstruction can be identified on the fluoroscopic monitor . It is especially useful for lesions proximal to the common hepatic duct . The technique is not easy and requires considerable experience . More than 25 % of attempts fail ( most often when the ducts can not be well visualized because they are not dilated , ie , not obstructed . ) Complications of this procedure include the possibility of allergic reaction to the contrast medium , peritonitis with possible intraperitoneal hemorrhage , sepsis , cholangitis , subphrenic abscess , and lung collapse . Severe complications occur in approximately 3 % of cases . The accuracy of PTC in elucidating the cause and site of obstructive jaundice is 90 - 100 % for causes within the biliary tract . The biliary tree can be successfully visualized in 99 % of patients with dilated bile ducts and in 40 - 90 % if the bile ducts are not dilated . Still , ERCP is generally preferred , and PTC is reserved for use if ERCP fails or when altered anatomy precludes accessing the ampulla . Endoscopic ultrasound ( EUS ) EUS combines endoscopy and US to provide remarkably detailed images of the pancreas and biliary tree . It uses higher - frequency ultrasonic waves compared to traditional US ( 3.5 MHz vs 20 MHz ) and allows diagnostic tissue sampling via EUS - guided fine - needle aspiration ( EUS - FNA ) . 10 Although endoscopic retrograde cholangiography is the procedure of choice for biliary decompression in obstructive jaundice , biliary access is not always achievable , in which case , interventional endoscopic ultrasound - guided cholangiography ( IEUC ) may offer an alternative to percutaneous transhepatic cholangiography ( PTC ) . Maranki et al reported their 5 - year experience with IEUC in patients who had unsuccessful treatment with ERCP . 11 The investigators used either a transgastric - transhepatic or transenteric - transcholedochal approach to the targeted biliary duct , then advanced a stent over the wire into the biliary tree . 11 Of the 49 patients who underwent IEUC , the cause of biliary obstruction was a malignancy in 35 , whereas 14 had a benign etiology . Forty - one of the 49 patients ( 84 % ) had successful overall therapy with IEUC , with an overall complication rate of 16 % . Resolution of obstruction had an 83 % success rate ( n = 29 ) . The transenteric - transcholedochal approach was used in 14 patients , with successful biliary decompress in 86 % ( n = 12 ) . No procedure - related deaths were reported . Thus , overall , the intrahepatic approach was successful in 73 % ( 29 / 40 ) of cases , and the extrahepatic approach was successful in 78 % ( 7 / 9 ) cases . An international multicenter retrospective analysis found comparable short - term outcomes between EUS - guided biliary drainage and ERCP in 208 patients with&malignant distal common bile duct obstruction who required the placement of self - expandable stents . 12 Ninety - seven of 104 patients ( 94.23 % ) who underwent EUS - guided biliary drainage and 98 of 104 patients ( 93.26 % ) who underwent ERCP had successful stent placement ( P = 1.00 ) ; each group had an 8.65 % frequency of adverse events , and the mean procedural times were similar ( 35.95 mins vs 30.10 mins , respectively ; P = 0.05 ) . However , the rates of postprocedure pancreatitis were higher in the ERCP group ( 4.8 % vs 0 % , = 0.059 ) . 12 EUS has been reported to have up to a 98 % diagnostic accuracy in patients with obstructive jaundice . This makes ERCP unnecessary in patients who are found to not have extrahepatic obstruction . In addition , those patients who may require operative biliary drainage are reliably identified and similarly need not undergo ERCP for further evaluation . 13 EUS provides highly detailed imaging of the pancreas . The sensitivity of EUS for the identification of focal mass lesions has been reported to be superior to that of CT scanning , both traditional and spiral , particularly for tumors smaller than 3 cm in diameter . Compared to MRCP for the diagnosis of biliary stricture , EUS has been reported to be more specific ( 100 % vs 76 % ) and to have a much greater positive predictive value ( 100 % vs 25 % ) , although the two have equal sensitivity ( 67 % ) . Neither transabdominal US nor CT scanning can help reliably exclude the presence of choledocholithiasis . ERCP is highly accurate for this diagnosis but , because of the associated risk of pancreatitis , is generally reserved for patients with known common duct stones . EUS has been reported to have sensitivity approximately equal to both ERCP and MRCP for the detection of common duct stones , with minimal risks directly associated with the procedure . EUS is more portable than ERCP or MRCP and is useful for patients in the intensive care unit . EUS ( if performed in the fluoroscopy suite ) can be followed immediately by therapeutic ERCP , which saves time . The positive yield of EUS - FNA for cytology in patients with malignant obstruction has been reported to be as high as 96 % . Treatment & Management Sections Biliary Obstruction Overview Presentation DDx Workup Treatment Medication Questions & Answers References
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[
"Biliary Obstruction Workup",
"Laboratory Studies",
"Serum bilirubin level"
] |
http://emedicine.medscape.com/article/1894146-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Clinical Procedures Breath Sound Assessment Updated : Mar 05 , 2018 Author : Casey Louis Stahlheber , MD ; Chief Editor : Zab Mosenifar , MD , FACP , FCCP more . . . Sections Background Technique Normal vs Abnormal ( Adventitious ) Breath Sounds Show All Media Gallery References Background Although many newer imaging techniques for the evaluation of lung pathology have been developed , auscultation of the chest remains an invaluable clinical tool and is still probably the most common method of evaluating the lung . Evaluation of lung sounds is a routine part of a clinical examination . Relevant lung anatomy is depicted in the images below . Anterior view of lungs and trachea . View Media Gallery Posterior view of lungs and trachea . View Media Gallery Breath sounds can be classified into the following two broad categories 1 Normal breath sounds Adventitious ( or abnormal ) sounds - These include wheezes , coarse crackles , fine crackles , and rhonchi Next : Technique What to Read Next on Medscape Related Conditions and Diseases Viral Pneumonia Chlamydial Pneumonias Fungal Pneumonia Hospital - Acquired Pneumonia ( Nosocomial Pneumonia ) and Ventilator - Associated Pneumonia Aspiration Pneumonitis and Pneumonia Pediatric Pneumonia News & Perspective Bawa - Garba Granted 2 - Year Conditional Registration to Return to Medical Practice New Antibiotics for Community - Acquired Pneumonia IPAF : Heterogeneity Hurts Clinical Utility Tools Drug Interaction Checker Pill Identifier Calculators Formulary Slideshow Idiopathic Pulmonary Fibrosis : Killer Without a Cause Most Popular Articles According to Pulmonologists Guideline Outlines Step - down Therapy for Asthma FDA Approves First Generic of Advair Diskus Diagnosing Obstructive Sleep Apnea : The Glass is Half Empty , Despite What You ' ve Been Told Recommended Changes to Methacholine Challenge Testing May Be Difficult to Apply for Most Labs FDA OKs Duaklir Fixed - Dose Combination Inhaler for COPD View More Sections Breath Sound Assessment Technique Normal vs Abnormal ( Adventitious ) Breath Sounds Show All Media Gallery References Recommended Diseases & Conditions Viral Pneumonia Diseases & Conditions Chlamydial Pneumonias
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[
"Breath Sound Assessment",
"lung pathology",
"lung sounds"
] |
http://emedicine.medscape.com/article/1894499-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Clinical Procedures Bartholin Gland Marsupialization Updated : Nov 18 , 2015 Author : Tabitha F Perry , MD ; Chief Editor : Christine Isaacs , MD more . . . Sections Overview Periprocedural Care Overview of Technique Post Procedure Medications and Medical Devices Show All Media Gallery References Overview Background The greater vestibular glands ( commonly known as the Bartholin glands ) make up an important part of the female reproductive system . The Bartholin glands have a primary function of secreting mucus to help provide vulvar and vaginal lubrication . 1 To fulfill this purpose , each Bartholin gland contains a duct that measures approximately 5 mm in diameter in the average female . For proper secretion , the epithelium of each gland is columnar in nature , while the epithelium of each duct is simple . The orifice is of the stratified squamous type . The secretion produced is a thick , mucoid , clear substance with a basic pH , and it provides lubrication during sexual activity . 2 Measuring from 1.5 - 2 cm on average , each Bartholin gland is oval in shape and resides just inferior and lateral to the bulbocavernosus muscle . Innervation is received from a small branch of the perineal nerve , while arterial blood supply is received from a small branch of the artery on the bulbocavernosus muscle . Likewise , venous drainage is also via vessels on the bulbocavernosus muscle . Lymphatics are via the vestibular plexus and pudendal vessels , and this drainage route is important to consider when in - depth surgery is needed . 2 See the image below . Bartholin gland nerve innervation View Media Gallery If a gland becomes infected or a duct becomes obstructed , the result is often the development of a Bartholin cyst or abscess that may require medical attention . 3 4 This occurs in 2 % of women . In addition , in rare cases , malignancy of the Bartholin gland can occur . 5 See the images below . Bartholin gland cyst View Media Gallery Bartholin gland abscess Treatment options for Bartholin gland cysts or abscesses include expectant management , sitz baths , antibiotics , Word catheter placement , marsupialization , and gland excision . 6 7 There has been no proven superiority between surgical and conservative management strategies . 8 This article discusses marsupialization , in which the cyst is opened and the edges sutured , forming an " open pocket " or " pouch . " Indications See the list below : History of recurrent Bartholin gland cysts or abscesses Significant patient pain or discomfort Failure of cyst resolution in a timely manner or with alternative treatments Patient declines or can not tolerate Word catheter placement in an office setting Contraindications Contraindications to marsupialization are few and far between , with patient refusal being virtually the only one identified . Technical Considerations Several things must be considered when deciding to perform a Bartholin gland marsupialization . These questions help to guide the choice of procedure location as well as preoperative , intraoperative , and postoperative treatment . Each of these is briefly addressed : Is this a procedure that must be performed in the operating room , or could an alternative procedure such as Word catheter placement be performed in the office ? Is it strictly a Bartholin cyst or is it a Bartholin abscess ? If it is an abscess , what are the organisms involved and are they being treated adequately ? Is the patient immunocompromised ? Are there comorbidities that may make postoperative healing a problem ? Is there significant concern for malignancy ? Word catheterization and marsupialization For information on Word catherization of Bartholin gland cyst or abscess , please see Bartholin Abscess Drainage In general , the effectiveness , complication rates , and recurrence rates are similar between marsupialization and Word catheterization . In a study of 30 Austrian women with Bartholin cyst or abscess that evaluated office implementation , recurrence rates , and costs between Word catheterization and marsupialization , investigators noted an 87 % success rate and 3.8 % recurrence rate in women treated using the Word cathether . 8 Word catherization was simpler to use and cost seven - fold less than marsupialization . In a different analysis , the investigators also evaluated quality of life and sexual activity during and following treatment of Bartholin cyst or abscess with Word catherization and reported improved pain levels as well as significantly improved pain / discomfort dring sexual activity . 9 The mental component summary score of the quality of life evaluation showed a significant improvement after treatment compared with the pretreatment period , although the physical component summary score did not show a significant change . 9 Periprocedural Care Anesthesia The typical anesthesia used for a Bartholin gland marsupialization is procedural sedation , a local anesthetic alone , or a combination of the two . A local anesthetic ( eg , lidocaine , mepivacaine ) should be administered and may minimize postoperative discomfort . Including a vasoconstrictive agent , such as epinephrine , with the local anesthetic may be beneficial . Although bleeding is usually minimal for the procedure , this step may help during those few times when bleeding may otherwise cloud the surgical field . For more information , see Infiltrative Administration of Local Anesthetic Agents The anesthesiologist usually chooses the anesthetic . Depending on body habitus , airway distortion , or prior history of adverse reactions to anesthesia , the anesthesiologist may decide that general anesthesia , which requires intubation , may be the best method , and procedural sedation may be forgone . Given that most marsupializations are relatively quick procedures , this happens rarely . Equipment Equipment needed for the procedure consists of the following 10 Scalpel Pickups / tissue forceps Sponges ( laparotomy or 4 x 4 gauze sponges ) Scissors ( Mayo , Metzenbaum ) Allis clamps Absorbable suture ; options and acceptable sizes vary and include the following : Polysorb ( usually 2 - 0 or 3 - 0 ) ; Vicryl ( usually 2 - 0 or 3 - 0 ) ; Chromic ( usually 2 - 0 or 3 - 0 ) ; and Caprosyn ( usually 2 - 0 or 3 - 0 ) . Culture swab and tube - Optional Povidone iodine ( eg , Betadine ) or alternative prep cleanser such as iodine povacrylex / isopropyl alcohol ( eg , DuraPrep ) Foley catheter or straight catheter - Optional Bovie cautery - Optional Small hemostatic clamps ( Criles or Mosquitoes ) Local anesthetic - Optional Positioning To ensure proper positioning , care must be taken to place the patient carefully in the lithotomy position . Stirrup choices include Yellow Fin , Allen , and Candy Cane . Proper positioning for any type of gynecological procedure is key to prevent unwanted injury to pelvic , buttock , or groin vasculature or nerve . See the image below . Lithotomy position Part of positioning the patient includes draping the patient appropriately . Sterile drapes or towels must cover unwanted areas while allowing the surgeon adequate exposure to the operative site . A sterile towel may be placed over the anal area to guard against anal and rectal bacteria . Complication Prevention The operative area should be prepared with an antimicrobial solution such as Betadine . Given that the vulva and vagina are closely linked , a vaginal prep / cleansing should also be performed . Avoidance of cross - contamination from the anal area is important , since those bacteria are numerous and can be easily transferred to the vulvar area . If not careful , this can lead to a postoperative wound infection in women who initially present for marsupialization of a known uninfected cyst . Depending on the timeframe between diagnosis and procedure , the patient may have already been on broad spectrum antibiotics if cellulits was noted or an abscess was suspected . In the case of a simple Bartholin gland cyst , antibiotics are usually not used . Overview of Technique The technique may be summarized as follows 11 12 13 Once the patient is properly anesthetized , a thorough bimanual examination should be performed . This helps the surgeon determine the borders and extent of the cyst or abscess . Once properly prepped and draped , the bladder is drained with a straight catheter . A Foley catheter can be placed at the discretion of the surgeon . The labia are retracted digitally and the introitus is exposed so that the entire surgical field is visualized . If local anesthetic is to be used , it is applied to the area immediately surrounding the cyst with care taken not to enter or puncture the cyst wall . A 1.5 - to 2 - cm vertical incision is then made over the mucosa just distal to the hymenal ring and on the wall of the gland at the cyst site . Care must be taken to ensure that the opening into the gland is sufficient to promote adequate drainage . Any bleeding noted can be controlled with sponges or suction . The wall of the gland is then incised and the cyst contents are evacuated . This can be accomplished with gentle expression or with irrigation . At this point , cultures of the fluid are obtained and sent to the lab . The walls of the cyst are grasped with Allis clamps . Absorbable suture such as Polysorb or Vicryl is used in an interrupted or continuous fashion to suture the wall of the cyst to the introitus laterally and the vaginal mucosa medially . The marsupialization is now complete . Post Procedure Postoperative care After the procedure , the patient is usually placed on a regimen that includes the following : Hot sitz baths starting post operative day 1 or 2 Oral pain medication such as Ibuprofen , acetaminophen , or an appropriate narcotic if pain is severe Antibiotics are not routinely prescribed for Bartholin gland cysts unless there is evidence of cellulitis . Broad spectrum antibiotics can then be used . For Bartholin gland abscesses , broad - spectrum antibiotics can also be administered until final culture results are obtained . 6 Antibiotic administration has not been shown to prevent recurrence . 14 The patient may resume sexual intercourse by 4 weeks after surgery . Complications Complications vary in their risk of development and can include recurrence , postoperative infection , dyspareunia and unresolved pain , scarring , and neuropathy ( rare ) . Recurrence Recurrence rates range from 2 % to 25 % with varying periods of follow up considered . A study by Randall and Downs found that 63 % of their study population ( 12 out of 19 ) reported a total of 28 incision and drainage procedures prior to marsupialization . After marsupialization , none of these patients had a recurrence in the first 1 week after surgery . 15 Andersen et al completed a study in 1992 that compared marsupialization alone to primary suture technique plus antibiotic coverage in 19 patients with Bartholin gland abscesses . They found no significant difference in recurrence rates between the two groups at 6 month follow - up . 16 Postoperative infection Postoperative infection can be due to preexisting Neissaria gonorrhea or Chlamydia trachomatis . Prophylactic antibiotics are not usually administered preoperatively for uncomplicated Bartholin gland cysts . Postoperative infection can be polymicrobial in origin , and it can have bacteria commonly associated with the gastrointestinal tract due to its proximity to the vulva . Dyspareunia and unresolved pain These may be associated with the size of the cyst / abscess and the size of the operative site . Long - term monitoring It is important to evaluate patients who have undergone Bartholin ' s Gland Marsupialization at their well woman visits for any signs or symptoms consistent with suspected healing difficulties or recurrence . In addition , it is important to discuss any new symptoms that have arisen since the procedure , such as dyspareunia , vaginal discharge , and vulvar or labial numbness . If found early , these symptoms can be evaluated and addressed appropriately to provide patient care and comfort . Medications and Medical Devices Medication Summary Infections of the Bartholin gland can be associated with N gonorrhea and C trachomatis infections . Infections are also often polymicrobial in nature . As such , they often require broad spectrum antibiotic coverage . Antibiotic choices for Bartholin gland infections are numerous . Likewise , the same can be said for local anesthetics often used during the marsupialization procedure . An overview of both is listed below and can also be found in Bartholin Gland Diseases Common antibiotics used include the following : Ceftriaxone ( broad - spectrum and N gonorrhea coverage ) Ciprofloxacin ( broad - spectrum coverage ) Doxycycline ( C trachomatis coverage ) Azithromycin ( Common local anesthetics include the following : Lidocaine : 1 % or 2 % concentrations available ; used with or without epinephrine Bupivicaine ( Marcaine , Sensorcaine ) : 0.25 % or 0.5 % concentrations available ; used with or without epinephrine Sections Bartholin Gland Marsupialization Show All Media Gallery References
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[
"Bartholin Gland Marsupialization",
"Background"
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http://emedicine.medscape.com/article/1923144-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Anatomy Pulmonic Valve Anatomy Updated : Sep 14 , 2017 Author : Juan Fernando Biguria , MD ; Chief Editor : Thomas R Gest , PhD more . . . Sections Overview Pathophysiologic Variants Show All References Overview The pulmonic valve divides the right ventricular outflow tract from the pulmonary artery . In normal conditions , the pulmonic valve prevents regurgitation of deoxygenated blood from the pulmonary artery back to the right ventricle . It is a semilunar valve with 3 cusps , and it is located anterior , superior , and slightly to the left of the aortic valve . An image depicting the pulmonary valve can be seen below . Heart valves , superior view . Gross and Microscopic Anatomy Like the aortic valve , the pulmonic valve is formed by 3 cusps , each with a fibrous node at the midpoint of the free edges ( similar to the nodes of Aranti in the aortic valve ) as well as lunulae , which are the thin , crescent - shaped portions of the cusps that serve as the coaptive surfaces of the valve . In contrast with the aortic valve , the cusps of the pulmonic valve are supported by freestanding musculature with no direct relationship with the muscular septum ; its cusps are much thinner and lack a fibrous continuity with the 1 2 3 4 The cusps of the pulmonic valve are defined by their relationship to the aortic valve and are thus termed anterior or nonseptal , right and left cusps . They can also be defined by their relationship to a commissure found in the pulmonic and aortic valves and hence termed right adjacent ( right facing ) , left adjacent ( left facing ) , and opposite ( nonfacing ) . The pulmonic valve , like the other 3 cardiac valves , is formed by endocardial folds that are supported by internal plates of dense collagenous and elastic connective tissue and are continuous with the cardiac skeleton . 5 Pathophysiologic Variants The pathologic variants of the pulmonic valve are more often related to congenital defects rather than to acquired disease , such as rheumatic valve disease or endocarditis . Pulmonic valvular stenosis ( PVS ) is the most prevalent pulmonary valve pathology , and it accounts for up to 80 % of the cases of right ventricular outflow tract obstruction . This condition can be detected throughout different stages of life , depending on its severity . The more severe the obstruction , the earlier in life , PVS manifests itself . Neonates usually present with critical stenosis , manifested as cyanosis at birth , although infants are usually diagnosed when a murmur auscultated in the pulmonic area . Pulmonic stenosis symptoms tend to worsen and progress with time . Adults usually present with symptoms Sections Pulmonic Valve Anatomy Show All References
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[
"Pulmonic Valve",
"deoxygenated blood",
"aortic valve"
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http://emedicine.medscape.com/article/1923166-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Anatomy Regions and Planes of the Abdomen Updated : Oct 23 , 2013 Author : Brian A Janz , MD ; Chief Editor : Thomas R Gest , PhD more . . . Sections Overview Abdominal Skin Superficial Fascia Muscles of the Abdominal Wall Transversalis Fascia Inguinal Ligament Inguinal Canal Show All Media Gallery References Overview The anatomy of the regions and planes of the abdomen is composed of many layers with varying blood supply and innervation . The abdomen has been bisected , trisected , and even divided into as many as 9 separate regions . The layers of the abdominal wall consist of the skin , superficial fascia , and muscles . Abdominal planes The anatomic planes of the abdominal wall are made up of multiple muscular and fascial layers that interdigitate and unite to form a sturdy , protective musculofascial layer that protects the visceral organs and provides strength and stability to the body ' s trunk . This anatomy varies with respect to the different topographic regions of the abdomen ; thus , a firm understanding of these layers , their blood supply , and their innervation is essential to surgical management of the abdomen . The abdominal cavity is the largest hollow space in the body . It is bound cranially by the xiphoid process of the sternum and the costal cartilages of ribs 7 - 10 ; caudally , by the anterior ilium and the pubic bone of the pelvis ; anteriorly , by the abdominal wall musculature ; and posteriorly , by the L1 - L5 vertebrae . Abdominal regions The abdominal wall has few anatomic landmarks . The flat abdominal plane is broken up only by the costal margins , anterior superior iliac spines , and the umbilicus . Thus , many attempts have been made over the years to describe what surface anatomy can not . The most common and widely accepted system for identification of the various regions of the abdomen is the simple division of the abdomen into 4 quadrants by a vertical and horizontal line bisecting the umbilicus and forming the right and left upper and lower quadrants ( see the image below ) . 1 Division of the abdomen into 4 quadrants . View Media Gallery Abdominal Skin Langer lines As elsewhere on the human body , the abdominal skin is transgressed by Langer lines , also called cleavage lines . This is a term used to define the direction within the skin along which the skin has the least flexibility and corresponds to the alignment of the collagen fibers within the dermis . Across the superior half of the anterior abdominal skin , these lines are oriented in a transverse direction . Toward the inferior half of the abdominal skin , these lines begin to assume a slightly more oblique course in an inferior medial direction toward the groin Innervation The abdominal skin is innervated in a segmental pattern by the anterior rami of the T7 - L1 thoracoabdominal nerves . T7 - T9 thoracoabdominal nerves innervate the skin above the umbilicus ; T10 thoracoabdominal nerves innervates the skin around the umbilicus ; and T11 thoracoabdominal nerves plus cutaneous branches of the subcostal ( T12 ) , iliohypogastric , and ilioinguinal ( L1 ) nerves supply the skin inferior to the umbilicus . 1 Superficial Fascia The superficial fascia of the abdominal wall is the next layer encountered just deep to the skin . It consists of connective tissue that contains a variable amount of fat . This layer can vary in thickness from less than 1 cm to greater than 15 cm , depending on a person ' s body habitus . Camper and Scarpa fasciae Superior to the umbilicus , the superficial fascia consists of a single layer . Inferior to the umbilicus , it splits into 2 layers . The more superficial and fatty layer is the Camper fascia . The deeper , more fibrous layer is the Scarpa fascia . The Scarpa fascia contains very little fat and is continuous with both the superficial fascia of the thigh known as the fascia lata and the superficial fascia of the perineum known as the Colles fascia . The fasciae are displayed in the image below . Muscular layers of the abdomen . Ext . = exterior ; fasc . = fascia ; Inf . = inferior ; Int . = interior ; m . = muscle . View Media Gallery Muscles of the Abdominal Wall The abdominal wall is composed of 5 paired muscles : 2 vertical muscles ( the rectus abdominis and the pyramidalis ) and 3 layered , flat muscles ( the external abdominal oblique , the internal abdominal oblique , and the transversus abdominis muscles ) . These muscles and their fascial attachments interdigitate and unite to form a sturdy , protective musculofascial layer that gives strength and support to the anterolateral abdominal wall ( see the images below ) . Layers of the abdominal wall . Muscular layers of the abdomen . Ext . = exterior ; fasc . = fascia ; Inf . = inferior ; Int . = interior ; m . = muscle . External abdominal oblique muscle The external abdominal oblique muscle is the largest and most superficial of the 3 paired , flat abdominal muscles . It arises from the lower 8 ribs and interdigitations of the serratus anterior muscle . As the external abdominal oblique courses in an inferior medial direction , its muscle fibers change from thick muscle to a fibrous aponeurosis that inserts medially in the linea alba . Inferiorly , the external abdominal oblique aponeurosis folds back on itself to form the inguinal ligament between the anterior superior iliac spine and the pubic tubercle before inserting onto the pubic tubercle and the 2 The external abdominal oblique is innervated in a segmental pattern by the anterior rami of the inferior 6 thoracoabdominal nerves ( T7 - T12 ) . Internal abdominal oblique muscle The internal abdominal oblique muscle is the intermediate layer of the 3 paired , flat abdominal muscles . It originates broadly from the anterior portion of the iliac crest , lateral half of the inguinal ligament , and thoracolumbar fascia . The internal abdominal oblique inserts on the inferior border of the 10th - 12th ribs , the linea alba , and the pubic crest via the conjoint tendon . The muscle fibers of the internal abdominal oblique course upward in a superomedial orientation , perpendicular to the muscle fibers of the external abdominal oblique . Like the external abdominal oblique , the internal abdominal oblique forms a broad aponeurosis that fuses into the midline and contributes to the rectus sheath . Superior to the arcuate line ( see the image below ) , the internal abdominal oblique aponeurosis splits anteriorly and posteriorly to enclose the rectus muscle and helps form the rectus sheath . However , inferior to the arcuate line , the internal abdominal oblique aponeurosis does not split and only passes anterior to the rectus muscle as part of the anterior rectus sheath . The arcuate line . a . = artery ; Ant . = anterior ; Ext . = exterior ; Inf . = inferior ; Int . = interior ; m . = muscle ; Post . = posterior ; v = vein . The inferior aponeurotic fibers of the internal abdominal oblique muscle course over the spermatic cord , through the inguinal canal , and the medial fibers fuse with the aponeurosis of the transversus abdominis muscle to form the conjoint tendon . 3 The internal oblique is innervated in a segmental pattern by the anterior rami of the inferior 6 thoracoabdominal nerves ( T7 - T12 ) and first lumbar nerves ( iliohypogastric and ilioinguinal nerves ) . Of note , all the neurovascular structures supplying the abdominal muscles run in the plane between the internal abdominal oblique muscle and the transversus abdominis muscle , except for the iliohypogastric and ilioinguinal nerves . Initially , they lie on the anterior surface of the quadratus lumborum , then pass laterally into the plane between the transversus abdominis and the internal abdominal oblique . Above the anterior superior iliac spine , they penetrate the internal abdominal oblique to run between this muscle and the aponeurosis of the external abdominal oblique muscle . Transversus abdominis muscle The transversus abdominis muscle is the deepest of the 3 paired , flat abdominal muscles . It originates on the internal surfaces of the 7th – 12th costal cartilages , thoracolumbar fascia , anterior three fourths of the iliac crest , and lateral third of the inguinal ligament . As with the other flat muscles , the transversus abdominis forms a broad aponeurosis that helps make up the rectus sheath before it fuses in the midline to the linea alba . Above the arcuate line , the transversus abdominis aponeurosis contributes to the posterior rectus sheath . Below the arcuate line , it is fused with the other flat muscles as the anterior rectus sheath . ( See the image above . ) As its name implies , the muscle and aponeurotic fibers run in a transverse direction , except for the inferior most aponeurotic fibers . These fibers curve in an inferomedial direction to unite with the aponeurosis of internal abdominal oblique to form the conjoint tendon , which attaches onto the pubic crest and the pectineal ( Cooper ) ligament . The inferior aponeurotic fibers are fused to the underlying transversalis fascia , thus forming the posterior wall of the inguinal canal . A small triangular opening in this posterior wall is known as the deep or internal inguinal ring . 4 The transversus abdominis is innervated in a segmental pattern by the anterior rami of the inferior 6 thoracoabdominal nerves ( T7 - T12 ) and first lumbar nerves ( iliohypogastric and ilioinguinal nerves ) . Rectus abdominis muscles The rectus abdominis muscles are paired , long muscles that run just lateral to the linea alba in a vertical direction from the xiphoid process of the sternum and costal cartilage of the 5th - 7th ribs to the pubic symphysis . These muscles function to tense the abdominal wall , flex the trunk , stabilize the pelvis , and aid in childbirth , defecation , micturition , and forced expiration . Each muscle is divided along its course by 3 or 4 transverse fibrous bands known as tendinous intersections , which essentially divide the muscle into a series of interconnected muscles . This results in one ' s " abs " or " six - pack . " The rectus muscles are contained within the rectus sheath , which is formed by the aponeuroses of the external abdominal oblique , internal abdominal oblique , and transversus abdominis muscles . The rectus muscles have a dual blood supply . The superior epigastric artery and vein , which are direct continuations of the internal thoracic vessels , supply the superior half of the rectus muscles . The inferior epigastric artery and vein , which arise from the external iliac vessels just proximal to their passage under the inguinal ligament , supply the inferior portion of the rectus muscles and run superiorly until they anastomose with the superior epigastric vessels . In addition , there are numerous small , segmental contributions from the lower 6 intercostal vessels ( see the image below 3 Abdominal wall vasculature . The rectus muscle is innervated in a segmental pattern by the anterior rami of the T7 - T12 thoracoabdominal nerves . Pyramidalis muscle The pyramidalis muscle is a small , triangular muscle that lies anterior to the inferior aspect of the rectus abdominis muscles . It originates at the pubic symphysis and attaches superiorly at the linea alba . This muscle functions to tense the linea alba and aid in midline stabilization . The pyramidalis muscle is generally considered insignificant in humans and is , in fact , absent in about 20 % of the population . Arcuate line Approximately midway between the umbilicus and the pubic symphysis is an arching , transverse anatomic line known as the arcuate line or the semicircular line of Douglas . Superior to this line , the anterior rectus sheath is composed of the fusion of the aponeuroses of the external abdominal oblique and the anterior leaf of the internal abdominal oblique aponeuroses . ( The internal abdominal oblique aponeurosis splits to envelop the rectus muscle at this level . ) The posterior rectus sheath above the arcuate line is composed of the fusion of the posterior leaf of the internal abdominal oblique aponeuroses and the transversus abdominis aponeuroses . Inferior to the arcuate line , the anterior rectus sheath is composed of the fusion of all 3 muscle aponeuroses , and little or no posterior sheath exists , because only the thin transversalis fascia runs posterior to the rectus muscle ( see the image below ) . 5 The arcuate line . a . = artery ; Ant . = anterior ; Ext . = exterior ; Inf . = inferior ; Int . = interior ; m . = muscle ; Post . = posterior ; v = vein . Linea alba The linea alba is a dense , tendinous line created by the decussating aponeuroses of the external abdominal oblique , internal abdominal oblique , and transversus abdominis muscles at the abdominal midline . Between the rectus muscles , it extends superiorly from the xiphoid , continuing inferiorly , where it passes superficially in front of the rectus muscles to attach to the symphysis pubis . Deeper fibers pass behind the rectus abdominis , attaching to the posterior pubic crest to create a triangular lamella known as the " adminiculum lineae albae . " 2 Above the umbilicus , the well - formed linea alba is wider , progressively narrowing and becoming more vague below the umbilicus to its inferior attachments . The midline laparotomy incision , dividing the linea alba , is one of the most common surgical approaches for abdominal exposure and the most common site of incisional hernia formation . 4 Widening of the superior linea alba can cause a noticeable midline bulge known as a diastasis recti , or separation of the rectus muscles . Diastasis recti is a common and normal condition in newborns and is very common in women who have had multiple pregnancies . Transversalis Fascia The transversalis fascia is a thin layer of connective tissue lining most of the abdominal cavity between the posterior surface of the transversus abdominis and superficial to the extraperitoneal fat and peritoneum . Superiorly , this fascia continues with the inferior diaphragmatic fascia ; inferiorly with the iliac and pelvic fascia ; posteriorly with the thoracolumbar fascia ; and laterally to the iliac crest . Above the arcuate line , the transversalis fascia contributes to the posterior sheath along with the posterior leaf of the internal abdominal oblique and the transversus abdominis muscles ( see the image below ) . Below the arcuate line , the transversalis fascia forms the posterior sheath alone . With attachments to the posterior margin of the inguinal ligament , it contributes to the formation of the femoral sheath , contributes the internal spermatic fascia , and becomes the only layer contributing to the inguinal floor . At the deep inguinal ring , the structures of the spermatic cord in Inguinal Ligament The inguinal ligament , or the Poupart ligament , is the thickened , inferior border of the external abdominal oblique aponeurosis that extends from the anterior superior iliac spine to the pubic tubercle and forms the floor of the inguinal canal ( see the image below ) . At the medial aspect , some fibers divide posteriorly , attaching to the pectineal line to form the lacunar ligament or the ligament of Gimbernat , whereas other fibers extend superomedially to join the rectus sheath and linea alba , forming the reflected inguinal ligament . Only fascial attachments originate into or Inguinal anatomy . The inguinal ligament also contributes to the inguinal ( Hesselbach ) triangle , forming the inferolateral border , whereas the epigastric vessels and the lateral edge of the rectus abdominis muscle form the superolateral and medial borders . Direct inguinal hernias are seen within the triangle , whereas indirect inguinal hernias form lateral to the epigastric vessels . 5 Inguinal Canal The inguinal canal is a natural space created within the layers of the lower anterior abdominal wall just above the inguinal ligament ( see the image below ) . Inguinal anatomy . In the newborn period , the inguinal canal is short and lengthens over time to its final oblique position . In an adult , the canal measures approximately 3 - 5 cm and extends from the deep or internal inguinal ring to the superficial or external inguinal ring . The deep ring , formed by an opening in the transversalis fascia , corresponds to the middle of the inguinal ligament midway between the anterior superior iliac spine and the pubic tubercle . The superficial inguinal ring is formed by an opening in the aponeurosis of the external abdominal oblique muscle The inguinal canal is formed superiorly by the lower edge of the internal abdominal oblique and transversus abdominis muscles ; inferiorly by the inguinal and lacunar ligaments ; and anteriorly by the external abdominal oblique aponeurosis . The lateral third of the anterior wall is further reinforced by a portion of the internal abdominal oblique . The posterior wall is formed by the conjoint tendon ( the union of internal abdominal oblique aponeurosis and transversus abdominis aponeurosis ) and the transversalis fascia . The canal is reinforced medially by the internal abdominal oblique aponeurosis , whereas laterally , the transversus abdominis aponeurosis and the transversalis fascia form the wall in approximately 75 % of individuals , with the remainder being formed only by transversalis fascia . This remains the most important boundary of the inguinal canal . Weakness or defects in the posterior wall may lead to formation of inguinal hernias . In males , the inguinal canal tends to be more developed , containing the spermatic cord and ilioinguinal nerve , whereas in females , it remains less developed and contains the 6 Sections Regions and Planes of the Abdomen Show All Media Gallery References
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Cardiology Noncoronary Atherosclerosis Overview of Atherosclerosis Updated : Apr 24 , 2014 Author : F Brian Boudi , MD , FACP ; Chief Editor : Yasmine S Ali , MD , FACC , FACP , MSCI more . . . Sections Practice Essentials Overview of Atherosclerosis Etiology of Atherosclerosis Risk Factors for Atherosclerosis Epidemiology of Atherosclerosis Patient Education in Atherosclerosis Patient History Physical Examination Lipid Profile Blood Glucose and Hemoglobin A1C Ultrasonographic Examination MRI and Scintigraphy Treatment of Atherosclerosis Drug Agents Show All References Practice Essentials Atherosclerosis is a disease of large and medium - sized muscular arteries and is characterized by endothelial dysfunction , vascular inflammation , and the buildup of lipids , cholesterol , calcium , and cellular debris within the intima of the vessel wall . This buildup results in plaque formation , vascular remodeling , acute and chronic luminal obstruction , abnormalities of blood flow , and diminished oxygen supply to target organs . Noncoronary atherosclerosis refers to atherosclerotic disease affecting large and medium - sized noncoronary arteries ( eg , extracranial cerebrovascular disease , lower extremity occlusive disease , aneurysmal disease ) . Signs and symptoms The signs and symptoms of noncoronary atherosclerosis are highly variable . Patients with mild atherosclerosis may present with clinically important symptoms and signs of disease . However , many patients with anatomically advanced disease may have no symptoms and experience no functional impairment . Signs and symptoms of noncoronary atherosclerosis that affect different organ systems include the following : Central nervous system : Stroke , reversible ischemic neurologic deficit , transient ischemic attack Peripheral vascular system : Intermittent claudication , impotence , nonhealing ulceration and infection of the extremities Gastrointestinal ( GI ) vascular system : Mesenteric angina characterized by epigastric or periumbilical postprandial pain — may be associated with hematemesis , hematochezia , melena , diarrhea , nutritional deficiencies , and weight loss ; abdominal aortic aneurysm that is typically asymptomatic ( sometimes pulsatile ) until the dramatic , and often fatal , signs and symptoms of rupture Target organ failure : Occult or symptomatic visceral ischemia Diagnosis Examination findings of noncoronary atherosclerosis are highly variable but may provide objective evidence of extracellular lipid deposition , stenosis or dilatation of large muscular arteries , or target organ ischemia or infarction , such as the following : Hyperlipidemia : Xanthelasma and tendon xanthomata Cerebrovascular disease : Diminished carotid pulses , carotid artery bruits , and focal neurologic deficits Peripheral vascular disease : Decreased peripheral pulses , peripheral arterial bruits , pallor , peripheral cyanosis , gangrene , and ulceration Abdominal aortic aneurysm : Pulsatile abdominal mass , peripheral embolism , and circulatory collapse Atheroembolism : Livedo reticularis , gangrene , cyanosis , ulceration , digital necrosis , GI bleeding , retinal ischemia , cerebral infarction , and renal failure Laboratory testing Lipid profile Blood glucose and hemoglobin A1c Imaging studies Ultrasonography : For evaluating brachial artery reactivity and carotid artery intima - media thickness ( measures of vessel wall function and anatomy , respectively ) Intravascular ultrasonography : Generally considered the criterion standard for the anatomic study of the vessel wall ( provides images of the thickness and the acoustic density of the vessel wall ) Magnetic resonance imaging : For noninvasive assessment of blood vessel wall structure and characterization of plaque composition Nuclear perfusion imaging with single - photon emission computed tomography ( SPECT ) scanning or positron emission tomography ( PET ) scanning Management The prevention and treatment of atherosclerosis require risk factor control , including the medical management of hypertension , hyperlipidemia and dyslipidemia , diabetes mellitus , and cigarette habituation . Pharmacotherapy The following medications may be used in the management of noncoronary atherosclerosis : HMG - CoA ( 3 - hydroxy - 3 - methylglutaryl - coenzyme ) reductase inhibitors ( eg , pravastatin , simvastatin , lovastatin , fluvastatin , atorvastatin , rosuvastatin , pitavastatin ) Fibric acid derivatives ( eg , fenofibrate , gemfibrozil ) Bile acid sequestrants ( eg , cholestyramine , colestipol ) Vitamin E Omega - 3 polyunsaturated fatty acid Overview of Atherosclerosis Atherosclerosis is a disease of large and medium - sized muscular arteries and is characterized by endothelial dysfunction , vascular inflammation , and the buildup of lipids , cholesterol , calcium , and cellular debris within the intima of the vessel wall . This buildup results in plaque formation , vascular remodeling , acute and chronic luminal obstruction , abnormalities of blood flow , and diminished oxygen supply to target organs . Go to Coronary Artery Atherosclerosis for complete information on this topic . Etiology of Atherosclerosis The mechanisms of atherogenesis remain uncertain . An incompletely understood interaction exists between the critical cellular elements — endothelial cells , smooth muscle cells , platelets , and leucocytes — of the atherosclerotic lesion . Vasomotor function , the thrombogenicity of the blood vessel wall , the state of activation of the coagulation cascade , the fibrinolytic system , smooth muscle cell migration and proliferation , and cellular inflammation are complex and interrelated biologic processes that contribute to atherogenesis and the clinical manifestations of atherosclerosis . The " response - to - injury " theory is most widely accepted explanation for atherogenesis . Endothelial injury causes vascular inflammation and a fibroproliferative response ensues . Probable causes of endothelial injury include oxidized low - density lipoprotein ( LDL ) cholesterol ; infectious agents ; toxins , including the byproducts of cigarette smoking ; hyperglycemia ; and hyperhomocystinemia . Circulating monocytes infiltrate the intima of the vessel wall , and these tissue macrophages act as scavenger cells , taking up LDL cholesterol and forming the characteristic foam cell of early atherosclerosis . These activated macrophages produce numerous factors that are injurious to the endothelium . Elevated serum levels of LDL cholesterol overwhelm the antioxidant properties of the healthy endothelium and result in abnormal endothelial metabolism of this lipid moiety . Oxidized LDL is capable of a wide range of toxic effects and cell / vessel wall dysfunctions that are characteristically and consistently associated with the development of atherosclerosis . These dysfunctions include impaired endothelium - dependent dilation and paradoxical vasoconstriction . These dysfunctions are the result of direct inactivation of nitric oxide by the excess production of free radicals , reduced transcription of nitric oxide synthase messenger ribonucleic acid ( mRNA ) , and posttranscriptional The decrease in the availability of nitric oxide also is associated with increased platelet adhesion , increased plasminogen activator inhibitor , decreased plasminogen activator , increased tissue factor , decreased thrombomodulin , and alterations in heparin sulfate proteoglycans . The consequences include a procoagulant milieu and enhanced platelet thrombus formation . Furthermore , oxidized LDL activates inflammatory processes at the level of gene transcription by up - regulation of nuclear factor kappa - B , expression of adhesion molecules , and recruitment of monocytes / macrophages . The lesions of atherosclerosis do not occur in a random fashion . Hemodynamic factors interact with the activated vascular endothelium . Fluid shear stresses generated by blood flow influence the phenotype of the endothelial cells by modulation of gene expression and regulation of the activity of flow - sensitive proteins . Atherosclerotic plaques characteristically occur in regions of branching and marked curvature at areas of geometric irregularity and where blood undergoes sudden changes in velocity and direction of flow . Decreased shear stress and turbulence may promote atherogenesis at these important sites within the coronary arteries , the major branches One study suggested that hypercholesterolemia - induced neutrophilia develops in arteries primarily during early stages of atherosclerotic lesion formation . 1 The earliest pathologic lesion of atherosclerosis is the fatty streak , which is the result of focal accumulation of serum lipoproteins within the intima of the vessel wall . Microscopy reveals lipid - laden macrophages , T lymphocytes , and smooth muscle cells in varying proportions . The fatty streak may progress to form a fibrous plaque , the result of progressive lipid accumulation and the migration and proliferation of smooth muscle cells . Platelet - derived growth factor , insulinlike growth factor , transforming growth factors alpha and beta , thrombin , and angiotensin II are potent mitogens that are produced by the activated platelets , macrophages , and dysfunctional endothelial cells that characterize early atherogenesis , vascular inflammation , and platelet - rich thrombosis at sites of endothelial disruption . The relative deficiency of endothelium - derived nitric oxide further potentiates this proliferative stage of plaque maturation . The proliferating smooth muscle cells are responsible for the deposition of extracellular connective tissue matrix and form a fibrous cap that overlies a core of lipid - laden foam cells , extracellular lipid , and necrotic cellular debris . Growth of the fibrous plaque results in vascular remodeling , progressive luminal narrowing , blood - flow abnormalities , and compromised oxygen supply to the target organ . Progressive luminal narrowing of an artery due to expansion of a fibrous plaque results in impairment of flow once more than 50 - 70 % of the lumen diameter is obstructed . Flow impairment causes symptoms of inadequate blood supply to the target organ in the event of increased metabolic activity and oxygen demand . Developing atherosclerotic plaques acquire their own microvascular network , which consists of a collection of vessels known as the vasa vasorum . These vessels are prone to hemorrhage and contribute to the progression of atherosclerosis . 2 Denudation of the overlying endothelium or rupture of the protective fibrous cap may result in exposure of the thrombogenic contents of the core of the plaque to the circulating blood . This exposure constitutes an advanced or complicated lesion . The plaque rupture occurs due to weakening of the fibrous cap . Inflammatory cells localize to the shoulder region of the vulnerable plaque . T lymphocytes elaborate interferon gamma , an important cytokine that impairs vascular smooth muscle cell proliferation and collagen synthesis . In addition , activated macrophages produce matrix metalloproteinases that degrade collagen . These mechanisms explain the predisposition to plaque rupture and highlight the role of inflammation in the genesis of the complications of the fibrous atheromatous plaque . A plaque rupture may result in thrombus formation , partial or complete occlusion of the blood vessel , and progression of the atherosclerotic lesion due to organization of the thrombus and incorporation within the plaque . Development of atherosclerosis from childhood through adulthood The process of atherosclerosis begins in childhood with the development of fatty streaks . These lesions can be found in the aorta shortly after birth and appear in increasing numbers in persons aged 8 - 18 years . More advanced lesions begin to develop when individuals are aged approximately 25 years . Subsequently , an increasing prevalence of the advanced complicated lesions of atherosclerosis exists , and the organ - specific clinical manifestations of the disease increase with age through the fifth and sixth decades of life . Risk Factors for Atherosclerosis A number of large epidemiologic studies in North America and Europe have identified numerous risk factors for the development and progression of atherosclerosis . The risk factors can be divided into modifiable and nonmodifiable types and include hyperlipidemia , hypertension , cigarette habituation , diabetes mellitus , age , sex , physical inactivity , and obesity . In addition , a number of novel risk factors have been identified that add to the predictive value of the established risk factors and may prove to be a target for future medical interventions . Hypertension Hypertension has been shown , in epidemiologic and experimental studies , to accelerate atherosclerotic vascular disease and increase the incidence of clinical complications . The mechanism by which hypertension causes these effects is not known , and some uncertainty exists as to what the primary and secondary factors are in a typically multifactorial syndrome . These factors may include the above - mentioned hyperlipidemia , hypertension , diabetes mellitus , obesity , and physical inactivity . Hypertension is associated with morphologic alterations of the arterial intima and functional alterations of the endothelium that are similar to the changes observed in hypercholesterolemia and established atherosclerosis . Endothelial dysfunction is a feature of hypertension , hyperlipidemia , and atherosclerosis and is known to represent and contribute to the procoagulant , proinflammatory , and proliferative components of atherogenesis . Diabetes mellitus This is an important risk factor for hyperlipidemia and atherosclerosis and is commonly associated with hypertension , abnormalities of coagulation , platelet adhesion and aggregation , increased oxidative stress , and functional and anatomic abnormalities of the endothelium , and endothelial vasomotion . Cigarette smoking Cigarette smokers have double the risk for stroke compared with nonsmokers . 3 C - reactive protein In a cohort of healthy men , baseline C - reactive protein ( CRP ) levels were found to be predictive of symptomatic peripheral vascular disease . CRP reflects systemic inflammation , and these results support the hypothesis that chronic inflammation may play a role in the pathogenesis and progression of atherosclerosis . Standardization of the CRP assay is required before this test may be clinically useful , and whether CRP levels are a truly modifiable risk factor remains unclear . Fibrinogen Fibrinogen may be elevated in association with risk factors for atherosclerosis , including smoking , age , and diet . Familial hypercholesterolemia Familial hypercholesterolemia is an autosomal dominant disorder caused by a defect in the gene for the hepatic LDL receptor . In the United States , heterozygous familial hypercholesterolemia occurs in approximately 1 in 500 individuals . Homozygous familial hypercholesterolemia occurs in approximately 1 in 1 million individuals in the United States , and total cholesterol may exceed 1000 mg / dL . Also see Risk Factors for Coronary Artery Disease Epidemiology of Atherosclerosis Rate of occurrence The true frequency of atherosclerosis is difficult , if not impossible , to accurately determine , because it is a predominantly asymptomatic condition . A study by Semba et al suggests that high concentrations of plasma klotho , a hormone that has been implicated in atherosclerosis , are independently associated with a lower likelihood of having CVD . 4 Sex predilection Atherosclerosis is more common in men than in women . The higher prevalence of atherosclerosis in men is thought to be due to the protective effects of female sex hormones . This effect is absent after menopause in women . Age predilection Most cases of atherosclerotic vascular disease become clinically apparent in patients aged 40 years or older . Prognosis The prognosis of atherosclerosis depends on a number of factors , including systemic burden of disease , the vascular bed ( s ) involved , and the degree of flow limitation . Wide variability exists , and clinicians appreciate that many patients with critical limitation of flow to vital organs may survive many years , despite a heavy burden of disease . ( Conversely , myocardial infarction or sudden cardiac death may be the first clinical manifestation of atherosclerotic cardiovascular disease in a patient who is otherwise asymptomatic with minimal luminal stenosis and a light burden of disease . ) Much of this phenotypic variability is likely to be determined by the relative stability of the vascular plaque burden . Plaque rupture and exposure of the thrombogenic lipid core are critical events in the expression of the atherosclerotic disease process and determine the prognosis of atherosclerosis . The ability to determine and quantify risk and prognosis in patients with atherosclerosis is limited by the inability to objectively measure plaque stability and other predictors of clinical events . Patient Education in Atherosclerosis For patient education information , see eMedicineHealth ' s Cholesterol Center and Brain and Nervous System Center , as well as High Cholesterol Cholesterol Charts Lifestyle Cholesterol Management , and Stroke Patient History The symptoms of noncoronary atherosclerosis are highly variable . Patients with mild atherosclerosis may present with clinically important symptoms and signs of disease . However , many patients with anatomically advanced disease may have no symptoms and experience no functional impairment . Although atherosclerosis was initially thought to be a chronic , slowly progressive , degenerative disease , it is now apparent that the disorder has periods of activity and quiescence . Although a systemic disease , atherosclerosis manifests in a focal manner and affects different organ systems in different patients for reasons that remain unclear . Stroke , reversible ischemic neurologic deficit , and transient ischemic attack are manifestations of the impairment of the patient ’ s vascular supply to his or her central nervous system and are characterized by the sudden onset of a focal neurologic deficit of variable duration . Peripheral vascular disease typically manifests as intermittent claudication , impotence , and nonhealing ulceration and infection of the extremities . Intermittent claudication describes calf , thigh , or buttock pain that is exacerbated by exercise and relieved by rest . Intermittent claudication may be accompanied by pallor of the extremity and paresthesias . ( A patient with limb claudication can be assumed to have a significant atherosclerotic plaque burden in multiple vascular beds , including the coronary and cerebral vessels . In evaluating preoperative risk in such a patient , pay particular attention to careful risk stratification and medical or Visceral ischemia may be occult or symptomatic prior to the signs and symptoms of target organ failure . Mesenteric angina is characterized by epigastric or periumbilical postprandial pain and may be associated with hematemesis , hematochezia , melena , diarrhea , nutritional deficiencies , and weight loss . Abdominal aortic aneurysm typically is asymptomatic prior to the dramatic , and often fatal , symptoms and signs of rupture , although patients may describe a pulsatile abdominal mass . Physical Examination As previously mentioned , the symptoms of noncoronary atherosclerosis are highly variable . Patients with mild atherosclerosis may present with clinically important disease signs and symptoms , while many patients with anatomically advanced disease display no symptoms and have no associated functional impairment . The physical signs of noncoronary atherosclerosis provide objective evidence of extracellular lipid deposition , stenosis or dilatation of large muscular arteries , or target organ ischemia or infarction . These symptoms include the following : Hyperlipidemia – Xanthelasma and tendon xanthomata Cerebrovascular disease - Diminished carotid pulses , carotid artery bruits , and focal neurologic deficits Peripheral vascular disease - Decreased peripheral pulses , peripheral arterial bruits , pallor , peripheral cyanosis , gangrene , and ulceration Abdominal aortic aneurysm - Pulsatile abdominal mass , peripheral embolism , and circulatory collapse Atheroembolism - Livedo reticularis , gangrene , cyanosis , ulceration , digital necrosis , gastrointestinal bleeding , retinal ischemia , cerebral infarction , and renal failure The Copenhagen City Heart Study found that xanthelasmata ( raised yellow patches around the eyelids ) but not arcus corneae ( white or grey rings around the cornea ) constitutes an independent risk factor for cardiovascular disease . Presence of xanthelasmata indicated increased risk for myocardial infarction , ischemic heart disease , and severe atherosclerosis . 5 With regard to atheroembolism , the presence of pedal pulses in the setting of peripheral ischemia suggests microvascular disease and includes cholesterol embolization . Lipid Profile Elevated LDL cholesterol is a risk factor for atherosclerotic vascular disease . High triglycerides associated with low high - density lipoprotein ( HDL ) cholesterol — a pattern categorized as atherogenic dyslipidemia and often found in insulin resistance — are also a risk factor for vascular disease . The National Cholesterol Education Program ( NCEP ) has issued guidelines for the diagnosis and optimal treatment of dyslipidemia . 6 7 8 The dal - PLAQUE trial tested the safety and efficacy of dalcetrapib , using novel noninvasive multimodality imaging to assess structural and inflammatory indices of atherosclerosis as primary endpoints . The results suggest that dalcetrapib showed no evidence of a pathological effect related to the arterial wall over 24 months ; however , dalcetrapib may have potential beneficial vascular effects , including the reduction in total vessel enlargement over 24 months . The long - term safety and efficacy needs to be further investigated . 9 Nicholls et al studied the efficacy and safety of cholesteryl ester transfer protein ( CETP ) inhibitors in combination with commonly used statins . They found that , compared with placebo or statin monotherapy , evacetrapib raised HDL - C and lowered LDL - C levels , with or without a statin drug . 10 In an industry - supported study , patients with atherosclerotic cardiovascular disease and LDL - C levels of < 70 mg / dl ( 1.81 mol / L ) experienced no incremental clinical benefit from the addition of niacin to statin therapy during a 36 - month follow - up period , despite significant improvements in HDL - C and triglyceride levels . 11 Blood Glucose and Hemoglobin A1C Routine measurement of blood glucose and hemoglobin A 1c is appropriate in patients with diabetes mellitus . Measuring any number of parameters that may reflect inflammation , coagulation , fibrinolytic status , and platelet aggregability is possible . These measurements may prove to be valuable , but at this time , how these measurements affect clinical decision - making is unclear , and including them in routine clinical practice is premature . Ultrasonographic Examination Ultrasonography aids in evaluating brachial artery reactivity and carotid artery intima - media thickness , which are measures of vessel wall function and anatomy , respectively . These evaluations remain research techniques at this time but hold promise as reliable , noninvasive ( and therefore repeatable ) measures of disease and surrogate end points for the evaluation of therapeutic interventions . Brachial artery reactivity The loss of endothelium - dependent vasodilation is a feature of even the early stages of atherosclerosis . Flow - mediated dilation of the brachial artery has been pioneered as a means of evaluating the health and integrity of the endothelium . The healthy endothelium dilates in response to an increase in blood flow , whereas vessels affected by atherosclerosis do not dilate and may paradoxically constrict . The availability of high - resolution ultrasonographic systems makes the visualization and measurement of small , peripheral conduit vessels , such as the human brachial artery , possible . Carotid artery intima - media thickness B - mode ultrasonography of the common and internal carotid arteries is a noninvasive measure of arterial wall anatomy that may be performed repeatedly and reliably in asymptomatic individuals . The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular risk factors and disease and an increased risk of myocardial infarction and stroke . This association is at least as strong as the associations observed with traditional risk factors . Intravascular ultrasonography Intravascular ultrasound ( IVUS ) is a catheter - based examination that provides images of the thickness and the acoustic density of the vessel wall . It has long been considered the criterion standard for the study of the anatomy of the vessel wall . MRI and Scintigraphy Magnetic resonance imaging ( MRI ) may be used to gain information noninvasively about blood vessel wall structure and to characterize plaque composition . Nuclear perfusion imaging is performed with the use of single - photon emission computed tomography ( SPECT ) scanning or positron emission tomography ( PET ) scanning , which relies on the administration of radionuclide isotope that is accumulated by the targeted tissue . Treatment of Atherosclerosis The prevention and treatment of atherosclerosis require risk factor control , including the medical treatment of hypertension , hyperlipidemia , diabetes mellitus , and cigarette habituation . Some studies have claimed reversal of atherosclerosis with pharmacologic agents such as statins and cilostazol , but these need to be further tested before it can be determined whether they offer any significant benefit in reducing clinical events . 12 Advances in the understanding of the vascular biology of atherosclerosis have raised the possibility of using novel therapies to address more directly the various aspects of endothelial dysfunction and the role of endothelial dysfunction in atherogenesis . Potential cellular targets include vascular smooth muscle cells , monocyte / macrophage cell lines , platelets , and endothelial cells . Evidence exists that antiplatelet agents , antioxidant therapies , amino acid supplementation , angiotensin - converting enzyme ( ACE ) inhibitors , and angiotensin receptor blockers may prove to prevent or slow the progression of the disease . Screeening New guidelines released in late 2013 by the American Heart Association / American College of Cardiology ( AHA / ACC ) , recommend use of a revised calculator for estimating the 10 - year and lifetime risk of developing a first atherosclerotic cardiovascular disease ( ASCVD ) event , including stroke ( fatal or nonfatal ) , in a person who was initially free from ASCVD . 13 For patients 20 - 79 years of age who do not have existing clinical ASCVD , the guidelines recommend assessing clinical risk factors every 4 - 6 years . For patients with low 10 - year risk ( < 7.5 % ) , the guidelines recommend assessing 30 - year or lifetime risk in patients 20 - 59 years old . Regardless of the patient ’ s age , clinicians should communicate risk data to the patient and refer to the AHA / ACC lifestyle guidelines , which cover diet and physical activity . For patients with elevated 10 - year risk , clinicians should communicate risk data and refer to the AHA / ACC guidelines on blood cholesterol and obesity . Treatment of hypertension The dietary and pharmacologic treatment of hypertension is associated with a decreased incidence of stroke . Management of hyperlipidemia and dyslipidemia The 3 - hydroxy - 3 - methyl Co - A ( HMG - CoA ) reductase inhibitors inhibit the rate - limiting step of cholesterol synthesis in the liver . They are effective in lowering the serum total cholesterol , LDL cholesterol , and triglyceride levels and in raising the serum HDL cholesterol level . HMG - CoA reductase inhibitors also have a low incidence of adverse effects , the most common being hepatotoxicity and myopathy . The success of the HMG - CoA reductase inhibitors in reducing circulating lipid levels and improving the clinical and anatomic course of atherosclerosis has focused attention on the management of hyperlipidemia . In addition , an important role remains for other hypolipidemic agents that may be of particular benefit for patients with refractory LDL hypercholesterolemia , hypertriglyceridemia , low HDL cholesterol , and elevated lipoprotein ( a ) . The 2013 AHA / ACC guidelines on the management of elevated blood cholesterol no longer specify LDL - and non - HDL - cholesterol targets for the primary and secondary prevention of atherosclerotic cardiovascular disease , including stroke and peripheral arterial disease . 14 The guidelines identify four groups of primary - and secondary - prevention patients in whom efforts should be focused to reduce cardiovascular disease events and recommend appropriate levels of statin therapy for these groups . Treatment recommendations include the following : In patients with atherosclerotic cardiovascular disease , or those with LDL cholesterol levels 190 mg / dL or higher ( eg , due to familial hypercholesterolemia ) , and no contraindications , high - intensity statin therapy should be prescribed to achieve at least a 50 % reduction in LDL cholesterol In patients aged 40 to 75 years of age with diabetes , a moderate - intensity statin that lowers LDL cholesterol by 30 % to 49 % should be used ; in those patients who also have a 10 - year risk of atherosclerotic cardiovascular disease exceeding 7.5 % , a high - intensity statin is a reasonable choice In individuals aged 40 to 75 years without cardiovascular disease or diabetes but with a 10 - year risk of clinical events > 7.5 % and an LDL - cholesterol level of 70 - 189 mg / dL , a moderate - or high - intensity statin should be used Management of diabetes mellitus For patients with diabetes mellitus , strict control of comorbid risk factors is especially important . Ample evidence exists that such control reduces the incidence of the clinical complications of microvascular and macrovascular disease . The benefit of strict glycemic control in the prevention of macrovascular disease has been difficult to confirm , although this intuitively is beneficial and is known to retard the progression of microvascular disease . Treatment of familial hypercholesterolemia Treatment options for familial hypercholesterolemia include combination drug therapy , although drug therapy alone often is inadequate because of the relative or absolute deficiency of hepatic LDL receptors . Lipid apheresis is an effective means of reducing circulating lipid levels . Liver transplantation has been performed on young patients with severe disease . Drug Agents HMG - CoA reductase inhibitors These agents are competitive inhibitors of 3 - hydroxy - 3 - methyl Co - A reductase , an enzyme that catalyzes the rate - limiting step in cholesterol biosynthesis , resulting in up - regulation of LDL receptors in response to the decrease in intracellular cholesterol . The HMG - CoA reductase inhibitors are indicated for the secondary prevention of cardiovascular events and for the treatment of hypercholesterolemia and mixed dyslipidemia . A number of HMG - CoA reductase inhibitors are indicated for patients with homozygous familial hypercholesterolemia as an adjunct to other lipid - lowering treatments . One study suggests that the maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis . Although rosuvastatin resulted in lower LDL cholesterol levels and higher HDL cholesterol levels , a similar degree of regression of percent atheroma value ( PAV ) was observed in the two groups . 15 However , these agents may be less effective in patients with rare homozygous familial hypercholesterolemia , possibly because these patients are lacking functional LDL receptors , making it more likely to raise serum transaminases . HMG - CoA reductase inhibitors include the following : Pravastatin ( Pravachol ) Simvastatin ( Zocor ) Lovastatin ( Mevacor , Altocor ) Fluvastatin ( Lescol ) Atorvastatin ( Lipitor ) Rosuvastatin ( Crestor ) Pitavastatin ( Livalo ) Fibric acid derivatives The precise mechanism of action of this class of drugs is complex and incompletely understood . These agents increase the activity of lipoprotein lipase and enhance the catabolism of triglyceride - rich lipoproteins , which is responsible for an increase in the HDL cholesterol fraction . A decrease in hepatic very low - density lipoprotein ( VLDL ) synthesis and an increase in cholesterol excretion into bile also appear to occur . The fibrates typically reduce triglyceride levels by 20 - 50 % and increase HDL cholesterol levels by 10 - 15 % . The decrease in VLDL and triglyceride levels results from the ability of fibric acid derivatives to enhance the synthesis of lipoprotein lipase . The effect of fibric acid derivatives on LDL cholesterol is variable . Levels may be expected to decrease by 10 - 15 % . In patients with marked hypertriglyceridemia , LDL cholesterol levels may increase , which likely reflects the ability of the LDL receptor to clear the increased LDL generated by increased VLDL catabolism . Fibrate therapy may also be responsible for a decrease in the clotting ability of platelets and fibrinogen levels , which may account for some of the reported clinical benefits . Fibric acid derivatives include fenofibrate ( Tricor ) and gemfibrozil ( Lopid ) . Bile acid sequestrants The bile acid sequestrants block enterohepatic circulation of bile acids and increase the fecal loss of cholesterol . This results in a decrease in intrahepatic levels of cholesterol . The liver compensates by up - regulating hepatocyte LDL - receptor activity . The net effect is a 10 - 25 % reduction in LDL cholesterol , but no consistent effect on triglycerides or HDL cholesterol exists . Bile acid sequestrants include cholestyramine ( Questran , LoCholest , Prevalite ) and colestipol ( Colestid ) . Vitamin E ( Vita - Plus E , Softgels , Aquasol E ) This antioxidant protects polyunsaturated fatty acids in membranes from attack by free radicals . Omega - 3 polyunsaturated fatty acid The possible benefits of omega - 3 polyunsaturated fatty acid in the treatment of atherosclerosis include effects on lipoprotein metabolism , hemostatic function , platelet / vessel wall interactions , antiarrhythmic actions , and the inhibition of proliferation of smooth muscle cells and therefore growth of the atherosclerotic plaque . Fish oil feeding has also been found to result in moderate reductions in blood pressure and to modify vascular neuroeffector mechanisms . Sections Noncoronary Atherosclerosis Show All References
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"Noncoronary",
"Atherosclerosis"
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http://emedicine.medscape.com/article/1950803-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Urology Bacillus Calmette - Guérin Immunotherapy for Bladder Cancer Overview of BCG Immunotherapy Updated : Jan 14 , 2017 Author : Gary David Steinberg , MD , FACS ; Chief Editor : Bradley Fields Schwartz , DO , FACS more . . . Sections Overview of BCG Immunotherapy Mechanism of Action of BCG Contraindications to BCG BCG Strains BCG Immunotherapy Technique Adverse Effects of BCG Show All References Overview of BCG Immunotherapy Bacillus Calmette - Guérin ( BCG ) , a live attenuated strain of Mycobacterium bovis , is currently the only agent approved by the US Food and Drug Administration for primary therapy of carcinoma in situ ( CIS ; see image below ) of the bladder . BCG supplanted cystectomy as the treatment of choice for CIS in the mid - 1980s . BCG therapy also reduces the risk of recurrence , and ongoing maintenance therapy with BCG reduces the risk of progression in patients with high - grade non – muscle invasive bladder cancer . 1 The classic appearance of carcinoma in situ as a flat , velvety patch . However , using special staining techniques such as 5 - aminolevulinic acid , it has been shown that significant areas of carcinoma in situ are easily overlooked by conventional cystoscopy . Courtesy of Abbott and Vysis Inc . Bladder cancer is the only cancer in which BCG is commonly used . Other agents have been used in bladder cancer , but none has surpassed the effectiveness of BCG . For BCG to be effective , all the following criteria should be met : The patient is immunocompetent The tumor burden is small BCG makes direct contact with the tumor The dose is adequate to incite a reaction Studies have consistently shown that BCG treatment can eradicate this cancer in 70 % of patients with CIS who meet these criteria . To prevent cancer recurrence , long - term maintenance therapy following the induction phase is necessary . Typically , BCG is administered in either an induction ( once weekly for 6 weeks ) or maintenance ( once weekly for 3 weeks ) course . Another 6 - week course may be administered if a repeat cystoscopy ( see image above ) reveals tumor persistence or recurrence . Induction therapy combined with maintenance therapy every 3 - 6 months for 1 - 3 years may provide more lasting results . Periodic bladder biopsies are usually necessary to assess response . A 2016 guideline from the American Urological Association ( AUA ) and the Society of Urologic Oncology ( SUO ) includes the following recommendations for use of BCG in non – muscle invasive bladder cancer 8 In a high - risk patient with newly diagnosed CIS , high - grade T1 , or high - risk Ta urothelial carcinoma , administer a 6 - week induction course of BCG ( strong recommendation ; evidence strength , grade B ) In an intermediate - risk patient who completely responds to an induction course of intravesical chemotherapy , maintenance BCG therapy may be used ( conditional recommendation ; evidence strength , grade C ) In an intermediate - risk patient who completely responds to induction BCG , consider maintenance BCG for 1 year , as tolerated ( moderate recommendation ; evidence strength , grade C ) In a high - risk patient who completely responds to induction BCG , maintenance BCG should be continued for 3 years , as tolerated ( moderate recommendation ; evidence strength , grade B ) In an intermediate - or high - risk patient with persistent or recurrent disease or positive cytology following intravesical therapy , consider performing prostatic urethral biopsy and an upper tract evaluation prior to administering additional intravesical therapy ( conditional recommendation , evidence strength , grade C ) In an intermediate - or high - risk patient with persistent or recurrent Ta or CIS disease after a single course of induction intravesical BCG , a second course of BCG should be offered ( moderate recommendation , evidence strength , grade C ) In a patient fit for surgery with high - grade T1 disease after a single course of induction intravesical BCG , radical cystectomy should be offered ( moderate recommendation , evidence strength , grade C ) Additional BCG should not be prescribed to a patient who is intolerant of BCG or has documented recurrence on transurethral resection of bladder tumor ( TURBT ) of high - grade , non – muscle - invasive disease and / or CIS within 6 months of two induction courses of BCG or induction BCG plus maintenance ( moderate recommendation , evidence strength , grade C ) If intermediate - or high - risk non – muscle - invasive bladder cancer persists or recurs after two courses of BCG and the patient is unwilling to undergo cystectomy or is unfit for it , clinical trial enrollment may be recommended ; if a trial is unavailable , the patient may be offered intravesical chemotherapy ( expert opinion ) In a high - risk patient with persistent or recurrent disease within 1 year following treatment with two induction cycles of BCG or BCG maintenance , radical cystectomy should be offered ( moderate recommendation , evidence strength , grade C ) For more information , see Bladder Cancer Mechanism of Action of BCG The mechanism of action of BCG therapy is incompletely understood . Some early studies purported that an immune response against bacillus Calmette - Guérin ( BCG ) surface antigens cross - reacted with putative bladder tumor antigens , and this was proposed as the mechanism for the therapeutic effect of BCG ; however , multiple subsequent studies refute this claim . Once in the bladder , the live organisms enter macrophages , where they induce the same type of histologic and immunologic reaction as found in patients with tuberculosis . BCG vaccine also has been shown to have a predilection for entering bladder cancer cells , where the proteins are broken down and fragments are combined with histocompatibility antigens and displayed on the cell surface . This induces a cytokine and direct cell - to - cell cytotoxicity response , which targets these cells for destruction . The overall response to BCG is limited if the patient is immunosuppressed . Dal Moro and collegues evaluated the influence of hypertension on the outcome of patients with noninvasive bladder cancer treated with BCG . In both univariate and multivariate analyses of 343 high - risk bladder cancer patients undergoing BCG with a median follow - up of 116 months , hypertension was a statistically significant parameter prognostic for recurrence after BCG treatment . Further study is needed to both evaluate hypertension as a possible prognostic factor to be used in selecting poor - prognosis BC patients as early candidates for surgical treatment . 7 Contraindications to BCG Contraindications to bacillus Calmette - Guérin ( BCG ) vaccine therapy include immunosuppression , cancer invading the bladder muscle , and large tumor volume . Because BCG is a live attenuated organism , it can cause an acute disseminated tuberculosislike illness if it enters the bloodstream ( BCG sepsis ) , possibly resulting in death . Reports have described BCG vaccine organisms identified on vascular grafts in patients who have died following BCG vaccine sepsis . Therefore , the use of BCG is contraindicated in patients with gross hematuria , traumatic catheterization , and recent bladder tumor resection . Additionally BCG Strains The original bacillus Calmette - Guérin ( BCG ) strain was developed at the Pasteur Institute from an attenuated strain of Mycobacterium bovis . Subcultures were made and sent to other parts of the world . Two BCG products are commercially available in the United States . The Tice strain , which is a substrain of the original Pasteur product , is manufactured by Organon Pharmaceuticals . The TheraCys strain is made by Aventis / Pasteur . These products , in addition to the Tokyo 172 substrain and the Danish substrain , are available in countries other than the United States . No one product has been shown to have consistent clinical superiority . BCG viability is an important consideration for the vaccine to be effective . This viability is measured in colony - forming units ( CFUs ) . A vaccine that contains no or very few live organisms would be clinically ineffective . One dose , either an ampule or vial , may vary in weight from one product to another , but the CFU should be similar . Tice BCG has 1 - 8 × 10 - 8 CFUs . TheraCys has 10.5 + / - 8.7 × 10 - 8 CFUs . In a study that compared Tokyo172 with the Connaught vaccines , Ikeda et al found that the Tokyo172 vaccine had 48.77 + / - 5.43 CFUs per dose , while the Connaught strain had 3.77 + / - 1.45 CFUs . 2 This implies that a smaller dose of Tokyo172 is likely to be as effective as a much larger dose of the Connaught strain . BCG Immunotherapy Technique Preparation The BCG solution is prepared by initially dissolving the freeze - dried powder with the diluent that comes with the preparation . This solution is diluted further with saline , so that the total volume is approximately 30 mL The individuals who prepare and administer BCG should wear gloves and avoid spilling or touching the vaccine . BCG may cause a strong local reaction in a sore or a cut . If the vaccine is splashed into an eye , it should immediately be washed . This is a preparation that contains live organisms ; care should be taken during preparation , administration , and disposal of the supplies . The BCG solution should be used within 2 - 3 hours . It is instilled into the bladder via a small catheter by gravity or a slow drip ( not forced into the bladder ) . The solution should be retained for 1.5 - 2 hours , after which time the patient voids . The patient is encouraged to move positions every 30 - 45 minutes to allow the BCG solution to contact all portions of the bladder lumen . If the patient ’ s bladder ordinarily retains more than 60 mL of urine , the bladder may need to be drained after the BCG solution is retained for 2 hours . Patients do not have to remain in the office during the retention time . Patients should not be given antibiotics at the time of the instillation . These medications can kill the live organisms and negate the effect of the treatment . The patient should wash out the toilet with bleach following the next 3 urinations to avoid exposing other family members to the vaccine . BCG induction therapy To a BCG reaction , multiple instillations of BCG are required . Typically , 6 weekly instillations constitute the induction phase , although some patients respond with fewer instillations and some require more . Each patient ' s response should be assessed each time the patient comes for an instillation . The induction phase is considered complete when the immunologic reaction has occurred . This is evident when the patient has irritative bladder symptoms , the urine contains WBCs without evidence of infection , and microscopic hematuria is present . Once the patient has been induced or vaccinated , this phase of therapy has been completed . BCG maintenance therapy When induction is completed , a course of immunoprophylaxis or maintenance therapy is begun . Prolonging the course of therapy has been shown to reduce the frequency of recurrence and progression . These intervals have varied from instillations administered monthly to every 3 months or every 6 months . The optimum frequency and duration of this therapy seems to vary , but a Southwest Oncology study found that 2 - 3 instillations every 3 months is effective . 3 Most experts agree that a maintenance program of at least 1 year is necessary . From the immunologic point of view , establishing this interval is difficult because patient variability is great and this is a biologic product whose dose may differ slightly with each instillation . The products also vary . Antigenic stimulation becomes greater with consecutive instillations but decreases dramatically when the stimulation is excessive . Data from a small study conducted by Palou et al indicated that patients who are tumor - free after 6 months of therapy are likely to remain so indefinitely and do not need additional maintenance . 4 Most studies have shown the benefit of using maintenance therapy for at least one year . Tolerability of therapy Patients often have difficulty completing long - term therapy because of irritative adverse effects in the bladder . In such cases , the intervals between instillations should be lengthened ; in addition , dose modification may also be necessary . Generally , a full ampule is administered , but some patients respond just as well to half or even one third of a dose and seem to have fewer adverse effects . The dose selection depends on the degree of reaction in the patient . Patients treated with the Tokyo172 substrain need only a 25 % dose because of the Adverse Effects of BCG Usually , the first 1 - 3 instillations of bacillus Calmette - Guérin ( BCG ) vaccine cause very few adverse effects , unless the patient has been previously vaccinated with BCG vaccine or has a history of tuberculosis . After the third instillation , patients usually begin experiencing irritative bladder symptoms and / or flulike symptoms that last 24 - 72 hours . These symptoms are usually mild and can be controlled with bladder antispasmodics , NSAIDs , and antihistamines , and they are often perceived as favorable immunological responses to the therapy . Nearly 80 % of patients In a randomized controlled study of 166 patients , the complete response rate for low dose BCG was 79 % compared to 85 % for standard dose BCG . However , low dose BCG was associated with significantly less fever and micturition pain and significantly higher quality of life scores . There were no significant differences between the groups in terms of recurrence , progression and overall survival . 6 A study by Rosevear et al found that a poor response to BCG plus interferon - α therapy in patients with carcinoma in situ were associated with prior tumor stage , 2 or more prior BCG failures , and a BCG failure pattern . 5 Patients who develop a fever of higher than 39 ° C ( 102.2 ° F ) and those who have gross hematuria , severe irritative symptoms lasting more than 72 hours , a urinary tract infection , elevated liver enzyme levels , arthritis , epididymoorchitis , or acute prostatitis should not receive additional BCG vaccine therapy until these findings have resolved . These are symptoms of a systemic BCG reaction , and further administration is unnecessary , immunosuppressive , and potentially lethal . BCG therapy should be administered at reduced doses half or a quarter dose can be administered . Severe reactions to BCG vaccine , including high - grade fevers ( ie , temperature > 40 ° C [ 104 ° F ] ) , hepatotoxicity , respiratory distress , chills , hemodynamic instability , and mental status changes , suggest life - threatening septicemia . These are emergencies , and patients should be hospitalized . A urine culture should be obtained because many cases of septicemia following BCG vaccine instillation are caused by more common uropathogens , rather than the organisms in the BCG vaccine . Tuberculosis organisms from the urine or tissues are usually difficult to culture . Treatment should be initiated without waiting for culture results . Broad - spectrum antibiotics should be administered intravenously , and the patient should be started on antituberculosis therapy , including rifampin , isoniazid , and cycloserine , which is the only antituberculosis drug to reach bactericidal levels within 24 hours of administration . Corticosteroids are also recommended in some patients . When BCG vaccine therapy was introduced , several deaths were reported , all of which could be attributed to improper use of this agent . At present , a death is extraordinary because clinicians have learned how to administer this agent and to stop therapy before a patient becomes ill . Sections Bacillus Calmette - Guérin Immunotherapy for Bladder Cancer Show All References
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"BCG Immunotherapy",
"Bladder Cancer"
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http://emedicine.medscape.com/article/195165-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > General Surgery Gallbladder Mucocele Updated : Jun 11 , 2018 Author : R Vijayaraghavan , MBBS , MS , FRCS ( Edin ) ; Chief Editor : John Geibel , MD , DSc , MSc , AGAF more . . . Sections Overview Practice Essentials Background Pathophysiology Etiology Epidemiology Prognosis Show All Presentation DDx Workup Treatment Questions & Answers Media Gallery References Practice Essentials The term gallbladder mucocele refers to an overdistended gallbladder filled with mucoid or clear and watery content . Usually noninflammatory , it results from outlet obstruction of the gallbladder and is commonly caused by an impacted stone in the neck of the gallbladder or in the cystic duct . ( See the image below . ) Stone in neck of gallbladder , with postacoustic shadowing . Minimal wall thickening and dilated gallbladder suggest mucocele . View Media Gallery Signs and symptoms Symptoms of a gallbladder mucocele include the following : Right - upper - quadrant ( RUQ ) pain or epigastric pain and discomfort Nausea and vomiting The following suggest other conditions : Continuance of pain or persistence of tenderness for longer than 6 hours - Acute cholecystitis Fever and chills - Infected bile , with possible gallbladder empyema Jaundice - Coexisting obstruction of the common bile duct ( CBD ) Physical findings include the following : Minimal acute inflammatory signs Large , palpable , somewhat tender mass See Presentation for more detail . Diagnosis Laboratory studies that may be helpful include the following : White blood cell ( WBC ) count - Mild leukocytosis with a left shift is common ; higher counts suggest acute cholecystitis or infected bile Bilirubin - Usually within the reference range but may be mildly raised with Mirizzi syndrome or associated CBD obstruction or cholangitis Liver enzymes - Usually within the reference range , though alkaline phosphatase may be mildly elevated ; large increases suggest an obstructed CBD Serum amylase levels - Usually within the reference range ; large increases suggests acute pancreatitis Imaging modalities that may be considered include the following : Ultrasonography - Extremely sensitive in detecting gallbladder stones and identifying intrahepatic biliary tree dilatation Plain radiography of the abdomen - Nonspecific , used only as a guideline in differential diagnosis Scintigraphy ( hepato - iminodiacetic acid [ HIDA ] scanning ) - Capable of offering only indirect evidence but possible worth considering in obscure cases Computed tomography ( CT ) - Indicated when the diagnosis is unclear or other associated conditions or complications are present that must be assessed Magnetic resonance cholangiopancreatography ( MRCP ) See Workup for more detail . Management Surgery is definitive treatment for gallbladder obstruction , and no absolute contraindication to such treatment exists . However , the following factors may be considered : The presence of any associated medical conditions or illnesses that preclude surgery would constitute a contraindication to surgical treatment . Laboratory research suggests that chemical ablation of the gallbladder mucosa may be an alternative in patients who are medically unfit , elderly , or critically ill Surgical options include the following : Laparoscopic cholecystectomy - The criterion standard procedure Open cholecystectomy - An option for patients who have a very large gallbladder , greatly thickened gallbladder walls , or an obliterated triangle of Calot Percutaneous or open cholecystostomy - A temporary measure , usually performed when the patient is very sick or the dissection is technically very difficult and followed by a completion cholecystectomy Laparoscopic subtotal cholecystectomy - An option for very difficult gallbladder dissections in which the inflammation is very severe and in the region of the neck Treatment Next : Background Sections Gallbladder Mucocele Overview Background Pathophysiology Etiology Epidemiology Prognosis Show All DDx Questions & Answers Media Gallery References Recommended Diseases & Conditions Biliary Disease News Cholecystectomy Should Be Delayed Until After Pregnancy : Group
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"Gallbladder Mucocele",
"epigastric pain"
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http://emedicine.medscape.com/article/1952251-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Neurology Homocystinuria / Homocysteinemia Updated : Jul 27 , 2018 Author : Pitchaiah Mandava , MD , PhD ; Chief Editor : Helmi L Lutsep , MD more . . . Sections Overview Pathophysiology Epidemiology Presentation Diagnosis Treatment Questions & Answers Show All References Overview Homocystinuria Homocystinuria is a disorder of methionine metabolism , leading to an abnormal accumulation of homocysteine and its metabolites ( homocystine , homocysteine - cysteine complex , and others ) in blood and urine . Normally , these metabolites are not found in appreciable quantities in blood or urine . Homocystinuria is an autosomal recessively inherited defect in the transsulfuration pathway ( homocystinuria I ) or methylation pathway ( homocystinuria II and III ) . Homocysteinemia Homocysteinemia , a separate but related entity , is defined as elevation of the homocysteine level in blood . This condition has also been referred to as homocyst ( e ) inemia to reflect metabolites that may accumulate . A mild elevation of plasma homocysteine may exist without homocystinuria . Homocysteinemia may be due to a genetic predisposition to abnormal activity in the same pathways as homocystinuria . Nutritional and environmental factors , as well as specific medications , may worsen this abnormality and provoke symptoms . Homocysteine level and stroke An increased homocysteine level is associated with a higher risk of strokes . Carotid stenosis appears to have a graded response to increased levels of homocysteine . Increased carotid plaque thickness has been associated with high homocysteine and low B - 12 levels . Yoo et al studied both intracranial and extracranial vessels by MR angiography and reported that homocysteine levels were higher in patients with 2 - or 3 - vessel stenoses than in those with 1 - vessel stenosis . 1 For more information on stroke , see the topics Hemorrhagic Stroke and Ischemic Stroke , as well as Thrombolytic Therapy in Stroke and Acute Stroke Management For patient education information , see the Stroke Center , as well as Stroke Pathophysiology The accumulation of homocysteine and its metabolites is caused by disruption of any of the 3 interrelated pathways of methionine metabolism — deficiency in the cystathionine B - synthase ( CBS ) enzyme , defective methylcobalamin synthesis , or abnormality in methylene tetrahydrofolate reductase ( MTHFR ) . Clinical syndromes resulting from each of these metabolic abnormalities have been termed homocystinuria I , II , and III . Three different cofactors / vitamins — pyridoxal 5 - phosphate , methylcobalamin , and folate — are necessary for the 3 different metabolic paths . The pathway , starting at methionine , progressing through homocysteine , and onward to cysteine , is termed the transsulfuration pathway . Conversion of homocysteine back to methionine , catalyzed by MTHFR and methylcobalamin , is termed the remethylation pathway . A minor amount of remethylation takes place via an alternative route using betaine as the methyl donor . 2 Homocysteine Metabolism Cycle Homocysteinemia theoretically could be a result of defects at any of these 3 locations . These abnormalities could arise from solely a genetic predisposition or from a genetic predisposition worsened by comorbid conditions and / or nutritional and environmental factors . These conditions and factors may be related to abnormal MTHFR , chronic renal failure , hypothyroidism , malignancies , methotrexate treatment , oral contraceptive use , consumption of animal proteins , and smoking . An abnormal gene on chromosome 1 has been proposed as the cause of reduction in MTHFR ; however , whether this mutation alone can lead to cerebrovascular events or whether it requires additional environmental or nutritional lack of folic acid to cause symptomatic homocysteinemia is unclear . 3 Increased homocysteine level is associated with a higher risk of strokes . Carotid stenosis appears to have a graded response to increased levels of homocysteine . Increased carotid plaque thickness has been associated with high homocysteine and low B - 12 levels . Yoo et al studied both intracranial and extracranial vessels by MR angiography and reported that homocysteine levels were higher in patients with 2 - or 3 - vessel stenoses than in those with 1 - vessel stenosis . 1 In patients with a baseline homocysteine level exceeding 9.1 umol / L , supplementation with B vitamins resulted in slowed progression of carotid intimal medial thickness ( CIMT ) . Several mechanisms have been suggested as the possible cause of accelerated vascular disease , including the following : Endothelial cell damage Smooth muscle cell proliferation Lipid peroxidation Upregulation of prothrombotic factors ( XII and V ) Downregulation of antithrombotic factors or endothelial - derived nitric oxide Epidemiology The incidence of homocystinuria in the United States is approximately 1 per 100,000 . Internationally , the reported incidence of homocystinuria varies between 1 in 50,000 and 1 in 200,000 . Early diagnosis and intervention have helped in preventing some of the complications of homocystinuria , including ectopia lentis , mental retardation , and thromboembolic events . A mortality rate of 18 % by age 30 has been reported by Mudd et al from a worldwide series of 629 patients with CBS enzyme deficiency . 4 Death is predominantly due to cerebrovascular or cardiovascular causes . Children with CBS deficiency ( homocystinuria I ) may be normal at birth . Data from Mudd et al suggest that starting at around age 20 years , these patients have an increasing likelihood of suffering a thromboembolic event . Patients with either defective methylcobalamin synthesis or defective tetrahydrofolate metabolism may present in early infancy . Clinical Presentation Homocystinuria Homocystinuria is associated with the following physical findings : Downward dislocation of lens ( ectopia lentis ) Marfanoid habitus Pes excavatum , pes carinatum , and genu valgum Mental retardation Signs and symptoms of strokes in any vascular distribution : hemiplegia , aphasia , ataxia , and pseudobulbar palsy are among the most common findings . Patients with classic homocystinuria may first be recognized because of downward dislocation of the lens ( ectopia lentis ) 5 , marfanoid habitus , mental retardation 5 , and / or seizures . Patients with defective methylcobalamin synthesis may have all of these features , along with symptoms of methylmalonic acidemia ( see Metabolic Disease and Stroke - Methylmalonic Acidemia ) . Acute stroke symptoms may occur in these patients . Traditional risk factors — hypertension , smoking , and diabetes — may or may not be present . The oral health of 14 patients with homozygote cystathionine beta synthase - deficient homocystinuria was evaluated in a Swedish study and found to be compromised in a majority of cases . The authors suggested that methionine restriction ( low - protein diet ) in the treatment of homocystinuria may result in a diet high in sugars . They therefore noted the need for regular dental checkups and preventive oral care for individuals suffering from homocystinuria . In addition , the authors noted that all patients had short dental roots , particularly of the central maxillary incisors . 6 In a Spanish cross - sectional survey sent to 35 hospitals , 75 patients were identified with homocystinuria : 41 with transsulfuration defects ( 1 death ) , 27 with remethylation defects ( 6 deaths ) , and 7 without a syndromic diagnosis . In 18 cases , more than one sibling was affected . Patients with remethylation defects had the most severe clinical manifestations . There was a high percentage of cognitive impairment , followed by lens diseases . Neurologic disorders were present in almost half of the patients , and there was increased vascular involvement in CBS - 7 Homocysteinemia Patients with homocysteinemia may present with vascular thrombotic events , with or without the traditional risk factors for a stroke . If the usual risk factors are not present , a more rigorous search for rarer causes of stroke should be undertaken . This group of patients may already have a history of strokes and myocardial infarctions in the third or fourth decade of life . Diagnosis Several studies have pointed out that early diagnosis and institution of treatment and dietary restriction is likely to slow the progression of disease in homocystinuria as well as to reverse some of the features . If family history and sibling history suggest homocystinuria , screening tests should be advised . Early signs of myopia and lens abnormalities can not be ignored . 8 Bony abnormalities and body habitus can be confused with Marfan syndrome ; however , Marfan syndrome follows an autosomal dominant inheritance pattern , while homocystinuria follows a recessive pattern . The differential diagnosis includes the following : Blood Dyscrasias and Stroke Metabolic Disease & Stroke : Fabry Disease Metabolic Disease & Stroke : Methylmalonic Acidemia Metabolic Disease & Stroke : Propionic Acidemia Other problems to be considered include carotid disease and stroke . Acute stroke diagnosis and treatment requires that certain laboratory studies such as complete blood count , chemistries , prothrombin / activated partial thromboplastin times ( PT / aPTT ) , brain imaging , echocardiography , and vascular studies be done to exclude the usual causes , some of which may be treatable or preventable . If homocystinuria is suspected on the basis of history , physical examination , and family history , the patient may be transferred to a tertiary care center , where expertise in a variety of relevant fields is more likely to be available . Laboratory studies for homocystinuria If patients present with systemic signs and symptoms , screening tests followed by confirmatory tests may be done . The urine screening test for sulfur - containing amino acids , called the cyanide nitroprusside test , can be undertaken ; however , high rates of false - negative as well as false - positive results are reported . A neonatal screening test , called the Guthrie test , detects high levels of methionine in heel - stick blood . This test is performed routinely in several states for detection of phenylalanine , leucine , and methionine . Because of high false - negative results in homocystinuric patients , a recent report suggested lowering the threshold of methionine to qualify as abnormal . Quantitative tests for homocystine in urine and blood are available commercially . The blood specimen needs to be handled in a specific manner described in the homocysteinemia testing section . Measurement of CBS activity in cultured fibroblasts provides definitive support for the diagnosis . Testing of amniotic cells and chorionic villi is also available . Laboratory studies for homocysteinemia Laboratory studies may be considered in patients who present with symptoms of acute stroke in the absence of traditional risk factors such as hypertension , smoking , and diabetes . Nutritional factors , environmental toxins , or medical conditions may worsen an inherent homocysteinemia . No consensus exists on the timing of the test with respect to an acute event . Whether a methionine challenge should be used for testing is not clear at this juncture . The methionine challenge test may be more appropriate if a deficiency is suspected in the transsulfuration pathway . Specimens for total and free homocystine measurement must be handled and processed in a specific way ; they must be put on ice and spun within 1 hour . Whether the specifications are always followed by all laboratories or medical offices is unclear . The risk for vascular disease is graded with respect to the level of homocysteine ; however , no threshold abnormal value is accepted widely . If homocysteinemia is determined by a test , then tests for deficiency in folic acid , vitamin B - 12 , and pyridoxine also may be performed . Genetic abnormalities are reported on chromosome 1 pertaining to methylene tetrahydrofolate reductase ( MTHFR ) ; however , the mere presence of this abnormality may not confer a risk for vascular disease . CT scanning and MRI On routine imaging studies , bony abnormalities including osteoporosis may be readily apparent . A CT scan of the head is obtained routinely in patients presenting with acute stroke . Where available , MRI with newer techniques such as diffusion and perfusion imaging and MR angiography also may be used in the acute setting . MRI 9 and CT findings with either homocystinuria or classic homocysteinemia may show both large - vessel or lacunar strokes , potentially in any vascular distribution . Treatment & Management Pyridoxine , at a dose of 100 - 500 mg / d , is the drug of choice . Patients may be divided into pyridoxine - sensitive and pyridoxine - insensitive groups . In the first group , pyridoxine , folic acid , and vitamin B - 12 are prescribed . These 3 vitamins , in combination , reduce the homocysteine levels as well as provide clinical benefit . Secondary stroke prevention rests on risk factor reduction . Aspirin clopidogrel , and aspirin - dipyridamole have been suggested for secondary stroke prophylaxis , but whether other antiplatelet agents or anticoagulation are equally or more effective is not known . Measuring homocystine levels can be used to monitor the effectiveness of treatment . If pyridoxine alone is not effective , folic acid and vitamin B - 12 can be added to the regimen . If patients are pyridoxine insensitive , a low - methionine diet initiated at diagnosis , along with betaine supplementation , may help reduce homocysteine levels . 10 No consensus exists on optimal approaches to the treatment of homocysteinemia . Plasma homocysteine levels are reduced by folic acid supplementation . With the mandated fortification of cereals with folic acid in the United States , B - 12 deficiency ( or relative B - 12 deficiency ) may influence homocysteinemia . The optimal dose and route of administration of B - 12 and dose of folic acid and the effect on clinical outcome have not been studied prospectively . Initiation of therapy with B - 12 , folic acid , and B - 6 tends to normalize homocysteine in 4 - 8 weeks . The Vitamin Intervention for Stroke Prevention ( VISP ) trial showed no difference in stroke outcome between high - and low - dose vitamin ( B - 12 , B - 6 , folic acid ) supplementation groups . 11 Subgroup analysis showed that patients with a high baseline homocysteine who were assigned to low - dose vitamins had a higher risk of stroke . Reanalysis of the Heart Outcomes Prevention Evaluation 2 ( HOPE 2 ) trial showed a reduced incidence of nonfatal stroke with long - term ( > 3 y ) treatment with B vitamins . 12 Consultations An experienced neurologist ( adult or pediatric ) should be consulted both for acute care of a patient with a stroke and for the diagnosis of uncommon causes of a stroke . Genetic counseling should be offered to the patient and the family on confirmation of homocystinuria . Dietary consultation may be required if a homocystinuric patient is found to be pyridoxine insensitive and requires dietary modification . Physical , occupational , and speech therapists may be consulted for patients with acute stroke . Prognosis Early diagnosis of homocystinuria along with prophylactic medical and dietary care is a key to better long - term prognosis ; it can halt or even reverse some of the complications . Complications Patients with homocystinuria are prone to thromboembolic events in the perioperative and postoperative periods , even with minor surgeries . Preoperative levels of homocysteine should be reduced to a near normal level . During and after surgery , aggressive hydration and prophylaxis for deep vein thrombosis ( DVT ) are strongly recommended . Questions & Answers What is homocystinuria ? What is homocysteinemia ? What is the association of homocystinuria and homocysteinemia with stroke ? What is the pathophysiology of homocystinuria ? What is the pathophysiology of homocysteinemia ? What causes accelerated vascular disease in homocystinuria and homocysteinemia ? What is the prevalence of homocystinuria and homocysteinemia ? Which physical findings are characteristic of homocystinuria ? Which physical findings are characteristic of homocysteinemia ? When is homocystinuria and homocysteinemia screening indicated ? How is Marfan syndrome differentiated from homocystinuria ? Which conditions should be included in the differential diagnoses for homocystinuria and homocysteinemia ? How is stroke differentiated from homocystinuria and homocysteinemia ? When should patient transfer be considered for the treatment of homocystinuria and homocysteinemia ? What is the role of lab testing in the diagnosis of homocystinuria ? What is the role of lab testing in the diagnosis of homocysteinemia ? What is the role of imaging studies in the diagnosis of homocystinuria and homocysteinemia ? How is homocystinuria treated ? How is homocysteinemia treated ? Which specialist consultations are beneficial to patients with homocystinuria ? What is the prognosis of homocystinuria ? What are the possible complications of homocystinuria ? Sections Homocystinuria / Homocysteinemia Presentation Treatment Show All References
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"Homocystinuria",
"methionine metabolism",
"homocysteine"
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http://emedicine.medscape.com/article/1962893-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pathology Pathology of Reactive Gastropathy Updated : Feb 22 , 2017 Author : Antonia R Sepulveda , MD , PhD ; Chief Editor : Mamoun Younes , MD more . . . Sections Overview Pathophysiology and Etiology Epidemiology Clinical Features Differential Diagnosis Gross Findings Microscopic Findings Immunohistochemistry Prognosis and Predictive Factors Show All Media Gallery References Overview Reactive gastropathy refers to the constellation of endoscopic and histologic findings caused by chemical injury to the gastric mucosa . 1 The histologic picture is characterized by foveolar hyperplasia with edema , smooth muscle hyperplasia , and congestion of superficial capillaries in the lamina propria in the absence of significant inflammation ( see an example in the image below ) . Mild reactive gastropathy involving gastric antral mucosa ( original magnification 200 × ) . View Media Gallery These features were originally described in biopsy specimens obtained from patients who had undergone gastric surgery and were felt to be specific for bile reflux . 2 3 4 It has since become apparent , however , that the constellation of histologic features seen in reactive gastropathy is a nonspecific response to chemical injury of the gastric mucosa . 5 6 7 Reactive gastropathy has also been referred to as chemical gastropathy , reflux gastritis , and type C gastritis . 5 The term " chemical gastropathy " was recommended by the Updated Sydney System , 1 because it indicates an underlying chemical injury that is not associated with infection . 8 Go to Peptic Ulcer Disease for complete information on this topic . Pathophysiology and Etiology The common underlying causes of reactive gastropathy include chronic bile reflux and long - term intake of nonsteroidal anti - inflammatory drugs ( NSAIDs ) . Bile reflux usually occurs in patients who have undergone a Billroth II partial gastrectomy ; it is also recognized to occur in intact stomachs in individuals with alcohol abuse , cigarette smoking , chronic respiratory disease , or duodenal ulcer , and even in healthy subjects . 8 9 The duodenogastric reflux results in disruption of the protective mucus barrier and direct injury to the gastric mucosa , causing backflow of hydrogen ions and epithelial damage . 10 The various bile acid species differ in their capacity to cause injury to the gastric mucosa . 4 The secondary ( deoxycholic and lithocholic ) and deconjugated bile acids are more injurious to the gastric mucosa than the primary ( colic and chenodeoxycholic ) and conjugated bile acids . In situations of upper gastrointestinal ( GI ) stasis , as is seen after gastric surgery , bacterial overgrowth occurs within the proximal small intestine . This increase in intraluminal bacteria leads to subsequent generation of relatively increased concentrations of deconjugated and secondary bile acids within the refluxate . The increased concentration of the more toxic forms of bile acid , coupled with the decreased gastric emptying time of the refluxed bile , results in gastric mucosal injury and subsequent reactive gastropathy ( chemical gastropathy ) . The predominant mechanism of NSAID - induced gastric injury involves decreased synthesis of mucosal prostaglandins . 11 12 Prostaglandins are derived from arachidonic acid via the cyclooxygenase ( COX ) pathway . Thus , inhibition of COX by NSAIDs reduces prostaglandin synthesis , thereby diminishing mucosal blood flow and decreasing mucus and bicarbonate secretion . Furthermore , NSAIDs , being weak organic acids , can freely diffuse into the gastric epithelium . As a result of the neutral pH within the surface epithelial cells , the NSAID compound dissociates into its ionized form , contributing to direct cell injury . 13 Although it is known that NSAIDs that selectively inhibit COX - 2 cause significantly fewer GI complications than nonselective COX inhibitors do , it is still unclear whether administration of selective inhibitors results in less severe reactive gastropathy ( chemical gastropathy ) . 14 However , most of these COX - 2 inhibitors have been withdrawn from the market or have had their indications drastically limited in view of their potential serious cardiovascular side effects . 15 The epithelial injury results in excessive exfoliation of the surface epithelial cells , which gives rise to a reactive foveolar hyperplasia . 2 The accompanying histamine - mediated vascular response leads to edema and hyperemia . Persistent epithelial damage may result in the release of platelet - derived growth factor ( PDGF ) , which stimulates smooth muscle proliferation , followed by fibroblastic proliferation . 10 The mucosal changes seen in reactive gastropathy are usually most prominent in the antrum and prepyloric region . When associated with bile reflux secondary to partial gastrectomy , the lesions develop near the surgical stoma , 16 but the more proximal oxyntic mucosa may also be affected . To date , no specific genetic predisposing factors for the development of reactive gastropathy have been identified . Epidemiology Reactive gastropathy is the second most common pathologic diagnosis rendered on gastric biopsies , after Helicobacter pylori gastritis H pylori - associated active gastritis is discussed in a separate pathology article ) . 14 17 This condition was originally described in patients who had undergone partial gastrectomy — most frequently , Billroth II gastric reconstruction . It has also been observed after Billroth I gastric reconstruction , truncal vagotomy , and pyloroplasty 3 and occasionally after cholecystectomy and ampullary sphincterotomy . 18 19 20 At present , reactive gastropathy is usually encountered in the clinical setting of chronic nonsteroidal anti - inflammatory drug ( NSAID ) use . The reported prevalence of reactive gastropathy among patients taking daily NSAIDs for at least 1 month ranges from 30 % to 40 % . 7 21 22 Clinical Features The clinical features associated with reactive gastropathy are determined by its underlying cause . ( See Pathophysiology and Etiology . ) Patients with reactive gastropathy secondary to bile reflux typically have an enterogastric anastomosis and most commonly present with continuous burning midepigastric pain that is often exacerbated by food and recumbency . Nausea , bilious vomiting , and other dyspeptic symptoms may also be present . 23 Although the findings are not specific , several authors claim that weight loss and a hypochromic microcytic anemia are also associated features . The most common complaint associated with NSAID - induced reactive gastropathy is mild dyspepsia . Chronic consumption of these drugs , however , can lead to the development of erosions and ulcers , increasing the risk for complications such as obstruction , perforation , and bleeding . 13 Differential Diagnosis Gastric antral vascular ectasia ( GAVE ) should be considered in the differential diagnosis . The presence of fibrin thrombi in the mucosal capillaries is a characteristic feature of GAVE rather than of reactive gastropathy . This finding , along with its distinctive endoscopic appearance ( " watermelon stomach " ) , aids in the differentiation of GAVE from other similar - appearing entities . Other conditions to consider include the following : H pylori - induced gastritis Portal hypertensive gastropathy Gross Findings The endoscopic findings of reactive gastropathy are mostly nonspecific . The mucosa may be normal or may exhibit erythema , congestion , edema , or erosions . The bile reflux may be visible . 24 Microscopic Findings Mucosal changes in reactive gastropathy are readily appreciated by comparison with normal gastric mucosa ( see the image below ) . Normal gastric antrum ( original magnification 100 × ) . View Media Gallery Reactive gastropathy is characterized by prominent foveolar hyperplasia with elongation and tortuosity of the gastric pits that gives these structures a corkscrew appearance . The surface may appear villiform . The foveolar cells show regenerative changes with mucin depletion , nuclear hyperchromasia , and increased mitoses . Superficial erosions may be observed . There is smooth muscle hyperplasia in the lamina propria with edema and congestion of superficial capillaries . There is a paucity of both acute and chronic inflammatory cells . However , in the presence of erosions , superficial neutrophils may be seen . Occasionally , focal intestinal metaplasia may be present . Special stains for H pylori are negative . Reactive gastropathy may range from mild to severe and , as noted ( see Pathophysiology and Etiology ) , may involve the oxyntic mucosa as well as the antral mucosa ( see the images below ) . Mild reactive gastropathy involving gastric antral mucosa ( original magnification 200 × ) . Moderate reactive gastropathy involving gastric oxyntic mucosa ( original magnification 100 × ) . Moderate reactive gastropathy involving gastric antral mucosa ( original magnification 200 × ) . Moderate reactive gastropathy . Arrow points to smooth muscle fibers in superficial lamina propria ( original magnification 200 × ) . Severe reactive gastropathy with mucosal erosion of gastric antral mucosa ( original magnification 200 × ) . The microscopic features of reactive gastropathy were well characterized by Dixon et al in their original description of reflux gastritis as a distinct histopathologic entity . In this study , a score ranging from 0 ( normal or absent ) to 3 ( severe ) was assigned to each of the following histologic features : ( 1 ) foveolar hyperplasia , ( 2 ) edema and smooth muscle fibers in the lamina propria , and ( 3 ) vasodilatation and congestion of the lamina propria . Two other features , ( 4 ) acute and ( 5 ) chronic inflammatory cells , were graded separately ; scores for each ranged from 0 ( severe increase ) to 3 ( absence of inflammatory cells ) , for Patients who had undergone gastric surgery were found to have a statistically significant increase in reflux gastritis score , gastric pH , and gastric bile acid concentration . Scores of 10 or higher were found to be highly characteristic of reactive gastropathy ( chemical gastropathy ) . A prospective multicenter study by Wolf et al developed a new score with visual analog scales . The study concluded that foveolar hyperplasia , smooth muscle fibers and vasodilatation and congestion as key histologic parameters for the diagnosis of reactive gastropathy . 25 Immunohistochemistry Mucin expression is reported to be altered in reactive gastropathy in comparison with normal gastric mucosa as well as gastritis . A patchy or complete loss of the membrane mucin MUC1 was observed in 67 % of cases . 26 Aberrant expression of the secreted mucins was also demonstrated . MUC5AC was seen in pyloric glands in 81 % of cases , and MUC6 was seen in the upper foveolar epithelium in 14 % of cases . These alterations in mucin expression were shown in cases of both nonsteroidal anti - inflammatory drug ( NSAID ) - associated and bile reflux – associated reactive gastropathy ( chemical gastropathy ) . Additionally , these changes are dissimilar to those seen in gastritis , reflecting the mechanistic differences between these gastropathies . 26 Reactive gastropathy is also characterized by differences in cytoskeletal structure and cell cycle kinetics , as compared with normal gastric mucosa and gastritis . Such changes have been studied in terms of immunohistochemical expression of CK7 , CK8 , CK18 , CK19 , CK20 , and Ki - 67 . In reactive gastropathy ( chemical gastropathy ) , the distribution of CK8 , CK18 , and CK19 was normally distributed but increased in intensity . The localization of CK7 and CK20 staining was modified , with extension toward the deep foveolar region . In contrast to gastritis , the surface epithelium lacked Ki67 expression and a downward elongation of the proliferative zone was noted . 27 Prognosis and Predictive Factors The finding of reactive gastropathy indicates the presence of an offending agent , usually nonsteroidal anti - inflammatory drugs ( NSAIDs ) or reflux of bile acid - containing duodenal contents into the stomach . The management of this condition may include discontinuance of NSAID use along with administration of proton pump inhibitors ( PPIs ) and prostaglandin analogues . Stump carcinoma has been reported in postgastrectomy stomachs . Bile reflux is thought to play a key role in the development of dysplasia and carcinoma in the gastric remnant . 28 In fact , some studies have reported improvement of preneoplastic changes after diversion of the enteric reflux . 29 Regular endoscopic surveillance starting 10 to 15 years after surgery is recommended . With the advent of highly effective medical treatment for infection , there has been a decline in such surgical procedures , paralleled by a reduction in the incidence of stump carcinoma . Despite the occasional development of stump carcinomas in postgastrectomy stomachs , reactive gastropathy is not a major risk factor for the development of gastric carcinoma Sections Pathology of Reactive Gastropathy Show All Media Gallery References
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"Pathology",
"Reactive Gastropathy",
"gastric mucosa"
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http://emedicine.medscape.com/article/1988699-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pathology Pathology of Asphyxial Death Updated : Jan 24 , 2016 Author : Michael A Graham , MD ; Chief Editor : J Scott Denton , MD more . . . Sections Overview Epidemiology Mechanism of Morbidity and Mortality Indications for Death Investigation Terminology Scene Findings Trace Evidence Gross Features Special Dissections and Procedures Microscopic Features Photography and Documentation Ancillary and Adjunctive Studies Issues Arising in Court Additional Resources Show All Media Gallery Tables References Overview " Asphyxia " is a term derived from Greek that literally translates as " stopping of the pulse . " This term refers to a multi - etiologic set of conditions in which there is inadequate delivery , uptake and / or utilization of oxygen by the body ’ s tissues / cells , often accompanied by carbon dioxide retention . Traditionally , the conditions leading to asphyxia have included breathing an oxygen - deficient atmosphere and / or interference with the act of breathing ( ie , inhaling and exhaling ) and / or respiration ( ie , gas exchange and the utilization of oxygen ) . Conditions that historically were thought to involve airway compromise but are now recognized to involve restriction of blood flow or altered hemodynamics ( eg , hanging , strangulation , and compression asphyxia ) continue to be classified as asphyxia . Although many natural disease processes may involve inadequate uptake and / or delivery of oxygen ( eg , chronic obstructive pulmonary disease [ COPD ] ) , the term " asphyxia " is generally reserved for conditions related to abnormal atmosphere and mechanical and chemical effects directly leading to the aforementioned abnormalities . Determination of the specific type ( s ) of asphyxia operative in a particular case , the cause of death , and the manner of death is dependent on information elicited during the medicolegal death investigation — namely , history ( circumstances ) , scene investigation , and postmortem examination ( including appropriate ancillary radiographic and laboratory studies ) . See also the following : Autopsy Request Process Adjuncts to the Forensic Autopsy Religions and the Autopsy Autopsy of the Transplant Recipient Autopsy Rate and Physician Attitudes Toward Autopsy Universal Precautions and High - Risk Autopsies Autopsy Quality Control Metrics Epidemiology According to the Centers for Disease Control and Prevention ( CDC ) site ' s searchable database for Multiple Cause of Death 1999 - 2004 , based on death certificates for United States residents , there are approximately 20,000 accidental and nonaccidental deaths within that period attributable to various types of mechanical asphyxia , such as drowning , hanging , strangulation , and suffocation . 1 The most common causes of asphyxial deaths differ among age groups . Drowning accounts for the overwhelming majority of asphyxial deaths in the 1 - 4 year age group , whereas hanging , strangulation , and drowning are the most common in the 35 - 44 year age group ( see the image below ) . Prevalence of various types of asphyxial deaths by age groups . Drowning accounts for the overwhelming majority of asphyxial deaths in the 1 - 4 year age group , whereas hanging , strangulation , and drowning are the most common in the 35 - 44 year age group . View Media Gallery Homicidal asphyxia is relatively uncommon and accounts for less than 5 % of homicide cases nationwide , ranking behind firearm injuries , sharp force wounds , and blunt force injuries 2 Mechanism of Morbidity and Mortality Breathing and respiration are complicated processes that have several components . The normal sequence is as follows : Environmental oxygen delivered into the lungs ( ventilation ) Oxygen diffuses from the air into the blood ( pulmonary gas exchange ) Blood delivers oxygen to tissues ( gas transport ) Cells uptake and then utilize oxygen for energy production Cellular respiration creates carbon dioxide . The carbon dioxide travels in reverse of oxygen and is eliminated from the body via exhaling . Normal breathing entails a patent airway , ability to expand the chest cavity via contraction of intercostal muscles and a functional diaphragm . Defects involving any of the above steps can result in asphyxia . The brain is the organ most sensitive to hypoxia . Asphyxial deaths typically involve respiratory arrest with bradycardia / asystole because of the hypoxia - induced dysfunction of the respiratory centers in the brainstem . 3 4 Individuals with comorbidities such as heart disease can be less tolerant of hypoxia , and relatively minor episodes of hypoxia can exacerbate the preexisting disease and , on occasion , precipitate a lethal cardiac rhythm disturbance . Asphyxia - related acidosis ( respiratory and / or metabolic ) may also have detrimental consequences . Tissue hypoxia Tissue hypoxia can occur for a few basic reasons . First , there may not be enough oxygen content within arterial blood even though the blood flow is normal . This usually occurs when breathing is impaired or when the inhaled air is deficient in oxygen . Second , blood flow and oxygen content are normal ; however , the blood does not release oxygen appropriately , or the cells do not utilize it . Chemical asphyxiants such as carbon monoxide ( CO ) and cyanide ( CN ) operate in this fashion . Third , the amount of oxygen Restriction of blood flow Restriction of blood flow from and to the brain is typically the major feature in nonjudicial hanging or strangulation . There is a significant difference in the amount of force required to occlude the adult airway and cervical blood vessels . Compression of the neck blood vessels is sufficient to cause unconsciousness and death . Thus , unconsciousness and death may occur without significant compromise of the airway . Table 1 . Adult Neck Structures and the Compression Pressures Needed to Cause Unconsciousness and Death ( Open Table in a new window ) Neck Structure Compression Pressure Jugular veins 4.4 lb Carotid arteries 5.5 - 22 lb Trachea 33 lb Vertebral arteries 18 - 66 lb Indications for Death Investigation A medicolegal death investigation is performed to evaluate the cause and manner of a death that occurs suddenly and unexpectedly ; that occurs under suspicious circumstances ; that may be due to " non - natural " causes such as violence or chemical agents ; or , that occurs under other statute or regulation defined circumstances . Deaths involving asphyxia typically fall within the jurisdiction of the medical examiner or coroner and are evaluated using a systematic medicolegal death investigation — examination of the circumstances , scene , and victim . Terminology Asphyxia is generally categorized as being either mechanical or chemical . There are various entities in each of these categories , and there is overlap among some of the entities . One or more entity can be operative in a particular case . Chemical vs mechanical asphyxia Chemical asphyxia involves the reaction between a chemical and tissue / cell that results in the interference of oxygen uptake , release , and / or utilization . Examples of chemical asphyxiants include carbon monoxide ( CO ) , cyanide ( CN ) , and hydrogen sulfide ( H 2 S ) . See the following image . Combination of chemical and environmental asphyxia due to carbon monoxide poisoning as a result of indoor charcoal grill usage . View Media Gallery Mechanical asphyxia involves some physical force or physical abnormality that interferes with the uptake and / or delivery of oxygen . Most mechanical asphyxiants affect breathing or blood flow , the latter usually due to neck vessel or thoracic compression . Breathing an oxygen - deficient atmosphere is typically considered a type of mechanical asphyxia . There are several subtypes of mechanical asphyxia , which are discussed below . Suffocation ( smothering ) The nose and / or mouth and / or upper pharynx are occluded by an object or body part in such a way that adequate breathing can not occur . Examples include a pillow or hand over the nose and mouth , a gag , and a head encased by a plastic bag . Environmental asphyxia When atmospheric oxygen is insufficient either due to exclusion , depletion , or displacement , environmental asphyxia may occur . This type of asphyxia is often considered a type of suffocation . Choking Choking involves the blockage of internal airways ( posterior pharynx , larynx , trachea , and / or bronchi ) by a foreign object ( eg , toy balloon lodged in child ' s airway , food bolus impacted at epiglottis ) . See the image below . Aspirated food particles present in trachea . There was a food bolus in the glottis as well as smaller particles in the trachea and mainstem bronchi . Aspiration Aspiration consists of the inhalation of nonbolus or nondiscrete foreign material ( eg , regurgitated stomach contents ) or site - inappropriate material . Site - inappropriate material includes such things as inhaled blood secondary to trauma . When aspiration leads to death , the " cause of death " is attributed to the condition ( disease or injury ) that led to the aspiration . A special type of aspiration is drowning . Drowning is defined by the 2002 World Congress on Drowning as the process resulting in primary respiratory impairment from submersion / immersion in a liquid . 5 The vast majority of drownings are the result of immersion / submersion in water . Compression ( traumatic ) asphyxia Compression or traumatic asphyxia involves the presence of external force on the chest and / or abdomen that prevents expansion of the chest that is necessary for proper breathing ( eg , constricting snake , overlying ) or causes a rapid increase in intrathoracic pressure with consequent vascular pressure effects ( eg , car falling on top of a mechanic ) . 6 7 See the following images . Photograph from a scene showing the position of the decedent ( white cutout ) pinned underneath car . Outline of a bookshelf on a child ' s chest after a period of compression . Postural ( positional ) asphyxia Postural or positional asphyxia is caused by the position of the body or part of the body leading to airway restriction , vascular compromise , or breathing fatigue ( eg , upside down suspension for prolonged period ) . Often , there is a degree of physical and / or mental impairment either due to trauma or intoxication . See the image below . Combination of positional and compressional asphyxia resulting from inversion for a prolonged period . Strangulation Application of force to the neck in such a way that the force applied is the result of other than the weight of the victim ' s body defines strangulation . Strangulation can be " manual " ( using hands to compress the neck , also known as throttling ) , " ligature " ( using an object such as a cord , wire , cloth , etc , to constrict the neck ) , or yoking ( using the forearm to apply neck pressure ) . The proper use of so - called " neck restraint holds " are Hanging Hanging consists of the application of force to the neck in such a way that the force applied is primarily the result of the weight of the victim ' s body . Contrary to popular belief , there does not have to be full suspension of the body for hanging to cause unconsciousness or death ( ie , the body can touch the floor ) , as shown in the image below . Self - suspension by ligature with feet contacting the floor . Compression of the neck blood vessels is sufficient to cause unconsciousness and death . Hanging is typically subclassified as nonjudicial or judicial . Nonjudicial hanging involves compression of the neck blood vessels with or without significant airway compression . Judicial hanging is designed to fracture and dislocate the upper cervical spine , thereby disrupting the upper cervical spinal cord and / or brainstem . Autoerotic asphyxia Autoerotic asphyxia is a purposeful solo activity during which an asphyxia - inducing apparatus or technique is used to enhance sexual stimulation and inadvertently causes death . Nearly all decedents are male . Cross - dressing and / or bondage are common . See the image below . Autoerotic asphyxial death in a man who cross - dressed and had a gag in the mouth . The escape mechanism from the bondage failed , resulting in death . Scene Findings The scene findings in asphyxial deaths are varied , reflecting the wide range of conditions that can lead to this condition . Law enforcement and medicolegal investigators should be aware that scene findings pointing the asphyxial nature of a death may be subtle in some cases . Reenactments of pediatric death scenes involving unsafe sleep conditions have been useful in elucidating the causes and manners of death in these cases . Caretakers are usually remarkably honest in showing the position of a child wedged between a bed and wall space , face down in multiple blankets , or in revealing co - sleeping ( see the following images ) . 8 ( See also Forensic Scene Investigation . ) Scene recreation demonstrating wedging . Scene recreation demonstrating positional asphyxia . In cases of autoerotic asphyxia , the victim is frequently in various stages of undress , surrounded by pornographic material and sexual aids . This setup can be embarrassing for the decedent ' s family or friends , and consequently , they may remove the ligatures / binding , move the body , or otherwise " clean up " the scene before notifying authorities . Establishing the manner of death relies on accurate documentation of scene findings . Notes suggesting intent ( " suicide notes " ) are useful but not necessarily definitive in establishing suicide , and they must be interpreted in the light of information generated by the history , examination , and / or scene findings . Excessive unpaid bills , overdrawn bank account statements , job firing notices , and eviction letters can be motivation for suicide and should be documented . Although most motor vehicle crash - related deaths are due to blunt trauma , asphyxia occasionally causes death in this setting . Vega and Adams and Conroy et al reviewed various types of asphyxia in motor vehicle crashes . 9 10 Often , the victim ' s body may be moved during the rescue efforts . It is imperative to determine the initial post crash position of the body and the location of the vehicle in relation to the body ( see the following image ) . Photograph from a scene showing the position of the decedent ( white cutout ) pinned underneath car . Similarly , successful evaluation of the scene in cases involving a vitiated atmosphere can be difficult due to rescue measures that can include forcing fresh air into the scene of death . Untoward effects experienced by initial rescuers who breathed the " original " air at the death scene can offer critical information about atmospheric conditions experienced by the victim . Historical information is extremely important in arriving at the correct understanding of a particular death , especially when multiple potential causes of death are present . For example , if a neck compression restraint hold caused death by asphyxia ( excluding the scenario of delayed airway occlusion due to neck structure injury ) , the victim should remain unconscious after the neck hold was released . A history of the victim verbalizing or carrying out volitional activity after the neck pressure was released is not consistent with death being due to the direct effect of the neck compression . Trace Evidence The forensic pathologist is trained to collect and preserve trace evidence . When a ligature is present , the ligature is removed with the knot intact . Even in cases in which ligatures have been removed , traces of foreign material may remain on the skin and can be collected for analysis ( see the following image ) . Ligature fibers may remain on the skin , which can then be collected for analysis . In homicidal cases of mechanical asphyxia , the assailant must be relatively close to the victim , and defensive maneuvers may result in transfer of evidence from the assailant to the victim and vice versa . Because mechanical asphyxia , especially strangulation or smothering , is a convenient way to kill in association with sexual activity ( usually , but not always , forced ) , evidence of sexual activity should be sought in an asphyxial death occurring in this scenario . The presence of bite mark evidence should be specifically sought in this type of case . Fingernail clippings / scrapings should be performed to preserve evidence for future analysis . Gross Features There are no pathognomonic signs of death by asphyxia . However , there are findings that are characteristically associated with the various forms of asphyxia . The nature and extent of these findings depend on the mechanisms ( s ) of asphyxia in the particular case , including features of the victim and , in some cases , the assailant . Even the presence of a ligature mark on the neck in a murder is not necessarily indicative of death by ligature strangulation , only that a ligature compressed the neck to some degree . Nevertheless , interpreting the constellation There are several common findings in asphyxial deaths , which may be present in multiplicity or not at all , such as the following : Congestion of the face ( plethora ) due to venous congestion and poor venous return to the heart ( see the image below ) Congestion of the face and cyanosis . Cyanosis due to excessively deoxygenated hemoglobin in the venous blood ( see the image above ) Facial edema due to increased venous pressure causing tissue fluid transudation ( see the image below ) Facial and upper neck edema . Petechiae in the eyelids , conjunctivae , sclerae , face , and gums due to raised pressure in the microvasculature . These are usually related to arterial blood flow persisting after venous flow is impeded . See the following images . Petechiae in the eyelids , sclerae , and face due to ruptures of the microvasculature . Gingival petechiae . Injury to skin and soft tissues of the central face , cheeks , lips , and / or neck . Internal neck structure damage due to applied force , particularly to the hyoid bone and laryngeal fractures ( see the image below ) Hyoid bone and laryngeal fractures due to manual strangulation . Airway obstruction by tissue ( most commonly the tongue ) , a gag , foreign material bolus , swollen tissue , or aspirated nonbolus material ( eg , blood , gastric material ) Note that none of the above findings is specific for asphyxia and can be present in other conditions . For example , patients with congestive heart failure may have a congested face with edema . Resuscitative efforts have been known to cause hemorrhage within the soft tissues of the neck . See the following image . Soft - tissue extravasation created during the autopsy dissection , which simulated hemorrhage . Special Dissections and Procedures Layer - by - layer dissection of the anterior neck tissues is typically performed after blood has been allowed to drain from the chest and head . This dissection technique allows demonstration of injuries to the neck soft tissues , hyoid bone , larynx , and blood vessels . See the image below . Layer - by - layer anterior neck dissection demonstrating injuries to the neck soft tissues , hyoid bone , and larynx . Radiographic findings in asphyxial deaths are typically limited to identifying fractures of the hyoid and larynx , cervical spine fractures in hangings ( occasionally seen in nonjudicial hanging scenarios involving victims who jump from high structures , especially if the victims are elderly or have preexisting cervical spine diseases [ eg , osteoporosis , ankylosing spondylitis , osteoarthritis ] ) , or identifying a foreign object in the airway . Microscopic Features Hypoxic / ischemic damage to tissues may be evident if the survival interval is prolonged . The presence / absence of an inflammatory infiltrate ( repair process ) associated with injuries may allow some assessment of when the injuries were sustained in relation to the time of death . Photography and Documentation Photography at the scene and in the morgue suite plays an important role in helping to determine and document the findings upon which the cause and manner of death opinions are based . In addition to routine identification and injury photographs , the forensic pathologist ' s report and / or file should include photographs and written description addressing the following : Presence / absence of injuries on the face , oral cavity , neck , chest , abdomen , and extremities ( eg , evidence of bondage or restraint ) All ligatures or bondage / binding devices before and after removal , if applicable Complete description of the ligature ( including composition , size ) Nature of the knot Hemorrhage ( including the extent and distribution ) Internal neck or chest injuries and status ( structural integrity and degree of pliability ) of the hyoid bone and larynx Material or object in the airway Documentation should address specific issues pertinent to the particular case details . Ancillary and Adjunctive Studies Comprehensive death investigation should include a thorough history , death scene investigation , and appropriate postmortem examination that includes toxicologic , other pertinent laboratory studies ( such as carboxyhemoglobin saturation in suspected carbon monoxide poisoning ) , and appropriate radiologic studies . Toxicologic findings are often key in helping to understand why someone died . If an individual is under the influence of either legal or illegal intoxicant ( s ) , it may enhance the likelihood of getting into a compromising situation or decrease the likelihood of extrication from a jeopardizing situation ( eg , inability to fight off an attacker in strangulation , escape from trapped position that compromises breathing / respiration , or making sound judgment decisions ) . See also the following : Postmortem Changes Postmortem Radiology and Imaging Postmortem Vitreous Analyses Forensic Toxicology - Drugs and Chemicals Forensic Pathology of Thermal Injuries Issues Arising in Court Several issues may arise during law enforcement investigation and / or adjudication of potential homicidal asphyxial deaths and are briefly discussed below . Handedness Determining handedness of the assailant can not be reliably established . Most adults can strangle with either the dominant or nondominant hand . Specifics of strangulation are also difficult to establish , as it can be accomplished using forehand or backhand , overhand or underhand , 1 or 2 hands . Absence / presence of neck markings Fingernail marks on the neck indicate injury to the neck caused by someone with nails sufficiently long to cause marks . The marks may be made by the assailant during strangulation or while attempting to control the victim . Occasionally , marks on the neck are made by the victim during attempts to alleviate pressure on his / her own neck ( eg , attempting to remove a ligature ) . Some ligature marks may have a sufficient pattern to allow recognition of the features of the ligature ( eg , woven cord ) . Determining the nature of a Some homicidal asphyxial deaths , including suffocation and strangulation , can occur in the absence of demonstrable injuries . The determination of cause and manner of death in such cases can be very problematic and may come down to considering and judging the reliability of witness accounts and / or observations and / or a perpetrator confession . Time to unconsciousness / death The time it takes to reach unconsciousness and the time it takes to die of asphyxia are influenced by the nature of the asphyxiant , duration of its application , efficiency of its application , and victim susceptibility . Experimental studies and witnessed ( sometimes videotaped ) events of neck compression ( hanging and strangulation ) indicate very rapid loss of consciousness after carotid artery compression . Studies of videotaped nonjudicial hangings have elucidated stereotypical behavior exhibited by the victim following the loss of consciousness . 12 13 The minimal duration of neck compression after loss of consciousness to cause death has not been clearly defined All the subjects studied by Rossen and Kabat who were subjected to 100 seconds of total carotid artery occlusion survived . 14 DiMaio and DiMaio cited information pertinent to the temporal sequence of events in infant smothering . 15 They indicated that during infant smothering there is bradycardia ( onset 30 sec after initiation of smothering ) ; decrease in breathing , agonal gasps , then apnea ; and , slowing and flattening of the electroencephalogram ( flattening at 90 seconds ) . DiMaio and DiMaio reported that the infant will not usually auto - resuscitate once there is apnea . Mechanical asphyxiation and deaths in custody The death of a suspect temporally related to apprehension by law enforcement can be consequent to a variety of potential causes and mechanisms . Occasionally , there may be an issue as to whether or not action by law enforcement personnel caused or contributed to death . Some of these actions potentially involve asphyxia . In some cases , the intention is to produce nonlethal mechanical asphyxia ( eg , application of neck restraint hold ) , whereas in others mechanical asphyxia is inadvertent ( eg , thoracoabdominal compression during a " dog pile " ) . In other cases , issues as to whether or not a particular restraint technique caused or contributed to asphyxia may need to be addressed . Examples of these issues include the effects of the restraint position ( eg , restrained in the prone position with or without hogtieing ) and the effect of chemical control agents ( eg Neck restraint holds Neck restraint holds , most typically involving carotid compression , have been used fairly commonly and represent a form of controlled strangulation . The hold is applied until unconsciousness ensues ; the subject is then immediately cuffed , and the hold released before the onset of any irreversible cerebral ischemic damage . Rarely , the delayed onset of asphyxia , sometimes lethal , may result from unrecognized laryngeal damage sustained during an episode of neck compression . Prone restraint positions For a period of time , restraint position was often implicated as being causal or contributory to death . This most often involved persons who had been hogtied and left in the prone position . Implication of the prone hogtied position was primarily based on studies in which recovery of oxygen saturation ( as measured by a transcutaneous earlobe blood oxygen saturation probe ) following exercise took longer in hogtied volunteers than in those who were not hogtied . 16 However , subsequent studies using more accurate measuring techniques ( arterial blood gas measurements ) failed to confirm the previous studies . 17 Currently , the prone restraint position ( with or without hogtie ) is generally considered a neutral position . Thoracoabdominal compression Inadvertent development of asphyxia consequent to thoracoabdominal compression sustained during apprehension may be an issue . Pressure can be applied to the chest , most commonly to the back , to facilitate the application of manacles . In many cases , the pressure is applied to the shoulders and lower back , buttock , or upper thighs using less than the full body weight of the restraining personnel . In other cases , multiple persons attempting to gain control of an unruly suspect can apply less targeted and less controlled pressure . Although it is clear that thoracoabdominal compression can cause death if it is heavy enough and prolonged enough , the quantity and duration of thoracoabdominal pressure necessary to cause or contribute to death is less clear . No significant differences in oxygen saturation or end tidal carbon dioxide were demonstrated in human volunteers between sitting , maximal restraint position or maximal restraint with up to 50 pounds ( lb ) of weight on the back . 18 Other studies indicate that 225 lb of pressure uniformly distributed over the back reduces the minute ventilation volume ( MVV ) to about 60 % of predicted . 19 Thus , the targeted , relatively brief application of pressure to the back during cuffing ( eg , knee on the back with less than full body weight applied ) is not likely to cause significant , if any , asphyxia . However , the authors are of the opinion that the prolonged continuous application ( probably measured in minutes ) of extreme pressure on the chest ( such as the nearly full body weight of several officers ) is capable of causing death . Summary To appropriately address these issues , as in any death investigation , detailed descriptions of the decedent and others involved in the incident are essential . A second - by - second account of the incident including the locations , actions , and effects of the actions of each of the participants is critical to properly evaluating the incident . Evidence of consciousness and volitional activity of the decedent following the release of any restraint hold or removal of weight from the chest is important to ascertain . Excluding delayed asphyxia caused by a structural internal injury ( eg , Additional Resources The reader is directed to the following sources for more information : Prahlow JA , ed . Basic Competencies in Forensic Pathology : A Forensic Pathology Primer . Northfield , Ill : College of American Pathologists ; 2006 . Dolinak D , Matshes EW , Lew EO . Forensic Pathology : Principles and Practice . Amsterdam , The Netherlands : Academic Press ; 2005 . DiMaio VJ , DiMaio D . Forensic Pathology . 2 nd ed . Boca Raton , Fla : CRC Press ; 2001 : 234 . Froede RC , ed . Handbook of Forensic Pathology . 2 nd ed . Boca Raton , Fla : CRC Press ; 2003 . Graham MA , Hanzlick , R . Forensic Pathology in Criminal Cases . 2 ed . Carlsbad , Calif : Lexis Law Publishing ; 1997 Spitz WU , Spitz DJ , Fisher RS , eds . Spitz and Fisher ' s Medicolegal Investigation of Death : Guidelines for the Application of Pathology to Crime Investigation . 4 th ed . Springfield , Ill : Charles C . Thomas ; 2006 . Sections Pathology of Asphyxial Death Show All Media Gallery Tables References
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Hematology Platelet Disorders Overview of Platelet Disorders Updated : Aug 05 , 2017 Author : Perumal Thiagarajan , MD ; Chief Editor : Srikanth Nagalla , MBBS , MS , FACP more . . . Sections Overview of Platelet Disorders Pathophysiology of Platelet Disorders Autoimmune Thrombocytopenias Disorders of Platelet Function Disorders of Secretion and Thromboxane Synthesis Platelet Dysfunction in Uremia Epidemiology of Platelet Disorders Clinical Presentation of Platelet Disorders Etiology of Platelet Disorders Laboratory Studies Imaging Studies Bone Marrow Examination Treatment of Acute ITP in Children Treatment of Chronic ITP in Adults Treatment of Thrombotic Thrombocytopenic Purpura Questions & Answers Show All Media Gallery References Overview of Platelet Disorders The hemostatic system consists of platelets , coagulation factors , and the endothelial cells lining the blood vessels . The platelets arise from the fragmentation of the cytoplasm of megakaryocytes in the bone marrow and circulate in blood as disc - shaped anucleate particles for 7 - 10 days . Under normal circumstances , the resistance of the endothelial cell lining to interactions with platelets and coagulation factors prevents thrombosis . When endothelial continuity is disrupted and the underlying matrix is exposed , a coordinated series of events are set in motion to seal the defect ( primary hemostasis ) . Platelets play a primary role in this process , interacting with subendothelium - bound von Willebrand factor ( vWf ) via the membrane glycoprotein ( GP ) Ib complex . This initial interaction ( platelet adhesion ) sets the stage for other adhesive reactions that allow the platelets to interact with each other to form an aggregate ( see image below ) . Normal hemostasis . View Media Gallery The platelet GP IIb / IIIa complex mediates platelet - to - platelet interactions ( platelet aggregation ) . On resting platelets , GP IIb / IIIa is unable to bind fibrinogen or vWf . Platelet activation allows binding of these proteins , which bridges adjacent platelets . Morphologically , the platelets change dramatically from discs to spiny spheres in a process called shape change . Platelets contain two unique types of granules : alpha granules and dense granules . The alpha granules contain hemostatic proteins such as fibrinogen , vWf , and growth factors ( eg , platelet - derived growth factor ) . The dense granules contain proaggregatory factors such as adenosine 5 ' - diphosphate ( ADP ) , calcium , and 5 - hydroxytryptamine ( serotonin ) . During activation , the granules are centralized and their contents are discharged into the lumen of the open canalicular system , from which they are then released to the exterior ( the release reaction Once activated , platelets have two major mechanisms to recruit additional platelets to the growing hemostatic plug . They release proaggregatory materials ( eg , ADP ) by the release reaction , and they synthesize thromboxane A 2 from arachidonic acid . Thus , the release reaction and prostaglandin synthesis act to consolidate the initial hemostatic plug by promoting the participation of other platelets in the growing hemostatic plug . In addition , when platelets are activated , negatively charged phospholipids move from the inner to the outer leaflet of the membrane bilayer . This negative surface provides binding sites for enzymes and cofactors of the coagulation system , resulting in the formation of a clot ( secondary hemostasis ) . Pathophysiology of Platelet Disorders Platelet disorders lead to defects in primary hemostasis and produce signs and symptoms different from coagulation factor deficiencies ( disorders of secondary hemostasis ) . The body ' s reaction to vessel wall injury is rapid adhesion of platelets to the subendothelium . The initial hemostatic plug , composed primarily of platelets , is stabilized further by a fibrin mesh generated in secondary hemostasis . The arrest of bleeding in a superficial wound , such as the bleeding time wound , almost exclusively results from the primary hemostatic plug . Hence , primary hemostatic disorders are characterized by prolonged bleeding time , and the characteristic physical examination findings are petechiae and purpura . In comparison , defects in secondary hemostasis result in delayed deep bleeding ( eg , into muscles and joints ) and the characteristic physical examination finding is hemarthrosis . Hemarthrosis and muscle hematomas are not present in primary hemostatic disorders . Autoimmune Thrombocytopenias Immune thrombocytopenic purpura Immune thrombocytopenia ITP ) is one of the most common autoimmune disorders . ITP is caused by autoantibodies to platelets . The antigenic target in most patients appears to be the platelet GP IIb / IIIa complex . Platelets with antibodies on their surface are trapped in the spleen , where they are efficiently removed by splenic macrophages . The mechanism of origin of these antibodies is not known . These antibodies may be directed toward viral antigens and then cross - react with platelet antigens . They persist because of the failure of immune surveillance mechanisms to repress these antibodies . These antibodies can also react with the developing megakaryocytes in the bone marrow , leading to decreased production of platelets ( ineffective thrombopoiesis ) . The success of thrombopoietin agonist therapy in chronic ITP underscores this mechanism as a major factor in inducing thrombocytopenia . ITP occurs commonly in otherwise healthy individuals and only rarely as the initial manifestation of lupus and other autoimmune disorders . Human immunodeficiency virus HIV ) infection is often associated with ITP in both adults and children . ITP occurs in two distinct clinical types : ( 1 ) an acute self - limiting form observed almost exclusively in children ( five cases per 100,000 persons ) and ( 2 ) a chronic form , observed mostly in adults ( three to five cases per 100,000 persons ) and rarely in children . 1 2 3 4 Acute ITP Acute ITP affects males and females equally and has a peak incidence in children aged 3 - 5 years . Most patients have a history of an antecedent acute viral syndrome . The onset is sudden , with symptoms and signs depending on the platelet count . Bleeding is usually mild , unless the platelet count drops below 20,000 / µL . With platelet counts from 20,000 / µL to 50,000 / µL , petechiae and ecchymoses are observed following mild trauma . With platelet counts less than 10,000 / µL , generalized petechiae , ecchymoses , and mucosal bleeding occur . With platelet counts below 2000 / µL , widespread ecchymoses , hemorrhagic bullae , and retinal hemorrhage occur . Physical examination reveals only the presence of petechiae and ecchymoses . The presence of lymphadenopathy or splenomegaly suggests other secondary causes of thrombocytopenia rather than ITP . The peripheral smear shows a decreased number of platelets . Often , the smear shows giant platelets , which is a reflection of increased thrombopoietin - induced stimulation of the bone marrow ( see images below ) . Examination of the peripheral smears in immune thrombocytopenic purpura often shows giant platelets . These platelets reflect the increased megakaryocytic mass in the marrow . View Media Gallery Peripheral smear of a patient with Bernard - Soulier syndrome showing giant platelets . These platelets are not counted as platelets in most particle counters . At times , the smear may show eosinophilia and lymphocytosis , possibly reflecting hypersensitivity to the inciting viral antigens . The bone marrow shows an increase in the number of megakaryocytes and signs of thrombopoietin - induced megakaryocyte stimulation ( increase in number and ploidy , decrease in cytoplasm ) , resulting in large platelets in the periphery ( see image below ) . Bone marrow in immune thrombocytopenic purpura . Bone marrow examination reveals an increased number of megakaryocytes . Thrombocytopenia in an otherwise healthy child with normal white and red blood cell counts almost always results from ITP . Findings from a careful history and physical examination help exclude other causes of thrombocytopenia , such as lupus and HIV infection . Acute leukemia is unlikely to manifest as an isolated thrombocytopenia without any abnormalities in the smear . Bone marrow examination is necessary only if atypical features ( ie , other abnormalities in the smear , sternal tenderness , lymphadenopathy , splenomegaly ) or an unusual clinical course is evident . Chronic ITP This condition is typically observed in adults aged 20 - 40 years . It has an insidious onset , and a history of an antecedent infection need not be present . Unlike childhood ITP , chronic ITP is more common in females than in males . As in childhood ITP , the bleeding manifestations depend on the platelet count . 5 6 7 The diagnosis of ITP is established by the exclusion of other causes of thrombocythemia . The peripheral blood film should be examined to rule out thrombotic thrombocytopenic purpura TTP ) ( fragments ) or spurious thrombocytopenia resulting from clumping ( see image below ) . Spurious thrombocytopenia . Peripheral smear of a patient reported to have platelet counts of 10,000 - 150,000 / μL on various occasions . The smear shows clumping of the platelets and satellitism involving neutrophils and platelets . Often , the smear shows giant platelets , which is a reflection of the increased thrombopoietin - induced stimulation of bone marrow . Bone marrow examination , which is not always necessary , shows increased megakaryocytes . Gestational thrombocytopenia This form of thrombocytopenia is defined as mild thrombocytopenia in an otherwise healthy pregnancy . How this can be distinguished from a mild form of ITP is not clear . This disorder does not result in neonatal thrombocytopenia . Hypertensive disorders of pregnancy These disorders of pregnancy ( ie , preeclampsia eclampsia syndrome ) are associated with increased platelet turnover , even when the platelet count is normal . Controlling hypertension and delivering the fetus lead to restoration of the platelet count . Occasionally , thrombocytopenia is associated with hemolysis and elevated liver enzymes ( ie , hemolysis , elevated liver enzymes , and low platelet [ HELLP ] syndrome ) . This serious disorder often mimics TTP . Posttransfusion purpura Platelet GP IIb / IIIa is a major antigen in platelets and is polymorphic . Most individuals have leucine at position 33 ( PLA 1 / PLA or human platelet alloantigen [ HPA ] – 1a ) . A small number of individuals , approximately 1 - 3 % of random populations , have proline at position 33 . Homozygotes with proline are termed PLA1 - negative ( or HPA - 1b , PLA / PLA ) . When PLA1 - negative patients receive blood products from HPA - 1a – positive individuals , they produce an antibody reactive against HPA - 1a . This alloantibody destroys the transfused platelets and the patient ' s own platelets , leading to a severe form of thrombocytopenia that lasts for several weeks and , sometimes , several months . Posttransfusion purpura typically occurs 10 days following a transfusion . This syndrome can be induced by a small amount of platelets contaminating a red blood cell transfusion or , occasionally , following fresh frozen plasma ( FFP ) transfusion . The thrombocytopenia responds to intravenous immunoglobulin ( IVIG ) . Other platelet alloantigens are occasionally implicated in posttransfusion purpura . A population - based study of inpatients aged 65 years and older found that posttransfusion purpura occurred at an overall rate of 1.8 per 100,000 hospital stays . Risk of posttransfusion purpura were significantly higher with platelet - containing transfusions , greater number of units transfused , and underlying health conditions including a history of cardiac arrhythmias , coagulopathy , leukemia , and transplantation . 8 Neonatal alloimmune thrombocytopenia The prevalence of neonatal alloimmune thrombocytopenia is approximately one case in 200 term pregnancies ; for clinically apparent disease , the prevalence is one case in 1500 term pregnancies . It is the most common cause of severe neonatal thrombocytopenia . 9 This disorder occurs when maternal antibodies against fetal platelet antigens inherited from the father but absent in the mother cross the placenta and induce severe thrombocytopenia . Most cases of neonatal alloimmune thrombocytopenia are due to platelet antigens HPA - 1a observed in mothers who are HPA - 1b . Less commonly , other platelet antigens , such as HPA - 5b , are responsible for neonatal alloimmune thrombocytopenia . Thus , the pathophysiology of this disease is similar to that of the hemolytic disease of newborns . Unlike hemolytic disease , however , thrombocytopenia occurs during the first pregnancy in 50 % of cases . Typically , the diagnosis of neonatal alloimmune thrombocytopenia is considered when bleeding or severe thrombocytopenia occurs in a baby after an otherwise uncomplicated pregnancy . The affected infant may have intracranial hemorrhage , and the disorder is associated with a relatively high mortality rate . The platelet count should be checked immediately after delivery and 24 hours later as it continues to fall . Drug - induced thrombocytopenia Drugs can induce thrombocytopenia by a number of mechanisms . 10 For example , the cytotoxic drugs can inhibit platelet production in the bone marrow , as can thiazide diuretics , interferon , and alcohol . More commonly , drug - induced thrombocytopenia results from the immunologic destruction of platelets . Drugs can induce antibodies to platelets , either acting as a hapten or as an innocent bystander . In addition , drugs such as gold salts and interferon can induce an ITP - like disorder . Common drugs associated with thrombocytopenia include the following : Amiodarone Captopril Sulfonamides Glyburide ( glibenclamide ) Carbamazepine Ibuprofen Cimetidine Tamoxifen Ranitidine Phenytoin Vancomycin Piperacillin The diagnosis of drug - induced thrombocytopenia is often empirical . A temporal relationship must be present between the initiation of the drug and the development of thrombocytopenia , with no other explanations for the thrombocytopenia . Recurrent thrombocytopenia following reexposure to the drug confirms the drug as the cause of thrombocytopenia . Identifying the drug that is causing severe thrombocytopenia in an acutely ill patient who is taking multiple drugs is often challenging . A complete list of all available reports of drug - induced thrombocytopenia is available at Platelets on the Web Heparin causes a unique situation among drug - induced thrombocytopenias in that the antibodies also activate platelets and induce a hypercoagulable state . 11 See Heparin - Induced Thrombocytopenia . Thrombotic thrombocytopenic purpura TTP is a rare but serious disorder that was initially described as having a pentad of manifestations , as follows : Thrombocytopenia ( with purpura ) Red blood cell fragmentation Renal failure Neurologic dysfunction Fever Evidence indicates that TTP results from the abnormal presence of unusually large multimers of von Willebrand protein . 12 These ultralarge precursors , normally synthesized in the endothelial cells , are hyperactive towards platelets . These large multimers are processed by a plasma enzyme to normal - sized multimers . This enzyme is identified as ADAMTS13 , a metalloproteinase synthesized in the liver . 12 The sporadic forms of TTP are caused by an antibody or toxin inhibiting the activity of ADAMTS13 . The chronic , recurrent form of TTP may result from a congenital deficiency of the enzyme . The ultralarge multimers are thought to induce the aggregation of platelets , causing platelet consumption . Occlusion of microvasculature by the platelets in the brain , kidney , and other organs leads to myriad symptoms . A TTP - like syndrome has been associated with lupus , pregnancy , HIV infection , and certain drugs ( eg , quinine , ticlopidine , clopidogrel , cyclosporine , chemotherapeutic agents ) . Patients with TTP often report an episode of flulike illness 2 - 3 weeks before presentation . Most patients with TTP do not have the classic pentad . The most common presentation is petechiae and neurologic symptoms . The neurologic symptoms can range from headache and confusion to seizures and coma . Fever is present in slightly more than 50 % of the patients . For more information , see the Thrombotic Thrombocytopenic Purpura Hemolytic - uremic syndrome Patients with hemolytic - uremic syndrome HUS ) have vascular lesions indistinguishable from those observed in patients with TTP , but the renal vasculature endures the most lesions , with minimal neurologic dysfunction . HUS is a catastrophic illness that predominantly affects children aged 4 - 12 months , sometimes affects older children , and rarely affects adults . HUS follows an upper respiratory tract infection . In the tropics , epidemics of HUS are frequent and resemble an infectious disease ; however , no causative organism has been identified . In North America , Shigella - like toxins ( secreted by Escherichia coli serotype 0157 : H7 or Shigella dysenteriae serotype I ) cause many cases of HUS . Diarrhea and abdominal cramps are very prominent symptoms . Disorders of Platelet Function Functional disorders of platelets are relatively rare , and most of these disorders are mild . Thus , they may not be recognized early in life . 13 von Willebrand disease von Willebrand disease vWD ) is the most common inherited bleeding disorder . It is autosomal dominant , and its prevalence is estimated to be as high as one case per 1000 population . The hallmark of von Willebrand disease is defective platelet adhesion to subendothelial components caused by a deficiency of the plasma protein vWf . This factor is a large , multimeric glycoprotein that is synthesized , processed , and stored in the Weibel - Palade bodies of the endothelial cells , and secreted constitutively and following stimulation . vWf has a major role in primary hemostasis as mediator of the initial shear - stress – induced interaction of the platelet to the subendothelium via the GP Ib complex . In addition , von Willebrand protein acts as a carrier and stabilizer of coagulation factor VIII by forming a complex in the circulation . In the absence of vWf , the factor VIII activity level is low . Unlike classic hemophilia A , in which the factor VIII activity level is low because of a defect in factor VIII itself , in von Willebrand disease the factor VIII activity level is low because of a deficiency in its carrier protein . von Willebrand disease is a relatively mild bleeding disorder , except in the occasional patient who is homozygous for the defect and who has severe bleeding often indistinguishable from classic hemophilia . The bleeding manifestations are predominantly skin - related and mucocutaneous ( ie , easy bruising , epistaxis , GI hemorrhage ) . Most bleeding episodes occur following trauma or surgery . In women , menorrhagia is common , often exacerbated by the concurrent administration of nonsteroidal anti - inflammatory drugs . Pregnant patients with this disease usually do not have problems . However , vWF and factor VIII activity fall after childbirth . In a prospective observational cohort study of 32 women with von Willebrand disease and 40 women without von Willebrand disease , vWF levels peaked at 250 % of baseline at 4 hours postpartum in the von Willebrand disease group and at 12 hours postpartum in the women without von Willebrand disease and then decreased rapidly , reaching baseline at 3 weeks in both groups . Fifteen of the women with von Willebrand disease received treatment with desmopressin or vWF concentrate before or after delivery . Except immediately postpartum , treatment did not raise vWF and factor VIII levels to normal or to the levels seen in women with milder , untreated von Willebrand disease . These researchers concluded that even with treatment , women with vWD may be at increased risk for postpartum hemorrhage . 14 Bleeding time is prolonged in persons with von Willebrand disease . Because the von Willebrand protein is phase - reactant ( ie , increased synthesis in the presence of inflammation , infection , tissue injury , and pregnancy ) , a mild prolonged bleeding time may be normalized , resulting in difficulty in diagnosis . In addition to the prolonged bleeding time , characteristic abnormalities in platelet aggregation tests occur . In patients with von Willebrand disease , platelets aggregate normally to all agonists except the antibiotic ristocetin , which induces binding of the von Willebrand protein to platelets , similar to what happens with platelets following vessel wall injury in vivo . Ristocetin - induced platelet aggregation correlates with the platelet - aggregating activity of the von Willebrand protein . The levels of coagulation factor VIII are also low , due to the decrease in vWf , the carrier of factor VIII in plasma Variants of von Willebrand disease Although the common form of von Willebrand disease ( type I ) results from a quantitative deficiency of vWf , the variants result from qualitative abnormalities in the von Willebrand protein . A common variant ( type IIA ) of von Willebrand disease results from functionally defective vWf that is unable to form multimers or be more susceptible to cleavage by ADAMTS13 . Larger multimers are more active in mediating platelet vessel - wall interaction . In these variants , the factor VIII level may be normal . In the type IIB variant , the von Willebrand protein has heightened interaction with platelets , even in the absence of stimulation . Platelets internalize these multimers , leading to a deficiency of von Willebrand protein in the plasma . The type IIN ( Normandy variant ) is caused by defect in vWf to bind coagulation factor VIII , resulting in the shortened half - life of factor VIII in the plasma . The ristocetin - induced platelet aggregation and vWf antigens are normal . Previous descriptions of autosomal recessive hemophilia A are most likely von Willebrand disease type IIN . Type IIM von Willebrand disease is due to a defect in binding to platelet glycoprotein Ib but no defect in multimerization . In this variant , the ristocetin cofactor activity and ristocetin - induced platelet aggregation are decreased but the vWf antigen and multimers are present in normal levels . A disorder of platelet GP Ib , mimicking type IIB von Willebrand diseas , has also been described . In this condition , increased affinity for von Willebrand protein in the resting stage leads to the deletion of plasma von Willebrand protein . This disease is called pseudo von Willebrand disease or platelet - type von Willebrand disease . Type III von Willebrand disease is a severe form that is characterized by very low levels of vWf and clinical features similar to hemophilia A , but with autosomal recessive inheritance . This condition results from a homozygous state or double heterozygosity . Bernard - Soulier syndrome Bernard - Soulier syndrome results from a deficiency of platelet glycoprotein protein Ib , which mediates the initial interaction of platelets with the subendothelial components via the von Willebrand protein . It is a rare but severe bleeding disorder . Platelets do not aggregate to ristocetin . The platelet count is low , but , characteristically , the platelets are large , often the size of red blood cells , and may be missed on complete blood counts because most automatic counters do not count them as platelets . 15 Glanzmann thrombasthenia Glanzmann thrombasthenia results from a deficiency of the GP IIb / IIIa complex . Platelets do not aggregate to any agents except ristocetin . The more severe type I results from a complete absence of the GP IIb / IIIa complex , whereas in the milder type II , some of the GP IIb / IIIa complex is retained . Both Bernard - Soulier syndrome and Glanzmann thrombasthenia are characterized by lifelong bleeding . Although platelet transfusions are effective , they should be used only for severe bleeding and emergencies , because alloantibodies often develop in these patients . Disorders of Secretion and Thromboxane Synthesis During primary hemostasis , thromboxane synthesis and released ADP play a major role . A mild bleeding diathesis ensues if these mechanisms are deficient . Thromboxane synthesis disorders are almost always caused by aspirin and nonsteroidal anti - inflammatory drugs ( NSAIDs ) . Because aspirin irreversibly inactivates cyclooxygenase in platelets , its effect lasts throughout the life span of platelets , which is approximately 1 week . Approximately 10 % of new nonaspirinized platelets are produced daily ; after 3 days have elapsed since the discontinuation of aspirin ( 30 % nonaspirinized platelets available ) , the bleeding time normalizes . Other NSAIDs are competitive inhibitors of cyclooxygenase , and their effect on platelets depends on the half - life of the drug . For example , the effect of ibuprofen , and most other NSAIDs , lasts only 1 day . Mutations in the enzyme that converts arachidonic acid to thromboxane A have been described and are associated with a lifelong bleeding diathesis . Similarly , an absent or defective receptor for thromboxane A also leads to an aspirinlike aggregation defect . In disorders of release reaction , platelets fail to secrete proaggregatory ADP following activation . The defects result from either the absence of granules in platelets or the defective storage of ADP . Inherited deficiency of ADP receptor P2Y12 , characterized by mild bleeding diathesis , has also been described . ADP is present in the dense granules of platelets as a storage pool , which is not used in the normal metabolic activity of platelets ( in contrast to the metabolic pool ) . These disorders are often associated with other systemic abnormalities ( eg , Hermansky - Pudlak syndrome ) . Disorders of secretion and thromboxane synthesis are mild platelet disorders and often respond to desmopressin ( DDAVP ) infusion , which seems to improve hemostatic function . If severe bleeding is present , these disorders can also be managed effectively with platelet transfusions . Platelet transfusions , however , should be avoided as much as possible because they can induce alloantibodies . Cryoprecipitate has also been reported to be very effective . Platelet Dysfunction in Uremia Abnormal bleeding is common in patients with uremia . Bleeding time is generally very prolonged . The bleeding has the characteristics of a platelet disorder , and GI tract bleeding is the most frequent manifestation . Platelet function in uremic patients improves after dialysis . A number of dialyzable factors have been shown to inhibit platelet function . Furthermore , uremic platelets synthesize less thromboxane A , and the blood vessels in patients with uremia produce greater quantities of platelet - inhibitory prostaglandin . Nitric oxide produced by the endothelial cells inhibits platelet function . Because the prolonged bleeding time and the hemostatic abnormalities are partly corrected by red blood cell transfusion or erythropoietin therapy , the failure of hemoglobin to quench excess nitric oxide synthesis has been suggested as partly responsible for the platelet dysfunction . Epidemiology of Platelet Disorders Inherited hemostatic disorders are relatively rare . The prevalence of von Willebrand disease has been estimated at 1 case per 1000 - 5000 population . In contrast , acquired hemostatic disorders are common , and ITP is one of the most common autoimmune disorders . The acute self - limiting form of ITP , which is observed almost exclusively in children , occurs at a rate of 5 cases per 100,000 population , and the chronic form , which is observed mostly in adults occurs at a rate of 3 - 5 cases per 100,000 population . Unlike hemophilia , most inherited disorders of platelets are not X - linked , and they are equally distributed in both sexes . Acute ITP is also observed equally in both sexes . Chronic autoimmune thrombocytopenia is more common in females than in males . Clinical Presentation of Platelet Disorders Patient history History and physical examination findings help clinicians to distinguish between primary and secondary hemostatic disorders and to determine whether the disorder is inherited or acquired . Epistaxis is common in individuals with primary hemostatic disorders , but it is also common in healthy individuals . Details about the frequency , duration , packing requirement , and previous treatment ( cautery or transfusion ) are helpful for assessing the severity of bleeding ( see also the Medscape Reference articles Anterior Epistaxis Nasal Pack and Posterior Epistaxis Nasal Pack ) . Bleeding gums is a common symptom in persons with primary disorders of hemostasis . The bleeding could be spontaneous or it could be associated with brushing or flossing . Bleeding from tooth extractions is possible . A molar tooth extraction is a traumatic procedure . Uneventful extraction of a molar is unlikely in a patient with a severe bleeding disorder . Hemoptysis , hematemesis , hematuria , hematochezia , and melena are rarely the initial symptoms of a bleeding disorder . However , these may be exacerbated by an underlying bleeding disorder . Menstrual history is important . Metromenorrhagia is often observed in women with primary hemostatic disorders . This is especially common in those with von Willebrand disease and is often exacerbated by the NSAIDs used to treat dysmenorrhea . Bleeding after childbirth may be the first manifestation of a mild bleeding disorder . Bleeding in the joints is the hallmark of hemophilia and other secondary hemostatic disorders . Details of previous surgeries , including the amount of blood transfused , if any , are helpful . In males , excessive bleeding following circumcision is often the initial manifestation of a congenital bleeding disorder . Delayed bleeding from the umbilical stump is characteristic of a factor XIII deficiency . Defective wound healing is observed in individuals with a factor XIII deficiency and abnormal fibrinogens . Medication history findings may be helpful because aspirin often accentuates a preexisting bleeding disorder . A history of previous iron therapy for anemia may be useful . Physical examination Bruising is common in individuals with a platelet disorder . A careful physical examination often reveals signs of a hemostatic disorder ( see image below ) . Purpuric spots . Petechiae are pinpoint hemorrhages ( < 2 mm ) in the skin , and purpura ( 0.2 - 1 cm ) and ecchymoses are larger hemorrhages . The purpura is not palpable , in contrast to the palpable and sometimes tender purpura observed in patients with vasculitis ( see image below ) . Vasculitis in childhood . Initially , purpura tends to form in the areas of increased venous pressure , such as the legs . Petechiae and purpura may develop following the application of a sphygmomanometer cuff . Splenomegaly is not observed in the typical patient with ITP . The spleen can engulf platelets and be several times normal size without becoming palpably enlarged . Hemarthrosis and deep muscle hematomas are unusual in patients with primary hemostatic disorders . Etiology of Platelet Disorders Platelet disorders can involve either a decreased number of platelets ( thrombocytopenia ) or defective platelet function . Functional disorders of platelets can be inherited ( rare ) or acquired ( common ) . Platelet aggregation tests are useful in differentiating various disorders of platelet function . In all cases of thrombocytopenia , the peripheral blood smear must be reviewed to confirm the thrombocytopenia . This review is crucial . Spurious thrombocytopenia can occur due to aggregates forming in the specimen . In addition , dilutional thrombocytopenia may occur in situations of fluid replacement or blood component replacement without platelet support . Thrombocytopenia can be further divided into increased destruction or decreased production . Thrombocytopenia resulting from increased destruction occurs either by an immune mechanism or increased consumption . Platelets are consumed intravascularly by the activation of the coagulation process ( diffuse / disseminated intravascular coagulation DIC ] ) or by deposition on damaged endothelial cells ( microangiopathy ) . Production defects result from those diseases that cause bone marrow failure , such as aplastic anemia , infiltration by leukemia or another malignancy , fibrosis or granulomatous disorders , or tuberculosis . Causes of thrombocytopenia related to increased destruction include ( 1 ) immune thrombocytopenias ( eg , autoimmune , alloimmune , drug - induced ) and ( 2 ) increased consumption ( eg , DIC , TTP ) . Causes of thrombocytopenia related to decreased production include bone marrow depression and inherited disorders . Genetic defects have been defined for 30 forms of inherited thrombocytopenia , but the underlying genetic or molecular mechanisms remain unidentified for nearly 50 % of cases . 16 Disorders of platelet function are as follows : Disorders of platelet adhesion ( von Willebrand disease , Bernard - Soulier syndrome ) Disorders of aggregation ( Glanzmann thrombasthenia ) Disorders of secretion Disorders of thromboxane synthesis Acquired disorders of platelet function ( drugs [ eg , aspirin , NSAIDs , alcohol ] ) Uremia Paraproteins Fibrin degradation products Myelodysplasia or a myeloproliferative syndrome Laboratory Studies A variety of studies are available for the assessment of patients with possible platelet disorders . A complete blood count and peripheral blood smear are the key laboratory components of the diagnosis of immune thrombocytopenic purpura ( ITP ) and thrombotic thrombocytopenic purpura ( TTP ) . In pediatric patients , immunoglobulin assays are often performed to exclude common variable immune deficiency ( CVID ) as a cause of ITP . Peripheral smear Careful examination of the peripheral smear is essential in a patient with thrombocytopenia . Spurious thrombocytopenia due to platelet clumping or platelets adhering to neutrophils ( platelet satellitism ) can be seen on a smear ( see image below ) . Spurious thrombocytopenia . Peripheral smear of a patient reported to have platelet counts of 10,000 - 150,000 / μL on various occasions . The smear shows clumping of the platelets and satellitism involving neutrophils and platelets . Giant platelets are often seen in patients with ITP ( see image below ) . Examination of the peripheral smears in immune thrombocytopenic purpura often shows giant platelets . These platelets reflect the increased megakaryocytic mass in the marrow . Rare disorders , such as Bernard - Soulier syndrome , can be diagnosed based on the results from the peripheral smear ( see image below ) . Careful examination of the smear is essential to exclude TTP and rare instances of acute leukemia presenting as thrombocytopenia . Peripheral smear of a patient with Bernard - Soulier syndrome showing giant platelets . These platelets are not counted as platelets in most particle counters . In TTP , a striking degree of red blood cell fragmentation is seen in addition to thrombocytopenia ( see image below ) . Examination of the peripheral smear shows red blood cell fragments , basophilic cells , in addition to thrombocytopenia in thrombotic thrombocytopenic purpura . The minimum criteria for the diagnosis of TTP are thrombocytopenia and microangiopathic hemolytic anemia without an apparent etiology . Examination of the smear shows thrombocytopenia and a microangiopathic picture ( characteristic helmet cells / schistocytes and basophilic red blood cells ) ( see image below ) . In addition , the lactic dehydrogenase ( LDH ) level is high , with brisk reticulocytosis . Signs of intravascular coagulation are characteristically absent in patients with TTP . Schistocytes ( thrombotic thrombocytopenic purpura ) . Platelet - associated immunoglobulin G The autoantibodies responsible for autoimmune thrombocytopenia do not induce complement - mediated lysis . Furthermore , when platelets are destroyed in the circulation , they internalize plasma proteins , including immunoglobulin . Platelets also have low affinity to the crystallizable fragment ( Fc ) receptor , FcgRIIa , that binds immunoglobulin . In patients with autoimmune thrombocytopenia , the larger platelets have proportionately more membrane surface and more Fc receptor than normal platelets . For these reasons , the detection of increased platelet - associated immunoglobulin is not useful because it is elevated in almost all conditions associated with thrombocytopenia , which limits the value of this test in the diagnosis of ITP . Specialized tests to identify antibodies that react specifically against platelet membrane glycoproteins are not clinically available . Test of primary hemostasis bleeding time This is a valuable test for disorders of primary hemostasis ; however , this test is highly operator - dependent and is not recommended as a routine screening test . Primary hemostasis bleeding time is performed by measuring the duration required for bleeding to stop from a fresh superficial cut ( 1 mm deep , 1 cm long ) made on the volar surface of the forearm using a template under standard conditions . Under these conditions , the cessation of bleeding results from the formation of a primary hemostatic plug . A fairly linear correlation exists between bleeding time and platelet counts of 10,000 - 100,000 / µL . Bleeding time is prolonged with platelet counts below 75,000 / µL , although that finding provides no insight into reason the count is low . Primary hemostasis bleeding time should not be performed on patients with thrombocytopenia . A prolonged bleeding time with a normal platelet count is very significant and indicates a qualitative platelet disorder . In disorders of secondary hemostasis ( eg , hemophilia A and B ) , bleeding time is almost invariably normal . In vitro platelet function analyzer 100 The platelet function analyzer 100 ( PFA - 100 ) is a bench - top automated instrument that assesses primary hemostasis under shear stress . The PFA - 100 uses a disposable test cartridge that contains a membrane impregnated with collagen plus ADP ( Col / ADP membrane ) or epinephrine ( Col / Epi membrane ) . A blood sample of 0.8 mL of citrated blood is placed in a cup and is aspirated through the aperture . The shear stress and the agonists in the membrane activate platelets , leading to platelet aggregation . The end point , expressed as closure time , is when blood flow stops because of occlusion of the aperture by platelet aggregates . The platelet aggregate formation depends on ( 1 ) vWf binding to collagen - coated nitrocellulose membranes , ( 2 ) platelet adhesion to vWf via platelet GP Ib platelet activation , and ( 3 ) platelet aggregation mediated by the interaction of GP IIb / IIIa with vWf and fibrinogen . Normal closure times range from 77 to 133 seconds for the Col / ADP membrane and 98 - 185 seconds for the Col / Epi membrane . The PFA - 100 has been tested in persons with bleeding disorders . The closure time using the Col / Epi cartridge is abnormal in patients with congenital platelet function defects , von Willebrand disease , or aspirin ingestion , whereas the closure time with the Col / ADP cartridge is abnormal mainly in patients with von Willebrand disease or congenital disorders . Aspirin prolongs the closure time 94 % of the time with the Col / Epi cartridge and only 27 % of the time with the Col / ADP cartridge . Glanzmann thrombasthenia , Bernard - Soulier syndrome , and most mild von Willebrand diseases are associated with a prolonged closure time with both cartridges , whereas a storage pool defect and giant platelet thrombopathy have a prolonged closure time only with the Col / Epi cartridge . The advantages of this instrument include simplicity and reproducibility . The PFA - 100 has been reported to have a coefficient of variation of less than 10 % . It may be useful for determining global platelet function and for assessing the efficacy of antiplatelet therapy . Platelet aggregation Platelet aggregation is measured by turbidimetric methods . When platelets aggregate , the opalescent suspension of platelet - rich plasma becomes clearer and allows more light transmission . The extent of aggregation is determined by measuring the increase in light transmission . Small doses of ADP ( < 1 µmol ) induce a reversible form of platelet aggregation ( primary wave ) , unaccompanied by thromboxane synthesis or release of intraplatelet ADP . However , with increasing doses of ADP , sufficient stimulation of platelets occurs and leads to the release of intraplatelet ADP and the synthesis of thromboxane A from arachidonic acid , thus resulting in more pronounced irreversible aggregation ( secondary wave ) . Ristocetin induces platelet aggregation by inducing von Willebrand protein binding to the platelet GP Ib complex . Platelet aggregation tests are useful in distinguishing different disorders of platelet function . They are also particularly useful in the diagnosis of von Willebrand disease , in which ristocetin - induced platelet aggregation is defective . Imaging Studies Imaging studies are not necessary to diagnose uncomplicated ITPs . Rarely , platelet survival studies may be necessary to document decreased platelet survival before splenectomy in a patient with possible bone marrow hypofunction . Typically , the platelet half - life is decreased from the normal 5 - 7 days . A normal platelet survival curve is not consistent with increased splenic destruction . In a patient who has relapsed following splenectomy , an indium - labeled platelet imaging study is sometimes useful for localizing an accessory spleen . Bone Marrow Examination Bone marrow examination is not necessary in most cases of platelet disorders . The isolated presence of large platelets in the peripheral blood , in the absence of any other signs of bone marrow dysfunction , is very suggestive of normal marrow activity . Bone marrow examination is necessary in patients whose condition has an atypical course , have splenomegaly , or will undergo splenectomy , and in patients over age 60 years , as thrombocytopenia may be the initial manifestation of myelodysplastic syndrome . Bone marrow examination in patients with ITP shows megakaryocytic hyperplasia ( see image below ) . Quantifying the megakaryocytes in the bone marrow is technically difficult . Usually , 2 - 3 megakaryocytes are present in each spicule in typical marrow . Clusters of immature megakaryocytes are often observed in patients with ITP . Bone marrow in immune thrombocytopenic purpura . Bone marrow examination reveals an increased number of megakaryocytes . Treatment of Acute ITP in Children Because acute immune thrombocytopenic purpura ( ITP ) in children is self - limited , most physicians do not routinely treat it . Treatment is necessary only to prevent intracranial or other serious internal hemorrhage . 17 The rate of intracranial hemorrhage is very low , possibly less than 0.1 % , and occurs with platelet counts of 10,000 - 20,000 / µL . Most physicians arbitrarily treat children with ITP when their platelet count levels are less than 20,000 / µL . Nevertheless , current guidelines from the American Society of Hematology recommend that children with no bleeding or mild bleeding ( defined as bruising and petechiae , with no mucosal bleeding ) be managed with observation alone regardless of platelet count . The guidelines note , however , that " the decision to manage with observation alone requires a detailed discussion with the family about health - related quality of life , medication side effects and efficacy , and anticipatory guidance about preventing and monitoring for bleeding , " and that individual circumstances , such as unreliable followup or distance from the hospital , may make treatment an appropriate choice . Treatment options include intravenous immune globulin ( IVIG ) and corticosteroids , alone or in combination . In select cases , anti - D immunoglobulin may be used . IVIG ( 0.8 - 1 g / kg for 2 d ) results in a prompt rise in the platelet count , and this response confirms the diagnosis of acute ITP . The mechanisms of action of IVIG are not clear . Suggested mechanisms include blocking the macrophage Fc receptors , suppressing autoantibody production by providing anti - idiotypes , and stimulating the clearance of autoantibodies . The adverse effects of IVIG include fever , nausea , vomiting , and , occasionally , renal failure . IVIG is also very expensive compared with prednisone and is not available in all countries . Oral prednisone ( 4 mg / kg , with tapering and discontinuation by day 21 ) or IV methylprednisolone ( 30 mg / kg for 3 d ) is also effective , although recovery is not as quick as with IVIG . The mode of action of prednisone is probably multifold , decreasing antibody production , increasing platelet formation , decreasing macrophage - mediated clearance of platelets in the spleen , and immunomodulating the immune response . The combination of steroids and IVIG is synergistic and can be used in patients with imminent hemorrhage . Inducing a mild hemolytic state by administering anti - D immunoglobulin ( 25 - 50 μg / kg for 2 d ) is effective in individuals who are Rh positive , but is recommended only in those patients who have a negative direct antiglobulin test ( DAT ) and who have not undergone splenectomy . This therapy is less expensive than IVIG . However , the US Food and Drug Administration ( FDA ) has provided a warning and specific monitoring requirements because of reports of fatal intravascular hemolysis reported with anti - D immunoglobulin . With these modalities , the platelet counts in most children can be maintained at more than 30,000 / µL until spontaneous remission occurs . Other supportive measures include avoiding drugs that impair platelet function ( eg , aspirin ) and avoiding competitive contact sports . ITP may develop in children after measles , mumps , and rubella ( MMR ) vaccination . However , such cases occur at a lower rate than after natural measles or rubella infection , and recurrence of ITP has not been reported after MMR vaccination of unimmunized patients with ITP or re - vaccination of patients with previous nonvaccine - or vaccine - associated ITP . American Society of Hematology guidelines therefore recommend that unimmunized children with a history of ITP receive their first MMR vaccine on schedule . In a child with ITP who has already received the first dose of MMR vaccine and whose titers demonstrate full immunity , no further MMR vaccine should be given . If the child does not have adequate immunity , however , MMR vaccination should continue according to the recommended schedule . Treatment of Chronic ITP in Children Approximately 25 % of children with ITP do not undergo spontaneous remission within 6 months and have a chronic course with remissions and relapse similar to adult - onset chronic ITP . The rate of chronic ITP appears to increase with advancing age , rising from 23.1 % in children younger than 12 months to 47.3 % in children older than 10 years , in one study . 18 In a retrospective study of 47 children with chronic ITP who were not receiving corticosteroid therapy , 21 ( 44.7 % ) showed spontaneous remission according to new International Working Group standards , maintaining a platelet count of at least 100 × 10 9 / L approximately 3 - 4 years following their diagnosis ; 31 children ( 66 % ) maintained a platelet count of 50 × 10 / L or higher through 5.4 years of follow - up . Lower age at diagnosis and longer follow - up were significantly associated with a better prognosis . 19 Because of the likelihood of spontaneous remission , splenectomy should be avoided if possible . Furthermore , splenectomy in patients younger than 6 years is associated with severe postsplenectomy sepsis . The American Society of Hematology recommends splenectomy for children only if they have had ITP longer than 1 year and their bleeding results in platelet counts below 30,000 / µL . If treatment with corticosteroids , IVIG , or anti - D has been successful , these agents may be used prophylactically while waiting for a possible spontaneous remission . Although a number of agents ( eg , dapsone ) have been studied for treatment of pediatric patients with chronic ITP that is refractory to conventional agents , the American Society of Hematology found insufficient evidence to support recommendations regarding their use ( with the possible exception of dapsone ) . American Society of Hematology guidelines recommend consideration of the following for treatment of refractory chronic ITP in children and adolescents Rituximab or high - dose dexamethasone , for patients with significant ongoing bleeding despite treatment with IVIG , anti - D , or conventional doses of corticosteroids Rituximab or high - dose dexamethasone as an alternative to splenectomy or in patients who do not respond favorably to splenectomy Children with chronic ITP who are scheduled for splenectomy should receive pneumococcal and Haemophilus influenzae vaccines before the operation . Many physicians recommend that patients receive a prophylactic antibiotic regimen after splenectomy . Alloimmune thrombocytopenia in neonates If left untreated , alloimmune thrombocytopenia in neonates persists from a few days to up to 3 weeks . The treatment of choice is the administration of IVIG and maternally compatible platelets . Maternal platelets should be radiated to avoid graft versus host disease in the infant , and washed to reduce the antibody concentration . Response to steroids is rare . Treatment of Chronic ITP in Adults No consensus has been reached regarding when to start steroid therapy for chronic immune thrombocytopenia ( ITP ) in adults and how long to treat it . 7 20 21 The American Society of Hematology 2011 guidelines recommend treating patients with a platelet count < 30,000 / µl . Patients with bleeding manifestations may need to be treated to keep platelet counts > 50,000 / µl or even higher depending on the severity and location of the bleed . Steroid therapy A course of steroid therapy is often administered upon the initial diagnosis in an effort to induce a sustained remission . The treatment of choice is high - dose dexamethasone given at a dose of 40 mg daily for 4 days for one or two courses . Wei et al reported that a high - dose dexamethasone regimen resulted in a higher overall initial response , complete response rates , and shorter time to response , compared with prednisone . 22 In another study , a 4 - day course of high - dose dexamethasone ( 40 mg / d ) was reported as an effective initial therapy for adults with ITP , with 50 % of patients showing sustained platelet count of over 50,000 / µL . 23 Prednisone is usually administered at a dose of 1 mg / kg . Approximately two thirds of patients can be expected to show a therapeutic response with steroid therapy . Steroids are usually continued until the platelet count reaches normal or greater than 50,000 / µL , and then they are gradually tapered in 4 - 6 weeks . Methylprednisolone ( 30 mg / kg IV days 1 - 3 , tapered every third day to 1 mg / kg ) has also been used with similar results . In general , only 15 - 25 % of patients with chronic ITP are expected to have lasting remission ; the remainder have disease characterized by frequent relapses and remissions . Even if the platelet count normalizes , many patients can maintain platelet counts of more than 20,000 - 30,000 / µL with lower doses of steroids during times of relapse . However , in approximately one third of patients with chronic ITP , steroids are not effective , either because of a failure in response or a steroid requirement that leads to unacceptable adverse effects ( eg , glucose intolerance , GI bleeding ) . Intravenous immunoglobulin IVIG at a dose of 1 gm / kg can be used as initial therapy in addition to steroids when a rapid increase in platelet count is desired . IVIG can also be used as the initial treatment of choice in patients with HCV or HIV . IVIG ( 1 g / kg / d for 1 - 2 d ) induces a short - term increase in the platelet count , starting within several days and lasting approximately 2 - 3 weeks , both in patients who have undergone splenectomy and in those who have not . No clear evidence indicates that repeated infusions induce a lasting remission . Anti - D immunoglobulin ( WinRho , 50 - 75 μg / kg IV ) is also as effective as IV immunoglobulin in Rh - positive adults with an intact spleen . Rarely , massive intravascular hemolysis with DIC and occasional death has occurred with the use of anti - D immunoglobulin . Both IVIG and anti - D immunoglobulin are relatively expensive therapy for adults compared with steroids , and these agents are primarily used on an interim basis during a crisis ( eg , before splenectomy or major surgery ) . Splenectomy The second line of treatment for the management of steroid failures is splenectomy . Splenectomy is considered for any patient who does not respond to steroids ( or who can not receive steroids ) and has clinically significant bleeding manifestations . 20 The appropriate time to perform the splenectomy is controversial . Most physicians wait for 3 - 6 months before recommending splenectomy because sometimes ITP goes into spontaneous remission , especially in younger patients . Often , other clinical considerations ( eg , coexistence of diabetes or peptic ulcer disease PUD ] ) may influence the decision for earlier splenectomy . Splenectomy is effective because it removes the major site of destruction and the major source of antiplatelet antibody synthesis . Even if complete remission is not achieved , the platelet count will be higher after splenectomy . 21 Before splenectomy , patients should receive a pneumococcal vaccine . Approximately 10 - 20 % of patients who undergo splenectomy remain thrombocytopenic and continue to have a bleeding risk that requires continued treatment . Both steroid therapy and splenectomy are considered to have failed in these patients , and the patients are challenging to treat . An accessory spleen should be excluded as the cause of treatment failure after splenectomy . Thrombopoietin receptor agonists In a significant proportion of patients with ITP , ineffective platelet production from megakaryocytes plays a major role in causing thrombocytopenia . Stimulation of megakaryopoiesis by exogenous agents improves the platelet count . Two thrombopoietin receptor agonists have been approved for the treatment of chronic refractory ITP : eltrombopag and romiplostim . Eltrombopag Eltrombopag is an oral nonpeptide thrombopoietin receptor agonist that interacts with the transmembrane domain of the thrombopoietin receptor and induces megakaryocyte proliferation and differentiation . It has been shown to increase the platelet count in refractory ITP and in thrombocytopenia associated with hepatitis C – induced cirrhosis . It will most likely also be effective in thrombocytopenia due to other causes , by stimulating megakaryocytes . Eltrombopag is approved for treatment of refractory chronic ITP in patients who are at increased risk of bleeding because of their platelet count and clinical condition . It has also proved useful as bridging therapy for surgery , to provide a temporary pre - procedure boost in platelet count for patients with ITP who do not normally require therapy . 24 Eltrombopag is given in doses of 25 - 75 mg daily . The adverse effects include hepatotoxicity , worsening of cataracts , and increased bone marrow reticulin fibers . Romiplostim Romiplostim is another thrombopoietin receptor agonist , consisting of human immunoglobulin Fc region covalently linked to a peptide sequence that binds to and activates the thrombopoietin receptor . The peptide sequence has no homology with human thrombopoietin so that the possibility of a cross - reacting antibody is minimized . The Fc domain extends the half - life of the molecule in the circulation . Weekly subcutaneous doses of 1 - 7 μg / kg , romiplostim can increase the platelet count in chronic ITP . The adverse effects include bone marrow reticulin formation . In 2 parallel trials that assessed the long - term administration of romiplostim in 63 splenectomized and 62 nonsplenectomized patients with ITP , both the splenectomized and nonsplenectomized patients achieved durable platelet counts over a longer period with romiplostim than with placebo ; patients receiving romiplostim were also more likely to reduce or discontinue concurrent other ITP therapy compared with patients in the placebo groups . 25 The responses to thrombopoietin receptor agonists take 10 - 15 days , and , hence , they are unlikely to replace steroids or intravenous immunoglobulins as initial therapy . Furthermore , relapses are common , necessitating long - term therapy . Thrombopoietin receptor agonists may help postpone or even prevent splenectomies . The advantages of thrombopoietin receptor agonist therapy should be weighed against the risk of marrow fibrosis seen in the limited long - term outcome data . There is also a theoretical possibility that these agents increase the risk of hematologic malignancies , as thrombopoietin receptor is present in Immunosuppression Limited benefit may be observed using immunosuppression with cytotoxic agents . Azathioprine ( 150 mg / d ) or cyclophosphamide ( 50 - 100 mg / d ) has been used with some success . These cytotoxic drugs can cause myelosuppression , alopecia , hemorrhagic cystitis ( cyclophosphamide ) , sterility , and secondary malignancy . They are given for a minimum duration and are withdrawn as soon as remission is achieved . Blood counts must be monitored during therapy . Vincristine infusion ( 0.02 mg / kg ) with a maximum dose of 2 mg every week for 3 weeks has also been shown to induce remission . Refractory ITP has also been treated with the combination chemotherapy regimen used for low - grade non - Hodgkin lymphoma ( 6 cycles of cyclophosphamide , vincristine , and prednisone ) , with some success . Rituximab , a monoclonal antibody directed against the lymphocyte antigen , has been reported to induce lasting remission in refractory ITP . A meta - analysis of adults suggests that surgery could be delayed and may be avoided altogether for patients who received rituximab earlier in the course of therapy . 26 Several studies reported improved platelet counts in patients with Helicobacter pylori – positive ITP following standard H pylori eradication therapy , with cohorts from Japan and Italy reporting higher response rates . 27 Several explanations , such as molecular and immunomodulation by macrolides , have been provided . However , a recent small , multicenter , randomized controlled study that evaluated 55 patients aged 4 - 18 years with chronic ITP found no beneficial effect of H pylori eradication on platelet recovery . 28 Further investigation is needed . Other treatments A number of treatments have been proposed for patients in whom splenectomy and steroid therapy have failed . Most of these treatments are not based on placebo - controlled studies , and evaluating their efficacy in a disease associated with spontaneous remissions and relapse is difficult . The anabolic steroid danazol ( 400 - 800 mg / d ) has been shown to induce remission in certain patients . Cyclosporine and alfa - interferon have also been used . Plasmapheresis and extracorporeal protein A adsorption have been tried in desperate situations . The autoantibodies responsible for ITP are primarily IgG , and plasmapheresis is of limited value because more than half of the normal IgG pool is in the extravascular space . Other evolving therapies for refractory ITP include autologous hematopoietic stem cell transplantation and anticytokine therapy with etanercept ITP During Pregnancy The optimal management of immune thrombocytopenic purpura ( ITP ) during pregnancy is considerably controversial . Most pregnant women with ITP are treated with steroids and have relatively few complications involving the fetus and mother . 4 Patients whose condition is resistant to prednisone can be treated with IVIG . Splenectomy has been performed during pregnancy but should be avoided whenever possible . A platelet count of 50,000 / µL is usually sufficient for major surgeries , including splenectomy and cesarean delivery . The overriding concern is thrombocytopenia developing in the fetus . The IgG autoantibodies in ITP can cross the placenta and may cause thrombocytopenia in the fetus . In most recent studies of ITP complicating pregnancy , severe fetal thrombocytopenia has been uncommon . However , thrombocytopenia is occasionally observed in infants born from mothers who have thrombocytopenia . No laboratory parameter helps predict the platelet count in the fetus . Previous obstetric history is the only useful predictor . The platelet count of the fetus before delivery can be determined by fetal scalp sampling or percutaneous cord blood sampling . However , these are invasive procedures associated with serious complications , carrying a risk of intracranial hemorrhage similar to or higher than that of ITP due to neonatal thrombocytopenia . Further , platelets are often clumped , leading to spuriously low platelet count and unnecessary cesarean delivery . Treatment of Thrombotic Thrombocytopenic Purpura Thrombotic thrombocytopenic purpura ( TTP ) is a medical emergency , and prompt recognition and immediate initiation of plasma exchange is necessary . Until plasma exchange is instituted , fresh frozen plasma should be administered . Plasma exchange therapy , introduced 30 years ago , has dramatically improved the prognosis for patients with TTP . Current mortality rates remain approximately 20 % , compared with the greater than 90 % mortality rate observed before the advent of plasma exchange therapy . Plasma exchange ( 3 - 5 L / d ) is instituted promptly and continued daily until the patient ' s platelet count is normalized and the LDH level is within the reference range . Several weeks of plasma exchange may be required before a durable remission is achieved . Antiplatelet agents have not been shown to alter the natural history of the disease . Milder forms of TTP may respond to steroids . Rituximab is now routinely recommended for treatment of acute TTP , typically in patients who have a suboptimal response to treatment , but also as first - line therapy . Early administration of rituximab is associated with faster remissions and fewer plasma exchanges . Rituximab therapy may also prevent relapses . 29 In more severe cases , salvage strategies may include twice - daily therapeutic plasma exchange , pulses of cyclophosphamide , and vincristine . 29 Anecdotal reports indicate cases of TTP responding to a variety of therapies , including the following : IVIG Recombinant ADAMTS13 Inhibitors of the glycoprotein - Ib / IX - von Willebrand factor axis Staphylococcal protein A adsorption N - acetylcysteine 30 Intravenous bortezomib 31 Patients who relapse frequently or patients who require large volumes of replacement therapy are candidates for splenectomy . Splenectomy decreases the rate of relapse in patients with chronic relapsing forms of the disease . Treatment of Hemolytic - Uremic Syndrome Therapy for HUS is directed toward the underlying process . Acute and chronic renal failure is managed with fluid and electrolytes and , if necessary , dialysis . Plasma exchange therapy is often administered , but whether this is beneficial remains unclear . Antiplatelet and anticoagulant therapies have been attempted but do not show a marked benefit . A role for the complement system in the pathogenesis of HUS is elucidated , and eculizumab , a monoclonal antibody that inhibits the formation of a cell membrane attack complex , is being studied . Treatment of Severe Thrombocytopenia With Bleeding A bleeding patient with a very low platelet count is a medical emergency . The presence of hemorrhagic bullae in the buccal mucosa and retinal hemorrhages are harbingers of internal and intracranial bleeding . Diseases that cause such severe thrombocytopenia are ITP , TTP , posttransfusion purpura , drug - induced thrombocytopenia , and aplastic anemia . Differentiating TTP from ITP is very important , because platelet transfusions are contraindicated in patients with TTP , and plasma exchange therapy should be initiated as soon as possible in patients with TTP . Careful examination of the peripheral smear helps differentiate ITP from TTP . Furthermore , the presence of neurologic signs , renal failure , fever , and a high LDH level also helps in the diagnosis of TTP . The patient ' s medication history should be reviewed , and drug - induced thrombocytopenia should be considered if a temporal relationship exists between the thrombocytopenia and drug exposure . Patients with liver disease and those who abuse alcohol often present with severe thrombocytopenia following binge drinking . These patients may have severe thrombocytopenia resulting from splenomegaly , alcohol - induced suppression of platelet production , folate deficiency , and DIC from active liver disease . Aplastic anemia is associated with pancytopenia , and the smear examination findings help differentiate it from ITP . Once the diagnosis of ITP with clinically significant bleeding is established , treatment with steroids ( IV methylprednisolone at 30 mg / kg ) and IVIG should be started immediately . Platelet transfusions are administered to patients with severe clinical bleeding , and a sustained increase in platelet counts is sometimes observed in those with ITP . Currently , emergency splenectomy is rarely necessary and is only considered before an emergency operation such as evacuation of an intracranial hematoma . Treatment of von Willebrand Disease Desmopressin ( DDAVP ) is a vasopressin analogue that releases vWf from endothelial cells . Most patients with type I von Willebrand disease can be treated with DDAVP for minor surgeries and dental procedures . The usual dose is 0.3 μg / kg infused slowly approximately 30 minutes before an operative procedure . This dose can be repeated once a day for 2 - 3 days , after which it is ineffective because of tachyphylaxis . Other adverse effects occasionally include a hypertensive response and hyponatremia . An intranasal preparation of DDAVP has been made available for individuals with von Willebrand disease and is administered at a dose of 150 μg or 300 μg ( ie , 150 μg per nostril ) . The more diluted preparation is used in patients with diabetes insipidus and does not increase vWf levels . DDAVP does not usually increase factor VIII levels in patients with type IIA and can induce thrombocytopenia in patients with type IIB or pseudo von Willebrand disease . Replacement therapy is used for more extensive surgeries or trauma and for patients with type II and type III disease . The treatment of choice is vWf concentrates . Purified plasma - derived concentrates of vWF / FVIII ( Humate - P or Alphanate ) are heat - treated , and the solvent is extracted ; therefore , they are considered safe from viral contamination . Recombinant von Willebrand factor ( Vonvendi ) was approved by the US Food and Drug Administration ( FDA ) in December 2015 . 32 The dose of vWf concentrate is calculated based on ristocetin cofactor units ( usual dose is 50 - 100 U / kg ) . The factor VIII level often rises following the infusion of von Willebrand protein concentrate , and it remains elevated for at least for 40 hours , reflecting the half - life of von Willebrand protein rather than that of factor VIII . The need for further doses is often assessed based on clinical criteria rather than blood test results . Cryoprecipitate has approximately 100 U of factor VIII per bag and has all multimeric forms of vWf . Despite screening tests , patients have a small risk developing viral infections . Highly purified preparations of factor VIII or recombinant factor VIII should not be administered to patients with von Willebrand disease , because these preparations have very little von Willebrand factor . Treatment of Uremic Bleeding The most effective therapy for this platelet dysfunction is vigorous dialysis . For a more immediate correction of uremic bleeding , DDAVP and cryoprecipitate have also been shown to be useful in providing hemostasis . These modalities provide a short - term benefit until dialysis corrects the hemostatic defects . In addition to effective dialysis , conjugated estrogen has been shown to decrease bleeding in patients with uremic hemorrhages . Prognosis Immune thrombocytopenic purpura ITP is generally a benign disorder . Severe ITP with a platelet count of less than 5000 / µL is occasionally associated with fatal hemorrhages in the brain or internal organs . Patients who are elderly , those whose disease is refractory to treatment , those who have a previous history of hemorrhage , and patients with concomitant bleeding disorders ( eg , hemophilia , uremia ) are at higher risk for serious life - threatening hemorrhage . Thrombotic thrombocytopenic purpura TTP is a very serious disorder . The introduction of plasma exchange therapy has improved the prognosis , but mortality rates remain approximately 20 % . Congenital disorders Among congenital bleeding disorders involving platelets , type III von Willebrand disease and type I Glanzmann thrombasthenia are severe diseases associated with lifelong hemorrhages . Most other platelet disorders are mild bleeding disorders . Splenectomized patients Patients who have undergone splenectomy should be warned about the low risk of severe sepsis following splenectomy . These patients should be immunized with pneumococcal vaccine before splenectomy . Questions & Answers Overview What are platelet disorders ? How do platelet disorders occur ? What are major mechanisms of platelet function in platelet disorders ? What is the pathophysiology of platelet disorders ? How is immune thrombocytopenia ( ITP ) characterized in platelet disorders ? What are the demographics of acute immune thrombocytopenia ( ITP ) ? What are the signs and symptoms of acute immune thrombocytopenia ( ITP ) platelet disorder ? What are the physical exam findings in acute immune thrombocytopenia ( ITP ) platelet disorder ? What is the most common cause of thrombocytopenia platelet disorder in otherwise healthy children ? What is the relationship between acute leukemia and thrombocytopenia platelet disorder ? What are the demographics of chronic immune thrombocytopenia ( ITP ) platelet disorder ? What is gestational thrombocytopenia platelet disorder ? What is the role of platelet dysfunction in hypertensive disorders of pregnancy ? What is the role of platelet disorders in posttransfusion purpura ? What is the role of platelet dysfunction in neonatal alloimmune thrombocytopenia ? How do drugs cause thrombocytopenia platelet disorders ? Which common drugs are associated with thrombocytopenia platelet disorders ? How is drug - induced thrombocytopenia platelet disorder diagnosed ? What are the manifestations of thrombotic thrombocytopenic purpura ( TTP ) platelet disorder ? What causes thrombotic thrombocytopenic purpura ( TTP ) platelet disorder ? What is hemolytic - uremic syndrome ( HUS ) platelet disorder ? What is von Willebrand disease ( vWD ) ? What is Bernard - Soulier syndrome platelet disorder ? What is Glanzmann thrombasthenia of platelet disorder ? How common are functional disorders of platelets ? What is the role of the von Willebrand factor ( vWf ) in hemostasis rand platelet disorders ? What are the bleeding manifestations of von Willebrand disease ( vWD ) ? How does von Willebrand disease ( vWD ) manifest in pregnancy ? How are the platelet disorders of von Willebrand disease ( vWD ) characterized ? What are variants of von Willebrand disease ( vWD ) ? What causes platelet thromboxane synthesis disorders ? What is the role of enzyme mutations in platelet thromboxane synthesis disorders ? What causes platelet release reaction disorders ? What is the role of platelet dysfunction in uremia ? What is the epidemiology of platelet disorders ? Which features of the history and physical exam are associated with platelet disorders ? What causes platelet disorders ? What are the disorders of platelet function ? Which lab studies are indicated in the workup of platelet disorders ? What are the peripheral smear findings in the workup of platelet disorders ? Which lab studies are indicated in the workup of platelet - associated immunoglobulin G ? What is the role of primary hemostasis bleeding time testing in the workup of platelet disorders ? What is the platelet function analyzer 100 ( PFA - 100 ) and how is it used in the workup of platelet disorders ? How is platelet aggregation measured in the workup of platelet disorders ? Which imaging studies are indicated in the workup of platelet disorders ? What is the role of bone marrow exam in the workup of platelet disorders ? How is acute immune thrombocytopenic purpura ( ITP ) platelet disorder in children treated ? What are treatment options for acute immune thrombocytopenic purpura ( ITP ) platelet disorder in children ? What are the guidelines on measles , mumps , and rubella ( MMR ) vaccination in children with acute immune thrombocytopenic purpura ( ITP ) platelet disorders ? How is chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in children treated ? What is the role of splenectomy in the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in children ? Which medications are recommended for the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder ? How is alloimmune thrombocytopenia platelet disorder in neonates treated ? How effective is eltrombopag for the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? How effective is romiplostim for the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? How is chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults treated ? What is the role of steroid therapy in the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? What is the role of IVIG and anti - D immunoglobulin in the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? When is splenectomy indicated in the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? What is the role of thrombopoietin receptor agonists in the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? What is the role of immunosuppressive therapy in the treatment of chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? What evolving treatments are available for chronic immune thrombocytopenic purpura ( ITP ) platelet disorder in adults ? How is immune thrombocytopenic purpura ( ITP ) platelet disorder managed in pregnancy ? How is thrombotic thrombocytopenic purpura ( TTP ) platelet disorder treated ? Which salvage strategies are used in the management of thrombotic thrombocytopenic purpura ( TTP ) platelet disorder ? How is hemolytic - uremic syndrome ( HUS ) platelet disorder treated ? How is thrombotic thrombocytopenia purpura platelet disorder treated ? How is von Willebrand disease ( vWd ) platelet disorder treated ? How is uremic bleeding in platelet disorders treated ? What is the prognosis of immune thrombocytopenic purpura ( ITP ) platelet disorder ? What is the prognosis of thrombotic thrombocytopenic purpura ( TTP ) platelet disorder ? What is the prognosis of congenital platelet disorders ? What is the prognosis of patients who have had a splenectomy in the treatment of a platelet disorder ? Sections Platelet Disorders Show All Media Gallery References
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[
"Platelet",
"hemostatic system",
"blood vessels"
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http://emedicine.medscape.com/article/2039975-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Infectious Diseases Pathophysiology of Complicated Urinary Tract Infection ( UTI ) Updated : Jul 24 , 2017 Author : John L Brusch , MD , FACP ; Chief Editor : Michael Stuart Bronze , MD more . . . Sections Overview Host Factors Diabetes Mellitus Calculi - Related UTI Focal and Multifocal Nephritis Xanthogranulomatous Pyelonephritis Abscesses Pregnancy Candiduria Show All Media Gallery References Overview Complicated urinary tract infections ( UTIs ) occur in the setting of a urinary tract that has metabolic , functional , or structural abnormalities . Complicated UTIs may involve both lower and upper tracts .Their primary significance is that they significantly increase the rate of therapy failures . The pathophysiology of complicated UTIs has the following 4 aspects : Structural abnormalities , such as calculi , infected cysts , renal / bladder abscesses , certain forms of pyelonephritis , spinal cord injury ( SCI ) , and catheters Metabolic / hormonal abnormalities , such as diabetes and pregnancy Impaired host responses , such as transplant recipients ( especially renal transplants ) and patients with AIDS Unusual pathogens , such as yeast A growing number of complicated UTIs are healthcare associated in origin . The most common pathogens include Escherichia coli , enterococci , Pseudomonas aeruginosa , candidal species , and Klebsiella pneumoniae . Pyelonephritis is almost always the result of bacteria migrating from the bladder to the renal parenchyma , which is enhanced by vesicourethral reflux . In uncomplicated pyelonephritis , the bacterial invasion and renal damage are limited to the pyelocalyceal - medullary region ; in complicated pyelonephritis , all regions of the kidney may be affected . If the infection progresses , bacteria may invade the bloodstream , resulting in bacteremia . 1 2 Host Factors Patients with a neurogenic bladder or bladder diverticulum and postmenopausal women with bladder or uterine prolapse have an increased frequency of urinary tract infection because of incomplete bladder emptying . This eventually allows residual bacteria to overwhelm local bladder mucosal defenses . Autosomal dominant polycystic kidney disease can lead to end - stage renal disease . Cysts may become infected from either bacteremia or bacteriuria . Subclinical pyelonephritis should be considered in patients with any of the following risk factors : Poverty Pregnancy Diabetes Alcoholism History of pyelonephritis Renal transplantation UTI before age 12 years More than 3 UTIs in the past year Diabetes Mellitus In patients with diabetes mellitus , high urine glucose content and defective host immune factors predispose to infection . Hyperglycemia causes neutrophil dysfunction by increasing intracellular calcium levels and interfering with actin and , thus , diapedesis and phagocytosis . Associated vaginal candidiasis and vascular disease also play a role in recurrent infections . Patients with diabetes may develop emphysematous or xanthogranulomatous pyelonephritis and necrotizing papillitis . Over time , patients with diabetes may develop cystopathy , nephropathy , and renal papillary necrosis , complications that predispose them to UTIs . Long - term effects of diabetic cystopathy include vesicourethral reflux and recurrent UTIs ; as many as 30 % of women with diabetes have some degree of cystocele , cystourethrocele , or rectocele . 3 For more information on this topic , see the Medscape Reference article Urinary Tract Infections in Diabetes Mellitus Focal and Multifocal Nephritis Acute focal bacterial nephritis is also known as acute lobar nephronia or focal pyelonephritis ( see the image below ) . This is an acute bacterial interstitial nephritis affecting a single renal lobe . Multiple abscesses , upper pole of left kidney . View Media Gallery Acute multifocal bacterial nephritis affects more than 1 lobe . Emphysematous pyelonephritis is a severe , necrotizing form of acute multifocal bacterial nephritis . 4 Retroperitoneal ( ie , extraluminal ) gas may be observed in the renal parenchyma and perirenal space on radiographs . This is observed most commonly in people with diabetes , but it also may be observed in patients with immunocompromise or obstruction . 5 6 Xanthogranulomatous Pyelonephritis Xanthogranulomatous pyelonephritis is a severe chronic infection of the renal parenchyma . The kidney is enlarged and is fixed to the retroperitoneum by either perirenal fibrosis or an extension of the granulomatous process . The inciting event in xanthogranulomatous pyelonephritis appears to be renal obstruction leading to a chronic UTI . Predisposing factors include renal calculi , lymphatic obstruction , renal ischemia , dyslipidemia , diabetes , and primary hyperparathyroidism . 5 .The pathological hallmark is the lipid - laden macrophage . This most likely represents a defect of intracellular killing . The chronic inflammation leads to massive destruction of the kidney . The classic appearance of xanthogranulomatous pyelonephritis on CT scan is that of low - density areas surrounded by a 2 - 1 that is enhanced by contrast . It often takes a tissue diagnosis to differentiate this process from renal cell carcinoma . 7 Abscesses A perinephric abscess is defined as a collection of purulent material between the renal capsule and Gerota fascia . A perinephric abscess may develop secondary to an intrarenal abscess , a renal cortical abscess , xanthogranulomatous pyelonephritis , or chronic or recurrent pyelonephritis or from hematogenous dissemination . Predisposing factors are similar to those for intrarenal abscess . Approximately 25 % of patients have diabetes . 8 Renal corticomedullary abscesses usually are associated with vesicoureteral reflux or urinary tract obstruction , and the usual organisms include Escherichia coli , Klebsiella species , and Proteus species . Clinical syndromes include acute focal bacterial nephritis , acute multifocal bacterial nephritis , emphysematous pyelonephritis , and xanthogranulomatous pyelonephritis . Renal cortical abscesses ( ie , renal carbuncles ) usually result from hematogenous spread of bacteria . Primary sources of infection include skin infections , osteomyelitis , and endovascular infections . These are observed commonly in users of injection drugs , people with diabetes , and patients on dialysis . The most common organism isolated is Staphylococcus aureus . Ten percent of cortical abscesses may rupture through the renal capsule and form a perinephric abscess . 9 Hematogenous spread Renal cortical abscesses ( ie , renal carbuncles ) usually result from hematogenous spread of bacteria . Primary sources of infection include skin infections , osteomyelitis , and endovascular infections . These are observed commonly in users of injection drugs , people with diabetes , and patients on dialysis . The most common organism isolated is Staphylococcus aureus . Ten percent of cortical abscesses may rupture through the renal capsule and form a perinephric abscess . Several factors increase the risk of UTI in pregnancy . These factors include relative obstruction of the ureters ( secondary to the enlarging uterus ) , smooth muscle relaxation of the ureter and bladder ( secondary to progesterone ) , and aminoaciduria and glycosuria , which provide a favorable environment for bacteria to grow . 10 E coli is the most common organism isolated from cultures , although Proteus mirabilis and Klebsiella pneumoniae also are observed . Less common agents include group B streptococci and Staphylococcus saprophyticus . Group B streptococci are isolated in approximately 5 % of infections and have been linked to preterm labor ; these patients should receive prophylactic antibiotics during delivery to reduce the risk of neonatal sepsis . 11 For more information on this topic , see the Medscape Reference article Urinary Tract Infections in Pregnancy Candiduria Risk factors for candiduria include diabetes mellitus , indwelling urinary catheters , and antibiotic use . The presence of Candida species in the urine usually represents colonization and not infection , and as such , not all patients with candiduria require treatment . A lower threshold for initiating treatment exists for patients with diabetes , a history of renal transplantation , or genitourinary abnormalities . 12 Sections Pathophysiology of Complicated Urinary Tract Infection ( UTI ) Calculi - Related UTI Show All Media Gallery References
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[
"urinary tract infections",
"Pathophysiology"
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http://emedicine.medscape.com/article/2047283-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Clinical Procedures Bakri Balloon Placement Updated : Jul 05 , 2016 Author : Gabor C Mezei , MD , PhD ; Chief Editor : Carl V Smith , MD more . . . Sections Overview Periprocedural Care Technique References Background Postpartum hemorrhage ( PPH ) is a life - threatening complication of delivery . It can occur after vaginal or cesarean delivery and is a major cause of maternal morbidity and mortality in both developing and developed countries as well . 1 2 3 The most common cause of PPH is uterine atony ; up to 80 % of the cases result from suboptimal contraction of the myometrium following placental separation . After excluding other etiologies of PPH such as retained placenta , uterine rupture , genital tract trauma , uterine inversion , and coagulopathy , the management of uterine atony should be timely and initiated to prevent hemorrhagic , hypovolemic shock , dilutional coagulopathy , tissue hypoxia , and acidosis . The pituitary gland , the kidneys , and the lungs are particularly susceptible organs to damage when perfusion pressure decreases resulting in feared sequelae of postpartum hypovolemic shock such as Sheehan syndrome ( ie , postpartum hypopituitarism ) , renal failure , and acute respiratory distress syndrome The repertoires of the management measures can be generally divided into operative and nonoperative interventions . In acute postpartum hemorrhage refractory to medical and other conservative interventions , invasive therapies may include arterial embolization , uterine compression sutures , uterine artery ligation , and , ultimately , hysterectomy . However , these measures are highly invasive , require extensive resources , expertise , and are associated with significant morbidities . Intrauterine balloon tamponade has been suggested as an effective , easily administered minimally invasive treatment option to control uterine bleeding while preserving the mother ’ s ability to bear additional children . 4 5 6 Multiple types of balloons are available , including Bakri balloon , BT - cath balloon tamponade catheter , Foley catheters , Rusch balloon , condom catheters and the Sengstaken - Blakemore tube . The Bakri postpartum balloon 7 and the BT - cath balloon tamponade catheter 8 are specifically designed for postpartum intrauterine tamponade , and they are the only such devices approved by the US Food and Drug Administration for this application . 9 However , in settings where these are unavailable , other balloons can be used to achieve a similar effect . In term of mechanism of action , the intrauterine balloon is believed to act by exerting inward to outward pressure against the uterine wall , resulting in a reduction in persistent capillary and venous bleeding from the endometrium and the myometrium . 10 In 2006 , the ACOG Practice Bulletin , published by the American College of Obstetricians and Gynecologists , made mention of the Bakri postpartum balloon for its specifically tailored design that enables conservative management of uterine bleeding in cases of uterine atony and other causes of PPH . 1 Global awareness and use of the Bakri postpartum device has grown steadily since 2006 as physicians , hospitals , and other medical institutions have sought effective , minimally invasive means to control uterine bleeding . Indications The Bakri balloon is used for temporary control or reduction of postpartum hemorrhage when conservative management of uterine bleeding is warranted , after bleeding from genital tract lacerations and retained product of conception has been excluded . The 2006 ACOG practice bulletin on postpartum hemorrhage by the American College of Obstetricians and Gynecologists states the following : “ When uterotonics fail to cause sustained uterine contractions and satisfactory control of hemorrhage after vaginal delivery , tamponade of the uterus can be effective in decreasing hemorrhage secondary to uterine atony . Such approaches can be particularly useful as a temporizing measure , but if a prompt response is not seen , preparations should be made for exploratory laparotomy . ” Although the use of intrauterine balloon catheter is often successful and serves as a definite therapy , it can also be used as a temporary measure to decrease hemorrhage while waiting and preparing for other definite treatment , such as open abdominal surgery ( ie , uterine artery ligation , uterine compression suture , hysterectomy ) or uterine artery embolization , or while the patient is being transferred to another unit with more experience and resources . Studies have used intrauterine balloons for bleeding following delivered pregnancies with low - lying placenta and / or placenta previa or invasive or adherent placenta and as an adjunctive treatment of cervical ectopic pregnancy with variable success . 11 Contraindications Few contraindications have been highlighted in the use of the Bakri . They include the following : Pregnancy Heavy arterial bleeding requiring surgical exploration or angiographic embolization Cervical cancer Congenital uterine anomaly Uterine distorting pathology ( leiomyoma ) Suspected uterine rupture Purulent infection of the vagina , cervix , or uterus Allergy to balloon material ( silicone ) Disseminated intravascular coagulation ( DIC ) DIC is listed as a contraindication for balloon tamponade given the complete lack of clinical data . However , theoretically , it can be used to decrease the volume of bleeding and gain time to replenish blood products in preparation for more invasive surgical techniques . Technical Considerations Best Practices The authors recommend that all procedures for management of postpartum hemorrhage be performed on the labor and delivery unit , with an operating room available if an emergency laparotomy becomes necessary . Procedure Planning Prior to the procedure , a bedside ultrasound should be used to help assess the uterine cavity to rule out retained product of conception and to assess the angulation and shape of the uterine cavity to help balloon catheter placement . Complication Prevention Complications related to intrauterine balloon placements are very rare but potentially include perforation of uterus during placement or inflation and cervical trauma due to inflation at an incorrect location . However , these complications have not been reported in the postpartum uterus . Infection has been reported , but determining whether it is related to the balloon placement is difficult . To avoid potential risk of air embolism , the balloon should not be insufflated with air or carbon dioxide . Outcomes The Bakri balloon is a successful method for postpartum hemorrhage management , and this has been borne out by studies in recent years . 12 13 14 15 Previously , most studies compared the effects of balloon tamponade and other methods to treat PPH , such as uterine compression sutures and arterial embolization , and concluded that no high quality evidence suggests that any one method of management of severe PPH was superior . 16 In a small case series , success rates of uterine balloon catheters for controlling hemorrhage ranged from 57 % after cesarean delivery to 100 % after vaginal delivery . 4 16 17 The Bakri balloon has clear advantages compared to other intrauterine tamponade devices . These advantages are as follows 9 Bakri balloon catheter is made of silicone , which is advantageous in patients with latex allergy . The shape more naturally conforms to the uterine cavity compared to other catheters . The risk of uterine perforation may be lower . It comes presterilized and ready to use , whereas the tip of the Sengstaken - Blakemore tube needs to be cut , has extra ports , and is more complicated to use . To date , no evidence suggests that a Bakri balloon or any other intrauterine tamponade devices would decrease the future reproductive potential and / or would increase adverse pregnancy outcomes in subsequent pregnancies . The literature , however , is limited and further studies are needed . 18 A study by Kaya et al evaluated the B - Lynch uterine compression suture and Bakri balloon tamponade in severe postpartum hemorrhage and found that the Bakri balloon and the B - Lynch suture had similar success rates in uterine atony during cesarean section . The study added that the Bakri balloon is less invasive and easier to learn , but more time consuming and expensive compared to the B - Lynch suture . 19 Periprocedure Sections Bakri Balloon Placement Overview Periprocedural Care Technique References
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[
"Bakri Balloon Placement",
"PPH"
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http://emedicine.medscape.com/article/206598-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Hematology Thrombotic Thrombocytopenic Purpura ( TTP ) Updated : Feb 18 , 2019 Author : Theodore Wun , MD , FACP ; Chief Editor : Srikanth Nagalla , MBBS , MS , FACP more . . . Sections Overview Practice Essentials Background Pathophysiology Epidemiology Show All Presentation DDx Workup Treatment Medication Follow - up Questions & Answers References Practice Essentials Thrombotic thrombocytopenic purpura ( TTP ) is a rare blood disorder characterized by clotting in small blood vessels ( thromboses ) , resulting in a low platelet count . 1 In its full - blown form , the disease consists of the following pentad : Microangiopathic hemolytic anemia Thrombocytopenic purpura Neurologic abnormalities Fever Renal disease To make an accurate diagnosis , the clinician must recognize the similarity between TTP and hemolytic - uremic syndrome ( HUS ) . 2 In addition to HUS , the differential diagnosis also includes immune thrombocytopenic purpura ( ITP ) and disseminated intravascular coagulation ( DIC ) , two entities with very different modes of therapy ( see the image below ) . Differential diagnosis of immune thrombocytopenic purpura ( ITP ) , thrombotic thrombocytopenic purpura ( TTP ) , and disseminated intravascular coagulation ( DIC ) . Secondary TTP has been associated with the use of certain drugs , including chemotherapy drugs such as gemcitabine and mitomycin and antiplatelet agents such as clopidogrel and ticlopidine . If secondary TTP is suspected , the offending drug should be discontinued . See Cancer Chemotherapy : Keys to Diagnosing Common Toxicities , a Critical Images slideshow , to help recognize some of the more common complications of chemotherapy . Signs and symptoms TTP can affect any organ system , but involvement of the peripheral blood , the central nervous system , and the kidneys causes the clinical manifestations . Patients with TTP typically report an acute or subacute onset of symptoms related to neurologic dysfunction , anemia , or thrombocytopenia . Neurologic manifestations include alteration in mental status , seizures , hemiplegia , paresthesias , visual disturbance , and aphasia Fatigue may accompany the anemia Severe bleeding from thrombocytopenia is unusual , although petechiae are common See Presentation for more detail . Diagnosis Laboratory studies for suspected TTP include a CBC , platelet count , blood smears , coagulation studies , BUN creatinine , and serum bilirubin and lactate dehydrogenase . The exact etiology of TTP is unknown . Most sporadic cases of TTP appear to be associated with severe deficiency of ADAMTS13 activity due to autoantibodies against this protease . 3 4 Measuring ADAMTS13 activity level may aid in diagnosis . Imaging studies and biopsies are not required for diagnosis . Workup for more detail . Management The therapy of choice for TTP is plasma exchange with fresh frozen plasma . Because only 20 - 30 % of patients present with the classic pentad , initiating total plasma exchange is justified by the presence of microangiopathic hemolytic anemia ( schistocytes , elevated LDH , and indirect hyperbilirubinemia ) and thrombocytopenia in the absence of other obvious causes ( DIC , malignant hypertension ) . Caplacizumab ( Cablivi ) , a nanobody that targets von Willebrand factor ( vWF ) was approved by the FDA in January 2019 . It is indicated for acquired thrombotic thrombocytopenic purpura ( aTTP ) in combination with plasma exchange and immunosuppressive therapy . It has been shown to reduce time to platelet count response and also to reduce aTTP - related death , recurrence , or major thromboembolic events . 5 Octaplas ( Octapharma ) , a blood plasma product extensively used in Europe , was approved by the FDA in January 2013 for use in the United States . The product is a sterile , frozen solution of pooled human plasma from several donors . It is a viable alternative to single - donor plasma , and it is treated with a solvent detergent process , which reduces the risk of infection . The FDA based approval on clinical studies of patients with liver disease , liver transplant , heart surgery , and TTP . 6 In those patients refractory to plasma exchange , using cryopoor plasma ( or cryosupernatant ) has sometimes led to a response . This is fresh frozen plasma that has had the cryoprecipitate removed and is thus depleted of high - molecular - weight von Willebrand multimers , which have a pathogenic role in TTP . Corticosteroids may also be used in refractory TTP . Rituximab , although not approved for use in TTP , is increasingly recommended for use in refractory cases . Treatment and Medication Next : Background Sections Thrombotic Thrombocytopenic Purpura ( TTP ) Overview Background Pathophysiology Epidemiology Show All DDx Follow - up Questions & Answers References
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[
"Thrombotic Thrombocytopenic Purpura",
"hemolytic-uremic syndrome",
"immune thrombocytopenic purpura"
] |
http://emedicine.medscape.com/article/2085837-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Laboratory Medicine Partial Thromboplastin Time , Activated Updated : Nov 23 , 2015 Author : Muhammad Bader Hammami , MD ; Chief Editor : Eric B Staros , MD more . . . Sections Reference Range Interpretation Collection and Panels Background Questions & Answers Show All References Reference Range Partial thromboplastin time ( PTT ) and activated partial thromboplastin time ( aPTT ) are used to test for the same functions ; however , in aPTT , an activator is added that speeds up the clotting time and results in a narrower reference range . The aPTT is considered a more sensitive version of the PTT and is used to monitor the patient ’ s response to heparin therapy . The reference range of the aPTT is 30 - 40 seconds . The reference range of the PTT is 60 - 70 seconds . Critical values that should prompt a clinical alert are as follows : aPTT : More than 70 seconds ( signifies spontaneous bleeding ) PTT : More than 100 seconds ( signifies spontaneous bleeding ) 1 2 Interpretation A prolonged aPTT result may indicate the following 1 2 Congenital deficiencies of intrinsic system clotting factors such as factors VIII , IX , XI , and XII , including hemophilia A and hemophilia B ( Christmas disease ) , two inherited bleeding disorders resulting from a deficiency in factors VIII and IX , respectively Congenital deficiency of Fitzgerald factor ( prekallikrein ) Von Willebrand disease , which is the most common inherited bleeding disorder , affecting platelet function owing to decreased von Willebrand factor activity Hypofibrinogenemia Liver cirrhosis ( the liver makes most of the clotting factors , including those that are vitamin K - dependent ones ) ; diseases of the liver may result in an inadequate quantity of clotting factors , prolonging the aPTT Vitamin K deficiency : The synthesis of some clotting factors requires vitamin K , so vitamin K deficiency results in an inadequate quantity of intrinsic system and common pathways clotting factors , as a result the aPTT is prolonged Disseminated intravascular coagulation ( DIC ) : The clotting factors involved in the intrinsic pathway are consumed , prolonging the aPTT Heparin therapy , which inhibits the intrinsic pathway at several points ( eg , prothrombin II ) , prolonging the aPTT 3 Coumarin therapy , which inhibits the function of factors I , IX and X , prolonging the aPTT Nonspecific inhibitors , such as lupus anticoagulant and anticardiolipin antibodies , which bind to phospholipids on the surface of platelets Specific circulating anticoagulants , inhibitor antibodies that specifically target certain coagulation factor , such as in individuals with hemophilia after many plasma transfusions , systemic lupus erythematosus rheumatoid arthritis tuberculosis , and chronic glomerulonephritis A shortened aPTT result may indicate the following Early stages of DIC : circulating procoagulants exist in the early stages of DIC , shortening the aPTT Extensive cancer ( eg , ovarian cancer pancreatic cancer colon cancer Immediately after acute hemorrhage An acute - phase response leading to high factor VIII levels Collection and Panels Many drugs can change the results of the activated partial thromboplastin time ( aPTT ) , including nonprescription drugs . No specific preparation is required . However , since lipemia may interfere with photoelectric measurements of clot formation , specimens should not be obtained after a meal . 4 If the patient is receiving heparin by intermittent injection , the sample should be drawn 30 - 60 minutes before the next dose , while , if the patient is receiving a continuous heparin infusion , the sample can be drawn at any time . Factors that interfere with the aPTT test are include the following Drugs that may prolong the test values , including antihistamines , ascorbic acid , chlorpromazine , heparin , and salicylates Incorrect blood - to - citrate ratio Hematocrit that is highly increased or decreased Blood samples drawn from heparin lock or a heparinized catheter Specimen preparation 4 5 Usually , 5 mL of citrated , platelet - poor plasma is prepared from 4.5 mL of peripheral venous blood collected via venipuncture and drawn directly into a blue - top tube that contains 0.5 mL of the anticoagulate sodium citrate at a ratio of 9 : 1 . Invert the tubegently several times to mix the anticoagulant , but do not agitate it . After collection , the whole blood sample is centrifuged , and the plasma is removed and placed in another blue - top tube . The plasma should be stored covered at 4 ° C . The test should be run within 4 hours of collection . Keep the specimen cool because a high temperature alters the results . Related tests Related tests include the following 5 Prothrombin time ( PT ) Coagulation factor concentration Fibrinogen testing Thrombin time testing Platelet counts Background Description Partial thromboplastin time ( PTT ) and activated partial thromboplastin time ( aPTT ) are used to test for the same functions ; however , in aPTT , an activator is added that speeds up the clotting time and results in a narrower reference range . The aPTT is considered a more sensitive version of the PTT and is used to monitor the patient ’ s response to heparin therapy . The aPTT test is used to measure and evaluate all the clotting factors of the intrinsic and common pathways of the clotting cascade by measuring the time ( in seconds ) it takes a clot to form after adding calcium and phospholipid emulsion to a plasma sample . The result is always compared to a control sample of normal blood . The aPTT evaluates factors I ( fibrinogen ) , II ( prothrombin ) , V , VIII , IX , X , XI and XII . When the aPTT test is performed in conjunction with prothrombin time ( PT ) test , which is used to evaluate the extrinsic and common pathways of the coagulation cascade , a further clarification of coagulation defects is possible . If , for example , both the PT and aPTT are prolonged , the defect is probably in the common clotting pathway , and a deficiency of factor I , II , V , or X is suggested . A normal PT with an abnormal aPTT means that the defect lies within the intrinsic pathway , and a deficiency of 6 Normal hemostasis Normal hemostasis is achieved when there is a balance between factors that encourages clotting and factors that encourages clot dissolution . Following damage to a blood vessel , the first reaction of the body is vascular constriction to reduce blood loss . In small - vessel injury , this may be enough to stop bleeding . However , for large blood vessels , hemostasis is required . Primary hemostasis occurs within seconds and results in platelet plug formation at sites of injury . Next , secondary hemostasis occurs , which consists of the reactions of the plasma coagulation system that result in fibrin formation . It requires several minutes for completion . The fibrin strands that are produced strengthen the primary hemostatic plug . In the first phase of reactions , called the intrinsic system , 3 plasma proteins , Hageman factor ( factor XII ) , high - molecular - weight kininogen , and prekallikrein , form a complex on vascular subendothelial collagen , and , through a series of reactions , activated factor XI ( XIa ) is formed and activates factor IX ( IXa ) . Then , a calcium - and lipid - dependent complex is formed between factors VIII , IX , and X , and activated X ( Xa ) is formed . At the same time , the extrinsic system is activated and provides a second pathway to initiate coagulation by activating factor VII ( VIIa ) . In this pathway , a complex formed between factor VII , calcium , and tissue factor results in activation of factor VII ( VIIa ) . VIIa can directly activate factor X and activated X ( Xa ) is formed . Alternatively , both factors IX and X can be activated more directly by factor VIIa , generated via the extrinsic pathway . Activation of factors IX and X provides a link between the The final step , the common pathway , converts prothrombin II to thrombin ( IIa ) in the presence of activated V ( Va ) , activated X ( Xa ) , calcium , and phospholipid . The main purpose of thrombin ( IIa ) is the conversion of fibrinogen to fibrin , which is then polymerized into an insoluble gel . The fibrin polymer is then stabilized by the cross - linking of fibrin polymers by factor XIII . Clot lysis and vessel repair begin immediately after the formation of the definitive hemostatic plug . Three potential activators of the fibrinolytic system , Hageman factor fragments , urinary plasminogen activator , and tissue plasminogen activator , diffuse from endothelial cells and convert plasminogen , which had previously been adsorbed to the fibrin clot , into plasmin . Plasmin then degrades fibrin polymer into small fragments , which are cleared by the macrophages . 7 Indications / Applications aPTT is indicated for the following Unexplained bleeding or bruising Thrombotic episode or recurrent miscarriages To evaluate the effectiveness of drug therapy ( eg , unfractionated heparin therapy ) To assess the integrity of the intrinsic and final common pathways As part of a presurgical screen ( if the patient has a history of bleeding or easy bruising ) As part of an evaluation for lupus anticoagulant or anticardiolipin antibodies As part of coagulation panel workup Considerations Because factors II , IX , and X are vitamin K – dependent , biliary obstruction , which precludes gastrointestinal absorption of fat and fat - soluble vitamins ( including vitamin K ) , can reduce their concentrations and thus prolong the aPTT . aPTT is used to monitor heparin anticoagulant therapy ; however , it can not be used to monitor therapy with newer low - molecular - weight heparin . Prolonged aPTT is usually followed by mixing studies ( when the cause is not obvious , eg , due to heparin contamination or to other preanalytical problems such as an insufficient or clotted blood sample ) to evaluate for deficient coagulation factor ( s ) or a coagulation inhibitor ( s ) . In mixing studies , the patient ’ s plasma is mixed with normal plasma . If mixing the two plasma samples corrects the aPTT result , there is clotting factor deficiency , and specific coagulation factor testing is performed to determine which factor ( s ) is deficient . If the mixing fails to correct the aPTT results within 3 - 4 seconds , it strongly suggests ( 1 ) a coagulation factor inhibitor ( eg , an acquired factor VIII antibody ) or ( 2 ) an antiphospholipid antibody or lupus anticoagulant ( a nonspecific inhibitor ) . In Questions & Answers Overview What is the reference range of partial thromboplastin time ( PTT ) and activated partial thromboplastin time ( aPTT ) ? Which values on partial thromboplastin time ( PTT ) or activated partial thromboplastin time ( aPTT ) should prompt a clinical alert ? How should a prolonged activated partial thromboplastin time ( aPTT ) be interpreted ? How should a shortened activated partial thromboplastin time ( aPTT ) be interpreted ? Which factors may interfere with an activated partial thromboplastin time ( aPTT ) test ? How is a specimen prepared for a partial thromboplastin time ( PTT ) and an activated partial thromboplastin time ( aPTT ) ? What tests are related to a partial thromboplastin time ( PTT ) and an activated partial thromboplastin time ( aPTT ) ? What is partial thromboplastin time ( PTT ) and activated partial thromboplastin time ( aPTT ) ? When is an activated partial thromboplastin time ( aPTT ) test indicated ? What are considerations when using activated partial thromboplastin time ( aPTT ) to monitor anticoagulant therapy ? Sections Partial Thromboplastin Time , Activated Show All References
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[
"PTT",
"aPTT"
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http://emedicine.medscape.com/article/2086864-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Laboratory Medicine Beta2 - Microglobulin Updated : Sep 05 , 2014 Author : Mahasweta Gooptu , MBBS ; Chief Editor : Eric B Staros , MD more . . . Sections Reference Range Interpretation Collection and Panels Background Show All Media Gallery References Reference Range Serum and plasma beta 2 microglobulin values have emerged as markers for the activation of the cellular immune system , as well as a tumor marker in certain hematologic malignancies . Urine beta 2 microglobulin values indicate renal filtration disorders . Measurement of values in both serum and urine can help distinguish a problem of cellular activation from a renal disorder . 1 The reference range of beta microglobulin in urine samples is 0 - 0.3 µg / mL . In serum or plasma samples , the reference range is 0 - 3 µg / mL . It is recommended that each laboratory establish its own normal and pathological ranges of urine levels . 3 4 Interpretation Interpretation depends on the specific clinical indication and context . Low serum levels of beta microglobulin essentially indicate decreased disease activity in conditions for which beta microglobulin is used as a prognostic marker ( multiple myeloma , lymphoma , leukemia ) or the absence of such a disease process . However , low beta microglobulin levels are never used to rule out a particular disease ( eg , lymphoma ) in the absence of other more definitive tests . 5 1 Increased serum beta microglobulin levels reflect increased activity of the disease process in question and can be an exquisitely sensitive marker for this purpose in many hematologic disorders . The absolute value is less important than the historical values , except in certain situations such as multiple myeloma , in which a value of less than 4 µg / mL was found to correlate with increased survival . 5 Increased urine beta microglobulin levels reflect tubular disorders of the kidney . In such cases , serum beta microglobulin levels are usually normal , since the dysfunction is in tubular reabsorption . Increased CSF beta microglobulin levels are seen in certain conditions such as multiple sclerosis , AIDS dementia complex , and meningeal spread of hematologic tumors . 6 Collection and Panels Beta microglobulin can be determined in urine , serum , or plasma samples . It is not necessary to draw the sample in a fasting state , and no special preparations are necessary . Blood is collected by venipuncture in a red - top tube and centrifuged to separate serum from cells after clot formation . Samples may be stored refrigerated at 2 - 8 ° C for 5 days . For longer storage ( up to 6 months ) , samples should be stored frozen at - 20 ° C . To avoid repeated thawing and freezing , the samples should be aliquoted . Bilirubin and hemolysis do not significantly affect the procedure . However , gross lipemia can interfere with results . Beta microglobulin is a component of certain panels , such as chronic lymphocytic leukemia ( CLL ) , lymphoma , or multiple myeloma prognostic / monitoring panels . 3 Background Description One of the important functions of the human immune system is distinguishing self from nonself molecules . Most nucleated cells in the human body carry class I antigens that help the immune system identify self molecules . These antigens have a heavy chain and an associated light chain . This light - protein chain , which can be shed into serum , is called beta microglobulin . The molecule was discovered initially as a serum protein . 7 microglobulin is an 11.8 - kD protein ( see first image below ) , which forms one of the chains of the major histocompatibility complex ( MHC ) class I molecule normally present on the surface of every nucleated cell in the human body . The other 3 include alpha , alpha , and alpha ( see second image below ) . This protein further functions to present antigens to cytotoxic T lymphocytes that are carrying out surveillance for infection . 7 Crystal structure of beta2 microglobulin . View Media Gallery MHC macromolecular structure . View Media Gallery The synthesis rate of beta microglobulin varies from 2 - 4 mg / kg / day , with a half - life of 2.5 hours . Plasma concentrations vary from 1 - 3 µg / mL . Ninety percent of beta microglobulin is eliminated via glomerular filtration and almost completely reabsorbed by the proximal tubules . Thus , in individuals with chronic kidney disease , particularly end - stage renal disease , beta microglobulin can accumulate in the blood . In vitro , the synthesis and release of beta microglobulin can be induced by acidosis , endotoxin , or inflammatory cytokines . 8 Serum beta microglobulin has now been identified as an important prognostic marker in a large number of hematologic and nonhematologic disorders . Urine beta microglobulin levels are high in renal tubular disorders despite normal plasma levels , reflecting a dysfunction in reabsorption by the proximal tubules . Indications / Applications Serum and plasma beta microglobulin values have emerged as markers for the activation of the cellular immune system , as well as a tumor marker in certain hematologic malignancies . Urine beta microglobulin values indicate renal filtration disorders . Measurement of values in both serum and urine can help distinguish a problem of cellular activation from a renal disorder . Malignancies Significantly elevated levels of beta microglobulin can be found in lymphoproliferative disorders such as monoclonal gammopathies of immunoglobulin G ( IgG ) ( multiple myeloma ) , malignant lymphomas , and chronic lymphocytic leukemia 9 Values have been shown to correlate with prognosis . However , elevated beta microglobulin levels are not a specific finding and can not be used to establish a diagnosis . In Waldenström macroglobulinemia 10 beta microglobulin levels , upon diagnosis , influenced timing of treatment and survival . In multiple myeloma , serum values of less than 4 µg / mL were associated with significant increase in survival . Prospective analyses has now confirmed that , along with karyotype and second only to it , beta - 2 microglobulin is a prognostic marker for survival in myelodysplastic syndromes . 11 Renal diseases microglobulin accumulates in the serum of individuals with renal failure . Although decreased clearance appears to be the primary reason for elevation of beta microglobulin levels in persons with end - stage renal disease , it has been postulated that the uremic state may result in increased production of the molecule . In some such patients , it can deposit in joint spaces and cause synovitis . This phenomenon is termed dialysis - related amyloid ( DRA ) , or AB - amyloid . Secondary modifications of the molecule , such as glycation , limited proteolysis , and conformational changes , contribute to this phenomenon , which can also affect uremic predialysis patients . 12 13 14 15 Interestingly , while this phenomenon is not seen in renal transplant recipients , rejection of the allograft has been associated with high serum beta microglobulin levels . HIV In cases of HIV infection , increasing levels of beta microglobulin exhibited an inverse correlation to the CD4 + T - lymphocyte count and indicated disease progression . 16 However , it is not currently being used clinically for this purpose . Neurologic diseases Elevated CSF beta microglobulin levels have been shown to correlate with disease activity in multiple sclerosis , neuro - Behçet disease , sarcoidosis , AIDS dementia complex , and meningeal dissemination of malignant hematologic malignancies . 6 Rheumatologic disease Some authors believe that ankylosing spondylitis is partly caused by deposition of beta microglobulin within the joints , in a similar mechanism as dialysis - related amyloid arthropathy . These authors note that this may in part explain the strong association between the HLA - B27 allele ( with beta microglobulin as its product ) and this inflammatory arthritis . 17 However , beta microglobulin levels are normal in this condition . Considerations microglobulin is shed from the surface of nucleated cells into serum ; increased levels can be seen in a wide variety of disorders that involve increased cell turnover and / or activation of the immune system . Whereas this makes beta microglobulin a marker for myriad diseases , it also makes it a relatively nonspecific marker . This has led to its use as a quantitative prognostic marker much more than as a diagnostic marker . Indeed , there are virtually no conditions in which beta microglobulin can be used to make a diagnosis . Despite this limitation , beta microglobulin is often part of the initial panels for certain diseases ( multiple myeloma , Waldenström macroglobulinemia , myelodysplastic syndromes ) in which the baseline value of beta microglobulin affects staging , prognosis , and treatment . The value of increased beta microglobulin levels in CSF and urine are less clearly defined than in serum . The value of following levels as a marker of disease progression still needs to be established in prospective trials . Finally , the role of anti – beta microglobulin monoclonal antibodies as potential immunotherapy for certain leukemias is actively being investigated , although such therapies are strictly experimental at this time . 18 Sections Beta2 - Microglobulin Show All Media Gallery References
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[
"Beta2-Microglobulin",
"Laboratory Medicine",
"renal disorder"
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http://emedicine.medscape.com/article/2103764-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Laboratory Medicine Bacterial Wound Culture Updated : Apr 16 , 2014 Author : Lemuel R Non , MD ; Chief Editor : Eric B Staros , MD more . . . Sections Reference Range Interpretation Collection and Panels Background Show All References Reference Range Bacterial wound cultures , together with clinical examination , are used to determine the presence of infection in wounds . The reference range for a negative bacterial wound culture result depends on the method , as follows : 1 Qualitative wound culture : No growth of any pathogenic organism or growth of normal skin flora Semiquantitative wound culture : Less than 4 + growth Quantitative wound culture : Less than 100,000 organisms per gram ( if tissue specimen is used ) , per milliliter ( if fluid collection is used ) , or per swab ( if swab is used ) . 2 Interpretation Wound cultures commonly serve as an adjunct to clinical examination , and both should therefore be interpreted concurrently . Interpretation of a qualitative bacterial wound culture requires determination of whether the isolated organism is the cause of the infection or is a contaminant / part of normal skin flora . Quantification by semiquantitative and quantitative methods is used to further determine whether the isolated pathogen is a true infection by standard cutoff values for wound bacterial burden as outlined in Reference Range . In general , qualitative cultures are useful in identifying pathogenic bacteria . Organisms that are commonly part of normal skin flora and that are not usually pathogenic include the following : Staphylococcus epidermidis or other coagulase - negative staphylococci Corynebacterium species and other diphtheroids Brevibacterium species Propionibacterium acnes Pityrosporum species Alpha or gamma streptococci Neisseria species ( except Neisseria meningitidis or Neisseria gonorrhoeae Bacillus species ( except Bacillus cereus or Bacillus anthracis Growth of aforementioned organisms usually represents contamination , 1 3 4 except for coagulase - negative Staphylococcus species , which could represent either contamination or true infection . The most common pathogenic bacteria isolated in acute and chronic wound infections are as follows : 5 Staphylococcus aureus Pseudomonas aeruginosa Enterococci Beta - hemolytic streptococci Coliform bacteria , including Escherichia coli , Enterobacter species , and Klebsiella pneumoniae Coagulase - negative staphylococci Pigmented gram - negative anaerobes ( Prevotella and Porphyromonas species ) Nonpigmented gram - negative anaerobes ( primarily Bacteroides , Prevotella , and Fusobacterium species ) Peptostreptococcus Clostridium Quantitative cultures obtained via biopsy are considered the criterion standard among wound culture techniques . Growth of more than 100,000 or 10 5 organisms per gram of tissue or per milliliter of fluid aspirate is considered positive for wound infection . 6 For semiquantitative cultures , blood agar plates are streaked 3 times on one quadrant and then 3 times on each remaining quadrant using a sterile loop for each quadrant . This is thought to create dilutions of the original swab in each quadrant . Growth of more than 30 colonies in a quadrant is read as 4 + growth and is considered positive for infection . Semiquantitative cultures are considered to have good correlation with quantitative cultures for detection of wound sepsis , with a positive predictive value of 100 % and a negative predictive value of 93.7 % . 2 7 Collection and Panels The 3 most common methods of collecting specimen for wound culture include wound tissue biopsy , needle aspiration of fluid , and swab . Wound tissue biopsy Container : Sterile tube or container Normal volume : 0.005 - 0.2 g of involved tissue or 3 - 4 mm punch biopsy Procedure : A tissue biopsy is obtained aseptically via either a punch biopsy instrument or excision using a scalpel . Other accepted techniques include curettage of superficial devitalized tissue , most commonly used in diabetic foot ulcers , and a dermabrasion procedure for deep tissues without being too invasive . 7 For optimum recovery , the specimen should be sent to the laboratory within 60 minutes . Needle aspiration Container : Sterile tube or container Normal volume : 0.5 - 2 mL Procedure : This is the best procedure for wounds involving focal fluid collections or abscesses . The area should be prepared aseptically . Multiple aspirations around the wound are performed using a 22 - gauge needle attached to a 10 - mL syringe . The syringe containing the specimen may be capped or the specimen can be transferred onto a sterile container and sent to the laboratory within 60 minutes after collection . Swab Normal amount : 1 swab Procedure : Swabbing , which is probably the most common method of collecting specimen for culture , is usually performed on open wounds . Because surface organisms can easily contaminate wounds , it is essential to clean and irrigate the surface of the wound with saline until it is free of drainage , necrotic debris , eschar , or purulent material . The Z - stroke technique involves rotating a swab between the fingers as the swab is moved in a zigzag fashion across the wound . The wound edges should be avoided . The Levine technique involves rotating the swab over a 1 cm area with sufficient pressure to express fluid within the wound . As above , wound edges should be avoided . This technique is found to be superior to the Z - stroke technique for identifying infected wounds , largely because of the technique ’ s ability to express pus from the wound . 8 Background Description Bacterial wound cultures , together with clinical examination , are used to determine the presence of infection in wounds . Additionally , cultures are used to identify the specific organism or organisms and to guide specific antimicrobial therapy . Indications / Applications Bacterial wound culture is indicated for surgical and nonsurgical wounds , both acute and chronic , suspected of being infected . It is also indicated for hospital or local surveillance protocols to monitor drug - resistant microorganisms . 9 Considerations Tissue biopsy is considered the criterion standard in collecting wound culture specimens . Culture of viable but potentially infected tissue is preferred over necrotic tissue . Swab cultures may be unreliable because they usually indicate contamination . When appropriate , perform tissue biopsy or aspiration to collect specimens . Ideally , specimens should be collected before starting antibiotics . Clinical examination of the wound and how it is progressing should always carry more weight than culture results . Cultures are best used to confirm clinical impression of infecting pathogen ( s ) , to suggest an unanticipated pathogen if the wound is not improving , and to guide alternative antimicrobials ( via susceptibility testing ) , as indicated . Serial wound cultures to evaluate response to treatment is discouraged . Sections Bacterial Wound Culture Show All References
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[
"Bacterial Wound Culture",
"clinical examination",
"pathogenic organism"
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http://emedicine.medscape.com/article/212861-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Infectious Diseases Bacterial Overgrowth Syndrome Updated : Jul 31 , 2018 Author : Saqib Zaheer Syed , MBBS ; Chief Editor : Michael Stuart Bronze , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers References Background Bacterial overgrowth syndrome ( BOS ) is a term that describes clinical manifestations that occur when the normally low number of bacteria that inhabit the stomach , duodenum , jejunum , and proximal ileum significantly increases or becomes overtaken by other pathogens . The upper intestinal tract was once thought to be a sterile environment ; however , low concentrations of various bacteria are now widely accepted to live within or attached to its luminal surface . These bacteria are thought to be present from the time of birth and through adulthood , living in symbiosis with the human host . This relationship is thought to be vital for normal digestive processes , immunity , and intestinal development . Bacterial species usually present include lactobacilli , enterococci , oral streptococci , and other gram - positive aerobic or facultative anaerobes . Various etiological processes can disrupt mechanisms that keep the number of these bacteria low . These include structural abnormalities ( congenital or surgical ) and disorders that cause decreased gastric acidity , reduced peristaltic activity , and mucosal damage or atrophy . The clinical manifestations of bacterial overgrowth syndrome stem from the increased bacterial burden on the normal functions of the upper GI system . Prompt recognition and treatment of bacterial overgrowth syndrome should be targeted to prevent and reverse malabsorptive processes . Pathophysiology Normally , colony counts of gram - positive bacteria and fungi in the duodenum and jejunum are less than 1X10 5 organisms / mL . Anaerobic bacteria are not found in the jejunum in healthy people . As many as one third of jejunal aspirates may be sterile in healthy people . Aerobic and anaerobic bacterial colony counts in the ileum are usually less than 1 X 10 8 organisms / mL . This is in sharp contrast to the 1 X 10 11 organisms / mL that colonize the colon . Prevalence of bacteria in different parts of GI tract depends on several factors such as peristalsis , pH , redox potential , bacterial adhesion , bacterial cooperation and antagonism , mucin secretion , diet , and nutrient availability . 1 Studies of duodenal aspirates have not identified any particular bacteria as a cause of bacterial overgrowth syndrome . However , 1 X 10 11 organisms / mL of aspirate fluid is diagnostic for bacterial overgrowth syndrome . Cultures grown from patients with bacterial overgrowth syndrome reveal abnormally large numbers of anaerobic bacteria in addition to normal flora . Several protective factors stabilize the number and type of bacteria that colonize the upper GI tract . Abnormalities in these mechanisms predispose to bacterial overgrowth . Two coordinated motor phenomena produce the continuous propulsive peristaltic action of the upper GI tract . Both the migrating motor complex and the migrating action potential complex clear the upper intestine of unwanted bacteria and undigested substances . Desynchronization of these complexes results in diarrhea and weight loss in animal models . Anatomical defects can reduce peristaltic efficacy ; for example , blind pouches result in a stagnant portion of the intestine . Gastric acid and bile destroy many micro - organisms before they leave the stomach . Enzymatic activity of intestinal , pancreatic , and biliary secretions help destroy bacteria in the small intestine . 2 The bowel mucosal integrity and mucin layer protect the gut from bacteria . Immunoglobulin secretion and immune cells ( eg , macrophages and lymphocytes ) protect the gut from bacteria . Normal intestinal flora ( eg , Lactobacillus ) protects the gut from bacterial overgrowth by maintaining a low pH ; however , normal flora can facilitate an abnormal intraluminal environment . Abnormal communications produce pathways that allow enteric bacteria to pass between the proximal and distal bowel . Ileocecal valve prevents retrograde translocation of bacteria from colon to the small intestine . 2 Malabsorption of bile acids , fats , carbohydrates , proteins , and vitamins results in direct damage to the lining of the luminal surface by bacteria or by transformation of nutrients into toxic metabolites , leading to many of the symptoms of diarrhea and weight loss associated with bacterial overgrowth syndrome . This leads to decreased function of the enterocytes within the intestinal lining and subsequent malabsorption . Diarrhea is potentiated by unabsorbed food products stimulating secretory cells within the colon . Anaerobes such as Bacteroides fragilis actively deconjugate bile acids , thereby preventing proper bile acid function and enterohepatic circulation . Fatty acid absorption is reduced because deconjugated bile acids can not form micelles . Deconjugated bile acids directly inhibit carbohydrate transporters . These unabsorbed sugars ferment into organic acids , thereby reducing the intraluminal pH and producing osmotic diarrhea . The unconjugated bile acids also damage intestinal enterocytes and induce water secretion by the colonic mucosa . Loss of bile acids in the stool reduces the bile acid pool . Epidemiology Frequency United States The exact prevalence of bacterial overgrowth syndrome is likely underestimated because the clinical manifestations overlap with those of many other malabsorptive and diarrheal disorders . Higher clinical suspicion should be given to individuals with underlying disorders that disrupt the known protective elements that prevent bacterial overgrowth syndrome . For example , approximately 20 % - 43 % of chronic diarrhea cases in patients with diabetes , as well as 50 % in neonates , may be associated with bacterial overgrowth syndrome . 3 In many cases , gastric and upper intestinal tract surgery results in bacterial overgrowth syndrome ; however , preservation of the normal anatomy and antroduodenal vagal innervation appear to be protective . The prevalence of bacterial overgrowth syndrome varies depending on the population studied and the diagnostic methods used . In healthy people , BOS has been described in 0 - 12.5 % by the glucose breath test , 20 - 22 % by the lactulose breath test , and 0 - 35 % when the 14 C D - xylose breath test is used . 4 Bacterial overgrowth syndrome is more prevalent in elderly population because of diminished gastric acid secretion and consumption of a large number of medications that can cause hypomotility . BOS has also been described as a cause of occult malabsorption in elderly patients . 5 Mortality / Morbidity Bacterial overgrowth syndrome can lead to worsening symptoms of malabsorption and diarrhea . In certain patient subgroups , bacterial overgrowth syndrome can lead to significant morbidity or death . However , exact mortality rates directly linked to bacterial overgrowth syndrome are not readily available . Patient populations at an increased risk of mortality due to bacterial overgrowth syndrome include the following : Neonates and young infants who are already malnourished or have congenital GI abnormalities Elderly patients with multiple medical problems and those who have underlying chronic diarrhea without known bacterial overgrowth syndrome Patients who have undergone prior upper intestinal surgery that alters the protective mechanisms that prevent bacterial overgrowth syndrome Patients with poor nutritional status at presentation Patients with underlying medical conditions such as diabetes and scleroderma , who are at risk for relapse if the underlying medical condition is not corrected or managed Prognosis If bacterial overgrowth syndrome is the result of an underlying medical problem that can not be controlled , relapse will occur , with symptom - free periods . Patient Education Patients with chronic diarrhea should be educated on avoidance of food products that may exacerbate symptoms . Patients with bacterial overgrowth syndrome should document which foods cause their diarrhea , as this can vary among patients . Some examples of such foods are those high in carbohydrates such as fruits and fruit juices , spicy food , milk - containing products , fried food , and high - fat foods . Patients should also be educated on early detection of symptoms such as diarrhea to avoid malabsorption . In high - risk patients ( eg , neonates and elderly patients ) , early recognition is challenging . Education should be extended to the primary care givers in this situation . Clinical Presentation Sections Bacterial Overgrowth Syndrome Overview Presentation DDx Workup Treatment Medication Questions & Answers References
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[
"Bacterial Overgrowth Syndrome",
"clinical manifestations",
"duodenum"
] |
http://emedicine.medscape.com/article/2172160-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Protocols Oral Hypoglycemic Agents Updated : Aug 19 , 2015 Author : Abimbola Farinde , PharmD , PhD ; more . . . Sections Oral Antihyperglycemic Drugs References Oral Antihyperglycemic Drugs Oral antihyperglycemic agents lower glucose levels in the blood . They are commonly used in the treatment of diabetes mellitus 1 Biguanides Biguanides decrease hepatic glucose production , decrease gastrointestinal glucose absorption , and increase target cell insulin sensitivity Example : Metformin Contraindications : Metabolic acidosis with or without coma , abnormal creatinine clearance from any cause including diabetic ketoacidosis , shock , acute myocardial infarction , septicemia , renal disease ( serum creatinine level ≥ 1.5 mg / dL in males or ≥ 1.4 mg / dL in females ) , lactation , radiologic contrast study within 48 hours Sulfonylureas Sulfonylureas increase beta - cell insulin secretion , decrease hepatic glucose output , and increase insulin receptor sensitivity at peripheral target tissues Examples : Glyburide glipizide glimepiride tolazamide tolbutamide Contraindications : Sulfa allergy , type 1 diabetes , diabetic ketoacidosis , concomitant use with bosentan Thiazolidinediones Thiazolidinediones increase insulin receptor sensitivity and influence the production of gene products involved in lipid and glucose metabolism ; their mechanism of action depends on the presence of insulin for activity Examples : Pioglitazone rosiglitazone Contraindications : Hypersensitivity to product or components , established NYHA class III / IV heart failure Alpha - glucosidase inhibitors Inhibit the upper gastrointestinal enzymes that convert dietary starch and other complex carbohydrates into simple sugars , which can be absorbed Examples : Acarbose ( Precose ) & Miglitol ( Glycet ) Contraindications : Diabetic ketoacidosis ; cirrhosis ; inflammatory bowel disease , colonic ulceration , partial intestinal obstruction , Sections Oral Hypoglycemic Agents References
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[
"Oral Antihyperglycemic Drugs",
"diabetes mellitus",
"Metformin"
] |
http://emedicine.medscape.com/article/218059-medication
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Infectious Diseases Gonorrhea Medication Updated : Sep 07 , 2018 Author : Brian Wong , MD ; Chief Editor : Pranatharthi Haran Chandrasekar , MBBS , MD more . . . Sections Overview Presentation DDx Workup Treatment Guidelines Medication Questions & Answers Media Gallery References Medication Summary Rapid cure of gonorrhea is critical to curtail transmission . Because of emerging resistance that has resulted in limited choices for antibiotics , it is imperative to follow treatment guidelines to avoid further resistance and to obtain optimal treatment results . For more information , see CDC Sexually Transmitted Diseases Treatment Guidelines , 2015 Antibiotics , Other Class Summary Medical therapy requires dual antibiotic treatment with efficacy against N gonorrhoeae . Until several years ago , the treatment of choice involved oral medication for as long as 10 days or an injection ; however , patients tend to be poorly compliant with medications for various reasons , and the availability of newer medications has allowed in - office single - doses of ceftriaxone IM plus azithromycin PO treatment to ensure compliance . After obtaining specimens for diagnosis , many practitioners presumptively treat patients based on history and examination , because of the risk of poor follow - up , complications , and continuing disease spread to other partners . In addition , because gonorrhea is often simultaneously diagnosed with chlamydia many practitioners treat patients for both diseases when treating for either one beyond the newborn period . Disseminated or complicated infections ( eg , endocarditis , meningitis ) require more prolonged , inpatient therapy . For these cases , an infectious disease consultation is essential . N gonorrhoeae in the United States is not adequately susceptible to penicillins , fluoroquinolones , or erythromycin for these antimicrobials to be recommended . Ceftriaxone ( Rocephin ) View full drug information Ceftriaxone is part of the dual - drug regimen ( along with azithromycin ) for treating gonorrhea because of the attainment of high , sustained bactericidal levels in the blood . Ceftriaxone binds to penicillin - binding proteins , inhibiting bacterial cell wall growth . Azithromycin ( Zithromax , Zmax ) View full drug information Azithromycin inhibits bacterial growth , possibly by blocking the dissociation of peptidyl transfer ribonucleic acid ( tRNA ) from ribosomes , causing RNA - dependent protein synthesis to arrest . It is part of the first - line preferred dual - drug regimen for gonococcal infections plus ceftriaxone IM . Cefixime ( Suprax ) Cefixime , a cephalosporin , inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin - binding proteins . It is not used first - line and it is an alternant therapy for uncomplicated gonorrhea if ceftriaxone is unavailable . For this situation , patients can be given a single oral dose of cefixime 400 mg plus a single dose of azithromycin 1 g PO . Doxycycline ( Vibramycin , Doxy ) Doxycycline inhibits protein synthesis and , thus , bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria . Doxycycline 100 mg PO BID for 10 - 14 days may be used in addition to a single dose of ceftriaxone 250 mg IM for gonococcal epididymitis or pelvic inflammatory disease . Erythromycin ophthalmic ( Ilotycin Ophthalmic ) Erythromycin is the only antibiotic ophthalmic ointment recommended for use in neonates for prophylaxis of gonococcal ophthalmia neonatorum . Silver nitrate and tetracycline ophthalmic ointments are no longer manufactured in the United States , bacitracin is not effective , and povidone iodine has not been studied adequately . Gentamicin ophthalmic ointment has been associated with severe ocular reactions in neonates and should not be used for ocular prophylaxis . Questions Sections Gonorrhea Overview Presentation DDx Workup Treatment Guidelines Medication Questions & Answers Media Gallery References
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[
"Gonorrhea",
"Medication",
"curtail transmission"
] |
http://emedicine.medscape.com/article/225243-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Infectious Diseases Bacterial Pharyngitis Treatment & Management Updated : Feb 08 , 2019 Author : Joseph Adrian L Buensalido , MD ; Chief Editor : Michael Stuart Bronze , MD more . . . Sections Overview Presentation DDx Workup Treatment Approach Considerations Medical Care Surgical Care Consultations Diet Activity Prevention Further Inpatient Care Show All Medication Questions & Answers Media Gallery Tables References Approach Considerations The following are the treatment goals for tonsillopharyngitis : 46 Symptom relief Complication avoidance Decreasing the number of disease - related school or work absences Management expense reduction Quality of life improvement Conservative treatment is first - line , while surgical management should be performed only if a patient meets recommended indications ( see below ) . 46 Next : Medical Care What to Read Next on Medscape Related Conditions and Diseases Otolaryngologic Manifestations of Wegener Granulomatosis Prophylactic Antibiotic Use in Head and Neck Surgery Hyperparathyroidism in Otolaryngology and Facial Plastic Surgery Allergic Rhinitis in Otolaryngology and Facial Plastic Surgery Pierre Robin Syndrome Fast Five Quiz : Do You Know Best Practices for Antibiotic Use in Respiratory Tract Infections ? News & Perspective CT , MRI Do n ' t Change Therapy in Children With Hearing Loss Diagnostic Error in Patients With Ear , Nose , or Throat Symptoms Volunteer Doctors Struggle to Provide Care on the Border Tools Drug Interaction Checker Pill Identifier Calculators Formulary Slideshow All About Allergies : Be Ready for Spring Most Popular Articles According to Family Medicine Physicians Drinking Tea : Are the Health Benefits Real ? Kale Is a Surprise on 2019 ' s ' Dirty Dozen ' List The Loneliness of Being a Physician Heavy Metals Found in Popular Fruit Juices Duke Settles Doctored Data Lawsuit for $ 112.5 Million View More Sections Bacterial Pharyngitis Overview Presentation DDx Workup Treatment Medical Care Surgical Care Consultations Diet Activity Prevention Further Inpatient Care Show All Medication Questions & Answers Media Gallery Tables References
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[
"Pharyngitis Treatment",
"Antibiotic therapy",
"Amoxicillin"
] |
http://emedicine.medscape.com/article/238064-clinical
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Nephrology Acute Tubular Necrosis Clinical Presentation Updated : Dec 19 , 2018 Author : Nikhil A Shah , MBBS , DNB ( Neph ) ; Chief Editor : Vecihi Batuman , MD , FASN more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery Tables References History The patient ’ s history is very important in the diagnosis of acute tubular necrosis ( ATN ) , as it can establish the risk factors for the development of ATN . A careful historical timeline of events leading to acute kidney injury ( AKI ) can frequently identify the underlying cause . The history commonly reveals recent surgery , hypotension , sepsis , muscle necrosis , or volume depletion , as well as exposure to nephrotoxic agents . Several of those may be present simultaneously , which increases the risk and severity of ATN . In addition , pre - existing medical conditions or medication use ( eg , diabetes mellitus , multiple myeloma , nonsteroidal anti - inflammatory drugs ) may contribute to the worsening of renal function . Hence , a thorough medical and medication history can also be key to the diagnosis . Physical Examination Physical examination findings are often unremarkable and acute kidney injury ( AKI ) is incidentally detected on routine laboratory studies ( ie , elevated blood urea nitrogen [ BUN ] and creatinine levels ) . Findings may suggest hypovolemia ( eg , low jugular venous pressure , loss of skin turgor , orthostatic hypotension , dry mucous membranes , tachycardia ) as a cause . Abdominal distension may raise the concern of intra - abdominal hypertension and compartment syndrome as a potential cause of ATN . Muscle tenderness could potentially be due to rhabdomyolysis , which can lead to ATN . Differential Diagnoses Sections Acute Tubular Necrosis Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery Tables References
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[
"Acute Tubular Necrosis",
"acute kidney injury",
"Nephrology"
] |
http://emedicine.medscape.com/article/242008-clinical
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Nephrology Hypokalemia Clinical Presentation Updated : Dec 06 , 2018 Author : Eleanor Lederer , MD , FASN ; Chief Editor : Vecihi Batuman , MD , FASN more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers References History The symptoms of hypokalemia are nonspecific and predominantly are related to muscular or cardiac function . Weakness and fatigue are the most common complaints . The muscular weakness that occurs with hypokalemia can manifest in protean ways ( eg , dyspnea , constipation or abdominal distention , exercise intolerance ) . Rarely , muscle weakness progresses to frank paralysis . With severe hypokalemia or total body potassium deficits , muscle cramps and pain can occur with rhabdomyolysis . Occasionally , a patient may complain of worsening diabetes control or polyuria due to a recent onset of hyperglycemia or nephrogenic diabetes insipidus . Patients also may complain of palpitations . Psychological symptoms may include psychosis , delirium , hallucinations , and depression . 52 Patients are often asymptomatic , particularly with mild hypokalemia . Symptoms that are present are often from the underlying cause of the hypokalemia rather than the hypokalemia itself . When the diagnosis of hypokalemia is discovered , investigate potential pathophysiologic mechanisms . Poor intake may result from the following : Eating disorders Dental problems Poverty Increased excretion may be due to the following : Medications ( eg , diuretics , antiretroviral agents , antibiotics ; see Etiology Polyuria Vomiting or diarrhea Shift of potassium into the intracellular space may occur due to the following : Recurrent episodes of paralysis Use of high doses of insulin High - dose beta - agonist therapy ( eg , for chronic obstructive pulmonary disease ) Ask whether the patient has had similar episodes in the past . Familial historical data may include surgery for pituitary or adrenal tumors or acute intermittent episodes of paralysis , with or without association with hyperthyroidism . Physical Examination Physical examination findings are often within the reference range . Vital signs generally are normal , except for occasional tachycardia with irregular beats or tachypnea resulting from respiratory muscle weakness . Hypertension may be a clue to primary hyperaldosteronism , renal artery stenosis , licorice ingestion , or the more unusual forms of genetically transmitted hypertensive syndromes , such as congenital adrenal hyperplasia , glucocorticoid - remediable hypertension , or Liddle syndrome . Relative hypotension should suggest occult laxative use , diuretic use , bulimia , or one of the unusual tubular disorders , such as Bartter syndrome or Gitelman syndrome . Bear in mind that occult diuretic use is far more common than either of those congenital tubular disorders and is , in fact , also called " pseudo - Bartter syndrome . " Muscle weakness and flaccid paralysis may be present . Patients may have depressed or absent deep - tendon reflexes . Hypoactive bowel sounds may suggest hypokalemic gastric hypomotility or ileus . Severe hypokalemia may manifest as bradycardia with cardiovascular collapse . Cardiac arrhythmias and acute respiratory failure from muscle paralysis are life - threatening complications that require immediate diagnosis . Tooth erosion may be present in patients with bulimia . This finding has particular significance in patients whose history indicates high risk ( eg , obsession with body image or participation in activities such as cheerleading , wrestling , or modeling ) . Differential Diagnoses Sections Hypokalemia Overview Presentation DDx Workup Treatment Medication Questions & Answers References
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[
"hypokalemia",
"cardiac"
] |
http://emedicine.medscape.com/article/245296-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Nephrology Uremia Updated : Jan 17 , 2019 Author : A Brent Alper , Jr , MD , MPH ; Chief Editor : Vecihi Batuman , MD , FASN more . . . Sections Overview Background Pathophysiology Etiology Epidemiology Prognosis Show All Presentation DDx Workup Treatment Medication Questions & Answers References Background Uremia is a clinical syndrome marked by elevated concentrations of urea in the blood and associated with fluid , electrolyte , and hormone imbalances and metabolic abnormalities , which develop in parallel with deterioration of renal function . 1 The term uremia , which literally means urine in the blood , was first used by Piorry to describe the clinical condition associated with renal failure . 2 ( See Pathophysiology . ) Uremia more commonly develops with chronic kidney disease ( CKD ) , especially the later stages of CKD , but it also may occur with acute kidney injury ( AKI ) if loss of renal function is rapid . Urea itself has both direct and indirect toxic effects on a range of tissues . 3 A number of substances with toxic effects , such as parathyroid hormone ( PTH ) , beta2 microglobulin , polyamines , advanced glycosylation end products , and other middle molecules , are thought to contribute to the clinical syndrome . 4 ( See and Workup . ) Complications Severe complications of untreated uremia include seizure , coma , cardiac arrest , and death . Spontaneous bleeding can occur with severe uremia and may include gastrointestinal ( GI ) bleeding , spontaneous subdural hematomas , increased bleeding from any underlying disorder , or bleeding associated with trauma . Cardiac arrest may occur from severe underlying electrolyte abnormalities , such as hyperkalemia metabolic acidosis , or hypocalcemia . ( See Prognosis Presentation , and Workup . Severe hypoglycemic reactions may occur in patients with diabetes if hyperglycemic medications are not adjusted for decreased creatinine clearance in these individuals . Renal failure associated bone disease ( renal osteodystrophy ) may lead to an increased risk of osteoporosis or bone fracture with trauma . Medication clearance is decreased in persons with renal failure and may lead to untoward adverse effects , such as a digoxin overdose , an increased sensitivity to narcotics , and a decreased excretion of normal medications . Patient education Patients should be seen by a nephrologist early for education regarding renal disease and renal replacement therapy options and for evaluation and diagnosis of their underlying renal disease process . ( See Treatment Inform patients with diabetes about potential changes in insulin or oral hypoglycemic medication needs . Educate patients and their families about dialysis to avoid the shock of emergent dialysis and the decreased quality of life that can occur with uremia . For patient education information , see Chronic Kidney Disease Next : Pathophysiology Sections Uremia Overview Etiology Epidemiology Show All DDx Medication Questions & Answers References
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[
"Uremia",
"Nephrology"
] |
http://emedicine.medscape.com/article/264966-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Obstetrics & Gynecology Benign Cervical Lesions Updated : Oct 08 , 2018 Author : Khanh - Ha D Nguyen , MD , MPH ; Chief Editor : Michel E Rivlin , MD more . . . Sections Embryology Anatomy Physiology Congenital Anomalies Inflammatory Diseases Benign Tumors Cervical Pregnancy Show All Tables References Embryology By 5 weeks ' gestational age , the wolffian ( ie , mesonephric ) and the müllerian ( ie , paramesonephric ) ducts have formed from intermediate mesoderm . In the absence of testosterone and müllerian inhibitory substance , the mesonephric ducts regress and the paramesonephric ducts continue to form the female reproductive structures with fusion of the distal portions of the paramesonephric ducts to give rise to the uterine fundus , the cervix , and the upper vagina . These developmental changes are genetically controlled in large part by a series of complex transcriptional signaling pathways including Wnt signaling Hox genes , and many others . In a female fetus , the wolffian duct disappears except for nonfunctional vestiges . The müllerian duct is lined by a columnar epithelium . This includes the entire cervix and upper vagina to the vaginal plate ( ie , sinovaginal bulb ) . Through a process of squamous metaplasia , the vagina and a variable portion of the ectocervix become covered with squamous epithelium . This process is complete by the fifth month of pregnancy . Anatomy The cervix ( Latin for neck ) is the inferior part of the uterus protruding into the vagina . Gross anatomy The cervix measures 2.5 - 3 cm in diameter and 3 - 5 cm in length . The normal anatomic position of the cervix is angulated slightly downward and backward . Inferiorly , the cervix projects into the vagina as the portio vaginalis with the opening of the cervical canal into the vagina called the external cervical os ( Latin for mouth ) . The external os is usually small and round in nulliparous women but can be seen as a transverse slit in those who have had cervical dilation during labor . The anterior and posterior fornices delimit the The lymphatic drainage of the cervix is first to the parametrial nodes , then to the obturator , internal iliac , and external iliac nodes . Secondary drainage is to the presacral , common iliac , and para - aortic lymph nodes . The innervation of the cervix is from the Frankenhãuser plexus , a terminal part of the presacral plexus . The nerves enter the lower uterine segment and upper cervix on either side and form 2 lateral semicircular plexuses . The major blood supply is from the descending branch of the uterine artery . Also contributing is the cervical branch of the vaginal artery . The venous return mirrors the arterial blood supply . Microscopic anatomy Microscopically , the cervical stroma is composed of an admixture of fibrous , muscular ( 15 % ) , and elastic tissue . The epithelium is squamous on the ectocervix and columnar in the endocervix . The exposed ( ie , vaginal ) portion of the cervix is lined by nonkeratinizing stratified squamous epithelium that becomes continuous with the vaginal epithelium . This is referred to as the native portio epithelium and is replaced every 4 - 5 days while glycogen stores respond to hormonal changes in estrogen and progesterone . In postmenopausal women , the squamous epithelium is atrophic The mucosa of the cervical canal ( endocervix ) is composed of a single layer of mucin - secreting columnar epithelium , which covers the surface and the underlying glandular crypts . Isolated neuroendocrine epithelial cells of argentaffin type or argyrophil type are admixed with the normal endocervical cells . Under normal conditions , mitotic figures are rarely identified in endocervical epithelium . True lymphoid follicles , with or without germinal centers , are encountered in the stroma of both the ectocervix and endocervix . During pregnancy , a marked increase occurs in the vascularity and edema within the cervical 1 Squamocolumnar junction The squamocolumnar junction is the border between the squamous epithelium of the ectocervix and the columnar epithelium of the endocervix . Just distal to the squamocolumnar junction , an area of immature squamous metaplastic epithelium is present . Trauma , chronic irritation , and cervical infections play a role in the development and maturation of the squamous epithelium of the cervix . Immature squamous metaplasia shares biochemical and immunohistochemical features of both mature squamous epithelium and columnar mucinous epithelium . The transformation zone The transformation zone is a dynamic area , usually located on the ectocervix . At times , the distal edge of the transformation zone extends into the upper vagina . The transformation zone , by definition , is the area between the original squamocolumnar junction and the current squamocolumnar junction . The transformation zone is that portion of the cervix that originally was columnar epithelium and through a process of squamous metaplasia is now squamous epithelium . Squamous metaplasia occurs continuously ; however , this process is most active during fetal development , around the time of menarche , and In newborns and young females , the endocervical tissue tends to roll out from the cervical os ; this is called cervical eversion ( ie , ectropion ) , and corresponds to the original squamocolumnar junction . In a normal transformation zone , one can find remnants of gland openings and nabothian cysts . In postmenopausal women , the squamocolumnar junction frequently is located within the cervical canal . In this position , it is not visualized through speculum examination or colposcopy , even when using an endocervical speculum . Colposcopy , or microscopically guided visualization of the cervix , Physiology Cervical mucus responds to hormonal stimulation . Under the influence of estrogen , the cervical mucus is profuse , watery , and alkaline . The rich concentration of sodium chloride and potassium are responsible for ferning . The degree of ferning reflects estrogen levels . 2 After ovulation and under influence of progesterone , the cervical mucus is thick , scant , and acidic and contains numerous leukocytes . In pregnancy , the cervical mucus is even thicker and more tenacious . It is rich in leukocytes and forms a mucous plug that obliterates the cervical canal . 3 During pregnancy , during the postpartum state , and in women who are on progestin therapy , microglandular hyperplasia may occur . This is discussed in detail later ( see Microglandular hyperplasia in the Benign Tumors section ) . Decidual changes within the cervical stroma can also occur during pregnancy and high - dose progestin therapy . Congenital Anomalies Congenital anomalies involving the cervix reflect only the lower part of the spectrum of congenital anomalies involving the müllerian system . The cervix has 3 types of anomalies : fusion abnormalities , congenital absence , and changes due to in utero exposure to diethylstilbestrol ( DES ) and other nonsteroidal estrogens . Müllerian congenital abnormalities are frequently associated with urinary tract anomalies because of associated mesometanephric duct developmental defects . 4 5 Fusion anomalies A failure to fuse or incomplete fusion of the müllerian ducts results in duplication of the vagina , cervix , or uterus . Failure of fusion of the distal müllerian duct can result in any of the anomalies discussed below . Uterus didelphys results from a complete lack of fusion of the müllerian ducts . Duplication of the vagina , cervix , and / or uterus occurs . A longitudinal vaginal septum is present , with 2 separate cervices and 2 separate endometrial cavities . With septate cervix , the appearance is that of 1 cervix with 2 separate cervical openings . The septum may be partial . The gross appearance is 1 of 2 separate cervices but 1 endometrial cavity . On the other hand , the septum may extend through the entire length of the uterus , with 2 separate endometrial cavities . Depending on the shape of the uterine fundus , the anomaly is either a septate uterus or an arcuate uterus . Laparoscopy is necessary to distinguish between these 2 anatomic variations . Congenital absence or hypoplasia of the cervix Congenital absence of the cervix usually occurs as part of the syndrome of müllerian agenesis , also known as Mayer - Rokitansky - Kuster - Hauser syndrome . This syndrome occurs in approximately 1 per 4000 female births . Women with müllerian agenesis typically have a blind vagina and normal ovaries . Approximately one third of patients have urinary tract anomalies , and 12 % have skeletal anomalies , usually involving the spine . Imaging of these structures should be part of the evaluation . 6 In women with partial müllerian agenesis , a uterine bud or fundus may be present without a cervix and proximal vagina . If endometrium is present in this uterine bud , hematometra occurs at puberty , producing cyclic abdominal pain . Obstructive conditions from absent or hypoplastic cervices may occur and require surgical intervention if hematometra or pyometra occurs . Vaginal patency has been surgically created in a few patients , and pregnancy has been reported in absence or atresia of the cervix via transmyometrial or transtubal embryo transfer . 7 In utero exposure to diethylstilbestrol and other nonsteroidal estrogens The use of diethylstilbestrol or DES , which initially was prescribed for thousands of women to prevent miscarriage , was discontinued in the 1970s when epidemiologic association of in utero exposure to DES with clear cell vaginal adenocarcinoma in the developing fetus ( 1 case in 1000 - 2000 exposed female fetuses ) was discovered . Changes associated with in utero exposure to DES and other nonsteroidal estrogens are less commonly encountered currently . However , unique anomalies of the müllerian system are present in women exposed to DES . The classic anomaly is a hypoplastic T - shaped uterus , referring to the T shape of the endometrial cavity . Defects limited to the cervix , in addition to hypoplastic cervix , include local interesting gross and colposcopic findings . These findings include the so - called cockscomb cervix , cervical rings , cervical collars , and cervical hoods . The cockscomb cervix refers to the abnormal stromal development causing the epithelium to be thrown into firm transverse ridges in the anterior vaginal fornix , including the upper ectocervix . Vaginal adenosis and other benign lesions are more prevalent Cervical insufficiency in pregnancy with recurrent loss and / or infertility are potential problems in females exposed to DES . 8 Inflammatory Diseases Prevalence and Tissue Response Inflammation of the cervix is extremely common . Chronic inflammation is present in the cervix of almost every sexually active woman . On a microscopic level , regardless of the etiology , the tissue response of the cervix is limited to inflammation and repair . 9 For a more complete review of infectious and noninfectious cervicitis , see Medscape Reference article Cervicitis Infectious Cervicitis Susceptibility of the cervix to bacterial infection depends on the virulence of the organism , the epithelial integrity , and the vaginal pH . Infections of the endocervical canal include infection with Neisseria gonorrhoeae and Chlamydia trachomatis . Organisms infecting the portio of the cervix can produce either exophytic or ulcerative lesions . These include human papilloma virus ( HPV ) , herpes simplex virus ( HSV ) , Treponema pallidum , Haemophilus ducreyi , and donovanosis . Infections of the endocervical canal ( mucopurulent cervicitis ) Infection with C trachomatis or N gonorrhoeae requires no predisposing factor and primarily depends on the size of the inoculum . Mucopurulent secretions have been reported in more than 60 % of women with cervical chlamydial infections . However , mucopurulent discharge is present in 12 % of women with no cervical pathology . Yellow mucopurulent discharge collected from the endocervix and visualized on a white cotton - tipped applicator may also correlate with chlamydia , gonorrhea , trichomonads or HSV infections . In published studies , the sensitivity , specificity , and positive predictive values from clinical evaluation of the discharge have been quite variable . Thus , the color and consistency of the discharge alone is not enough to 10 Because mucopurulent cervicitis may be a sign of upper genital tract disease , women presenting with mucopurulent cervicitis should be tested for gonorrhea and chlamydia with the most sensitive and specific test available . 11 12 They should also be evaluated for bacterial vaginosis and trichomoniasis . HSV should be selectively tested for if there is clinical suspicion and identifiable lesions . Gram stain findings of gram - negative intracellular diplococci within the cytoplasm of neutrophils are highly specific for gonorrhea but can be identified in only 50 - 60 % of women with gonococcal infections . On occasion , cervical cytology identifies inclusion - containing vacuoles in endocervical or metaplastic cells . The presence of these inclusions correlates well with C trachomatis infection . Nucleic Acid Amplification Tests ( NAATs ) are currently the most sensitive tests available for both chlamydia and gonorrhea . In women , they are collected from the first catch urine samples or from self or clinician collected vaginal swabs . 13 The best guide to therapy for endocervicitis is identification of the specific microbiologic agent . The current United States Preventative Services Task Force ( USPSTF ) chlamydia screening guidelines for women are as follows : 14 Screen for chlamydia infection in all sexually active nonpregnant women age 24 and younger and in older nonpregnant women who are at increased risk . Screen all pregnant women age 24 and younger and older pregnant women who are at increased risk . Do not routinely screen women age 25 and older , regardless of pregnancy status , if they are not at increased risk . Treatment for mucopurulent cervicitis after identifying the causative organism is outlined in Table 1 . The US Centers for Disease Control and Prevention do not recommend a test of cure in uncomplicated gonorrheal or chlamydial infection when treated with any of the outlined regimens , unless symptoms persist . Pregnant women should not be treated with quinolones or tetracyclines . 15 In April 2007 , the Centers for Disease Control and Prevention ( CDC ) updated treatment guidelines for gonococcal infection and associated conditions . Fluoroquinolone antibiotics are no longer recommended to treat gonorrhea in the United States 16 . The recommendation was based on analysis of new data from the CDC ’ s Gonococcal Isolate Surveillance Project ( GISP ) . The data from GISP showed the proportion of fluoroquinolone - resistant gonorrhea ( QRNG ) cases in heterosexual men reached 6.7 % , an 11 - fold increase from 0.6 % in 2001 . The data were published in the April 13 , 2007 issue of the Morbidity and Mortality Weekly Report . This limits treatment of gonorrhea to drugs in the cephalosporin class ( eg , ceftriaxone 125 mg IM once as a single dose ) . Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented . For more information , see the CDC ’ s Antibiotic - Resistant Gonorrhea Web site ; CDC Updated Gonococcal treatment recommendations ( April 2007 ) ; or Medscape Medical News on CDC Issues New Treatment Recommendations for Gonorrhea Table 1 . Treatment for Mucopurulent Cervicitis ( Open Table in a new window ) Diagnosis Primary Treatment Alternative Treatment C trachomatis Azithromycin 1 g PO or Doxycycline 100 mg PO bid for 7 d Erythromycin base 500 mg PO qid for 7 d or Erythromycin ethylsuccinate 800 mg PO qid for 7 d N gonorrhoeae Cefixime 400 mg PO Ceftriaxone 125 mg IM Azithromycin 1 g PO Doxycycline 100 mg PO bid for 7 d Spectinomycin 2 g IM Ceftizoxime 500 mg IM Cefotaxime 500 mg IM Cefotetan 1 g IM Cefoxitin 2 g + probenecid 1 g PO HSV Acyclovir 400 mg PO tid for 7 - 10 d Acyclovir 200 mg PO 5 times / d for 7 - 10 d Famciclovir 250 mg PO tid for 7 - 10 d Valacyclovir 1 g PO bid for 7 - 10 d T vaginalis Metronidazole 2 g PO Metronidazole 500 mg bid for 7 d Infections involving the portio of the cervix See the list below : Human papilloma virus ( HPV ) Currently , more than 100 serotypes of HPV are described and more than 40 serotypes infect mucosal surfaces . The typical exophytic warts that present on the vulva , vagina , and cervix are type 6 or type 11 . Types 16 , 18 , 31 , 33 , and 35 are more commonly associated with flat warts and have an epidemiologic link to cervical intraepithelial neoplasia or CIN 17 18 . Kits are available that classify HPV lesions as either benign ( ie , 6 or 11 ) or at risk ( ie , 16 , 18 , 31 , 33 , and 35 ) . Currently , for reflex HPV testing of thin layer cervical cytology , 14 different oncogenic HPV types are tested : 16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , 59 , 66 , and 68 . Co - infections with multiple serotypes occur in 5 - 20 % of those infected 19 Approximately 15 % of Americans , or 20 million people , are currently infected with HPV ; half of these are sexually active adolescents and young adults aged 15 - 24 years . 19 HPV can infect the ectocervix and can cause warty lesions similar to those seen in the vagina or on the vulva . However , the lesions on the cervix typically are flat , macular or papular lesions that become more visible to the naked eye when swabbed with 3 - 5 % acetic acid . The acetic acid causes cellular dehydration . The resulting increase in nuclear density appears clinically as a transient white lesion . The term aceto - white describes this finding . In addition to HPV , squamous metaplasia and cervical intraepithelial neoplasia can also appear aceto - white . HPV lesions tend to have indistinct and feathered borders , and the lesions may appear broken or flocculated . Unlike CIN , satellite lesions may be present , and HPV lesions may be within or outside the transformation zone on the portio of the cervix . Another appearance of HPV may be snow - white , shiny , and raised lesions . Frequently , fine - caliber blood vessels are present . The appearance of HPV lesions are described by the Reid ' s colposcopic index , which assesses margin , color , vascular patterns , and iodine uptake . Lesions suggestive of HPV should be confirmed by performing a biopsy . The hallmark histologic feature is the koilocyte . On both cytologic preparations of cervical biopsy specimens , koilocytes are cells with wrinkled nuclear membranes ( like raisins ) that are frequently binucleate and occasionally multinucleate . The nuclei are surrounded by a clear halo , which gives the cells their name . Cytologic and nuclear atypia is typically present . In cervical biopsy specimens , a few normal mitotic figures may be seen in the basal layer of the squamous epithelium , while koilocytes occupy the intermediate and 20 The prevalence of high - risk HPV in abnormal vaginal smear findings parallels that of cervical smear findings , with equivalent degrees of abnormality . 21 Women with abnormal vaginal smear findings may benefit from reflex high - risk HPV testing . Three vaccines for the prevention of HPV - related cervical , vaginal , and vulvar cancer and warts have been approved by the FDA . 22 23 Gardasil is a quadrivalent HPV recombinant vaccine containing activity against HPV types 6 , 11 , 16 , and 18 . 24 The vaccine is indicated for prevention of HPV - associated dysplasias and neoplasias , including cervical cancer , genital warts ( condyloma acuminata ) , and precancerous genital lesions ( eg , cervical adenocarcinoma in situ ; cervical intraepithelial neoplasia grades 1 , 2 , and 3 ; vulvar intraepithelial neoplasia grades 2 and 3 ; vaginal intraepithelial neoplasia grades 2 and 3 ) . The immunization series should be administered to girls and young women aged 9 - 26 years . It is administered as a series of 3 doses , typically at 0 , 2 , and 6 11 In October 2009 , the Gardasil vaccine received FDA approval for the prevention of genital warts in men and boys . 25 Cervarix is the second HPV vaccine and is also a recombinant formulation . This vaccine is designed to create immunity against the L1 protein of HPV subtypes 16 and 18 , which cause 70 % of cervical cancer . It received FDA approval in September 2009 . 26 In 2014 , the FDA approved Gardasil 9 , a nonavalent HPV vaccine that contains HPV types 6 , 11 , 16 , 18 , 31 , 33 , 45 , 52 , and 58 . It is indicated in females aged 9 - 45 years for the prevention of cervical , vulvar , vaginal , and anal cancer . Additionally , it is indicated to prevent genital warts and precancerous or dysplastic lesions caused by HPV . It is also indicated in males aged 9 - 45 years to prevent genital warts ( condyloma acuminata ) caused by HPV 27 28 Most parents accept HPV vaccination of their daughters , but at this time they also want more information . 29 The Advisory Committee on Immunizations Practices recommends that the HPV vaccination be administered to girls at the age of 11 or 12 years . While most practitioners do not care for patients that young , catch - up vaccinations are recommended for females aged 13 - 26 years . HPV vaccines are most effective if given prior to exposure to HPV , but sexually active females can benefit from the vaccination . Healthcare providers are encouraged to discuss the benefits and limitations of the vaccine and the need for routine cervical cytology examinations in patients older than 21 years . 23 Herpes simplex virus ( HSV ) Both serotypes of HSV ( HSV - 1 and HSV - 2 ) can cause genital tract lesions . Of women with their first episode of HSV - 2 infection , 70 - 90 % have herpetic cervicitis as part of the manifestation . In recurrent infections , cervicitis is present in 15 - 20 % of women . Primary herpetic cervicitis frequently is asymptomatic ; however , it may present as a purulent or bloody vaginal discharge . Grossly , the cervix may appear diffusely red and friable . At times , ulcerations , which may be extensive , are present on the ectocervix . Making a clinical diagnosis may be difficult . Colposcopic findings of acute cervicitis are identifiable in two thirds of women with primary herpes cervicitis . Multinucleate cells with typical ground - glass inclusions may be identified on cervical cytology results in 60 % of these women . The differential diagnosis includes the chancre of syphilis . Gonorrhea and chlamydia infection can cause a similar type of discharge , although ulceration in these conditions is uncommon . Syphilis , gonorrhea , and chlamydia infection may coexist with HSV - 2 infection . Women with primary genital herpes involving the cervix should be started on antiviral therapy . Treatment with Acyclovir , Famvir , or Valacyclovir is appropriate . The other presentation of herpes involving the cervix is asymptomatic shedding . In these instances , the classic multinucleate cells with ground - glass inclusions may be identified on cervical cytology results as an incidental finding . In a sexually transmitted disease clinic , HSV was isolated from 4 % of randomly selected women . Treatment for asymptomatic shedding in the non - pregnant patient is not recommended . Recommendations regarding the specific treatment and management of HSV in pregnancy can be found at the American College of Obstetricians and Gynecologists ( ACOG ) Practice Bulletin 82 30 Treponema pallidum Treponema pallidum is a spirochete that causes syphilis . The primary lesion of syphilis develops at the site of inoculation 2 - 6 weeks after infection . The primary lesion begins as a papule and then ulcerates . Typically , the diameter is 0.5 - 1.5 cm . 31 In women , besides the labia and posterior fourchette , the cervix is a common site for the primary chancre . Because the primary lesion is asymptomatic and the cervix is not visualized readily , primary lesions in this location frequently remain undiagnosed . If untreated , they heal in 3 - 6 weeks and the disease then enters the latent period . 32 The differential diagnosis of these ulcers includes HSV - 2 and Hemophilus ducreyi . Diagnosis is best made using a dark - field microscopic examination of exudate taken from the surface of the lesion . The rapid plasma reagin ( RPR ) test results may be positive at a relatively low titer ( 1 : 16 or less ) at this time . If syphilis is strongly considered and both the dark - field examination and the RPR test findings are negative , a repeat RPR test in 2 weeks will have positive results . Treatment for primary syphilis is benzathine penicillin G at 2.4 million units . If the patient is allergic to penicillin , doxycycline at 100 mg twice daily for 2 weeks by mouth or tetracycline at 500 mg 4 times / d by mouth for 2 weeks is acceptable . If the patient is pregnant , desensitization followed by treatment with penicillin is recommended . All patients with a diagnosis of syphilis should be tested for HIV . Hemophilus ducreyi The primary ulcer is a painless chancroid and is typically on the fourchette , labia , or vestibule . Vaginal wall ulcers can occur and , at times , involve the cervix . Involvement of the cervix alone is very rare . Calymmatobacterium granulomatis C granulomatis causes a sexually transmitted disease called granuloma inguinale . The typical site of infection in women is the labia minora and the fourchette . Lesions of the cervix are uncommon but are easily confused with cervical carcinoma . Four distinct types of lesions are described ; the most common lesion on the cervix is the necrotic , deep , foul - smelling ulcer associated with tissue destruction . A tissue smear is the mainstay of diagnosis . A Giemsa stain typically is used . The Donovan bodies are identified in monocytes . The characteristic histologic picture is that of chronic inflammation , with plasma cells and polymorphonuclear leukocytes . Rarely , Donovan bodies are identified on cervical cytology . Treatment is with trimethoprim - sulfamethoxazole double - strength tablets twice daily or doxycycline at 100 mg orally twice daily . Alternative regimens include ciprofloxacin at 750 mg twice daily or erythromycin base at 500 mg 4 times daily . Treatment is for a minimum of 3 weeks . Actinomyces organisms Actinomyces organisms are isolated most commonly in women with intrauterine devices ( IUDs ) , but infection can be a result of surgical instrumentation and abortion . Demonstrating the organism in the center of large abscesses confirms the diagnosis . Lesions appear yellow and granular to the naked eye , hence the term sulfur granule . If this is an incidental finding , it does not need to be treated . Treatment with long course penicillin therapy is indicated only in the rare instances where an abscess is present . Tuberculosis When the cervix is involved , the lesion almost always is secondary to tuberculous salpingitis , which is secondary to pulmonary tuberculosis . The gross appearance can be confused with invasive carcinoma . Histologically , multiple granulomas or tubercles with central caseation necrosis , epithelioid histiocytes , and multinucleated Langerhans giant cells characterize the lesions . 33 The differential diagnosis includes lymphogranuloma venereum and sarcoidosis . An unequivocal diagnosis requires the identification of acid - fast Mycobacterium tuberculosis Protozoal and parasitic cervicitis : These are usually part of a more generalized process . Schistosomiasis and amebiasis : These are common in certain geographic areas . Atypia of Repair This is a response to any injury that is characterized by epithelial disorganization and nuclear atypia . In reactive atypia , the nuclei are uniform in shape and size and the chromatin is aggregated in prominent nucleoli . Mitotic figures are normal and confined to the parabasal and basal cells . Maturation occurs in a normal manner . In the endocervix , reparative changes include nuclear enlargement , hyperchromasia , cytoplasmic eosinophilia , and loss of the mucin droplets . 34 Hyperkeratosis and Parakeratosis This usually involves the cervical portio and may appear as whitish plaques ( ie , leukoplakia ) . When diffuse , the portio is covered by a thickened , white , wrinkled epithelial membrane . The thick keratin layer on the surface is referred to as hyperkeratosis . When pyknotic nuclei are found within the keratin layer , the term parakeratosis is used . Acanthosis ( ie , elongation of the rete pegs ) is usually present . Noninfectious Cervicitis This includes chemical irritation ( eg , deodorants , douching ) , local trauma from foreign bodies ( eg , tampons , pessaries , IUDs ) , surgical instrumentation , and therapeutic intervention . Clinically , the cervix is swollen , erythematous , and friable , and an associated purulent discharge may be present . The epithelium may be denuded and ulcerated . In chronic cervicitis , the cervix may be extremely friable and postcoital bleeding is a presenting complaint . Microscopically , lymphocytes , histiocytes , and plasma cells are present , with varying amounts of granulation tissue and Benign Tumors Endocervical polyps Endocervical polyps are the most common benign neoplasms of the cervix . They are focal hyperplastic protrusions of the endocervical folds , including the epithelium and substantia propria . They are most common in the fourth to sixth decades of life and usually are asymptomatic but may cause profuse leukorrhea or postcoital spotting 35 Grossly , they appear as typical polypoid structures protruding from the cervical os . At times , endometrial polyps protrude through the cervical os . They can not be distinguished from endocervical polyps by gross appearance . Microscopically , a variety of histologic patterns are observed , including ( 1 ) typical endocervical mucosal , ( 2 ) inflammatory ( granulation tissue ) , ( 3 ) fibrous , ( 4 ) vascular , ( 5 ) pseudodecidual , ( 6 ) mixed endocervical and endometrial , and ( 7 ) pseudosarcomatous . Treatment is removal , which can usually be accomplished by twisting the polyp with ringed forceps if the pedicle is slender . Smaller polyps may be removed with punch biopsy forceps . Polyps with a thick stalk may require surgical removal . Microglandular hyperplasia Microglandular hyperplasia refers to a clinically polypoid growth measuring 1 - 2 cm . It occurs most often in women who are on oral contraceptive therapy or Depo - medroxyprogesterone acetate resulting from the influence of progesterone . It also occurs in pregnant or postpartum women . On thin layer cytology , it may be confused with atypical squamous cells , can not exclude high - grade lesion . 36 37 38 Microscopically , it consists of tightly packed glandular or tubular units , which vary in size , lined by a flattened - to - cuboidal epithelium with eosinophilic granular cytoplasm containing small quantities of mucin . Nuclei are uniform , and mitotic figures are rare . Squamous metaplasia and reserve cell hyperplasia are common . An atypical form of hyperplasia can be mistaken for clear cell carcinoma . Unlike clear cell carcinoma , it lacks stromal invasion , has scant mitotic activity , and lacks intracellular glycogen . 39 Squamous papilloma Squamous papilloma is a benign solid tumor typically located on the ectocervix . It arises most commonly as a result of inflammation or trauma . Grossly , the tumors are usually small , measuring 2 - 5 mm in diameter . Microscopically , the surface epithelium may show acanthosis , parakeratosis , and hyperkeratosis . The stroma has increased vascularity and a chronic inflammatory infiltrate . Treatment is removal . The squamous papilloma resembles a typical condyloma acuminatum but lacks the koilocytes microscopically . Smooth muscle tumors ( leiomyomas ) These benign neoplasms may originate in the cervix and account for approximately 8 % of all uterine smooth muscle tumors . They are similar to tumors in the fundus . When located in the cervix , they usually are small , ie , 5 - 10 mm in diameter . Symptoms depend on size and location . Microscopically , leiomyomas resemble the typical smooth muscle tumor found in the uterine corpus . Treatment is required only for those patients who are symptomatic . The cervical leiomyoma is usually part of the spectrum of uterine smooth muscle tumors . Mesonephric duct remnants When present , mesonephric duct remnants are typically located at the 3 - o ' clock and the 9 - o ' clock positions , deep within the cervical stroma . They usually are incidental findings and are present in approximately 15 - 20 % of serially sectioned cervices . As the name implies , mesonephric duct remnants are vestiges of the mesonephric or Wolffian duct . Usually , they are only a few millimeters in diameter and seldom are grossly visible . Microscopically , they consist of a proliferation of small round tubules lined by epithelium that is cuboidal to low columnar . The tubules tend to cluster around a central duct . The cells lining the tubules contain no glycogen or mucin , but the center of the tubule may contain a pink material that contains glycogen or mucin . 40 Endometriosis When present in the cervix , endometriosis is usually an incidental finding . However , it may present as a mass or abnormal bleeding , particularly postcoital . Grossly , it may appear as a bluish - red or bluish - black lesion , typically 1 - 3 mm in diameter . Diagnosis is made by colposcopy and colposcopically directed biopsy but at times is difficult . 41 Microscopically , the implants are typical endometriosis , consisting of endometrial glands , endometrial stroma , and hemosiderin - laden macrophages . The implants usually gain access to the cervix during childbirth or previous surgery . Management is expectant in almost all instances . 42 Papillary adenofibroma This neoplasm is uncommon . Grossly , it appears as a polypoid structure . On ultrasound , cystic areas within the neoplasm may be identified . Microscopically , the neoplasm contains branching clefts and papillary excrescences lined by mucinous epithelium with foci of squamous metaplasia . A compact , cellular , fibrous tissue composed of spindle - shaped and stellate fibroblasts supports the epithelium . The stroma is devoid of smooth muscle , and mitoses are rare . Similar growths occur in the endometrium and the fallopian tubes . 43 Heterologous tissue Heterologous tissue includes cartilage , glia , and skin with appendages . This type of tumor rarely occurs in the cervix . While they may arise de novo , these tumors probably represent implants of fetal tissue from a previous aborted pregnancy . 44 Hemangiomas Hemangiomas in the cervix are rare and are similar to those found elsewhere in the body . If symptomatic , they cause pain or vaginal bleeding . 45 The differential diagnosis includes cervical malignancy . Treatment is surgical . 46 Cervical Pregnancy The cervix is the least common site for ectopic pregnancy . The implantation may be within the cervical canal or present as an exophytic lesion on the cervix . Grossly , a bluish hue may be present . In rare instances , a gestational sac and live fetus can be identified on ultrasonography . The trophoblast invades the stroma of the cervix . Because the pregnancy is not in a confined space , life - threatening hemorrhage may occur . Cervical pregnancy is uncommon and the best treatment is not known ; however , medical management is preferred . In one series , 36 cases have been treated with 50 mg of methotrexate injected under ultrasonographic guidance . In pregnancies with cardiac activity , 2 mL potassium chloride ( KCL ) is injected . 47 Case reports exist of angiographic uterine artery embolization followed by immediate curettage for controlling heavy bleeding or for recurrent heavy bleeding . 48 Sections Benign Cervical Lesions Show All Tables References
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Perioperative Care Perioperative Management of the Patient With Liver Disease Updated : Nov 09 , 2015 Author : Avital Yehudit O ' Glasser , MD ; Chief Editor : William A Schwer , MD more . . . Sections Overview Surgical Risk Assessment Preoperative Assessment and Management Intraoperative Factors Postoperative Monitoring Conclusion Show All Tables References Overview The number of patients with cirrhosis who require surgery is on the rise . Despite advances in antiviral therapeutics , the prevalence of cirrhosis secondary to hepatitis C continues to increase , as does the prevalence of cirrhosis due to chronic alcoholic liver disease . Additionally , nonalcoholic fatty liver disease ( NAFLD ) and nonalcoholic steatohepatitis ( NASH ) are gaining more attention , especially in association with metabolic syndrome and obesity . At the same time , the amount of medications and treatments aimed at improving survival among patients with cirrhosis has been increasing . Therefore , it can be expected that a growing number of patients with liver disease , both known and as yet undiagnosed and asymptomatic , will undergo surgery . An estimated 1 in 700 patients admitted for elective surgery has abnormal liver enzyme levels . Some authors have estimated that as many as 10 % of patients with advanced liver disease will undergo surgery in the last 2 years of their lives . 1 This article focuses on the challenges of perioperative care of patients with liver disease . Identification of the surgical risk is imperative in the care of any patient , especially as patients develop an increasing number of chronic comorbid medical conditions . Patients with liver disease are at particularly high risk for morbidity and mortality in the postoperative period due to both the stress of surgery and the effects of general anesthesia . del Olmo et al compared 135 patients with cirrhosis with 86 patients without cirrhosis , all undergoing nonhepatic general surgery . 2 At 1 month , mortality rates were 16.3 % for patients with cirrhosis compared with 3.5 % in the control group . What is further evident in the literature is that decompensated liver disease increases the risk of postoperative complications ( eg , acute hepatic failure , infections including sepsis , bleeding , poor wound healing , and renal dysfunction ) . Assessing risk in these patients is a challenging but important endeavor . The liver is vital for protein synthesis , coagulation homeostasis , glucose homeostasis , bilirubin excretion , drug metabolism , and toxic removal , among other critical functions . In general , the liver has substantial functional reserve because of its dual blood supply : portal - venous ( 75 % ) and hepatic - arterial ( 25 % ) . Hence , clinical manifestations of liver damage occur only after considerable injury . Liver disease comprises a large spectrum of hepatic dysfunction . It includes asymptomatic transaminitis , cirrhosis , and end - stage liver disease . The most common causes of advanced liver disease are chronic viral infections ( hepatitis C [ HCV ] and B [ HBV ] ) , alcohol abuse , NAFLD / NASH autoimmune disease , drugs or toxins , metabolic disorders ( eg , alpha - 1 antitrypsin deficiency hemochromatosis , and Wilson disease ) , and biliary tract diseases . For patient education resources , see the Hepatitis Center and Liver , Gallbladder , and Pancreas Center , as well as Liver Transplant and Cirrhosis Surgical Risk Assessment Basis for risk assessment Secondary to the loss of hepatic reserve capacity and because of other systemic derangements that are the result of liver dysfunction ( such as hemodynamic impairments ) , patients with liver disease have an inappropriate response to surgical stress . These individuals are accordingly at an increased risk of bleeding , infection , impaired wound healing , postoperative hepatic decompensation , including hepatic coma or death . Therefore , the decision to perform surgery in these patients must be heavily weighed . Prediction of surgical risk is based on the degree of liver dysfunction , the type of surgery , and the preclinical status of the patient . The extent of liver dysfunction and type of surgery play key roles in determining a patient ’ s specific risk . In addition , liver disease can affect almost every organ and system in the body , including the cardiorespiratory and circulatory systems , the brain , the kidneys , and the immune system . The extent to which secondary manifestations of liver disease affect these systems may be just as important as the manifestations of primary liver dysfunction in predicting the outcome after surgery . Such comorbid conditions responsible for perioperative morbidity and mortality ( eg , coagulopathy , intravascular volume , renal function , electrolytes , cardiovascular status , and nutritional status ) should be identified and addressed before surgery . Optimal preparation may decrease death and complications after surgery . Issues to anticipate and address include manifestations of acute liver decompensation including encephalopathy , acute renal failure , coagulopathy , adult respiratory 3 4 5 Algorithm for a patient with liver disease for whom surgery is being considered . Quantitative risk stratification Two risk stratifications schemes have been used to estimate the perioperative risk of patients with cirrhosis : the Child - Turcotte - Pugh score and the Model for End - Stage Liver Disease ( MELD ) score . The Child - Turcotte - Pugh ( CTP ) score incorporates a combination of 3 biochemical elements ( ie , prothrombin time [ PT ] , albumin level , and bilirubin level ) and 2 clinical features ( ie , presence of ascites and encephalopathy ) to assess the primary functions of the liver ( see the table below ) . A patient ’ s score is translated to 1 of 3 CTP classes : A , B , or C , with A reflecting the least severe disease . Patients who are CTP class B and C have worse outcomes and are candidates for liver transplantation The CTP score was first developed to predict mortality after portocaval shunt surgery , but it has since been used to predict perioperative morbidity and mortality rates for patients undergoing hepatic and nonhepatic intra - abdominal surgeries . 1 6 7 8 Patients with CTP class A disease are estimated to have a 10 % mortality rate after abdominal surgery . That mortality rate increases to 30 - 31 % for CTP class B and 76 - 82 % for CTP class C . 8 A 2010 study by Telem et al demonstrated lower mortality rates ( CTP 2 % , CTP B 12 % , CTP C 12 % ) when surgeries were performed at an institution specializing in hepatology and liver transplantation . 9 However , the CTP scoring system has been challenged for its ambiguity and interobserver variability because it includes subjective parameters ( eg , degree of ascites and encephalopathy ) . Additionally , all the factors are weighted equally . Patients within a given class are not homogenous but also not distinguished between , a feature for which it has also been criticized . 10 The MELD score was originally developed to predict short - term mortality for patients undergoing transjugular intrahepatic portosystemic shunt TIPS ) placement . It has since been adopted as the tool to prioritize patients with cirrhosis for liver transplantation . The MELD score is based on a patient ' s serum bilirubin , creatinine , and international normalized ratio ( INR ) for prothrombin time and is calculated from a validated predictive equation , as follows : ( 3.8 × ln bilirubin value ) + ( 11.2 X ln INR ) + ( 9.6 ln creatinine value ) , where bilirubin and creatinine values are in milligrams per deciliter ( mg / dL ) and ln represents natural logarithm . See the MELD Score calculator The MELD score originally included the etiology of liver failure , but this criterion was subsequently dropped from the equation because it was proved prognostically insignificant . The Organ Procurement and Transplantation Network ( OPTN ) also provides an online calculator With regard to its original utilization , a MELD score < 8 predicts good outcome after TIPS and a score > 18 predicts poor outcome , with best outcomes seen in patients with scores < 14 . Avoidance of TIPS is generally recommended in patients with a MELD score > 24 , unless the procedure is used as a measure of last resort to control active variceal bleeding . Since its implementation , the MELD score ’ s use has been expanded to also predict the risk of mortality and morbidity after other procedures . A MELD score of at 11 and cardiac surgery requiring cardiopulmonary bypass . 12 Several authors have also shown that the MELD score predicts morbidity and mortality after hepatic resection for hepatocellular carcinoma . Cucchetti et al showed that MELD scores < 9 were associated with 0 % postoperative liver failure ; MELD scores 9 - 10 were associated with 3.6 % postoperative liver failure ; and MELD scores > 10 were associated with 37.5 % postoperative liver failure . 13 Teh et al showed that a MELD score less than or equal to 8 was associated with 0 % postresection mortality compared with 29 % mortality for MELD scores > 8 . 14 In general , the MELD score fairs well compared to the CTP score . However , some might argue that the MELD score may be a more objective predictor of postoperative mortality than the CTP score , 11 12 15 16 especially as patients fall along a continuum of values instead of into 3 discrete groups . The MELD score has been validated as an independent prediction tool to calculate postoperative mortality . A retrospective analysis by Northup et al found that the MELD score was the only statistically significant predictor of 30 - day mortality . For example , with a MELD of 5 was associated with 5 % risk ; 10 , with a 7 % risk ; 15 , with an 11 % risk ; 20 , with a 17 % risk ; or 25 , with a 26 % risk . 17 Teh et al performed a retrospective , multivariate analysis that showed among patients with cirrhosis undergoing multiple types of major surgeries , the MELD but not the CTP score predicted increased mortality at 30 and 90 days , 1 year , and over the long term . 18 Age and American Society of Anesthesiologists ( ASA ) class also predicted postoperative mortality . The MELD was the strongest predictor of mortality after 7 days and over the long term . For example , the 30 - day mortality associated with MELD < 8 was 5.7 % but > 50 % for MELD score > 20 . 18 The relative risk of mortality also increased 14 % for each 1 point increase in the MELD score . The same study by Telem et al demonstrated an improved though still increased mortality rate for MELD ≥ 15 ( 29 % ) ; if an albumin ≤ 2.5 mg / dL was added to a MELD score ≥ 15 , mortality increased to 60 % . 9 The 2007 review by Hanje et al posited the general recommendation that patients with MELD < 10 can undergo elective surgery and patients with a MELD of 10 - 15 should proceed with caution . Notation was made that patient - and surgery - specific factors also contribute to the risk / benefit decisions . 19 More recently , the MELD score has been adapted with additional clinical risk factors , creating the " integrated MELD " score ( iMELD ) : iMELD = MELD + ( 0.3 X age ) - ( 0.7 X serum sodium [ mEq / L ] ) + 100 . In a retrospective study of 190 patients with cirrhosis , Costa et al demonstrated that the iMELD score had better prognostic strength compared with the MELD or CTP scores . In brief , iMELD scores of < 35 , 35 - 45 , and > 45 were associated with perioperative 20 Most recently , a 2011 study again showed that perioperative mortality increased with the CTP and MELD scores ( 10 % Child A , 17 % Child B , 63 % Child C ; P < .01 ; 9 % MELD < 10 , 19 % MELD 10 – 15 , 54 % MELD > 15 ; P < .001 ) . However , on multivariate analysis , the CTP and ASA classes , need for intraoperative transfusions , and preoperative sodium < 130 mmol / L were independent prognostic factors ; MELD score was not prognostic . Further subgroup analysis of elective surgeries revealed only preoperative creatinine ≥ 1.1 mg / dL to be predictive of mortality . For emergent surgeries , CTP but not MELD score was again predictive of outcomes . 21 Table . Child - Turcotte - Pugh classification of liver disease . ( CTP A = 5 - 6 points , CTP B = 7 - 9 points , CTP C = 10 - 15 points ) ( Open Table in a new window ) Criterion 1 point each 2 points each 3 points each Ascites None Controlled with diuretics Poorly controlled Encephalopathy None Grade I - II Grade III - IV Total bilirubin , µmol / L ( normal = 17.1 µmol / L or 1.0 mg / dL ) < 34 ( 0 - 2 mg / dL ) 34 – 50 ( 2 - 3 mg / dL ) > 50 ( > 3 mg / dL ) Albumin , g / L > 35 ( > 3.5 g / dL ) 25 - 35 ( 2.5 - 3.5 g / dL ) < 25 ( < 2.5 g / dL ) INR < 1.7 1.7 – 2.2 > 2.2 Other risk stratification systems The ASA physical status class risk stratification system is based on comorbid conditions that are a threat to life or that limit activity and thus helps in predicting preoperative risks . In general , an ASA class greater than 2 increases the risk 1.5 - to 3.2 - fold . 22 The ASA class independently predicted postoperative mortality in patients undergoing hepatic resection for hepatocellular carcinoma . 14 Teh et al also found the ASA class significantly predicts increased mortality and morbidity among patients with cirrhosis undergoing major surgery , with ASA class V the strongest predictor of postoperative mortality at 7 days . The mortality related to ASA IV was the equivalent of 5.5 MELD points in terms of risk . It is also important to not overlook the preoperative cardiopulmonary evaluation . This is required of any patient , regardless of the functional status of their liver . Cardiac risk stratification should include an assessment of functional capacity ( metabolic equivalent [ MET ] or exercise duration ) . Additional noninvasive testing such as stress testing might be considered if it will change perioperative management . Cardiac surgery performed in patients with cirrhosis is associated with a high surgical mortality rate and will be discussed separately . In 1997 , the American College of Physicians ( ACP ) published guidelines in the form of algorithms for assessing and managing perioperative risks based on the results of the tests mentioned above . The Goldman cardiac risk index is used to predict postoperative pulmonary and cardiac complications . 23 It is a classification system based on points assigned to a patient ' s clinical history , physical findings , ECGs , general medical status ( based on arterial blood gases [ ABGs ] , electrolytes , and liver disease ) , and type of operation . The guidelines were updated by the American College of Cardiology / American Heart Association in 2007 and now include the Revised Cardiac Risk Index . 24 25 Preoperative Assessment and Management Asymptomatic patients The evaluation of any patient undergoing surgery should include thorough history taking and physical examination . In asymptomatic patients , this is an extremely valuable screening tool . Risk factors ( eg , pervious blood transfusions , tattoos , illicit drug use , sexual history , alcohol use , and personal or family history of jaundice ) for liver disease should be explored . A complete medication review including other - the - counter ( OTC ) and herbal agents should be performed . Symptoms or physical signs suggestive of liver dysfunction / disease ( eg , hepatosplenomegaly , spider angiomata , jaundice , gynecomastia , palmar erythema , scleral icterus , asterixis , encephalopathy ) should prompt further examination with liver function tests , coagulation studies , complete blood cell ( CBC ) counts and metabolic panels . However , routine preoperative testing of liver function is not recommended because of the low prevalence of liver abnormalities in clinically asymptomatic patients . 26 27 28 Asymptomatic patients with significantly abnormal liver function should have their elective surgery postponed and their liver disease investigated ; their perioperative risk should be reassessed after their liver dysfunction is characterized . 29 Acuity of liver disease Though most studies have focused on patients with end - stage liver disease or cirrhosis , patients with fulminant hepatic failure have been associated with an increased risk of surgical morbidity and mortality This also applies to patients with acute alcoholic hepatitis and acute viral hepatitis . Patients with these conditions tend to have morbidity rates higher than those with chronic cholestatic disease . Therefore , it is prudent to postpone surgery , especially elective surgery , until transaminitis is resolved . 30 Patients with chronic liver disease but with preserved hepatic function may not have an increased operative risk , 31 but these individuals need to be closely evaluated nonetheless . Severity and specific derangements of known chronic liver disease In patients with known liver disease , especially with cirrhosis , optimal preparation for surgery , that appropriately addresses the primary features and secondary manifestations of liver disease may decrease the risk of complications or death after surgery . This includes laboratory tests to assess blood counts , coagulopathy , electrolyte abnormalities , and markers of hepatic synthetic function . Coagulopathy and thrombocytopenia Coagulopathy is one of the primary features of advanced liver disease . In addition to hepatic synthetic dysfunction ( all of the coagulation factors with the exception of von Willebrand factor are produced in the liver ) , malnutrition and vitamin K malabsorption due to cholestasis contribute to this abnormality . Additionally , portal hypertension leads to hypersplenism with resultant platelet trapping and peripheral thrombocytopenia . Vitamin K supplementation and administration of fresh - frozen plasma ( FFP ) are recommended to correct coagulopathy before surgery . Cryoprecipitate might also be required to reduce the prothrombin time . A prolongedbleeding time can also be corrected with diamino - 8 - D - arginine vasopressin ( DDAVP ) . Finally , platelet transfusion ( see platelets ) may be necessary based on the patient ’ s platelet level and the desired level as dictated by the type of surgery . A recent study explored the effect of preoperative eltrombopag , an oral thrombopoietin - receptor agonist , on the need for platelet transfusions for patients with chronic liver disease and thrombocytopenia . The authors saw a statistically significant difference in the need for platelet transfusions ( 28 % in the treatment group vs 81 % ) without a significant difference in bleeding episodes . Portal vein thrombosis occurred much more frequently in the treatment group , leading to early termination of the study . 32 Ascites Ascites is important to assess and manage before surgery because it can lead to wound dehiscence , abdominal wall herniation , and respiratory compromise secondary to reduced lung expansion . In a study by Conn , ascites in patients with cirrhosis was associated with a 37 - 83 % mortality rate compared with 11 - 53 % in those without ascites . 33 In general , ascites should be treated aggressively with diuretics and / or large - volume paracentesis before surgery . A low sodium diet is another important component of ascites management . Patients on diuretics need to have their creatinine and electrolytes monitored . Ascites fluid can also be removed intraoperatively at laparotomy . 31 It is important to take note of the volume of fluid removed and the patient ’ s baseline renal function and to consider albumin repletement to maintain intravascular volume and prevent paracentesis - induced circulatory dysfunction . Ascitic fluid should also be analyzed to rule out spontaneous bacterial peritonitis . Encephalopathy Many patients with cirrhosis may have portosystemic encephalopathy at baseline , which increases their risk of postoperative encephalopathy . A retrospective study of 40 patients with chronic liver failure undergoing nonhepatic surgery demonstrated that encephalopathy was associated with an 88 % risk of mortality , which was even higher than the 50 % risk associated with emergency surgery . 34 Multiple factors in the preoperative and postoperative periods may precipitate encephalopathy , such as infection and / or sepsis , diuretics , hypokalemia , metabolic alkalosis , constipation , use of central nervous system ( CNS ) depressants such narcotics and benzodiazepines , hypoxia , azotemia , and gastrointestinal bleeding . Addressing the underlying precipitant through correction of electrolyte abnormalities , treatment of infection , management of gastrointestinal bleeding , and restriction of sedatives may help prevent or decrease encephalopathy . Hepatic encephalopathy is also often treated by administering lactulose or poorly absorbed antibiotics such as rifaximin Renal dysfunction Patients with chronic liver disease are at risk for renal dysfunction at baseline due to the propensity for hemodynamic derangements that increase the risk of renal hypoperfusion . This risk is increased by diuretics , nephrotoxic agents including nonsteroidal anti - inflammatory drugs ( NSAIDs ) , large - volume paracentesis performed without albumin supplementation , infections , and gastrointestinal bleeding . Hepatorenal syndrome is another concerning occurrence in this patient population . The risk of renal dysfunction in the postoperative period is increased because of hemodynamic changes and fluid shifts or losses , particularly if ascites fluid is removed at laparotomy . Renal function should be closely monitored pre - and postoperatively , with appropriate measures taken to address or eliminate potential insults . Attention should also be given to the fact that serum creatinine levels often overestimate the glomerular filtration rate ( GFR ) in patients with cirrhosis ; a seemingly normal creatinine level may indeed represent impaired renal function . Vasoactive compounds such as midodrine and terlipressin appear to be at least as effective as intravenous albumin in preventing circulatory dysfunction with resultant renal impairment in patients with cirrhosis who have lost third - spaced volume . 35 36 Pulmonary disease Pulmonary complications of end - stage liver disease include hepatopulmonary syndrome , portopulmonary hypertension , and hepatic hydrothorax . Hepatopulmonary syndrome is associated with vascular shunt , and the risk of hypoxia and ventilation - perfusion mismatch should be addressed before surgery . Portopulmonary hypertension can eventually lead to right heart failure and hypoxia . Hepatic hydrothorax , usually unilateral and in the right hemithorax , can occur and impair ventilation . However , the associated hypoxemia is usually not severe . 37 Drainage is usually not recommended because the effusion often rapidly reaccumulates . Finally , the risk of chronic obstructive pulmonary disease ( COPD ) should be assessed in any patient who has previously smoked tobacco or who has alpha - 1 antitrypsin deficiency . Malnutrition Severe malnutrition is associated with an increased need for packed red blood cells , FFP , and cryoprecipitate during liver transplantation . It is also associated with a prolonged postoperative stay . Stephenson et al suggest that preoperative improvement in the patient ' s nutritional status may improve outcomes . 38 In patients with end - stage liver disease , steps to improve nutritional health should be started , preferably in the preoperative period , because they are expected to have increased energy expenditure after surgery . 39 Supplements can be used . Patients with alcoholic liver disease and Wernicke encephalopathy benefit from preoperative vitamin B - 1 supplementation . Advanced liver disease can also predispose to hypoglycemia because of impaired gluconeogenesis and decreased glycogen stores . Disease - specific considerations Patients with autoimmune hepatitis on daily steroids may be appropriate candidates for stress - dosed steroids with surgery , depending on their average daily steroid dose . D - penicillamine can impair wound healing ; patients taking it for Wilson disease should decrease their dose for 1 - 2 weeks preoperatively and postoperatively . Wilson disease might predispose to an increased risk of neurologic changes postoperatively . Patients with hemochromatosis should be assessed for a history of extrahepatic hemochromatosis - related complications , such as diabetes or cardiomyopathy . In addition , it is worth noting that patients with a history of alcohol abuse are at increased risk of other complications , including poor wound healing , bleeding , delirium , and infections . Patients who have continued to actively drink are at risk for withdrawal . Though studies indicate that preoperative alcohol cessation improves outcomes , patients with cirrhosis were excluded from the intervention . 40 41 However , it seems reasonable to recommend a period of abstinence for patients with known chronic liver disease / cirrhosis or to delay elective surgery until such can be achieved . Intraoperative Factors Anesthesia Impaired hepatic synthetic function and derangement of other hepatic functions are especially pertinent to note when choosing anesthetic and other agents used in the perioperative period . These changes include decreased synthesis of plasma - binding proteins . Hypoalbuminemia impairs drug binding and metabolism and elevates serum drug levels . Impaired drug metabolism , detoxification , and excretion by the liver can prolong drug half - lives . Thus , the absorption , distribution , metabolism , and excretion of anesthetics , muscle relaxants , analgesics , and sedatives may be affected . Patients with liver disease are more likely than patients without liver disease to have hepatic decompensation with the use of anesthesia . General anesthesia reduces total hepatic blood flow , especially the contribution of the hepatic artery . Patients with liver disease tend to have several baseline cardiovascular abnormalities , including decreased systemic vascular resistance and increased cardiac index , which may further affect hepatic blood flow . In addition , catecholamine and other neurohormonal responses are impaired in patients with liver disease ; therefore , intraoperative hypovolemia or hemorrhage may not trigger adequate compensatory mechanisms . Anesthetics causing sympathetic blockade further blunt this response . The result of this reduction in hepatic perfusion is a drastic loss of their remaining marginal hepatic function Of all the inhaled anesthetics , halothane and enflurane appear to reduce hepatic artery blood flow the most because of systemic vasodilation and a mild negative inotropic effect . 42 43 44 Halothane is also associated with the greatest risk of hepatotoxicity , with the incidence of fulminant hepatitis approximating 1 case in 6,000 - 35,000 patients after exposure . 45 Isoflurane has fewer effects on hepatic blood flow and less hepatic metabolism it is the preferred anesthetic agent in patients with liver disease . Newer haloalkanes , such as sevoflurane desflurane , also undergo less hepatic metabolism than halothane or enflurane . The drug effects of neuromuscular blocking agents may be prolonged in patients with liver disease because of impaired biliary excretion . Atracurium has been recommended as the agent of choice because it relies on neither the liver nor kidney for excretion . 46 Likewise , drugs such as morphine meperidine , benzodiazepines , and barbiturates should be used with caution because of their dependence on the liver for metabolism . In general , the doses of these agents should be decreased by 50 % . 47 Fentanyl is the preferred narcotic . 48 Surgery The type of surgery is potentially an important determinant of postoperative hepatic dysfunction . Because of traction on abdominal viscera , intra - abdominal operations are more likely than extra - abdominal surgeries to cause reflex systemic hypotension and to subsequently reduce hepatic blood flow . Hypercarbia - induced splanchnic vasoconstriction is also a threat to hepatic perfusion . Surgeries that result in a large amount of blood loss increase the risk for ischemic hepatic injury , as can intraoperative hypotension . Sufficient surgical hemostasis and autologous platelet - rich plasma have been demonstrated to be useful for prevention of 3 Examples of specific surgeries and considerations Cholecystitis cholelithiasis are common in patients with liver disease . The odds ratio for perioperative mortality in patients with liver disease who undergo cholecystectomy is 8.47 . In fact , open cholecystectomy in patients with cirrhosis has been called a formidable operation , although recent studies have demonstrated lowered but still considerable mortality rates in patients with cirrhosis who undergo abdominal surgery . Perkins et al confirmed that a MELD score greater to or equal to 8 predicts an increased risk of postoperative complications in this type of surgery ( see the MELD Score calculator ) . However , laparoscopic cholecystectomy can be safely performed in selected patients who have well - compensated cirrhosis and no signs of portal hypertension . A case - controlled retrospective review of laparoscopic cholecystectomy in 48 patients with Child - Pugh class A ( 80 % of patients ) and Child - Pugh class B cirrhosis demonstrated no increase in morbidity and mortality rates or worsening of outcome compared with control subjects . 49 Another small series had similar results 50 ; the authors concluded that laparoscopic cholecystectomy is relatively safe in patients with Child - Pugh class A or B cirrhosis . In addition , Ji et al showed that laparoscopic cholecystectomy was associated with lower rates of postoperative complications than open cholecystectomy in patients with cirrhosis matched for disease severity . 51 A large study of 747 patients from 1990 to 1997 who underwent liver resection demonstrated that mortality was significantly higher in patients with cirrhosis ( 8.7 % ) or obstructive jaundice ( 21 % ) than in patients with a normal liver ( 1 % ; < 0.001 ) . 52 Other groups have also demonstrated that the MELD score predicts risk of postresection morbidity and mortality . 13 53 54 Cardiac surgery in patients with cirrhosis is associated with a high operative mortality rate . A lone study found the following risk factors for operative mortality : obstructive jaundice , hematocrit value < 30 % , serum bilirubin level > 11 mg / dL , malignant biliary obstruction , azotemia , and cholangitis . In a small study , patients with cirrhosis and a CTP class A were found to have 0 % mortality ; B , 50 % mortality ; and C , 100 % mortality after cardiac surgery , 55 with another group finding that a CTP score > 7 was more sensitive and as specific as the MELD score in predicting poor outcome . Another small study of 27 patients demonstrated that cardiac surgery could be safely performed in patients with CTP class A and selected patients with CTP class B . Also shown was that the use of cardiopulmonary bypass increased with of mortality . 56 A 2012 study demonstrated consistent results , showing that a CTP < 8 was associated with mortality comparable to matched controls , aswell as a lower risk of renal failure and dialysis than patients with CTP ≥ 8 . 57 Like other major open abdominal procedures , open abdominal aortic aneurysm ( AAA ) repair may be associated with an increased risk of postoperative mortality , even with mild chronic liver disease . 58 However , a recent study by Marrocoo - Trischitta et al noted that the procedure can be safely performed in patients with compensated cirrhosis , though they noted a nearly double length - of - stay in patients with cirrhosis , despite predominantly mild disease with CTP score A and average MELD 8 . They also cautioned that patients with MELD ≥ 10 may not benefit from the vascular procedure given their overall limited life expectancy . 59 Bush et al have also demonstrated endovascular AAA repair to be safe in patients with multiple comorbid medical conditions , including hepatic disease . 60 Various types and indications for orthopedic procedures also affect perioperative risk for patients and cirrhosis . Cohen et al performed a retrospective review of outcomes of primary total hip arthroplasties and total knee arthroplasties for cirrhotic patients versus matched controls . Significantly worse outcomes were seen in patients with cirrhosis ( 20.7 % vs 3.23 % ) . Higher complication rates were seen in cirrhotic patients undergoing emergent total hip arthroplasties for hip fracture repair ( 80 % had a major complication , with 60 % mortality rate ) . More advanced liver disease trended towards worse clinical outcomes , 61 In some parts of the world , parasitic diseases , such as hydatid disease or echinococcosis , may cause liver lesions that need to be surgically removed . In such cases , the surgical technique is important , and sepsis can cause perioperative morbidity . 62 Emergency surgery Patients undergoing emergency surgery are at substantial risk for liver dysfunction . Intuition suggests , the more urgent the surgery , the less opportunity that is available to correct reversible factors , such as electrolyte abnormalities , coagulopathy , and clinical manifestations of portal hypertension ( eg , ascites , hepatic encephalopathy ) . Emergency surgery is an important predictor of adverse outcome . In a series of 100 patients with cirrhosis who underwent abdominal surgery for a variety of reasons , 80 % of nonsurvivors and 40 % of survivors who had serious complications had undergone emergency surgery . A series of 92 patients with cirrhosis who underwent abdominal surgeries had a 50 % mortality rate in association with emergency procedures ( 22 % for CTP class A , 38 % for CTP class B , 100 % for CTP class C ) versus 18 % for elective surgery ( = 0.001 ) . This study showed that the most accurate predictor of outcome is the patient ' s preoperative CTP class . A 2004 study demonstrated that patients with cirrhosis had a higher perioperative morbidity and mortality rate with emergency surgery than with elective surgery . Mortality rates significantly differed between the groups ( emergency group , 1 mo = 19 % mortality rate , 3 mo = 44 % ; elective group , 1 mo = 17 % mortality rate , 3 mo = 21 % ; < 0.05 ) . 15 A 2007 study found that 100 % of patients with cirrhosis undergoing emergency surgery died , with a median survival 2 days ; all these patients had higher MELD scores and were ASA class V . The 2011 study by Neeff et al again demonstrated significantly increased mortality with emergent surgeries ( CTP A 0 % , CTP B 30 % , CTP C 72 % , = .0001 ; MELD < 10 20 % , MELD 10 - 15 33 % , MELD > 15 60 % , P = .03 ) . 21 More specifically , cirrhosis diagnosis made at the time of laparotomy for trauma is associated with an increased risk of mortality ( 45 % vs 24 % ) . 63 Another study confirmed the elevated mortality when cirrhosis and trauma combined : 12 % versus 6 % overall mortality , 40 % versus 15 % mortality after emergent abdominal exploration . 64 65 Postoperative ICU admission and care is recommended for such patients , even for mild injuries . Alternatives to surgery Relatively noninvasive techniques or advances in medical management have replaced surgical intervention for many conditions ( eg , extrahepatic biliary obstruction , refractory variceal hemorrhage , coronary artery disease ) . TIPS has become the treatment of choice for managing cases of refractory variceal bleeding , and surgical shunts are created only in special circumstances . Percutaneous stenting or endoscopic retrograde cholangiopancreatography ( ERCP ) is now commonly used for biliary strictures and choledocholithiasis . Coronary angioplasty and percutaneous coronary interventions have decreased the need for coronary artery bypass grafting ( CABG ) . The use of proton - pump inhibitors ( PPIs ) along with antibiotic treatment of Helicobacter pylori has usurped the need for surgical treatment of peptic ulcer disease ( PUD ) with antrectomy and / or vagotomy . Postoperative Monitoring In patients with cirrhosis , liver failure is the most common cause of postoperative death . 48 Hepatocellular injury is most commonly due to the effects of anesthesia , intraoperative hypotension , sepsis , or viral hepatitis . A low threshold is generally maintained for postoperative transfer to the intensive care unit ( ICU ) . Patients must be observed closely for signs of acute hepatic decompensation , such as worsening jaundice , encephalopathy , and ascites . Sedatives and pain medications should be carefully titrated to prevent an exacerbation of hepatic encephalopathy ; the increased half - life of hepatically metabolized drugs will make patients with liver disease more sensitive to standard doses . Benzodiazepines can be particularly problematic in patients predisposed to hepatic encephalopathy . Poor stooling , for example due to postoperative ileus or narcotic - or immobility - related constipation , despite lactulose dosing , can also contribute to postoperative encephalopathy . Renal function should also be monitored because of the risk of hepatorenal syndrome and fluid shifts that occur due to surgery . These patients should also be monitored for surgical site complications such as infections , bleeding , and dehiscence . Additionally , it is now recognized that an elevated international normalized ratio ( INR ) in the setting of chronic liver disease does not appear to protect patients from hospital - acquired deep venous thromboses or pulmonary emboli . 66 Serious sequelae of decompensated cirrhosis include severe sepsis and secondary disseminated intravascular coagulation ( DIC ) . These potential complications emphasize the need for maintaining a low threshold for ICU - level monitoring . Conclusion Surgery in a patient with liver disease , especially end - stage liver disease with cirrhosis and portal hypertension , poses a formidable challenge for all physicians involved . Targeted interventions before surgery may help to prevent complications and improve outcomes . The cornerstones of perioperative management are medical treatment of the complications of liver disease , including coagulopathy , ascites , encephalopathy , and malnutrition . Attention must also be paid to risk factors for infection and renal dysfunction after surgery . Sepsis , coagulopathy , and emergency surgery are most strongly correlated with postoperative mortality . Evolving knowledge of the effects of anesthesia , improving surgical techniques , and use of improved diagnostic tests will help reduce perioperative complications . 29 Established risk stratification systems such as the CTP score , the MELD score , and the ASA physical status class should also be used when evaluating a patient with liver disease for potential surgery . Surgery - specific factors should also be strongly weighed . Therefore , a multidisciplinary approach to postoperative care is imperative and should include input from anesthesiologists , surgeons , internists , and hepatologists . Algorithm for a patient with liver disease for whom surgery is being considered . General considerations are as follows ( see image above ) : Surgery is contraindicated in patients with CTP class C , high MELD score , ASA class V , acute hepatitis , severe coagulopathy , or severe extrahepatic manifestations of liver disease ( eg , acute renal failure , hypoxia , cardiomyopathy ) . Avoid surgery if possible in patients with a MELD score of greater than or equal to 8 or CTP class B unless they have undergone a thorough preoperative evaluation and preparation . Use caution with sedatives and neuromuscular blocking agents . Optimize medical therapy for patients with cirrhosis . Correct coagulopathy with vitamin K and FFP to achieve prothrombin time within 3 seconds of normal . The goal platelet count is > 50 - 100 × 10 / L but may vary depending on the specific surgery . Minimize ascites to decrease risk of abdominal - wall herniation , wound dehiscence , and problems with ventilation . Address nutritional status . Perform close postoperative monitoring Admission to the ICU may be appropriate after prolonged surgeries , intraoperative hypotension , excessive blood loss , or cardiac and / or pulmonary surgery . Monitor for signs of acute liver failure , including worsening jaundice , encephalopathy , and ascites . Monitor renal function . Monitor and correct electrolyte abnormalities , especially hypokalemia and metabolic alkalosis . Show All Tables References
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[
"Perioperative Management",
"Liver Disease",
"alcoholic liver disease ."
] |
http://emedicine.medscape.com/article/287464-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Psychiatry Conversion Disorders Updated : Nov 09 , 2015 Author : Scott A Marshall , MD ; Chief Editor : David Bienenfeld , MD more . . . Sections Overview Background Pathophysiology Epidemiology Show All Presentation DDx Workup Treatment Medication Follow - up References Background Conversion disorder ( Functional Neurological Symptom Disorder ) is categorized under the new Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition ( DSM - 5 ) category of Somatic Symptom and Related Disorders . 1 It involves symptoms or deficits affecting voluntary motor or sensory function that suggest a neurologic or other general medical condition . Yet , following a thorough evaluation , which includes a detailed neurologic examination and appropriate laboratory and radiographic diagnostic tests , no neurologic explanation exists for the symptoms , or the examination findings are inconsistent with the complaint . In other words , symptoms of an organic medical disorder or disturbance in normal neurologic functioning exist that are not referable to an organic medical or neurologic cause . 2 Common examples of conversion symptoms include blindness , diplopia , paralysis , dystonia , psychogenic nonepileptic seizures ( PNES ) , anesthesia , aphonia , amnesia , dementia , unresponsiveness , swallowing difficulties , motor tics , hallucinations , pseudocyesis and difficulty walking . Reports of less common manifestations of conversion disorder abound in the literature and include camptocormia , clenched fist syndrome , recumbent gait , odd vocalizations , and pseudo foreign accent syndrome . 3 4 5 6 7 Multiple symptoms suggest a somatization disorder . Conversion disorder is a type of somatoform disorder where physical symptoms or signs are present that can not be explained by a medical condition . Very importantly , unlike factitious disorders and malingering , the symptoms of somatoform disorders are not intentional or under conscious control of the patient . See the image below . French neurologist Jean Martin Charcot shows colleagues a female patient with hysteria at La Salpêtrière , a Paris hospital . Case study A young woman ’ s family brings her to the hospital and she presents with a chief complaint of “ spells . ” It seems that over the past several weeks , the patient has suffered from attacks of bilateral arm jerking , followed by bilateral leg jerking after she lowers herself to the floor . Often , her head shakes violently side to side and her eyes are seen to " roll back in her head " followed by forced eye closure . These incidents follow episodes of emotional outbursts , and the patient is fortunately able to warn These spells are not accompanied by loss of bladder or bowel continence , but often the patient bites the tip of her tongue and kicks over tables or strikes family members during an episode . This most recent spell occurred while the patient was driving her car , in which she warned of an impending seizure and pulled the car to the shoulder just before losing consciousness ; her spell was much more intense than she has had in the past . She has no significant past medical history and takes no medications . She reports a past history of childhood sexual abuse from a paternal uncle several years ago . On exam , her vitals signs are normal and her neurologic evaluation is without significant findings . She is not orthostatic . Laboratory work - up , including urine toxin screen , is negative . Next : Pathophysiology Sections Conversion Disorders Overview Pathophysiology Epidemiology Show All Presentation DDx Workup Treatment Medication Follow - up References Recommended Diseases & Conditions Pediatric Conversion Disorder Diseases & Conditions Conversion Disorder in Emergency Medicine
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[
"Conversion Disorders",
"Mental Disorders",
"Statistical Manual"
] |
http://emedicine.medscape.com/article/295807-differential
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pulmonology Obstructive Sleep Apnea ( OSA ) Differential Diagnoses Updated : Mar 22 , 2019 Author : Himanshu Wickramasinghe , MD , MBBS ; Chief Editor : Zab Mosenifar , MD , FACP , FCCP more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Diagnostic Considerations A diagnosis of narcolepsy may be delayed if obstructive sleep apnea ( OSA ) is considered the only condition . Patients should be routinely screened clinically for symptoms of narcolepsy . These patients do not typically have normal sleepiness when OSA has been treated ; they may experience improvement in sleepiness , but it is important to question the diagnosis of sleepiness due to OSA despite ideal treatment . 137 Indices for sleep - disordered breathing The indices commonly used to assess sleep disordered breathing ( SDB ) are the apnea - hypopnea index ( AHI ) and the respiratory disturbance index ( RDI ) . The AHI is defined as the average number of episodes of apnea and hypopnea per hour . The RDI is defined as the average number of respiratory disturbances ( obstructive apneas , hypopneas , and respiratory event – related arousals [ RERAs ] ) per hour . If the AHI or RDI is calculated based on less than 2 hours of continuous recorded sleep , the total number of recorded events to calculate the AHI or RDI during sleep testing is at least the number of events that would have been required in a 2 - hour period . No universal consensus exists on whether the AHI or the RDI should be the standard index used to determine treatment by specialists and insurance carriers , with Medicare being the most confusing as it varies by region as to whether AHI and RDI can be used . This needs to be resolved as soon as possible . One study found that 30 % of symptomatic patients would have been left untreated if the AHI were used rather the RDI . 33 In the authors ’ view , the RDI is preferable to the AHI because it includes flow - limitation events that end with arousals . The RDI is better suited to meet the new American Academy of Sleep Medicine ( AASM ) diagnostic criteria for OSA ( see below ) . One study has demonstrated that use of the AHI alone leads to the underdiagnosis of OSA in 30 % as compared to the use of the RDI . 33 AASM diagnostic criteria for OSA According to the Centers for Medicare & Medicaid Services criteria for the positive diagnosis and treatment of obstructive sleep apnea 32 a positive test for OSA is established if either of the following criteria using the AHI or the RDI is met : AHI or RDI greater than or equal to 15 events per hour , or AHI or RDI greater than or equal to 5 and less than or equal to 14 events per hour with documented symptoms of excessive daytime sleepiness ( EDS ) ; impaired cognition ; mood disorders ; insomnia ; or documented hypertension , ischemic heart disease , or history of stroke The AASM has developed its own criteria , as listed in the International Classification of Sleep Disorders : Diagnostic and Coding Manual , Second Edition . 4 At least 1 of the following criteria must apply for OSA to be diagnosed : The patient reports daytime sleepiness , unrefreshing sleep , fatigue , insomnia , and / or unintentional sleep episodes during wakefulness . The patient awakens with breath holding , gasping , or choking . The patient ’ s bed partner reports loud snoring , breathing interruptions , or both during the patient ’ s sleep . Polysomnography ( PSG ) shows more than 5 scoreable respiratory events ( eg , apneas , hypopneas , RERAs ) per hour of sleep and / or evidence of respiratory effort during all or a portion of each respiratory event . PSG shows more than 15 scorable respiratory events ( eg , apneas , hypopneas , RERAs ) per hour of sleep and / or evidence of respiratory effort during all or a portion of each respiratory event . Another current sleep disorder , medical or neurologic disorder , medication use , or substance use does not better account for the patient ’ s condition . Accreditation of sleep centers by the AASM is critical because there are still more centers that are unaccredited than there are centers that have chosen to meet the highest standards in the field ( as evidenced by achieving AASM accreditation ) . Whether AASM accreditation translates into insurance companies deciding to pay for studies performed at an AASM - accredited center has yet to be determined , although in the authors ’ opinion , payment should depend on achieving AASM accreditation . include the following : Chronic insufficient sleep Dyspnea due to pulmonary edema Idiopathic hypersomnia Nocturnal panic attacks Nonobstructive alveolar hypoventilation Obesity - hypoventilation syndrome ( pickwickian syndrome ) Periodic limb movement disorder Simple snoring Approximately 25 % of narcoleptic persons also have obstructive sleep apnea 137 Differential Diagnoses Asthma Central Sleep Apnea Syndromes Chronic Obstructive Pulmonary Disease ( COPD ) Depression Gastroesophageal Reflux Disease Hypothyroidism Narcolepsy Obstructive Sleep Apnea ( OSA ) Periodic Limb Movement Disorder Workup Sections Obstructive Sleep Apnea ( OSA ) Overview Presentation DDx Treatment Medication Questions & Answers Media Gallery References
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[
"Obstructive Sleep Apnea",
"sleep disordered breathing",
"respiratory disturbance index"
] |
http://emedicine.medscape.com/article/300341-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pulmonology Fungal Pneumonia Overview of Fungal Pneumonia Updated : Dec 28 , 2018 Author : Romeo A Mandanas , MD , FACP ; Chief Editor : Guy W Soo Hoo , MD , MPH more . . . Sections Overview of Fungal Pneumonia Risk Factors Epidemiology of Fungal Pneumonia Effects of Disseminated Fungal Disease Patient History Physical Examination Differentials in Fungal Pneumonia Workup Considerations CBC Count With Differential Sputum Examination and Potassium Hydroxide Stain Blood and Urine Cultures Nonculture Methods for Detecting Fungal Infections Serology Chest Radiography CT Scanning and MRI Procedures Histologic Findings Histopathology Treatment of Fungal Infection Inpatient Considerations Outpatient Considerations Clinical Consultations Deterrence and Prevention of Fungal Pneumonia Questions & Answers Show All Media Gallery Tables References Overview of Fungal Pneumonia Pneumonia is the leading infectious cause of death in developed countries . 1 2 Among the vast diversity of respiratory pathogens , fungi account for only a small portion of community - acquired and nosocomial pneumonias . However , fungal respiratory infections generate concern in the expanding population of immunosuppressed patients . 1 Fungi may colonize body sites without producing disease or they may be a true pathogen , generating a broad variety of clinical syndromes . Fungal pneumonia is an infectious process in the lungs caused by one or more endemic or opportunistic fungi . Fungal infection occurs following the inhalation of spores , after the inhalation of conidia , or by the reactivation of a latent infection . Hematogenous dissemination frequently occurs , especially in an immunocompromised host . Endemic fungal pathogens ( eg , Histoplasma capsulatum Coccidioides immitis Blastomyces dermatitidis Paracoccidioides brasiliensis Sporothrix schenckii Cryptococcus neoformans ) cause infection in healthy hosts and in immunocompromised persons , in defined geographic locations of the Americas and around the world . Opportunistic fungal organisms ( eg , Candida species , Aspergillus species , Mucor species ) tend to cause pneumonia in patients with congenital or acquired defects in the host immune defenses . Hyalohyphomycosis is a broad term that describes infections due to a number of rare and emerging heterogeneous fungi that when isolated from infected lung tissue , appear as hyaline ( lightly colored ) , filamentous fungi difficult to distinguish from Aspergillus . These genera include Scedosporium , Fusarium , Paecilomyces , Acremonium , and Trichoderma and are described in more detail in the article " Rare and Emerging Fungal Pulmonary Infections " . The diagnosis of fungal pneumonias is difficult to prove and is often made on a presumptive basis . It relies on a combination of clinical , radiologic , and microbiological factors . 3 Candida organisms and some ubiquitous filamentous fungi ( and Scedosporium ) can be isolated from oropharyngeal and respiratory tracts as colonizers without evidence of invasion or symptoms until a breakdown of tissue barriers or of the host ' s immune system occurs . Nonmolecular fungal markers in serum or other biological samples represent a noninvasive diagnostic tool , which can help in therapeutic decisions . The individual prognosis is often linked to the severity and outcome of the underlying disease and to whether a reversal of factors affecting the patient ' s immune status is possible . Pulmonary nodules resulting from fungal infection are seen below . Chest radiograph showing multiple pulmonary nodules . The patient was treated with corticosteroids for acute graft versus host disease following bone marrow transplantation for chronic myeloid leukemia . The patient smoked marijuana for 2 weeks prior to this chest radiograph being taken . Bronchoalveolar lavage revealed Aspergillus niger and other species on fungal cultures . View Media Gallery Complications of fungal pneumonia Complications of fungal pneumonia include ( 1 ) disease dissemination to other sites ( ie , brain , meninges , skin , liver , spleen , kidneys , adrenals , heart , eyes ) and sepsis syndrome and ( 2 ) blood vessel invasion , which can lead to hemoptysis , pulmonary infarction , myocardial infarction , cerebral septic emboli , cerebral infarction , or blindness . Other complications may include the following : Bronchopleural or tracheoesophageal fistulas Chronic pulmonary symptoms Mediastinal fibromatosis ( histoplasmosis ) Broncholithiasis ( histoplasmosis ) Pericarditis and other rheumatologic symptoms Treatment of fungal infection Therapy for fungal pneumonias must include antifungal agents . The type of antifungal drug employed must be selected based on the particular pathogen that is isolated or that is clinically suspected . Many classes of antifungal agents are now available , including the classic antibiotics ; first - , second - , and third - generation triazoles ; and the echinocandins . Amphotericin B is less frequently used and , when used , is often given as a liposomal formulation to decrease toxicity . 4 Risk Factors Workers or farmers with heavy exposure to bird , bat , or rodent droppings or other animal excreta in endemic areas are predisposed to any of the endemic fungal pneumonias , such as histoplasmosis , in which the environmental exposure to avian or bat feces encourages the growth of the organism . In addition , farmers , nursery workers , landscapers , and gardeners are at higher risk of acquiring sporotrichosis because of their chance of cuts or puncture wounds while working with soil . The Pseudoallescheria boydii / Scedosporium apiospermum complex has been implicated as an important pathogen in delayed disseminated infections among victims of near - drowning in polluted waters 5 or recent natural disasters such as the Indonesian tsunami in 2004 . 6 Coccidioides species are dimorphic existing as mold in the environments and as spherules in vivo . Arthroconidia in mold state are easily dispersed and inhaled into the lungs . 4 Therefore , because of its high virulence , it is also a threat among laboratory personnel working with this fungus . Conditions that predispose patients to any of the opportunistic fungal pathogens are as follows : Acute leukemia or lymphoma during myeloablative chemotherapy Bone marrow or peripheral blood stem cell transplantation Solid organ transplantation on immunosuppressive treatment Prolonged corticosteroid therapy Acquired immunodeficiency syndrome Prolonged neutropenia from various causes Congenital immune deficiency syndromes Postsplenectomy state Genetic predisposition With regard to predisposition through stem cell transplants , certain toll - like receptor ( TLR ) polymorphisms ( eg , TLR 4 haplotype S4 ) in an unrelated stem cell donor can increase the risk of invasive aspergillosis in the transplant recipient . 7 Similarly , TLR1 and TLR6 polymorphisms in the recipient have been associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation . 8 Epidemiology of Fungal Pneumonia Distribution endemic fungi in the United States Endemic fungi are prevalent in the Mississippi River Valley and the Ohio River Valley ( eg , H capsulatum B dermatitidis ) , the southwestern United States , and northwestern Mexico ( eg , C immitis ) . The environmental niche for H capsulatum is soil enriched by nitrogen contained in birds ' and bats ' droppings , whereas B dermatitidis is found in the soil and decaying wood , especially in waterways . Coccidioides species is found in alkaline , highly salinic , sandy soils and extreme temperatures . Sporotrichosis has been described worldwide ; prevalence is higher in tropical and temperate zones . Infection generally occurs following traumatic inoculation with soil , plants , and organic matter contaminated with the fungus . However , it occasionally may be inhaled , causing pneumonitis that often cavitates . 9 International distribution and incidence of fungal infection These fungi have caused several pneumonia outbreaks in Argentina and other areas of Central and South America . P brasiliensis is restricted to Central and South America . African histoplasmosis , which is caused by H capsulatum duboisii , is limited to equatorial Africa between 20 ° N and 10 ° S , which includes Gabon , Uganda , and Kenya . The other opportunistic organisms are ubiquitous , are usually found worldwide , and tend to cause disease in hosts with abnormal immune defenses . For instance , C neoformans can affect people with intact immune systems at a rate of 0.2 cases per million population per year . Prior to the advent of highly active antiretroviral therapy ( HAART ) , approximately 80 - 90 % of patients with acquired immunodeficiency syndrome ( AIDS ) developed cryptococcosis 10 Morbidity and mortality in fungal infection and pneumonia The endemic fungal pneumonias are generally self - limited in healthy hosts . C immitis is the most virulent , yet 90 % of patients recover without treatment . However , patients with fungal pneumonias may develop chronic pulmonary complications ( eg , cavitation , pleural effusions , bronchopleural fistulas ) or extrapulmonary complications . In patients with AIDS , the mortality rate is as high as 70 % . Aspergillosis represents the leading cause of invasive pulmonary lung infection and death among patients who are neutropenic ( from either leukemia chemotherapy or bone marrow transplantation ) with a mortality rate of 50 - 85 % . More often , in the case of aspergillosis and candidal infections or meningoencephalitis in the case of cryptococcosis , the cause of mortality in patients who are immunocompromised is disseminated fungal disease . 11 Mucormycosis represents the second most common cause of fungal pneumonia , accounting for approximately 10 % of all invasive pulmonary infections in immunosuppressed patients and resulting in significant morbidity and mortality . Patients with hematologic malignancies are at highest risk , but uncontrolled diabetes mellitus and iron overload are important predisposing factors . Rhizopus Mucor Absidia Lichtheimia ) , and Rhizomucor species are the most commonly implicated . P boydii or its asexual form , S apiospermum , is now considered an emerging pathogen causing pneumonia and disseminated infections in the same immunocompromised hosts as aspergillosis . Scedosporium species ( including prolificans ) are inherently resistant to amphotericin B and echinocandins , and infections carry high mortality rates , especially in the persistently profound neutropenic patient . 12 The mortality rate for untreated disseminated histoplasmosis is 80 % , but , with treatment , the rate is reduced to 25 % . Candida albicans and Candida glabrata are ubiquitous commensals of humans and can be found especially in the oral cavity and gastrointestinal tract of most healthy humans . On the other hand , they are also the most pathogenic yeasts . 13 Among the C albicans C glabrata rank as the two most frequently isolated organisms . 13 Despite the frequent isolation of species from respiratory samples in nonneutropenic patients , the organisms are not considered causes of pneumonia regardless of the species isolated . 14 Pneumonia from species is exceptional in nonneutropenic patients . 14 Sporothrix schenckii is the etiological agent of sporotrichosis , a chronic fungal infection that most frequently affects cutaneous and subcutaneous tissues and adjacent lymphatics . 9 However , extracutaneous forms have been described with no history of traumatic injuries , making the diagnosis difficult . Pulmonary presentation is rare and may be caused by the dymorphic fungus S schenckii and even more rarely by other Sporothrix species . Lately , recognition of this condition has increased as more cases have been reported . 15 In immunocompromised patients , disseminated sporotrichosis may be associated with significant morbidity and , possibly , mortality . Race - associated characteristics Although no race predilection is described , causes more severe disease in patients of African American or Philippine descent . Sex predilection Endemic fungal disease affects men ( 75 - 95 % ) more often than women . Estrogen - mediated inhibition of mycelium - to - yeast transformation may be responsible for the male predominance . Estrogen also seems to have a protective effect against cryptococcal infection . Cryptococcosis has a male - to - female ratio of 2 - 3 : 1 . Effects of Disseminated Fungal Disease Fungi may simply colonize body sites with no apparent disease , or they may invade , producing a wide variety of syndromes . The development of disease is a result of the susceptibility of the host and the virulence of the pathogen . Endemic mycoses with associated dissemination can affect skin ( eg , papules , pustules , plaques , ulcers , abscesses , proliferative lesions that may mimic skin cancer as in infection ) , bone and joints , and the brain and meninges ( meningitis with poor prognosis [ 10 - 20 % ] , brain abscess in infection with species ) . Other affected sites include the following : Kidneys Liver and spleen ( hepatosplenic candidiasis ) Muscle ( species ) Eye ( endophthalmitis ; in species infection ) Nasal passages and sinuses ( species ) Bloodstream and bone marrow ( septicemia or sepsis syndrome ) Patient History History findings in persons with fungal pneumonia may include the following : Fever Cough , usually nonproductive Pleuritic chest pain or dull discomfort Progressive dyspnea leading to respiratory failure Airway obstructive symptoms from enlarged mediastinal adenopathy in the endemic mycoses Hemoptysis ( in invasive aspergillosis or mucormycosis ) History of travel to or exposure in areas containing endemic mycoses Symptoms from involvement of extrapulmonary systems ( may suggest disease ) Rheumatologic syndromes ( common among endemic mycoses ) - Arthritis and arthralgia , erythema nodosum , erythema multiforme , and pericarditis Endemic mycoses with associated dissemination Hypersensitivity or allergic reactions Extrapulmonary sites in individuals who are immunocompromised Meningoencephalitis in patients with AIDS and cryptococcosis In individuals who are neutropenic or immunocompromised , persistent fever ( even before pulmonary findings ) may be an early sign of infection , especially if the fever is unresponsive to broad - spectrum antibiotics . Hypersensitivity or allergic reactions include allergic bronchial asthma ( species ) , allergic bronchopulmonary mycoses ( species ) , bronchocentric granulomatosis ( necrotizing granulomatous replacement and eosinophilic infiltration of bronchial mucosa in infection with species ) , and extrinsic allergic alveolitis ( malt worker ' s lung , farmer ' s lung ) . Physical Examination Signs and symptoms of fungal pneumonia are not specific , and are indistinguishable from those associated with respiratory infections of other origins . Physical examination findings in patients with fungal pneumonia may include the following : Temperature elevation Tachycardia Tachypnea Respiratory distress Rales Signs of pulmonary consolidation Pleural rub Important possible extrapulmonary findings include the following : Meningitis ( neck stiffness , headaches , mental status change ) Brain abscesses Skin lesions ( pustules , papules , plaques , nodules , ulcers , abscesses , hemorrhagic lesions , mycetomas ) Rheumatologic and allergic findings Pericardial rub Differentials in Fungal Pneumonia Conditions that can mimic the symptoms of fungal pneumonia include the following : Acute respiratory distress syndrome Chemical worker ' s lung Chlamydial pneumonias Coal worker ' s pneumoconiosis Eosinophilic pneumonia Pneumocystis carinii pneumonia Aspiration pneumonia Bacterial pneumonia Viral pneumonia Cardiogenic pulmonary edema Neurogenic pulmonary edema Idiopathic pulmonary fibrosis Interstitial pulmonary fibrosis ( nonidiopathic ) Tuberculosis Workup Considerations The mortality due to fungal respiratory infections among immunosuppressed populations has remained elevated despite the arrival of new antifungal medications . The paucity of specific signs of infections and the low sensitivity of conventional culture - based methods for its diagnosis results in delayed initiation of antifungal therapy . Nonculture - based diagnostic tools , such as galactomannan ( GM ) and beta - D - glucan ( BG ) , are part of the diagnostic workup of invasive fungal pneumonia with other clinical , radiologic , and microbiologic criteria . CBC Count With Differential The total white blood cell ( WBC ) count may be elevated in normal hosts with endemic mycoses . Eosinophilia can be observed in the differentials , particularly in persons with coccidioidomycosis . If the patient presents with neutropenia or leukopenia , the possibility of an opportunistic infection with Candida , Aspergillus , Mucor , or organisms is increased . Sputum Examination and Potassium Hydroxide Stain This study may show fungal hyphae or yeasts . However , the results must correlate with the clinical situation , because saprophytic colonization occurs in the oropharyngeal or respiratory tract of some patients and may not necessarily indicate invasive infection . Carefully transport , process , and culture specimens that may be contaminated by bacteria , may be saprophytic yeasts endogenous to the oral cavity , and may be airborne conidia of saprophytic fungi . The diagnosis of pulmonary cryptococcal infection is confirmed if the organism is grown in culture from sputum or BAL fluid in a patient who has clinical symptoms and radiographic finding compatible with cryptococcosis . Histoplasmosis is definitively diagnosed by growth of the organism in sputum ; BAL fluid , lung tissue , or mediastinal nodes can be cultured . In pulmonary sporotrichosis , the recovery of the fungi by culture of sputum and / or positive bronchoscopy are required for diagnosis . 15 Cultures from sputum samples collected by fiber optic bronchoscopy are not valuable for the diagnosis of pneumonia by To make the diagnosis , a biopsy is required to demonstrate tissue invasion . Colonization of the respiratory tract by C andida is very frequent in critically ill patients with mechanical ventilation , but pneumonia by is extremely rare because the innate defense mechanisms of the lungs make them relatively resistant to candida invasion . species tend to grow well on routine fungal media , but , when dealing with BAL fluid or tenacious respiratory secretions , selective media ( cycloheximide or benomyl agar ) are recommended for their isolation . 12 Blood and Urine Cultures Obtain a blood culture to identify species ( lysis centrifugation ) or if the patient has disseminated disease . Obtain a urine fungal culture in men after a prostatic massage , to identify Cryptococcus or Blastomycosis species . Nonculture Methods for Detecting Fungal Infections These provide a more rapid and sensitive test when compared with culture methodology . Various antigen detection assays , such as galactomannan enzyme immunoassay for detection of invasive aspergillosis , are now in clinical use . Polymerase chain reaction ( PCR ) – based assays are also available for detecting various pathogens , including Histoplasma , and species . 16 17 18 Comparison of these assays ( antigen detection using enzyme - linked immunosorbent assay [ ELISA ] or latex agglutination and molecular detection with PCR ) show equal specificities for all 3 assays ( ≥ 97 % ) in the detection of species . PCR - based assays are most sensitive compared with ELISA and latex agglutination ( 95 % , 75 % , and 25 % , respectively ) . The newest available testing in the diagnosis of blastomycosis is an enzyme immunoassay performed on urine or serum that detects a cell wall galactomannan antigen found in . However , the cross reactivity with is close to 100 % . Therefore , in patients with blastomycosis , the sensitivity or specificity of these tests is not clear . For species antigen , galactomannan assay findings may be positive in the blood very early prior to clinical suspicion of invasive fungal infection and may be of use in monitoring and preemptive treatment in high - risk populations . 19 20 21 Using a galactomannan platelia enzyme immunoassay approved by the US Food and Drug Administration ( FDA ) , investigators showed that two consecutive samples with an optical index of 0.5 provided the highest test accuracy ( specificity , 97.5 % ; sensitivity , 92.1 % ; positive predictive value , 87.5 % ; negative predictive value , 98.5 % ) . 22 Testing in bronchoalveolar lavage ( BAL ) fluid increased the sensitivity compared with serum galactomannan assay from 71 - 100 % . 23 Care should be taken , however , because false - positive results have been reported in patients taking piperacillin - tazobactam antibiotics and certain intravenous fluids , such as plasmalyte . 24 Beta - glucan testing is also available and may be comparable or more sensitive than galactomannan assays in diagnosing invasive aspergillosis and can detect a broad spectrum of invasive fungal pathogens , including Pneumocystis jirovecii Several kits are available worldwide . False - positive results have also been reported in patients receiving fungal - derived antibiotics and cross - reactions have been reported with Pseudomonas aeruginosa infections . 25 The molds causing mucormycosis , which belong to the subphylum Mucoromycotina , do not contain galactomannan or beta - glucan in their cell wall . Therefore , mucormycosis can not be diagnosed with the galactomannan or beta - glucan assays . PCR is most sensitive ( 100 % ) when performed on the bronchial lavage fluid of patients with invasive pulmonary aspergillosis , but it is only 40 - 66 % sensitive when performed on the blood . No standardized protocols have been established among laboratories performing this assay . 11 17 25 ELISA or latex agglutination is 70 - 80 % sensitive for identifying . PCR for from the bronchoalveolar lavage fluid aids in the rapid detection within 24 hours in a patient with AIDS , and this has been confirmed 10 days later based on the growth and culture isolation of the organism from various tissues . Serology The utility of serology depends on the individual fungal infectious agent . Antibody detection for the identification of is highly useful for all forms of pulmonary infection caused by this fungi . Serology also plays an important role in the diagnosis of acute pulmonary and chronic cavitary pulmonary histoplasmosis . Both complement fixation and immunodiffusion tests should be ordered , but these tests are of less utility if the pulmonary infection is due to other fungi . Serology testing for blastomycosis provides little clinical diagnostic help because of the insensitivity of testing for this fungus and the antibody cross - reactivity that occurs with other fungal infections . Patients with pulmonary sporotrichosis will have antibody against S schenckii ; however , it is highly variable in sensitivity and specificity . Thus , it may not be useful in the diagnosis of the disease . Detection of the polysaccharide capsule antigen in serum plays an important role in the diagnosis of disseminated cryptococcosis , but its sensitivity decreases in those patients not infected with human immunodeficiency virus , and also disease limited to the lung . Chest Radiography Patchy infiltrate , nodules ( seen in the image below ) , consolidation , cavitation , or pleural effusion may be observed . Mediastinal adenopathy is common in patients with endemic fungal pneumonias . The adenopathy may be either unilateral or bilateral . In neutropenic patients infected with aspergillosis ( 60 % ) , pulmonary nodules surrounded by ground - glass opacity called “ halo sign ” is a common finding . On the other hand , lung transplant recipients present less specific patchy infiltrates . Miliary infiltration occurs in patients with disseminated disease . Chest radiograph showing multiple pulmonary nodules . The patient was treated with corticosteroids for acute graft versus host disease following bone marrow transplantation for chronic myeloid leukemia . The patient smoked marijuana for 2 weeks prior to this chest radiograph being taken . Bronchoalveolar lavage revealed Aspergillus niger and other species on fungal cultures . View Media Gallery CT Scanning and MRI Chest CT scanning This imaging study plays a role in the early diagnosis of nonspecific infiltrates in patients who are immunocompromised . High - resolution chest computed tomography ( CT ) scanning allows observation of the halo sign in patients with aspergillosis . This is a nodular lesion usually surrounded by a ground - glass opacity or halo . As many as 61 % of 235 patients with invasive aspergillosis were found to have the halo sign in one study . 26 Lung lesions from aspergillosis are shown below . Obtaining a CT scan of the abdomen and brain may reveal sites of dissemination . CT scan of a patient with invasive aspergillosis showing multiple lung lesions . The cavitary lesion on the left lung shows a ground - glass halo sign . CT scan of aspergillosis of the lungs showing multiple pleural - based and lung parenchymal lesions . CT scans should be obtained at the first hint of pulmonary infection in patients at risk of mucormycosis because of the high mortality in this patient population . In patients with hematological malignancies , several nonspecific findings have been proposed to differentiate mucormycosis from other infections , especially aspergillosis . These include the presence of multiple nodules and pleural effusions and the development of a “ reversed halo , ” which is a ground - glass attenuation in the center of a nodule with a surrounding zone of consolidation . 27 The reversed halo sign is not exclusive to mucormycosis ; it might also be found in patients with paracoccidioidomycosis , histoplasmosis , cryptococcosis , 27 and even nonfungal causes like tuberculosis and sarcoidosis . 28 In the setting of severe neutropenia however , it warrants a high suspicion for pulmonary mucormycoses 29 and initiation of appropriate empiric treatment while awaiting culture results . MRI of lung lesions Magnetic resonance imaging ( MRI ) may reveal the hemorrhagic content of lesions . Procedures Fiberoptic bronchoscopy ( procedure of choice ) is used to obtain bronchial lavage specimens for staining and culture techniques and transbronchial biopsy specimens for identification of fungal tissue invasion . This procedure reveals positive results in 75 - 90 % of endemic mycoses , shows a 50 - 90 % yield in cryptococcal disease , and shows varying yields in infections , for which clinical correlation is still important . The yield of isolating from bronchoalveolar lavage specimens may also depend upon the underlying condition and the leukocyte count of the patient . One study demonstrated that there was little value in doing bronchoscopy and bronchoalveolar lavage in acute leukemia patients with leukocyte counts of less than 100 / µL compared with nonleukemia patients such as allogeneic hematopoietic stem cell recipients . 30 Transthoracic CT - guided fine - needle aspiration of pulmonary nodules can provide material for histopathology and for special staining techniques and culture . Obtaining specimens in this manner might allow for avoidance of an open lung biopsy . Occasionally , performing an open lung biopsy is the only way to prove invasive disease for or organisms . However , this procedure may be difficult to perform in patients with severe neutropenia and thrombocytopenia who are in respiratory failure . Perform a lumbar spinal puncture in patients with suspected cryptococcosis or disseminated disease with central nervous system ( CNS ) symptomatology in order to detect the polysaccharide capsule antigen by latex agglutination or enzyme immunoassay . Conduct a bone marrow aspiration and biopsy if the patient has persistent fever or suspected disseminated disease or if the patient has hematologic findings , such as thrombocytopenia or neutropenia . Histologic Findings Biopsy specimens show the following : Caseating or necrotizing granulomas with intracellular organisms inside macrophages ( eg , H capsulatum , C immitis Fungal hyphae in infection with Aspergillus , Mucor , or species Intracellular yeast organisms in species infections Histopathology Histopathology findings are as follows : Aspergillosis : Nonpigmented ( hyaline ) , septate hyphae with acute angle branching , but not specific Mucormycosis : Nonpigmented ( hyaline ) , broad non - septate hyphae presumptive evidence for mucormycosis Cryptococcosis ; Yeast forms with clear surrounding area are suggestive ; mucicarmine stain is specific Blastomycosis : Broad based budding yeast ( 10 - 15 µm ) ; forms provide presumptive evidence of infection Histoplasmosis : Small yeasts ( 2 - 4 µm ) with narrow - based budding grouped in clusters inside macrophages ; characteristic yeast forms provide presumptive evidence of infection Coccidioidomycosis : Spherules large and specific , give presumptive diagnosis Candidiasis : Small yeasts ( 3 - 5 µm ) intermingled with pseudohyphae and / or hyphae ; C glabrata does not produce filaments or pseudohyphae Sporotrichosis : Dimorphic fungus , conidiophores , and conidia ; cigar - shaped yeast may be visualized in tissue specimens stained with periodic acid - Schiff , Gomori methenamine - silver , or immunohistochemical stains Scedosporium : Haphazardly branching hyphae and lemon - shaped conidia ; parallel hyphae bridged at right angles producing letter - H patterns ; purple conidia in tissue 31 Treatment of Fungal Infection In persons with endemic mycoses , spontaneous recovery usually occurs without treatment , especially in patients who are mildly affected and immunocompetent without dissemination ; otherwise , administer treatment as outlined in the table below . In cases in which aspergillosis , mucormycosis , and candidiasis occur in an immunocompromised host , reversing the factors affecting the patient ' s immune status is linked to successful recovery from the infection . Attempt ancillary interventions that may help to promote recovery from the opportunistic infection . These include ( 1 ) ensuring , with the use of growth factors , neutropenia recovery in patients receiving chemotherapy and bone marrow transplants ; ( 2 ) withdrawing or tapering immunosuppressive drugs and steroids ; and ( 3 ) removing infected or highly colonized catheters in patients with candidiasis . Table . Medical and Surgical Fungal Therapy ( Open Table in a new window ) Fungal Pathogen Indication for Antifungal Therapy Surgical Care and Other Treatments Antifungal Drugs Used Histoplasmosis Acute pulmonary histoplasmosis with hypoxia ; prolonged moderate symptoms for more than 1 month ; disseminated disease ; immunosuppressed host Mortality rate for untreated disseminated disease at 80 % ; reduced to 25 % with treatment Significant hemoptysis ; recurrent pneumonia ; repair of bronchopleural fistula Corticosteroids in severe hypoxia or ARDS Anti - inflammatory agents to treat rheumatologic syndromes Amphotericin B induces rapid response in patients who are severely ill or immunocompromised Azoles / triazoles in patients with milder illness Coccidioidomycosis Disseminated disease ; chronic pulmonary disease ; acute pulmonary infection with hypoxia or protracted morbidity ( > 1 - 2 mo ) ; immunosuppressed host ( worst outcome , 70 % mortality ) Surgical debridement or resection of infective tissue often necessary adjunct to antifungal treatment Anti - inflammatory agents for rheumatologic syndromes Amphotericin B effective in more than 90 % of cases ; first choice in severe cases or immunocompromised Fluconazole / itraconazole first choice in mild to moderate infection ( or after improvement ) Treatment less effective than in other endemic mycoses Blastomycosis Persistent or recurrent symptoms of acute or chronic pulmonary disease or with pleural involvement ; disseminated disease Steroids for ARDS Amphotericin B response rates of 77 - 90 % of cases ; for severe infection or immunocompromised Itraconazole successful in 90 % of cases ; for mild to moderate infection Ketoconazole response of 80 % ; poor outcome in patients who are immunosuppressed Fluconazole less effective , 65 % response rate Chronic maintenance treatment essential for all patients with AIDS or meningitis Cryptococcosis Patients who are immunosuppressed and symptomatic ; patients who are immunocompetent with disease progression ; any patients with meningitis or disseminated disease N / A Amphotericin B in patients who are severely ill Fluconazole in milder cases or after clinical response to amphotericin B Lifelong maintenance therapy in AIDS patients may not be necessary as long as the patient ' s CD4 count is maintained above 100 cells / µL with HAART 32 Flucytosine may be of benefit when combined with amphotericin B in patients with severe or disseminated disease . Aspergillosis All patients with invasive disease ; in patients who are immunosuppressed , early diagnosis and empiric treatment for persistent fever not responding to broad - spectrum antibiotics ; high mortality once infiltrates and symptoms appear ; prognosis ultimately linked to severity and outcome of underlying disease Mortality rate of 50 - 60 % in patients with AIDS Rapid tapering of immunosuppressive agents and corticosteroids and reversal of neutropenia ( if possible ) Voriconazole is the new standard of care for invasive aspergillosis based on superiority over amphotericin B in primary therapy Lipid formulations of amphotericin B have at least equal efficacy but less toxicity compared with amphotericin B desoxycholate Oral voriconazole can be used to complete treatment with initial response to IV voriconazole or amphotericin B Posaconazole is second line agent Echinocandins second line agent when voriconazole is not tolerated or in combination with voriconazole in an attempt to enhance antifungal activity Isavuconazole has been shown to be not inferior to voriconazole for aspergillosis 33 Mucormycosis Mortality rates as high as 70 % in patients with invasive pulmonary mucormycosis Aggressive surgical debridement of necrotic tissue important in mucormycosis , especially if confined to lungs Lipid amphotericin B is the mainstay of therapy ; posaconazol is poorly absorbed , considered second line species generally resistant to azoles ( voriconazole has no activity against them ) Echinocandins ( Caspofungin ) useful as salvage therapy Isavuconazole has been shown to be comparable to amphotericin B and posaconazole for mucormycosis 33 Candidiasis All patients with invasive disease or dissemination ; important to reverse factors affecting immune status Expert recommendations and clinical practice guidelines do not recommend antifungal treatment facing isolation in respiratory samples regardless the number of positive samples Rapid tapering of immunosuppressive agents and corticosteroids ; important to remove indwelling infected intravenous lines or urinary catheters in setting of hematogenous spread Amphotericin B is mainstay Flucytosine may be of benefit when added to amphotericin B Fluconazole use in pulmonary disease not studied but is effective in hepatosplenic candidiasis and candidemia Echinocandins may be useful alternatives Sporotrichosis Management should be based in clinico - radiological manifestations ; two presentations of pulmonary sporotrichosis : non - cavitary disease ( multifocal ) and cavitary disease ( primary ) Surgical interventions when presence of cavitations and initial medical therapies have failed ; used as adjunctive therapy Itraconazole as first line agent in mild to moderate cases Amphotericin B first line in life threatening conditions Scedosporiosis Emerging opportunistic pathogen in similar scenario as aspergillosis but highly resistant to amphotericin B and echinocandins ; mortality rate is 54 - 78 % in transplant recipients In near - drowning victims , close surveillance for clinical and radiographic findings with low threshold for empiric treatment Aggressive surgical debridement for disseminated disease in the form of subcutaneous abscesses , brain abscess , and others Granulocyte transfusions or growth factors to enhance neutrophil recovery Resistant to amphotericin B and echinocandins Voriconazole as single agent or in combination with other agents such as terbinafine 34 Pharmacologic treatment When treatment is indicated , initiate antifungal agents as appropriate . Amphotericin B is the mainstay of initial therapy in many cases , especially for patients who are acutely ill . More expensive liposomal preparations of amphotericin B offer equal efficacy with less toxicity . In patients with invasive aspergillosis , including pulmonary aspergillosis , voriconazole is the new standard of care , based on its superiority over amphotericin B as primary therapy . 35 36 37 Vary the dose and treatment duration depending on the underlying pathogen causing the pneumonia . Care should be taken regarding patients on long - term voriconazole treatment . Bone pain with radiologic evidence of periostitis and 10 - fold increased fluoride levels have been reported in allogeneic stem cell transplant patients taking the drug for at least 3 months . Symptoms and findings were reversed with discontinuation of voriconazole . 38 There is a possible association between the use of voriconazole in markedly immunosuppressed patients as prophylactic agent and the development of mucormycosis , but this matter is still controversial . Amphotericin B is available in a variety of formulations . Conventional amphotericin B injection contains amphotericin B and sodium deoxycholate as the solvent vehicle . Amphotericin B cholesteryl sulfate complex ( ABCD , Amphotec ) consists of a 1 : 1 molar ratio of amphotericin B to cholesteryl sulfate in a colloidal dispersion , forming a bilayer in microscopic , disk - shaped particles that have a diameter of approximately 115 nm and a thickness of 4 nm . Amphotericin B lipid complex ( ABLC , Abelcet ) is composed of amphotericin B and phospholipid complex , with a microscopic , ribbonlike structure having a diameter of approximately 2 - 11 µm . Liposomal amphotericin B ( L - AmB , AmBisome ) contains amphotericin B intercalated in a unilamellar bilayer liposomal membrane ; has a liposomal membrane diameter of less than 100 nm ; and consists of hydrogenated soy phosphatidylcholine , cholesterol , distearoyl phosphatidylglycerol , and alpha tocopherol . Some clinicians offer empiric therapy with conventional amphotericin B or liposomal amphotericin B for presumed fungal infections in patients who are febrile and neutropenic ( eg , cancer , bone marrow transplantation , solid organ transplantation ) and whose febrile state persists after receiving broad - spectrum antibiotics for a few days . Other agents that could be used in this setting are itraconazole and an echinocandin , namely , caspofungin . 39 The therapy is continued until the neutropenia resolves and the patient does not show a documented fungal infection or radiographic infiltrate . Prophylactic therapy ( suppressive therapy ) with amphotericin B is used against recurrence or relapse of coccidioidomycosis , cryptococcosis , or histoplasmosis in individuals infected with the human immunodeficiency virus ( HIV ) who have received adequate treatment for the infection . Other formulations , however , are starting to replace amphotericin B because of their ease of use ( oral formulations ) and lower toxicity for more long - term suppression . Posaconazole is used in the prophylaxis of invasive infections in severely immunocompromised patients receiving hematopoietic stem cell transplants who have graft versus host disease and in patients with hematologic malignancies who have chemotherapy - induced neutropenia . 40 While it used to be available only as an oral suspension given thrice daily , a delayed - release tablet formulation of posaconazole for once - daily administration allows for better bioavailability without being affected by food . The intravenous formulation is also administered once daily , but it has to be through a central line because of the presence of a solubilizing excipient SBECD ( sulfobutylether - β - cyclodextrin ) , which can be potentially renal toxic and can accumulate in patients with moderate - to - severe renal failure . 41 Because of the large interindividual and intraindividual variations in bioavailability and drug - to - drug - interactions , therapeutic drug monitoring is recommended for posaconazole , especially if used in the therapeutic setting to treat invasive aspergillosis or zygomycosis . Other antifungal agents used in the treatment of fungal pneumonia are fluconazole ( Diflucan ) , itraconazole ( Sporanox ) , flucytosine ( Ancobon ) , and ketoconazole ( Nizoral ) . Newer antifungal agents , such as the third - generation triazoles or the echinocandins , are more tolerable than amphotericin B or its liposomal preparations are and may even be more effective in first - or second - line treatment . Isavuconazole has been approved by the FDA and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis . Studies have shown it to be not inferior to voriconazole for aspergillosis and comparable to amphotericin B and posaconazole for mucormycosis . There have been increasing reports of azole resistance in species . This might be the result of the increasing use of these agents for prophylaxis and treatment of fungal infections ; also there are associations with exposure to azole - like compounds used in the agricultural industry in some countries . In addition , some species have intrinsic resistance to various azoles . Caspofungin is approved for the treatment of invasive infections in patients unresponsive to or unable to receive amphotericin B . Combinations of a triazole with an echinocandin with or without amphotericin B have been anecdotally reported to be effective in some cases of resistant organisms , such as Zygomycetes 39 Echinocandins such as caspofungin , micafungin anidulafungin 42 43 44 offer a broad spectrum of activity for the many species , including fluconazole - resistant strains . They also show effectiveness in infections alone or in combination with an azole . Because of the introduction of these safer and ( possibly ) more potent agents , and owing to the ability to combine them together , the outlook for patients with invasive pulmonary infections , especially immunocompromised hosts , may be improving . The role of combination therapy has been studied only in small retrospective studies with very unclear results . Combination therapy is usually not indicated in first - line treatment . In rare cases , it might be offered with a great deal of caution as second - line or salvage treatment . 34 The establishment of neutrophil recovery or engraftment and the reduction of immunosuppression in certain patients who are at risk for fungal infections are likely to improve the chances of a successful treatment outcome . Granulocyte - macrophage colony - stimulating factor can theoretically augment pulmonary host defenses against A fumigatus infection . Surgical care Surgery may be indicated in invasive aspergillosis . 45 Surgery is indicated in patients with documented invasive aspergillosis who have been treated with antifungal agents but who have residual lesions . The surgery is performed to prevent disease relapse when additional immunosuppression is required . Surgery is also indicated as a means to prevent or treat massive bleeding , especially when the lung lesion is contiguous with a large blood vessel . In cavitary pulmonary sporotrichosis , surgical management should be considered in the course of the disease , even for bilateral presentation , providing that the patient has adequate predicted respiratory reserves post - surgery , as delayed surgery may result in complications and poorer outcomes . Inpatient Considerations Watch for rapidly progressive respiratory failure in patients who are neutropenic . Patients may require intubation and mechanical ventilatory support . In patients who are severely neutropenic , rapid progression of fungal pneumonia and dissemination of fungal infection ( eg , aspergillosis , mucormycosis ) necessitate a high degree of suspicion , early empiric antifungal therapy , and corrective measures ( if possible ) to reverse neutropenia or other causes of immunosuppression . Consider rapidly reducing or withdrawing immunosuppressive therapy ( eg , corticosteroids ) , if feasible . Correct hyperglycemia and acidosis . Consider the correction of neutropenia via the administration of growth factors ( eg , filgrastim [ Neupogen ] , pegfilgrastim [ Neulasta ] , sargramostim [ Leukine ] ) or granulocyte transfusions . Outpatient Considerations Offer maintenance therapy to suppress disease reactivation or recurrent disease in patients infected with HIV or in other individuals who are immunocompromised . Ensure appropriate follow - up care to monitor for possible recurrence . Patients with ongoing immune deficiencies may require prolonged or lifelong maintenance therapy with triazole agents to prevent recurrences . Clinical Consultations A pulmonologist may perform diagnostic procedures ( eg , bronchoscopy , bronchoalveolar lavage , transbronchial biopsy ) . Interventional radiologists can perform needle aspirations , when necessary , for diagnosis . Patients who are severely ill and progressively hypoxic may require intensive care , ventilatory support , and pressor support in the ICU under the care of a critical care intensivist . Rheumatologists can assist with the rheumatologic syndromes manifesting with the endemic mycoses . Infectious disease consultants may assist with the intricacies of antifungal treatment , especially with respect to the exact drugs , dose , duration , therapy length , maintenance treatment , and follow - up . Deterrence and Prevention of Fungal Pneumonia Instruct patients to avoid travel to and exposure in endemic areas . Patients undergoing bone marrow transplantation or any period of prolonged neutropenia are advised to avoid activities ( eg , gardening , cleaning , agitating debris ) or objects ( eg , potted plants , flowers , fresh fruits and vegetables , uncooked spices ) that may unduly cause exposure to spores of species or other ubiquitous fungi . For patients undergoing bone marrow transplantation , solid organ transplantation , or antileukemic chemotherapy , the use of high efficiency particulate air ( HEPA ) filtration systems in the treatment units may minimize patient risk of exposure to spores . Administer prophylactic antifungal therapy ( ie , treatment with intranasal or intravenous amphotericin B or its other formulations ) in patients at high risk for opportunistic fungal infection , including patients with a history of fungal infection . 46 In a study , prophylactic posaconazole was shown to be superior to fluconazole in reducing invasive aspergillosis incidence ( 1 % vs 5.9 % , respectively ) in allogeneic hematopoietic stem cell transplant recipients with clinically significant graft - versus - host disease . 47 In another trial , conducted using neutropenic patients undergoing chemotherapy for acute leukemia or myelodysplasia , prophylactic posaconazole again reduced the incidence of invasive aspergillosis to 1 % . The incidence in patients in the study who received either fluconazole or itraconazole was 7 % . 48 Questions & Answers Overview Which groups are at increased risk for fungal pneumonia ? What causes fungal pneumonia ? How is fungal pneumonia diagnosed ? What are possible complications of fungal pneumonia ? What are the treatment options for fungal pneumonia ? Which occupations increase the risk for fungal pneumonia ? Which medical conditions are risk factors for opportunistic fungal pneumonia ? Where are the fungal pathogens that cause pneumonia most prevalent in the US ? What is the global incidence of fungal pneumonia ? What is the associated morbidity and mortality in fungal pneumonia ? How does the prevalence of fungal pneumonia vary by race ? How does the prevalence of fungal pneumonia vary by sex ? Which body sites are affected by disseminated fungal infections ? What are the signs and symptoms of fungal pneumonia ? What are early signs suggestive of fungal pneumonia ? What are allergic reactions suggestive of fungal pneumonia ? Which signs and symptoms are specific for fungal pneumonia ? What are physical findings suggestive of fungal pneumonia ? What are extrapulmonary findings suggestive of fungal pneumonia ? Which conditions should be included in the differential diagnosis of fungal pneumonia ? Why does the mortality rate for fungal pneumonia remained elevated ? What is the role of lab testing in the workup of fungal pneumonia ? Which WBC count is characteristic of fungal pneumonia ? What does a finding of eosinophilia suggest in the workup of fungal pneumonia ? What does a finding of neutropenia and leukopenia suggest in the workup of fungal pneumonia ? What is the role of sputum cultures in the workup of fungal pneumonia ? What is the role of blood culture in the workup of fungal pneumonia ? What is the role of urine culture in the workup of fungal pneumonia ? What is the role of antigen testing in the workup of fungal pneumonia ? What is the role of serology testing in the workup of fungal pneumonia ? What is the role of radiography in the workup of fungal pneumonia ? What is the role of CT scanning in the workup of fungal pneumonia ? When are CT scans indicated in the workup of fungal pneumonia ? What is the role of MRI in the workup of fungal pneumonia ? What is the role of bronchoscopy in the workup of fungal pneumonia ? What is the role of CT - guided FNA for the workup of fungal pneumonia ? What is the role of open lung biopsy in the workup of fungal pneumonia ? What is the role of lumbar puncture in the workup of fungal pneumonia ? What is the role of bone marrow aspiration in the workup of fungal pneumonia ? Which biopsy findings are characteristic of fungal pneumonia ? Which histologic findings are characteristic of fungal pneumonia ? What are the treatment options for fungal pneumonia ? Which antifungal agents are used in treatment of fungal pneumonia ? What are possible adverse effects of long - term voriconazole treatment for fungal pneumonia ? What is the role of amphotericin B in the treatment of fungal pneumonia ? Which antifungal agents may be alternatives to amphotericin B for treatment of fungal pneumonia ? What is the role of combination therapy in the treatment of fungal pneumonia ? When is surgery indicated for fungal pneumonia ? What are in - patient treatment options for fungal pneumonia ? What monitoring is needed following treatment for fungal pneumonia ? Which specialist consultations are needed for the diagnosis and treatment of fungal pneumonia ? How is fungal pneumonia prevented ? Sections Fungal Pneumonia Show All Media Gallery Tables References
|
[
"Fungal Pneumonia",
"infectious"
] |
http://emedicine.medscape.com/article/301450-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pulmonology Idiopathic Pulmonary Arterial Hypertension Updated : Jun 21 , 2018 Author : Ronald J Oudiz , MD , FACP , FACC , FCCP ; Chief Editor : Zab Mosenifar , MD , FACP , FCCP more . . . Sections Overview Practice Essentials Background Pathophysiology Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Guidelines Medication Questions & Answers References Practice Essentials Idiopathic pulmonary arterial hypertension ( IPAH ) is a rare disease characterized by elevated pulmonary artery pressure with no apparent cause . IPAH is also termed precapillary pulmonary hypertension and was previously termed primary pulmonary hypertension . Untreated IPAH leads to right - sided heart failure and death . In approximately a third of patients with pulmonary arterial hypertension ( PAH ) , echocardiography demonstrates right - to - left shunting across a patent foramen ovale ( see the image below ) . Two - dimensional short - axis echocardiogram image . Note the flattened interventricular septum due to right ventricular overload . Signs and symptoms Symptoms of IPAH are nonspecific and commonly include the following : Dyspnea Weakness Recurrent syncope Cardiovascular examination in patients with PAH often reveals the following findings : The pulmonic component of the second heart sound is usually increased , which may demonstrate fixed or paradoxic splitting in the presence of severe right ventricular dysfunction ; occasionally , the second heart sound may be palpable A pulmonic regurgitation ( Graham Steell murmur ) may be apparent A murmur of tricuspid regurgitation can be present , and a right ventricular lift ( heave ) may be noted Jugular venous pulsations may be elevated in the presence of volume overload , right ventricular failure , or both ; large V waves are often present because of the commonly present severe tricuspid regurgitation , and large a waves thought to be secondary to poor right ventricular compliance may also be present Right - sided S3 gallop Other findings may include the following : Hepatomegaly with palpable pulsations of the liver Abnormal abdominal - jugular reflex Ascites - Not uncommon in untreated patients and in patients with worsening decompensated right heart failure Pitting edema - In the extremities Presacral edema - In patients who are bedridden See Clinical Presentation for more detail . Diagnosis Cardiac catheterization Cardiac catheterization is the criterion standard test to definitively confirm any form of PAH . It is essential in the workup of all patients suspected of IPAH . Excluding left - sided heart disease , including diastolic dysfunction , is especially important in these patients because of major treatment implications . Catheterization is also performed to determine pulmonary vasoreactivity , which can be prognostic and figures in the initiation and titration of high - dose calcium channel blocker ( CCB ) therapy . Laboratory studies Antinuclear antibody Thyroid function B - type natriuretic peptide Imaging studies Radiography Echocardiography Computed tomography ( CT ) , magnetic resonance imaging ( MRI ) , and lung scanning Pulmonary angiography Electrocardiography Electrocardiographic results are often abnormal in patients with PAH , revealing right atrial enlargement , right axis deviation , right ventricular hypertrophy , and characteristic ST depression and T - wave inversions in the anterior leads . Sometimes , an incomplete RBBB may be seen ( usually in patients with atrial septal defects ) . However , some patients with IPAH have few or no abnormal electrocardiographic findings . Histology Several histologic subtypes are associated with pulmonary arteriopathy in IPAH , one of which involves in situ thrombosis . Exercise testing In patients with IPAH , values for peak exercise oxygen consumption , oxygen pulse , and ventilator equivalents ( ratio of expired volume to carbon dioxide output [ ie , wasted ventilation fraction ] at the anaerobic threshold ) during exercise are abnormal to varying degrees . Commonly , a 6 - minute walk test is performed in the office as a crude measurement of exercise capacity . See Workup for more detail . Management Calcium channel blocker therapy Long - term treatment improves the quality of life and survival rate in patients who are proven responders to calcium channel blockers ( CCBs ) . In general , CCBs are used at high doses in patients with IPAH . PAH - specific therapy For patients with IPAH in whom CCBs are contraindicated ( most IPAH patients ) , or in whom CCBs are ineffective or poorly tolerated , guidelines from the American College of Chest Physicians ( ACCP ) recommend using the patient ’ s New York Heart Association ( NYHA ) functional class to guide the choice of PAH - specific therapy . 1 2 More comprehensive guidelines encompass several clinical parameters that are used to determine risk of adverse outcomes . These include functional class , exercise capacity , symptom progression rate , the presence or absence of heart failure on examination , certain biomarkers , and findings on echocardiography . 3 Transplantation and septostomy Lung transplantation - A single - or double - lung transplant is indicated for patients who do not respond to medical therapy Septostomy - Atrial septostomy is a palliative procedure that may afford some benefit to patients whose condition is deteriorating Treatment and Medication Next : Background Sections Idiopathic Pulmonary Arterial Hypertension Overview Background Pathophysiology Etiology Epidemiology Prognosis Patient Education Show All Presentation DDx Guidelines Questions & Answers References Recommended Diseases & Conditions Pulmonary Arterial Hypertension Diseases & Conditions Pediatric Idiopathic Pulmonary Artery Hypertension
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[
"IPAH",
"echocardiography",
"Dyspnea"
] |
http://emedicine.medscape.com/article/306036-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Physical Medicine and Rehabilitation Cervical Spondylosis Updated : Mar 30 , 2018 Author : Hassan Ahmad Hassan Al - Shatoury , MD , PhD , MHPE ; Chief Editor : Dean H Hommer , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Follow - up Questions & Answers Media Gallery References Background Cervical spondylosis is a chronic degenerative condition of the cervical spine that affects the vertebral bodies and intervertebral disks of the neck ( in the form of , for example , disk herniation and spur formation ) , as well as the contents of the spinal canal ( nerve roots and / or spinal cord ) . Some authors also include the degenerative changes in the facet joints , longitudinal ligaments , and ligamentum flavum . Spondylosis progresses with age and often develops at multiple interspaces . Chronic cervical degeneration is the most common cause of progressive spinal cord and nerve root compression . Spondylotic changes can result in stenosis of the spinal canal , lateral recess , and foramina . Spinal canal stenosis can lead to myelopathy , 1 whereas the latter 2 can cause radiculopathy . ( See image below ) A T2 - weighted cervical magnetic resonance imaging scan shows obliteration of the subarachnoid space as a result of spondylotic changes . View Media Gallery Pathophysiology Intervertebral disks lose hydration and elasticity with age , and these losses lead to cracks and fissures . The surrounding ligaments also lose their elastic properties and develop traction spurs . The disk subsequently collapses as a result of biomechanical incompetence , causing the annulus to bulge outward . As the disk space narrows , the annulus bulges , and the facets override . This change , in turn , increases motion at that spinal segment and further hastens the damage to the disk . Annulus fissures and herniation may occur . Acute disk herniation may complicate chronic spondylotic changes As the annulus bulges , the cross - sectional area of the canal is narrowed . This effect may be accentuated by hypertrophy of the facet joints ( posteriorly ) and of the ligamentum flavum , which becomes thick with age . Neck extension causes the ligaments to fold inward , reducing the anteroposterior ( AP ) diameter of the spinal canal . As disk degeneration occurs , the uncinate process overrides and hypertrophies , compromising the ventrolateral portion of the foramen . Likewise , facet hypertrophy decreases the dorsolateral aspect of the foramen . This change contributes to the radiculopathy that is associated with cervical spondylosis . Marginal osteophytes begin to develop . Additional stresses , such as trauma or long - term heavy use , may exacerbate this process . These osteophytes stabilize the vertebral bodies adjacent to the level of the degenerating disk and increase the weight - bearing surface of the vertebral endplates . ( See images below ) A cervical myelogram shows advanced spondylotic changes and multiple compression of the spinal cord by osteophytes . View Media Gallery A 59 - year - old woman presented with a spastic gait and weakness in her upper extremities . A T2 - weighted sagittal magnetic resonance imaging scan shows cord compression from cervical spondylosis , which caused central spondylotic myelopathy . Note the signal changes in the cord at C4 - C5 , the ventral osteophytosis , buckling of the ligamentum flavum at C3 - C4 , and the prominent loss of disk height between C2 and C5 . A 48 - year - old man presented with neck pain and predominantly left - sided radicular symptoms in the arm . The patient ' s symptoms resolved with conservative therapy . An axial , gradient - echo magnetic resonance imaging scan shows moderate anteroposterior narrowing of the cord space due to a ventral osteophyte at the C4 level , with bilateral narrowing of the neural foramina ( more prominently on the left side ) . A 48 - year - old man presented with neck pain and predominantly left - sided radicular symptoms in the arm . The patient ' s symptoms resolved with conservative therapy . A T2 - weighted sagittal magnetic resonance imaging scan shows ventral osteophytosis , most prominent between C4 and C7 , with reduction of the ventral cerebrospinal fluid sleeve . Degeneration of the joint surfaces and ligaments decreases motion and can act as a limiting mechanism against further deterioration . Thickening and ossification of the posterior longitudinal ligament ( OPLL ) also decreases the diameter of the canal . 2 3 4 The blood supply of the spinal cord is an important anatomic factor in the pathophysiology . Radicular arteries in the dural sleeves tolerate compression and repetitive minor trauma poorly . The spinal cord and canal size also are factors . A congenitally narrow canal does not necessarily predispose a person to myelopathy , but symptomatic disease rarely develops in individuals with a canal that is larger than 13 mm . Epidemiology Frequency United States Cervical spondylosis is a common condition that is estimated to account for 2 % of all hospital admissions . It is the most frequent cause of spinal cord dysfunction in patients older than 55 years . On the basis of radiologic findings , 90 % of men older than 50 years and 90 % of women older than 60 years have evidence of degenerative changes in the cervical spine . Evidence from a 2009 report indicated that cervical spondylosis with myelopathy was the most common primary diagnosis ( 36 % ) among elderly US patients admitted to the hospital for surgical treatment of a degenerative cervical spine between 1992 and 2005 . 5 The study , which looked at 156,820 hospital admissions for elderly Medicare beneficiaries , also determined that fusion was the most common procedure ( 70 % ) performed in these patients for cervical spine degeneration , with 58 % of the fusions being anterior . International Investigators in a study involving Ghanaians reported , " out of 225 patients who carried loads on their head , 143 ( 63.6 % ) had cervical spondylosis , and of the 80 people who did not carry load on their head , 29 ( 36 % ) had cervical spondylosis . " Mortality / Morbidity The course of cervical spondylosis may be slow and prolonged , and patients may either remain asymptomatic or have mild cervical pain . Long periods of nonprogressive disability are typical , and in a few cases , the patient ' s condition progressively deteriorates . Morbidity ranges from chronic neck pain , radicular pain , diminished cervical range of motion ( ROM ) , headache , 6 myelopathy leading to weakness , and impaired fine motor coordination to quadriparesis and / or sphincteric dysfunction ( eg , difficulty with bowel or bladder control ) in advanced cases . The patient may eventually become chair bound or bedridden . A retrospective cohort study by Lin et al suggested that cervical spondylosis increases the risk for migraine headaches . The investigators found the overall incidence of migraines in persons with cervical spondylosis to be 5.16 per 1000 people annually , compared with 2.09 per 1000 people annually in controls . The adjusted hazard ratio for migraine in cervical spondylosis was reported to be 2.03 . In cervical spondylosis patients with myelopathy , the incidence of migraine was 2.19 times greater than in controls . 7 A study by Woodworth et al suggested that cervical spondylosis leads to cortical thinning and atrophy in the brain , with resultant increases in neurologic symptoms and pain . Using high - resolution T1 - weighted structure magnetic resonance imaging ( MRI ) , the investigators reported that in patients with cervical spondylosis , changes were seen in parts of the brain associated with sensorimotor function and pain processing , including cortical thinning in the superior frontal gyrus , anterior cingulate , and precuneus and volume reduction in the putamen . 8 Race No apparent correlation between race and cervical spondylosis exists . Sex Both sexes are affected equally . Cervical spondylosis usually starts earlier in men than in women . Age Symptoms of cervical spondylosis may appear in persons as young as 30 years but are found most commonly in individuals aged 40 - 60 years . Radiologic spondylotic changes increase with patient age ; 70 % of asymptomatic persons older than 70 years have some form of degenerative change in the cervical spine . A retrospective study by Wang et al of 1276 cases of cervical spondylosis found an aging - related increase in the incidence of the condition — including bulge or herniation at C3 - C4 , C4 - C5 , C5 - C6 , and C6 - C7 — in patients up to age 50 years and a decrease in the condition ’ s incidence with aging in patients older than 50 years , with the decrease particularly seen after age 60 years . Additionally , an aging - related increase in the incidence of hyperosteogenesis and spinal stenosis was found 9 Cervical spondylosis usually starts earlier in men than in women . When cervical spondylosis develops in a young individual , it is almost always secondary to a predisposing abnormality in one of the joints between the cervical vertebrae , probably as a result of previous mild trauma . Clinical Presentation Sections Cervical Spondylosis Overview Presentation DDx Workup Treatment Medication Follow - up Questions & Answers Media Gallery References
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[
"Cervical Spondylosis",
"chronic degenerative",
"Spondylotic"
] |
http://emedicine.medscape.com/article/323409-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Physical Medicine and Rehabilitation Vertebrobasilar Stroke Updated : Feb 02 , 2018 Author : Vladimir Kaye , MD ; Chief Editor : Stephen Kishner , MD , MHA more . . . Sections Overview Anatomy of the Vertebral and Basilar Arteries Pathophysiology of Vertebrobasilar Stroke Etiology of Vertebrobasilar Stroke Epidemiology of Vertebrobasilar Stroke Clinical Presentation in Vertebrobasilar Stroke Vertebrobasilar Artery Stroke Syndromes Diagnostic Considerations Laboratory Studies for Vertebrobasilar Artery Stroke Computed Tomography Magnetic Resonance Imaging Angiography Ultrasonography Electrocardiography Echocardiography Treatment of Acute Vertebrobasilar Artery Stroke Rehabilitation After Vertebrobasilar Artery Stroke Follow - up After Vertebrobasilar Stroke Prognosis Patient Education Questions & Answers Show All Media Gallery References Overview The vertebrobasilar arterial system perfuses the medulla , cerebellum , pons , midbrain , thalamus , and occipital cortex . Occlusion of large vessels in this system usually leads to major disability or death . Vertebrobasilar stroke carries a mortality rate of more than 85 % . Because of involvement of the brainstem and cerebellum , most survivors have multisystem dysfunction ( eg , quadriplegia or hemiplegia , ataxia , dysphagia , dysarthria , gaze abnormalities , cranial neuropathies ) . However , many vertebrobasilar lesions arise from small vessel disease and are correspondingly small and discrete . The clinical correlates of these smaller lesions consist of a variety of focal neurologic deficits , depending on their location within the brainstem . Patients with small lesions usually have a benign prognosis with reasonable functional recovery . See the images below regarding vertebrobasilar stroke . Lesion of the medial longitudinal fasciculus ( MLF ) resulting in internuclear ophthalmoplegia ( INO ) . ( Courtesy of BC Decker Inc . ) View Media Gallery Illustration of afferent ( CN V ) and efferent ( CN VII ) limbs of the blink reflex . ( Courtesy of BC Decker Inc . ) View Media Gallery Visceral motor component of CN III and pathways involved in pupillary constriction . ( Courtesy of BC Decker Inc . ) Note the horizontal eye movement . Also note a topographic relationship of the center for vertical gaze . ( Courtesy of BC Decker Inc . ) Vestibular nuclei and their connections . ( Courtesy of BC Decker Inc . ) Distinction of vertebrobasilar and hemispheric stroke Lesions in the vertebrobasilar system have some characteristic clinical features that distinguish them from lesions in the hemispheres , including the following 1 When cranial nerves or their nuclei are involved , the corresponding clinical signs are ipsilateral to the lesion and the corticospinal signs are crossed , involving the opposite arm and leg Cerebellar signs ( eg , dysmetria , ataxia ) are frequent Involvement of the ascending sensory pathways may affect the spinothalamic pathway or the medial lemniscus ( dorsal columns ) , resulting in dissociated sensory loss ( ie , loss of 1 sensory modality on one side and preservation of other sensory modalities in the opposite limbs ) Dysarthria and dysphagia typically are present Vertigo , nausea , and vomiting , along with nystagmus , represent involvement of the vestibular system Unilateral Horner syndrome occurs with brainstem lesions Occipital lobe lesions result in visual field loss or visuospatial deficits Cortical deficits , such as aphasia and cognitive impairments , are absent Next : Anatomy of the Vertebral and Basilar Arteries Recommended Diseases & Conditions Ischemic Stroke Diseases & Conditions Carotid Artery Stenosis Imaging
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[
"Vertebrobasilar Stroke",
"mortality rate",
"medial longitudinal fasciculus"
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http://emedicine.medscape.com/article/354666-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Radiology Congestive Heart Failure Imaging Updated : Mar 16 , 2018 Author : Vibhuti N Singh , MD , MPH , FACC , FSCAI ; Chief Editor : Eugene C Lin , MD more . . . Sections Practice Essentials Echocardiography Radiography Computed Tomography Magnetic Resonance Imaging Nuclear Imaging Angiography Show All Media Gallery References Practice Essentials Congestive heart failure ( CHF ) is a clinical syndrome in which the heart fails to pump blood at the rate required by the metabolizing tissues or in which the heart can do so only with an elevation in filling pressure . The heart ' s inability to pump a sufficient amount of blood to meet the needs of the body ' s tissues may be a result of insufficient or defective cardiac filling and / or impaired contraction and emptying . Compensatory mechanisms increase blood volume , as well as the cardiac filling pressure , heart rate , and The clinical manifestations of HF vary enormously and depend on a variety of factors , including the age of the patient , the extent and rate at which cardiac performance becomes impaired , and which ventricle is initially involved in the disease process . A broad spectrum of severity of impairment of cardiac function is ordinarily included in the definition of HF . These impairments range from the mildest forms , which are manifest clinically only during stress , to the most advanced forms , in which cardiac pump function is unable to sustain life without external support . 1 Echocardiography Echocardiography is the preferred examination in CHF . Two - dimensional and Doppler echocardiography may be used to determine systolic and diastolic LV performance , the cardiac output ( ejection fraction ) , and pulmonary artery and ventricular filling pressures . 2 Echocardiography also may be used to identify clinically important valvular disease . 3 4 Although echocardiography is simple and noninvasive , it proves to be inadequate in 8 - 10 % of cases ; in addition , the results are difficult to interpret in patients with lung disease . In a joint report by the American College of Radiology ( ACR ) and the American College of Cardiology Foundation ( ACCF ) regarding the appropriate use of imaging in HF , their strongest recommendations for newly suspected HF were for echocardiography utilizing 2D transthoracic ultrasound and Doppler . 5 Radiography In cardiogenic cases , radiographs may show cardiomegaly , pulmonary venous hypertension , and pleural effusions . Pulmonary venous hypertension ( PVH ) may be divided into 3 grades : In grade I PVH , an upright examination demonstrates redistribution of blood flow to the nondependent portions of the lungs and the upper lobes . In grade II PVH , there is evidence of interstitial edema with ill - defined vessels and peribronchial cuffing , as well as interlobular septal thickening . In grade III PVH , perihilar and lower - lobe airspace filling is evident , with features typical of consolidation ( eg , confluent opacities , air bronchogram and the inability to see pulmonary vessels in the area of abnormality ) . The airspace edema tends to spare the periphery in the mid and upper lung . In noncardiogenic cases , cardiomegaly and pleural effusions are usually absent . The edema may be interstitial but is more often consolidative . No cephalization of flow is noted , though there may be shift of blood flow to less affected areas . The edema is diffuse and does not spare the periphery of the mid or upper lungs . In cases of large , acute myocardial infarction ( MI ) and infarction of the mitral valve , support apparatus may produce atypical patterns of pulmonary edema that may mimic noncardiogenic edema in patients who in fact have cardiogenic edema . Signs of CHF are demonstrated in the image below . Chest radiograph shows signs of congestive heart failure ( CHF ) . View Media Gallery Computed tomography scanning In cases that are clinically troublesome , multidetector - row gated computed tomography ( CT ) scanning may provide excellent analysis of the heart and reveal the nature of the pulmonary edema . 6 Electrocardiography In cardiogenic cases , the electrocardiogram ( ECG ) may show evidence of MI or ischemia . In noncardiogenic cases , the ECG is usually normal . The ECG image below depicts biventricular pacing . ECG shows biventricular pacing ( double ventricular pacing spikes ) . View Media Gallery Two - dimensional echocardiography is recommended as an initial part of the evaluation of patients with known or suspected congestive heart failure . Ventricular function may be evaluated , and both primary and secondary valvular abnormalities may be accurately assessed . 3 4 7 Echocardiography is also used for assessing prognosis and can be used serially to evaluate treatment . 8 Appropriate use criteria also support the re - evaluation of cardiac function by echocardiography in patients with heart failure , arrhythmia , and known valvular disease in the event of a change in clinical status without a clear precipitant . 5 Doppler echocardiography may play a valuable role in determining diastolic function and in establishing the diagnosis of diastolic HF . HF in association with normal systolic function but abnormal diastolic relaxation affects 30 - 40 % of patients presenting with CHF . Because the therapy for this condition is distinctly different from that for systolic dysfunction , establishing the appropriate etiology and diagnosis is essential . The combination of 2 - dimensional echocardiography and Doppler echocardiography is effective for this purpose . Two - dimensional and Doppler echocardiography may be used to determine systolic and diastolic LV performance , cardiac output ( ejection fraction ) , and pulmonary artery and ventricular filling pressures . Echocardiography may also be used to identify clinically important valvular disease . 9 The major limitation of echocardiography has been patient specific factors that lead to suboptimal acoustic windows . 8 The degree of confidence in echocardiography is high , and the rates of false - positive and false - negative findings are low . Two principal features of the chest radiograph are useful in the evaluation of patients with congestive heart failure : ( 1 ) the size and shape of the cardiac silhouette , and ( 2 ) edema at the lung bases ( see the image below ) . 9 Chest radiograph shows signs of congestive heart failure ( CHF ) . The size and shape of the cardiac silhouette provide important information concerning the precise nature of the underlying heart disease . The cardiothoracic ratio and the heart volume , as determined on plain film , are relatively specific but insensitive indicators of increased LV end - diastolic volume . There is a weak inverse correlation between the cardiothoracic ratio and LV ejection fraction ( LVEF ) in patients with HF ; the relationship is not clinically useful in the individual patient . In the presence of normal pulmonary capillary and venous pressures , the lung bases are better perfused than the apices when the patient is in the erect position , and the vessels supplying the lower lobes are significantly larger than those supplying the upper lobes . With elevation of left atrial and pulmonary capillary pressures , interstitial and perivascular edema develops ; such edema is most prominent at the lung bases because hydrostatic pressure is greater there . When pulmonary capillary pressure is slightly elevated ( 13 - 17 mm Hg ) , the resultant compression of pulmonary vessels in the lower lobes causes equalization in the size of the vessels at the apices and bases ( early grade I PVH ) . With greater pressure elevation ( 18 - 23 mm Hg ) , actual pulmonary vascular redistribution into nondependent portions of the lung occurs ( ie , with the patient in an upright patient , there is further constriction of the vessels that lead to the lower lobes , and there is dilatation of the vessels When pulmonary capillary pressures exceed 20 - 25 mm Hg , interstitial pulmonary edema occurs ( grade II PVH ) . With grade II PVH , there is evidence of interstitial edema , with ill - defined vessels and peribronchial cuffing , as well as interlobular septal thickening . The interlobular septal thickening is referred to as Kerley B lines . Early blunting of the lateral and posterior costophrenic angles may occur ; such blunting indicates the presence of pleural fluid . When pulmonary capillary pressure exceeds 25 mm Hg , images may show large pleural effusions and grade III PVH , with consolidative alveolar edema in a perihilar and lower - lobe distribution . With elevation of the systemic venous pressure , the azygos vein , brachiocephalic veins , and superior vena cava may become enlarged . In patients with chronic LV failure , higher pulmonary capillary pressures may be accommodated with fewer clinical and radiologic signs , presumably because of enhanced lymphatic drainage . In a study of 22 patients with advanced HF who were referred for cardiac transplant evaluation and whose pulmonary capillary wedge pressure measurements were 25 mm Hg or greater , 68 % had no or minimal pulmonary congestion , as shown on chest radiographs . In summary , the typical findings of CHF on the plain radiograph are cardiomegaly ; grade I , II , or III PVH ; and increased central systemic venous volume , with enlargement of the mediastinal veins ( including the azygous vein ) and pleural effusions . Degree of confidence The degree of confidence is low . The weak negative correlation between the cardiothoracic ratio and the ejection fraction does not permit accurate determination of systolic function in the absence of radiographic evidence of PVH or pleural effusions in individual patients with HF . For this reason , a chest radiograph may not be very useful for determining the type of LV dysfunction . During the treatment phase of CHF , chest radiographic findings often lag behind clinical improvement . False - negative findings are frequent . Computed Tomography CT scanning of the heart is usually not required in the routine diagnosis and management of congestive heart failure . Multichannel CT scanning is useful in delineating congenital and valvular abnormalities ; however , echocardiography and magnetic resonance imaging ( MRI ) may provide similar information without exposing the patient to ionizing radiation . The degree of confidence in CT scanning is moderate , and the rates of false - positive and false - negative findings in the modality are low . Magnetic Resonance Imaging Because of the widespread acceptance of echocardiography , MRI is used only infrequently in the workup of patients with congestive heart failure . Its main use involves delineation of congenital cardiac abnormalities and assessment valvular heart disease ; it is also used in patients with other conditions . 10 In newly suspected or potential HF , appropriate use criteria supports cardiovascular magnetic resonance imaging ( CMR ) . Although LV volume and ejection fraction ( EF ) measurements are as accurate as those obtained with echocardiography , viability and fibrosis imaging can assist in identification of etiology and assess prognosis . LV mass quantitation by CMR predicts future risk in patients with HF . Delayed enhancement cardiovascular magnetic resonance imaging ( DE - CMR ) may be used to identify the underlying etiology of acute chest pain . A subendocardial or transmural hyperenhancement pattern is most frequently observed in ischemic injury , based on the wave front phenomenon of ischemic myocardial injury , whereas a mid - to epicardial hyperenhancement pattern suggests nonischemic pathology ( eg , myocarditis ) . CRM is highly accurate to detect structural heart disease that may be responsible for stable and mildly abnormal high - sensitivity cardiac troponin ( hs - cTn ) levels ( eg , dilated , 11 The degree of confidence in MRI is high , and the rates of false - positive and false - negative findings are low . Nuclear Imaging Nuclear imaging can be used in the assessment of heart function and damage in CHF . 12 ECG - gated myocardial perfusion imaging The high photon flux of compounds labeled with technetium - 99m ( 99m TC ) makes it feasible to acquire myocardial perfusion images in an ECG - gated mode . ECG - gated myocardial perfusion images may be displayed as an endless - loop cine on the computer screen . ECG - gated single - photon emission CT ( SPECT ) images allow for assessment of global LVEF , regional wall motion , and regional wall thickening . Regardless of whether the injection of radiopharmaceutical was performed during peak stress or at rest , because the acquisition is performed at rest , ECG - gated SPECT images reveal resting global function and wall motion and resting wall thickening in areas with defects of exercise - induced myocardial perfusion . On ECG - gated SPECT images , regional wall thickening may be quantified as a percentage of wall thickening in comparison to end - diastole . Commercially available and validated software packages are available for the automatic calculation of resting global LVEF , LV volume , and regional wall thickening from ECG - gated SPECT sections . In general , LVEF from gated SPECT agrees well with resting LVEF , as determined with other modalities . Quality assurance is important . Determinations of LVEF with gated SPECT may be less accurate , even invalidated , in the presence of an irregular heart rate , low count density , intense extracardiac radiotracer uptake adjacent to the LV , or a small LV . Combined interpretation of perfusion and function on ECG - gated images substantially increases the confidence of interpretation . Taillefer and associates reported that the interpretation of stress and rest end - diastolic section , rather than summed ungated sections , may enhance the overall sensitivity for the detection of mild coronary artery disease ( CAD ) . 13 ECG - gated images are useful for recognizing artifactual defects caused by attenuation ( breast and diaphragm ) and thus are useful in the quality control of SPECT imaging . ECG - gated SPECT imaging is considered the state of the art of radionuclide myocardial perfusion imaging . Assessment of myocardial viability For patients with angina , known CAD , previous infarction , and LV dysfunction , a reliable method for assessing the presence , extent , and location of viable myocardium is of considerable clinical importance . It is well established that global or regional ischemic LV dysfunction is not always an irreversible condition . Approximately 25 - 40 % of patients may experience improvement in function after adequate revascularization . Two important practical issues need to be addressed in the evaluation of patients with presumed ischemic dysfunction : ( 1 ) One should consider assessment of the relative regional myocardial uptake of thallium - 201 ( 201 Tl ; often after rest reinjection ) , 99m Tc - sestamibi , or Tc - tetrofosmin ( often after rest administration of nitroglycerin ) . When the resting uptake of radiotracer is greater than 50 % of normal , one may expect recovery of function after revascularization . ( 2 ) One should consider assessment of the presence of demonstrable ischemia ( eg , partially reversible defect ) in a myocardial segment with decreased uptake , even if the resting uptake is less than 50 % . Equilibrium radionuclide angiocardiography Equilibrium radionuclide angiocardiography ( ERNA ) uses ECG events to define the temporal relationship between the acquisition of nuclear data and the volumetric components of the cardiac cycle . Sampling is performed repetitively over several hundred heartbeats , with physiologic segregation of nuclear data in accordance with their occurrence within the cardiac cycle . Data are quantified and displayed in an endless - loop , cinegraphic format for additional qualitative visual interpretation and analysis . Equilibrium blood - pool labeling is achieved by use of Tc . The intravascular label is affixed to the patient ' s own red blood cells by use of an in vitro or modified in vitro technique . Unlabeled stannous pyrophosphate is used to facilitate this reaction . Conventional Anger scintillation cameras are used for these studies . Data are analyzed by use of a computer , generally with some operator interaction . Analysis may be obtained in either the frame or list mode . Radionuclide data are collected and segregated temporally . The process generally requires 3 - 10 minutes for completion of each view . Following data acquisition , data from the several hundred individual beats are summed , processed , and displayed as a single representative cardiac cycle . Data from the left anterior oblique ( LAO ) view are also used for qualitative analysis of global LV function . On this view , overlap of the 2 ventricles is minimal . In a count - based approach , LVEF and other indices of filling and ejection are calculated from the LV radioactivity preset at various points throughout the cardiac cycle . Right ventricular function is best evaluated by first - pass techniques . The LAO view provides qualitative information concerning contraction of the septal , inferoapical , and lateral walls . The anterior view provides data concerning regional motion of the anterior and apical segments . The left lateral or left posterior oblique view provides optimal qualitative information concerning contraction of the inferior wall and posterobasal segment . Ventricular aneurysm may be best assessed in the lateral views as well . Each segment is generally graded on a 5 - point scale , with specific numerical grades assigned for dyskinesis , akinesis , mild and severe hypokinesis , and normal function . ERNA may easily be combined with additional physiologic stress testing or provocation , which may be in the form of physiologic stress , such as exercise ; pharmacologic stress , with the use of positive inotropic agents such as dobutamine or isoproterenol ; or psychological stress . Angiography Cardiac catheterization and coronary angiography have a useful role in patients with congestive heart failure , those with valvular heart disease , and those with congenial heart disease , as well as patients with other conditions . 14 CHF For patients with CHF , cardiac catheterization and coronary angiography are clearly indicated in the following situations : CHF caused by systolic dysfunction in association with angina or regional wall motion abnormalities and / or scintigraphic evidence of reversible myocardial ischemia when revascularization is being considered Before cardiac transplantation CHF secondary to postinfarction ventricular aneurysm or other mechanical complications of MI For these patients , the procedures are frequently indicated when systolic dysfunction of unexplained cause is present on noninvasive testing or when normal systolic function with episodic HF suggests ischemically mediated LV dysfunction . Valvular heart disease In patients with valvular heart disease , cardiac catheterization and coronary angiography are clearly indicated in the following situations : Before valve surgery or balloon valvotomy in an adult with chest discomfort , ischemia by noninvasive imaging , or both Before valve surgery in an adult who is free of chest pain but who has many risk factors for CAD Infective endocarditis with evidence of coronary embolization Congenital heart disease In patients with congenital heart disease , cardiac catheterization and coronary angiography are clearly indicated in the following situations : Before surgical correction of congenital heart disease when chest discomfort or noninvasive evidence is suggestive of associated CAD The patient has a form of congenital heart disease that is frequently associated with coronary artery anomalies that may complicate surgical management Unexplained cardiac arrest in a young patient For these patients , the procedures are frequently indicated before corrective open heart surgery for congenital heart disease in an adult whose risk profile is associated with an increased risk of coexisting CAD . Other conditions In patients with other conditions , cardiac catheterization and coronary angiography are clearly indicated in the following situations : Diseases affecting the aorta when knowledge of the presence or extent of coronary artery involvement is necessary for management ( eg , aortic dissection or aneurysm with known CAD ) Hypertrophic cardiomyopathy with angina despite medical therapy when knowledge of coronary anatomy might affect therapy Hypertrophic cardiomyopathy with angina when heart surgery is planned For these patients , the procedures are frequently indicated in the following situations : There is a high risk of CAD when other cardiac surgical procedures are planned ( eg , pericardiectomy or removal of chronic pulmonary emboli ) Prospective immediate cardiac transplant donors have a risk profile that increases the likelihood of CAD Asymptomatic patients with Kawasaki disease have coronary artery aneurysms on echocardiography Before surgery for aortic aneurysm / dissection in patients without known CAD Recent blunt chest trauma and suspicion of acute MI , without evidence of preexisting CAD Sections Congestive Heart Failure Imaging Show All Media Gallery References
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[
"Congestive heart failure",
"Echocardiography",
"Radiography"
] |
http://emedicine.medscape.com/article/392997-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Radiology Imaging in Osteomalacia and Renal Osteodystrophy Updated : Jul 05 , 2018 Author : Ali Nawaz Khan , MBBS , FRCS , FRCP , FRCR ; Chief Editor : Felix S Chew , MD , MBA , MEd more . . . Sections Practice Essentials Radiography Computed Tomography Magnetic Resonance Imaging Ultrasonography Nuclear Imaging Show All Media Gallery References Practice Essentials Osteomalacia is characterized by incomplete mineralization of normal osteoid tissue following closure of the growth plates . Osteomalacia may be part of the spectrum of osseous abnormalities that can be observed in patients with chronic renal insufficiency . This condition is referred to as renal osteodystrophy . Renal osteodystrophy combines features of secondary hyperparathyroidism , rickets , osteomalacia , and osteoporosis . Findings of rickets and osteomalacia occur in children , and findings of osteomalacia and secondary hyperparathyroidism occur in adults . 1 2 3 4 5 Clinically , osteomalacia is subtler than rickets , particularly in mild or moderate disease . Mildly affected patients may present with nonspecific bone pain and tenderness and possibly hypotonia . Severely affected patients may have difficulty ambulating and may walk with a waddling gait . Milkman syndrome is a condition in which the patient experiences multiple insufficiency fractures that are often bilateral and symmetric . 6 Typical sites include the concave surface of the femoral neck , axillary margin of the scapula , pubic rami , and ribs . Skeletal deformity can occur in the vertebral bodies and skull ( basilar invagination ) , and fractures can occur in the vertebrae and long bones . The immature skeleton may reveal the following characteristic findings : In neonates , posterior flattening and squaring of the skull ( eg , craniotabes ) may be observed . In early childhood , bowing deformities of arms and legs are common ( see the image below ) . Lateral radiograph of the leg in a child with chronic renal failure reveals anterior bowing of the distal tibia . View Media Gallery In older children , scoliosis , vertebral endplate deformities , basilar invagination of the skull , triradiate deformity of the pelvis , and slipped capital femoral epiphysis may be observed . Renal osteodystrophy also may present with nonspecific signs and symptoms , including weakness , bone pain , and skeletal deformity . Presentation varies markedly with age . Adults may present with findings of osteomalacia , while children typically show growth retardation . As a result , complications differ depending on the patient ' s age . The most common complication of renal osteodystrophy is fracture , which may be insufficiency fractures through osteomalacic bone or pathologic fractures through brown tumors or amyloid deposits . Dialysis patients may experience carpal tunnel syndrome , osteomyelitis , septic arthritis , and osteonecrosis . Anteroposterior radiograph of the hip in a dialysis patient reveals erosion of a large portion of the medial femoral neck and trochanteric region from amyloid deposition ( arrowheads ) with a pathologic fracture in the basocervical portion of the femoral neck ( arrow ) . View Media Gallery Coronal T1 - weighted MRI of the knee in a renal transplant patient on steroids reveals serpentine hypointensity in the metaphyseal and subchondral regions ( black arrows ) with secondary chondral collapse of the lateral femoral condyle ( white arrow ) . Rickets and osteomalacia are different manifestations of the same underlying pathologic process , depending on whether the patient is a child or an adult , respectively . The demarcation is made at the time of closure of the growth plates . Renal osteodystrophy causes rachitic and some osteomalacic changes in the child and osteomalacia and secondary hyperparathyroidism in adults . The ESRD patient profile in the United States , by age range , according to the US Renal Data System , is as follows 7 Younger than 21 years - 1.4 % of patients Ages 21 - 44 years - 14.6 % of patients Ages 45 - 64 years - 44.0 % of patients Ages 65 - 74 years - 23.8 % of patients Older than 74 years - 16.2 % of patients Preferred examination Radiographic examination in patients with osteomalacia may reveal only osteopenia . Characteristically , however , coarsened trabecula is observed . Complications such as Looser zones ( see the image below ) and complete fractures can be diagnosed radiographically . 8 9 Magnified anteroposterior radiograph of the proximal tibia in a patient with chronic renal failure reveals a Looser fracture ( pseudofracture ) at the proximal medial tibia ( arrow ) . The findings of renal osteodystrophy diagnosed with conventional radiography include osseous resorption , soft tissue calcification , osteopenia , amyloid deposition , and fracture . 10 Bone biopsy is considered the gold standard for diagnosis and classification of renal osteodystrophy . 11 12 Bone scans may reveal diffuse skeletal uptake of radiopharmaceutical with a superscan appearance that can be confused with metastatic disease . However , the extremities typically have a greater level of increased uptake with secondary hyperparathyroidism than is expected with metastatic disease . In addition , bone scans may reveal pseudofractures or sites of extraskeletal calcification , which also may be distinctive for secondary hyperparathyroidism . Bone scan findings usually are supportive of , but are of limited primary diagnostic value to , renal osteodystrophy . CT helps evaluate pathologic fracture . Amyloidosis may cause erosion in and around a joint , resulting in subtle radiographic signs that are more clearly delineated with cross - sectional imaging techniques such as CT . 13 MRI helps evaluate the soft tissues for ligament rupture , and CT can help evaluate pathologic fracture . Amyloidosis may cause erosion in and around a joint , resulting in subtle radiographic signs , while amyloid deposits can be visualized directly on MRI . 13 Radiographic usefulness in the diagnosis of hyperparathyroidism is limited because of the accuracy of current laboratory testing . However , secondary pathology may result from osteomalacic changes in the skeleton ( eg , insufficiency fractures ) , and pathologic fractures may occur through a brown tumor . If this pathology is suggested ( and may not be evident on radiographic studies ) , cross - sectional imaging may be warranted to exclude the findings . Cross - sectional imaging may be needed to exclude hip fracture in a severely osteomalacic hip , similar to the imaging needed in older persons with osteoporosis . Substantial morbidity and mortality are associated with delayed diagnosis or misdiagnosis in these patients . Differential diagnosis The radiographic appearance of osteomalacia may be normal or similar to findings noted with osteoporosis . However , coarseness of the trabeculae may differentiate osteomalacia from osteoporosis . The differential diagnosis of generalized osteopenia includes osteomalacia , hyperparathyroidism , and multiple myeloma . 14 The differential diagnosis of renal osteodystrophy varies depending on the sites of involvement . The causes of soft tissue calcification include collagen vascular disease , hydroxyapatite crystal deposition disease , hypervitaminosis , and idiopathic tumoral calcinosis . Bone resorption in a periarticular distribution may resemble rheumatoid arthritis . Sacroiliac joint involvement by subchondral bone resorption resembles disease from ankylosing spondylitis and inflammatory bowel disease . Focal deposition of amyloid and brown tumors may resemble neoplasm . Diffuse spinal osteopenia may be a manifestation of multiple myeloma . A differential diagnosis for osseous sclerosis typically includes metastatic disease , sickle cell disease , radiation , myelofibrosis , mastocytosis , hypoparathyroidism , and Paget disease . ( See the images below . ) Anteroposterior radiograph of the distal forearm in a patient with chronic renal failure reveals an expansile lytic lesion ( brown tumor ) in the distal ulna ( arrows ) . A . Lateral radiograph of the spine in a patient with multiple myelomas reveals diffuse osteopenia with no focal lesions . B . Sagittal T1 - weighted MRI of the spine in the same patient reveals diffuse marrow replacement ( arrows ) indicative of diffuse myelomatoid involvement . Chondrocalcinosis can be seen with pyrophosphate arthropathy , hemochromatosis , ochronosis , and gout . The differential diagnosis for rachitic changes includes hypophosphatasia and the Schmid type of metaphyseal chondrodysplasia . Anatomy Sclerosis may appear patchy and nonspecific , or it may show a characteristic pattern , such as predominant endplate involvement in the spine ( see the images below ) . Soft tissue calcifications may take the form of the large , cloudlike collections in a periarticular distribution known as tumoral calcinosis . These collections are composed mostly of calcium hydroxyapatite and may form a milky substance that may contain fluid levels . Tumoral calcinosis typically is periarticular and noted frequently around the hips and shoulders , although it also may be found around smaller joints . Anteroposterior radiograph of the forefoot in a patient with chronic renal failure reveals diffuse osteosclerosis . Lateral radiograph of the spine in a patient with chronic renal failure reveals characteristic endplate sclerosis ( arrows ) referred to as rugger - jersey spine . Oblique radiograph of the hand in a dialysis patient reveals multifocal , large , amorphous calcific deposits ( tumoral calcinosis ) around the hand and wrist ( arrows ) . Chondrocalcinosis may occur in fibrocartilage and hyaline cartilage and often occurs in the knee ( see the images below ) . Other sites commonly affected by chondrocalcinosis include the pubic symphysis and triangular fibrocartilage of the wrist . Calcification also may occur in ligaments and tendons and in the vasculature . Anteroposterior radiograph of the knee in a patient with chronic renal failure reveals chondrocalcinosis of the meniscal fibrocartilage ( white arrow ) and articular hyaline cartilage ( black arrow ) . Oblique radiograph of the wrist in a patient with chronic renal failure reveals chondrocalcinosis of the triangular fibrocartilage ( arrow ) . Lateral radiograph of the knee in a patient with chronic renal failure reveals calcification of the patellar tendon ( arrows ) . Anteroposterior radiograph of the fingers in a patient with chronic renal failure reveals calcification of the vasculature ( arrows ) , as well as resorption of the distal tufts ( arrowheads ) . Bone resorption typically is classified as subchondral , trabecular , endosteal , intracortical , subperiosteal , subligamentous , and subtendinous ( see the images below ) . Involvement of the hands and feet by subperiosteal resorption typically occurs along the radial aspect of the middle phalanges and the cortical bone of the tufts of the distal phalanges . Subperiosteal resorption at the joint margins resembles marginal erosions of rheumatoid arthritis . Classically , the skull is affected by trabecular bone resorption , creating a salt - and - pepper appearance in the calvarium . Anteroposterior radiograph of the finger in a patient with renal failure reveals subperiosteal resorption along the radial aspect of the middle phalanx ( arrows ) , as well as resorption of the distal tuft ( arrowheads ) . Anteroposterior radiograph of the hand in a patient with chronic renal failure reveals subchondral and subperiosteal bone resorption predominating at the joint margins ( arrows ) , which resembles the erosions of rheumatoid arthritis . Lateral radiograph of the calvarium reveals punctate trabecular bone resorption that has a salt - and - pepper appearance . Subligamentous and subtendinous bone resorption typically occurs in the clavicle underlying the coracoclavicular ligaments , as well as at the calcaneal attachment of the plantar aponeurosis , the triceps insertion on the olecranon , the humeral tuberosities , the femoral trochanters , and the ischial tuberosities ( see the images below ) . Subchondral bone resorption may be seen in locations that include the distal clavicles , sacroiliac joints , and pubic symphysis . Other characteristic sites involved by bone resorption include the proximal medial cortical surface of long bones and the lamina dura of the mandible . Anteroposterior radiograph of the shoulder in a patient with renal failure reveals subligamentous resorption underlying the clavicular attachment of the coracoclavicular ligament ( white arrow ) and subchondral erosion of the distal clavicle ( black arrow ) . Anteroposterior radiograph of the sacroiliac joints reveals subchondral erosion at the articular surface bilaterally ( arrows ) . Anteroposterior radiograph of the humerus in a patient with chronic renal failure reveals subperiosteal resorption at the proximal medial aspect of the bone ( arrow ) . When renal osteodystrophy is encountered in children , rachitic changes and osteomalacia are the dominant findings ( see the images below ) . Rachitic changes are apparent at the growth plates and include increased lucency , widening , elongation , irregularity , and cupping of the metaphyses . Changes of osteomalacia involve the mature trabecular bone . The parts of the skeleton affected most are the costochondral junctions of the middle ribs , distal femur , both ends of the tibia , distal radius and ulna , and proximal humerus . Anteroposterior radiograph of the wrist in a child with renal failure reveals cupping and fraying of the metaphysis and irregularity of the epiphyseal margins compatible with renal rickets ( arrowheads ) . The coarsened trabeculae are a feature of osteomalacia ( arrows ) . Anteroposterior radiograph of the right hemithorax in a child with chronic renal failure and rachitic rosary reveals abnormal widening of the anterior ribs at the costochondral junctions ( arrows ) . Pathophysiology Renal osteodystrophy is a global term applied to all pathologic features of bone in patients with renal failure . The primary retention of phosphate by abnormal kidneys results in hyperphosphatemia , which causes hypocalcemia , resulting in secondary hyperparathyroidism . 15 16 Therefore , the spectrum of clinical and radiographic findings in renal osteodystrophy may be a manifestation of any of these disorders . Osteomalacia is a disorder of bone that results from hypomineralization following the cessation of bone growth . In contrast to rickets , which affects mineralization of growing bones , osteomalacia does not affect the growth plates ; however , hypomineralization of trabecular and cortical bone occurs . 17 18 19 20 Normal bone mineralization depends on interdependent factors that supply adequate calcium and phosphate to the bones . Vitamin D maintains calcium and phosphate homeostasis through its action on bone , the GI tract , kidneys , and parathyroid glands . Vitamin D may be supplied in the diet or produced from a sterol precursor in the skin following exposure to ultraviolet light . Sequential hydroxylation is then required to produce the metabolically active form of vitamin D . Hydroxylation occurs first in the liver and then in the kidneys to produce 1 , 25 - dihydroxyvitamin D3 . Dysfunction in The histopathology of osteosclerosis in renal osteodystrophy is complex and incompletely understood . Histologic evaluations of patients with renal osteodystrophy typically reveal osteoclastosis , osteoblastosis , and evidence of abnormally increased bone turnover . Additionally , an increased proportion of cancellous bone often exists . Calcium may be deposited in this cancellous bone as amorphous calcium phosphate rather than hydroxyapatite . This may help explain the increased osteosclerosis noted in some patients with renal osteodystrophy . Osteosclerosis also may be due to an increase in thickness and number of trabeculae in cancellous bone . Osteosclerosis is typically evident in areas Bone resorption in renal osteodystrophy is also quite complex . Renal retention of phosphate results in hyperphosphatemia , which reduces serum ionized calcium levels , therefore inducing hyperparathyroidism . The hyperparathyroidism increases bone resorption , which may normalize serum calcium levels by releasing the osseous storage of calcium . The various sites of bone resorption include the subperiosteal region of the phalanges , the phalangeal tufts , proximal femur , proximal tibia , proximal humerus , distal clavicle , and calvarial trabeculae . The cause of osteomalacia in renal osteodystrophy is multifactorial . The low serum calcium level directly induced by hyperphosphatemia is a major factor . Hyperphosphatemia also decreases the efficacy of 1 - hydroxylase , which decreases the levels of 1 - 25 dihydroxyvitamin D and , thus , the ability of the gut to absorb calcium . 21 Aluminum - induced bone disease is an additional cause of osteomalacia . Aluminum negatively affects bone formation through inhibition of osteoblastic activity , as well as by hydroxyapatite crystal formation . Aluminum may be introduced from dialysate solutions , antacids , or aluminum - containing phosphate - binding agents used to combat the hyperphosphatemia of renal failure . Metastatic deposition causes soft tissue calcifications . Elevated phosphate levels may result in a high calcium - phosphate product causing deposits in the soft tissues . This also can be affected by the degree of alkalosis , as well as by local tissue injury . Areas that are particularly affected by soft tissue calcification include medium - sized blood vessels , periarticular soft tissues ( tumoral calcinosis ) , and viscera such as the heart , lung , and kidney . Isaksson et al studied iliac crest biopsies from healthy bone and from patients with renal osteodystrophy and hyperparathyroid disease to characterize the composition of bone in high - turnover renal osteodystrophy , by use of Fourier transform infrared spectroscopic imaging ( FTIRI ) . The samples from the renal osteodystrophy patients showed significantly lower carbonate - to - phosphate and carbonate - to - amide I ratios , and spatial variation across the trabeculae established a significantly lower degree of mineralization at the edges of the trabeculae in the osteodystrophy samples . 22 Oncogenic osteomalacia Oncogenic osteomalacia is a rare paraneoplastic syndrome associated with neoplasms that produce fibroblast growth factor - 23 ( FGF - 23 ) , which inhibits phosphate reabsorption in the kidneys ; bone demineralization follows . Most of these are peripheral tumors , but it has been described with an intracranial tumor that mimics a meningioma on imaging ; histologically , the tumor is a low - grade phosphaturic mesenchymal tumor , mixed connective tissue variant . 23 The tumor ' s low prevalence , small size , and variable location often result in years of muscular weakness and bone pain before diagnosis . With complete treatment , symptoms swiftly dissipate . Niemeier et al reported a case of a 63 - year - old previously healthy man with a 20 - month history of musculoskeletal symptoms before diagnosis and resection of the posterior tibial tumor . Postoperatively , the patient returned to his previous lifestyle when an insufficiency fracture required a prophylactic stabilization . 24 25 Antiviral - induced osteomalacia The long - term use of antiviral medications ( eg , adefovir and tenofovir ) to treat chronic hepatitis B and HIV infection has been reported to be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemic osteomalacia . 26 27 28 Cases of low - dose adefovir - induced hypophosphatemic osteomalacia that initially presented with diffuse musculoskeletal pain have been reported . { ref19 Radiography Radiographic examination in patients with osteomalacia may reveal only osteopenia . Characteristically , however , coarsened trabecula is present . Complications such as Looser zones and complete fractures can be diagnosed radiographically . Findings of renal osteodystrophy diagnosed with conventional radiography include osseous resorption , soft tissue calcification , osteopenia , amyloid deposition , and fracture . 29 30 ( See the images below . ) Magnified anteroposterior radiograph of the proximal tibia in a patient with chronic renal failure reveals a Looser fracture ( pseudofracture ) at the proximal medial tibia ( arrow ) . Lateral radiograph of the leg in a child with chronic renal failure reveals anterior bowing of the distal tibia . Anteroposterior radiograph of the hip in a dialysis patient reveals erosion of a large portion of the medial femoral neck and trochanteric region from amyloid deposition ( arrowheads ) with a pathologic fracture in the basocervical portion of the femoral neck ( arrow ) . Anteroposterior radiograph of the forefoot in a patient with chronic renal failure reveals diffuse osteosclerosis . Lateral radiograph of the spine in a patient with chronic renal failure reveals characteristic endplate sclerosis ( arrows ) referred to as rugger - jersey spine . Oblique radiograph of the hand in a dialysis patient reveals multifocal , large , amorphous calcific deposits ( tumoral calcinosis ) around the hand and wrist ( arrows ) . Anteroposterior radiograph of the knee in a patient with chronic renal failure reveals chondrocalcinosis of the meniscal fibrocartilage ( white arrow ) and articular hyaline cartilage ( black arrow ) . Oblique radiograph of the wrist in a patient with chronic renal failure reveals chondrocalcinosis of the triangular fibrocartilage ( arrow ) . Lateral radiograph of the knee in a patient with chronic renal failure reveals calcification of the patellar tendon ( arrows ) . Anteroposterior radiograph of the fingers in a patient with chronic renal failure reveals calcification of the vasculature ( arrows ) , as well as resorption of the distal tufts ( arrowheads ) . Anteroposterior radiograph of the finger in a patient with renal failure reveals subperiosteal resorption along the radial aspect of the middle phalanx ( arrows ) , as well as resorption of the distal tuft ( arrowheads ) . Anteroposterior radiograph of the hand in a patient with chronic renal failure reveals subchondral and subperiosteal bone resorption predominating at the joint margins ( arrows ) , which resembles the erosions of rheumatoid arthritis . Lateral radiograph of the calvarium reveals punctate trabecular bone resorption that has a salt - and - pepper appearance . Anteroposterior radiograph of the shoulder in a patient with renal failure reveals subligamentous resorption underlying the clavicular attachment of the coracoclavicular ligament ( white arrow ) and subchondral erosion of the distal clavicle ( black arrow ) . Anteroposterior radiograph of the sacroiliac joints reveals subchondral erosion at the articular surface bilaterally ( arrows ) . Anteroposterior radiograph of the humerus in a patient with chronic renal failure reveals subperiosteal resorption at the proximal medial aspect of the bone ( arrow ) . Anteroposterior radiograph of the wrist in a child with renal failure reveals cupping and fraying of the metaphysis and irregularity of the epiphyseal margins compatible with renal rickets ( arrowheads ) . The coarsened trabeculae are a feature of osteomalacia ( arrows ) . Anteroposterior radiograph of the right hemithorax in a child with chronic renal failure and rachitic rosary reveals abnormal widening of the anterior ribs at the costochondral junctions ( arrows ) . Anteroposterior radiograph of the distal forearm in a patient with chronic renal failure reveals an expansile lytic lesion ( brown tumor ) in the distal ulna ( arrows ) . A . Lateral radiograph of the spine in a patient with multiple myelomas reveals diffuse osteopenia with no focal lesions . B . Sagittal T1 - weighted MRI of the spine in the same patient reveals diffuse marrow replacement ( arrows ) indicative of diffuse myelomatoid involvement . Magnetic Resonance Imaging MRI helps evaluate soft tissues for ligament rupture and can evaluate pathologic fracture ( see the image below ) . Amyloidosis may cause erosion in and around a joint , resulting in subtle radiographic signs , while amyloid deposits can be visualized directly on MRI . Coronal T1 - weighted MRI of the knee in a renal transplant patient on steroids reveals serpentine hypointensity in the metaphyseal and subchondral regions ( black arrows ) with secondary chondral collapse of the lateral femoral condyle ( white arrow ) . Ultrasonography Ultrasound provides a noninvasive , cost - effective , quick , repeatable , and portable modality in the diagnosis of renal osteodystrophy . Ultrasound is especially proficient at the evaluation of soft tissues , the parathyroid glands , and pathologic changes of the joints , as well as for detection of metastatic calcifications . 31 Parathyroid glands are readily accessible for the detection of enlarged parathyroid gland in patients with secondary hyperparathyroidism ; for the monitoring of pathologic changes ; and for making decisions regarding the method of treatment on the basis of size and number of parathyroid glands . US can distinguish nodal from diffuse parathyroid hyperplasia and can provide a reliable method for obtaining a fine - needle aspiration biopsy . Ultrasound can detect the pathologic changes associated with beta - 2 amyloidosis , especially in the shoulder , which is most pronounced as rotator cuff thickness , hyperechoic amyloid deposits , and fluid in the joint . It can also be used for other joints and soft tissues for metastatic calcifications . Quantitative bone ultrasound is based on different physical characteristics of the ultrasound , including transmission , speed of sound in m / sec , and broad - band attenuation in dB / MHz . These measures depend on the strength and architecture of the bones and can describe the changes in bone structure in dialysis patients by calculation of the Stiffness Index . The Stiffness Index is better than the standard bone densitometry by dual - energy x - ray absorptiometry , which only measures bone density . Combined ultrasound measurements of the bone in several locations may be successful 31 Ultrasound is operator dependent , and bone penetration of the ultrasound beam has limitations , particularly in negotiating dense cortical bone . The differential diagnosis of bone resorption is wide . Nuclear Imaging F - 18 Fluorodeoxyglucose positron emission tomography and computed tomography ( F - 18 FDG PET / CT ) may reveal diffuse skeletal uptake of radiopharmaceutical with a superscan appearance that can be confused with metastatic disease . 32 However , the extremities typically have a greater level of increased uptake with secondary hyperparathyroidism than expected with metastatic disease . In addition , bone scans may reveal pseudofractures or sites of extraskeletal calcification , which also may be distinctive for secondary hyperparathyroidism . Sections Imaging in Osteomalacia and Renal Osteodystrophy Computed Tomography Show All Media Gallery References
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[
"Osteomalacia",
"Renal Osteodystrophy",
"secondary hyperparathyroidism"
] |
http://emedicine.medscape.com/article/405454-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Radiology Ultrasonography in Biophysical Profile Updated : Dec 30 , 2015 Author : Peter A Gearhart , MD ; Chief Editor : Eugene C Lin , MD more . . . Sections Overview Biophysical Profile Procedure Amniotic Fluid Index The Modified Biophysical Profile Application of the Biophysical Profile Reliability of the Biophysical Profile Show All Media Gallery Tables References Overview The biophysical profile ( BPP ) is a noninvasive test that predicts the presence or absence of fetal asphyxia and , ultimately , the risk of fetal death in the antenatal period . 1 When the BPP identifies a compromised fetus , measures can be taken to intervene before progressive metabolic acidosis leads to fetal death . 2 3 4 5 6 7 The BPP combines data from 2 sources ( ie , ultrasonographic imaging and fetal heart rate [ FHR ] monitoring ) . Dynamic realtime B - mode ultrasonography is used to measure the amniotic fluid volume ( AFV ) and to observe several types of fetal movement . The FHR is obtained using a pulsed Doppler transducer integrated with a high - speed microprocessor , which provides a continuously updated reading . 8 9 Originally described by Manning and colleagues , 10 11 the BPP has become a standard tool for providing antepartum fetal surveillance . The BPP integrates 5 parameters to yield a biophysical profile score ( BPS ) and includes ( 1 ) the nonstress test ( NST ) , ( 2 ) ultrasonographic measurement of the AFV , ( 3 ) observation of the presence or absence of fetal breathing movements , ( 4 ) gross body movements , and ( 5 ) tone . Table 1 , below , describes specific criteria for the BPS . The BPP allows 2 points for each parameter that is present , yielding a maximum score of 10 ; however , if all of the ultrasonographic variable findings are normal , the FHR variable may be excluded , because no change is made in the predicative accuracy of the BPP by including the FHR ( see the graph below ) . If 1 or more ultrasonographic variable findings are abnormal , the NST should be performed . Reactive nonstress test . The top graph plots the fetal heart rate over time . Each small box represents 10 seconds along the horizontal axis and 10 beats per minute along the vertical axis . The baseline fetal heart rate is from 140 - 150 beats per minute . This tracing is reactive , since at least 2 accelerations of the fetal heart rate occur within less than 20 minutes . View Media Gallery A basic principle of antepartum testing is that a more accurate prediction of fetal wellness is achieved in direct proportion to the number of variables considered . The BPP is a clinical tool that integrates levels of dynamic biophysical activities into a usable standard . 12 The BPP allows 2 points for each parameter that is present , yielding a maximum score of 10 ; however , if all ultrasonographic variables are normal , the FHR variable may be excluded because no change is made in the predictive accuracy of the BPP by including the FHR . If 1 or more ultrasonographic variables are abnormal , the NST should be performed . 13 Table 1 . Criteria for Coding Fetal Biophysical Variables as Normal or Abnormal ( Open Table in a new window ) Biophysical Variable Normal ( Score = 2 ) Abnormal ( Score = 0 ) Fetal breathing movements * 1 or more episodes of ≥ 20 s within 30 min Absent or no episode of ≥ 20 s within 30 min Gross body movements 2 or more discrete body / limb movements within 30 min ( episodes of active continuous movement considered as a single movement ) < 2 episodes of body / limb movements within 30 min Fetal tone 1 or more episodes of active extension with return to flexion of fetal limb ( s ) or trunk ( opening and closing of hand considered normal tone ) Slow extension with return to partial flexion , movement of limb in full extension , absent fetal movement , or partially open fetal hand Reactive FHR 2 or more episodes of acceleration of ≥ 15 beats per minute ( bpm ) and of > 15 s associated with fetal movement within 20 min 1 or more episodes of acceleration of fetal heart rate or acceleration of < 15 bpm within 20 min Qualitative AFV 1 or more pockets of fluid measuring ≥ 2 cm in vertical axis Either no pockets or largest pocket < 2 cm in vertical axis * Note : The current clinical management guidelines from the American College of Obstetrics and Gynecology maintain the original findings from Manning et al in 1987 . 13 These include the following : Fetal breathing movements should include 1 or more episodes of rhythmic fetal breathing for at least 30 s or more in 30 min . Manning et al ' s revised findings from 1999 are modified to include only 20 s , as stated in the table . Gross body movements should include 3 or more discrete body or limb movements within 30 min . Reprinted with permission from Manning , 1999 Each of the movements evaluated in the BPP results from efferent signals originating in different central nervous system ( CNS ) centers , which mature at different gestational ages ( see Table 2 ) . Table 2 . Maturation of Central Nervous System Regulatory Centers ( Open Table in a new window ) Activity Gestational Age of Maturation ( wk ) Gross body movements 6 Breathing movements 12 - 14 FHR accelerations resulting from fetal movement 18 - 20 Sleep - wake cycles 18 - 22 Integrated behavioral patterns 28 Table 3 shows a variety of factors , other than hypoxemia , that have been shown to affect different BPP parameters . Table 3 . Factors Affecting the Biophysical Profile Activity FHR Accelerations Tone Gross Movement Fetal Breathing AFV Fetal sleep ⇓ ⇓ Early gestational age ( < 33 wk ) Late gestational age ( > 42 wk ) Maternal glucose ingestion ⇑ Maternal alcohol ingestion ⇓ / — ⇑ / — Maternal magnesium administration Artificial rupture of membranes Premature rupture of membranes Labor Key : A blank box indicates that no data are available for that parameter . Horizontal lines indicate that the parameter has been studied and that no change is demonstrated . Arrows indicate that the parameter has been studied and that it increases or decreases as shown . Next : Biophysical Profile Procedure
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[
"BPP",
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http://emedicine.medscape.com/article/441510-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Urology Horseshoe Kidney Updated : Dec 29 , 2016 Author : Robert C Allen , Jr , MD , FACS ; Chief Editor : Bradley Fields Schwartz , DO , FACS more . . . Sections Overview Workup Treatment Media Gallery References Practice Essentials The horseshoe kidney is the most common type of renal fusion anomaly . It consists of two distinct functioning kidneys on each side of the midline , connected at the lower poles by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline of the body . Intravenous pyelography ( IVP ) protocol computed tomography ( CT scanning of the abdomen and pelvis , with and without intravenous contrast ) is the best initial radiologic study to determine anatomy and relative renal function ( see Workup ) . Horseshoe kidneys are susceptible to medical renal disease . These diseases , if present , are treated as indicated . For patient education information , see the Kidneys and Urinary System Center , as well as Kidney Stones Epidemiology Frequency Horseshoe kidney occurs in 1 per 400 - 800 live births . The true incidence probably lies somewhere between these two extremes . Horseshoe kidney is twice as common in males as in females . No genetic determinant is known , although horseshoe kidney has been reported in identical twins and in siblings within the same family . Etiology Two theories regarding the embryogenesis of the horseshoe kidney have been proposed . The classic teaching of mechanical fusion holds that the horseshoe kidney is formed during organogenesis , when the inferior poles of these early kidneys touch , fusing in the lower midline . The theory of mechanical fusion is valid for horseshoe kidneys with a fibrous isthmus . Alternatively , more recent studies postulate that the abnormal fusion of tissue associated with the parenchymatous isthmus of some horseshoe kidneys is the result of a teratogenic event involving the abnormal migration of posterior nephrogenic cells , which then coalesce to form the isthmus . 1 This teratogenic event may also be responsible for the increased incidence of related congenital anomalies and of certain neoplasias , such as Wilms tumor and carcinoid tumor associated with the isthmus of the horseshoe kidney . Pathophysiology By itself , the horseshoe kidney does not produce symptoms . However , by virtue of its embryogenesis and anatomy , it is predisposed to a higher incidence of disease than the normal kidney . The variable blood supply , presence of the isthmus , high insertion point , and abnormal course of the ureters all contribute to these problems . Because of these embryogenic and anatomical factors , the rates of hydronephrosis , stone formation , infection , and certain cancers are higher , resulting in a diseased horseshoe kidney ( see image below ) . Excretory urogram shows a horseshoe kidney with left hydronephrosis . View Media Gallery The most common associated finding in horseshoe kidney is ureteropelvic junction ( UPJ ) obstruction , which occurs in up to 35 % of patients . It causes most problems . Obstruction is due to the high insertion of the ureter into the renal pelvis . The crossing of the ureter over the isthmus may also contribute to obstruction . Nonobstructive dilatation must be distinguished from obstructive dilatation using diuresis radioisotope renal scans . The prevalence of stones in the horseshoe kidney ranges from 20 - 60 % . Stone disease is thought to be due to the associated hydronephrosis or UPJ obstruction that causes urinary stasis , which hinders stone passage . Metabolic factors , as in the normal population , have also been suggested as contributing to stone formation in these patients . The orientation of the calyces also impairs drainage , resulting in stasis . These kidneys appear dilated or abnormal on most imaging studies , although the radionuclide scans are generally accepted as being diagnostic . Urinary stasis and stone disease also predispose the horseshoe kidney to infection , which occurs in 27 - 41 % of patients . Ascending infection from vesicoureteral reflux is another cause of infection in the horseshoe kidney . Certain cancers are more common in the horseshoe kidney . 2 This is thought to be due to teratogenic factors present at birth and the susceptibility of the diseased horseshoe kidney to certain cancers . Renal cell carcinoma is the most common renal cancer in horseshoe kidney , accounting for 45 % of tumors . 3 4 The incidence of renal cell cancer in the horseshoe kidney is no different from that of the normal kidney . Transitional cell cancer and sarcoma account for 20 % and 7 % of tumors , respectively . The relative risk of transitional cell carcinoma in the horseshoe kidney is increased 3 - to 4 - fold . This is thought to be due to chronic obstruction , stones , and / or infection in the affected kidneys . The incidence of both Wilms and carcinoid tumors is also higher in the horseshoe kidney . Examination of these tumors may provide an insight into the development and embryogenesis of the horseshoe kidney and the predilection of these two tumors to form in the horseshoe kidney . Wilms tumor accounts for 28 % of malignant lesions . The relative risk of Wilms tumor is increased 2 - fold . Half of these arise from the isthmus . Renal carcinoids are rare , with only 32 reported cases . Of the 32 cases , 5 of these renal carcinoids arose in a horseshoe kidney . The relative risk of a carcinoid tumor in a patient with a horseshoe kidney is 62 times that found in the normal population . Of the 5 reported carcinoid tumors reported in patients with horseshoe kidneys , 3 have originated in or have involved the isthmus . The location of these tumors in the isthmus may be explained by the embryogenesis involving abnormal migration of posterior nephrogenic cells , leading to the formation Presentation Nearly one third of patients with a horseshoe kidney remain asymptomatic , and the horseshoe kidney is an incidental finding during radiological examination . Physical examination may reveal a midline lower - abdominal mass . Symptoms , when present , are usually due to obstruction , stones , or infection . In children , urinary tract infection is the most common presenting symptom . Clinical signs of disease are similar to those that would be found in a normal kidney . However , symptoms may be vague . Instead of flank pain , abdominal pain , and gastrointestinal symptoms such as nausea , abdominal distension and fullness may predominate . The Rovsing sign , consisting of abdominal pain , nausea , and vomiting with hyperextension of the spine , is rare . The horseshoe kidney may be predisposed to blunt abdominal trauma because it is unprotected by the rib cage and may be compressed or fractured across the lumbar vertebral column by an abdominal blow . This can occur during a car crash when the victim is restrained by a seat belt ; the kidney is compressed between the belt and the spine . Associated genitourinary anomalies in horseshoe kidney are common and occur in as many as two thirds of patients . Vesicoureteral reflux is present in approximately half the patients . Ureteral duplication is present in 10 % . Hypospadias or undescended testis is present in 4 % of males . Bicornuate uterus or septate vagina is present in 7 % of females . Other anomalies occur in other organ systems . In autopsy series , these abnormalities are more prevalent in children because the congenital anomalies associated with horseshoe kidney are incompatible with long - term survival . Therefore , the incidence of other anomalies is greater in those who die at birth or early infancy than in those who reach adulthood . These coexisting abnormalities in the cardiovascular , gastrointestinal , and skeletal systems occur in up to 85 % of patients . These include ventriculoseptal defects , hemivertebrae with scoliosis , myelomeningocele , and colobomata of the iris . Horseshoe kidney Turner syndrome , oral - cranial - digital syndrome , and trisomies 18 and E . Autosomal - dominant polycystic kidney disease has also been found in the horseshoe kidney , with 20 such cases reported in the literature . Relevant Anatomy Horseshoe kidneys may be found at any location along the path of normal renal ascent from the pelvis to the mid abdomen . The kidneys may be lower than normal because the isthmus is tethered by the inferior mesenteric artery during renal ascent . The isthmus usually lies anterior to the great vessels , at the level of the third to fifth lumbar vertebra . Rarely , it is posterior to these vessels or runs between them . The vascular supply is variable and originates from the aorta , the iliac arteries , and the inferior mesenteric artery . Bilateral single renal hilar arteries occur in 30 % of cases , and various combinations of single and multiple renal hilar and isthmus vessels are seen in 70 % of cases . The isthmus of the kidney may not have a separate blood supply or , in 65 % of cases , is supplied by a single vessel from the aorta . The blood supply to the isthmus may arise from the common iliac or inferior mesenteric arteries . The collecting system has a characteristic appearance on intravenous urography because of an incomplete inward rotation of the renal pelvis , which faces anterior . The axis of the collecting system is deviated inward at the lower poles because of the lower pole ' s connection with the isthmus . The ureter may have a high insertion point into the renal pelvis and may cross anteriorly over the isthmus as it descends to the bladder . Rarely does the collecting system cross the isthmus to the contralateral kidney . Contraindications In the presence of UPJ obstruction , symphysiotomy ( division of the isthmus ) was once recommended routinely after pyeloplasty to improve drainage . However , this procedure is associated with an increased risk of hemorrhage , fistula , and renal infarction . Also , because of their abnormal vasculature , the kidneys return to their original position after division of the isthmus . Because of this , symphysiotomy is rarely , if ever , indicated in conjunction with pyeloplasty . The presence of obstruction or hydronephrosis precludes treatment of kidney stones using extracorporeal shockwave lithotripsy ( ESWL ) . 5 Sections Horseshoe Kidney Overview Treatment Media Gallery References
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[
"Horseshoe Kidney",
"Urology"
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http://emedicine.medscape.com/article/461577-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Vascular Surgery Internal Jugular Vein Thrombosis Updated : Mar 26 , 2018 Author : Dale K Mueller , MD ; Chief Editor : Vincent Lopez Rowe , MD more . . . Sections Overview Presentation Workup Treatment Medication Questions & Answers References Background Internal jugular ( IJ ) vein thrombosis refers to an intraluminal thrombus occurring anywhere from the intracranial IJ vein to the junction of the IJ and the subclavian vein to form the brachiocephalic vein . It is an underdiagnosed condition that may occur as a complication of head and neck infections , surgery , central venous access , local malignancy , polycythemia , hyperhomocysteinemia , neck massage , and intravenous ( IV ) drug abuse . It is also reported to occur spontaneously . Currently , with the widespread use of the IJ vein for venous access , central venous catheters are the most common underlying cause of IJ thrombosis . Of concern is a trend reflecting a growing number of IV drug abusers who present with IJ thrombosis secondary to repeated drug injection directly into the IJ vein . Other causes include local malignancies and head , neck , and cardiac surgical procedures . Rare causes include polycythemia , hyperhomocysteinemia , and neck massage . IJ thrombosis itself can have serious potentially life - threatening complications , including systemic sepsis , chylothorax , papilledema , airway edema , and pulmonary embolism ( PE ) . 1 Secondary infection of the thrombosis may result in septic thrombophlebitis . An infected IJ thrombus caused by extension of an oropharyngeal infection is referred to as Lemierre syndrome ; this has also been termed necrobacillosis or postanginal septicemia . The diagnosis often is highly challenging and requires , first and foremost , a high degree of clinical suspicion . The best approach to making the diagnosis once suspicion is raised has not been definitively established . The morbidity and mortality of IJ vein thrombosis are comparable to those of upper - extremity deep vein thrombosis ( DVT ) ; accordingly , consideration should be given to treating these two entities in a similar fashion . Thrombolytic treatment has rarely been used to treat IJ vein thrombosis . For patient education resources , see the Lung Disease and Respiratory Health Center , as well as Pulmonary Embolism Venous Access Devices Phlebitis , and Blood Clot in the Legs Anatomy The IJ vein begins in the cranium at the conclusion of the sigmoid sinus . It exits the cranium via the jugular foramen and then courses through the anterior neck lateral to the carotid artery , covered by the sternocleidomastoid muscle for most of its length . It concludes by joining the subclavian vein , thus forming the brachiocephalic vein . The styloid process divides the lateral pharyngeal space into an anterior ( muscular ) compartment and a posterior compartment containing the carotid artery within the carotid sheath , the IJ vein , cranial nerves IX - XII , and lymph nodes . Pathophysiology The classic triad predisposing to intravascular thrombosis was described first by Virchow and includes the following : Blood vessel trauma Stasis of blood flow Hypercoagulable state In the case of central venous lines , the catheter itself acts as the nidus for clot formation , despite being bonded and flushed with heparin . Additionally , the catheter tip itself may produce damage to the vessel wall and disrupt venous flow , further augmenting clot formation . Various oropharyngeal infections ( eg , odontogenic infections and infections of the tonsils , peritonsillar tissue , pharynx , sinuses , middle ear , and parotids ) may lead to Lemierre syndrome . The primary infection spreads to the posterior compartment of the lateral pharyngeal space , leading to thrombophlebitis of the IJ vein . The infection spreads via local tissue planes , venules , or lymphatic vessels . Subsequent sepsis syndrome may occur , usually a week or more after the primary infection . The factors responsible for bacterial invasion are not well understood , though bacterial toxins , primary viral infection , and smoking have all been implicated . IV drug injection promotes clot formation via vascular damage , local infection , or a combination of the two . Malignancy may cause IJ vein thrombosis through local compression and invasion , production of a systemic hypercoagulable state , or both . Etiology Thrombosis associated with central venous catheters occurs more frequently than was previously believed . One study found that 66 % of patients who had an IJ vein catheter in place at some time during their hospital course had either ultrasonographic or autopsy evidence of IJ thrombus . The frequency was even greater in more critically ill patients , especially those with low cardiac output or shock syndromes . Causes of IJ thrombosis include the following : Central venous or Swan - Ganz catheters in the IJ vein Central venous or Swan - Ganz catheters in the subclavian vein Individuals who abuse IV drugs using the IJ vein for access Lemierre syndrome Deep neck infections Necrotizing soft - tissue infections Neck dissection surgical complications Head and neck malignancy Distant malignancy producing a hypercoagulable state Hypercoagulable state secondary to factor V Leiden , protein C , protein S , or antithrombin III deficiency Jugular bulb catheters Any neck surgery involving prolonged retraction of the IJ vein Trauma Association with ovulation induction with gonadotropins Hyperhomocysteinemia Neck massage Polycythemia Spontaneous causes ( often secondary to an undiagnosed malignancy or hypercoagulable state ) Gram - positive organisms that often have high - grade resistance to beta - lactam antibiotics frequently cause septic thrombophlebitis associated with central venous catheters . One study reported a 40 % incidence of beta - lactam – resistant organisms with catheter - induced IJ vein thrombosis . Individuals who abuse IV drugs have a very high risk of septic thrombophlebitis caused by methicillin - resistant Staphylococcus aureus ( MRSA ) . In cases of Lemierre syndrome , anaerobic organisms often predominate . Fusobacterium species ( eg , F nucleatum , F necrophorum ) are anaerobic gram - negative rods that are often mistaken for Bacteroides species . F necrophorum is the most virulent and commonly isolated pathogen . 2 Other organisms include Bacteroides and Peptostreptococcus species , Eikenella corrodens , and S aureus . Epidemiology Some studies suggest that the rate of thrombosis may be lower for Silastic ( Dow Corning , Midland , MI ) hemodialysis catheters inserted percutaneously than for those inserted surgically . Additionally , the rate of thrombosis may be lower in patients undergoing hemodialysis than in other critically ill patients . The incidence of Lemierre syndrome has fallen dramatically since the use of antibiotics began in the late 1950s . However , this syndrome still occurs , particularly in underserved populations . Case series have described IJ vein thrombosis rates of 25 - 30 % after functional neck dissection and hemodialysis catheter placement . However , a significant percentage of affected patients have been advised to undergo recanalization , with excellent long - term patency rates . The frequency of IJ vein thrombosis in individuals who abuse IV drugs is not known , but this condition usually occurs in people who have been using injectable drugs for years and have exhausted all peripheral access sites . Prognosis The outcome is generally good , but with morbidity and mortality similar to those for subclavian and axillary vein thrombosis . PE can occur but is uncommon when full - strength systemic anticoagulation is in place . The incidence of PE is 0.5 % for isolated IJ vein thrombosis and 2.4 % for combined IJ vein and subclavian / axillary vein thrombosis . Mortality has been reported to be 14 % at 1 month , 33 % at 3 months , and 42 % at 12 months . 3 Before the antibiotic era , Lemierre syndrome was associated with a mortality exceeding 50 % . Today , however , death is uncommon when the syndrome is recognized early and treated with appropriate aggressive medical and surgical therapy . In one series of patients with septic thrombophlebitis occurring over a 9 - year period , death occurred in 17 % of patients . Many patients have ongoing critical illness , often with multisystem involvement . This makes it difficult to determine how much the thrombus itself is contributing to mortality . The advantage of being aware of the diagnosis is that the physician can be more vigilant for potential complications and perhaps treat them earlier . Clinical Presentation Sections Internal Jugular Vein Thrombosis Overview Presentation Workup Treatment Medication Questions & Answers References
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[
"Thrombosis",
"Internal jugular"
] |
http://emedicine.medscape.com/article/760220-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Emergency Medicine Sinus Bradycardia Treatment & Management Updated : Dec 27 , 2017 Author : Mark W Livingston , MD ; Chief Editor : Erik D Schraga , MD more . . . Sections Overview Presentation DDx Workup Treatment Prehospital Care Emergency Department Care Long - Term Monitoring Show All Medication Questions & Answers References Prehospital Care Intravenous access , supplemental oxygen , and cardiac monitoring should be initiated in the field . In symptomatic patients , intravenous atropine may be used . In rare cases , transcutaneous pacing may need to be initiated in the field . Next : Emergency Department Care What to Read Next on Medscape Related Conditions and Diseases Malignant Arrhythmia and Cardiac Arrest in the Operating Room Complications of Myocardial Infarction Pediatric Ventricular Tachycardia Hypertensive Heart Disease Arrhythmogenic Right Ventricular Dysplasia ( ARVD ) Cardiac Risk Index in Noncardiac Surgery ( Detsky et . al . ) News & Perspective Atrial Arrhythmias in Takotsubo Syndrome Stress - Related Disorders Increase CVD Risk , Study Suggests Unexplained Tachycardia ' Triples Cancer Mortality Risk ' Tools Drug Interaction Checker Pill Identifier Calculators Formulary Slideshow New Guidelines and Recommendations Most Popular Articles According to Cardiologists Alcohol and the Electric Atrium : How Drinking Promotes AF ? Marijuana Edible Linked to Myocardial Infarction The Remarkable Story of a Wonder Drug , Which Now Comes to an End in the Primary Prevention Setting : Say Bye - bye to Aspirin ! A Morning Walk , Less Sitting Can Lower Blood Pressure for Hours New AHA / ACC CVD Primary Prevention Guideline View More Sections Sinus Bradycardia Overview Presentation DDx Workup Treatment Emergency Department Care Long - Term Monitoring Show All Medication Questions & Answers References Recommended Diseases & Conditions Malignant Arrhythmia and Cardiac Arrest in the Operating Room News Thai Cave Rescue : Details for Preventing Hypothermia , Panic
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[
"Sinus Bradycardia",
"Prehospital Care",
"supplemental oxygen"
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http://emedicine.medscape.com/article/761451-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Emergency Medicine Vertebral Artery Dissection Updated : Feb 21 , 2019 Author : Eddy S Lang , MDCM , CCFP ( EM ) , CSPQ ; Chief Editor : Barry E Brenner , MD , PhD , FACEP more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Practice Essentials Vertebral artery dissection ( VAD ) is a relatively rare but increasingly recognized cause of stroke in patients younger than 45 years . Although the term spontaneous VAD is used to describe cases that do not involve significant blunt or penetrating trauma as a precipitating factor , many patients with so - called spontaneous VAD have a history of trivial or minor injury involving some degree of cervical distortion . See the image below . A , Dissection of the left vertebral artery secondary to guidewire injury . B , Complete resolution occurred in 6 months with only aspirin and clopidogrel ( Plavix ) therapy . View Media Gallery Signs and symptoms The typical patient with VAD is a young person who experiences severe occipital headache and posterior nuchal pain following a head or neck injury and subsequently develops focal neurologic signs attributable to ischemia of the brainstem or cerebellum . The focal signs may not appear until after a latent period lasting as long as three days , however , and delays of weeks and years also have been reported . Many patients present only at the onset of neurologic symptoms . When neurologic dysfunction does occur , patients most commonly report symptoms attributable to lateral medullary dysfunction ( ie , Wallenberg syndrome ) . Patient history may include the following : Ipsilateral facial dysesthesia ( pain and numbness ) 1 - Most common symptom Dysarthria or hoarseness ( cranial nerves [ CN ] IX and X ) Contralateral loss of pain and temperature sensation in the trunk and limbs Ipsilateral loss of taste ( nucleus and tractus solitarius ) Hiccups Vertigo 1 Nausea and vomiting Diplopia or oscillopsia ( image movement experienced with head motion ) Dysphagia ( CN IX and X ) Disequilibrium Unilateral hearing loss 2 Rarely , patients may manifest the following symptoms of a medial medullary syndrome : Contralateral weakness or paralysis ( pyramidal tract ) Contralateral numbness ( medial lemniscus ) Depending upon which areas of the brainstem or cerebellum are experiencing ischemia , the following signs may be present : Limb or truncal ataxia Nystagmus 3 Ipsilateral Horner syndrome 4 5 Ipsilateral hypogeusia or ageusia ( ie , diminished or absent sense of taste ) Ipsilateral impairment of fine touch and proprioception Contralateral impairment of pain and thermal sensation in the extremities ( ie , spinothalamic tract ) Lateral medullary syndrome 6 Cerebellar findings may include the following : Nystagmus Medial medullary syndrome Tongue deviation to the side of the lesion ( impairment of CN XII ) Contralateral hemiparesis Ipsilateral impairment of fine touch and proprioception ( nucleus gracilis ) Internuclear ophthalmoplegia ( lesion of the medial longitudinal fasciculus ) See Presentation for more detail . Diagnosis Imaging studies in patients with suspected VAD may include the following : Computed tomography ( CT ) scanning – Identifies subarachnoid hemorrhage 3 ; CT angiography ( CTA ) , along with magnetic resonance angiography ( MRA ) , are the imaging modalities of choice for vertebral artery dissections ; however , CTA is less accurate in the presence of calcified arteries . Magnetic resonance imaging 7 8 9 10 11 – Detects both the intramural thrombus and intimal flap that are characteristic of VAD 7 ; hyperintensity of the vessel wall seen on T1 - weighted axial images is considered by some to be pathognomonic of VAD MRA 8 9 10 11 12 – Can identify a pseudolumen and aneurysmal dilation of the artery Four - vessel cerebral angiography – Once the criterion standard for diagnosis , now largely supplanted by noninvasive techniques Vascular duplex scanning – Demonstrates abnormal flow in 95 % of patients with VAD , but shows signs specific to VAD ( eg , segmental dilation of the vessel , eccentric channel ) in only 20 % Transcranial Doppler ultrasonography – Approximately 75 % sensitive to the flow abnormalities seen in VAD useful also in detecting high - intensity signals ( HITS ) , which are characteristic of microemboli propagating distally as a result of the dissection ; ultrasonography may have a role in the initial diagnosis of dissections if CT - A or MRA are unavailable . Because VAD occurs in young , generally healthy individuals , laboratory evaluation is directed toward establishing baseline parameters in anticipation of anticoagulant therapy , as follows : Prothrombin time ( PT ) with international normalized ratio ( INR ) Activated partial thromboplastin time ( aPTT ) In addition , elevation of the erythrocyte sedimentation rate ( ESR ) may suggest vasculitis involving the cerebrovascular circulation . See Workup for more detail . Management Acute management of proven or suspected spontaneous VAD is as follows 13 Anticoagulants and antiplatelet agents are the drugs of choice to prevent thromboembolic disorders ; the data suggest no difference between the two modalities on outcomes and adverse effects More potent agents ( eg , intra - arterial thrombolytics ) have been used in selected cases ; there may be a role for these medications during acute ischemic events Endovascular and surgical treatments are reserved for patients with concomitant complications or whose maximal medical therapy is unsuccessful Treatment and Medication Background Vertebral artery dissection ( VAD ) is an increasingly recognized cause of stroke in patients younger than 45 years . 4 14 15 16 17 Although its pathophysiology and treatment closely resemble that of its sister condition , carotid artery dissection ( CAD ) , the clinical presentation , etiology , and epidemiologic profile of VADs are unique . In particular , advances in imaging have contributed to growing awareness of this entity . Pathophysiology An expanding hematoma in the vessel wall is the root lesion in vertebral artery dissection ( VAD ) . This intramural hematoma can arise spontaneously or as a secondary result of minor trauma , through hemorrhage of the vasa vasorum within the media of the vessel . It also can be introduced through an intimal flap that develops at the level of the inner lumen of the vessel . Major trauma is also an increasingly recognized cause of VAD . 18 This intramural hemorrhage can evolve in a variety of ways , resulting in any of the following consequences : The hematoma may seal off and , if sufficiently small , remain largely asymptomatic . If the dissection is subintimal , the expanding hematoma may partially or completely occlude the vertebral artery or one of its branches . Extensive dissections ( those that extend intracranially and involve the basilar artery ) result in infarctions of the brainstem , cerebellum or , rarely , the spinal cord . Subintimal dissections also may rupture back into the vertebral artery , thus creating a false lumen ( pseudolumen ) . Subadventitial dissections tend to cause pseudoaneurysmal dilation of the vertebral artery , which may compress adjacent neurologic structures . These subadventitial dissections are prone to rupture through the adventitia , resulting in subarachnoid hemorrhage . In an autopsy series of more than 100 patients with subarachnoid hemorrhage , 5 % of the hemorrhages were deemed the result of VAD . The intimal disruption and low flow states that arise in VAD create a thrombogenic milieu in which emboli may form and propagate distally . This results in transient ischemia or infarction . An understanding of the anatomy of the vertebral artery is helpful . The course of the vertebral artery usually is divided into four sections as follows : Segment I runs from its takeoff at the first branch of the subclavian artery to the transverse foramina of cervical vertebra C5 or C6 . Segment II runs entirely within the transverse foramina of C5 / C6 to C2 . Segment III , a tortuous segment , begins at the transverse foramen of C2 , runs posterolaterally to loop around the posterior arch of C1 , and passes subsequently between the atlas and the occiput . This segment is encased in muscles , nerves , and the atlanto - occipital membrane . Segment IV , the intracranial segment , begins as it pierces the dura at the foramen magnum and continues until the junction of the pons and medulla , where the vertebral arteries merge to join the larger proximal basilar trunk . Spontaneous dissection of the vertebral artery usually occurs in the tortuous distal extracranial segment ( segment III ) but may extend into the intracranial portion or segment IV . Etiology Spontaneous vertebral artery dissection ( VAD ) is the term used to describe all cases that do not involve blunt or penetrating trauma as a precipitating factor . However , a history of trivial or minor injury is elicited frequently from patients with so - called spontaneous VAD . The diagnosis of traumatic VAD is reserved for those patients with a history of significant trauma , including motor vehicle accidents ( MVAs ) , falls , or penetrating injuries . Despite the severity of the injury mechanism , dissections of the vertebral artery are exceedingly rare in these contexts . Several risk factors have been associated with the development of VAD . These include the following : Spinal manipulation 6 15 16 19 20 21 22 : Has one of the best studied and strongest demonstrated associations with VAD ( The Canadian Chiropractic Association , Canadian Federation of Chiropractic Regulatory Boards , Clinical Practice Guidelines Development Initiative , Guidelines Development Committee have specific recommendations on assessment of signs of impaired vertebral artery flow and recommendations for treating or not treating patients with suspected impaired flow . 23 Vertebral artery hypoplasia 24 Yoga Ceiling painting Nose blowing Minor neck trauma Judo Medical risk factors Hypertension 25 ( 48 % in one series ) Oral contraceptive use Chronic headache syndromes / migraines Intrinsic vascular pathology Fibromuscular dysplasia Cystic medial necrosis Female sex Postpartum ( rare ) 26 Recent infection 12 When patients with serious cervical trauma , such as cord injuries or cervical spine fractures , are screened for vertebral artery injury , 20 - 40 % may demonstrate traumatic occlusion . This traumatic vertebral artery occlusion ( as opposed to dissection ) is asymptomatic , and its management is controversial . Epidemiology United States statistics Dissections of the extracranial cervical arteries are relatively rare . The combined incidence of both verterbral artery dissection ( VAD ) and carotid artery dissection ( CAD ) is estimated to be 2.6 per 100,000 . However , cervical dissections are the underlying etiology in as many as 20 % of the ischemic strokes presenting in younger patients aged 30 - 45 years . Among all extracranial cervical artery dissections , CAD is 3 - 5 times more common than VAD . Sex - and age - related demographics The female - to - male ratio is 3 : 1 . In contrast to atherothrombotic disease of the vertebrobasilar circulation , VAD occurs in a much younger population . The average age is 40 years ; the average age of a patient with CAD is closer to 47 years . Prognosis Extracranial dissection Most patients with extracranial dissection do remarkably well if they survive the initial crisis . As many as 88 % of these patients demonstrate a complete clinical recovery at follow - up . However , this suggests an overall risk of death , recurrent transient ischemic attacks , or stroke of approximately 10 % . One series suggests that the severity of neurologic deficits at the time of presentation is related directly to the functional outcome . Follow - up angiography demonstrates spontaneous healing in as many as two thirds of these patients . Intracranial dissection Patients with intracranial vertebrobasilar dissection constitute a more severely affected subgroup of all patients with verterbral artery dissection ( VAD ) . 13 The presentation of a dissection involving the intracranial portion of the vertebral artery ( segment IV ) is characterized by rapidly progressive neurologic deficits , including depressed consciousness . VAD is associated with subarachnoid hemorrhage , brainstem infarctions , and high mortality rate . Morbidity / mortality VAD has been associated with a 10 % mortality rate in the acute phase . Death is the result of extensive intracranial dissection , brainstem infarction , or subarachnoid hemorrhage Those who survive the initial crisis do remarkably well , with long - term sequelae rare . Complications Complications include the following : Brainstem infarction Cerebellar infarction Subarachnoid hemorrhage Vertebral artery pseudoaneurysm causing compressive cranial neuropathy Major complications of vertebral artery dissection include stroke and death . Previous observational studies have yielded stroke rates between 0.3 % and 8.5 % after vertebral or carotid artery dissection . However , one randomized clinical trial observed a much lower stroke rate of 1.2 % at 3 month follow - up and no deaths were reported in this time . 27 28 As recurrences are rare , any definitive study examining complications following dissection will require large sample sizes . Clinical Presentation Sections Vertebral Artery Dissection Overview DDx Questions & Answers Media Gallery References
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"Vertebral Artery Dissection",
"Dysarthria",
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http://emedicine.medscape.com/article/767624-clinical
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Emergency Medicine Hyponatremia in Emergency Medicine Clinical Presentation Updated : Dec 28 , 2018 Author : Kartik Shah , MD ; Chief Editor : Romesh Khardori , MD , PhD , FACP more . . . Sections Overview Presentation History Physical Causes Complications Show All DDx Workup Treatment Medication Questions & Answers References History The number and severity of symptoms increase with the degree of hyponatremia and the rapidity with which it develops . When the serum sodium level falls gradually , over a period of several days or weeks , sodium levels as low as 110 mEq / L may be reached with minimal symptomatology . In contrast , an equivalent fall in serum sodium level over 24 - 48 hours may overwhelm compensatory mechanisms , leading to severe cerebral edema , coma , or brainstem herniation . Symptoms range from mild anorexia , headache , and muscle cramps , to significant alteration in mental status including confusion , obtundation , coma , or status epilepticus . Hyponatremia is often seen in association with pulmonary / mediastinal disease or CNS disorders . Hyponatremia must be considered in patients with pneumonia , active tuberculosis , pulmonary abscess , neoplasm , or asthma , as well as in patients with CNS infection , trauma , or neoplasm . Patients with carcinoma of the nasopharynx , duodenum , stomach , pancreas , ureter , prostate , or uterus also have an increased risk . Hyponatremia is associated with numerous medications . The patient ' s medication list should be examined for drugs known to cause hyponatremia . Hyponatremia has been noted in patients with poor dietary intake who consume large amounts of beer ( known as beer potomania ) and after use of the recreational drug N - methyl - 3 , 4 - methylenedioxyamphetamine ( ie , MDMA or ecstasy ) . MDMA - induced hyponatremia occurs via multiple mechanisms ; these include the induction of syndrome of inappropriate antidiuretic hormone secretion ( SIADH ) , the encouragement to drink large amounts of water to prevent unpleasant side effects of the drug , and the tendency among those intoxicated to be involved in vigorous physical activity that results in heavy sweating . A history of hypothyroidism or adrenal insufficiency should be sought because each is associated with hyposmolar hyponatremia . Patients with clinically significant hyponatremia present with nonspecific symptoms attributable to cerebral edema . These symptoms , especially when coupled with a recent history of altered fluid balance , should suggest the possibility of hyponatremia . Anorexia Nausea and vomiting Difficulty concentrating Confusion Lethargy Agitation Headache Seizures Next : Physical Recommended Diseases & Conditions Hyponatremia Diseases & Conditions Pediatric Hyponatremia
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"Hyponatremia",
"Emergency Medicine Clinical Presentation",
"adrenal insufficiency"
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http://emedicine.medscape.com/article/793582-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Emergency Medicine Spinal Cord Injuries Updated : Nov 01 , 2018 Author : Lawrence S Chin , MD , FACS , FAANS ; Chief Editor : Brian H Kopell , MD more . . . Sections Overview Presentation DDx Workup Treatment Guidelines Medication Questions & Answers References Practice Essentials Spinal cord injury ( SCI ) is an insult to the spinal cord resulting in a change , either temporary or permanent , in the cord ’ s normal motor , sensory , or autonomic function . Patients with SCI usually have permanent and often devastating neurologic deficits and disability . The most important aspect of clinical care for the SCI patient is preventing complications related to disability . Supportive care has shown to decrease complications related to mobility . Further , in the future our increasing fund of knowledge of the brain - computer interface might mitigate some of Signs and symptoms The extent of injury is defined by the American Spinal Injury Association ( ASIA ) Impairment Scale ( modified from the Frankel classification ) , using the following categories : 1 2 A = Complete : No sensory or motor function is preserved in sacral segments S4 - S5 3 B = Incomplete : Sensory , but not motor , function is preserved below the neurologic level and extends through sacral segments S4 - S5 C = Incomplete : Motor function is preserved below the neurologic level , and most key muscles below the neurologic level have a muscle grade of less than 3 D = Incomplete : Motor function is preserved below the neurologic level , and most key muscles below the neurologic level have a muscle grade that is greater than or equal to 3 E = Normal : Sensory and motor functions are normal Definitions of complete and incomplete spinal cord injury , as based on the above ASIA definition , with sacral - sparing , are as follows : 1 2 3 Complete : Absence of sensory and motor functions in the lowest sacral segments Incomplete : Preservation of sensory or motor function below the level of injury , including the lowest sacral segments Respiratory dysfunction Signs of respiratory dysfunction include the following : Loss of ventilatory muscle function from denervation and / or associated chest wall injury Lung injury , such as pneumothorax , hemothorax , or pulmonary contusion Decreased central ventilatory drive that is associated with head injury or exogenous effects of alcohol and drugs A direct relationship exists between the level of cord injury and the degree of respiratory dysfunction , as follows : With high lesions ( ie , C1 or C2 ) , vital capacity is only 5 - 10 % of normal , and cough is absent With lesions at C3 through C6 , vital capacity is 20 % of normal , and cough is weak and ineffective With high thoracic cord injuries ( ie , T2 through T4 ) , vital capacity is 30 - 50 % of normal , and cough is weak With lower cord injuries , respiratory function improves With injuries at T11 , respiratory dysfunction is minimal ; vital capacity is essentially normal , and cough is strong See Clinical Presentation for more detail . Diagnosis Laboratory studies The following laboratory studies can be helpful in the evaluation of spinal cord injury : Arterial blood gas ( ABG ) measurements - May be useful to evaluate adequacy of oxygenation and ventilation Lactate levels - To monitor perfusion status ; can be helpful in the presence of shock Hemoglobin and / or hematocrit levels - May be measured initially and monitored serially to detect or monitor sources of blood loss Urinalysis - Can be performed to detect any associated genitourinary injury Imaging studies Imaging techniques in spinal cord injury include the following : Plain radiography - Radiographs are only as good as the first and last vertebrae seen , therefore , radiographs must adequately depict all vertebrae Computed tomography ( CT ) scanning - Reserved for delineating bony abnormalities or fracture ; can be used when plain radiography is inadequate or fails to visualize segments of the axial skeleton Magnetic resonance imaging ( MRI ) - Used for suspected spinal cord lesions , ligamentous injuries , and other soft - tissue injuries or pathology See Workup for more detail . Treatment Emergency department care Airway management - The cervical spine must be maintained in neutral alignment at all times ; clearing of oral secretions and / or debris is essential to maintaining airway patency and preventing aspiration Hypotension - Hypotension may be hemorrhagic and / or neurogenic in acute spinal cord injury ; a diligent search for occult sources of hemorrhage must be made Neurogenic shock - Judicious fluid replacement with isotonic crystalloid solution to a maximum of 2 L is the initial treatment of choice ; maintain adequate oxygenation and perfusion of the injured spinal cord ; supplemental oxygenation and / or mechanical ventilation may be required 4 5 Head injuries - Amnesia , external signs of head injury or basilar skull fracture , focal neurologic deficits , associated alcohol intoxication or drug abuse , or a history of loss of consciousness mandates a thorough evaluation for intracranial injury , starting with noncontrast head CT scanning Ileus - Placement of a nasogastric ( NG ) tube is essential ; antiemetics should be used aggressively Pressure sores - To prevent pressure sores , turn the patient every 1 - 2 hours , pad all extensor surfaces , undress the patient to remove belts and back pocket keys or wallets , and remove the spine board as soon as possible Pulmonary management Treatment of pulmonary complications and / or injury in patients with spinal cord injury includes supplementary oxygen for all patients and chest tube thoracostomy for those with pneumothorax and / or hemothorax . Surgical decompression Emergent decompression of the spinal cord is suggested in the setting of acute spinal cord injury with progressive neurologic deterioration , facet dislocation , or bilateral locked facets . The procedure is also suggested in the setting of spinal nerve impingement with progressive radiculopathy , in patients with extradural lesions such as epidural hematomas or abscesses , and in the setting of the cauda equina syndrome . and Medication Background Spinal cord injury ( SCI ) is an insult to the spinal cord resulting in a change , either temporary or permanent , in its normal motor , sensory , or autonomic function . Patients with spinal cord injury usually have permanent and often devastating neurologic deficits and disability . According to the National Institutes of Health ( NIH ) , " among neurological disorders , the cost to society of automotive SCI is exceeded only by the cost of mental retardation . " 6 After a suspected SCI , the goals are to establish the diagnosis and initiate treatment to prevent further neurologic injury from either mechanical instability secondary to injury from the deleterious effects of cardiovascular instability or respiratory insufficiency . SCI terminology and classification The International Standards for Neurological and Functional Classification of Spinal Cord Injury ( ISNCSCI ) is a widely accepted system describing the level and extent of injury based on a systematic motor and sensory examination of neurologic function . The following terminology has developed around the classification of spinal cord injuries : Tetraplegia ( replaces the term quadriplegia ) : Injury to the spinal cord in the cervical region , with associated loss of muscle strength in all 4 extremities Paraplegia : Injury in the spinal cord in the thoracic , lumbar , or sacral segments , including the cauda equina and conus medullaris The percentage of spinal cord injuries as classified by the American Spinal Injury Association ( ASIA ) is as follows : Incomplete tetraplegia : 29.5 % Complete paraplegia : 27.9 % Incomplete paraplegia : 21.3 % Complete tetraplegia : 18.5 % The most common neurologic level of injury is C5 . In paraplegia , T12 and L1 are the most common level . The following image depicts the ASIA classification by neurologic level . American Spinal Injury Association ( ASIA ) method for classifying spinal cord injury ( SCI ) by neurologic level . See also Hypercalcemia and Spinal Cord Injury Spinal Cord Injury and Aging Rehabilitation of Persons With Spinal Cord Injuries Central Cord Syndrome Brown - Sequard Syndrome , and Cauda Equina and Conus Medullaris Syndromes Historical information in SCI classification In 1982 , ASIA first published standards for neurologic classification of patients with spinal injury , followed by further refinements to definitions of neurologic levels , identification of key muscles and sensory points corresponding to specific neurologic levels , and validation of the Frankel scale . In 1992 , the International Medical Society of Paraplegia ( IMSOP ) adopted these guidelines to create true international standards , followed by further refinements . A standardized ASIA method for classifying spinal cord injury ( SCI ) by neurologic level was developed ( see the image above ) . Anatomy The spinal cord is divided into 31 segments , each with a pair of anterior ( motor ) and dorsal ( sensory ) spinal nerve roots . On each side , the anterior and dorsal nerve roots combine to form the spinal nerve as it exits from the vertebral column through the neuroforamina . The spinal cord extends from the base of the skull and terminates near the lower margin of the L1 vertebral body . Thereafter , the spinal canal contains the lumbar , sacral , and coccygeal spinal nerves that comprise the cauda equina . As a result Neuropathways The spinal cord itself is organized into a series of tracts or neuropathways that carry motor ( descending ) and sensory ( ascending ) information . These tracts are organized somatotopically within the spinal cord . The corticospinal tracts are descending motor pathways located anteriorly within the spinal cord . Axons extend from the cerebral cortex in the brain as far as the corresponding segment , where they form synapses with motor neurons in the anterior ( ventral ) horn . They decussate ( cross over ) in the medulla before entering the spinal cord . The dorsal columns are ascending sensory tracts that transmit light touch , proprioception , and vibration information to the sensory cortex . They do not decussate until they reach the medulla . The lateral spinothalamic tracts transmit pain and temperature sensation . These tracts usually decussate within 3 segments of their origin as they ascend . The anterior spinothalamic tract transmits light touch . Autonomic function traverses within the anterior interomedial tract . Sympathetic nervous system fibers exit the spinal cord between C7 and L1 , whereas parasympathetic system pathways exit between S2 and S4 . Injury to the corticospinal tract or dorsal columns , respectively , results in ipsilateral paralysis or loss of sensation of light touch , proprioception , and vibration . Unlike injuries of the other tracts , injury to the lateral spinothalamic tract causes contralateral loss of pain and temperature sensation . Because the anterior spinothalamic tract also transmits light touch information , injury to the dorsal columns may result in complete loss of vibration sensation and proprioception but only partial loss of light touch sensation . Anterior cord injury causes paralysis and incomplete loss of light touch sensation . Autonomic function is transmitted in the anterior interomedial tract . The sympathetic nervous system fibers exit from the spinal cord between C7 and L1 . The parasympathetic system nerves exit between S2 and S4 . Therefore , progressively higher spinal cord lesions or injury causes increasing degrees of autonomic dysfunction . Vascular supply The blood supply of the spinal cord consists of 1 anterior and 2 posterior spinal arteries . The anterior spinal artery supplies the anterior two thirds of the cord . Ischemic injury to this vessel results in dysfunction of the corticospinal , lateral spinothalamic , and autonomic interomedial pathways . Anterior spinal artery syndrome involves paraplegia , loss of pain and temperature sensation , and autonomic dysfunction . The posterior spinal arteries primarily supply the dorsal columns . The anterior and posterior spinal arteries arise from the vertebral arteries in the neck and descend from the base of the skull The primary watershed area of the spinal cord is the midthoracic region . Vascular injury may cause a cord lesion at a level several segments higher than the level of spinal injury . For example , a lower cervical spine fracture may result in disruption of the vertebral artery that ascends through the affected vertebra . The resulting vascular injury may cause an ischemic high cervical cord injury . At any given level of the spinal cord , the central part is a watershed area . Cervical hyperextension injuries may cause ischemic injury to the central part of the cord See also Topographic and Functional Anatomy of the Spinal Cord Pathophysiology Spinal cord injury ( SCI ) , as with acute stroke , is a dynamic process . In all acute cord syndromes , the full extent of injury may not be apparent initially . Incomplete cord lesions may evolve into more complete lesions . More commonly , the injury level rises 1 or 2 spinal levels during the hours to days after the initial event . A complex cascade of pathophysiologic events related to free radicals , vasogenic edema , and altered blood flow accounts for this clinical deterioration . Normal oxygenation , perfusion , and acid - base balance Spinal cord injury can be sustained through different mechanisms , with the following 3 common abnormalities leading to tissue damage : Destruction from direct trauma Compression by bone fragments , hematoma , or disk material Ischemia from damage or impingement on the spinal arteries Edema could ensue subsequent to any of these types of damage . Neurogenic shock Neurogenic shock refers to the hemodynamic triad of hypotension , bradycardia , and peripheral vasodilation resulting from severe autonomic dysfunction and the interruption of sympathetic nervous system control in acute spinal cord injury . Hypothermia is also characteristic . This condition does not usually occur with spinal cord injury below the level of T6 but is more common in injuries above T6 , secondary to the disruption of the sympathetic outflow from T1 - L2 and to unopposed vagal tone , leading to a decrease in vascular resistance , with the associated vascular dilatation . Neurogenic shock needs to be Spinal shock Shock associated with a spinal cord injury involving the lower thoracic cord must be considered hemorrhagic until proven otherwise . In this article , spinal shock is defined as the complete loss of all neurologic function , including reflexes and rectal tone , below a specific level that is associated with autonomic dysfunction . That is , spinal shock is a state of transient physiologic ( rather than anatomic ) reflex depression of cord function below the level of injury , with associated loss of all sensorimotor functions . An initial increase in blood pressure due to the release of catecholamines , followed by hypotension , is noted . Flaccid paralysis , including of the bowel and bladder , is observed , and sometimes sustained priapism develops . These symptoms tend to last several hours to days until the reflex arcs below the level of the injury begin to function again ( eg , bulbocavernosus reflex , muscle stretch reflex [ MSR ] ) . Primary vs secondary SCIs Spinal cord injuries may be primary or secondary . Primary spinal cord injuries arise from mechanical disruption , transection , or distraction of neural elements . This injury usually occurs with fracture and / or dislocation of the spine . However , primary spinal cord injury may occur in the absence of spinal fracture or dislocation . Penetrating injuries due to bullets or weapons may also cause primary spinal cord injury . More commonly , displaced bony fragments cause penetrating spinal cord and / or segmental spinal nerve injuries . Extradural pathology may also cause a primary spinal cord injury . Spinal epidural hematomas or abscesses cause acute cord compression and injury . Spinal cord compression from metastatic disease is a common oncologic emergency . Longitudinal distraction with or without flexion and / or extension of the vertebral column may result in primary spinal cord injury without spinal fracture or dislocation . The spinal cord is tethered more securely than the vertebral column . Longitudinal distraction of the spinal cord with or without flexion and / or extension of the vertebral column may result in spinal cord injury without radiologic abnormality ( SCIWORA ) . SCIWORA was first coined in 1982 by Pang and Wilberger . Originally , it referred to spinal cord injury without radiographic or computed tomography ( CT ) scanning evidence of fracture or dislocation . However with the advent of magnetic resonance imaging ( MRI ) , the term has become ambiguous . Findings on MRI such as intervertebral disk rupture , spinal epidural hematoma , cord contusion , and hematomyelia have all been recognized as causing primary or secondary spinal cord injury . SCIWORA should now be more correctly renamed as " spinal cord injury without neuroimaging abnormality " and 7 8 9 Vascular injury to the spinal cord caused by arterial disruption , arterial thrombosis , or hypoperfusion due to shock are the major causes of secondary spinal cord injury . Anoxic or hypoxic effects compound the extent of spinal cord injury . Complete vs incomplete spinal cord syndrome One of the goals of the physician is to classify the pattern of the neurologic deficit into one of the cord syndromes . Spinal cord syndromes may be complete or incomplete . In most clinical scenarios , physicians should use a best - fit model to classify the spinal cord injury syndrome . A complete cord syndrome is characterized clinically as complete loss of motor and sensory function below the level of the traumatic lesion . Incomplete cord syndromes have variable neurologic findings with partial loss of sensory and / or motor function below the level of injury ; these include the anterior cord syndrome , the Brown - Séquard syndrome , and the central cord syndrome . Anterior cord syndrome involves a lesion causing variable loss of motor function and pain and / or temperature sensation , with preservation of proprioception . Brown - Séquard syndrome , which is often associated with a hemisection lesion of the cord , involves a relatively greater ipsilateral loss of proprioception and motor function , with contralateral loss of pain and temperature sensation . Central cord syndrome usually involves a cervical lesion , with greater motor weakness in the upper extremities than in the lower extremities , with sacral sensory sparing . The pattern of motor weakness shows greater distal involvement in the affected extremity than proximal muscle weakness . Sensory loss is variable , and the patient is more likely to lose pain and / or temperature sensation than proprioception and / or vibration . Dysesthesias , especially those in the upper extremities ( eg , sensation of burning in the hands or arms ) , are common . Other cord syndromes The conus medullaris syndrome , cauda equina syndrome , and spinal cord concussion are briefly discussed below . Conus medullaris syndrome is a sacral cord injury , with or without involvement of the lumbar nerve roots . This syndrome is characterized by areflexia in the bladder , bowel , and to a lesser degree , lower limbs , whereas the sacral segments occasionally may show preserved reflexes ( eg , bulbocavernosus and micturition reflexes ) . Motor and sensory loss in the lower limbs is variable . Cauda equina syndrome involves injury to the lumbosacral nerve roots in the spinal canal and is characterized by an areflexic bowel and / or bladder , with variable motor and sensory loss in the lower limbs . Because this syndrome is a nerve root injury rather than a true spinal cord injury , the affected limbs are areflexic . Cauda equina syndrome is usually caused by a central lumbar disk herniation . A spinal cord concussion is characterized by a transient neurologic deficit localized to the spinal cord that fully recovers without any apparent structural damage . Etiology Since 2005 , the most common causes of spinal cord injury ( SCI ) remain : ( 1 ) motor vehicle accidents ( 40.4 % ) ; ( 2 ) falls ( 27.9 % ) , most common in those aged 45 y or older . Older females with osteoporosis have a propensity for vertebral fractures from falls with associated SCI ; ( 3 ) interpersonal violence ( primarily gunshot wounds ) ( 15.0 % ) , which is the most common cause in some US urban settings . Among patients who had suffered an assault , spinal cord injury 10 ; ( 4 ) and sports ( 8.0 % ) , in which diving is the most common cause ) . 11 Spinal cord injury ( SCI ) due to trauma has major functional , medical , and financial effects on the injured person , as well as an important effect on the individual ' s psychosocial well - being . 12 13 14 Other causes of spinal cord injury include the following : Vascular disorders Tumors 15 Infectious conditions Spondylosis Iatrogenic injuries , especially after spinal injections and epidural catheter placement Vertebral fractures secondary to osteoporosis Developmental disorders Injuries often associated with traumatic spinal cord injury also include bone fractures ( 29.3 % ) , loss of consciousness ( 17.8 % ) , and traumatic brain injury affecting emotional / cognitive functioning ( 11.5 % ) . The rate of alcohol intoxication among individuals who sustain spinal cord injuries is 17 – 49 % . Epidemiology The incidence of spinal cord injury in the United States is approximately 40 cases per million population , or about 12,000 patients , per year based on data in the National Spinal Cord Injury database . 11 However , this estimate is based on older data from the 1990s as there has not been any new overall incidence studies completed . Estimates from various studies suggest that the number of people in the United States alive in 2010 with spinal cord injury was about 265,000 persons ( range , 232,000 - 316,000 ) . Spinal cord injuries occur most frequently in July and least commonly in February . The most common day on which these injuries occur is Saturday . Spinal cord injuries also occur more frequently during daylight hours , which may be due to the increased frequency of motor vehicle accidents and of diving and other recreational sporting accidents during the day . Racial , sexual , age - related differences in incidence A significant trend over time has been observed in the racial distribution of persons with spinal cord injury . Since 2005 , 66.5 % are white , 26.8 % are black , 8.3 % are Hispanic , and 2.0 % are Asian . Males are approximately 4 times more likely than females to have spinal cord injuries . Overall , males account for 80.7 % of reported injuries in the national database . Since 2005 , the average age at injury is 40.7 years , reflecting the rise in the median age of the general population in the United States . About 50 % of spinal cord injuries occur between the ages of 16 and 30 years , 3.5 % occur in children aged 15 years or younger , and about 11.5 % in those older than 60 years ( 11.5 % ) . Greater mortality is reported in older patients with spinal cord injury . Pediatric SCI data The pediatric data parallels that of the adult data on spinal cord injuries . Using information from the Kids ' Inpatient Database ( KID ) and the National Trauma Database ( NTDB ) , Vitale and colleagues found that , with regard to the annual pediatric incidence rate a significantly greater incidence of spinal cord injuries was found in black children ( 1.53 cases per 100,000 children ) than in Native American children ( 1.0 case per 100,000 children ) and Hispanic children ( 0.87 case per 100,000 children ) , and the frequency in Asian children was significantly lower 16 In addition , the likelihood that boys would suffer spinal cord injuries ( 2.79 cases per 100,000 ) was found to be more than twice that of girls ( 1.15 cases per 100,000 ) . 16 The overall incidence of pediatric SCI is 1.99 cases per 100,000 US children . As estimated from the above data , 1455 children are admitted to US hospitals annually for treatment of spinal cord injuries . Vitale et al also looked at the major causative factors of pediatric cases , reporting the following incidences , again paralleling adult data : Motor vehicle accidents - 56 % Accidental falls - 14 % Firearm injuries - 9 % Sports injuries - 7 % Among children in the study , 67.7 % of those injured in a motor vehicle accident were not wearing a seatbelt . Alcohol and drugs were found to have played a role in 30 % of all pediatric cases of spinal cord injuries . Other epidemiologic data Marital , educational , and employment status of patients with spinal cord injuries are discussed below . Marital status Single persons sustain spinal cord injuries more commonly than do married persons . Research has indicated that among persons with spinal cord injuries whose injury is approximately 15 years old , one third will remain single 20 years postinjury . The marriage rate after SCI is annually about 59 % below that of persons in the general population of comparable gender , age , and marital status . Marriage is more likely if the patient is a college graduate , previously divorced , paraplegic ( not tetraplegic ) , ambulatory , living in a private residence , and independent in the performance of activities of daily living ( ADL ) . The divorce rate annually among individuals with spinal cord injury within the first 3 years following injury is approximately 2.5 times that of the general population , whereas the rate of marriages contracted after the injury is about 1.7 times that of the general population . The divorce rate in those who were married at the time of their injury is higher if the patient is younger , female , black , without children , nonambulatory , and previously divorced . The divorce rate among those who were married after the spinal cord injury is higher if the individual is male , has less than a college education , has a thoracic level injury , and was previously divorced . Educational status The rate of injury differs according to educational status , as follows : Less than a high school degree : 39.8 % High school degree : 49.9 % Associate degree : 1.6 % Bachelors degree : 5.9 % Masters or doctorate degree : 2.1 % Other degree : 0.7 % . Employment status Patients with spinal cord injury classified as American Spinal Injury Association ( ASIA ) level D are more likely to be employed than individuals with ASIA levels A , B , and C ( see Neurologic level and extent of injury under Clinical ) . Persons employed tend to work full - time . Individuals who return to work within 1 year of injury tend to return to the same job . Those individuals who return to work after 1 year of injury tend to work for a different employer at a different job requiring retraining . 17 The likelihood of employment after injury is greater in patients who are younger , male , and white and who have more formal education , higher reported intelligence quotient ( IQ ) , greater functional capacity , and less severe injury . Patients with greater functional capacity , less severe injury , history of employment at the time of injury , greater motivation to return to work , nonviolent injury , and ability to drive are more likely to return to work , especially after more elapsed time following injury . Prognosis Patients with a complete spinal cord injury ( SCI ) have a less than 5 % chance of recovery . If complete paralysis persists at 72 hours after injury , recovery is essentially zero . In the early 1900s , the mortality rate 1 year after injury in patients with complete lesions approached 100 % . Much of the improvement since then can be attributed to the introduction of antibiotics to treat pneumonia and urinary tract infection ( UTI ) . The prognosis is much better for the incomplete cord syndromes . If some sensory function is preserved , the chance that the patient will eventually be able walk is greater than 50 % . Ultimately , 90 % of patients with spinal cord injury return to their homes and regain independence . Providing an accurate prognosis for the patient with an acute SCI usually is not possible in the emergency department ( ED ) and is best avoided . Life expectancy and mortality Approximately 10 - 20 % of patients who have sustained a spinal cord injury do not survive to reach acute hospitalization , whereas about 3 % of patients die during acute hospitalization . Originally the leading cause of death in patients with spinal cord injury who survived their initial injury was renal failure , but , currently , the leading causes of death are pneumonia , pulmonary embolism , or septicemia . Heart disease , 18 19 subsequent trauma , suicide , and alcohol - related deaths are also major causes of death in these patients . 20 21 In persons with spinal cord injury , the suicide rate is higher among individuals who are younger than 25 years . Among patients with incomplete paraplegia , the leading causes of death are cancer and suicide ( 1 : 1 ratio ) , whereas among persons with complete paraplegia , the leading cause of death is suicide , followed by heart disease . Life expectancies for patients with spinal cord injury continues to increase but are still below the general population . Patients aged 20 years at the time they sustain these injuries have a life expectancy of approximately 35.7 years ( patients with high tetraplegia [ C1 - C4 ] ) , 40 years ( patients with low tetraplegia [ C5 - C8 ] ) , or 45.2 years ( patients with paraplegia ) . Individuals aged 60 years at the time of injury have a life expectancy of approximately 7.7 years ( patients with high tetraplegia ) , 9.9 years ( patients with low tetraplegia ) , and 12.8 years ( patients with paraplegia ) . A 2006 study by Strauss and colleagues reported that among patients with spinal cord injury , during the critical first 2 years following injury , a 40 % decline in mortality occurred between 1973 and 2004 . 22 During that same 31 - year period , there had been only a small , statistically insignificant reduction in mortality in the post 2 - year period for these patients . Life satisfaction Studies have found that patients with spinal cord injury who suffer from pain have less life satisfaction than do patients in whom pain is well controlled ; this may also affect the patients ' general outlook on life . 23 24 Rehabilitation Patients younger than 65 years with muscle grade of 3 or greater in the myotome L3 and S1 , and light touch sensation in the dermatome L3 and S1 within 15 days of injury ( all within American Spinal Injury Association [ ASIA ] impairment scale D ) , are more likely to be independent indoor walkers within a year of injury . 25 Rehabilitation goals in this group should therefore be geared toward functional capacity and within expected independent walking . Brain - computer interface for SCI SCI can leave patients with severe or complete permanent paralysis . Brain - computer interface ( BCI ) can potentially restore or substitute for motor behaviors in patients with a high - cervical SCI . 26 Recent studies have shown that patients with SCI are able to control virtual keyboards , 27 a computer cursor , 26 and a limb prosthetic device 28 using BCI technologies . The BCI outputs are accomplished by acquiring neurophysiological signals associated with a motor process in the cerebral cortex , analyzing these signals in real time , and subsequently translating them into commands for a limb prosthesis . These are promising findings ; in the future , BCI may provide a permanent solution for restoration of motor functions in SCI patients . Walking assistance systems In 2014 , the FDA approved a wearable , motorized device to help individuals with paraplegia due to an SCI sit , stand , and walk with assistance from a companion . 29 30 The device , which is intended for patients with SCIs at levels T7 - L5 and for those with level T4 - T6 injuries when used only in rehabilitation institutions , consists of the following : Fitted metal brace that supports the legs and part of the upper body Motors that provide movement to the hips , knees , and ankles Tilt sensor Computer and power supply worn on the back Before using the device , caregivers and patients are required to undergo extensive training . Patient Education As part of inpatient therapy , patients with spinal cord injury ( SCI ) should receive a comprehensive program of physical and occupational therapy . Prevention Many spinal cord injuries result from incidents involving drunk driving , assaults , and alcohol or drug abuse . Spinal cord injuries from industrial hazards , such as equipment failures or inadequate safety precautions , are potentially preventable causes . Unfenced , shallow , or empty swimming pools are known hazards . Clinical Presentation Sections Spinal Cord Injuries Overview Presentation DDx Guidelines Questions & Answers References
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"Spinal cord injury",
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"spinal cord"
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http://emedicine.medscape.com/article/813342-medication
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Emergency Medicine Beta - Blocker Toxicity Medication Updated : Jan 18 , 2018 Author : Adhi Sharma , MD ; Chief Editor : Gil Z Shlamovitz , MD , FACEP more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Medication Summary Because of the nature of overdoses , definitive evidence - based recommendations are limited . However , commonly used agents include crystalloids , atropine , pressors with catecholamine action , glucagon , and phosphodiesterase inhibitors . Gastrointestinal Tract Decontaminants Class Summary These agents are used to minimize the absorption of ingested compound . Activated charcoal ( Requa Activated Charcoal , EZ - Char , Actidose - Aqua ) View full drug information Although most useful if administered within 4 hours of ingestion , repeated doses may be used , especially with ingestions of sustained - released agents . Limited outcome studies exist , especially when activated charcoal is used more than 1 hour postingestion . No clinical data exist to suggest a benefit of multiple - dose activated charcoal with beta - blockers , even sustained - release preparations . The dose may be repeated q4h at 0.5 g / kg . Alternate with use of a cathartic ; monitor for active bowel sounds . Cardiovascular agents Class Summary These agents are used for symptomatic bradycardia and / or hypotension . Catecholamines are considered a primary treatment for more severe cases of beta - blocker poisoning . Atropine IV / IM ( Atropine Care , Isopto Atropine ) View full drug information Atropine enhances sinus node automaticity by blocking the effects of acetylcholine at the atrioventricular ( AV ) node , decreasing refractory time and speeding conduction through the AV node . Glucagon ( GlucaGen ) Glucagon is considered the drug of choice for beta - blocker toxicity by many authors . This agent stimulates production of cyclic adenosine monophosphate ( cAMP ) through nonadrenergic pathways . Result is enhanced myocardial contractility , heart rate , and AV conduction . An upper dose limit has not been established . Epinephrine ( Adrenalin ) Agents with combined alpha - and beta - selective properties may be necessary to maintain blood pressure . A beta - agonist may competitively antagonize the effect of the beta - blocker . The amount of beta - agonist required might be several orders of magnitude above those recommended in standard Advanced Cardiac Life Support ( ACLS ) protocols Dopamine Agents with combined alpha - and beta - selective properties may be necessary to maintain blood pressure . A beta - agonist may competitively antagonize the effect of the beta - blocker . The amount of beta - agonist required might be several orders of magnitude above those recommended in standard ACLS protocols . In a canine model , the doses of isoproterenol and dopamine had to be increased 15 and 5 times , respectively , in order to effect similar hemodynamic changes that occurred before beta - blockade with 1 mg / kg of propranolol . Inamrinone Inamrinone produces vasodilation and increases the inotropic state . Tachycardia occurs more commonly with this agent than with dobutamine . Inamrinone may exacerbate myocardial ischemia . Case reports describe it as effective when other agents fail . Calcium chloride Calcium chloride moderates nerve and muscle performance by regulating the action potential excitation threshold . At high doses , propranolol blocks the calcium channels that may induce asystole , AV block , and depressed myocardial contraction . Magnesium sulfate Magnesium sulfate acts as antiarrhythmic agent and diminishes the frequency of premature ventricular contractions ( PVCs ) , particularly those secondary to acute ischemia . This agent is used to treat torsade de pointes associated with sotalol intoxication . Insulin regular human ( Novolin , Humulin ) High - dose insulin therapy is highly investigational but should be considered when other therapies are failing . Dextrose infusion of 10 - 75 g / h may be required . Consult a toxicologist if this regimen is considered . Benzodiazepines These agents prevent seizure recurrence and terminate clinical and electrical seizure activity . Lorazepam ( Ativan ) Benzodiazepines are considered the treatment of choice for beta - blocker – induced seizures . Of the benzodiazepines , lorazepam has the longest anticonvulsant activity ( 4 - 6 h ) and is preferred . By increasing the action of GABA , which is a major inhibitory neurotransmitter in the brain , all levels of CNS , including limbic and reticular formation , may be depressed . It is important to monitor the patient ' s blood pressure after administering dose . Adjust as needed . Diazepam ( Valium , Diastat ) Diazepam depresses all levels of CNS ( eg , limbic and reticular formation ) , possibly by increasing activity of GABA . It is considered second - line therapy for seizures . Anticonvulsants , Barbiturates Phenobarbital Phenobarbital may be necessary to control status epilepticus . Questions Sections Beta - Blocker Toxicity Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References
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[
"Beta-Blocker Toxicity Medication",
"crystalloids",
"phosphodiesterase inhibitors"
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http://emedicine.medscape.com/article/815213-treatment
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Emergency Medicine Iron Toxicity Treatment & Management Updated : Feb 04 , 2019 Author : Clifford S Spanierman , MD ; Chief Editor : Michael A Miller , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers References Prehospital Care In patients with acute iron overdose , intravenous access should be established immediately . Patients who are hypovolemic should receive fluid boluses of 20 mL / kg of normal saline or lactated Ringer ( LR ) solution . Provide oxygen to patients in shock . Emergency Department Care Assume that symptomatic patients are hypovolemic . Administer vigorous volume therapy with isotonic crystalloids ( eg , normal saline , LR solution ) in 20 mL / kg boluses to attain and maintain hemodynamic stability . Give supplemental oxygen . Gastric lavage with a large - bore orogastric tube may remove iron from the stomach . Ideally , lavage should be performed 1 - 2 hours postingestion , although later use may be appropriate if evidence of iron products in the stomach is observed on a radiograph . However , iron has a gelatinous texture and may be difficult to remove by lavage . Whole - bowel irrigation may be used in patients with a radiopacity on kidneys , ureters , bladder ( KUB ) plain radiographs , until the radiopacity clears . Ipecac has been used for gastric decontamination in patients with iron poisoning . Ipecac might be considered when it can be administered within 60 minutes of iron ingestion , in an alert patient who has ingested a very large amount of iron . Ipecac is not used routinely for iron removal because it can mask clinical signs of iron toxicity ( vomiting ) . Significant iron overdose may cause hypotension and unstable vital signs , in which case ipecac is contraindicated , as it may endanger the patient ' s airway as an aspiration risk . The American Academy of Clinical Toxicology advises that the routine administration of ipecac in the emergency department should definitely be avoided . Some reports suggest that ipecac may offer possible benefits in rare situations involving iron poisoning ; this may be a moot point , however , since the availability of ipecac is rapidly diminishing . 4 In any case , iron toxicity itself typically causes vomiting , because of its caustic effect on the gastrointestinal mucosa , so iron - poisoned patients routinely perform self - decontamination even without ipecac . Activated charcoal does not bind iron . However , it should be utilized if co - ingestants are suspected . Deferoxamine ( Desferal ) can be used to chelate iron . 5 Patients who are symptomatic should receive deferoxamine regardless of their iron level . In acute or chronic iron toxicity , chelation therapy with deferoxamine is indicated for patients with serum iron levels > 350 mcg / dL who have evidence of toxicity , or levels of > 500 mcg / dL regardless of signs or symptoms ( see Medication ) . In patients with significant clinical manifestations of toxicity , chelation therapy should not be delayed while one awaits serum iron levels . In acute iron poisoning , intramuscular ( IM ) administration is indicated for patients who are not in shock ; intravenous ( IV ) administration should be reserved for patients in a state of cardiovascular collapse or shock . However , note that rapid IV administration of deferoxamine may itself result in hypotension and shock . For chronic iron overload , administration can be subcutaneous , IV , or IM . Aggressive hydration aids in eliminating chelated iron by maintaining an appropriate urine output . Asymptomatic patients observed for 6 hours with serum iron levels less than 300 - 350 mcg / dL may be discharged . Features of further inpatient care are as follows : Conservative management may be adequate in severe intoxication . 6 Persistently symptomatic patients with serum iron levels higher than 350 mcg / dL should be admitted . Patients who have been hemodynamically unstable , and those with serum iron levels higher than 1000 mcg / dL , should be admitted to a facility that can provide age - appropriate intensive care . Other modalities that may be essential include mechanical ventilation and blood product transfusions . Exchange transfusion has been reported to be successful in management of a case of severe iron poisoning . 7 Hemodialysis has been used in severe intoxications . 8 Iron bezoars may be removed laparoscopically or endoscopically . 9 10 Medical Care Consultations Consultation with a toxicologist is recommended . Obtain a gastroenterology consultation for patients who have large iron bezoars . Transfer patients if intensive care or deferoxamine is not available locally . Sections Iron Toxicity Overview Presentation DDx Workup Treatment Questions & Answers References
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"Iron Toxicity Treatment",
"hypovolemic",
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http://emedicine.medscape.com/article/825060-treatment
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Drugs & Diseases > Emergency Medicine Foot Fracture Treatment & Management Updated : Sep 23 , 2018 Author : Robert Silbergleit , MD ; Chief Editor : Trevor John Mills , MD , MPH more . . . Share Email Print Feedback Emergency Department Care Immediate care includes icing , immobilizing , and elevating the foot and providing analgesia to all patients with significant foot fractures . 24 Patients with forefoot fractures frequently also have associated soft tissue damage , which may necessitate external fixation . 10 Options for initial immobilization include the following : Posterior or stirrup splints Reinforced bulky dressing , also termed Jones splint , which consists of a web roll and an elastic compression bandage Rigid , flat - bottom orthopedic shoe also termed postop or Reece shoe Definitive immobilization often requires application of a cylindrical cast , applied during the acute phase ( and often bivalved to accommodate further swelling ) or after a few days when edema has begun to decrease . Toe fracture Toe fractures are common and generally heal well with little or no therapy . Buddy tape the broken toe to an adjacent , uninjured toe ( with padding in between the toes to prevent skin maceration ) and apply a rigid flat - bottom orthopedic shoe . While union of fracture segments occurs in 3 - 8 weeks , symptoms usually improve much earlier . Significantly displaced fractures , especially of the first toe , may be treated more aggressively with closed reduction and rigid immobilization . Irreducible fractures sometimes require open reduction and internal fixation . 25 First metatarsal fracture The first metatarsal is the least commonly fractured metatarsal . 10 The first metatarsal head bears twice the weight of other metatarsal heads . Treat minimally displaced or nondisplaced fractures with immobilization without weight bearing . Displaced fractures usually require open reduction and internal fixation ( see image below ) . Fractures , foot . CT scan showing fracture of first cuneiform and proximal first metatarsal . View Media Gallery Internal metatarsal fracture Fractures of internal ( second , third , fourth ) metatarsals are very common . Nondisplaced and displaced fractures usually heal well , with weight bearing as tolerated , in a cast or rigid flat - bottom orthopedic shoe . In fact , data suggest that elastic support bandages are equivalent or superior to casts for such metatarsal fractures . 26 Exclude disruptions of the Lisfranc ( tarsometatarsal ) joint by maintaining a high level of suspicion . March fracture is a stress fracture of the second and / or third metatarsal that commonly occurs in joggers . Radiographs are often negative , and sometimes a bone scan helps determine this diagnosis . Treatment is cessation of aggravating activity for 4 - 6 weeks . Fifth metatarsal fracture The proximal fifth metatarsal is the most common site of midfoot fractures . 3 9 Fractures are of 2 general types , the Jones fracture and the pseudo - Jones or tennis fracture . Midshaft ( see first image below ) and distal fifth metatarsal fractures ( see second image below ) are less common ; these are shown in the images below . Fractures , foot . Spiral fracture of the shaft of the fifth metatarsal . This fracture was treated conservatively with immobilization . View Media Gallery Fractures , foot . Minimally displaced fracture of the distal fifth metatarsal . This fracture was treated conservatively with immobilization in a rigid flat bottom shoe . Proximal avulsion fracture Fractures at the proximal tuberosity are very common and termed pseudo - Jones or tennis fractures ( see image below ) . This avulsion injury usually is associated with a lateral ankle strain and occurs at the attachment of the peroneus brevis tendon . It heals well with a compression dressing and weight bearing as tolerated . Fractures , foot . Proximal fifth metatarsal avulsion fracture ( also termed pseudo - Jones , tennis , or dancer fracture ) . Jones fracture This less common but more problematic fracture occurs transversely at the base of the fifth metatarsal , 1.5 - 3 cm distal to the proximal tuberosity ( see image below ) . Displacement of this fracture tends to increase with continued weight bearing . Forefoot adduction has been found to be a risk factor for Jones fracture , with the presence of metatarsus adductus being associated with a 2.4 times greater risk of Jones fracture , according to one study . 27 Patients with this fracture often ( 35 - 50 % ) develop persistent nonunions requiring bone grafting and internal fixation . 4 Initial therapy must include immobilization without weight bearing . 28 One study suggested that the short controlled ankle movement ( CAM ) walker boot more effectively offloads the fifth metatarsal during common gait activities than a postoperative sandal or a standard athletic shoe after treatment of Jones fractures and other base of fifth metatarsal fractures . 29 Fractures , foot . Jones fracture of the fifth metatarsal . Fracture at Lisfranc ( tarsometatarsal ) joint The Lisfranc joint is found at the base of second metatarsal and is formed by a 6 - bone arch that includes the first , second , and third cuneiforms and first , second , and third metatarsals . Fracture - dislocations at this joint are rare , yet are still the most commonly misdiagnosed foot injuries ( see images below ) . It has been estimated that 20 % of Lisfranc fracture - dislocations are misdiagnosed . 8 A Lisfranc fracture - dislocation involves injury to the bony and soft tissue structures of the tarsometatarsal joint , and patients typically present to the ED with pain particularly with weight bearing ; with swelling ; and after a characteristic mechanism of injury such as high - velocity trauma . Stable injuries can be immobilized in the ED and patients discharged home , but unstable injuries require an orthopedic referral for consideration of surgical fixation . 30 They can result in posttraumatic arthritis and reflex sympathetic dystrophy . Displaced fractures are clinically and radiographically obvious , yet nondisplaced or minimally displaced fractures may be subtle . 6 Fractures , foot . Lisfranc fracture - dislocation . Fractures , foot . Subtle fracture of the first cuneiform at the Lisfranc joint . Another fracture at the base of the first metatarsal is not seen here but was found on subsequent computed tomography . To facilitate diagnosis , grasp first and second metatarsals and move them alternately through plantarflexion and dorsiflexion . Radiographic diagnosis is made by detecting widening ( diastasis ) of 2 - 5 mm between the bases of the first and second metatarsals or between the middle and medial cuneiforms . Fracture at the base of the second metatarsal strongly suggests the diagnosis . If standard radiographs appear normal despite clinical suspicion , radiographs of the injured foot bearing weight may reveal the fracture . These fractures require immediate orthopedic consultation for reduction and fixation . CT imaging is useful if clinical suspicion is high despite nondiagnostic plain radiography . 31 Talar fracture Talar fracture is the second most common fracture of the tarsal bones . Blood supply is somewhat tenuous , resulting in a high incidence of avascular necrosis following displaced fractures . According to Dale et al , talar fracture patterns can not be characterized by radiography alone , and CT is critical for detecting and characterizing talar fractures . 32 Neck and body fracture are the most common talar fractures and may be associated with subtalar dislocation . 33 Displaced fractures usually require surgical fixation . Nondisplaced fractures are treated with non – weight - bearing short leg cast for 6 - 10 weeks . Lateral process fracture was previously rare , yet now is more common because of snowboarding injuries . Treatment should include immobilization with strict avoidance of weight bearing . Posterior process ( Shepherd ) fracture is aused by damage to the posterior process of the talus , this fracture ' s usual mechanism is sudden plantarflexion or repetitive motion , especially in athletes who dance or kick . Diagnosis usually is not confirmed in the ED , because clinical examination is typically nonspecific and plain film radiography normal . Suspicion warrants referral to an orthopedist . Treatment includes immobilization with either partial or full weight bearing . Note that this fracture often is confused with an accessory bone that occurs at this location , the os trigonum . Transchondral / osteochondral talar dome fracture is a rare injury that often presents as a nonhealing ankle sprain and is caused by small cartilaginous avulsions or body chips in tibial articulation . Tenderness of the talar dome can be appreciated with the foot in dorsiflexion . Radiographs may be normal , and injuries can not be distinguished clinically from ankle sprains . Delayed presentation may show crepitus , joint locking , and laxity of lateral and anterior ankle ligaments . Suspicion warrants referral to an orthopedist for bone scan or other definitive imaging . Initial therapy for this injury is Navicular fractures are rare and most often represent stress fractures in young athletes . They usually heal well with immobilization and weight bearing as tolerated . 34 Displaced fractures through the navicular body have a high incidence of avascular necrosis and require open reduction and internal fixation ( see images below ) . Comminuted navicular fracture in a young drunk driver involved in a motor vehicle crash . The patient sustained no other injuries and was discharged in a plaster splint with strict nonweightbearing . The patient subsequently had a computerized tomography ( CT ) scan and underwent open reduction and internal fixation 9 days after the injury . A standard anteroposterior ( AP ) view is shown here . An added oblique view of this same patient with a navicular fracture was performed in the ED to help verify the absence of other significant fractures . Obtaining views that are not part of the routine foot series can be helpful and should be added when needed . Calcaneal fracture Calcaneal fractures usually occur in patients aged 30 - 50 years , with a peak incidence at 45 years . They occur in males 5 times more often than in females . They are most commonly caused by motor vehicle crashes or falls from a height . 35 36 37 38 When caused by falls from a height , these fractures have a high rate of associated injuries . Identification of a calcaneal fracture should prompt a search for other related findings . Calcaneal fractures are part of the " lover ' s triad " ( named for the constellation of injuries that may occur when jumping out of a second - story bedroom window ) , with lumbar compression fractures and forearm fractures . Ankle , femur , and elbow fractures are also common . 39 A high index of suspicion for thoracic aortic rupture and renal vascular pedicle disruption must be maintained when calcaneal fractures are seen . Intra - articular joint depression fracture is the most common form of calcaneal fracture . Lateral foot radiograph reveals a reduction in the Böehler ' s angle , the posterior angle formed by intersection of a line from the posterior to the middle facet and a line from the anterior to the middle facet ( see images below ) . Böehler ' s angle is normally between 20 and 40 ° . Angles less than 20 ° , or more than 5 ° smaller than that of uninjured side , indicate a fracture . Although often useful , the sensitivity 40 Obtain an urgent orthopedic consultation for calcaneal fractures , since open reduction and internal fixation is usually necessary . Fractures , foot . CT scan showing fracture of first cuneiform and proximal first metatarsal . Fractures , foot . Spiral fracture of the shaft of the fifth metatarsal . This fracture was treated conservatively with immobilization . Extra - articular calcaneal fractures should be treated with a bulky compression dressing , rest , ice , and elevation . Arrange orthopedic follow - up care . Open calcaneus fractures are severe , high - energy injuries that have the potential for considerable morbidity , especially considering the high rate of concomitant orthopedic and whole body system injuries . Patients with type III open injuries are at increased risk of amputation . Management of these injuries include intravenous antibiotics , tetanus prophylaxis , and urgent debridement and irrigation . 41 Consultations Nonemergent referral or urgent consultation with an orthopedic surgeon ( or podiatrist if appropriate ) is often necessary ; which is appropriate depends on the type of fracture . Complications Compartment syndrome is the most dangerous acute complication of foot fractures . This syndrome is associated primarily with midfoot fractures sustained as the result of a crush mechanism . Clinical signs include marked swelling ( early ) and neurovascular compromise ( late ) . Recent data emphasize that compartment syndrome is a subjective clinical diagnosis . Measurement of compartment pressures may provide useful supplemental information , but pressure thresholds defining compartment syndrome in lower extremity fractures are elusive , 42 and the osseofascial spaces of the foot are not distinct or isolated . 43 Suspicion of compartment syndrome warrants emergent orthopedic consultation ; treatment is fasciotomy when the diagnosis is confirmed . Long - term complications of foot fracture include the following : Arthritis Infection Nonunion or instability Gait disturbances Guidelines
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[
"Foot Fracture Treatment",
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http://emedicine.medscape.com/article/832336-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Emergency Medicine Chlorine Toxicity Updated : Dec 11 , 2015 Author : Gerald F O ' Malley , DO ; Chief Editor : Zygmunt F Dembek , PhD , MPH , MS , LHD more . . . Sections Overview Presentation DDx Workup Treatment Medication Media Gallery References Practice Essentials Chlorine gas is a pulmonary irritant with intermediate water solubility that causes acute damage in the upper and lower respiratory tract . Occupational exposures constitute the highest risk for serious toxicity from high - concentration chlorine ( see the image below ) . Mixing of chlorine bleach ( sodium hypochlorite ) with ammonia or acidic cleaning agents is a common source of household exposure . As with all poisons , the dose determines the toxicity . Exposure to low concentrations of chlorine for prolonged periods may have destructive effects , as might very short - term exposure to high concentrations Chest radiograph of a 36 - year - old chemical worker 2 hours postexposure to chlorine inhalant . She had severe resting dyspnea during the second hour , diffuse crackles / rhonchi on auscultation , and a partial pressure of oxygen of 32 mm Hg breathing room air . The radiograph shows diffuse pulmonary edema without significant cardiomegaly . Used with permission from Medical Aspects of Chemical and Biological Warfare , Textbook of Military Medicine . 1997 : 256 . View Media Gallery Signs and symptoms Symptoms may vary depending on the degree of exposure . Exposure possibilities include acute low levels , acute high levels , and chronic low levels . Low - level ( 3 - 5 % , 1 - 15 ppm ) acute exposure Most poisonings fall into this category and are caused by household exposure to low - concentration cleaning products . Manifestations are as follows : Eye tearing , nose and throat irritation Sneezing Excess salivation General excitement or restlessness High - level ( 20 % , > 30 ppm ) acute exposure In addition to the symptoms seen with low - level exposure , high - level exposure may result in the following : Dyspnea : Upper airway swelling and obstruction may occur Violent cough Nausea and vomiting ( with the smell of chlorine in emesis ) Lightheadedness Headache Chest pain or retrosternal burning Muscle weakness Abdominal discomfort Dermatitis ( with liquid exposure ) : Corneal burns and ulcerations may occur from splash exposure to high - concentration chlorine products Esophageal perforation Chronic exposure Manifestations of chronic exposure include the following : Acne ( chloracne ) Chest pain Cough Sore throat Hemoptysis Findings on physical examination may include the following : Tachypnea Cyanosis ( most prevalent during exertion ) Tachycardia Wheezing Intercostal retractions Decreased breath sounds Rales ( pulmonary edema ) Nasal flaring Aphonia , stridor , or laryngeal edema Ulceration or hemorrhage of the respiratory tract Rhinorrhea Lacrimation , salivation , and blepharospasm Chloracne or tooth enamel corrosion ( with chronic exposure ) Redness , erythema , and chemical burns to the skin from dose - dependent exposure to liquid See Clinical Presentation for more detail . Diagnosis Studies in patients with significant exposure to chlorine gas may include the following : Pulse oximetry Serum electrolyte , blood urea nitrogen ( BUN ) , and creatinine levels Arterial blood gases Chest radiography Electrocardiogram ( ECG ) CT scan of the chest Ventilation - perfusion scan Pulmonary function testing Laryngoscopy or bronchoscopy Abnormalities include hypoxia ( from bronchospasm or pulmonary edema ) 1 and metabolic acidosis . The metabolic acidosis may be hyperchloremic ( nonanion gap ) . Chest radiograph findings are frequently normal initially but later may show nonspecific abnormalities , pulmonary edema , pneumonitis , mediastinal free air , myocardial depression , 2 or signs of ARDS . See Workup for more detail . Management The most important aspect of treating patients exposed to chlorine gas is the provision of good supportive care , as follows : Supplemental oxygen ( humidified if possible ) as necessary Fluid restriction and diuretics for impending pulmonary edema PEEP in patients with noncardiogenic pulmonary edema Beta2 agonists and other bronchodilators as necessary for bronchospasm Nebulized lidocaine for analgesia and reduction of cough Consider nebulized sodium bicarbonate Consider inhaled or parenteral corticosteroids Copious saline irrigation for skin or eye exposures Consider admission and observation for the following patients , even if they are initially asymptomatic , as they are at increased risk of progression to respiratory failure : Patients exposed to large concentrations in an enclosed environment Patients with underlying respiratory or cardiovascular disease Children Treatment and Medication Background Chlorine gas is a pulmonary irritant with intermediate water solubility that causes acute damage in the upper and lower respiratory tract . Chlorine gas was used as a chemical weapon in World War I . Currently , occupational exposures constitute the highest risk for serious toxicity from high - concentration chlorine . Mixing of chlorine bleach ( sodium hypochlorite ) with ammonia or acidic cleaning agents is a common source of household exposure . See Etiology . The respiratory and mucous membrane irritant effects of chlorine have been well known for many years . John Doughty , a New York City schoolteacher , first suggested use of chlorine gas as a chemical warfare agent during the American Civil War . This proposal was never acted upon during that war . Chlorine gas was officially introduced into the chemical warfare arsenal in 1915 at Ypres , Belgium . Accounts of chlorine attacks at Ypres describe an olive - green cloud rolling over the Allied positions , following the ground contours , and sinking into the trenches . Soldiers seeking safety in those trenches were overcome by the gas and experienced tearing eyes , vomiting , and difficulty breathing . They abandoned their trenches and suffered great losses from artillery and rifle fire . An estimated 93,800 tons of chlorine gas was produced during World War I , with more than half produced by Germany . Total gas casualties in World War I were estimated at almost 1.3 million troops . Of the 70,552 American soldiers poisoned with various gases in World War I , 1843 were exposed to chlorine gas . 3 Chlorine was abandoned as a warfare agent when the use of gas masks was introduced and more effective compounds were created and deployed . Chlorine liquid is presently used in cleaning agents ( eg , bleach , disinfectants ) , in water purification , and in the manufacture of items such as plastics . It is used in the following industries : pesticide , refrigerant , paper and pulp , textile , metallurgy , pharmaceutical , cosmetic , battery , water and sewage purification , and food processing . More than 200 significant industrial accidents involving chlorine have occurred since World War I . Symptoms of exposure vary , depending on the degree of exposure . Low - level acute exposure ( eg , from household cleaning products ) may consist primarily of upper airway irritation . The hallmark of pulmonary injury associated with chlorine toxicity is pulmonary edema , manifested clinically as hypoxia . ( See Pathophysiology and Presentation . ) The most important aspect of treating patients exposed to chlorine gas is the provision of good supportive care . Provide supplemental oxygen as necessary . Positive pressure ventilation with positive end - expiratory pressure may improve oxygenation in patients with noncardiogenic pulmonary edema . Bronchospasm may require treatment with beta - agonists or other bronchodilators . Other medications that may be used include nebulized sodium bicarbonate and inhaled or systemic corticosteroids . See Treatment . Educate patients on the risks associated with the improper handling of chlorine pool chemicals and the improper mixing of household cleaning chemicals . For patient education resources , see Chemical Warfare Personal Protective Equipment , and Bronchoscopy Pathophysiology Chlorine is a greenish - yellow , noncombustible gas at room temperature and atmospheric pressure . Prolonged exposure to chlorine gas may occur because its moderate water solubility delays onset of upper airway symptoms for several minutes . In addition , chlorine gas is heavier than air in its pure form , causing it to remain near ground level and increasing exposure time . The odor threshold for chlorine is approximately 0.3 - 0.5 parts per million ( ppm ) ; however , distinguishing toxic air levels from permissible air levels may be difficult until irritative symptoms develop . As the concentration of chlorine gas exposure increases , the severity of symptoms and rapidity of onset increase . The IDHL ( immediately dangerous to life or health ) is 10 ppm . Concentrations above 400 ppm are often fatal . 4 Chlorine is moderately soluble in water and reacts in combination to form hypochlorous ( HOCl ) and hydrochloric ( HCl ) acids . Elemental chlorine and its derivatives , hydrochloric and hypochlorous acids , may cause biological injury . The chemical reactions of chlorine combining with water and the subsequent derivative reactions with HOCl and HCl are as follows : a1 ) Cl 2 + H O ⇔ HCl ( hydrochloric acid ) + HOCL ( hypochlorous acid ) or a2 ) Cl + H O ⇔ 2 HCl + [ O ] ( nascent oxygen ) b ) HOCl ⇔ HCl + [ O Chlorine gas , when mixed with ammonia , reacts to form chloramine gas . In the presence of water , chloramines decompose to ammonia and hypochlorous acid or hydrochloric acid . 5 Because of their high water solubility , chloramine exposures result in rapid symptom development . However , for mechanistic reasons that are not clear , chlorine 88 nitrogenous compounds result in less severe symptoms at onset . Because these initial symptoms are often mild , however , they may not prompt immediate retreat , thus resulting in prolonged exposure , with pulmonary and ocular symptoms predominating . 6 Mechanism of activity The mechanisms of biological activity are poorly understood and the predominant anatomic site of injury may vary , depending on the chemical species produced . Because of its intermediate water solubility and deeper penetration , elemental chlorine frequently causes acute damage throughout the respiratory tract . 7 Cellular injury is believed to result from the oxidation of functional groups in cell components , from reactions with tissue water to form hypochlorous and hydrochloric acid , and from the generation of free oxygen radicals . Although chlorine was at one time thought to cause direct tissue damage by generating free oxygen radicals , 8 this concept is now considered controversial . 9 10 Solubility effects While chlorine gas is only moderately soluble in water , hydrochloric acid is highly soluble . The predominant targets of the acid are the epithelia of the ocular conjunctivae and upper respiratory mucous membranes . 11 Hypochlorous acid is also highly water soluble with an injury pattern similar to hydrochloric acid . Hypochlorous acid may account for most of the toxic effects of chlorine to the human body . 12 Physiologic response The early response to chlorine exposure depends on the ( 1 ) concentration of chlorine gas , ( 2 ) duration of exposure , ( 3 ) water content of the tissues exposed , and ( 4 ) individual susceptibility . 1 The immediate effects of chlorine gas toxicity include acute inflammation of the conjunctivae , nose , pharynx , larynx , trachea , and bronchi . Irritation of the airway mucosa leads to local edema secondary to active arterial and capillary hyperemia . Plasma exudation into the alveoli results in pulmonary congestion and edema . Pathologic findings Pathologic findings are nonspecific . They include the following 13 Pulmonary edema Pneumonia Pneumonitis Hyaline membrane formation Multiple pulmonary thrombosis Ulcerative tracheobronchitis The hallmark of pulmonary injury associated with chlorine toxicity is pulmonary edema , manifested clinically as dyspnea , adventitious lung sounds , and hypoxia . Noncardiogenic pulmonary edema is thought to occur when there is a loss of pulmonary capillary integrity , and subsequent transudation of fluid into the alveolus . The onset can occur within minutes or hours , depending upon severity of exposure . Persistent hypoxemia is associated with a higher mortality rate . In animal models of chlorine gas toxicity , immediate respiratory arrest occurs at 2000 ppm , with the lethal concentration for 50 % of exposed animals in the range of 800 - 1000 ppm . 12 Bronchial constriction occurs in the 200 - ppm range , with evidence of effects on ciliary activity at exposure levels as low as 18 ppm . With acute exposures of 50 ppm and subacute inhalation as low as 9 ppm , chemical pneumonitis and bronchiolitis obliterans have been noted . Mild focal irritation of the nose and trachea without lower respiratory effects occur at 2 ppm . The extent of tissue response varies with both the concentration of exposure as well as underlying tissue sensitivity . In one study of chlorine gas toxicity conducted on human volunteers , 4 hours of exposure to chlorine at 1 ppm produced significant decreases in forced vital capacity ( FVC ) , forced expiratory volume in one second ( FEV1 ) , and peak expiratory flow rate , as well as an increase in airway resistance . 14 Volunteers with hyperreactive airways were noted to experience an exaggerated airway response to exposure of 1 ppm chlorine gas . 15 In another study , patients with rhinitis and advanced age demonstrated a significantly greater nasal mucosal congestive response to chlorine gas challenge than patients who did not have rhinitis or those of younger age . 16 Eye injury The eye is rarely damaged severely by chlorine gas toxicity ; however , burns and corneal abrasions have occurred . Acids formed by the chlorine gas reaction with the conjunctival mucous membranes are partially buffered by the tear film and the proteins present in tears . Consequently , acid burns to the eye are typically limited to the epithelial and basement membrane , rarely extending to the deep endothelial cells . Acid burns to the periphery of the cornea and conjunctiva often heal uneventfully . Burns to the center of the cornea may lead to corneal ulcer formation and subsequent scarring . Etiology Occupational exposures constitute the highest risk for serious exposure to high - concentration chlorine . Other exposures occur during industrial or transportation accidents . Wartime exposure is rare but possible . Household exposure occurs with chlorination tablet accidents during swimming pool maintenance , 17 18 19 or with inappropriate mixing of sodium hypochlorite ( bleach ) cleaning agents with ammonia products , which produces chloramine gas . Typically , this occurs in an enclosed environment such as a restroom . Chlorine gas also may be released in the household by mixing sodium hypochlorite with acidic cleaning agents ( toilet bowl cleaners ) . Epidemiology In the United States , chlorine is the most common inhalational irritant . In 2014 , the American Association of Poison Control Centers ( AAPCC ) reported 3,604 exposures to chlorine gas , 1,998 single exposures to chlorine gas when household acid is mixed with hypochlorite , and 1,888 single exposures to chloramine gas . 20 Internationally , chlorine gas accounts for the largest single cause of major toxic release incidents . 21 Chlorine is used in chemical , paper , and textile industries , along with sewage treatment . In each of these industries , the potential exists for accidental release . In addition , chlorine can be used in sabotage , warfare , and terrorist actions . 22 23 For example , insurgents in Iraq incorporated chlorine tanks in vehicle - based improvised explosive device attacks . 24 Prognosis Most individuals exposed to chlorine gas recover without significant sequelae . Even exposure to high - concentration chlorine gas is unlikely to result in significant , prolonged pulmonary disease . Morbidity from moderate and severe exposures is typically caused by noncardiogenic pulmonary edema . This may occur within 2 - 4 hours of exposure to moderate chlorine concentrations ( 25 - 50 ppm ) and within 30 - 60 minutes of severe exposures ( > 50 ppm ) . In serious exposures , sloughing of the pulmonary mucosa occurs in 3 - 5 days , and oozing areas become covered with mucopurulent exudate . This chemical pneumonitis is often complicated by secondary bacterial invasion . Resolution of pulmonary abnormalities in most individuals occurs over the course of 1 week to 1 month after the exposure . Smokers and persons with asthma are most likely to demonstrate persistence of obstructive pulmonary defects . 8 In a study of patients exposed to chlorine gas released after a train derailment , hypoxia on room air and the ratio of partial pressure of oxygen to fractional concentration of oxygen in inspired air ( PO / FiO ) predicted the duration of hospitalization and the need for intensive care support . 22 Residual effects Long - term follow - up studies of acute human exposures to chlorine gas provide conflicting data on the potential for long - term adverse effects from short - term chlorine exposure . In one study , after 2 years of follow - up , subjects displayed decreased vital capacity , diffusing capacity , and total lung capacity with a trend towards higher airway resistance . 25 Other studies demonstrated no consistent pattern of pulmonary function deficits after acute exposure . 26 27 28 29 Although no definite conclusion can be drawn concerning the long - term effects of an acute chlorine gas exposure , findings suggest increased risk of persistent nonspecific airway responsiveness . Furthermore , following an acute exposure , some patients with injured pulmonary epithelium have progressed to develop pulmonary fibrosis . 30 Bronchiolitis obliterans and emphysema have also been described in patients following acute exposures . Irritant - induced asthma ( formerly known as reactive airway dysfunction syndrome [ RADS ] ) , is a variant of occupational asthma that occurs after a single , high - dose exposure or after repeated low - level exposure . 31 Within minutes to hours , these individuals develop respiratory symptoms 32 followed by persistent bronchial hyperresponsiveness . 33 Persistent anxiety after acute exposure to chlorine gas has been observed . In one large - scale accident , 37 % of respondents had a positive posttraumatic stress screen 8 - 10 months post disaster , 44 % of which were considered severe ; 27 % of all individuals had a positive indication for tendency to panic . Tendency to panic was significantly associated with acute injury and female sex . 34 Clinical Presentation Sections Chlorine Toxicity Overview Presentation DDx Media Gallery References
|
[
"Chlorine Toxicity",
"respiratory tract .",
"sodium hypochlorite"
] |
http://emedicine.medscape.com/article/846915-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Otolaryngology and Facial Plastic Surgery General Principles of Maxillofacial Prosthetics Updated : Nov 17 , 2015 Author : Mounir Kharchaf , DDS , MDS ; Chief Editor : Arlen D Meyers , MD , MBA more . . . Sections Overview Intraoral Defects Extraoral Defects Show All Media Gallery References Overview Maxillofacial prosthetics is a branch of dentistry that deals with congenital and acquired defects of the head and neck . Maxillofacial prosthetics integrates parts of multiple disciplines including head and neck oncology , congenital malformation , plastic surgery , speech , and other related disciplines . This article deals with restoration of acquired defects , which may be intraoral or extraoral . Intraoral defects may involve the mandible , tongue , soft palate , or hard palate , while extraoral defects may involve any other area of the head or neck . 1 The image below depicts an example of maxillofacial prosthetics . Ocular prosthesis replaces a missing right eye . View Media Gallery Intraoral Defects Mandibular Defects Cantor and Curtis classified mandibular defects into 6 different categories based on extent of the defect and the method of restoration in edentulous patients . Class I - Radical alveolectomy with preservation of mandibular continuity Class II - Lateral resection of the mandible distal to the cuspid area Class III - Lateral resection of the mandible to the midline Class IV - Lateral bone graft and surgical reconstruction Class V - Anterior bone graft and surgical reconstruction Class VI - Anterior mandibular resection without surgical reconstruction Treatment of mandibular defects Surgical reconstruction using a bone graft is the best approach that a surgeon can take to correct defects of the mandible . The bone graft restores continuity to the mandible and provides a prosthesis - bearing area . However , surgical reconstruction may be contraindicated in patients receiving radiation therapy or in individuals with residual tumors . If mandibular resection involves the lower border of the mandible , the remaining segments deviate toward the defect side , backward , and upward . Using intermaxillary fixation for 5 - 7 weeks following the resection can reduce the deviation . The placement of a resection guidance appliance can also help minimize the deviation . These appliances are temporary and are removed once acceptable occlusal relationship and proper proprioception are attained . Surgical reconstruction of mandibular defects through myocutaneous , osteomyocutaneous , or microsurgical techniques is the treatment of choice for establishment of mandibular continuity . However , use of bone graft alone seldom provides an optimal base for removable prostheses . Optimal treatment involves placement of endosseous implants in the bone graft , which help to anchor removable or fixed prostheses . The implants also minimize bone resorption and add to patient comfort . When surgical reconstruction is contraindicated because of the presence of residual tumors or the patient ' s poor physical condition , perform prosthetic rehabilitation of the partially edentulous mandible with a mandibular guidance prosthesis . Optimally , design of such a prosthesis incorporates a rigid major connector and allows the device to obtain major support from adjacent soft tissue and teeth . In edentulous mandibulectomy , extending the denture into the soft tissue area on the resected side beyond the bony resection forms an outrigger that helps make the denture stable . On insertion of this denture , an occlusal Tongue Defects Tongue ( glossal ) defects can be partial or total . Factors influencing prosthetic prognosis of restoring the tongue include the presence or absence of teeth and the type of procedure that is combined with the glossectomy ( eg , mandibulectomy , palatectomy , radiation therapy ) . Patients with partial glossectomy ( ie , < 50 % of tongue removed ) suffer minimal functional impairment and require no prosthetic intervention . Removal of more than 50 % of the tongue requires construction of a palatal or lingual augmentation prosthesis . Total glossectomy causes a large oral cavity , loss of verbal communication , and pooling of saliva and liquid . Patients with a total glossectomy require a total tongue prosthesis . In dentulous patients , such a prosthesis can be attached to the mandibular teeth through a lower partial denture . 2 Treatment of tongue defects In edentulous patients , tongue prosthesis can be retained to either a mandibular or maxillary denture ( see the image below ) . Common problems associated with tongue prosthesis include lack of salivary control and loss of ability to maneuver food from the buccal vestibule . Therefore , it is best to fabricate 2 prosthetic tongues , 1 for swallowing and 1 for speech . A partial glossectomy with an artificial tongue attached to the maxillary arch is depicted . View Media Gallery A typical prosthetic tongue for speech is flat with wide anterior elevation , which aids in articulation of anterior lingual alveolar sounds ( eg , / t / , / d / ) . The typical prosthetic tongue also has a posterior elevation , which aids in production of posterior lingual alveolar sounds ( eg , / k / , / g / ) and helps shape the oral cavity for improved vowel productions ( see the image below ) . Total glossectomy with an artificial tongue for speech is shown . Note the anterior and posterior elevations . The tongue prosthesis for swallowing is made with a trough in its posterior slope to guide the food bolus into the oropharynx . A speech pathologist and , when necessary , a nutritionist should monitor all patients who have a glossectomy . Hard and Soft Palate Defects Hard and soft palate defects are best treated with obturator or speech aid regardless of the presence or absence of teeth . Saving as much of the maxillae as possible without compromising tumor resection is important . Retention of the premaxillae and / or key teeth ( eg , cuspids , first molars ) helps enhance prosthesis stability and support . Using a split - thickness skin graft to line the cheek flap enhances prosthesis tolerance . In addition , the mucodermal junction forms a lateral scar band , which helps retain and stabilize the prosthesis ( see the image Scar band formed by the muco - dermal junction helps retain the maxillary obturator . Maxillectomy Rehabilitation In prosthetic rehabilitation of maxillectomy , the surgical obturator is placed immediately after maxillae resection . A wrought wire clasp , sutures , or screws attached to the remaining palatal bone can retain the obturator ( see the image below ) . The obturator helps maintain surgical packing , helps the patient speak and swallow , and adds to the patient ' s comfort and psychological stability . A defect in the medial portion of the hard palate is pictured . Two bars screwed to 4 implants retain the obturator . Prior to resection , the surgical obturator is fabricated from the impression made of the maxillary arch . This cast is modified according to the planned surgery . From the modified cast , the surgical obturator is waxed and processed in clear acrylic resin and inserted immediately after surgery . After 5 - 7 days , the surgical obturator and packing are removed , the defect area is cleaned with mineral oil , and the surgical obturator is adjusted and relined with tissue - conditioning material . The patient then returns weekly for adjustment and change of relining material . Delay fabrication of the final obturator until the surgical site is stable and fully healed . This process usually takes at least 4 months . Extend the lateral wall of the definitive prosthesis as high as possible in order to engage the scar band . This extension helps in retention and stability of the prosthesis . Several authors have recommended different techniques for enhancing retention of the maxillary obturator , including fabrication of a hollow bulb obturator , making the bulb without a top , use of a 2 - part obturator , or use of a sectional obturator with 3 4 Maxillary prosthesis retained by implants positioned in the remaining maxillae as well as the Zygomatic bone . Treatment of patients that had radiation therapy Patients , who undergo radiation therapy to the head and neck region , will experience several effects of radiation to the oral cavity . These effects include mucositis , loss of taste , xerostomia and trismus . Patients who have ill fitting dentures are instructed not to wear their dentures during the course of radiation therapy . Fabrication of new denture should be delayed until the oral soft tissue has adequately healed . Healing could take 3 - 12 month before the new dentures could be fabricated . Soft tissues should be manipulated very gently when developing the denture border The use of dental implants has been studied by several authors . Some authors recommended the use if hyperbaric oxygen treatment ( HBO ) prior to implant placement . Others do n ’ t recommend the use of HBO . Literatures seem to find equal implant success and failure rates regardless of the use of HBO . Overall , implants in radiated patients experienced a very high success rate that is slightly less than the success achieved in patients that had no radiation . The benefits gained by the use of implants are great . This makes it highly recommended to use dental implants in radiated patients whenever it is possible . Treatment of soft palate defects Prosthetic treatment of soft palate defects varies based on the extent and site of the defect . The goal of treatment is to attain velopharyngeal closure during function , which allows normal speaking and swallowing and keeps the patient relatively comfortable . In edentulous patients , after the conventional maxillary denture is fabricated , a wire is attached to the palatal end of the denture and extended to the defect area . An impression of the defect area is attained and duplicated in clear , cold , cured acrylic , thus , forming the speech bulb . The speech bulb can be attached to a removable partial denture framework in the same manner for dentulous patients ( see the image below ) . Following fabrication , the prosthesis is positioned in the mouth and checked for overextension using pressure - indicating paste Soft palate defect and a speech bulb that is attached to the maxillary denture are depicted . Extraoral Defects Restoration of facial defects can be accomplished either surgically , prosthetically , or by using a combination of both methods . 5 The choice of method depends on many factors ( eg , size and location of the defect , age of patient ) . Surgical reconstruction is indicated when the defect is small in size , involves mobile structures ( eg , eyelid , lip ) , or occupies the cranial vault , especially if the margins of the defect are clear of cancer . The prosthetic approach is superior to the surgical approach if the defect is large or the blood supply to the area is compromised ( eg , nasal septal defects , tracheoesophageal fistula , radiated bed ) . Superior color match and patient acceptance , especially in nasal or auricular prostheses , make prosthetic rehabilitation superior to the surgical approach , especially if the defect is large in size . 6 It is important to use prosthetic materials with certain properties in order to achieve clinical success and patient acceptance . These properties include color stability , ease of fabrication , dimensional stability , and edge strength . Flexibility , low thermal conductivity , biocompatibility , and surface texture are also important . Silicones are the most widely used materials for facial restorations in the United States . 7 The type most commonly used , RTV Silicone MDX - 4 - 4210 , has surface texture and hardness within the range of human skin . Methods for attaching and holding facial prostheses must be as invisible as possible to make them aesthetically pleasing . Using tissue undercuts or attaching the prosthesis to the patient ' s eyeglasses or dentures can help mechanically retain the device . Medical - grade adhesives or tapes are also under study for this purpose ( see the image below ) ; however , they collect dirt and are unhygienic . 8 An artificial nose is attached with medical - grade adhesive . Endosseous implants placed in surrounding facial bone to help anchor different facial prostheses have been widely used . Implants in the mastoid process retain auricular prostheses . Orbital rim implants may anchor orbital prostheses , and implants placed in malar bone and / or the anterior nasal spine can be used to secure nasal prostheses . Sections General Principles of Maxillofacial Prosthetics Show All Media Gallery References
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[
"Maxillofacial Prosthetics",
"congenital malformation",
"plastic surgery"
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http://emedicine.medscape.com/article/84829-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Sports Medicine Nasal Fracture Updated : Dec 06 , 2018 Author : Samuel J Haraldson , MD ; Chief Editor : Craig C Young , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Follow - up Questions & Answers Media Gallery References Practice Essentials Nasal fractures seen in participants of athletic activities occur as a result of direct blows in contact sports and as a result of falls . The nasal bones are the most commonly fractured bony structures of the maxillofacial complex . 1 2 3 4 5 6 See the images below . Lateral radiographic view of a displaced nasal bone fracture in a patient who sustained this injury because of a punch to the face during a hockey game . View Media Gallery Lateral radiographic view of a nasal bone fracture in an elderly patient who fell forward on her face as a result of syncope . Marked comminution is present . View Media Gallery The nasal bone ' s protruding position coupled with its relative lack of support predisposes it to fracture . Prompt appropriate treatment prevents functional and cosmetic changes . Because of the nose ' s central location and proximity to important structures , the clinician should carefully search for other facial injuries in the presence of facial fractures . For excellent patient education resources , visit eMedicineHealth ' s First Aid and Injuries Center . Also , see eMedicineHealth ' s patient education articles , Facial Fracture and Broken Nose Epidemiology Frequency United States Nasal fractures occur nearly twice as often in males as in females . Athletic injuries and interpersonal altercations account for the greatest proportion of causes . Less common causes include falls and motor vehicle accidents . 7 8 In a retrospective study , Erdmann et al investigated the medical records of 437 patients with 929 facial fractures . 3 These authors noted that the most common etiology of facial trauma was assault ( 36 % ) , followed by motor vehicle collision ( MVC , 32 % ) , falls ( 18 % ) , sports ( 11 % ) , occupations ( 3 % ) , and gunshot wounds ( 2 % ) . Of the facial fractures sustained , the most common fracture type was nasal bone fracture . A study by Hanba et al found that risk factors for facial fracture included being white , Asian , female , or ≥ 60 years of age . 9 A study by Plawecki et al evaluated the incidence of 20,519 patients , 55 years of age or older , who went to the ED for recreational activity - associated facial fractures . The study reported that the annual incidence of facial fractures increased by 45.3 % from 2011 through 2015 . Nasal fractures were the most common site of fracture ( 65.4 % ) and cycling ( 26.6 % ) was the most common cause in this cohort of older patients . 10 International In a retrospective study of Brazilian children aged 5 - 17 years , Cavalcanti and Melo found that facial injuries were most frequent in males ( 78.1 % ; 3 - fold more common than in females ) aged 13 - 17 years ( 60.9 % ) , and the most common causes of these injuries were falls ( 37.9 % ) and traffic accidents ( 21.1 % ) . 1 Of the facial injuries , nasal fractures were also most common ( 51.3 % ) , followed by the zygomatic - orbital complex ( 25.4 % ) . In another retrospective study , Hwang et al reviewed and analyzed the medical records of 236 patients with facial bone fractures from various sports who were treated at one hospital between 1996 and 2007 . 11 The investigators noted the age group with the highest frequency of such injuries was 11 - 20 years ( 40.3 % ) , with a significant male predominance across all age groups ( 13.75 : 1 ) . There were 128 isolated nasal fractures , with soccer accounting for 39 % of these ; baseball , 18 % ; basketball , 12.5 % ; martial arts , 5 % ; and skiing or snowboarding , 5 % . 11 Functional Anatomy The lay term nose consists of bone and cartilage . The nasal septum , a commonly injured structure , consists of the vomer , the perpendicular plate of the ethmoid , and the quadrangular cartilage . Paired protrusions from the frontal bones and the ascending processes of the maxilla complete the bony component . The upper lateral and lower lateral cartilages , as well as the cartilaginous septum , compose the nonbony portion . The blood supply occurs via branches of the ophthalmic artery , the ethmoidal and dorsal arteries , the facial artery , the nasopalatine , the sphenopalatine , and the greater palatine arteries . Sensation results from many small nerve branches ; the external surface superiorly receives sensation from the supratrochlear and infratrochlear nerves , and the inferior portion receives sensation from branches of the infraorbital and anterior ethmoidal nerves . Internally , sensation is supplied by branches of the anterior ethmoidal ganglion and the sphenopalatine ganglion . Sport - Specific Biomechanics Any force directed to the mid face , either frontally or laterally , can disrupt the nasal anatomy , causing bony or cartilaginous injury . Frontally directed forces must be greater than normal to cause bony injury because the upper and lower lateral cartilages absorb a great deal of impact . Children are more likely to sustain cartilaginous injury for a variety of reasons . This is mainly because children have a greater proportion of cartilage to bone , and the cartilage provides increased protection from fracture . Children ' s bones are also more elastic than adults ' bones . This explains the increased incidence of greenstick fractures in children ( fracture without displacement ) . Clinical Presentation Sections Nasal Fracture Overview Presentation DDx Workup Treatment Medication Follow - up Questions & Answers Media Gallery References
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[
"Nasal Fracture",
"Practice Essentials",
"athletic activities"
] |
http://emedicine.medscape.com/article/849516-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Otolaryngology and Facial Plastic Surgery Neck , Cervical Metastases , Detection Updated : Mar 08 , 2016 Author : Benoit J Gosselin , MD , FRCSC ; Chief Editor : Arlen D Meyers , MD , MBA more . . . Sections Overview Anatomy of the Cervical Lymphatics Classification of Cervical Node Groups Mechanisms of Lymph Node Metastasis Evaluation of the Neck for Cervical Metastases : Physical Examination Detection of Cervical Metastasis : Radiological Investigations Conclusions Show All Media Gallery References Overview Cervical metastasis by a tumor is firm statement of its aggressive malignant nature . Nothing is more controversial than the management of cervical metastatic disease . This is not surprising considering the lack of knowledge of carcinogenesis , pathophysiology of metastases , and implications of tumor spread . Fortunately , great strides have been made in the understanding of the intricate processes related to metastatic disease . Proper understanding of anatomy and the detection of cervical metastatic disease is crucial to this process . Forthcoming techniques will also facilitate the detection of primary and metastatic disease . For excellent patient education resources , visit eMedicineHealth ' s Cancer Center . Also , see eMedicineHealth ' s patient education article Cancer of the Mouth and Throat Photograph showing an aspirate being placed on a glass slide . After the 20 - mL disposable syringe with an attached 21 - gauge needle is placed under the skin surface and the mass is aspirated , a small drop of aspirated fluid is placed on a glass slide . View Media Gallery Anatomy of the Cervical Lymphatics The lymphatic system has 3 components : the capillaries , vessels , and nodes . Capillaries Larger than arteriovenous capillaries , lymphatic capillaries are thin - walled , with a single layer of endothelial cells . Lymphatic capillaries are found in all tissues ; however , they are more abundant in the upper respiratory and GI tracts . Pooled capillaries drain lymphatic fluid into lymphatic vessels , which have 3 layers . Vessels As in the capillaries , the vessels have a single layer of endothelial cells surrounded by an inner , longitudinal elastic layer . This first muscle layer is surrounded by a circular smooth muscle layer , which , in turn , is enveloped by an outer connective tissue layer . Lymphatic vessels contain many more valves than the venous system , with the lymph circulation entirely dependent on compression by surrounding muscles . Lymphatic vessels drain into lymph nodes . Nodes These nodules of tissue are of variable size . Typically , as many as 75 nodes are located on each side of the neck . Nodes contain a subcapsular sinus below a prominent capsule , into which lymphatic fluid drains . This capsule is often the first site of metastatic growth . The fluid permeates the substance of the node ( composed of a cortex and a medulla ) and exits through the hilum to enter more lymphatic vessels . These nodes are located between the superficial cervical and prevertebral fascia and , thus , are very amenable to surgical The occipital nodes are in the superficial group , which includes 3 - 5 nodes . This group of nodes is localized between the sternocleidomastoid ( SCM ) and trapezius muscles , at the apex of the posterior triangle . These nodes are superficial to the splenius capitis . The deep posterior cervical group includes 1 - 3 nodes . This group of nodes is located deep to the splenius capitis and follows the course of the occipital artery . These nodes drain the scalp , the posterior portion of the neck , and it ' s the deep muscular layers of the neck . The postauricular nodes vary in number from 2 to 4 ; they are located in the fibrous portion of the superior attachment of the SCM muscle to the mastoid process . Postauricular nodes drain the posterior parietal scalp and the skin of the mastoid region . The parotid nodes can be divided into intraglandular and extraglandular groups . The extraglandular parotid nodes are located outside but adjacent to the parotid gland , where they drain the frontolateral scalp and face , the anterior aspects of the auricle , the external auditory canal , and the buccal mucosa . Embryologically , the lymphatic system develops before the parotid gland , which surrounds the intraglandular nodes as it develops . This explains why the parotid gland contains lymphoid tissue . The intraglandular nodes drain the same regions as the extraglandular nodes , to which they interconnect and then The submandibular nodes are divided into 5 groups : preglandular , postglandular , prevascular , postvascular , and intracapsular . The preglandular and prevascular groups are located anterior to the submandibular gland and facial artery , respectively . The postglandular and postvascular groups are posterior to these structures . Differing from the parotid gland in embryological development , there is no true intraglandular node ; however , occasionally , a node has been identified inside the capsule of the gland . The submandibular nodes drain the ipsilateral upper and lower lip , cheek , nose , nasal mucosa , medical For the submental nodes , 2 - 8 nodes are located in the soft tissues of the submental triangle between the platysma and mylohyoid muscles . These nodes drain the mentum , the middle portion of the lower lip , the anterior gingiva , and the anterior third of the tongue . The efferent vessels drain into both the ipsilateral and contralateral submandibular nodes or into the internal jugular group . The sublingual nodes are located along the collecting trunk of the tongue and sublingual gland and drain the anterior floor of the mouth and ventral surface of the tongue . These nodes subsequently drain into the submandibular or jugular group of nodes . The retropharyngeal nodes are divided into a medial and lateral group , located between the pharynx and the prevertebral fascia . The lateral group , located at the level of the atlas near the internal carotid artery , consists of 1 - 3 nodes , which may extend to the skull base . The medial group extends inferiorly to the postcricoid level . This group drains the posterior region of the nasal cavity , sphenoid and ethmoid sinuses , hard and soft palates , nasopharynx , and posterior pharynx down to the postcricoid area . Management of these nodes must The anterior cervical nodes are divided into the anterior jugular chain and the juxtavisceral chain of nodes . The anterior jugular chain nodes follow the anterior jugular vein , located superficial to the strap muscles . These nodes drain the skin and muscles of the anterior portion of the neck , and the efferent vessels empty into the lower internal jugular nodes . The juxtavisceral nodes are separated into the prelaryngeal , prethyroid , pretracheal , and paratracheal nodes . Prelaryngeal nodes are located from the thyrohyoid membrane to the cricothyroid membrane and drain the larynx and the thyroid lobes . A single delphian node is often found overlying the thyroid cartilage . The pretracheal group consists of nodes between the isthmus of the thyroid gland down to the level of the innominate vein . Varying from 2 - 12 in number , these nodes drain the region of the thyroid gland and the trachea and receive afferent flow from the prelaryngeal group . The pretracheal efferents empty in the internal jugular group and the anterior superior mediastinal nodes . The paratracheal nodes lie near the recurrent laryngeal nerve and drain the thyroid lobes , parathyroid glands , subglottic larynx , trachea , and upper esophagus . The efferent vessels travel to the lower jugular group or directly toward the junction of the internal jugular vein and the subclavian vein . The anterior nodes drain bilaterally because the midline of the neck has no division . Treatment must be planned accordingly when a tumor is located in subjacent draining areas . The lateral cervical nodes are divided into superficial and deep groups . The superficial group follows the external jugular vein and drains into either the internal jugular or transverse cervical nodes of the deep group . The deep group forms a triangle bordered by the internal jugular nodes , the spinal accessory nodes , and the transverse cervical nodes . The transverse cervical nodes , forming the base of the triangle , follow the transverse cervical vessels and may contain as many as 12 nodes . These nodes receive drainage from the spinal accessory group and from collecting trunks of the skin of the neck and upper chest . The spinal accessory chain follows the nerve of the same name and may account for as many as 20 nodes . This chain receives lymph from the The internal jugular chain consists of a large system covering the anterior and lateral aspects of the internal jugular vein , extending broadly from the digastric muscle superiorly to the subclavian vein inferiorly . As many as 30 of these nodes may exist , and they have been arbitrarily divided into upper , middle , and lower groups . The efferents of these nodes eventually pass into the venous system via the thoracic duct on the left and multiple lymphatic channels on the right . These nodes drain all the other groups mentioned . Direct efferents may be present from Although fairly consistent , these drainage patterns are subject to alteration with malignant involvement or after radiotherapy . In such cases , rerouting is possible , with metastases arising in unusual sites . Metastases have also been shown to skip first - echelon nodes and manifest in the lower internal jugular group . Classification of Cervical Node Groups Spread patterns of cancer from various primary sites in the head and neck to the cervical nodes have been documented in retrospective analyses of large groups of patients undergoing neck dissections . Since the first descriptions of nodal groups , various classification systems have been described . To address surgical management of early - stage neck metastases via neck dissection , various authors have proposed a number of classification schemes . This lack of uniformity and standardization results in redundancy , misinterpretation , and confusion among clinicians . The most widely accepted terminology was originally described by a group of head and neck surgeons at Memorial Sloan - Kettering Hospital . This classification uses neck levels or zones and divides each side of the neck into 6 separate regions . This system is still used today . Level I is bordered by the body of the mandible , anterior belly of the contralateral digastric muscle , and anterior and posterior bellies of the ipsilateral digastric muscle . Two nodal subgroups are found . The submental group ( Ia ) is found in the submental triangle ( anterior belly of the digastric muscles and the hyoid bone ) , and the submandibular group ( Ib ) is found within the submandibular triangle ( anterior and posterior bellies of the digastric muscle and the body of the mandible ) . The nodes found in level II are located around the upper third of the internal jugular vein , extending from the level of the carotid bifurcation inferiorly to the skull base superiorly . The lateral boundary is formed by the posterior border of the SCM muscle ; the medial boundary is formed by the stylohyoid muscle . Two subzones are also described ; nodes located anterior to the spinal accessory nerve are part of level IIa , and those nodes posterior to the nerve are located in level IIb . The middle jugular lymph node group defines level III . Nodes are limited by the carotid bifurcation superiorly and the cricothyroid membrane inferiorly . The lateral border is formed by the posterior border of the SCM muscle ; the medial margin is formed by the lateral border of the sternohyoid muscle . Level lV contains the lower jugular group and extends superiorly from the omohyoid muscle to the clavicle inferiorly . The lateral border is formed by the posterior border of the SCM muscle ; the medial margin is formed by the lateral border of the sternohyoid muscle . The lymph nodes found in level V are contained in the posterior neck triangle , bordered anteriorly by the posterior border of the SCM muscle , posteriorly by the anterior border of the trapezius , and inferiorly by the clavicle . Level V includes the spinal accessory , transverse cervical , and supraclavicular nodal groups . Level VI lymph nodes are located in the anterior compartment . These nodes surround the middle visceral structures of the neck from the level of the hyoid superiorly to the suprasternal notch inferiorly . A complete understanding of these anatomic relationships allows various practitioners to exchange information in an unbiased fashion and is critical in the decision - making processes involved in management of nodal metastases . Mechanisms of Lymph Node Metastasis The current hypotheses on the development of malignancies relate to alterations in the normal mechanisms of cellular proliferation and differentiation and a failure of cell death ( apoptosis ) . This loss of growth control is the result of genetic mutations , including the activation of proto - oncogenes and / or inactivation of tumor suppressor genes . The resulting phenotypic changes provide cancer cells a growth advantage , including loss of response to normal growth controls , defects in response signals for programmed cell death , resistance to cytotoxicity , and defects in terminal differentiation . Proposed by Fidler , the concept of tumor heterogeneity suggests that tumors are composed of heterogeneous subpopulations of cells differing in immunogenicity , invasiveness , cellular growth kinetics , sensitivity to cytotoxic drugs , and ability to metastasize . The local tumor environment may favor the development of more aggressive clones in the formation of metastases . Although the size of individual clones with metastasizing potential in a given tumor is significant , only a very small percentage of circulating cells lead to the development of metastatic colonies . The events surrounding the initiation of local tumor invasion by epithelial tumors include a loss of cellular adhesion to surrounding tumor cells and basement membrane , invasion by malignant cells of the subjacent connective tissues by the production of cellular enzymes and growth mediators , cellular attachment to extracellular membrane molecules , neovascularization , and entry or exit from the circulation through the attachment to endothelial cell ligands . A repeat of these events occurs at metastatic sites . In the case of head and neck squamous cell carcinomas , malignant cells may progress from carcinoma in situ , to microinvasive carcinoma , to a deeply invasive tumor with lymphatic metastases . Interestingly , a head and neck squamous cell carcinoma has the ability to manifest at both extremes of histopathological development in the same anatomic location . The critical step in the transition from carcinoma in situ to microinvasive and invasive carcinoma is the destruction of the basement membrane . This destruction is accomplished by the production of specific proteolytic molecules by tumor cells , including matrix metalloproteinases Angiogenesis is the growth of new capillaries by sprouting from established vessels . In normal tissues , self - limiting angiogenesis is part of reproduction and organogenesis in addition to wound repair and healing . Conversely , pathological angiogenesis is not autoregulated , but results from alterations in growth - control mechanisms of disease processes ( eg , malignant transformation ) . Various tumor - derived factors ( eg , prostaglandin E2 , platelet - derived growth factor , transforming growth factor - beta , transforming growth factor - alpha , beta - fibroblast growth factor ) are still being Recent research looking specifically at the production of cytokines regulating immune , inflammatory , and angiogenetic responses in patients with laryngeal squamous cell cancer has revealed higher serum concentrations of the cytokines interleukin - 6 , interleukin - 8 , and vascular endothelial growth factor . These agents may be important in proinflammatory and proangiogenetic responses of tumor cells . The ability of a tumor to stimulate an angiogenic response should directly determine the capability of a tumor to metastasize and ultimately kill the host . A clear correlation between tumor angiogenesis and nodal metastasis has been demonstrated in early and invasive breast carcinoma , ovarian and endometrial carcinoma , non – small - cell carcinomas , prostatic carcinoma , adenocarcinoma of the colon , and squamous cell carcinoma of the esophagus . The literature notes conflicting reports regarding microvessel density and nodal metastasis in head and neck squamous cell carcinomas . Tumor sites of varying origins with different vascularization patterns at their primary sites may behave differently . Malignancies of the head and neck , especially head and neck squamous cell carcinomas , are the result of a series of genetic misadventures of squamous epithelial cells leading to malignant transformation . Variable genetic susceptibility , prolonged tobacco and alcohol exposure , viruses , and immune suppression all can facilitate these genetic derangements . Tumors invade local connective tissues by the production of proteinases and the expression of surface markers that facilitate attachment to extracellular matrix components . Tumor growth and size being limited by available nutrients from the surrounding milieu , recruitment of host capillaries leads to the formation of an intratumoral blood supply . Capillary and lymphatic invasion by tumor cells allow malignant cell dissemination and the establishment of histologically identical tumors at distant sites . Most recently , the expression of vascular endothelial factor - D in a mouse tumor model was found to lead to the lymphatic spread of tumor cells , tumor angiogenesis , and tumor growth . Further research in this area will likely provide more details in the multiple steps involved in the lymphatic spread of squamous cell cancer . The dissemination of tumor cells beyond the primary site unfortunately remains the most significant factor in prognosis and needs further study . Evaluation of the Neck for Cervical Metastases : Physical Examination Evaluating neck metastases based on physical examination findings has been the classic method for patients with new tumors in the head and neck . The single most important factor in determining prognosis is whether nodal metastasis is present . Survival rates decrease by 50 % when nodal metastases are present . Furthermore , the presence of cervical adenopathy has been correlated with an increase in the rate of distant metastasis . During the clinical evaluation , careful palpation of the neck , with specific attention to location , size , firmness , and mobility of each node , is noted . Attention is particularly directed to nodes that appear fixed to underlying neurovascular structures , visceral organs , or nodes that demonstrate skin infiltration . The description of each node becomes an important part of the medical record , which can be used to assess the response to treatment or the progression of the disease . Unfortunately , clinical palpation of the neck demonstrates a large variation of findings among various examiners . Although both inexpensive to perform and repeat , palpation findings are generally accepted as inaccurate . Both the sensitivity and specificity are in the range of 60 - 70 % , depending on the tumor studied . Because of the known low sensitivity and specificity of palpation , a neck side without palpable metastases is still at risk of harboring occult metastasis , with the risk determined by the characteristics of the primary tumor . The incidence of false - negative ( occult Detection of Cervical Metastasis : Radiological Investigations Debate persists over the relative merits of imaging in the evaluation of the neck for metastatic disease . 1 Studies that correlate radiologic and histopathologic findings show that early microscopic metastases can be present in nodes smaller than 10 mm that demonstrate no stigmata of neoplasia ( ie , central necrosis , extracapsular spread ) . Evidence of early metastatic disease in clinically occult nodes is minimal and may evade the efforts of the pathologist and radiologist . Ultrasound Ultrasound is reported superior to clinical palpation for detecting lymph nodes and metastases . The advantages of ultrasound over other imaging modalities are price , low patient burden , and possibilities for follow - up . Sonographs of metastatic lymph node disease characteristically find enlargement with a spherical shape . Commonly , nodes are hypoechoic , with a loss of hilar definition . In cases of extranodal spread with infiltrative growth , the borders are poorly defined . Common findings of metastases from squamous cell carcinoma are extranodal spread and central necrosis together with liquid areas in the lymph nodes . Lymph node metastases from malignant melanoma and papillary thyroid carcinoma have a nonechoic appearance that mimics a cystic lesion . Sonography may also be useful for assessing invasion of the carotid artery and jugular vein Because lymph nodes of borderline size can not be reliably diagnosed using ultrasound alone , ultrasound - guided fine - needle aspiration and cytologic examination of the nodes in question can be easily performed . The result of the aspirate examination depends on the skill of the ultrasonographer and the quality of the specimen ( ie , harboring an adequate number of representative cells ) . Using this technique , most studies report that a sensitivity of up to 70 % can be obtained for the N0 neck Photograph showing the smear technique for plating a sample aspirate . After a small drop of fluid is placed on a glass slide , a second slide is used to smear the aspirate evenly over the surface of the slide . The slide is then prepared for cytologic evaluation . View Media Gallery Photograph showing an aspirate being placed on a glass slide . After the 20 - mL disposable syringe with an attached 21 - gauge needle is placed under the skin surface and the mass is aspirated , a small drop of aspirated fluid is placed on a glass slide . CT scan Since its debut in the 1970s , CT scans have been an invaluable tool in all fields of medicine , including the evaluation of head and neck cancer . Since the advent of high - resolution systems and specific contrast media , fine - cut CT scanning has allowed the detection of pathological cervical nodes of smaller size that may be missed by clinical examination . CT scanning is now used routinely for the preoperative evaluation of the neck because , presumably , it helps decrease the incidence of occult cervical lymphadenopathy . 2 Introduced in 1998 , multiple - spiral CT scanning promises further improvement of temporal and spatial resolution ( in the longitudinal axis ) . This technique permits rapid scanning of large volumes of tissue during quiet breathing . The volumetric helical data permit optical multiplanar and 3 - dimensional reconstructions . Improvement of the assessment of tumor spread and lymph node metastases in arbitrary oblique planes is another advantage of the spiral technique . Criteria for the identification of questionable nodes are also evolving as technology advances . Central necrosis remains the most specific finding suggestive of nodal involvement , but its absence does not exclude metastasis . Unfortunately , metastasis is usually quite rare or not visible in small lymph nodes , where detection would be crucial . Because of the higher imaging resolution , various studies have reduced the traditional values of 10 - 15 mm for a node to be suggestive . Many authors have proposed a minimal axial diameter of 11 mm for the submandibular triangle and 10 mm for An imaging - based classification has also been proposed by Som et al , 3 and due to its specificity , has also been endorsed by clinicians managing head and neck cancer . The boundaries of the nodal levels were easily discerned by radiologists and yielded consistent nodal classifications . For an evaluation of the diagnostic abilities of Ga - SPECT , see Kotani et al . 4 Magnetic resonance imaging The value of MRI is its excellent soft tissue resolution . MRI has surpassed CT scanning as the preferred study in the evaluation of cancer at primary sites such as the base of the tongue and the salivary glands . The sensitivity of MRI exceeds that of clinical palpation in detecting occult cervical lymphadenopathy . Size , the presence of multiple nodes , and necrosis are criteria shared by CT scanning and MRI imaging protocols . 5 6 Many reports indicate that CT scanning still has an edge over MRI for detecting cervical nodal involvement . Advances in MRI technology ( eg , fast spin - echo imaging , fat suppression ) have not yet surpassed the capacity of CT scanning to identify lymph nodes and to define nodal architecture . Central necrosis , as evaluated by unenhanced T1 - and T2 - weighted images , has been shown to provide an overall accuracy rate of 86 - 87 % compared with CT scanning , which has an accuracy rate of 91 - 96 % . 7 The use of newer contrast media , especially supramagnetic contrast media agents , hopefully will improve the sensitivity of MRI . Positron emission tomography imaging This new imaging modality has been increasingly studied in the staging of head and neck cancer . 8 9 The technique relies on the uptake of 2 - fluoro - 2 - deoxy - D - glucose ( FDG ) in metabolically - active lesions . The study may also be fused to a corresponding CT scan to facilitate the localization of the lesion of concern . In comparing their usefulness in the detection of cervical metastasis , PET / CT fusion images have been found to be superior and more accurate for the detection of cervical metastasis , compared with PET alone or with conventional imaging modalities . In addition , PET can contribute to the detection of residual or early recurrent tumors , leading to the institution of earlier salvage therapy . 2 A study by Tan et al indicated that FDG - PET / CT scanning is more sensitive than contrast - enhanced multislice helical CT ( MSCT ) imaging in detecting paraesophageal lymph node metastases in patients with esophageal cancer . The study involved 115 patients with esophageal cancer , in whom a total of 946 lymph node groups were resected ; metastases were confirmed histopathologically in 221 of these groups . Although no significant differences were found between FDG - PET / CT scanning and enhanced 64 - slice helical CT imaging with regard to specificity and accuracy in detecting 10 The investigators ’ findings also indicated , however , that enhanced MSCT imaging can effectively distinguish false - negative lymph node metastases visualized on FDG - PET / CT scans . Tan and colleagues concluded that combining FDG - PET / CT scanning with MSCT imaging should increase accuracy in staging lymph node metastases in esophageal cancer . 10 A study by Jung et al suggested that in papillary thyroid carcinoma , a primary tumor with a high avidity for FDG and a high maximum standardized uptake value ( SUVmax ) is predictive for cervical lymph node metastasis . The study included 193 patients with papillary thyroid carcinoma who underwent FDG - PET / CT scanning prior to treatment , with the FDG - avid tumors being larger than the nonavid tumors ( 0.93 cm vs 0.59 cm , respectively ) and the incidence of cervical lymph node metastasis being greater in the avid tumors than in the nonavid 11 Conclusions None of the currently available imaging techniques can help depict small tumor deposits inside lymph nodes . Characteristics of metastatic lymph nodes that can be depicted are the size and presence of noncontrast - enhancing parts inside metastatic lymph nodes caused by tumor necrosis , tumor keratinization , or cystic areas inside the tumor . Only rarely does tumoral tissue enhance more than reactive lymph node tissue ; in these rare cases , the tumor can be visualized within a reactive lymph node . Patients who need an evaluation for a possible nodal malignancy require a comprehensive multidisciplinary evaluation of all potential sites of drainage to that node to identify its primary source . This includes a thorough evaluation of potential primary sites using endoscopic techniques . When appropriate , include laryngoscopy , esophagoscopy , bronchoscopy , and examination of the nasopharynx . If no primary source is identified , taking blind mucosal biopsy samples of the most likely head and neck subsites is essential . 12 PET / CT techniques have a promising role ; however , greater clinical experience is needed prior to making this modality the standard for the detection of metastasis in head and neck cancer . Complete documentation of nodal characteristics by clinical examination and palpation guide the examiner in using adjunctive radiological tools to exclude occult nodal metastasis .
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"Cervical Metastases",
"Otolaryngology",
"Benoit J Gosselin"
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http://emedicine.medscape.com/article/860642-overview
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Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Otolaryngology and Facial Plastic Surgery Benign Tumors of the Middle Ear Updated : Jun 12 , 2018 Author : Lawrence R Lustig , MD ; Chief Editor : Arlen D Meyers , MD , MBA more . . . Sections Overview Glomus Tympanicum Tumors Peripheral Nerve Sheath Tumors Middle Ear Adenoma Choristomas Hemangiomas and Vascular Malformations Langerhans Cell Histiocytosis ( Eosinophilic Granuloma ) Other Tumors of the Middle Ear Show All References Overview Benign lesions of the middle ear comprise a diverse spectrum of local and systemic diseases that have manifestations within the temporal bone . Despite their benign histopathological characteristics , these lesions may be locally destructive . Prompt diagnosis and treatment are therefore necessary to prevent progression of audiologic , vestibular , and facial nerve dysfunction , which may also be present . Some of these uncommon lesions are not well characterized , with a variety of confusing nomenclature and classification schemes based upon historical precedent or an incomplete knowledge base . As understanding of the underlying pathophysiology and molecular biology 1 Glomus Tympanicum Tumors The most common tumor of the middle ear and second most common tumor found in the temporal bone is the paraganglioma , commonly referred to as the glomus tumor . 2 Chemodectoma is another term occasionally used to describe this tumor . Glomus tumors originate in the paraganglia , which exist throughout the temporal bone , including on the jugular dome , the promontory of the middle ear , and along the Jacobson and Arnold nerves . This anatomy accounts for the predilection of glomus tumors toward these anatomic sites . The term glomus was applied to these tumors when their origin was believed to be similar to true glomus ( arteriovenous ) complexes . Despite being a misnomer , the nomenclature has persisted . An image depicting glomus tympanicum tumor can be seen below . Glomus tympanicum tumor . Axial CT image shows a small vascular mass along the right tympanic membrane . Note the adjacent opacified mastoid air cells . Reprinted with permission . Copyright Springer - Verlag . Glomus tumors involving the temporal bone are classified according to their anatomic location and size . Fisch and Oldring classified paragangliomas based on anatomic site , location and the presence of bony erosion . 3 Glasscock and Jackson categorized glomus tumors as glomus tympanicum or glomus jugulare tumors and classified glomus tympanicum tumors according to the anatomic site ( s ) involved . 4 Glomus tympanicum tumors arise along the course of the Jacobson nerve and are subclassified by size ( see below ) . Glomus jugulare tumors arise from the dome of the jugular bulb and involve the jugular foramen and related structures . Both types are marked by slow , progressive growth , spreading via the pathways of least resistance ( eg , temporal bone air cell tracts , neural foramina , vascular channels , bony haversian systems , and the eustachian tube ) . Pathophysiology Although most glomus tumors appear to arise sporadically , familial disease has been reported with an unusual genomic imprinting mode of inheritance . In this manner of transmission , tumors only occur in the offspring of an affected female when the gene is transmitted through a carrier male . This accounts for the observed tumor occurrence in skipped generations . A clear predilection for these tumors is found in females , and patients usually present after the fifth decade of life . 5 Glomus tumors are typically reddish purple , vascular lobulated masses . Histologically , they resemble normal paraganglia with characteristic clusters of chief cells , termed zellballen ( the literal German translation is " cell balls " ) in a highly vascular stroma . This pattern is enhanced on silver staining , which is useful diagnostically . Sustentacular cells and nerve axons , seen in normal paraganglia , rarely appear in paragangliomas . Clinical presentation Because of the vascularity of these tumors , pulsatile tinnitus is often the first presenting symptom . Further growth causes conductive hearing loss as ossicular mobility is impaired . Hearing loss is present in approximately half of patients . Continued expansion may cause the tumor to erode laterally through the eardrum , mimicking a friable bleeding polyp , or it may expand medially , causing facial nerve dysfunction , sensorineural hearing loss , or vertigo . As with other paragangliomas , glomus tympanicum tumors have the potential to secrete catecholamines . Less than 25 cases of catecholamine - secreting glomus In a large series of 80 patients , presenting symptoms , in order of decreasing frequency , were pulsatile tinnitus ( 73 % ) , hearing loss ( conductive 49 % , mixed 11 % , sensorineural 6 % ) , aural pressure / fullness ( 39 % ) , vertigo / dizziness ( 16 % ) , otalgia ( 16 % ) , and bloody otorrhea ( 6 % ) . The Brown sign , which consists of a purple - red middle ear mass that blanches with positive pneumatic otoscopy , was seen in less than 10 % of patients . Diagnosis Differentiation between glomus tympanicum and jugulare tumors is not always possible by physical examination alone since both lesions typically involve the middle ear . Furthermore , other vascular lesions of the middle ear ( eg , aberrant carotid artery or high - riding jugular bulb ) may mimic a glomus tumor . Thus , radiographic evaluation prior to biopsy or surgical intervention is important . A high - resolution temporal bone CT scan demonstrating a contrast - enhancing mass limited to the middle ear at the level of the cochlear promontory with an intact plate of bone at the lateral aspect of the jugular fossa suggests the diagnosis of glomus tympanicum . CT scanning is also useful for evaluating the degree of bony erosion and the tumor ' s relationship to surrounding temporal bone structures . MRI , though not as helpful as CT scanning in evaluating bony changes within the temporal bone , is superior in identifying the extent of the tumor and defining the relationship of the tumor to surrounding structures once it has extended beyond the confines of the middle ear . Because the middle ear mass could be the tip of a larger glomus jugulare invading the middle ear from the jugular foramen , both CT scan and MRI are critical components of the diagnosis . 6 The appearance of a paraganglioma on MRI reflects its highly vascular nature . Glomus tumors are isointense on T1 - weighted images and brightly enhance with gadolinium . They typically possess numerous signal voids due to the vascular channels within them . On T2 - weighted images , they demonstrate increased signal intensity in the solid portions of the tumor with persistent flow voids in the vascular portions . This characteristic “ salt - and - pepper ” pattern secondary to punctuate flow voids seen in larger paragangliomas is not appreciated in tumors smaller than 2 cm . Some advocate If the lesion is extensive , angiography may help further evaluate glomus tumors , but it should be deferred until the preoperative period , when both diagnostic and therapeutic ( embolization ) 7 measures can be accomplished in a single study . Angiography allows determination of arterial supply , degree of vascularity , degree of arteriovenous shunting , evidence of major venous sinus occlusion , and confirmation of the diagnosis . It can evaluate the right , left , internal , and external carotid systems for evidence of multiple early lesions with a single study . Embolization is usually performed at the time of angiography as a preoperative maneuver to limit surgical blood loss . Because of the limited size and extent of most glomus tympanicum tumors , angiography and embolization are rarely Magnetic resonance angiography and venography can also aid in the diagnosis of vascular lesions of the temporal bone , including glomus tumors . The role of these newer radiographic modalities in the evaluation of glomus tumors is still being defined . As previously stated , angiography , while useful for larger lesions , is not required for small glomus tympanicum tumors limited to the middle ear that can be visualized by less invasive techniques such as magnetic resonance angiography . Treatment Surgery is the principle mode of therapy for glomus tympanicum tumors . 3 8 9 Small lesions limited to the promontory that can be visualized completely by otoscopy and are confined to the mesotympanum on a CT scan can be approached via a transcanal incision and a tympanomeatal flap to expose the middle ear . Some authors have advocated the use of the diode or potassium titanyl phosphate ( KTP ) laser for tumor resection . Lesions extending to the hypotympanum are best exposed through a postauricular extended facial recess approach combined with an anterior tympanotomy . Extremely large lesions may require an infratemporal fossa approach , similar to a glomus jugulare . 10 Using these methods , complete tumor removal can be achieved in more than 90 % of patients . Closure of the air - bone gap can be expected in most patients , while approximately 10 % experience some sensorineural worsening . A study by Killeen et al indicated that some glomus tympanicum tumors can be safely and effectively resected endoscopically . The report involved attempted endoscopic resection of 14 middle ear paragangliomas ( mean size 6.2 mm ) , with an exclusively endoscopic approach achieved in 11 cases . No significant postoperative complications were noted in any of the study ’ s patients . 11 For poor surgical candidates , radiotherapy alone may be an option for palliation . Although radiation therapy does not eradicate the tumor , good local control and symptomatic relief may be achieved without significant morbidity . Peripheral Nerve Sheath Tumors Peripheral nerve sheath tumors originate from Schwann cells in the peripheral nervous system . The most common benign peripheral nerve sheath tumors are schwannomas and neurofibromas , and up to 45 % of these lesions occur in the head and neck . The most common tumor of the temporal bone and cerebellopontine angle is the schwannoma , accounting for approximately 6 % of all intracranial tumors and approximately 91 % of tumors in and around the temporal bone . Schwannomas usually arise within the internal auditory canal , cerebellopontine angle , or jugular foramen . However , they occasionally occur within or adjacent to the middle ear and in these cases usually arise from the facial nerve . Extension of a schwannoma from outside the middle ear may also present as a middle ear mass . Schwannomas of the facial nerve are rare , and although the exact incidence is unknown , temporal bones studies have found facial nerve schwannomas in less than 0.1 % of specimens . Schwannomas arising from the facial nerve are reported to occur at Pathophysiology Middle ear schwannomas may arise from the facial nerve , chorda tympani nerve , Jacobson nerve , or Arnold nerve , with the facial nerve being the most common nerve of origin . Schwannomas have been identified along the entire course of the facial nerve , although intratemporal tumors appear to be much more common than intracranial tumors . Within the temporal bone , the most common sites of involvement , in descending order , are the geniculate ganglion , labyrinthine segment , tympanic and vertical segments , and the internal auditory canal . Multiple sites of involvement are common In contrast to the more commonly appearing vestibular schwannoma ( ie , acoustic neuroma ) , facial nerve schwannomas tend to grow at a slower rate and are often present for years before detection . Because of the facial nerve ' s intimate relationship with the sensory organs , otic capsule erosion is more common in facial nerve schwannomas , occurring in as many as 30 % of patients . Clinical presentation Facial nerve dysfunction ( eg , palsy , twitch ) is the hallmark of clinical presentation and is evident on clinical examination in 25 - 50 % of patients . The most common pattern is a slowly progressive palsy , often accompanied by hyperfunction manifested as limited twitch or full hemifacial spasm . Recurrent acute paralytic episodes with partial or complete recovery may also occur . Patients are commonly misdiagnosed with Bell palsy with the first episode of paralysis . Successive bouts of palsy then ensue , with increasingly poor facial nerve function . This presentation of recurrent and progressive Patients may also present with normal facial nerve function , as the facial nerve is surprisingly resistant to compression . An estimated 50 % of facial nerve fibers must degenerate before clinical signs of palsy are detected . In one study of 48 patients with facial nerve neuromas , 26 presented with normal facial function . Additional presenting symptoms that have been described include conductive or sensorineural hearing loss , tinnitus , vertigo , and otorrhea . A surgeon performing an exploratory tympanotomy for conductive hearing loss may occasionally encounter a small facial nerve schwannoma impinging upon the stapes bone Diagnosis Facial nerve schwannomas are often found incidentally during routine middle ear or mastoid surgery . Since biopsy of a facial nerve schwannoma in the middle ear usually results in facial paralysis , appropriate imaging studies are recommended prior to obtaining a biopsy of any middle ear tumor . In cases of a facial nerve schwannoma , high - resolution temporal bone CT scan typically reveals enlargement of the fallopian canal along its length . Ossicular erosion and involvement of the horizontal semicircular canal may also be seen ; however , these findings are nonspecific and may be present in other middle ear pathologic conditions such as paraganglioma and cholesteatoma . One study of 4 patients with facial nerve schwannoma concluded that a soft tissue mass in the middle ear bounded anteriorly by a thin rim of bone ( “ bony crescent sign ” ) may be a specific The characteristic MRI appearance of schwannomas is isointense or hypointense on T1 - weighted images , hyperintense on T2 - weighted images , and marked enhancement with gadolinium . An enhancing enlargement of varying thickness along a large segment of facial nerve is considered highly suggestive of schwannoma . Although high - resolution CT scanning can reveal these tumors because of their osseous erosion , MRI is a more sensitive diagnostic tool . However , both modalities are useful for surgical planning . Site - of - lesion tests ( eg , Schirmer test of lacrimation , stapedial reflex testing ) , while theoretically attractive , are not completely reliable and have become largely obsolete because of the availability of CT and MRI scans . Treatment Treatment for facial nerve schwannomas involves either conservative observation , conventional microsurgery , or stereotactic radiosurgery . Simple observation with serial MRI scanning is warranted for tumors that are identified incidentally and are small and nonsymptomatic . However , for tumors that are larger , symptomatic , and growing , causing facial nerve weakness , treatment is indicated . Although a conservative approach is warranted at times for lesions limited to the transverse or descending portions of the nerve , excision is often indicated , as growth of the lesion may lead to erosion of surrounding structures . A tympanomastoid approach may be used , but lesions that involve the labyrinthine segment of the facial nerve , internal auditory canal , or geniculate ganglion require the addition of an extradural middle cranial fossa approach . If cochlear function has been destroyed , then a translabyrinthine approach may be used . 12 Occasionally , removing a facial nerve schwannoma with preservation of the nerve itself is possible ; 13 more commonly , nerve repair with an interposition graft is necessary . This is typically accomplished with a greater auricular or sural nerve graft . In general , patients with long - standing facial nerve paralysis tend to have poorer postoperative facial nerve function . The decision of when to remove a facial nerve neuroma depends upon a number of factors . The advantages of removing the tumor early , while it is small , include assurance that the tumor is completely resected with the least likelihood of injuring adjacent structures , including the hearing and balance organs . Additionally , a maximum number of surviving healthy neurons for grafting the nerve are available . However , the principle disadvantage of removing the tumor early is that the patient often has good nerve function in this situation , and tumor removal nearly always destroys residual nerve function . Further , grafting a transected nerve rarely results in facial function better than a grade III / VI ( House - Brackmann Grading Scale ) . Thus , many surgeons take a middle - of - the - road approach by delaying surgery until facial nerve function has deteriorated beyond a grade III / VI . However , surgery should be instituted sooner if adjacent structures are Stereotactic radiosurgery has been advocated as a treatment for facial nerve schwannomas , the primary goal of this treatment being to maintain the existing level of facial nerve function in the patient by preventing further growth of the neoplasm . However , long - term data is as yet insufficient to adequately evaluate this treatment modality in comparison with conventional surgery . 14 15 A study by Li et al indicated that in patients with neurofibromatosis type 2 , vestibular schwannoma response to antiangiogenic therapy can be predicted by dynamic contrast - enhanced MRI findings , including the baseline tumor volume , relaxation rate , and contrast transfer coefficient . 16 Middle Ear Adenoma Introduction Middle ear adenomas ( MEA ) , also recognized as neuroendocrine adenomas , are benign neoplasms first described in 1976 . Previous nomenclature applied to this class of tumors includes ceruminoma , ceruminous adenoma , and monomorphic adenoma . Carcinoid tumors of the middle ear were previously thought to be a distinct entity , but are now recognized as a subtype of middle ear adenomas . No single classification scheme has yet been established . 17 MEAs are thought to arise from pluripotent cells in the middle ear mucosa and may have mixed patterns of differentiation , ranging from purely epithelial ( adenoma ) to purely neuroendocrine ( carcinoid ) . They are nonencapsulated and demonstrate solid , glandular , or trabecular architecture . Various immunohistochemical markers have been reported to be present in middle ear adenomas . 18 Most tumors are positive for human pancreatic polypeptide , cytokeratin , and chromogranin . Other common markers include synaptophysin , CAM 5.2 , CK7 , vimentin , and neuron specific enolase . Not all markers may be positive in a given tumor , and no single marker is considered pathognomonic for MEA . Cells do not demonstrate papillary features , which would suggest a papillary adenocarcinoma ( also known as endolymphatic sac tumor ) . Middle ear carcinoid tumors , also described as middle ear adenoma with neuroendocrine differentiation , exhibit similar immunohistochemical features and tumor architecture as other types However , a study by Rooper et al found that various head and neck neuroendocrine tumors tested , including middle ear adenomas , were positive for insulinoma - associated protein 1 ( INSM1 ; 99.0 % sensitivity ) , while almost all non - neuroendocrine tumors tested were negative for the protein ( 97.6 % specificity ) , indicating that INSM1 is an effective standalone first - line marker of neuroendocrine differentiation for head and neck tumors . 19 Presenting symptoms of middle ear adenomas , as with most middle ear neoplasms , are nonspecific and include hearing loss , tinnitus , vertigo , and ear fullness . Patients often have conductive hearing loss due to entrapment or erosion of the ossicles . Rare cases of facial weakness have been reported , thought to be caused by compression of the facial nerve . Only one case of carcinoid syndrome associated with palpitation , dizziness , and flush attacks similar to that seen in carcinoid tumors of the gastrointestinal tract has been reported . No gender predominance for middle ear Diagnosis and treatment High - resolution CT scans add to the clinical examination and usually demonstrate a soft tissue mass confined to the middle ear without associated bone destruction . MRI characteristics include low - to - intermediate intensity on T1 - weighted images , high intensity on T2 - weighted images , and enhancement with gadolinium . Because these lesions are commonly confused with chronic otitis media , the diagnosis is rarely made preoperatively ; it is typically made during a routine mastoidectomy . Surgical excision is the only curative treatment for these lesions . If the ossicular chain is enveloped by Choristomas Introduction Choristoma is the pathological term given to a cohesive mass of histologically normal tissue occurring in an inappropriate anatomic location . While most reports address salivary gland choristomas , neural and sebaceous choristomas have also been described . Choristomas are extremely rare in the temporal bone ; less than 30 cases of middle ear choristomas have been reported in the English - language literature . One theory on the development of middle ear choristoma is that salivary gland tissue becomes trapped during the embryonic fusion of the tympanic , mastoid , and squamous portions of the temporal bone , leading to the formation of salivary choristomas . Neural rests of tissue are believed to gain access to the middle ear via Hyrtl ’ s ( tympanomeningeal ) fissures during development , giving rise to the less common neural choristoma . Microscopically , choristomas of the middle ear are characterized by well - formed serous and mucous acini arranged randomly or in a lobular formation . Mucinous microcysts and fibroadipose tissue components have also been described . Macroscopically , the tumors are lobulated and firm . Occasionally the tumor is attached to the middle ear by a fine stalk . Choristomas typically arise in the posterosuperior tympanum , although they vary in size and may fill the entire tympanic cavity . They are frequently associated with ossicular anomalies , particularly an absent or malformed incus or stapes . Facial nerve dehiscence or displacement is also common . Because of this frequent association , a second branchial arch embryologic etiology has been proposed . Clinical presentation and treatment Choristomas have been reported in individuals aged 11 months to 52 years , and no sex predilection is described . They are typically unilateral , although bilateral involvement has been reported . These benign tumors grow slowly and tend to produce few symptoms other than a conductive hearing loss in the affected ear correlating with the degree of ossicular involvement . Other reports describe serous otitis media , tinnitus and otorrhea as presenting symptoms . Treatment is determined by the size and location of the tumor . Small tumors or those attached solely by a thin stalk may be readily excised . However , larger or broad - based tumors must be approached with a degree of caution . Because of the frequent association of choristomas with the facial nerve , temporary or permanent palsy has been reported in 25 % of patients after tumor resection . Ossiculoplasty has been successful in correcting conductive hearing loss in approximately two thirds of patients . Because little to no tumor growth over time is usually observed , Hemangiomas and Vascular Malformations Historically , the literature on benign vascular tumors has lacked consistent nomenclature , contributing to widespread misunderstanding of these lesions . The term hemangioma has often been used to describe any vascular lesion and is commonly preceded by descriptive but confusing and nonspecific terms , such as strawberry , cavernous , and capillary . In 1982 , a new system of classification of vascular tumors was developed based upon the clinical behavior and growth characteristics of these lesions . The classification groups vascular tumors into two categories , hemangiomas and vascular malformations . Hemangiomas usually manifest during the first month of life and are characterized by a rapid growth period ( proliferative phase ) followed by a slow period of involution . Hemangiomas are categorized further on the basis of depth within the dermis into cutaneous ( ie , entirely within papillary dermis ) , subcutaneous ( ie , into the reticular dermis or subcutaneous fat ) , or compound , which contains elements of both . Less than 15 cases of isolated middle ear hemangiomas have been reported in the literature . There has been one report of an endothelial hemangioendothelioma occurring Vascular malformations are always present at birth and grow in proportion to body growth without regression . They can be arterial , capillary , venous , lymphatic , or any combination . Some have further divided these vascular malformations into low - flow lesions ( venous malformations ) and high - flow lesions ( arteriovenous malformations ) . Vascular malformations of the temporal bone are also exceedingly rare entities , comprising fewer than 1 % of all temporal bone tumors . Unfortunately , even recent otologic literature does not differentiate between these two types of lesions , which makes clinical comparisons difficult . To add a further element of confusion , some have reported that vascular lesions of the temporal bone frequently contain elements of both hemangiomas and vascular malformations . However , most vascular lesions of the temporal bones are probably subcategories of vascular malformations . Histologically , hemangiomas are characterized by endothelial hyperplasia and an increase in the number of mast cells during the proliferative phase , followed by fibrosis , fatty infiltration , decreased cellularity , and normalization of the mast cell count during involution of the lesion . In contrast , vascular malformations are collections of abnormal vessels with normal endothelium and mast cell counts . Using these histologic criteria , lesions commonly identified by the term cavernous hemangioma are more appropriately classified as vascular malformations . Alternatively , the term capillary hemangioma describes a true hemangioma , but as some authors have indicated , these have not been reported in the temporal bone . The overwhelming majority of vascular malformations manifest within the internal auditory canal or at the geniculate ganglion . In rare cases , they may arise within the middle ear . The extensive blood Patients typically present between the third and seventh decades of life . When the geniculate ganglion is the site of origin , a cranial nerve VII dysfunction ( e.g. , weakness , twitch , or both ) is nearly always present . Overall , facial nerve dysfunction is present in approximately 80 % of temporal bone vascular malformations and is usually the reason patients seek medical attention . Other symptoms noted on clinical presentation include tinnitus , conductive hearing loss ( more common with geniculate ganglion malformations ) , progressive sensorineural hearing loss ( more common with internal auditory canal Diagnosis and treatment High - resolution CT scanning and MRI reveal the lesion and provide complementary information . MRI demonstrates all tumors within the internal auditory canal and some tumors near the geniculate ganglion . The lesions appear hyperintense on T2 - weighted images and tend to be more hyperintense than vestibular schwannomas . Some geniculate ganglion lesions are difficult to visualize on MRI , but calcium deposits within the tumor can be detected on a high - resolution CT scan . Venous malformations of the geniculate region may be differentiated from other temporal bone tumors based upon radiographic appearances . A focal , enhancing lesion of the geniculate ganglion that is sessile upon the middle fossa floor , erodes bone diffusely , has irregular margins , and contains flecks of calcification is most likely a meningioma . In contrast , facial nerve schwannomas typically cause smoothly marginated expansion and tend to be less focal , extending along the fallopian canal longitudinally . The treatment of choice is surgical excision with removal of normal bony margins by drill . The choice of surgical approach depends on tumor location and size , but middle fossa , transmastoid , and translabyrinthine approaches are commonly used . Because of the destructive nature of these benign tumors , intratemporal facial nerve grafting is frequently required . Facial nerve repairs are required more often for geniculate vascular malformations than for those originating within the internal auditory canal . When facial paralysis is of recent origin or when partial function remains , the native facial nerve can often be preserved . However , in long - standing complete palsies , a graft is almost always required . Surgery is generally successful at eradicating lesions , with a low likelihood of recurrence after complete excision . Results of facial nerve function following repair are good ( i.e. , House - Brackmann grade II - IV ) except when nerve repair is delayed more than 1 year from the onset of the palsy . Approximately two thirds of patients undergoing middle fossa or transmastoid procedures can expect postoperative hearing preservation to within 10 dB of preoperative speech thresholds . 20 Langerhans Cell Histiocytosis ( Eosinophilic Granuloma ) Langerhans cell histiocytosis , previously referred to as histiocytosis X and reticuloendotheliosis , is a rare disorder characterized by the accumulation of Langerhans cells that may occur in solitary or multiple forms . The diffuse disease spectrum comprises 3 clinical entities . Eosinophilic granuloma is the mildest form and consists of multifocal bony erosions limited to the skull , long bones , ribs , vertebrae , pelvis , maxilla , and mandible . Hand - Schüller - Christian syndrome and Letterer - Siwe syndrome are the more chronic and severe forms of Langerhans cell histiocytosis , respectively , and are The underlying pathology in all 3 forms of Langerhans cell histiocytosis is the proliferation of Langerhans cells , which are histiocytes involved in cell - mediated immunity , osteoclastic activity , and eosinophilic infiltration . The cause of the abnormal proliferation is unknown , as is whether the Langerhans cells are normal or pathologic . Proposed theories of the genesis of the disease include metabolic , genetic , infectious , neoplastic , and immunologic causes . 21 Eosinophilic granuloma consists of a soft , friable , red mass containing histiocytes , eosinophils , lymphocytes , plasma cells , and multinucleated giant cells . The presence of histiocytes , with characteristic Birbeck granules ( i.e. , trilaminar rod - shaped organelles within the nuclear cytoplasm ) seen under electron microscopy , is considered diagnostic . Solitary eosinophilic granuloma most commonly appears in children older than 5 years and in young adults , in contrast to the more severe systemic forms of Langerhans cell histiocytosis , which tend to occur in infants and young children . Temporal bone lesions have been described within the lateral mastoid and petrous apex , and they may also involve the entire temporal bone . Prevalence of otologic involvement in Langerhans cell histiocytosis has been estimated from 15 - 61 % of patients and may be the sole presenting symptom in 5 - 25 % of children . The lesions typically manifest as a painful postauricular soft tissue swelling . Otorrhea , granulation tissue within the external auditory canal , and otitis externa are also common at presentation . Conductive hearing loss by either soft tissue obstruction or , less commonly , ossicular erosion may also be present . Sensorineural hearing loss from destruction of the bony labyrinth has also been described . Facial palsy may be associated with the more severe forms of Langerhans cell histiocytosis in approximately 3 % of patients . Skull and plain radiographs demonstrate destructive osteolytic lesions of the temporal bone that are commonly mistaken for symptoms of suppurative mastoiditis , cholesteatoma , or a metastatic osteolytic lesion . High - resolution CT scanning reveals a destructive lesion and is helpful in demarcating the areas of temporal bone involvement . On an MRI study , the lesion is usually hypointense on T1 - and T2 - weighted images and enhances with gadolinium . Once the diagnosis is made , treatment consists of conservative curettage followed by low - dose radiotherapy . Intralesional steroid injections have also been successful in some reported cases . When multisystem involvement is present , chemotherapy and intravenous steroids are advocated . Patients may be at risk for developing secondary acquired cholesteatoma in the setting of Langerhans cell histiocytosis and should be managed surgically to rule out recurrent disease . When the disease is limited to the temporal bone , eosinophilic granuloma typically resolves after local excision or radiation without recurrence . Surgery usually consists of curetting the bony cavity created by the tumor . However , the disease may progress to a more disseminated form , and close follow - up observation is warranted . With multisystem non - osseous involvement , the prognosis is much poorer , with the mortality rate reported at approximately 40 % . Other Tumors of the Middle Ear Primary extracranial meningiomas are rare neoplasms that occur in fourth and fifth decades of life . Although they most often affect the skin , they may occur in the middle ear , external auditory canal , or temporal bone . Histologic findings are similar to intracranial meningiomas , and the primary treatment modality is surgical excision . An endolymphatic sac tumor confined to the middle ear without apparent connection to the endolymphatic sac , as well as a lymphatic malformation isolated to the middle ear , have been reported .
|
[
"Benign Tumors",
"middle ear",
"vestibular"
] |
http://emedicine.medscape.com/article/871609-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Otolaryngology and Facial Plastic Surgery NK - Cell Lymphomas of the Head and Neck Updated : Feb 01 , 2019 Author : Benjamin Daniel Liess , MD ; Chief Editor : Arlen D Meyers , MD , MBA more . . . Sections Overview Presentation DDx Workup Treatment Medication Questions & Answers Media Gallery References Background Natural killer ( NK ) - cell lymphoma is a type of non - Hodgkin lymphoma ( NHL ) . Most NHLs ( 90 % ) are of B - cell origin . In the past , the rarity of non – B - cell malignancies and their similar morphologic findings , coupled with the unavailability of cell markers , made it impossible to establish definitive classifications of subtypes of non – B - cell NHL . This lack of knowledge also prevented clinicians from gathering meaningful information about the natural history of the disease and its prognosis . The unavailability of this information is demonstrated in previous classification systems , including the Lukes - Collins , Kiel , and Working Formulation systems , which did not identify subclasses of NK / T - cell malignancies . Advances in tumor cell biology have led to the ability to subclassify NHL via the World Health Organization ( WHO ) classification of lymphomas ( see below ) . This terminology will likely become more precise as our ability to genetically characterize these tumors improves . 1 Previous terms for NK - cell malignancies and other forms of non – B - cell NHL included lethal midline granuloma , angiocentric lymphoma , malignant granuloma , malignant midline reticulosis , and polymorphic reticulosis . These terms were based on clinical and pathologic characteristics of the diseases encountered . Controversy still exists over the normal counterpart of NK - cell lymphoma . Whether NK - cell lymphoma represents the presence of a true NK cell or merely the presence of a T cell with abnormal cell markers is under debate . In the absence of unequivocal proof of the exact lineage of NK - cell lymphoma , many investigators prefer to use the term NK / T - cell lymphoma ( NKTCL ) when classifying this condition . Further understanding of its development and identification of more specific cell markers of NK and T cells will likely resolve this The peripheral T - and NK - cell lymphomas classified by the WHO have many subclasses ( see below ) . The subgroupings , which primarily involve the head and neck region , include the nasal and nasal - type extranodal NKTCLs . The term extranodal is used because these forms of malignancies are found outside of the traditional lymph node groupings . The nasal and nasal - type NKTCLs have distinct presentations and prognoses , and they are believed to have different pathogeneses . Otolaryngologists should understand the importance of differentiating NKTCL from other similar pathologic entities found in the head and neck region ; the prognoses differ substantially . World Health Organization classification of lymphomas In the WHO lymphoma classification , B - cell neoplasms include the following : Precursor B - lymphoblastic leukemia / lymphoma Chronic lymphocytic leukemia / small lymphocytic lymphoma Lymphoplasmacytic lymphoma Plasma cell myeloma Extraosseous plasmacytoma Extranodal marginal zone B - cell lymphoma of mucosa - associated lymphoid tissue ( MALT ) Follicular lymphoma Mantle cell lymphoma Diffuse large B - cell lymphoma Intravascular large B - cell lymphoma B - cell proliferations of uncertain malignant potential include the following : Lymphomatoid granulomatosis Posttransplant lymphoproliferative disorder , polymorphic T - cell and NK - cell neoplasms include the following : Precursor T - lymphoblastic leukemia / lymphoma Blastic NK - cell lymphoma Adult T - cell leukemia / lymphoma Extranodal NKTCL , nasal type Subcutaneous panniculitislike T - cell lymphoma Mycosis fungoides Sézary syndrome Primary cutaneous anaplastic large cell lymphoma Peripheral T - cell lymphoma Angioimmunoblastic T - cell lymphoma Anaplastic large - cell lymphoma T - cell proliferations of uncertain malignant potential include the following : Lymphomatoid papulosis Hodgkin lymphoma Histiocytic and dendritic - cell neoplasms Mastocytosis Pathophysiology Extranodal NKTCL manifests in the nasal cavity . Patients with this type tend to have earlier disease ( stage I ) . However , later - stage presentations are observed , and the stage at presentation has an impact on the survival rate . Nasal NKTCLs are almost always ( > 95 % of cases ) associated with Epstein - Barr virus ( EBV ) , irrespective of the ethnicity of the patient . The exact mechanism of malignant transformation via EBV has not been clearly elucidated . 2 3 4 Extranodal nasal - type NKTCL demonstrates a predilection for the nasopharynx ( see the image below ) , palate , skin , soft tissues , orbit , gastrointestinal ( GI ) tract , and testes . Secondary lymph nodes may be involved in some cases ; a disseminated leukemic picture is even possible . Lymphomas that manifest outside of the nose have a strong association with EBV in Asian patients , but this strong association is not present in whites . Coronal ( left ) and axial ( right ) CT scans of the sinus reveal severe pansinusitis with abnormal nasopharyngeal thickening , right facial edema and right temporal bone opacification . View Media Gallery The pattern of involvement of the extranasal sites has been hypothesized to be related to the marker CD56 . CD56 represents the neural cell adhesion molecule ( NCAM ) that has been shown to have homophilic binding properties . With the skin , GI tract , and testes expressing the CD56 marker in large amounts , the neoplastic cells travel to these areas and set up foci of disease . The skin is the most common site of dissemination in NKTCL . Etiology Risk factors for NKTCL are as follows : Inherited immunodeficiencies – Klinefelter syndrome , Chédiak - Higashi syndrome , ataxia telangiectasia syndrome , Wiskott - Aldrich syndrome , and common variable immunodeficiency disease Acquired immunodeficiency diseases – Iatrogenic immunosuppression , HIV - 1 infection , and acquired hypogammaglobulinemia Autoimmune disease – Sjögren syndrome , celiac sprue , rheumatoid arthritis , and systemic lupus erythematosus Chemical or drug exposures – Phenytoin , dioxin , phenoxyl herbicides , irradiation , and prior chemotherapy or radiotherapy Association with infectious agents – EBV , human T - cell leukemia / lymphoma virus - I , and ataxia telangiectasia syndrome Epidemiology NKTCL is very rare in whites ; its prevalence is significantly higher in people of Asian descent . In Western populations , the prevalence of nasal lymphomas is estimated at 0.17 - 1.5 % of all NHLs , 45 % of which are thought to be NK - / T - cell in origin . Worldwide , NKTCL has a low prevalence , but it is much more prevalent in Asia , Mexico , and Central and South America . 5 6 7 Reported rates of nasal lymphoma in Hong Kong and South America range from 2.6 % to 8 % of all NHLs , of which 45 % are thought to represent NKTCL . Patients with NKTCL commonly present in their sixth decade of life , which is almost a decade younger than the age at which people with B - cell neoplasms present . However , the disease has been seen in both geriatric and pediatric populations . 8 9 Men are more commonly affected with the disease than women , with a male - to - female ratio of almost 3 : 1 . 8 9 6 Using the Surveillance , Epidemiology , and End Results ( SEER ) Program database , Kommalapati et al determined that between 2001 and 2014 , the US incidence of nasal NKTCL doubled , from 0.4 to 0.8 per 1,000,000 individuals . The incidence in Hispanic patients was significantly higher than that in non - Hispanic patients . 10 Prognosis Compared with other subtypes of lymphoma found in the head and neck region , NKTCL carries a much higher mortality and responds less well to traditional chemotherapy and radiotherapy regimens . 11 Overall , median survival time is reported as 12.5 months ( although the aforementioned study by Kommalapati et al reported the median overall survival time for nasal NKTCL to be 20 months , with this period varying significantly with the disease ’ s primary site and NKTCL ’ s stage at diagnosis 10 ) . Survival time for patients who present with a disseminated leukemic picture is reported to be less than 6 months . A complete response to primary treatment is reported in 56 % of patients . Overall , the 2 - year survival rate is 45 % , and the 2 - year disease - free survival ( DFS ) rate is reported at 31 % . A retrospective study by Su et al of 101 patients with extranodal NKTCL indicated that age 60 years or greater and the presence of Ann Arbor stage III / IV disease are independent risk factors for poor progression - free and overall survival . Median periods of progression - free and overall survival in the advanced - stage patients were 2.3 and 4.8 months , respectively . 12 The poor survival rates and low rates of response to treatment in NKTCL are theorized to be secondary to the CD56 cell marker and the presence of a multidrug resistance ( P - glycoprotein – positive ) phenotype . CD56 is thought to facilitate tumor cell dissemination by virtue of its binding properties . A study by Zhang et al indicated that higher levels of myeloid - derived suppressor cells ( MDSCs ) , specifically , HLA - DR CD33 + CD11b + MDSCs and CD14 monocytic MDSCs , independently predict poor disease - free and overall survival in patients with extranodal NKTL . The MDSCs were found to suppress T - cell proliferation in these patients . 13 On the other hand , a literature review by Chen et al indicated that the prognosis in extranodal NKTCL tends to be better when CD30 , a tumor necrosis factor receptor superfamily member , is expressed . The investigators reported that CD30 expression is associated with a 41 % relative decrease in hazard of death . 14 NKTCLs have a higher local relapse rate ( 21.4 % ) than do either T - cell lymphomas presenting in the nasopharynx ( 5 % ) or B - cell lymphomas presenting in the nasopharynx ( 0 % ) . Fewer recurrences in the cervical nodes are reported for NKTCLs ( 2.4 % ) than are reported for T - cell ( 10 % ) and B - cell ( 14.3 % ) malignancies . Hemophagocytic syndrome , associated with fever , marked pancytopenia , hemophagocytic histiocytes in the bone marrow , and rapid liver function deterioration , is a devastating complication of NHL . This syndrome appears to be much more common in NKTCLs . In a study involving 69 patients with early - stage extranodal nasal - type NKTCL ( 58 with stage I and 11 with stage II ) who received primary radiotherapy , high pretreatment Epstein - Barr virus ( EBV ) – DNA concentrations were associated with B symptoms , elevated lactic dehydrogenase ( LDH ) levels and a high International Prognostic Index score . 15 The investigators suggested that circulating EBV - DNA levels could serve both as a valuable biomarker of tumor load for accurate classification of early stage disease and as a prognostic factor . Similarly , a literature review by Liu et al indicated that in patients with NKTCL , circulating EBV - DNA concentrations predict patient survival and treatment response . The investigators reported that overall and progression - free survival are poorer in individuals with both a high pretreatment EBV - DNA level and a detectable posttreatment concentration . Moreover , an apparent association was found between a high pretreatment level and a decreased treatment response . 16 Clinical Presentation
|
[
"Natural killer ( NK )-cell",
"non-Hodgkin lymphoma",
"lethal midline granuloma"
] |
http://emedicine.medscape.com/article/933135-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pediatrics : General Medicine Cyclic Vomiting Syndrome Updated : Oct 31 , 2018 Author : Thangam Venkatesan , MD ; Chief Editor : Carmen Cuffari , MD more . . . Sections Overview Presentation DDx Workup Treatment Medication Tables References Background Cyclic vomiting syndrome ( CVS ) , first described in children by Samuel Gee in 1882 , is a chronic functional disorder of unknown etiology that is characterized by paroxysmal , recurrent episodes of vomiting . The pathophysiology is unknown ( see Pathophysiology and Etiology ) , but data suggest a strong genetic component in children with CVS , with evidence of mitochondrial heteroplasmies that predispose to CVS and other related disorders ( eg , migraine and chronic fatigue syndrome ) . Other theories include autonomic dysfunction and , possibly , corticotropin - releasing factor ( CRF ) because stress is known to be a trigger for these episodes . The possible role of cannabis in causing CVS has been examined , though it remains controversial . CVS is characterized by recurrent , discrete , stereotypical episodes of rapid - fire vomiting between varying periods of completely normal health ( see Presentation ) . This on - and - off stereotypical pattern of vomiting is nearly pathognomonic . Because no biochemical markers for CVS have been identified , physicians must initially look for alarming symptoms and then tailor the subsequent workup accordingly ( see Workup ) . Depending on the presenting symptoms and signs other than vomiting , different diagnostic approaches are recommended . In the absence of known pathophysiology , treatment of CVS remains empiric ( see Treatment ) . For ongoing support and information , families are encouraged to contact the Cyclic Vomiting Syndrome Association , which is an international voluntary organization that serves the needs of patients in the United States and Canada . Pathophysiology and Etiology The etiology and pathophysiology of CVS are not known . However , studies have suggested several potential brain - gut mechanisms . Migraine - related mechanisms have been proposed . 1 2 In one study , patients with CVS have a significantly higher prevalence of family members with migraine headaches ( 82 % vs 14 % of control subjects with a chronic vomiting pattern ) . Furthermore , 28 % of patients with CVS whose vomiting subsequently resolved developed migraine headaches . Approximately 80 % of affected patients with family histories positive for migraine respond to antimigraine therapy . 1 2 Mitochondrial DNA ( mtDNA ) mutations may be involved in the pathogenesis of CVS . Boles et al demonstrated that 86 % of children with CVS and neuromuscular disease had a history of migraines on the matrilineal side . In children with CVS , 2 mtDNA polymorphisms ( 16519T and 3010A ) are expressed with a high degree of frequency and may serve as a surrogate marker for predisposition to the disease . 3 The 16519T polymorphism is 6 times more common in pediatric CVS patients than in control populations . 4 The 3010A polymorphism increases the likelihood of CVS in subjects with 16519T by as much as 17 times . These mtDNA polymorphisms may account for the clustering of functional conditions and symptoms in the same individuals and families . One small ( and possibly underpowered ) study found that adult - onset CVS , unlike pediatric CVS , CVS is not associated with these polymorphisms , suggesting a degree of genetic distinction . Sympathetic hyperresponsiveness and autonomic dysfunction also appear to contribute to the pathogenesis of CVS . 5 Many associated symptoms , such as pallor , flushing , fever , lethargy , salivation , and diarrhea , are mediated by the autonomic nervous system . 6 7 8 Several studies support altered autonomic function in CVS . Rashed et al 9 and To et al 10 demonstrated heightened sympathetic cardiovascular tone in patients with CVS . Kasawinah et al reported the successful use of dexmedetomidine , an alpha2 - adrenergic agonist , to treat CVS . 11 In a small study involving 6 children with CVS , all patients had sympathetic autonomic dysfunction , affecting mainly the vasomotor and sudomotor systems . Symptoms developed during tilt testing in half of these patients , suggesting that these findings may play a role in the pathophysiology of CVS . 12 To evaluate this association with autonomic dysfunction , a cross - sectional study was performed in which the Ohio dysautonomia ( ODYSA ) questionnaire was administered to 21 patients with CVS ( 3 children ) and 46 patients with migraines . 13 The 2 patient groups had similar comorbid conditions , with fibromyalgia noted in 38 % of subjects with CVS , orthostatic intolerance in 47 % of subjects with CVS , functional dyspepsia in 9.5 % of subjects with CVS , and complex regional pain syndrome in 24 % of subjects with CVS . The main limitation of this study was that the findings were not corroborated by means of either a physical examination or standard autonomic function testing . 13 However , the findings of orthostatic intolerance are of clinical significance because the use of pharmacologic therapy ( eg , fludrocortisone and beta - blockers ) may be considered in these patients . In a prospective trial in adult CVS patients , Venkatesan et al found that most subjects with CVS ( 90 % ) had impairment of the sympathetic nervous system with postural tachycardia or sudomotor dysfunction while parasympathetic nerve function was intact . 14 In this study , 17 ( 85 % ) of 20 adult CVS subjects and 2 ( 10 % ) of 20 control subjects had abnormalities on thermoregulatory sweat testing . 14 A total of 7 ( 35 % ) patients and 1 control subject had evidence of postural tachycardia with an increase of more than 30 beats / min in heart rate ( HR ) on standing . Of the subjects , 18 ( 90 % ) had abnormal sudomotor function , postural tachycardia , or both . The HR response to deep breathing was normal in 19 ( 95 % ) subjects with CVS and 18 ( 95 % ) controls . The stress response , mediated by the hypothalamic - pituitary - adrenal ( HPA ) axis , can also potentially induce episodes of CVS . Infectious , psychological , and physical stressors are known triggers of episodes . 15 16 17 18 19 68 Sato et al documented increased levels of adrenocorticotropic hormone ( ACTH ) and cortisol , associated with extreme lethargy and hypertension , before the onset of vomiting . 20 21 22 23 Furthermore , Taché showed that central CRF induced gastric stasis , emesis , or both in animals . 24 Therefore , CRF may be a brain - gut mediator of CVS that directly connects stress and vomiting . 25 If this theory holds true , CRF receptor antagonists currently in development could theoretically ablate vomiting by blocking the CRF receptor ’ s vagally mediated actions . 26 Cannabis use in CVS has received considerable attention . Chronic marijuana use has been associated with hot showers or compulsive hot water bathing and CVS , though a cause - and - effect relation has not been confirmed . The endocannabinoid system ( ECS ) consists of the ligands 2 - AG and anandamide and the cannabinoid receptors CB1 and CB2 . This system is thought to play a role in nausea and vomiting and in coping with stress . There is considerable evidence that activation of central and peripheral CB1 cannabinoid receptors inhibits nausea and vomiting ; conversely , both nausea and vomiting are frequent adverse effects accompanying CB1 receptor antagonist use in humans . These and other data strongly suggest that that tone of the ECS regulates nausea and vomiting ; further studies are needed to explore this possibility more fully . 27 28 That CVS has a central component has been suggested by functional magnetic resonance imaging ( MRI ) studies using whole - brain seed - based analysis . Patients with CVS exhibited a distinct alteration in resting state functional connectivity involving connections from the cingulate and inferior frontal gyrus ( IFG ) , a known neural correlate of nausea . 29 In conclusion , the pathogenesis of CVS is likely to be multifactorial , with multiple genetic , autonomic , central , and environmental factors playing a role . Further studies are needed to elucidate the exact mechanisms underlying this disorder . Epidemiology United States statistics The true incidence and prevalence of CVS in the United States are unknown . In central Ohio , amid a predominantly white population , the prevalence of CVS in children ( evaluated by the sole pediatric gastroenterology referral center ) was 0.04 % . 30 International statistics On the basis of limited epidemiologic data , Cullen and MacDonald estimated the prevalence of periodic vomiting in western Australia to be 2.3 % . 6 Similarly , Abu - Arafeh and Russell observed a prevalence of 1.9 % in school - aged children in Aberdeen , Scotland . 31 Both of these figures are derived from white populations and may not accurately reflect prevalence in all races or ethnic populations . In a study performed at KEM Hospital in Pune , India , CVS accounted for 0.5 % of admissions to pediatric wards during 1998 - 2000 . In a population - based study from Ireland , the incidence of CVS was relatively high at 3.15 cases per 100,000 children . This incidence is comparable to those of other major GI diseases of childhood ( eg , Crohn disease ) in Ireland . 32 Age - , sex - , and race - related demographics The median age at onset is 4.8 years ; however , CVS has been observed in infants as young as 6 days and in adults as old as 73 years . The typical interval from onset of symptoms to diagnosis is 2.7 years . In adults , the average age of onset is 21 years and the average age of evaluation for recurrent vomiting 34 years . 8 Females show a slight predominance over males ( female - to - male ratio , 57 : 43 ) . CVS occurs in all races but seems to affect whites disproportionately . Prognosis Most published series indicate that CVS lasts an average of 2.5 - 5.5 years , resolving in late childhood or early adolescence . A few patients continue to be symptomatic through adulthood . As early as 1898 , clinicians observed that some patients went on to develop migraine headaches . That some children with CVS progress to abdominal migraines and then to migraine headaches implies that there may be a sequential progression of age - dependent manifestations of migraine . A survey by Abu - Arafeh et al found the mean ages of children with CVS , abdominal migraines , and migraine headaches to be 5.3 years , 10.3 years , and 11.5 years , respectively . 31 This finding supports the developmental progression from vomiting to abdominal pain to headache . In unpublished data , Li and Hayes determined that nearly one third of patients develop migraines after resolution of CVS and predicted that nearly 75 % would develop migraines by age 18 years . A study of 31 patients with CVS by Hikita et al found that the median overall duration of the disorder was 66 months and that 44 % of the patients seen for follow - up ( 25 patients ) developed migraine . The authors also found abnormally high adrenocorticotropic hormone and antidiuretic hormone levels among the 25 patients for whom follow - up data were available . Significant correlations between attack duration and adrenocorticotropic hormone levels and attack duration and antidiuretic hormone levels were noted . 33 Although patients are well about 90 % of the time , CVS can be medically and socially disabling . More than 50 % of patients require intravenous ( IV ) fluids , compared with less than 1 % of patients with rotavirus gastroenteritis . The average annual cost of testing , treatment , and absenteeism totals $ 17,000 . Children miss an average of 24 school days per year and often need home tutoring or , occasionally , home schooling . Additionally , because of its frequency during times of excitement , CVS has ruined many birthdays , holidays , 30 In adults , substantial morbidity is associated with CVS , perhaps because of lack of awareness and resultant delays in diagnosis . In a study of 41 CVS patients , Fleisher found that 32 % were completely disabled at the time of diagnosis . A total of 293 procedures were performed in the 41 patients , and none were indicative of organic etiology . In addition , 17 surgical procedures , including 10 cholecystectomies , appendectomies , exploratory laparotomies , a pyloroplasty , and a hysterectomy , were performed without any therapeutic benefit . Adults and children with CVS also have multiple emergency department ( ED ) visits ( see Table 1 below ) , and the diagnosis is often unrecognized . 34 Table 1 . Characteristics of Emergency Department Visits in Patients With Cyclic Vomiting Syndrome ( Open Table in a new window ) Characteristic Adults ( n = 104 ) Children ( n = 147 ) Number of ED visits per patient with CVS ( median ) 15 ( range , 1 - 200 ) 10 ( range , 1 - 175 ) Number of ED visits before diagnosis of CVS ( median ) 7 ( range , 1 - 150 ) 5 ( range , 0 - 65 ) Diagnosis not made in ED 89 ( 93 % ) 119 ( 93 % ) Diagnosis not recognized in ED in patients with established diagnosis of CVS 84 ( 88 % ) 97 ( 80 % ) Number of different EDs visited ( mean ± SD ) 4.69 ± 4.72 2.6 ± 2.42 CVS = cyclic vomiting syndrome ; ED = emergency department ; SD = standard deviation . Clinical Presentation Sections Cyclic Vomiting Syndrome Overview Presentation DDx Workup Treatment Medication Tables References
|
[
"Cyclic Vomiting",
"Syndrome"
] |
http://emedicine.medscape.com/article/948360-overview
|
Please confirm that you would like to log out of Medscape . If you log out , you will be required to enter your username and password the next time you visit . Log out Cancel Drugs & Diseases > Pediatrics : Genetics and Metabolic Disease Pyruvate Dehydrogenase Deficiency ( PDCD ) Updated : Aug 17 , 2018 Author : Richard E Frye , MD , PhD ; Chief Editor : Luis O Rohena , MD , FAAP , FACMG more . . . Sections Overview Background Pathophysiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Guidelines Medication References Background Pyruvate dehydrogenase complex ( PDC ) deficiency ( PDCD ) is one of the most common neurodegenerative disorders associated with abnormal mitochondrial metabolism . PDC metabolically converts pyruvate into acetyl - coenzyme A ( ACoA ) , one of the first steps in the citric acid cycle ( CAC ) . The CAC is a major biochemical process in the mitochondrial matrix that derives energy from several metabolic substrates , including carbohydrates , fatty acids , and amino acids . Malfunction of this cycle deprives the body of energy . In PDCD , pyruvate , which is derived from the In PDCD , progressive neurological symptoms usually start in infancy but may be evident at birth or in later childhood and very rarely in adulthood . Symptoms may include developmental delay , intermittent ataxia , poor muscle tone , abnormal eye movements , or seizures . Childhood - and adult - onset forms of this disorder are often associated with intermittent periods of decompensation but normal or mildly delayed neurological development . Therapies are suboptimal for most forms of pyruvate dehydrogenase complex deficiency ; although resolution of the lactic acidosis may occur , cessation of the underlying progressive neurological damage The key feature of this condition is gray matter degeneration with foci of necrosis and capillary proliferation in the brainstem in many but not all patients . The group of disorders that result in this pathology are termed Leigh syndrome . Defects in one of many of the mitochondrial enzymes involved in energy metabolism may demonstrate similar brain pathology . Leigh syndrome may be caused by mitochondrial defects other than PDCD . Next : Pathophysiology What to Read Next on Medscape Related Conditions and Diseases Pyruvate Carboxylase Deficiency Genetics of Pyruvate Carboxylase Deficiency Pyruvate Kinase Deficiency Fast Five Quiz : Anemia Disorders of Carbohydrate Metabolism Lactic Acidosis News & Perspective A 2 - Month - Old Boy With Yellow Eyes : Osmosis USMLE Study Question of the Week Pheochromocytoma / Paraganglioma : A Poster Child for Cancer Metabolism Possible Mechanism Identified for ' Chronic Fatigue Syndrome ' Tools Drug Interaction Checker Pill Identifier Calculators Formulary Most Popular Articles According to Endocrinologists Intermittent Fasting Plus Lower - Calorie Diet May Be Best Levothyroxine Dosing : Morning , Night , or In Between ? Interval Training May Be Best for Weight Loss Stop the Patient Blame Game : What Actually Causes Obesity ? Excess Vitamin D Linked to Kidney Damage View More Sections Pyruvate Dehydrogenase Deficiency ( PDCD ) Overview Pathophysiology Epidemiology Prognosis Patient Education Show All Presentation DDx Workup Treatment Guidelines Medication References Recommended A 2 - Month - Old Boy With Yellow Eyes : Osmosis USMLE Study Question of the Week Diseases & Conditions Pyruvate Carboxylase Deficiency
|
[
"PDCD",
"citric acid cycle",
"biochemical process"
] |
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