tag:blogger.com,1999:blog-56584617109578337962024-03-19T00:45:06.532-07:00medical ebook, journal, and article freefree journal, ebook, and medical articleNurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.comBlogger106125tag:blogger.com,1999:blog-5658461710957833796.post-76776826066120343602012-05-20T01:18:00.000-07:002012-05-20T01:22:44.598-07:00<h2 style="color: black;">
Conceptual organization of hematologic malignancies</h2>
<h2 style="color: black;">
Organization of tumors of the hematopoietic and lymphoid tissues as described by the World Health Classification 2008.
</h2>
<div class="reference">
Swerdlow, SH, Campo, E, Harris, NL, et al.
(Eds). World Health Organization Classification of Tumours of
Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.</div>
<h2 style="color: black;">
</h2>
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpXzDTN8Z_TV5CUJUEGucdilr772HvEztEg9rtFlMVkbGJFr0VoJIYoJjsHpSBP8IJv4E-nSGcOKdbBgvl4N-6HHEsa8vmr9lvZ-RA8mKBwqMhJh-kwy5py7kyAOl4K1zqEVzuit7UPAI/s1600/Organiz_heme_malignancies.gif" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpXzDTN8Z_TV5CUJUEGucdilr772HvEztEg9rtFlMVkbGJFr0VoJIYoJjsHpSBP8IJv4E-nSGcOKdbBgvl4N-6HHEsa8vmr9lvZ-RA8mKBwqMhJh-kwy5py7kyAOl4K1zqEVzuit7UPAI/s640/Organiz_heme_malignancies.gif" width="514" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Add caption</td></tr>
</tbody></table>
<br />Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-5217008479982976412012-05-19T17:15:00.004-07:002012-05-20T00:47:48.422-07:00<br />
<div class="MsoNormal" style="line-height: normal;">
<span style="font-size: large;"><b><span style="font-family: "Times New Roman","serif";">Goldman
Cardiac Risk factors</span></b></span></div>
<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Nine independent risk factors are evaluated on a point scale : </span><br />
<ul>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
Third
heart sound (S3); 11</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
Elevated
jugulovenous pressure; 11</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
Myocardial
infarction in past 6 months; 10</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
ECG:
premature arterial contractions or any rhythm other than sinus; 7</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
ECG
shows > 5 premature ventricular contractions per minute; 7</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
Age more than 70 years; 5</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
Emergency
procedure; 4</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
Intra-thoracic,
intra-abdominal or aortic surgery; 3</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
Poor
general status, metabolic or bedridden; 3</span></li>
</ul>
<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
<br />
Patients with scores >25 had a 56% incidence of death, with a 22% incidence
of severe cardiovascular complications.<br />
<br />
Patients with scores <26 had a 4% incidence of death, with a 17% incidence
of severe cardiovascular complications.<br />
<br />
Patients with scores <6 had a 0.2% incidence of death, with a 0.7%
incidence of severe cardiovascular complications.<br style="mso-special-character: line-break;" />
<br style="mso-special-character: line-break;" />
</span>Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-9383369267085797322010-06-04T00:10:00.000-07:002010-06-04T00:13:12.460-07:00Neonatology and Blood Transfusion (Developments in Hematology and Immunology, Vol. 39)<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://pixhost.ws/avaxhome/ee/de/0014deee_medium.jpeg"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 211px; height: 300px;" src="http://pixhost.ws/avaxhome/ee/de/0014deee_medium.jpeg" border="0" alt="" /></a><br /><br />Proceedings of the Twenty-Eighth International Symposium on Blood Transfusion, Groningen, NL, Organized by the Sanquin Division Blood Bank North-East, Groningen.<br />It is in many ways fitting that the last of these international symposia on blood transfusion should end with neonatal blood transfusion. The most fragile, least well studied and most at risk population requires special care and concern. We need to expand our knowledge of their unique physiology, biochemical pathways and in planning treatment and interventions, always "do no harm."<br />This proceedings of the last Groningen symposium presents a wealth of information on developmental immunology, the molecular basis of haematopoeisis, physiological basis of bleeding and thrombosis, transfusion risks and benefits and lastly, future therapies. Infants provide us with much to learn but in turn they will be the providers of (through cord blood) and the recipients of (through cellular engineering) the best that science can offer. Translational research, which has been the thrust of these presentations for 28 years, will benefit them in a way that no scientist could have ever predicted.<br /><a href="http://depositfiles.com/files/ca3zn20sx"><br />depositfiles.com</a><br /><br /><a href="http://uploading.com/files/1efcmmbb/transfusion_development.rar/%20">uploading.com</a><br /><br /><a href="http://www.megaupload.com/?d=52SBHRQS%20">megaupload.com</a>Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com1tag:blogger.com,1999:blog-5658461710957833796.post-89399002411251679792010-06-02T20:47:00.000-07:002010-06-02T20:52:20.302-07:00Lippincott's Illustrated Reviews: Pharmacology, 4th Edition<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://ecx.images-amazon.com/images/I/51ToS4ksQXL._BO2,204,203,200_PIsitb-sticker-arrow-click,TopRight,35,-76_AA300_SH20_OU01_.jpg"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 300px; height: 300px;" src="http://ecx.images-amazon.com/images/I/51ToS4ksQXL._BO2,204,203,200_PIsitb-sticker-arrow-click,TopRight,35,-76_AA300_SH20_OU01_.jpg" border="0" alt="" /></a><br />download link : <a href="http://www.amazon.com/Lippincotts-Illustrated-Reviews-Pharmacology-4th/dp/0781771552/ref=pd_sim_b_3">please click here</a><br /><span style="font-weight:bold;"><br />Product Description</span><br />Lippincott's Illustrated Reviews: Pharmacology, Fourth Edition enables rapid review and assimilation of large amounts of complex information about the essentials of medical pharmacology. Clear, sequential pictures of mechanisms of action actually show students how drugs work, instead of just telling them. As in previous editions, the book features an outline format, over 500 full-color illustrations, cross-references to other volumes in the series, and over 125 review questions. Content has been thoroughly updated, and a new chapter covers toxicology. New to this edition will be a companion Website containing all of the illustrations, fully searchable text, and an interactive question bank. NOTE: International Edition available for sales outside North America and Caribbean (ISBN: 978-1-60547-200-3) "Doody's Core Titles™ 2009."<br /><span style="font-weight:bold;"><br />Product Details</span><br /> * Paperback: 560 pages<br /> * Publisher: Lippincott Williams & Wilkins; Fourth Edition edition (July 1, 2008)<br /> * Language: English<br /> * ISBN-10: 0781771552<br /> * ISBN-13: 978-0781771559<br /> * Product Dimensions: 10.8 x 8.4 x 0.9 inches <br />download link : <a href="http://www.amazon.com/Lippincotts-Illustrated-Reviews-Pharmacology-4th/dp/0781771552/ref=pd_sim_b_3">please click here</a>Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-45205227592684084042010-06-02T05:21:00.000-07:002010-06-02T06:40:27.032-07:00Pathophysiology of Disease An Introduction to Clinical Medicine, Sixth Edition (Lange Medical Books) (Paperback)<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjalJYpUn-S2Kduy9PH-_YKd8PA4b-CoAF1PvVJp6h0b-I4aj3SlT_jMsxVeYG4UVPlQeAAbo3dSXslm-uFTTfYW2uOxzqdHJdns-sGqNYQ8wSgU2sHEfCEzdyPs13K2votNmPxMk-XWik/s1600/buku+1.jpg"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 300px; height: 300px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjalJYpUn-S2Kduy9PH-_YKd8PA4b-CoAF1PvVJp6h0b-I4aj3SlT_jMsxVeYG4UVPlQeAAbo3dSXslm-uFTTfYW2uOxzqdHJdns-sGqNYQ8wSgU2sHEfCEzdyPs13K2votNmPxMk-XWik/s400/buku+1.jpg" border="0" alt=""id="BLOGGER_PHOTO_ID_5478153430404744034" /></a><br />download link :<a href="http://www.amazon.com/Pathophysiology-Disease-Introduction-Clinical-Medicine/dp/0071621679/ref=cm_cr_pr_product_top">please click here</a><br /><br /><span style="font-weight:bold;">Review</span><br />"The book does an excellent job of integrating basic science concepts with clinical medicine. Each of the organ system chapters reviews the normal anatomy, physiology and histology, then follows with the pathophysiology, clinical findings, and pathology of the more commonly encountered disorders. Additionally there are chapters on genetic diseases, immune diseases and neoplasia which similarly link basic science principles with clinical disease entities. Each chapter contains periodic "checkpoint" questions which guide the reader to the most important concepts. Each chapter also ends with several case studies with questions and discussions, similar to those encountered on board examinations."<br /><br /><span style="font-weight:bold;">Product Description</span><br /><br /><span style="font-weight:bold;">A complete case-based review of the essentials of pathophysiology – covering all major organs and systems</span><br /><br />This trusted text introduces you to clinical medicine by reviewing the pathophysiologic basis of the signs and symptoms of 100 diseases commonly encountered in medical practice. Each chapter first describes normal function of a major organ or organ system, then turns attention to the pathology and disordered physiology, including the role of genetics, immunology, and infection in pathogenesis. Underlying disease mechanisms are described, along with their systems, signs, and symptoms, and the way these mechanisms themselves determine the most effective treatment.<br /><br />This unique interweaving of physiological and pathological concepts will put you on the path towards thinking about signs and symptoms in terms of their pathologic basis, giving you an understanding of the “whys” behind both illness and treatment.<br /><br /><span style="font-weight:bold;">Features</span><br /> * NEW full-color presentation<br /> * 111 case studies (22 new ones) provide an opportunity for you to test your understanding of the pathophysiology of each clinical entity discussed<br /> * A complete chapter devoted to detailed analyses of the cases<br /> * “Checkpoint” review questions appear throughout every chapter<br /> * Numerous tables and diagrams encapsulate important information<br /> * References for each chapter topic<br /> * NEW sections in the chapters on liver disease and inflammatory rheumatic diseases and a completely rewritten chapter on male reproductive tract disorders<br /><span style="font-weight:bold;"><br />Product Details</span><br /> * Paperback: 752 pages<br /> * Publisher: McGraw-Hill Medical; 6 edition (October 20, 2009)<br /> * Language: English<br /> * ISBN-10: 0071621679<br /> * ISBN-13: 978-0071621670<br /> * Product Dimensions: 10.9 x 8.5 x 1.2 inches<br /> * Shipping Weight: 3.3 pounds (View shipping rates and policies)<br /><br />download link :<a href="http://www.amazon.com/Pathophysiology-Disease-Introduction-Clinical-Medicine/dp/0071621679/ref=cm_cr_pr_product_top">please click here</a>Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-78373402179608976642009-10-17T05:04:00.000-07:002009-10-17T05:08:54.270-07:00Blood Supply of the Heart<span style="font-weight:bold;">Heart Structure and Blood Supply</span><br /><br />It seems odd that the tissues making up the heart must have their own separate blood supply. You might think that the torrent of blood rushing through the heart every minute would more than adequately meet the needs of the organ. The walls of the heart, however, consist of layers of specialized muscle. These walls are quite thick—the wall of the left ventricle is often over 1 inch thick. Since the lining of the heart is watertight, the blood cannot seep through the layers of muscle to provide the nourishment essential to these constantly working masses. Blood is carried through the muscle layers that form the heart wall by means of the two coronary arteries. These two small vessels branch off the aorta just after it leaves the heart and curl back across the surface of the chambers, sending twigs through the walls (Fig. 4-1).<br />The coronary arteries are so named because of the supposed resemblance to a crown or “corona†of the little arteries as they encircle the heart. These arteries divide into smaller and smaller branches, like all blood vessels in the body, until they become so small that only one blood cell at a time can move through them. At this point the vessels are called capillaries. After the blood has passed through the capillaries, and the tissues have extracted the needed oxygen, it returns by way of veins, which become larger and larger until they, like all other veins in the body, empty into the right atrium. The veins from the wall of the heart, or coronary veins, empty into the right atrium through a structure called the coronary sinus.<br />The blood supply of the tissues in the wall of the heart is not very good; thousands of people die every year because of this curious fact. Most organs and tissues of the body have a “reserve†or collateral blood supply. Each finger, for instance, has two arteries, one on each side. These arteries are connected by many cross-channels, or collateral vessels. If the artery is cut on one side, the collateral or cross-connections from the artery on the other side would probably provide sufficient blood to maintain life in the tissues of the finger. The same “safety†feature is true in most of the major areas of the body. It is not true in the wall of the heart.<br />The coronary arteries tend to be end arteries, meaning that each branch follows its own course to some area of the heart muscle with relatively few connections to other branches nearby. If one of these coronary branches is plugged by hardening or by a blood clot, the muscle that depends on it for blood will die. A form of gangrene actually sets in. (Some people's coronary arteries have many more cross-connections than others. The more of these cross-connections an individual has, the less likely he or she is to die of coronary artery disease. In 10,000 or 20,000 years the process of evolution may result in a race with a good coronary blood supply by virtue of the early death of those without it.)<br />The names of the chief branches of the coronary arteries are important because they will be used repeatedly in this book. Learn them now; they're very simple.<br />There are two main coronary arteries leading out of the aorta—the right and left coronary arteries. After about an inch, the left coronary artery divides into two principal branches. The left anterior descending branch comes down the front of the heart, roughly along the septum between the two ventricles. The circumflex branch of the left coronary artery coils around the left side and back of the heart. The right coronary artery divides into a number of branches that course through the right chambers of the heart as well as through a large part of the left ventricle.<br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiCgHfGxaMEzC7uNN-hyAvCqIFmeruDqHII8eiOELl0tdTl9sx_tFgGbTa6F88_tWgWIz2YuqRDqJwNLTPxvLXpt1sDZEFsZbhZx_m0PypbmzS-fo0Vd9VjhrHaW2ieLpOe-5MgJi3GHJo/s1600-h/4.1.bmp"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 400px; height: 356px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiCgHfGxaMEzC7uNN-hyAvCqIFmeruDqHII8eiOELl0tdTl9sx_tFgGbTa6F88_tWgWIz2YuqRDqJwNLTPxvLXpt1sDZEFsZbhZx_m0PypbmzS-fo0Vd9VjhrHaW2ieLpOe-5MgJi3GHJo/s400/4.1.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393539381184376242" /></a><br />Note: There are four coronary arteries to remember:<br />The left main coronary artery (before it divides): LMCA.<br />The right coronary artery: RCA.<br />The left anterior descending branch of the left main coronary artery: LAD.<br />The circumflex branch of the left main coronary artery: LCA or LCirc.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com1tag:blogger.com,1999:blog-5658461710957833796.post-33978501867064732712009-10-17T04:59:00.000-07:002009-10-17T05:04:08.736-07:00Pumping Action of the Heart<span style="font-weight:bold;">Blood Flow Through the Heart</span><br />Blood is pumped through the chambers of the heart and out through the great vessels by a simple squeezing action of the heart chambers. You have probably seen a bulb syringe with a glass nozzle like the one pictured in Figure 3-1. Suppose it is full of water. If you squeeze forcefully, expelling the water, you would be imitating the contraction of a heart chamber. This is called systole (sis-toe-lee). After the syringe had been emptied, imagine that you placed the nozzle in a container of water and let the bulb expand so that it filled. This is what a heart chamber does when it relaxes and fills with blood. The movement is called diastole (die-as-toe-lee). You can picture the process by holding your left hand over your right, fists clenched. If your left hand represents the atria, your right hand will represent the ventricles. Now clench your left fist (the atria) while opening your right fist (the ventricles). This is what happens during atrial systole when the atria are pumping blood down into the ventricles. Next, open your left fist and clench your right. This is what happens during ventricular systole when the ventricles are pumping blood out into the two great arteries and the atria are refilling. By alternately opening and clenching your two fists you can similate the coordinated beat of the heart.<br />Note: The cycle of a heartbeat, in other words, goes through these stages:<br />Atrial systole: The atria contract, forcing the blood down into the ventricles.<br />Ventricular systole: The ventricles contract, forcing the blood out the pulmonary artery and aorta.<br />Atrial diastole: This starts during ventricular systole as the atria begin refilling with blood from the great veins.<br />Ventricular diastole: This takes place during atrial systole as blood from the atria fills the ventricles.<br /><br />The rhythmic contraction and relaxation of the ventricles does the work of pumping the blood: atrial contraction is much less important and, in fact, many patients live for years without any pumping action from the atria. If the ventricles stop beating, death follows within minutes.<br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiiWGc6_JhVVIu_cboAcP9ZflQNO-ZBbhQQvMXeoqTG4SCdjWHA5E8JB9bBRheU-Mqf1beonryO6qYV_F3MkWjuXC0hwww8EIqtQ0d_Uri30d6k6q5ZyelmuaKURZzxSjnLek_be5USWbg/s1600-h/3.1.bmp"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 400px; height: 356px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiiWGc6_JhVVIu_cboAcP9ZflQNO-ZBbhQQvMXeoqTG4SCdjWHA5E8JB9bBRheU-Mqf1beonryO6qYV_F3MkWjuXC0hwww8EIqtQ0d_Uri30d6k6q5ZyelmuaKURZzxSjnLek_be5USWbg/s400/3.1.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393537775713198178" /></a>Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-51418992777219601452009-10-17T04:26:00.000-07:002009-10-17T05:04:16.966-07:00Valves of the Heart<span style="font-weight:bold;"><br />Valve Structure and Function</span><br />Like any pump, the heart has valves to keep the blood flowing in the right direction. Proper function of these small flaps of tissue spells the difference between good health and sickness, and often between life and death.<br />Almost everyone is familiar with the word valve. Very few people, however, really know what a valve is or what it does. Imagine pumping water through a pipe with a farm pump. To keep the water from flowing back toward the pump between strokes, you could place a valve in the pipe leading out of the pump. The simplest kind of valve would consist of two semicircular flaps hinged to open only one way—forward with the flow of water. These flaps would close the pipe completely when they swung shut. When the water flowed forward from the pump, the flaps of the valve would swing open allowing the water to pass. Between strokes the valves would snap shut if any water attempted to flow back toward the pump (Fig. 2-1).<br /><span style="font-weight:bold;"><br />Note: The heart is equipped with four sets of valves that function on this simple principle:<br />tricuspid valve<br />mitral valve<br />pulmonic valve<br />aortic valve</span><br />The valves between the atria and ventricles are called the atrioventricular (AV) valves. The AV valve leading into the right ventricle has three flaps and is called the tricuspid valve (a cusp is a valve flap or leaflet).<br />The AV valve that swings into the left ventricle is called the mitral valve. (It has two cusps and therefore looks something like a bishop's miter.)<br />Each of the outlet valves from the ventricles has three cusps. The valve at the entry to the pulmonary artery is called the pulmonic valve. The valve at the entry to the aorta is called the aortic valve.<br />As stated, an AV valve is located between each atrium and ventricle (Fig. 2-2). This valve opens downward into the ventricle. During diastole, or relaxation, the valves swing open, allowing the blood to flow down into the ventricles. When the ventricles contract, these valves snap shut, preventing any blood from flowing back up into the atria.<br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5aJnhWK3SH06Qy98_HAZz6Y5tELJ29sAbOssUnCXZlX7FYwLLGqwPpQSKqLa5nkpDGNcgHpb9771Sgrf7TcIQcCswpnXwWRJQio0hTaKN5faFfIypt_6CH79t1dFBTIMrffO9KTBgwEg/s1600-h/2.3.bmp"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 320px; height: 285px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5aJnhWK3SH06Qy98_HAZz6Y5tELJ29sAbOssUnCXZlX7FYwLLGqwPpQSKqLa5nkpDGNcgHpb9771Sgrf7TcIQcCswpnXwWRJQio0hTaKN5faFfIypt_6CH79t1dFBTIMrffO9KTBgwEg/s320/2.3.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393530494896018002" /></a><br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEje3PFgXHt85geACu0o13HxxCh7L_FzfSb74p2AmdnilOX7KI9LvkUexA6b97vzY9T0_P3tfLuTsqEfs68xC8PE9y2860oDnHUoOSwZa8JjcqUQtsNgUc7eDulxZpZkEm7gMczMeG0ApgU/s1600-h/2.2.bmp"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 320px; height: 285px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEje3PFgXHt85geACu0o13HxxCh7L_FzfSb74p2AmdnilOX7KI9LvkUexA6b97vzY9T0_P3tfLuTsqEfs68xC8PE9y2860oDnHUoOSwZa8JjcqUQtsNgUc7eDulxZpZkEm7gMczMeG0ApgU/s320/2.2.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393530487006246050" /></a><br /><br />A valve is also located at the outlet from each ventricle into the great vessel leaving the chamber. When the ventricles contract, these valves are forced open; the blood rushes into the pulmonary artery and the aorta. When the ventricles relax, the valves close, shutting off any backward flow into the ventricles.<br />If the heart is to function efficiently, these valves must be absolutely watertight, or more properly, bloodtight. Further, they must open freely and widely to let the blood flow forward with the pumping action of the heart. If the valves leak or if they are partly closed by adhesions or hardening, the heart works against a mechanical load, often an impossible and fatal load, as will be discussed in later chapters.<br />Layers of the Heart<br />The heart does not simply hang freely in the chest cavity; around it is a loose protective sack of tissue called the pericardium. The heart lies inside this sack, which is loose enough to permit the heart to beat easily. Picture a turnip held in a heavy, double thickness plastic bag. This is about the way the heart looks inside the pericardium (Fig. 2-3).<br />If the pericardium is cut open, the surface of the heart itself appears shiny and reddish in color. You can actually peel away a thin, shiny membrane from the outer surface of the heart. This membrane is called the epicardium. The mass of the heart is muscle; under the epicardium is a thick layer of muscle called the myocardium, which forms the actual working part of the heart. The myocardium is thickest in the left ventricle; it is thinnest in the atria. The cells in the myocardium are a specialized type of muscle, different from anything else in the body.<br />The inside of the heart, or cavity, is lined with another smooth, shiny membrane much like the inside surface of the cheek. This thin membrane, called the endocardium, covers the inside of the chambers of the heart. It also covers the heart valves and the small muscles associated with the opening and closing of these valves.<br /><br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpY-B-jeOUGgSTD-C1LS_QOb4hGOcm3-wycU_i8FjWJMnsaBRqBLrli6RaAvntCAY7vhOYAoTzbNSxyjuBIuw-JblmL56nUckJ6dYgRK6kvLpSUScqBYvU8VGjKYUU6zQVRfhK0RFTnjk/s1600-h/2.1.bmp"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 320px; height: 218px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpY-B-jeOUGgSTD-C1LS_QOb4hGOcm3-wycU_i8FjWJMnsaBRqBLrli6RaAvntCAY7vhOYAoTzbNSxyjuBIuw-JblmL56nUckJ6dYgRK6kvLpSUScqBYvU8VGjKYUU6zQVRfhK0RFTnjk/s320/2.1.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393530474861492770" /></a>Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-82200457847705897252009-10-15T21:06:00.001-07:002009-10-15T23:26:49.603-07:00Structure and Function of the Normal HeartBefore you begin to learn about heart disease, you must learn how the normal heart is constructed and how it functions. This is easier than you might think, because the heart is a surprisingly simple organ. An hour's easy reading will give you all the information you need to begin.<br /><span style="font-weight:bold;">The Chambers of the Heart and their Connections</span><br />The heart is a hollow organ divided into four chambers, two on the top and two on the bottom (Fig. 1-1). Study this simple diagram until you know it as well as your own name: it's basic to everything else in the book.<br />The top two chambers are thin-walled structures that act primarily as holding chambers for the blood. They are called atria. This is the plural of the Latin word atrium, meaning “anteroom†or “porch,†and, in fact, these chambers do act as entryways to the great chambers below. The ventricles are large, thick-walled chambers that do the real work of pumping the blood. (This name comes from the Latin ventriculum, meaning a “cavity†or “pouch.â€)<br />Look again at Figure 1-1 and note the wall, or septum, that divides the left atrium from the right atrium and the left ventricle from the right ventricle. This wall of tissue is much like the septum in your nose that separates the two nostrils. The important thing to remember about the heart's septum is that it is absolutely watertight, or, more properly, “bloodtight.†Normally, no blood can pass through this septum from one side to the other. (It took the human race about 4,000 years to discover this simple fact. The ancient Greeks and Romans were convinced that blood somehow oozed through the septum from one side to the other. It doesn't.)<br />Physicians commonly refer to the right atrium and right ventricle together as the right heart and to the left atrium and left ventricle as the left heart.<br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjS-F3nPheb6OldZNzIlziNhxc0inUvAngB69OnCbyGJ4lO8yJzxzmCUEdaWkQ5zFMwxjPs-hDRXkDEpH3xgy_8SJCE9xbYhdA4gTaYjpUImVT6pzEkjHqPy64U_htwFDolFXlikgDcg7c/s1600-h/1.2.bmp"><img style="float:left; margin:0 10px 10px 0;cursor:pointer; cursor:hand;width: 200px; height: 136px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjS-F3nPheb6OldZNzIlziNhxc0inUvAngB69OnCbyGJ4lO8yJzxzmCUEdaWkQ5zFMwxjPs-hDRXkDEpH3xgy_8SJCE9xbYhdA4gTaYjpUImVT6pzEkjHqPy64U_htwFDolFXlikgDcg7c/s200/1.2.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393053468399665762" /></a><br /><br /><span style="font-weight:bold;">The Motion of the Blood Through the Heart</span><br />The function of the heart can be described as a simple pump that forces blood forward by squeezing, in exactly the way that a bulb syringe forces out fluid when it's compressed.<br />The alert reader will at once ask, “If the blood doesn't flow from one side of the heart to the other through the septum, how does it ever move forward?†The answer to that question eluded philosophers and scientists until the English medical doctor William Harvey, in the early seventeenth century, discovered the simple circuit that is the basis of all modern cardiology.<br />The blood moves from the right heart to the left heart by way of the lungs. In other words, the right heart pulls the blood out of the veins and pumps it into the lungs. The left heart pulls the blood out of the lungs and pumps it on to the body.<br />(The outraged squalling of Harvey's contemporaries and the hoots of disbelief that greeted this profound truth are amusing to contemplate; they are also a little frightening.) Thus the heart and lungs together form a machine that takes oxygen out of the air, dissolves it in the blood, and pumps it to the tissues of the body.<br /><br /><span style="font-weight:bold;">Back to Structure: How Are the Heart and Lungs Connected?</span><br />The blood that has completed its course through the tissues of the body flows back to the heart through the veins. The veins come together, growing larger, like streams combining into a river, until they end in two great veins that empty into the top and bottom of the right atrium. The word cava in Latin refers to something large or cavelike; hence the vein that empties into the top of the right atrium is called the superior vena cava, or, literally, “large top vein.†The great vein that empties into the bottom of the right atrium is logically called the inferior vena cava (Fig. 1-2). Blood flows from the right atrium down into the right ventricle and out to the lungs through the pulmonary artery (Fig. 1-3).<br /><br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgkL9VP26pLFwTWPR-eCpqIgpkzxEbLCu3oMc_WAD2jUWnndRAa1DrMTvoowWluuf_GBcvoVsH6NAF6Z8m4T769fO19Qvc5JtfRfqmqTLdg5C3W26A3-dSfKUS24fUq5iolMiEQT6cNGVU/s1600-h/1.1.bmp"><img style="float:left; margin:0 10px 10px 0;cursor:pointer; cursor:hand;width: 200px; height: 132px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgkL9VP26pLFwTWPR-eCpqIgpkzxEbLCu3oMc_WAD2jUWnndRAa1DrMTvoowWluuf_GBcvoVsH6NAF6Z8m4T769fO19Qvc5JtfRfqmqTLdg5C3W26A3-dSfKUS24fUq5iolMiEQT6cNGVU/s200/1.1.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393049333294650274" /></a><br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgN4sf9pyInq6Aqb7l4AdtXNTq8E9x8hd960zKAQPMUM94A46BAELt7Po5aUSIlBlJY1RxGDG76KmTklw7n0LFrGMLk8QFdDUbyZJYLGpuF52MWEonHGOUZfWSbd3El6LIlsVFTjrJziPQ/s1600-h/1.3.bmp"><img style="float:left; margin:0 10px 10px 0;cursor:pointer; cursor:hand;width: 200px; height: 136px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgN4sf9pyInq6Aqb7l4AdtXNTq8E9x8hd960zKAQPMUM94A46BAELt7Po5aUSIlBlJY1RxGDG76KmTklw7n0LFrGMLk8QFdDUbyZJYLGpuF52MWEonHGOUZfWSbd3El6LIlsVFTjrJziPQ/s200/1.3.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393073464737270674" /></a><br /><br />Within the lungs, the pulmonary artery branches into ever smaller arteries until it ends in a mass of capillaries—tiny vessels just wide enough to let one blood cell through at a time (Fig. 1-4). After the blood has been oxygenated it flows back to the heart through the four veins that empty into the left atrium (Fig. 1-5). Since these veins flow from the lungs to the heart they are called the pulmonary veins.<br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7NZ0uMKn1xLhYKO1uj4vVzehvoXwQBsbil7iTniF030bbp35IIuC8vFcWJr8JlEOilvgae7bH0st1zK-s_K-LpsrWfJzPVVddOUSOv3QoKxyQ6puLNNSA1toF9RHbMHX2AYqHO-aH3Ts/s1600-h/1.4.bmp"><img style="float:left; margin:0 10px 10px 0;cursor:pointer; cursor:hand;width: 200px; height: 136px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7NZ0uMKn1xLhYKO1uj4vVzehvoXwQBsbil7iTniF030bbp35IIuC8vFcWJr8JlEOilvgae7bH0st1zK-s_K-LpsrWfJzPVVddOUSOv3QoKxyQ6puLNNSA1toF9RHbMHX2AYqHO-aH3Ts/s200/1.4.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393057993237218914" /></a><br /><br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhfExcA9IYll9iUl8WO7dlVSBancx9QfCNjBoobOw_ySTDG63Z0q7MmhqI2Qnar6Ar7neYQm5qLrPQYW9lIfEqIC9sI6aRft3SldbjYAr00T_sQY5HDUMRyimcJ0TcWkEN7ON-V3bYbLOQ/s1600-h/1.5.bmp"><img style="float:left; margin:0 10px 10px 0;cursor:pointer; cursor:hand;width: 200px; height: 136px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhfExcA9IYll9iUl8WO7dlVSBancx9QfCNjBoobOw_ySTDG63Z0q7MmhqI2Qnar6Ar7neYQm5qLrPQYW9lIfEqIC9sI6aRft3SldbjYAr00T_sQY5HDUMRyimcJ0TcWkEN7ON-V3bYbLOQ/s200/1.5.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393076755933094626" /></a><br /><a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPnPO1ci4fIA4q_iRgd5jWFZDH7IR_bWZKqHDcOiRiENmHfHPo3uKVX1neuG1erkwZ2RhSSf7yLcczgvG9sfixDkXFSQtws8g91JT6R7aFVjdaTVoYl2QVxamioYbDAQOw8Sxy36Kr2bM/s1600-h/1.6.bmp"><img style="float:left; margin:0 10px 10px 0;cursor:pointer; cursor:hand;width: 200px; height: 136px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPnPO1ci4fIA4q_iRgd5jWFZDH7IR_bWZKqHDcOiRiENmHfHPo3uKVX1neuG1erkwZ2RhSSf7yLcczgvG9sfixDkXFSQtws8g91JT6R7aFVjdaTVoYl2QVxamioYbDAQOw8Sxy36Kr2bM/s200/1.6.bmp" border="0" alt=""id="BLOGGER_PHOTO_ID_5393079043462003874" /></a><br />From the left atrium, blood flows down into the left ventricle and then out the aorta to the body (Fig. 1-6).<br />You must be thoroughly familiar with this circuit and with the names and function of the great vessels of the heart and lungs. The great vessels of the heart is the term used to include both arteries and veins.<br />Note: The great vessels of the heart are as follows:<br /><span style="font-weight:bold;">The superior and inferior vena cavae, that empty all the blood from the body into the right atrium.<br />The pulmonary artery, which carries blood from the right ventricle to the lungs.<br />The pulmonary veins, which carry oxygenated blood from the lungs to the left atrium.<br />The aorta, or great artery, which carries the oxygenated blood out of the left ventricle to the body.<span style="font-style:italic;"></span></span>Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-53438700173871238482009-02-11T23:33:00.000-08:002009-02-11T23:47:07.498-08:00Pediatric History and Physical Examination History<span style="font-weight:bold;">Identifying Data:</span> Patient's name; age, sex. List the<br />patient’s significant medical problems. Name and<br />relationship to child of informant (eg, patient, parent, legal<br />guardian).<br /><span style="font-weight:bold;">Chief Complaint:</span> Reason given for seeking medical care<br />and the duration of the symptom(s).<br /><span style="font-weight:bold;">History of Present Illness (HPI)</span>: Describe the course of<br />the patient's illness, including when it began and the<br />character of the symptom(s); aggravating or alleviating<br />factors; pertinent positives and negatives. Past diagnostic<br />testing.<br /><span style="font-weight:bold;">Past Medical History (PMH):</span> Past diseases, surgeries,<br />hospitalizations; medical problems; history of asthma.<br /><span style="font-weight:bold;">Birth History:</span> Gestational age at birth, whether preterm,<br />obstetrical problems.<br />Developmental History: Motor skills, language<br />development, self-care skills.<br /><span style="font-weight:bold;">Medications:</span> Include prescription and over-the-counter<br />drugs, vitamins, herbal products, homeopathic drugs,<br />natural remedies, nutritional supplements.<br /><span style="font-weight:bold;">Feedings:</span> Diet, volume of formula per day.<br />Immunizations: Up-to-date?<br /><span style="font-weight:bold;">Drug Allergies:</span> Penicillin, codeine?<br /><span style="font-weight:bold;">Food Allergies:</span><br /><span style="font-weight:bold;">Family History:</span> Medical problems in family, including the<br />patient's disorder. Asthma, cancer, tuberculosis, HIV,<br />diabetes, allergies.<br /><span style="font-weight:bold;">Social History:</span> Family situation, living conditions,<br />alcohol, smoking, drugs. Level of education.<br /><span style="font-weight:bold;">Review of Systems (ROS)</span>: General: Weight loss or weight gain, fever, chills, fatigue, night sweats. Skin: Rashes, skin discolorations. Head: Headaches, dizziness, seizures. Eyes: Visual changes. Ears: Tinnitus, vertigo, hearing loss. Nose: Nose bleeds, nasal discharge. Mouth and Throat: Dental disease, hoarseness, throat pain. Respiratory: Cough, shortness of breath, sputum (color and consistency). Cardiovascular: Dyspnea on exertion, edema, valvular disease. Gastrointestinal: Abdominal pain, vomiting, diarrhea, constipation. Genitourinary: Dysuria, frequency, hematuria. Gynecological: Last menstrual period (frequency, duration), age of menarche; dysmenorrhea, contraception, vaginal bleeding, breast masses. Endocrine: Polyuria, polydipsia. Musculoskeletal: Joint pain or swelling, arthritis, myalgias. Skin and Lymphatics: Easy bruising, lymphadenopathy. Neuropsychiatric: Weakness, seizures. Pain: Quality (sharp/stabbing, aching, pressure), location, duration<br /><br /><span style="font-weight:bold;">Physical Examination</span><br /><span style="font-weight:bold;">General appearance:</span> Note whether the patient looks “ill,”<br />well, or malnourished.<br /><span style="font-weight:bold;">Physical Measurements:</span> weight, height; head<br />circumference if less than 36 months, body mass index<br />(BMI). Plot on age-appropriate growth charts.<br /><span style="font-weight:bold;">Vital Signs:</span> Temperature, heart rate, respiratory rate,<br />blood pressure.<br /><span style="font-weight:bold;">Skin:</span> Rashes, scars, moles, skin turgor, capillary refill (in<br />seconds).<br /><span style="font-weight:bold;">Lymph Nodes</span>: Cervical, axillary, inguinal nodes: size,<br />tenderness.<br /><span style="font-weight:bold;">Head</span>: Bruising, masses, fontanels.<br /><span style="font-weight:bold;">Eyes:</span> Pupils: equal, round, and reactive to light and<br />accommodation (PERRLA); extra ocular movements<br />intact (EOMI). Funduscopy (papilledema, hemorrhages,<br />exudates).<br /><span style="font-weight:bold;">Ears:</span> Acuity, tympanic membranes (dull, shiny, intact,<br />infected, bulging).<br /><span style="font-weight:bold;">Mouth and Throat:</span> Mucous membrane color and<br />moisture; oral lesions, dentition, pharynx, tonsils.<br /><span style="font-weight:bold;">Neck:</span> Thyromegaly, lymphadenopathy, masses.<br /><span style="font-weight:bold;">Chest:</span> Equal expansion, rhonchi, crackles, rubs, breath<br />sounds.<br /><span style="font-weight:bold;">Heart:</span> Regular rate and rhythm (RRR), first and second<br />heart sounds (S1, S2); gallops (S3, S4), murmurs (grade<br />1-6), pulses (graded 0-2+).<br /><span style="font-weight:bold;">Breast:</span> Discharge, masses; axillary masses.<br /><span style="font-weight:bold;">Abdomen:</span> Bowel sounds, bruits, tenderness, masses;<br />hepatomegaly, splenomegaly; guarding, rebound,<br />percussion note (tympanic), suprapubic tenderness.<br /><span style="font-weight:bold;">Genitourinary:</span> Inguinal masses, hernias, scrotum,<br /><span style="font-weight:bold;">testicles.<br />Pelvic Examination:</span> Vaginal mucosa, cervical discharge,<br />uterine size, masses, adnexal masses, ovaries.<br /><span style="font-weight:bold;">Extremities:</span> Joint swelling, range of motion, edema<br />(grade 1-4+); cyanosis, clubbing, edema (CCE);<br />peripheral pulses.<br /><span style="font-weight:bold;">Rectal Examination:</span> Sphincter tone, masses, fissures;<br />test for occult blood<br /><span style="font-weight:bold;">Neurological:</span> Mental status and affect; gait, strength<br />(graded 0-5), sensation, deep tendon reflexes (biceps,<br />triceps, patellar, ankle; graded 0-4+).<br /><span style="font-weight:bold;">Labs:</span> Electrolytes [sodium, potassium, bicarbonate,<br />chloride, blood urea nitrogen (BUN), creatinine], CBC<br />(hemoglobin, hematocrit, WBC count, platelets,<br />differential); X-rays, ECG, urine analysis (UA), liver<br />function tests (LFTs).<br /><span style="font-weight:bold;">Assessment (Impression):</span> Assign a number to each<br />problem and discuss separately. Discuss differential<br />diagnosis and give reasons that support the working<br />diagnosis; give reasons for excluding other diagnoses.<br />Plan: Describe therapeutic plan for each numbered<br />problem, including testing, laboratory studies,<br />medications.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-17216677768933881092009-02-11T06:56:00.000-08:002009-02-11T06:59:52.557-08:00HYPERBILIRUBINEMIA<span style="font-weight:bold;">DEF:</span> Elevated serum bilirubin.<br /><span style="font-weight:bold;">ETIOL:</span> In the first 3 to 4 postnatal days, healthy term infants can experience a physiologic increase in unconjugated serum bilirubin from cord levels of 1.5 mg/dL or less at birth to a mean value of 6.5 ± 2.5 mg/dL, with means of 7.3 ± 3.9 mg/dL and 5.7 ± 3.3 mg/dL for breast-fed infants and formula-fed infants, respectively. Although most new-borns have hyperbilirubinemia by adult standards, physiologic jaundice is linked to normal development and is usually benign and self-limited. It arises from a developmental delay in the conjugation and excretion of bilirubin; thus, preterm infants can have maximum serum bilirubin levels 30% to 50% higher than term babies, with elevated levels persisting for 6 to 7 days postnatally. Unconjugated or indirect hyperbilirubinemia is also caused by isoimmune hemolytic disease (e.g., ABO, Rh, or minor blood group incompatibilities); structural or metabolic abnormalities of RBCs (e.g., G6PD deficiency, hereditary spherocytosis); hereditary defects in bilirubin conjugation (e.g., Crigler-Najjar syndrome, Gilbert disease); bacterial sepsis; poly-cythemia; hypothyroidism; hemorrhage/hematoma; and breast milk jaundice. Conjugated, or direct, hyperbilirubinemia can be caused by congenital biliary atresia, extrahepatic biliary obstruction, neonatal hepatitis, inspissated bile syndrome, postasphyxia, a1-antitrypsin deficiency, and neonatal hemosiderosis.<br /><span style="font-weight:bold;">CLIN: </span>Jaundice in the first day of life is pathologic and mandates a thorough evaluation. Neonates who are not clinically jaundiced do not require routine bilirubin level determination. Visible cutaneous and scleral jaundice in the newborn is noted when the bilirubin level exceeds 7 to 8 mg/dL. Jaundice progresses from the head downward with increaseing severity of hyperbilirubinemia (i.e., scleral and facial icterus, 6 to 8 mg/dL; shoulder and trunk, 8 to 10 mg/dL; lower body, 10 to 12 mg/dL;generalized, > 12 to 15 mg/dL). When visible jaundice is detected, the rapidity of onset, the presence of blood group incompatibilities between mother and infant, the presence of hematomas or signs of infection, the method of feeding, and the duration and clinical course of jaundice beyond the third day should be noted. Daily inspection of the baby, undressed and in adequate light, is required for monitoring the progression of jaundice. A thorough abdominal examination includes palpation of the liver and spleen to evaluate for hepatosplenomegaly. Clinical manifestations of bilirubin toxicity include opisthotonos, extensor rigidity, tremors, oculomotor paralysis, and hearing loss (i.e., manifestations of basal ganglia and cranial nerve involvement). Fatal cases in the new-born period are characterized by a loss of the suck response and lethargy, followed by hyperirritability, seizures, and death.<br />STUDIES: A serum bilirubin concentration is obtained when significant visible jaundice is detected on the physical examination. When the indirect bilirubin is ³10 mg/dL and the calculated rate of increase exceeds 0.2 mg/dL/hour, repeat levels should be determined every 12 hours until the levels stabilize or a clear indication for treatment exists. Important studies to review include maternal blood type, infant's blood type, Coombs tests, hematocrit, hemoglobin, reticulocyte count, RBC indices, and RBC smear. Elevation of direct bilirubin (above 1.5 to 2.0 mg/dL) should prompt evaluation for intrinsic liver disease or biliary tract obstruction.<br /><span style="font-weight:bold;">TX: </span>Most cases of neonatal hyperbilirubinemia are developmental, benign, and self-limited, and therefore can be managed with observation, serial bilirubin determinations, and reassurance. For more severe or complicated cases, a specific diagnosis should be sought after initial stabilization of the neonate. Phototherapy can be used to stabilize indirect hyperbilirubinemia resulting from any cause and is generally used to manage hyperbilirubinemia of greater than 15 to 20 mg/dL. When the levels of bilirubin exceed 25 to 30 mg/dL or are rising rapidly in association with hemolysis, exchange transfusion (with phototherapy) is the treatment of choice. Hyperbilirubinemia occurring within the first 3 to 5 days of life in breast-fed infants may be a result of infrequent feedings and/or delayed production of adequate milk (breast-feeding jaundice); continued, frequent feedings usually lead to resolution. Prolonged hyperbilirubinemia in breast-fed infants may be caused by specific factors in breast milk (breast milk jaundice) and resolves with temporary cessation of nursing (24 to 48 hours); serum bilirubin level usually declines promptly (2 to 4 mg/dL), and nursing is subsequently resumed with little or no further increase in bilirubin.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-15105457624211447032009-02-11T06:47:00.000-08:002009-02-11T06:53:24.099-08:00HEPATITIS<span style="font-weight:bold;">DEF:</span> Infectious or idiopathic inflammation of the liver.<br /><span style="font-weight:bold;">ETIOL:</span> Neonatal hepatitis can be caused by a variety of infectious agents, including cytomegalovirus (CMV), rubella, reovirus type 3, herpes simplex, herpes zoster, herpesvirus type 6, adenovirus, enteroviruses, parvovirus B19, hepatitis viruses, human immunodeficiency virus, bacterial sepsis (gram-negative rods, staphylococci, streptococci), syphilis, listeriosis, tuberculosis, and toxoplasmosis. Idiopathic neonatal hepatitis describes neonatal cholestatic liver disease for which all other known causes, including metabolic, infectious, and extrahepatic obstruction, have been ruled out. The incidence of idiopathic neonatal hepatitis is 1 in 5,000 births and accounts for 50% of cases of prolonged neonatal jaundice.<br /><span style="font-weight:bold;">CLIN/STUDIES/TX:</span> The history should focus on maternal infection during pregnancy and delivery and family history of pediatric liver disease. The major types of neonatal hepatitis are as follows:<br />Idiopathic: More common in premature or small-for-gestational-age (SGA) infants. Fifty percent have jaundice in the first week of life. Hepatosplenomegaly is common. One-third of these infants fail to thrive. Acholic stools may or may not be present. Radionuclide hepatobiliary imaging shows slow liver uptake with positive intestinal excretion. Liver histology is variable, with inflammation, hepatocellular unrest, multinucleated giant cells, and extramedullary hematopoiesis. Diagnosis is made through exclusion of other etiologies, including biliary atresia. Therapy is directed at addressing the malabsorptive consequences of cholestasis, which include malnutrition, growth retardation, fat-soluble vitamin deficiencies, and calcium deficiency.<br />Toxoplasmosis: Sixty percent have hepatomegaly, and 40% have hyperbilirubinemia. Hepatic pathology is nonspecific and includes mononuclear periportal inflammation and canalicular bile stasis. Diagnosis is made serologically or through identification of the parasite in cerebrospinal fluid (CSF) sediment. Antiparasitic therapy (pyrimethamine and sulfadiazine) may arrest disease progression.<br />Rubella: Sixty-five percent have hepatomegaly, and 15% have jaundice. Clinical presentation and hepatic pathology are nonspecific. Elevated aspartate aminotransferase (AST) and alanine amino transferase (ALT) levels may occur in addition to acholic stools. Progressive hepatic disease, including fibrosis and failure, is uncommon. No specific therapy is indicated.<br />Cytomegalovirus (CMV): Hepatosplenomegaly, jaundice, and elevated AST and ALT levels may occur. Liver biopsy shows focal areas of hepatocyte necrosis with portal inflammation composed of lymphocytes and neutrophils. Intranuclear viral inclusions are more commonly noted in bile duct epithelia than in hepatocytes. Giant cell transformation, bile stasis, and extramedullary hematopoiesis may be seen. Diagnosis is made through culture of the organism from urine or tissue. Progression to severe chronic liver disease is rare. Severe disease may be treated with ganciclovir.<br />Herpes Simplex: Jaundice and massive hepatic necrosis with liver failure may occur. Coxsackievirus and echovirus (types 11, 14, and 19) infection may present similarly. Diagnosis is made through viral isolation and serology. Documented infection is treated with adenine arabinoside or acyclovir.<br />Syphilis: Eighty percent have hepatomegaly, and 40% are jaundiced. Biopsy may show extramedullary hematopoiesis, parenchymal or portal inflammatory infiltrates, and granulomatous lesions. Although spirochetes may be seen, the diagnosis is typically made by serologic studies. Although penicillin is essential for the therapy of infants infected with syphilis, it may exacerbate syphilitic hepatic disease.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-6110127586331184162009-02-11T06:45:00.000-08:002009-02-11T06:47:31.523-08:00BRONCHOPULMONARY DYSPLASIA (BPD)<span style="font-weight:bold;">DEF:</span> Chronic lung disease characterized by persistent tachypnea, dyspnea, hypoxemia, and hypercarbia in neonates surviving hyaline membrane disease.<br /><span style="font-weight:bold;">ETIOL: </span>BPD occurs in neonates with a history of pulmonary immaturity and acute lung injury who have been treated with ventilatory support. The premature lung is believed to be particularly susceptible oxygen (O2) toxicity and iatrogenic barotrauma, resulting in persistent respiratory insufficiency. Whether infection (e.g., Ureaplasma), oxidant injury, or barotrauma is the primary insult, the inflammatory process likely exacerbates the prolonged lung damage characteristic of BPD.<br /><span style="font-weight:bold;">CLIN:</span> Most neonates with acute lung disease recover completely within the first week of life. The diagnosis of BPD is suspected when an affected neonate (typically premature) fails to recover as anticipated and instead may have a gradual increase in O2 and ventilatory requirements during the first month of life.<br /><span style="font-weight:bold;">STUDIES:</span> No specific tests exist to confirm the diagnosis of BPD. However, chest radiographic findings of strandlike densities in both lung fields alternating with areas of normal or increased lucency are consistent with BPD. Other disorders to rule out include cystic fibrosis (sweat chloride test), a1-antitrypsin deficiency (a1-antitrypsin levels), patent ductus arteriosus (PDA) (murmur, echocardiography), and viral pneumonia (viral cultures).<br /><span style="font-weight:bold;">TX:</span> Ideally, management of acute lung disease in premature infants should be aimed at preventing BPD by limiting exposure to mechanical ventilation and O2 therapy (if possible), judicious fluid administration, prompt management of PDA, and attention to optimal nutrition. Once diagnosed with BPD, neonates benefit from chronic administration of O2 with maintenance of PaO2 greater than 60 mm Hg or an O2 saturation greater than 90%; this chronic O2 therapy reduces the risk of developing pulmonary hypertension and cor pulmonale, severe complications of BPD. Additional O2 may be required during sleep and feedings. Congestive heart failure can frequently complicate the treatment of BPD. The development of pulmonary and systemic edema often requires chronic parenteral fluid restriction. Enteral fluid is better tolerated. Diuretics may be used with care; thiazide diuretics are preferred because they decrease urinary calcium excretion and may help prevent osteopenia of prematurity. Increased airway resistance and bronchial hyperreactivity may be treated with theophylline or b-adrenergic agents. Antiinflammatory therapy may also reduce O2 requirements and shorten the period of ventilator support. The tachypnea and heightened respiratory effort associated with BPD require that these infants receive increased caloric intake to achieve adequate growth. Caloric intake should be adjusted to enable a sustained weight gain of at least 10 g/kg/day. Infants with BPD have an increased susceptibility for developing severe pneumonia; therefore, respiratory infections should be prevented by avoiding exposure of the infant to patients, hospital personnel, and family members with respiratory symptoms. When viral respiratory infections occur in infants with BPD, O2, bronchodilator, and diuretic use are often increased for at least 1 week. If respiratory failure develops and ventilator therapy is required, mortality is high and recovery prolonged. In comparison with premature infants lacking BPD, survivors of BPD may have an increased incidence of neurodevelopmental abnormalities, visual and hearing deficits, and rehospitalization for respiratory illness in the first year of life. Because lung growth continues for the first few years of life, pulmonary function improves over that time, with most survivors achieving normal exercise tolerance by school age; evidence of increased airway reactivity can persist into adult life in a high percentage of patients.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-8399377246286055662009-02-11T06:43:00.000-08:002009-02-11T06:44:58.021-08:00BOTULISM<span style="font-weight:bold;"><br />DEF: </span>Neurotoxicity caused by Clostridium botulinum exotoxin, which irreversibly blocks acetylcholine release from presynaptic terminals of cholinergic neurons at the neuromuscular junction.<br /><span style="font-weight:bold;">ETIOL</span>: Infant botulism is distinct from food-borne and wound botulism in that it is caused by ingestion of C. botulinum spores rather than the exotoxin itself. Spores germinate in the intestine and generate exotoxin, which is distributed hematogenously. Infant botulism accounts for two-thirds of reported botulism cases in the United States. Although the toxin does not cross the blood–brain barrier, it accesses the cyto-plasmic membrane of peripheral cholinergic nerve endings, preventing exocytosis of acetylcholine at the neuromuscular junction. The resulting flaccid paralysis is potentially fatal. Infant botulism occurs almost exclusively within the first year of life and typically between 5 and 12 weeks of life. Honey has been implicated as the source of spores in 20% of cases; the contaminants have also been recovered from corn syrup. Yard soil is an environmental source of spores.<br /><span style="font-weight:bold;">CLIN:</span> History should focus on food intake and environmental exposures. Constipation often is the first sign of illness and typically is overlooked. Infants become listless and weak over the course of several days to weeks. Bulbar muscle involvement results in difficulty feeding and a weak cry. Drooling and pooling of food and secretions in the posterior pharynx may occur. Ptosis, ophthalmoplegia, diminished facial expression, and generalized muscle weakness and hypotonia (manifested initially as a loss of head control) are common findings. In severe cases, respiratory arrest can occur abruptly and may account for some cases of unexpected sudden death in infancy.<br /><span style="font-weight:bold;">STUDIES:</span> The diagnosis is confirmed by stool culture for C. botulinum, identification of toxin in the blood or stool, and electromyography.<br /><span style="font-weight:bold;">TX:</span> Treatment is directed toward aggressive supportive care, with particular attention to respiratory support. Infant botulism is a self-limited disease, typically lasting 2 to 6 weeks. Antitoxin and antibiotics do not influence the disease course; in fact, bacterial death caused by antibiotics can result in increased toxin release in the GI tract. In severe cases, infants may require prolonged ventilatory support. Constipation may persist for months and may improve with the use of stool softeners and adequate hydration. Close follow-up is required because relapse of infant botulism can occur after apparent resolution of clinical symptoms. The mortality rate of recognized cases of infant botulism is approximately 3%.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-33064675747790131682009-02-11T06:30:00.000-08:002009-02-11T06:39:59.531-08:00BILIARY ATRESIA<span style="font-weight:bold;">DEF:</span> Progressive atresia or hypoplasia of any portion of the biliary system.<br /><span style="font-weight:bold;">ETIOL:</span> The incidence of biliary atresia ranges from 1 in 8,000 to 1 in 20,000 live births. The disorder appears to be acquired rather than a result of abnormal development, based on the rarity of biliary atresia in autopsied fetuses and premature newborns. One causative factor is believed to be infection with reovirus type 3.<br /><span style="font-weight:bold;">CLIN:</span> Infants with biliary atresia are typically born at term and have a normal birth weight. Jaundice develops at age 3 to 6 weeks in otherwise well-appearing, thriving infants. Fifteen percent of infants may have associated defects, including polysplenia (i.e., splenic tissue divided into several equally sized masses), cardiovascular anomalies, and malrotation of the intestine. Family history is usually negative.<br /><span style="font-weight:bold;">STUDIES:</span> Stool is acholic, collected duodenal fluid lacks bilirubin pigment or bile acids, and abdominal ultrasound may show absence of the gallbladder. Radionuclide hepatobiliary imaging demonstrates rapid uptake by the liver without intestinal excretion. Characteristic pathologic findings from percutaneous liver biopsy include bile duct proliferation, bile plugs, and portal and perilobular fibrosis. If the diagnosis is still uncertain after biopsy, surgical exploration with intraoperative cholangiography is used. This procedure enables recognition of biliary atresia and exclusion of other forms of bile duct disease, including stenosis or common bile duct perforation.<br /><span style="font-weight:bold;">TX:</span> If biliary obstruction occurs as a discrete lesion, surgical intervention is directed at drainage of patent portions of bile duct proximal to the atresia. Commonly, the atretic area extends above the level of the porta hepatis and affects intrahepatic bile ducts, making drainage difficult. In 80% of cases, a noncorrectable atresia is found. In these infants, further exploration is indicated to establish drainage of any small, persisting bile duct remnants. This procedure, known as the Kasai hepatoportoenterostomy, consists of transection of the porta hepatis followed by apposition of a Roux-en-Y loop of intestine. The success rate is 90% in infants younger than 2 months. In addition to infant age, the size of the residual duct lumina found during surgery is a factor in the success of this procedure; diameters less than 150 µm are associated with a poor prognosis. Treatment is not definitive, and patients may have progressive liver disease and bouts of bacterial cholangitis, requiring prompt treatment and nutritional support. Biliary atresia without intervention is universally fatal, with the mean age of death younger than 1 year. The Kasai procedure offers valuable time for the infant to grow before hepatic transplantation is necessary. Liver transplantation is essential in infants in whom the Kasai procedure fails, who are referred late (older than 120 days), and who develop liver failure despite some degree of biliary drainage.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-58885483957057910572009-02-11T06:10:00.000-08:002009-02-11T06:29:10.726-08:00ANEMIA IN CHILDREN<span style="font-weight:bold;">ANEMIA</span><br /><br /><span style="font-weight:bold;">DEF</span>: Hematocrit and hemoglobin concentration below normal levels.<br /><span style="font-weight:bold;">CONDITION</span>: Physiologic anemia of infancy/anemia of prematurity.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: Soon after birth, erythropoiesis almost ceases because of the oxygen-rich milieu and relative excess of red blood cells (RBCs); this results in a decrease in hemoglobin values during the first several months of life, the severity of which is related to birth weight, perinatal complications, blood transfusion history, and vitamin E deficiency. Nadir hemoglobin values can reach 9.5 g/dL at 3 months in term infants and 6 g/dL in 6- to 8-week-old premature infants. Recovery is heralded by a slight elevation in the reticulocyte count and a rise in hemoglobin levels to those seen throughout the remainder of infancy.<br /><span style="font-weight:bold;">Tx</span>: Healthy term infants and asymptomatic growing premature infants require no therapy. Iron supplementation may be indicated during the recovery phase to support erythropoiesis.<br /><br /><span style="font-weight:bold;">CONDITION</span>: Blood loss.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: Anemia owing to blood loss is more common in the new-born period than in any other time in childhood. Acute hemorrhage (>20% to 30% blood volume) results in shock. Jaundice is absent. External blood loss commonly occurs from the gastrointestinal (GI) tract. To determine whether hematemesis or melena derives from the infant's or mother's blood, the Apt test for fetal hemoglobin is used. The Kleihauer-Batke stain for fetal hemoglobin–containing RBCs in the mother's blood can provide an estimate of the degree of transplacental hemorrhage. In sick premature infants, the most common cause of blood loss is the iatrogenic withdrawal of multiple specimens for testing.<br /><span style="font-weight:bold;">TX</span>: Treatment depends on the amount and duration of blood loss. Signs of hypovolemia dictate that the infant receive immediate volume replacement [crystalloid, plasma protein fraction, whole blood, packed RBCs (pRBCs)]. pRBCs alone may be indicated for less acute degrees of anemia.<br /><br /><span style="font-weight:bold;">CONDITION</span>: ABO incompatibility.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: Maternal alloantibody can cross the placenta and may bind antigens on fetal/neonatal RBCs, causing hemolytic anemia. Affected babies present with jaundice during the first several days of life. In some cases, symptomatic anemia does not manifest until 4 to 6 weeks after birth. Although the reticulocyte count is elevated (5% to 15%), anemia is absent or mild. The peripheral smear shows increased nucleated RBCs and microspherocytes. Maternal and fetal blood type testing show the corresponding ABO incompatibility “set-up” (mother is blood group O; baby is A or B). Direct and indirect Coombs testing is positive.<br /><span style="font-weight:bold;">TX</span>: Phototherapy or exchange transfusion may be required to treat hyperbilirubinemia.<br /><br /><span style="font-weight:bold;">CONDITION</span>: Rh incompatibility.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: Incompatibility between the mother and child in the major antigen of the rhesus complex can cause erythroblastosis fetails. Rh-negative mothers sensitized to D-positive blood produce antibodies that cross the placenta and coat D-positive fetal blood, resulting in hemolytic anemia. Severely anemic fetuses may die in utero, or neonates may be born with hydrops fetails, characterized by anasarca (from hypoalbuminemia and congestive heart failure), severe anemia, and massive hepatosplenomegaly. Less severely affected neonates (benefiting from early detection and vigorous treatment during pregnancy and delivery) may have less severe anemia. Direct and indirect Coombs testing is positive. Hyperbilirubinemia is present. The peripheral smear shows polychromasia, nucleated RBCs, and no microspherocytes.<br /><span style="font-weight:bold;">TX</span>: Early detection during prenatal care and Rhogam therapy prevent maternal sensitization. Intrauterine transfusion of pRBCs can correct fetal anemia. Treatment during the neonatal period consists of exchange transfusion for marked anemia and hyperbilirubinemia and pRBCs for less severe anemia. Careful follow-up is required during the first 2 to 3 months of life to monitor for delayed anemia resulting from persistent anti-D antibody.<br /><br /><span style="font-weight:bold;">CONDITION</span>: Glucose-6-phosphate dehydrogenase (G6PD) deficiency.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: G6PD deficiency is the most common inherited intrinsic disorder of RBCs. It typically occurs in black, Mediterranean, and Asian males. Oxidant stresses from drugs or infection cause hemoglobin to precipitate, forming Heinz bodies seen on the peripheral smear. Oxidant stresses at delivery and premature birth may trigger neonatal hemolysis and hyperbilirubinemia. The diagnosis is made with specific screening tests and enzyme assays.<br /><span style="font-weight:bold;">TX</span>: Hemolysis and hyperbilirubinemia may require exchange transfusion.<br /><span style="font-weight:bold;"><br />CONDITION</span>: Hereditary spherocytosis.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: Hereditary spherocytosis is the most common congenital hemolytic anemia presenting with jaundice and anemia during the neonatal period. It is an autosomal dominant disorder common in whites of northern European descent. The blood smear contains numerous microspherocytes. There is no evidence of ABO incompatibility (i.e., negative Coombs test).<br /><span style="font-weight:bold;">TX</span>: Hemolysis and hyperbilirubinemia may require exchange transfusion.<br /><span style="font-weight:bold;"><br />CONDITION</span>: Anemia related to mechanical or toxic factors.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: Mechanical or toxic factors. Damage to erythrocytes can occur from toxins produced by infection or from mechanical injury mediated by fibrin strands or altered microvasculature, such as in disseminated intravascular coagulation (DIC).<br /><span style="font-weight:bold;">TX</span>: Treatment depends on the etiology. Blood product transfusion may be required.<br /><br /><span style="font-weight:bold;">CONDITION</span>: Decreased RBC production.<br /><span style="font-weight:bold;">ETIOL/CLIN</span>: Anemia resulting from diminished RBC production is uncommon at birth and is reflected by a diminished or absent reticulocyte count. Causes include malignancy, sepsis (relative myelosuppression), iron deficiency, Diamond-Blackfan syndrome (congenital pure RBC aplasia), and a-thalassemia syndromes.<br /><span style="font-weight:bold;">TX</span>: Treatment depends on the etiology. Vigorous resuscitation measures and blood transfusions may be required.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-81248513821492521792009-02-04T06:12:00.000-08:002009-02-04T06:16:37.833-08:00Ototoxicity<span style="font-weight:bold;">Rita M. Schuman<br />Gregory J. Matz</span><br /><br />Drug-induced inner ear damage is a common finding in present-day medical practice. In many developing countries, where drugs such as the aminoglycosides are frequently prescribed to treat pneumonia, diarrhea, and tuberculosis, the incidence of ototoxicity is high (1). Physicians in practice need to recognize that ototoxic drugs can cause significant auditory and in many instances, poorly recognized, vestibular toxicity. Physicians therefore need to be cognizant of the many categories of drugs that produce ototoxicity.<br /><br />Early examples of drug ototoxicity are arsenic, the salicylates, and quinine. Salicylates, for example, administered in doses in excess of 2,700 mg a day, once commonly used to treat arthritis, were found to cause a transient flat, bilateral sensorineural hearing loss and tinnitus. There has never been a case of permanent hearing loss following salicylate use in therapeutic drug dosing; however, most patients experience complete reversal within 2 to 3 days. Later, in the 1960s, thalidomide, a well-known drug used at that time and now known to cause amelia and phocomelia, was also discovered to cause aplasia of the inner ear.<br /><br />The introduction of the first aminoglycoside, streptomycin, in 1944 by Waxman, who was awarded the Nobel prize for this discovery, heralded a new era of antibiotic therapy for the treatment of tuberculosis. Unfortunately, Hinshaw and Feldman at the Mayo Clinic described a significant number of patients with vestibular toxicity from this drug (2). A few years later, an analog of streptomycin, dihydrostreptomycin, was used in clinical practice with the hopes of reducing the streptomycin ototoxicity. Dihydrostreptomycin, however, was also shown to have an unacceptably high incidence of cochlear toxicity and was subsequently withdrawn from the market. Likewise, other early aminoglycosides, such as kanamycin and neomycin had unacceptably high rates of cochlear toxicity when used systemically and therefore are rarely used in that manner today. Later, a newer aminoglycoside, gentamicin, was shown to have about a 3% incidence of vestibular injury (3). Subsequent aminoglycosides such as netilmicin, tobramycin, and amikacin were developed to reduce this incidence of toxicity. In fact, netilmicin has been found to be the least ototoxic of all of the aminoglycosides available (4).<br /><br />Other considerations must include the cancer chemotherapeutic agents, such as cisplatin, which has been found to result in a moderate level of ototoxicity with resultant permanent bilateral hearing loss. Clinicians are also faced with a sporadic low incidence of ototoxicity with drugs such as vancomycin and the macrolides. Most studies in the literature regarding the ototoxicity of the macrolides have been found to be reversible. The mechanism by which these drugs are toxic is unknown. Finally, numerous case reports have also indicated that hydrocodone in combination with acetaminophen can cause a rapidly progressive sensorineural hearing loss. (5). The mechanism of toxicity at this time is unknown.<br /><br /><span style="font-weight:bold;">Ototoxicty of Ototopical Antibiotics</span><br />It is well known that systemic administrations of aminoglycosides can cause both cochlear and vestibular toxicity. This naturally leads to the question of whether these drugs, which are used extensively to treat ear infections through topical administration to the middle ear, can cause ototoxicity. Animal data have been quite uniform in that almost all of the aminoglycoside antibiotics used in the middle ear as topical otic preparations are ototoxic (6). The use of aminoglycoside ototopical drops confined to the external auditory canal, however, presents little, if any, risk of ototoxicity.<br /><br />Current review of the literature reveals documentation of a total of 54 cases of gentamicin vestibular toxicity from ototopical use in the middle ear or open mastoid cavity (7) (Table 148.1). In addition, 24 of these patients developed an associated auditory toxicity. A review of the literature in the above cited study also included 11 patients who experienced auditory toxicity from the topical use of neomycin-polymyxin-based eardrops. It was therefore recommended that when possible,<br />topical antibiotic preparations free of potential ototoxic side effects should be used in preference to ototopical preparations that have had the potential for ototoxic injury if the middle ear or mastoid are open (17). Aminoglycoside-containing antibiotic topical drops are not FDA approved for use in the middle ear or open mastoid cavity. Indeed, current labels contain warnings against the use of these drugs if the tympanic membrane is not intact. Although the evidence suggests that otologic damage from topical preparations with ototoxic potential is infrequent, the evidence also indicates that they offer no advantage over nonototoxic agents (17). If these ototoxic agents are considered, potentially ototoxic, antibiotic preparations should be used only in acutely infected ears and use should be discontinued shortly after the infection has resolved. Finally, if the clinician must use potentially ototoxic antibiotics in the middle ear or mastoid space, the patient or parents should be warned of the risk of ototoxicity (17).<br /><br /><span style="font-weight:bold;">Ototoxicity of Systemic Drugs</span><br /><br />Table 148.2 lists the major classes of drugs that cause ototoxicity—the aminoglycoside antibiotics, the macrolides, loop diuretics, cisplatin, and the salicylates. These drugs are listed because they are commonly seen in otolaryngology consultation practice. There are currently no meta-analysis studies that evaluate ototoxicity for these drugs. Included in the bibliography are two reviews that include ototoxic evaluations for gentamicin and cisplatin in a large cohort of patients. Omitted for the sake of brevity in Table 148.2 are the low-incidence ototoxic drugs, such as chloroquine, which is rarely used in clinical practice in the United States.<br /><br />For various reasons, the incidence of aminoglycoside ototoxicity in neonates and children is lower than adults (23). In children, it can be useful to obtain pretreatment audiograms to rule out preexisting hearing loss in patients who are to receive a course of aminoglycoside antibiotics. In the United States, that drug is usually gentamicin.<br /><span style="font-weight:bold;"><br />Genetics of Otoxicity</span><br /><br />It is well known that aminoglycosides are some of the most common ototoxic drugs causing acquired hearing loss. It was observed that many patients were developing hearing loss, despite the low dosages of aminoglycosides administered. It was also noted that certain families had an exceptionally high number of members with similar findings of aminoglycoside ototoxicity. Based on these observations and the ongoing research regarding the pathophysiology of hearing loss, it has been proposed that certain individuals may have a genetic predisposition or susceptibility to the ototoxic effects of certain drugs and in particular, the aminoglycosides (24).<br />Recent advances have identified that certain mutations in mitochondrial DNA are found to be associated with a number of hearing disorders, including ototoxicity. Mitochondrial DNA is a double-stranded molecule forming a closed circle. Replication and transcription occurs within the mitochondria, ultimately forming proteins involved with ATP synthesis and electron transport. This specific type of DNA is transmitted exclusively by the maternal line, equally affecting both male and female offspring.<br /><br />In the early 1990s it was first discovered that a mutation at position 1555 in the nucleotides of the mitochondrial 12S ribosomal RNA was responsible for aminoglycoside toxicity in several Chinese families (25). It was also cited as a cause for a number of cases of nonsyndromic deafness in patients with no previous aminoglycoside exposure. Since that discovery, similar research has been conducted on numerous other families, as well as on sporadic patients with documented sensorineural hearing loss following the administration of intravenous aminoglycosides. These subsequent studies confirmed that these patients also had identical nucleotide mutations of their mitochondrial DNA. It has been proposed that the specific mutation creates another binding site for the aminoglycosides, thus increasing the patient's sensitivity to ototoxicity (26). Most of this work was conducted on an international basis, where severe infections such as tuberculosis more often require widespread use of intravenous aminoglycosides.<br /><br />A large quantity of research continues in this area. As more becomes known about the genetics of hearing loss and the specific mutations that predispose patients to the ototoxic effects of some drugs, it may be possible to develop molecular tests to identify these patients prior to treatment. With that information, it may be possible to reduce the number of patients suffering from the toxicities of these antibiotics.<br /><span style="font-weight:bold;"><br />Chemoprevention of Ototoxicity</span><br />In some instances, it may be necessary to use ototoxic drugs in order to effectively treat patients. In light of this fact, it is necessary to develop mechanisms by which it is possible to protect the inner ear from the toxicities of both the ototoxic intravenous antibiotics and the chemotherapeutic agents such as cisplatin. Some of the agents that have been proposed and studied include iron chelators (deferoxime) (27,28), antioxidants including L-N-acetyl cysteine (29), vitamin E, alpha-tocopherol (30,31,32), as well as the salicylates (33,34).<br /><br />Recent research has demonstrated that administration of aminoglycosides causes the formation of an iron complex that is involved in the generation of free radicals, resulting in hair cell death and subsequent hearing loss (28). Based on this discovery, attempts have been made to use deferoxamine, an iron chelator, to help attenuate these toxic effects. Animal studies have been promising, but considerations must be taken so as to not alter the serum concentrations of the drugs, and a better understanding is needed of the side effects of administering iron chelators to patients and the potential of altering serum iron levels (27).<br />Cisplatin, a common chemotherapeutic agent used in head and neck cancer, is well known to cause bilateral, irreversible sensorineural hearing loss. Evidence suggests that glutathione reduction secondary to free radical production ultimately causes hair cell damage. Various chemoprotectants have been shown to exert antioxidant properties that ultimately reduce the ototoxic effects of cisplatin. Recent studies with vitamin E (31), L-N-Acetyl cysteine (29), and sodium thiosulfate (35) confirm this theory. Most of the research, however, has thus far been with animals. Further human studies must be done to truly know if these advances will be clinically significant and will ultimately reduce the ototoxic effects.<br /><span style="font-weight:bold;"><br />Summary</span><br /><br />One of the authors of this chapter (GJM) has written previously about the use of high-frequency audiometry (8 to 12 Hz) as a predictor of drug-induced ototoxicity (36). Although conventional audiometry may still have a role in monitoring patients exposed to ototoxic medications, high frequency testing is often problematic. It is an extremely difficult test to do for all practical purposes and is often not done clinically for that reason. Few centers perform pretreatment conventional audiograms from 0.25 Hz to 8 Hz when the two most common ototoxic drugs, gentamicin and cisplatin, are given. The authors are not aware of any outcome studies that demonstrate that pretreatment and post-treatment audiograms reduce the incidence of predicted ototoxicity. Some centers have found, however, that it may be beneficial to perform one pretreatment audiogram followed by serial audiograms, in addition to closely monitoring the serum drug levels of the ototoxic medications being administered. The use of vestibular testing both pretreatment and post-treatment for patients receiving long-term gentamicin is also difficult to do in the clinical setting. This is an important factor because gentamicin is mostly a vestibular toxic drug. Some centers do perform electronystagmography, rotational testing, and platform posturography in working up possible vestibular symptoms and have found these tests to be helpful.<br />It is now well known that the aminoglycoside antibiotics act synergistically with some drugs, thus increasing the incidence of ototoxicity. For example, the use of aminoglycoside antibiotics with loop diuretics can produce an unexpectedly high incidence of ototoxicity. This has been extensively documented in human case reports as well as in animal studies. Ethacrynic acid, an ototoxic loop diuretic, has been shown to increase the permeability of the stria vascularis, facilitating the diffusion of the aminoglycoside into the endolymph. Finally, it has been found that diuretics given prior to the administration of aminoglycosides are less damaging than if done in the reverse (37). Most recently noted is a similar response to aminoglycoside antibiotics and the use of metronidazole (38).<br />It is unclear at this time if antiviral and protease inhibitors are responsible for the anecdotal reporting of neurosensory hearing loss in patients with human immunodeficiency virus (39). Prospective studies are needed to confirm whether nucleoside analog reverse transciptase inhibitor or antiviral agents cause hearing loss in this patient population. The use of chemoprevention measures as described in animal studies show promise, but so far no prospective clinical trials have been performed and the authors are not aware of any medical centers with protocols to address this issue at this time.<br />The two most common ototoxic drugs given today in clinical practice are gentamicin and cisplatin. The patients selected in these groups are different. Gentamicin is normally monitored not by audiograms but by serum peak and trough levels. When gentamicin has to be given for long-term therapy (i.e., osteomyelitis), consideration has to be given to genetic testing to see if a patient is going to be more susceptible to ototoxic injury, thus giving the clinician the opportunity to obtain informed consent from the patient. Likewise, accurate dosing during chemotherapy has reduced the incidence of ototoxicity. Further research is necessary to determine if any of the chemopreventative agents will be successful in further animal and ultimately human trials to reduce the unfortunate toxicities of these necessary drugs.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com2tag:blogger.com,1999:blog-5658461710957833796.post-11361186292444131202009-02-04T05:56:00.000-08:002009-02-04T06:06:25.289-08:00Balance Function Tests<span style="font-weight:bold;">Colin L. W. Driscoll<br />J. Douglas Green Jr</span><br /><br />Balance is maintained through complex interaction of the vestibular, visual, and somatosensory information that is combined within the brainstem to generate a motor response correcting the perturbation. Abnormalities within any portion of the system can cause a sensation of imbalance or dizziness. Dizziness is one of the most common reasons for seeking medical evaluation, and the otorhinolaryngologist is often the primary contact. Evaluating patients for dizziness can be frustrating for both patient and physician. The symptoms are difficult for patients to describe, the differential diagnosis is broad, and many tests have to be considered. An understanding of the balance tests currently available and the pathophysiologic principles on which they are based improves treatment of these challenging patients. The particular approach to dizziness is affected by type of practice, available resources, and patient population.<br />The main goals of the diagnostic evaluation are to determine the location and severity of lesions within the balance system and to help formulate and guide a treatment plan. The etiologic evaluation of the balance system dysfunction necessitates compilation of other data, including those from a comprehensive history and physical examination and other directed laboratory and radiologic examinations. In most cases, clues revealed during the history and physical examination lead to a diagnosis, and treatment can begin without additional testing. Balance function testing should be interpreted in light of the history and physical exam findings and often provides confirmatory information as to pathophysiologic processes involved. Formal balance function testing provides information as to the site and side of the lesion, to ascertain who is likely to benefit from vestibular rehabilitation, to assess recovery of vestibular function, and to document contralateral function when a destructive procedure is contemplated. Clinical decision support systems have been described to help office personnel determine which patients may need balance function testing (1).<br />This chapter reviews tests for assessing the balance system (Table 131.1). These balance system tests, usually administered by an audiologist or trained technician, require specialized equipment and dedicated space. The basic physiologic principles of the tests are reviewed.<br /><br /><span style="font-weight:bold;">Electronystagmography</span><br />The electronystagmography (ENG) test battery is the workhorse of balance function testing. It is a combination of tests that together provide complementary information about the vestibular and oculomotor systems. Rather than a diagnosis, the tests provide data that must be used in conjunction with the findings of the history, physical examination, and other studies to determine a diagnosis. The ENG battery typically consists of the vestibular and oculomotor tests listed in Table 131.2.<br />The ENG tests are based on the well-studied neurophysiologic characteristics of the vestibulo-ocular reflex. Motion of the head, or simulated motion through labyrinthine stimulation, produces compensatory eye movement. These eye movements are observable and recordable responses that provide the basis for interpretation of the various tests. Changes in eye position are recorded by means of taking advantage of the natural difference in electrical charge between the cornea (+) and the retina (-), the corneal-retinal potential. Electrodes record the changes in potential when the eye moves [electrooculography (EOG)]. The advantages of this recording technique are low cost, ease of administration, noninvasiveness, avoidance of head restraint, and extensive experience in interpreting the data. The technique does have technologic limitations. The signal is susceptible to changes in skin resistance due to perspiration, interference from eye-blink artifacts, and a poor signal-to-noise ratio. Although abnormal eye movements can be revealed by means of direct visualization during testing, it is preferable in most cases to have quantifiable data to characterize the abnormalities. Furthermore, some parts of the test require that the eyes be closed to prevent fixation suppression. Nystagmus is the primary ocular movement measured and is defined by its direction (horizontal, vertical, or torsional) and velocity (degrees per second). Direction is determined by the fast component, and velocity is calculated from the slow-phase component.<br />New technologies for observing and recording eye movement continue to be developed (2,3). Video ENG systems, vidoenystagmography, are now available that use small video cameras to observe and monitor horizontal, vertical, and torsional eye movement during vestibular evaluations (Fig. 131.1). With this system, tests that require the patient to move are performed with a lightweight goggle assembly. Pursuit, gaze, and saccade testing can be performed with an oculomotor module with tracking targets for each eye. The eyes are illuminated with near-infrared light that is not visible to the patient but allows the cameras to pick up and project images of the eyes on video monitors. This system has several advantages over traditional ENG testing techniques. Nonelectrode eye movement recording eliminates artifacts, the need for frequent recalibration, and impedance testing. Vertical eye movements can be accurately recorded. Torsional eye movements can be visualized and recorded without fixation suppression. Disconjugate eye movements are more easily identified. A portable unit allows testing at home, in an intensive care unit, or at any other remote location. The disadvantages are high cost, need to wear goggles, and unfamiliarity with the equipment. Most companies that manufacture ENG equipment now offer a videonystagmography system to make use of these advantages.<br />Virtual reality testing systems are being developed and promise to provide a means to produce visual stimuli that were previously impossible (4). Images can be produced on a visual display, and because the system is software driven, the images can be manipulated quickly and with tremendous flexibility. For example, cross-axis stimulation (head motion in one plane and eye motion in another) becomes easy to perform.<br />The sequence of ENG tests is important to prevent obtaining misleading results. For example, testing for benign paroxysmal positional vertigo is performed at the beginning of the test series to avoid fatiguing of the response. The tests must be performed with proper attention to detail and accurate calibration. Patient anxiety, fatigue, lack of cooperation, and medications can adversely affect test results.<br />Interpretation of ENG results is critical to proper diagnosis and treatment and should be performed by qualified audiologists and physicians who are trained and familiar with the equipment being used for testing. Increasingly, specialists in other fields, chiropractors, and poorly trained medical doctors are investing in ENG equipment in hopes of financial gain, often without knowledge of how to interpret the ENG test results and how to apply them in clinical practice. It is essential that otorhinolaryngologists offering ENG testing be familiar with interpretation of the results. Several excellent courses are available to otorhinolaryngologists offering ENG testing within their offices.<br /><span style="font-weight:bold;"><br />Spontaneous and Gaze Nystagmus</span><br />Spontaneous nystagmus refers to nystagmus that is present without visual or vestibular stimulation. Spontaneous nystagmus can sometimes be seen only with loss of visual fixation (e.g., milder forms of spontaneous vestibular nystagmus) or may be seen with both eyes open and with loss of visual fixation (e.g., congenital nystagmus and severe vestibular nystagmus). Spontaneous nystagmus can be observed both at the bedside and in the vestibular laboratory. However, although reduction of visual fixation can be achieved easily in the laboratory using infrared video goggles or EOG with eye closure, at the bedside, achieving a reduction in visual fixation while still maintaining an ability to observe eye movements can be challenging. Observing a patient's eye with an ophthalmoscope while the other eye is occluded allows the examiner to assess spontaneous nystagmus with reduced visual fixation. The most common type of spontaneous nystagmus, that is, spontaneous vestibular nystagmus, occurs with unilateral peripheral vestibular lesions. Spontaneous vestibular nystagmus is always unidirectional and increases when the patient gazes in the direction of the quick component of the nystagmus. This gaze dependent change in nystagmus intensity is called “Alexander's Law.†As noted previously, loss of visual fixation also increases the magnitude of spontaneous vestibular nystagmus. Thus, judicious use of gaze direction and presence or absence of visual fixation can aid the examiner both at the bedside and in the laboratory in judging whether or not a spontaneous nystagmus is a result of a vestibular abnormality. Failure of fixation suppression is highly suggestive of a central pathologic condition.<br />Gaze nystagmus, also known as gaze-evoked nystagmus, is a bidirectional nystagmus with right beating nystagmus on right gaze and left beating nystagmus on left gaze. Many patients with gaze-evoked nystagmus also will manifest an up-beating nystagmus on upward gaze. Note that down-beating nystagmus in any gaze position, even in downward gaze, is not considered a component of gaze-evoked nystagmus and should be regarded as a manifestation of a central nervous system abnormality at the level of the craniocervical junction unless proven otherwise. Gaze-evoked nystagmus can be seen in normal individuals when horizontal gaze exceeds 30 degrees from the straight-ahead position. Thus, it is best to limit the amount of gaze deviation when assessing a patient for gaze-evoked nystagmus to less than 30 degrees. Gaze-evoked nystagmus occurs as a result of inadequate gaze-holding, thereby leading to a slow drift of the eyes back toward the straight ahead gaze position with the drift interrupted intermittently by rapid, nystagmus fast phases in the direction of gaze. Bidirectional gaze-evoked nystagmus is always a result of a central nervous system abnormality and never is the result of a peripheral vestibular abnormality. There are many etiologies for gaze-evoked nystagmus. The most common cause of gaze-evoked nystagmus is a medication effect (e.g., from anticonvulsants).<br /><br /><span style="font-weight:bold;">Positional and Positioning Tests</span><br />Positional tests are designed to detect the response to changes in direction of gravitational force. The patient is moved slowly into a series of stationary positions with the eyes closed, and presence or absence of nystagmus is assessed. The nystagmus can be either fixed or direction changing. If nystagmus is elicited in the positional tests, the entire body is turned to determine whether neck torsion is responsible. Interpretation of results is controversial and necessitates consideration of the number of positions that elicit nystagmus and the velocity of the nystagmus. Positional nystagmus of peripheral origin can fatigue with repeated testing, is usually direction fixed, and often is associated with caloric weakness. The direction of nystagmus caused by a peripheral lesion typically does not change independently of head movement (5). Direction-changing nystagmus without an accompanying change in head position indicates the presence of a central disorder.<br />The positioning test used most often is the Dix-Hallpike maneuver. The patient is rapidly moved from sitting to supine with the head turned and hanging below the level of the table. If nystagmus is elicited, the maneuver is repeated to determine the existence of fatigability. A response that fatigues suggests a peripheral problem. The patient's eyes are kept open to allow the examiner to evaluate for torsional nystagmus, which can indicate benign positional vertigo due to loose otoconia within the labyrinth. Torsional nystagmus cannot be recorded with conventional ENG. Head hanging to the right produces counterclockwise torsional nystagmus, and head hanging to the left produces clockwise torsional nystagmus. A variant of benign positional vertigo affecting the horizontal semicircular canal produces pure horizontal nystagmus.<br /><br /><span style="font-weight:bold;">Bithermal Caloric Tests</span><br />Bithermal caloric tests are used to evaluate the function of the horizontal semicircular canals. Changes in temperature stimulate fluid flow (equivalent to a very slow frequency of only 0.002 to 0.004 Hz) within the horizontal semicircular canal; if the system is functioning, nystagmus is elicited. The very slow frequency of stimulation is not a condition normally experienced during daily life. Each ear is tested independently, and the responses are compared.<br />Caloric testing is performed with the patient supine and head elevated 30 degrees. The external auditory canal is irrigated directly with 250 mL of water at 7 degrees above and below body temperature for 30 seconds. An alternative is to place a small, distensible balloon in the ear canal and fill it with water (closed-loop system). Ocular movements are recorded for approximately 2 minutes, beginning with stimulation. Fixation suppression is evaluated during this time. The slow-phase velocity of elicited nystagmus is calculated and recorded as an objective measure of the response. Warm and cool air irrigation or a closed-loop system can be substituted for direct irrigation if the tympanic membrane is perforated. The responses of the right and the left ears are compared. A difference greater than 20% usually is considered abnormal and is reported as left- or right-sided weakness. The total right-beating responses is compared with the total left-beating responses, and the result is reported as a right or left directional preponderance. A difference greater than 30% is considered significant. Abnormal directional preponderance without unilateral weakness suggests a central pathologic condition. The results indicating central or peripheral disorders are summarized<br />A monothermal caloric screening test has been suggested to minimize procedure time and patient discomfort. This test has been criticized for a high false-negative rate. However, the results of a study by Jacobson et al. (6) suggest that if appropriate failure criteria are used, the sensitivity reaches 93% and the specificity 98%. Patients who fail the screening test need conventional bithermal testing.<br />Patients with a complete unilateral or bilateral caloric loss should be tested with ice caloric irrigation of the affected ear(s). Frequently, nystagmus can be elicited with this stronger stimulus. Ice caloric stimulation is uncomfortable for the patient and should be limited in use. It should be noted that the absence of caloric response to warm, cool, or ice water irrigations cannot be taken as an indication of complete lack of function. This should be confirmed by rotational chair testing.<br /><br /><span style="font-weight:bold;">Electronystagmography Fistula Test</span><br />If a fistula exists between the middle ear space and the inner ear fluid, application of positive or negative pressure in the external ear canal may produce a fluid shift resulting in nystagmus. Objective nystagmus or a clear subjective response suggests a perilymph fistula or dehiscence of the horizontal or superior semicircular canal.<br /><br /><span style="font-weight:bold;">Saccadic System</span><br />The saccadic system is used to move a target from theperiphery of the retina to the fovea. Targets more than20 degrees from the line of sight are normally located by means of a combination of eye and head movement, called gaze saccade (7). This test is performed while the patient sits facing a light bar and keeps his or her head stationary. Lights on the bar are activated to the left and right of center by 10 to 20 degrees, and the patient is asked to shift gaze to each new target. Electrooculographic recording techniques are used. Latency, maximum velocity, duration, gain (overshoot or undershoot), refixation saccade, glissade (postsaccadic drift, or slip of the eye), and other variables are measured and observed.<br />Abnormal saccades can be caused by lesions in a wide variety of locations. However, they are most commonly caused by a central pathologic disorder rather than a peripheral vestibular one. An abnormal saccadic response can be caused by lesions in the cerebellum (dorsal cerebellar vermis), brainstem (particularly the paramedian pontine reticular formation and medial longitudinal fasciculus), or ocular muscles and nerves. Cerebellar lesions typically manifest as saccadic overshoot or undershoot dysmetria. Dysmetria is an error in range, rate, or direction in performance of precision voluntary movement. It usually is found through past pointing in a finger-to-nose test (8). Different patterns of abnormalities and testing paradigms can help to localize a lesion (9). Age, fatigue, lack of attention, sedatives, drug intoxication (phenytoin), and other factors can cause slow saccades or increase latency.<br /><span style="font-weight:bold;"><br />Pursuit System</span><br />The smooth pursuit system stabilizes images of moving objects on the fovea (7). Healthy persons can pursue an object moving at a velocity of about 30 degrees per second. At faster rates, the image can slip, and a corrective saccade is used to catch up. Smooth pursuit usually is tested with sinusoidal stimuli, such as a pendulum, light-emitting diodes, or a laser, with a frequency range of 0.2 to 0.7 Hzand a horizontal range less than 20 degrees to the left and right. Electrooculographic techniques are used to record gain, phase lead or lag, symmetry, and other variables. Because the smooth pursuit system is distributed throughout the brainstem and cerebellum, anatomic localization is not possible (9). If age, alertness, medications, and congenital nystagmus are eliminated as causes of abnormal test results, a central cause is suggested. Saccadic pursuit suggests cerebellar disease. Reduced bilateral gain can be caused by a brainstem lesion. Patients with Alzheimer disease and schizophrenia can perform worse with sinusoidal stimuli than with fixed velocity stimuli (9).<br /><br /><span style="font-weight:bold;">Optokinetic System</span><br />The optokinetic system differs slightly from the pursuit system in that it allows persons to keep the visual field in focus while they or most of the environment are moving. The vestibulo-ocular reflex alone is not adequate to generate compensatory eye movements at low frequency. In clinical testing, this effect is achieved by keeping the patient stationary and moving the environment. About 90% of the visual field must be filled with the target to avoid simply testing the pursuit system. A rotating drum with thin vertical stripes or stripes projected on the wall are common stimuli. The patient is instructed to look straight ahead. As the targets pass by, there should be small amplitude excursions of the eye (stare nystagmus). If the patient fixes on the target, longer excursions occur, and the pursuit system is being tested (look nystagmus) (9). Separating the smooth pursuit system and the optokinetic system can be even more difficult. Experiments indicate that both systems are responsible for eye movement during stimulation. If, however, the lights are extinguished, the smooth pursuit system response drops to zero almost instantly. With the lights out, patients continue to have nystagmus for approximately 25 seconds. It is believed that this nystagmus [optokinetic afternystagmus (OKAN)] is caused by the optokinetic system alone (7). Because of the contribution of the pursuit system, it is not possible to conclude that the optokinetic system is normal without having nystagmus for approximately 25 seconds following optokinetic stimulation.<br />The optokinetic system is widely distributed throughout the brainstem and cerebellum; therefore, abnormalities are not site specific. Absence or asymmetry of the OKAN occurs with peripheral vestibular lesions. Bilateral labyrinthectomy profoundly reduces or eliminates OKAN (10). These findings suggest an interaction between the vestibuloocular reflex and the optokinetic system (7). The OKAN becomes asymmetric after unilateral vestibular ablation; the result is stronger and more prolonged nystagmus directed at the side of the lesion (10). A problem is that the sensitivity in identifying unilateral vestibular disease is not high (10). In a study involving 12 patients who had undergone removal of acoustic neuroma, OKAN helped identify the side of the lesion for only 7 of the patients (10). Baloh et al. (11) found abnormal test results among patients with cerebellar atrophy.<br />Optokinetic testing is not routinely used but can be indicated as a confirmatory examination when abnormal pursuit is identified. Combining the results of OKAN with those of rotary testing can be helpful in determining the side of the lesion. Another potential use might be to exclude vestibular disease, especially for patients who cannot undergo caloric testing (10). As more is learned about the production of optokinetic nystagmus, clinical usefulness can expand.<br /><span style="font-weight:bold;"><br />Rotary Chair, Sinusoidal Harmonic Acceleration</span><br />Rotational testing paradigms offer the theoretic ability to test the semicircular canals under more physiologic, that is, higher frequency, conditions than can be achieved with caloric testing. The stimulus can be precisely controlled and is repeatable. Because both ears are tested simultaneously, the results reflect the integrated function of both ears (12). In this test, the rotary chair is oscillated from side to side at a series of preprogrammed rates (Fig. 131.2). The acceleration frequencies tested range from 0.01 to1.28 Hz with a maximum velocity of 50 degrees per second. <br />More rapid rotational velocities may result in head slippage adversely affecting test results. An infrared camera is mounted to the chair to monitor the patient and eye movement. Mental alerting tests are used, as in ENG. As the chair begins to rotate to the right, standard EOG techniques are used to record slow compensatory eye movement to the left. Saccadic eye movement returns the eye to a central position. This movement is eliminated mathematically, and slow-phase movement is compared with chair movement. Three basic characteristics are measured—phase, gain, and symmetry of eye movement. Testing is comfortable for the patient and takes approximately 15 minutes.<br />Interpretation of the results requires integration with complementary data and the clinical history. Symmetry represents a comparison between the peak slow-wave velocity when the patient is rotated to the left and the peak slow-wave velocity with rotation to the right. For a patient with acute, uncomplicated unilateral peripheral weakness, the symmetry measure shows weakness on the affected side. A problem is that symmetry can be misleading in many cases. Spontaneous nystagmus, irritation of the labyrinth, vestibular compensation, and cerebellar lesions can produce erroneous data. The value of symmetry alone as an indicator of the side of a lesion is controversial. Caution is needed in interpretation of the results. Symmetry often improves with compensation after a vestibular insult and can be useful for monitoring recovery (11). Asymmetry or directional predominance can also be seen withmigraine-associated dizziness, a common form of dizziness.<br />The phase variable is the relation between maximum chair velocity and maximum slow-phase velocity. Eye velocity typically leads chair velocity, the so-called phase lead. The phase lead often is exaggerated among patients with central or peripheral vestibular disease. If abnormal, this value is nonlocalizing. Some laboratories also include a step test in addition to sinusoidal acceleration testing described previously. In the step test, the system time constant is measured by varying the speed at which the chair rotates. This test can be performed simultaneously with the sinusoidal acceleration testing, providing additional vestibulo-ocular reflex information.<br />Gain is the ratio of maximum eye velocity to maximum chair velocity. A gain of one indicates that slow-phase eye velocity equals chair velocity and is opposite in direction. If there is no eye movement, the gain is zero. A problem is that gain can fluctuate markedly with changes in alertness. Consistent testing is critical to obtain valid results. The gain values used in calculating phase and symmetry must be accurate. Low gain values alert the physician that the results may be inaccurate. Depressed gain values under good testing conditions suggest bilateral peripheral lesions. Abnormally high gain can indicate the presence of a cerebellar lesion that is decreasing vestibular inhibition. Another caution is that there can be considerable differences in results between laboratories, depending on the specific data analysis algorithms used and operator intervention (13).<br />Rotary testing is useful to (a) monitor changes in vestibular function over time, especially bilateral lesions or lesions due to vestibular toxicity, (b) monitor compensation after acute injury, and (c) identify residual labyrinthine function for patients with no response during caloric testing or low-frequency rotary chair testing (12,14).<br />Off-vertical-axis rotation is a variation of rotary chair evaluation (15). The testing procedure is similar, except that the chair can be tilted 30 degrees. Earth horizontal axis (barbecue spit) rotation is another variation. The proposed advantage is that otolith function is incorporated into the response. The role of this type of testing is being investigated. Data suggest that a single labyrinth is sufficient to produce normal semicircular canal–otolith interaction; therefore, the value of the test may be limited (15). Another modification is to test unilateral otolith-ocular response. During constant angular rate rotation, the patient is displaced laterally on the rotating turntable, so that one labyrinth becomes aligned with the rotary axis and the second (eccentric) labyrinth is solely exposed to inertial acceleration (16).<br /><br /><span style="font-weight:bold;">Vestibular Autorotation Test</span><br />The vestibular autorotation test is a method of evaluating the vestibuloocular reflex (head-shaking nystagmus) that has distinct clinical and practical advantages over rotary chair testing and ENG (2,17,18,19,20,21). Patients are wired with conventional EOG electrodes to record horizontal and vertical eye movement and are fitted with a lightweight headband containing an EOG amplifier and rotational velocity sensor. The patient is instructed to fix on a target and to rotate the head in synchrony with an auditory cue. The auditory cue accelerates to a maximum of 6 Hz and maintains this velocity for 13 seconds for a total test time of 18 seconds. The test is repeated three times in the horizontal and vertical dimensions. Phase, gain, and symmetry data are collected over the frequency range of 2 to 6 Hz (17).<br />The vestibular autorotation test has several attractive characteristics. The vestibular system is evaluated at frequencies more physiologic than the ultralow frequencies used in conventional ENG or rotary chair testing (20,22,23,24). The vestibular autorotation test can be performed efficiently, does not require dedicated space, is portable, allows testing in the vertical plane, and is well tolerated by patients. A potential disadvantage is that it includes the cervical-ocular reflex, but this is thought to be an unimportant contribution at the frequencies used. Vestibular autorotation testing also requires patients to rotate their heads appropriately, which may be problematic for elderly patients or patients with cervical pathology. Interpretation of the results is the same as with ENG and rotary chair testing. The clinical value of headshake nystagmus in evaluating dizziness has been challenged. Jacobson et al. (21) reported a sensitivity of only 27% and a specificity of 85%.<br /><br /><span style="font-weight:bold;">Dynamic Posturography</span><br />Computerized dynamic posturography came into the clinical realm in 1985 with the introduction of the Equitest system developed by NeuroCom. Posturography consists of two tests—the sensory organization test and the movement coordination test. The sensory organization test protocol calls for evaluation under six conditions in which sensory and proprioceptive inputs are varied (Fig. 131.3). During the sensory organization test portion, the patient's anterior and posterior body sway is recorded, and a performance index is calculated on a scale of 0% to 100% (fall, 0; no sway, 100). During the movement coordination test, the patient stands quietly on a platform, with the visual surround fixed (Fig. 131.4). The platform then undergoes a series of translational and rotational movements. The principal measurement recorded is the latency to onset of active recovery from destabilizing perturbation. Amplitude and symmetry of the neuromuscular responses also are recorded.<br />Several classification systems to assist with interpretation of results have been proposed (25). Table 131.4 summarizes one system (9). Although these patterns seem to suggest the site of the lesion, the test is not designed or suited for this purpose. A patient with abnormal scores on tests 5 and 6 can have a central or peripheral vestibular disorder. Patients with a compensated unilateral peripheral vestibular dysfunction have normal performance on tests 5 and 6. A patient with abnormal scores on conditions 1, 2, 3, and 4 is more likely to have a nonvestibular lesion or functional disorder (aphysiologic sway). A diagnosis of functional disorder is suggested when test results on the more difficult conditions (tests 4, 5, and 6) are equal to or better than those recorded during testing of the easier conditions (tests 1, 2, and 3).<br />The postural evoked responses in the movement coordination test portion of the evaluation are useful in validating the sensory responses and in identifying a central pathologic disorder. The tests are based on the automatic muscle responses thought to be triggered by proprioceptive changes. The response requires normal muscle, nerve, spinal cord, cerebellar, brainstem, and cortical function and is thus a diffusely distributed response. It is likely that the response is modulated by vestibular and other sensory input.<br />The most common test for perilymphatic fistula is ENG of the vestibuloocular reflex. Dynamic posturography offers an alternative testing strategy that eliminates potentially confounding effects from the visual and proprioceptive systems. Dynamic posturography can eliminate visual and somatosensory input and therefore better isolate the vestibular apparatus. Positive and negative pressures can be applied to the external auditory canal by means of standard tympanometry techniques, and postural adjustments can be analyzed (23). This test can be more sensitive than the traditional ENG fistula test (26,27). However, lack of a definitive test for the existence of a perilymph fistula impedes development of a clear relation.<br />Posturography can be combined with standard electro-myographic techniques. Electromyography is beneficial in identifying particular muscle response patterns triggered by changes in visual or somatosensory input controlled by the computerized dynamic posturography apparatus. These testing strategies are most useful in research aimed at understanding the complex interactions that allow maintenance of postural control.<br />Posturography is especially beneficial in documenting overall postural stability and in identifying particular balancing strategies. It is useful for vestibular rehabilitation and for monitoring improvement or decompensation. The computerized dynamic posturography evaluation is comfortable for patients, and they feel that their balance is being thoroughly tested. The test results correlate more closely than those of other balance function test results with the Dizziness Handicap Inventory, which is a subjective measure of overall balance limitations (28).<br /><br /><span style="font-weight:bold;">Pediatric Testing</span><br />Vestibular testing of children presents several challenges. Mental alerting, lack of tolerance of uncomfortable stimuli, inability to follow verbal commands, and inability to remain still all make testing difficult. Modifications of the standard adult ENG battery allow oculomotor, positional, and caloric testing (29). Simultaneous minimal caloric irrigations improve tolerability by reducing the degree of induced nystagmus and time of the procedure. Of course, the data obtained are not as informative as those provided by alternate binaural testing. Closed-loop irrigation systems can improve tolerance. Vestibular autorotation testing can prove useful in children, but more experience is needed. Rotational chair testing can be performed on most children, and very young children can sit on a parent's lap. Computerized dynamic posturography can be performed on older children, but normative data are not available. Most testing protocols can be shortened to minimize testing time and improve compliance.<br /><br /><span style="font-weight:bold;">Vestibular Evoked Myogenic Potentials</span><br />Standard caloric testing performed as part of an ENG battery evaluates the superior vestibular nerve because the lateral semicircular canal is being stimulated. A relatively new test can be performed using equipment traditionally used for auditory brainstem response testing to evaluate the function of the inferior vestibular nerve. Colebatch and Halmagyi (30) described the electromyographic response of the neck musculature to a loud, ipsilateral, broad band click. The afferent limb of the response is thought to be due to stimulation of the saccule with transmission via the inferior vestibular nerve to the brainstem and vestibular nuclei. The efferent limb of the response is via the spinocerebellar tract with the response typically recorded on the ipsilateral sternocleidomastoid muscle. The desire for inferior vestibular nerve evaluation has greatly increased the use of this test, which is termed the vestibular evoked myogenic potential (VEMP).<br />As experience with VEMP accumulates, the limitations and benefits of testing are becoming more apparent. Patients older than 60 years may have a reduced response in VEMP amplitude, which is thought to potentially be due to deterioration of saccular function (31). Pathologic changes in the brainstem, such as multiple sclerosis, may result in delayed potentials with variability noted in the response of the test to common conditions such as acoustic neuromas, Ménière disease, and vestibular neuritis (32). Surprisingly, early Ménière disease frequently demonstrates normal VEMP responses with progressive loss of the potentials with disease progression.<br /><span style="font-weight:bold;"><br />Dynamic Visual Acuity</span><br />Movement of the head causes significant retinal slip and loss of visual acuity unless the vestibulo-ocular reflex produces an appropriate compensatory response. Patients with dizziness frequently complain of visual blurring and unsteady visual sensations, particularly with head movement. The lack of visual stability on the retina can be quite disconcerting to patients and may prove dangerous forpatients during driving. Several commercial devices are available that can assess dynamic visual acuity. These tests use a rotational velocity sensor in combination with a computer screen to evaluate vision during head movement, giving a functional assessment of the vestibulo-ocular reflex in both horizontal and vertical planes (33).<br />Age does seem to affect dynamic visual acuity results with older patients demonstrating reduction in visual stability. Although some variability has been noted, the test does show good sensitivity and specificity in distinguishing normal patients from those with abnormalities.Patients with bilateral vestibular deficits were shown to have a greater degree of reduction in comparison with unilateral vestibular deficits and patients with nonvestibular dizziness. Surprisingly, oscillopsia did not correlate with abnormalities on vertical dynamic visual acuity in patients with bilateral vestibular loss. This seems to be due to the central preprogramming and the predictability of the head movements. Recent studies demonstrate recovery of the dynamic visual acuity following deterioration after traumatic brain injury associated with dizziness (34).Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-37389339473179729112009-02-04T05:10:00.000-08:002009-02-04T05:39:24.769-08:00Vestibular Function and AnatomyThe vestibular system, defined as the peripheral vestibular motion detectors and related central nervous system structures, senses motion in space and converts that motion into information that the remainder of the central nervous system can use to generate appropriate motor reflexes or facilitate complex processes such as the coordination of head, eye, and trunk movements or updating one's perception of his or her orientation in the world. The vestibular system, like the auditory system, converts physical stimuli into neural signals, but the vestibular system detects angular and linear acceleration, rather than sound. The vestibular system is present in all vertebrates and many invertebrates. Yet, despite the importance of spatial orientation in all mobile animals, the vestibular system is largely underappreciated until a malfunction occurs, at which point patients present to a physician, often an otolaryngologist, for treatment and education. This chapter discusses the anatomy of the peripheral vestibular system, the biophysics of sensory transduction, vestibular hair cell types and physiology, vestibular afferent types and physiology, and the organization of sensory inputs to the central nervous system, but it is only an introduction to this important, complex system.<br /> The complexity of challenges presented to the vestibular system on a daily basis is elucidated with a simple example. Figure 130.1 follows an office worker through the simple processes of looking for a book on a shelf. She pushes her chair back, stands, and turns left to face the shelf. She then tilts her head (right ear down) to scan the book titles. One way to describe the motion the worker's head makes between the two positions is to decompose the movement into linear (straight-line) motion and angular (rotational) motion, by considering a path made by the center of her head. In this example, the linear motion can be described as backing away from the desk 2 m, with a leftward motion of 3 m and an upward motion of 1 m (Fig. 130.1B). In terms of rotary motion, the woman pitches her head upward 40 degrees from looking down at the paper to looking horizontal. She turns 90 degrees to the left around a vertical axis to face the bookshelf. She then tilts her head 75 degrees toward the right-ear-down position to read the book titles (Fig. 130.1A). Thus, the motion the worker uses to complete the movement between the starting and ending positions can be characterized by three linear movements and three angular movements.<br /> The vestibular system must be able to detect both linear and angular motion in order for the brain to estimate the orientation of the body in space. An important additional piece of information needed for orientation is the direction of gravitational pull or the gravity vector. Among other things, the knowledge of the orientation of gravity allows humans to maintain a vertical stance. Even in the previous simple example, there is not only a complex interaction between the motions of the head, eyes, and body relative to one another, all of which use information generated by the vestibular system, but there is a visual, somatosensory, and vestibular system interaction that allows the worker to know her orientation relative to her surroundings<br /><br /><span style="font-weight:bold;">Gross Anatomy of Thevestibular System</span><br /> Vertebrates have what amounts to an inertial guidance system made up of multiple sensors of linear acceleration and multiple sensors of angular acceleration in each inner ear.This guidance system, the vestibular labyrinth, is housed in a portion of the otic capsule in the petrous portion of the temporal bone. The bony labyrinth is the thick bone of the otic capsule that houses the membranous labyrinth suspended in perilymph. The membranous labyrinth holds endolymphatic fluid and the neuroepithelial structures of sensory transduction. The perilymphatic and endolymphatic spaces of the labyrinth are continuous with those of the cochlea; therefore, the composition and homeostatic mechanisms of the perilymph and endolymph discussed in the cochlea chapter (Chapter 129) apply to the vestibular system as well. As in the cochlea, proper function of the vestibular system depends on the unique composition of these fluids.<br /> The vestibular labyrinth is a paired structure, with the right and left labyrinth mirroring one another. Subdivisions of the vestibular labyrinth include the three semicircular canals: the lateral or horizontal canal, the posterior canal, and the anterior or superior canal, all of which detect angular accelerations. The geometric layout of the canals is shown in Figure 130.2. The horizontal canals lie parallel to the line between the external auditory canal and the outer canthus of the eye, which is inclined 30 degrees above the horizontal axial plane. The vertical canals are roughly at right angles to the horizontal canals and to each other. When looking down at the top of the head, the anterior canal is oriented at approximately 45 degrees off midsagittal and 45 degrees anterior to the intraaural line. The posterior canal is aligned roughly 45 degrees behind the intraaural line; thus, the anterior canal on the left is roughly parallel to the posterior canal on the right, and the left posterior canal and the right anterior canal are similarly aligned.<br /> Housed in the vestibule are the otolith organs—the utricle and the saccule—which detect linear acceleration. Neither organ is perfectly planar, but the utricle is primarily aligned parallel to the earth and is roughly aligned with the ipsilateral horizontal canal (Fig. 130.3). At rest, the saccule is perpendicular and at right angles to the utricle. The sensitivity of detection of translational acceleration is greatest in the plane of the macula. Thus, the utricular macula is sensitive in the horizontal plane, and the saccular macula is sensitive in the sagittal plane<br /><span style="font-weight:bold;"><br />Basic Physics of Mechanotransduction</span><br /> Both the linear (utricle and saccule) and the angular (semicircular canal) acceleration sensors for the inner ear use a three-step process to convert accelerations of the head into useful information for the nervous system (Fig. 130.4). The elements used in these three steps are inertial mass, one or more sensory hair cells, and the nerve fibers connected to the hair cells through synaptic junctions. Figure 130.4A shows the system at rest (no acceleration). Figure 130.4B shows the response when the system is accelerated to the left. The resulting rightward movement of the mass (M) relative to the sensory hair cell deflects the sensory hairs, depolarizes the cell body, and increases the discharge rate of the attached nerve fiber.<br /><span style="font-weight:bold;"><br />Neuroepithelium</span><br /> The sensory hair cells in the membranous labyrinth are similar to those in the cochlea in that both detect small deflections and transmit the information provided by the displacement to the central nervous system (Fig. 130.5). However, significant differences are found between the cochlea and the vestibular neuroepithelia. The vestibular hair cell body is surrounded by supporting and other haircells. Sensory bundles extend from the apical surface of the vestibular hair cell body and are usually in contact with a gelatinous membrane, the motion of which is affected by displacement of the mass element: either the cupula of the semicircular canal or the otolithic membrane for the utricle and saccule. These sensory hair bundles have two distinct ciliary types. The kinocilium is the tallest cilia and is near the edge of the top of the hair cell. Kinocilia are not found on cochlear hair cells. The position of the kinocilium determines the orientation of the hair cell. There are many stereocilia, arranged in columns and rows, and the closer they are to the kinocilium, the taller they are. This arrangement produces an orderly array of stereocilia and a means by which alignment of an individual hair cell can be determined by its so-called morphologic polarization vector, which is shown as an arrow in Figure 130.6. Experimental data show that a functional axis of alignment corresponds with the morphologic one. It is in this axis that a cell responds most vigorously to the displacement of the stereocilia. Displacement of the stereocilia perpendicular to the polarization axis causes no change in the resting potential of the hair cells. On any one sensory organ, neighboring hair cells tend to have polarization vectors that are aligned.<br /> The electrical potential inside the body of hair cells differs from that of the fluids surrounding them because of active transport at the cell membrane. Bending the stereocilia on top of the cell toward the kinocilium opens potassium channels and temporarily increases the resting potential, depolarizing the cell. Deflection away from the kinocilium hyperpolarizes the cell. The channels responsible for transduction are located at the top of stereocilia in the utricle and are opened by relative motion of the stereocilia (1). The hair cells release a neurotransmitter (believed to be glutamate) that is excitatory to the hair cell afferents with which they connect. At rest, there is a baseline release of the neurotransmitter. This release is important because not only does deflection of the hair cell bundle toward the kinocilium (depolarizing the hair cell) increase transmitter release, but deflection of the hair cell bundle away from the kinocilium (hyperpolarizing the hair cell) reduces transmitter release. Thus, one hair cell detects both acceleration and deceleration along the axis of the morphologic polarization vector.<br /> There are two morphologically and physiologically distinct types of hair cell bodies: type I or chalice hair cells and type II or cylindrical hair cells. The body of a type I hair cell is entirely engulfed by one afferent terminal. Efferent innervation is indirect, as the efferent nerve has its synapse on the afferent nerve ending. Type II hair cells can have one or more afferent nerve endings on the body of the cell. Type II hair cells can also be directly or indirectly innervated by vestibular efferent terminals. Type I and type II hair cells are not evenly distributed throughout the neuroepithelium of either the semicircular canal ampullae or the utricular maculae. As discussed later, they are innervated by different classes of vestibular afferents.<br /> The neuroepithelium contains other cell types as well. Supporting cells have the nuclei located at the basal end of the sensory epithelial, above the basement membrane. These cells are believed to make and secrete the extracellular macromolecules of the cupula and otolith membrane. Dark cells can be found at the margins of the transitional epithelium surrounding the neuroepithelium. These dark cells are located directly above pigmented cells and are thought to produce the ionic composition of the endolymph.<br /><br /><span style="font-weight:bold;">Microanatomy and Biophysics of the Semicircular Canals</span><br /> The semicircular canal is a membranous structure shaped like a torus or hollow doughnut (Fig. 130.7). Maximum sensitivity is to rotation in the plane of the torus. At one end of the torus, there is an enlargement, the ampulla. A gelatinous flap, the cupula, completely seals one side of the ampulla from the other. Because the cupula is elastic, any pressure difference causes it to deflect. The interior of the torus is filled with endolymph, a liquid with the density and viscosity of water. The membranous portion of the canal is attached to the temporal bone. When the head is turned, the membranous labyrinth moves with it, but the endolymph inside has an inertial mass that tends to oppose the turning motion. This oppositional force causes pressure buildup across the cupula, deflecting the cupula from its equilibrium position. Within the physiologic range of motion, this deflection most nearly resembles the motion of the head of a drum or clamped diaphragm when pressure is uniformly applied to one side.<br /> Cilia are embedded in the gelatinous cupula. As the cupula is deflected, the stereocilia bend either toward or away from the kinocilium, producing an increase or decrease, respectively, in the firing rate of the vestibular nerve. The kinocilia are parallel to the long axis of the canal. In the lateral semicircular canal, hair cells are arranged such that the kinocilia are closest to the vestibule; maximal excitation occurs with ampullopetal flow of endolymph. In the posterior and superior semicircular canals, this arrangement is reversed—the kinocilium are farthest from the vestibule. Thus, ampullofugal flow is excitatory.<br /> The crista ampullaris has been divided into central, intermediate, and peripheral zones. In humans and other mammals, type I hair cells are relatively more common in the central zone than in the intermediate and peripheral zones (2). In contrast, type II cells are relatively less common in the central zone than in other zones.<br />More than half a century ago, Steinhausen constructed a biophysical model of the semicircular canal known as the torsion pendulum model The behavior of this model is determined by the mass of the endolymph, the viscous damping properties of the endolymph, and the springlike restoring force of the cupula. Estimates of these physical properties and knowledge of the geometric properties of the semicircular canal allow observers to relate deflection of the cupula to angular acceleration of the head. With this model, it can be predicted that cupular deflection is proportional to head velocity over a frequency bandwidth of approximately 0.1 to 10 Hz. Above and below this frequency bandwidth, the cupular deflection is not as great, and the sensitivity of the semicircular canal to velocity decreases. At 0 Hz, which corresponds to constant-velocity rotation, the torsion-pendulum model predicts there will be no response at all. The prediction made with this model agrees with the perception of a person who is turned at a constant velocity around a vertical axis. Subjects sense initial acceleration, but in the absence of other cues such as vision, subjects feel they are no longer rotating after 30 to 60 seconds. Rotating subjects who are suddenly brought to a full stop feel a sensation of turning in the opposite direction. This sensation is due to the inertia of the endolymph, which continues to rotate, deflecting the cupula in the direction opposite to that experienced with the initial rotation. Reflexive eye movements measured during these steps of velocity mirror the sensation felt by the subjects and are the basis of cupulometry used in the Bárány test and other tests of the vestibuloocular reflex.<br /> <br /><span style="font-weight:bold;">Microanatomy and Biophysics of the Otolith Organs</span><br /> All the sensors in the vestibular system combine a mass element connected to sensory hair cells (Fig. 130.4). In the case of the otolith organs (utricle and saccule), the mass is composed of calcium carbonate crystals known as otoconia that are embedded in a gelatinous supporting substrate. Displacement of this structure due to linear acceleration or change in orientation with respect to gravity affects a number of sensory hair cells. Each cell has a polarization vector oriented in a slightly different direction, making each one maximally sensitive to acceleration in that particular direction.<br /> The calcium carbonate crystals are suspended in the otolith membrane. Under this membrane are a number of sensory hair cells, each of which can have one or more afferent connections to the vestibular nerve. The drawing in Figure 130.8 is an exploded view. In reality, the stereocilia from the hair cells are in direct contact with the otolith membrane. In Figure 130.8, each of the sensory hair cells has a polarization vector with a small arrow indicating its direction of maximal excitation in the plane. The large arrow at the top of the otolithic mass represents linear acceleration that deflects the otolith mass in the direction of the arrow. Hair cells that have polarization vectors aligned with the arrow and in the same direction are excited maximally, whereas hair cells that have polarization vectors perpendicular to the acceleration are not stimulated.<br /> In the maculae of the utricle and saccule, type I hair cells are relatively more prevalent close to the striola than in the peripheral zone areas. The striola is a zone that runs the length of the macula, is about 100 microns wide, and divides the macula into the medial and lateral extra striola zones. The orientation of the hair cells on either side of the striola is roughly 180 degrees out of phase. Because the striola is C-shaped in the utricle, orientation vectors of hair cells in the utricle are aligned in all directions of the plane of the utricular macula.<br /> It is from an array of these hair cells that the brain can estimate the magnitude and direction of linear acceleration. If all polarization vectors were identically aligned, it would be impossible to determine the magnitude and direction of an acceleration vector in the plane of the otolithic macula. At least two different orientations are needed to resolve the vector in two dimensions. At least three separate orientations are needed to resolve the magnitude and direction of an acceleration vector in three dimensions.<br /> As in the simple example described earlier, each otolith organ has sensory hair cells arranged in a wide variety of orientations of its polarization vectors (Fig. 130.9). Because of this architecture, the asymmetries inherent in the sensitivity of a single hair cell can be canceled out within one otolith organ itself. The orientation of the polarization vectors is toward the striola in the utricular macula and away from the striola in the saccular macula. The right and left otolith organs, like semicircular canals, have mirror symmetry around the sagittal plane. The exact neural connections of the otolith organs have not been as extensively studied as those of the pairs of semicircular canals. Thus, the exact circuitry for resolving linear acceleration in three-dimensional space has not been determined.<br /> A simplified model of the response of the otolith organ to linear acceleration and changes in orientation with respect to gravity can be made with a mass, a spring, and a damper (Fig. 130.4). In this case, the mass is the otoconia macula minus the buoyant force placed on it by the surrounding endolymph. The spring and the damping factors come from the viscoelastic properties of the gelatinous structure in which the otoconia are embedded.<br /> The response characteristics of the otolith organs can be predicted with the above model. Although the specific gravity of the otoconia has been found to be 2.7 times that of the endolymph, the damping forces of the otolithic membrane are more difficult to measure. These damping forces prevent oscillation of the otolith membrane in response to a given linear acceleration. However, when direct recordings are taken from otolith afferents, physiologic performance deviates from that predicted in the model. There are two types of neuronal otolith afferent populations that can be defined that are similar to those in the semicircular canals. The first population appears to respond to head position, and its responses closely follow those predicted with the model for sinusoidal stimulation at frequencies up to 0.1 Hz. A second population of neurons encodes information on linear acceleration. These neurons display increasing gain in proportion to higher-frequency stimuli.<br /> theoretically, how two otolith organs operating in the same plane react to head tilt or to acceleration of the head in the plane of the otolithic macula. If there is no acceleration in that plane, the nerve firing rate of each otolith organ is constant and equal. When the head is tilted to the left, the firing rate of the nerve innervating the left otolith organ increases, while the firing rate of the nerve innervating the right otolith organ decreases. Maximum sensitivity is obtained by means of subtracting the firing rate of the right nerve from that of the left. Acceleration of the head to the right causes deflection of both otoconia to the left in a manner similar to a head tilt to the left. This acceleration produces an increase of the firing rate of the left nerve and decrease in the firing rate of the right nerve. This model (Fig. 130.10) shows that the asymmetry present in one hair cell innervating an otolith organ can be canceled by combining it with a signal from a hair cell that has the same polarization factor in the other side. It also shows that the otolith organs are influenced by both tilt orientation with respect to gravity and linear acceleration.<br /> Einstein recognized that an ambiguity presented between linear acceleration and gravity, and in aviation, is a problem during the acceleration of takeoff, when pilots have trouble differentiating the acceleration of the airplane from the gravity vector. Because translational motion in one direction creates the same inertial force as gravity to tilt in the opposite direction (Fig. 130.10), this problem is known as a tilt-translational ambiguity. Recent research has demonstrated that the central nervous system uses semicircular canal information (activated during tilt but not during translation) in combination with the otolith input to distinguish, for example, tilting the head upward versus accelerating forward as in a car, sled, or airplane (3). This mechanism works poorly at low frequency rotations. In the circumstance where the rotational component of the motion is at low frequency (<0.1 Hz), the brain uses visual or tactile information to help interpret the otolith's signal. In the absence of non-otolith input, such as vision or rotation at frequencies above 0.1 Hz, the system defaults to interpreting linear acceleration as tilt (or gravity). Returning to the aviation example, fighter pilots taking off from an aircraft carrier deck at night will feel as if they are tilted backwards during forward acceleration. The natural correction for this feeling is to steer the plane downward, which could result in disaster.<br /><br /><span style="font-weight:bold;">Vestibular Afferents</span><br /> Based on the anatomy of peripheral termination, there are three distinct vestibular afferent types: calyx, dimorphic, and bouton. Calyx afferents terminate exclusively on type I hair cells at the calyx endings. Calyx endings may terminate on one or several hair cells. Dimorphic afferents have both calyx endings on type I hair cells and bouton endings on type II hair cells. Dimorphic afferents are likely the most prevalent. Bouton afferents have only bouton endings and thus only terminate on type II hair cells. These three afferent types differ immunohistochemically. Calrentinin, a calcium binding protein, is seen only in calyx afferents; peripherin, which is an intermediate filament protein, is seen in bouton afferents; and neither of these markers is seen in dimorphic afferents.<br /> There are other anatomic distinctions between these afferent types. Calyx afferents have characteristically thick axons, whereas bouton afferents are thinner. Dimorphic afferents, however, can be thick or thin. The processes to the calyx endings are thicker than the processes to the bouton endings. The distribution of the three fiber types is also characteristic. Calyx afferent endings are found in the central zone of the crista ampullaris, whereas dimorphic afferents terminate in the central, intermediate, and peripheral zones, and bouton fibers terminate in the peripheral zone. Similarly, utricular calyx afferents terminate in the striola region, whereas dimorphic afferent terminals are seen throughout the macula and bouton afferents and generally terminate peripherally.<br /> Afferents also differ in their discharge regularity, conduction velocity, and sensitivity to vestibular and galvanic stimulation. Although response gains, conduction velocity, and discharge regularity over a population of neurons all fall along a continuum, based on these characteristics, vestibular afferents fall into three general groups that correspond well with the three groups (calyx, dimorphic, and bouton) determined by peripheral morphology. Calyx afferents innervating the central ampulla or striola are large fibers that are irregularly firing, sensitive to galvanic stimulation, and have a low sensitivity to angular motion. Dimorphic afferents may have thick or thin axons. Those terminating more centrally tend to have thicker axons and are irregularly firing, galvanically sensitive, and sensitive to (rotational or linear) stimulation. Dimorphic afferents terminating peripherally (either in the macula or crista) and bouton afferents tend to be thinner fibers with lower galvanic and natural stimulation thresholds and are regularly firing with slower conduction velocities (4). These different afferent types may be of more interest than just physiologic curiosity. The high sensitivity irregular afferents are sensitive to small perturbations but have nonlinear dynamics because they readily silence when the head moves in the inhibitory direction. These afferents may be best suited for quick, nonlinear reflexes such as vestibulospinal responses to inhibit a fall. In contrast, the linear characteristics of the thinner, more regular afferents are appropriate for linear vestibular reflexes, like the vestibuloocular reflex, that must work over a wide range of frequencies and peak velocities (5).<br /> Both semicircular canal afferents and otolith afferents are cosine tuned, which means they have one best characteristic response vector. For utricular afferents, these vectors can lie anywhere in the horizontal plane and are dependent on the orientation vector of the hair cells that they innervate. The response of the afferent is proportional to the cosine angle between the direction of stimulation and the orientation vector of the afferent. Similarly, the rotational vector of maximum stimulation for semicircular canal afferents is in the plane of rotation of the canal. The response of the fiber decreases as cosine of the angle between the plane of rotation and the canal plane. The cosine tuning of the afferent is consistent with the fact that transmitter release by hair cells is proportional to the cosine of the angle between the displacement of the hair cell bundle and the direction of stimulation (Fig. 130.6). Thus, both the hair cells and the afferents are cosine tuned. The coding of the vestibular system is such that the direction of stimulation is encoded by the afferent population stimulated, and the intensity of the movement is encoded by the intensity of the response of the stimulated afferent.<br /> All of the vestibular epithelium are also innervated by vestibular efferent neurons. These neurons have cell bodies in the brainstem in areas around the genu of the facial nerve. Their fibers in humans run mixed with the vestibular afferent fibers and can terminate either presynaptically (on type II hair cells) or postsynaptically on calyx or bouton endings. The function of the vestibular efferent system in mammals is unknown.<br /><br /><span style="font-weight:bold;">Vestibular Brainstem</span><br /> Vestibular afferents are bipolar neurons that have cell bodies in the inferior and superior Scarpa (vestibular) ganglion. The peripheral (dendritic) processes of these neurons exit the neuroepithelium and collect in the inferior and superior vestibular nerves. The inferior division includes neurons from the posterior canal and saccule, and the anterior division includes utricular, horizontal canal, and anterior canal afferents (Fig. 130.11). Axonal branches of primary afferent ramify in the vestibular nuclei. Afferent terminals from the different end organs primarily innervate the various divisions of the vestibular nuclei, although terminations are seen in the cerebellum and other brainstem nuclei as well. The precise terminations by end organ (semicircular canal or otolith) in the central nervous system are similar in many species (6). Not only does the brainstem region receive convergent output from different branches of the vestibular nerve, but individual neurons receive afferent input from one, two, or more end organs (canal ampullae or otolith maculae). Thus, the vestibular nuclei integrate information from multiple ipsilateral receptors.<br /> There are four major vestibular nuclei in the brainstem: the lateral (Deiters), superior, medial, and inferior (spinal, descending) nuclei. In addition, there are several minor vestibular nuclei, including nucleus y, that are identified in various species by various investigators. The vestibular nuclei not only receive vestibular information but other information pertaining to spatial orientation as well. These inputs include optokinetic signals through the accessory optic system, neck proprioceptive signals, and Purkinje cell projections from the cerebellar cortex. From the vestibular nuclei, vestibular signals are passed throughout the central nervous system. The dominant output of the vestibular nuclei are to the ocular motor nuclei, via the medial longitudinal fasciculus and the ascending tract of Deiters; to the spinal cord, via the medial and lateral vestibulospinal tracts; to the cerebellum, via the cerebellar peduncles; and to the contralateral vestibular nuclei, via the vestibular commissural system. Other pathways connect the vestibular nuclei with the autonomic system, which has implications in motion sickness and blood pressure control, and with the thalamus.<br /> One important function of the vestibular commissural system is inhibition. Experimental data show that the discharge frequencies of neurons excited during ipsilateral angular acceleration are also excited due to a decrease of crossed inhibition, which is caused by a decrease in discharge rate from the contralateral paired semicircular canal. This reciprocal mechanism is the basis of the so-called push-pull connection that increases the sensitivity of the system through use of the difference in signals between the functionally paired semicircular canals (left horizontal–right horizontal, left anterior–right posterior, left posterior–right anterior) in either ear. In this way, the paired canals complement one another and tend to cancel out the asymmetries inherent in the hair cell transduction mechanisms and afferent firing patterns mentioned earlier. The neural signals from these pairs of canals converge in a synergistic way in the nervous system, allowing the system to function even in the presence of a complete unilateral lesion. However, responses in patients with unilateral lesions are more asymmetric than those among healthy persons given high enough angular acceleration to reveal these inherent asymmetries, which are apparent when the push-pull redundancy is not available.<br /> The best studied vestibular reflex is the vestibuloocular reflex. Vestibuloocular reflexes are of two types: compensatory reflexes that stabilize gaze during motion and orienting reflexes that align the eye with the gravitational vector. One of the challenges for the nervous system is to translate signals from the semicircular canal planes into coordinates appropriate for effector action. Those who study the vestibular system use an external frame of reference, as shown in Figure 130.3. Linear acceleration or rotational acceleration occurs around three axes that are perpendicular to each other: the interaural or pitch axis, the nasal-occipital or roll axis, and the rostral-caudal or yaw axis. The vestibule-oculo-motor system, however, is thought to use a coordinate system based on the orientation of the three pairs of semicircular canals. Experiments have shown that stimulation of afferent branches of the eighth cranial nerve that come exclusively from one semicircular canal produces reflexive eye movements that tend to rotate around the axis of greatest sensitivity for that canal. The three agonist-antagonist pairs of eye muscles themselves do not produce eye movements that completely correspond to these axes of orientation of the semicircular canals. Thus, there is a distribution of signals from the semicircular canals to produce compensatory eye movement of the desired magnitude and direction.<br /> According to a simplified analysis, the connection between the three pairs of semicircular canals and the three pairs of eye muscles can be described with a set of nine constant coefficients. First-order analysis indicates that the translation of incoming vestibular systems needed to produce compensatory eye movement is a relatively simple operation for the brain to perform. This operation is contrasted to the more complicated series of commands that must be given when signals from the vestibular system are used to stabilize the head on the neck or the body with leg muscles.<br /> The nervous system can adapt its response by comparing vestibular input to other sensory input. When the head moves, the vestibuloocular reflex tends to stabilize the image of an object in space on the retina by producing an eye movement compensatory to the head movement. At any time, the functional anatomic connections needed to stabilize an object can be thought of as a set of nine constant coefficients that distribute the incoming vestibular systems to the ocular motor neurons to form the reflexive eye movement response. For example, the motion of the head 10 degrees to the right produces eye movement 10 degrees to the left.<br /> Provisions have been made in the nervous system for this response to adapt when necessary, owing to factors such as disease or aging. One such example is people with myopia who wear eyeglasses. If the magnification of the lens is 1.2 times, rotation of the head 10 degrees to the right produces rotation of the world as viewed by the eye 12 degrees to the left and therefore demands a corresponding reflexive eye movement 12 degrees to the left. The nervous system makes this form of adaptive change to resolve a conflict between afferent inputs, in this case vestibular and visual inputs. In this example, the nervous system can correspondingly increase the amount of eye movement produced for a given head movement so that the error between the head motion input and eye motion response is reduced to nearly zero. This gain plasticity requires participation of the floccular lobe of the cerebellum.<br /><span style="font-weight:bold;"><br />Current Vestibular Issues</span><br /> Like most fields in basic sciences, the vestibular system is actively studied in a number of excellent laboratories. Among the many actively investigated areas are the pharmacology of the vestibular periphery, interactions between active head movements and the passive vestibular reflexes, the role of vestibular signals in spatial orientation, the function of vestibular efferent system, physiologic and cellular mechanisms of adaptation and compensation after vestibular injury, and the adaptation of the vestibular system to microgravity. In addition, efforts are ongoing to develop prosthetic devices to aid patients with vestibular deficits. This research holds the promise of improving our understanding of this vital, well conserved, and underappreciated “sixth†sensory system.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-86398481822572030912009-02-04T04:43:00.000-08:002009-02-04T05:43:23.681-08:00Anatomy and Physiology of Hearing<span style="font-weight:bold;">John H. Mills<br />Samir S. Khariwala<br />Peter C. Weber</span><br /><br /> This chapter provides a brief summary of the most basic features of the anatomy and physiology of the ear. It is divided into sections on the external and middle ear, cochlea, and central nervous system (CNS). The focus is on the anatomic and physiologic bases of audition with an effort directed at functional features. Surgical anatomy, vasculature, and eustachian tube function are not discussed.<br /><br /><span style="font-weight:bold;">External Ear</span><br /><br /> The external ear consists of the pinna (auricle) and the external auditory canal from the meatus to the tympanic membrane (Fig. 129.1). The pinna of humans is composed mostly of cartilage and has no useful muscles. The center of the pinna, the concha, leads to the external auditory meatus, which is about 2.5 cm long. The lateral third of the canal is the cartilaginous portion. It contains cerumen-producing glands and hair follicles. The remaining medial two thirds is the bony portion, including an epithelial lining over the tympanic membrane (1).<br />The external ear and the head have a passive but important role in hearing because of their acoustic properties. The concha, or bowl of the auricle, has a resonance of about 5 kHz, and the irregular surface of the pinna introduces other resonances and antiresonances. These acoustic features are useful to help differentiate whether sound sources are in front of the listener or behind.<br /> The external auditory canal (EAC) is essentially a tube that is open at one end and closed at the other; thus the EAC behaves like a quarter-wave resonator. The resonant frequency (f0) is determined by the length of the tube; the curvature of the tube is irrelevant. For a tube of 2.5 cm, the resonant frequency is approximately 3.5 kHz:f0 = Velocity of sound @ 350m/s/(4×2.5 cm)<br /> A flat, wide-band sound measured in a sound field is changed considerably by the acoustic properties of the head and external ear. As Figure 129.2 demonstrates, a gain of about 15 dB occurs in the 3-kHz range of the human, cat, and chinchilla, and 10 dB between 2 and 5 kHz. The acoustic properties of the external ear are one of the reasons noise-induced hearing losses occur first and most prominently at the 4-kHz frequency region (boilermaker notch).<br /> In addition to the prominence of noise-induced hearing loss in the 4-kHz region, the acoustic properties of the head and external ear have an important role in several hearing functions. In localization of sound sources, the head acts as an attenuator at frequencies at which the width of the head is greater than the wavelength of the sound. Thus at frequencies greater than 2 kHz, a head shadow effect occurs, in which interaural intensity differences of 5 to 15 dB are used to localize sound sources. At lower frequencies, at which the wavelength of the sound is larger than the width of the head, little attenuation is provided by the head. Interaural time differences (~0.6 ms for sound to travel across the head) are the salient cues for localization. The head-shadow effect is the reason right-handed hunters using rifles and shotguns have larger hearing losses in their left ears than in their right ears and vice versa. The muzzle of the gun, where the acoustic energy is greatest, is closer to the left ear, and the right ear is protected by the head-shadow effect.<br /> The 10- to 15-dB gain provided by the external ear in the 3- to 5-kHz region is useful for improving the detection and recognition of low-energy, high-frequency sounds such as voiceless fricatives. The importance of the acoustic properties of the external ear and head is reflected in hearing-aid design and evaluations. Finally, the resonance of the external canal is approximately 8 kHz in infants and decreases to adult values after approximately 2.5 years of age. This developmental feature has several clinical implications, especially for sound-field testing and for hearing-aid design and evaluation of infants.<br /><span style="font-weight:bold;"><br />Middle Ear</span><br /><br /> The middle ear transmits acoustic energy from the air-filled EAC to the fluid-filled cochlea. It functions as an impedance-matching device inasmuch as it couples the low impedance of air to the high impedance of the fluid-filled cochlea. The impedance match is achieved in three ways. The first and most important factor is that the effective vibratory area of the tympanic membrane is approximately 17 to 20 times greater than the effective vibratory area of the stapes footplate (Fig. 129.3). A second factor involves the lever action of the ossicular chain. The arm of the long process of the incus is shorter, by a factor of 1.3, than the length of the manubrium and neck of the malleus. A third and minor factor is the shape of the tympanic membrane. The combined result of these three factors is a pressure gain of approximately 25 to 30 dB. The variance in published measurements of the transformer ratio is noteworthy. With the exception of studies of acoustic impedance of the ear, most data are from studies of human cadavers, with all of their shortcomings, or of animals, usually cats. In addition to its role in the transfer of power to the inner ear, the tympanic membrane protects the middle ear space from foreign material of the ear canal and maintains the air cushion that prevents insufflation of foreign material from the nasopharynx through the eustachian tube.<br /> The vibratory behavior of the ossicular chain is described in Figure 129.3. The transformer action of the tympanic membrane and ossicular chain provides for relatively efficient transfer of power to the inner ear, and the fidelity of sound transmission across the middle ear is outstanding. Distortion of sound signals does not occur in the middle ear, even for input signals with sound levels greater than 130 dB sound pressure level (SPL).<br /> The middle ear, including the tympanic membrane, ossicular chain with supporting ligaments, and middle ear space, can be viewed as a passive mechanical system with both mass and compliant elements and therefore resonant properties. This linear system is coupled to the cochlea, which contributes a large resistance. The result is a middle ear system that is highly damped and linear and has a wide frequency response. The input–output function or transfer function of the middle ear is shown in Figure 129.4A. The ratio of the volume velocity of the stapes to sound pressure at the tympanic membrane increases in humans to approximately 800 to 900 Hz, which is the resonant frequency of the middle ear, and decreases at higher frequencies. Phase shift or time lag between movement of the tympanic membrane and the stapes generally increases with frequency (Fig. 129.4B). Although the middle ear is an impressive system in terms of frequency response, linearity, and transformer properties, considerably less than half of the power entering the middle ear actually reaches the cochlea because of the absorption of energy by the ligaments and middle ear. As shown in Figure 129.5, the human middle ear is particularly inefficient at frequencies greater than 2 kHz, especially in comparison with the ears of cats and chinchillas. It also is important to recall that a 50% loss of power is a loss of only 3 dB.<br /> Auditory function is profoundly affected by cochlear impedance as well as the combined acoustic effects of the head, external ear, and middle ear. The combined effects of the acoustic properties of the head, external ear, and middle ear, as well the input impedance of the cochlea, have a profound effect on auditory function. For example, these factors determine the shape of the audibility curve and therefore the frequency range of human hearing (Fig. 129.6). For example, humans do not detect and recognize sounds greater than approximately 20 kHz because such high-frequency sounds are not transmitted efficiently through the middle ear to the cochlea. A second example of this sound transformation is shown in Figure 129.7, in which the spectrum of a cannon measured in a sound field is compared with the spectrum of the cannon by the time it is transformed and shaped by the acoustic properties of the external ear, head, middle ear, and input impedance of the cochlea. Low-frequency energy is not transmitted to the cochlea, and the frequency region of greatest energy concentration is 3 to 4 kHz. Thus, these acoustic properties are primarily responsible for the ability of intense low-frequency sounds (measured in a sound field) to produce high-frequency hearing losses and injuries in the basal region of the cochlea.<br /> Two striated muscles, the tensor tympani and the stapedius, are located in the middle ear. The former attaches to the malleus and is innervated by the trigeminal nerve. The stapedius muscle attaches to the stapes and is innervated by the stapedial branch of the facial nerve. Noticeably the stapedius and tensor tympani muscles are the smallest striated muscles in the body and also have a high innervation ratio, that is, nerve fibers per muscle fiber. Although no question remains that contraction of these muscles affects sound transmission through the middle ear, the details of the effect and the extent of the influence of the middle ear muscles are still not fully understood. A number of disparate functions have been attributed to the middle ear muscles.<br /> One function of the middle ear muscles is to protect the cochlea from loud sounds (2). When sounds louder than approximately 80 dB SPL are presented monaurally or binaurally, consensual (bilateral) reflex contraction of the stapedius muscle occurs. This contraction increases the stiffness of the ossicular chain and tympanic membrane, attenuating sounds less than approximately 2 kHz. Although the tensor tympani contracts as part of a startle response, acoustic reflex data from human subjects with neurologic involvement of cranial nerves V and VII suggest that the tensor tympani does not normally respond to intense acoustic stimulation. Laboratory and field studies of noise-induced hearing loss have shown convincingly that the stapedial reflex protects the cochlea, particularly from low-frequency (<2 kHz) sounds in excess of 90 dB. Inasmuch as the latency of the acoustic reflex is greater than 10 ms, the cochlea may be unprotected from short-duration, unanticipated impulsive sounds.<br /> The following functions have been attributed to the middle-ear muscles. Some of these functions include providing strength and rigidity to the ossicular chain; contributing to the blood supply of the ossicular chain; reducing physiologic noise caused by chewing and vocalization; improving the signal-to-noise ratio for high-frequency signals, especially high-frequency speech sounds such as voiceless frica-tives, by means of attenuating high-level, low-frequency background noise; functioning as an automatic gain control and increasing the dynamic range of the ear; and smoothing out irregularities in the middle-ear transfer function.<br /><br /><span style="font-weight:bold;">Cochlea</span><br /><br /> The human cochlea is a coiled, bony tube approximately 35 mm long, divided into the scala vestibuli, scala media, and scala tympani (Fig. 129.8). The scalae vestibuli and tympani contain perilymph, an extracellular fluid-like material with a potassium concentration of 4 mEq/L and a sodium concentration of 139 mEq/L. The scala media is bounded by the Reissner membrane, the basilar membrane and osseous spiral lamina, and the lateral wall. It contains endolymph, an intracellular-like fluid with a potassium concentration of 144 mEq/L and a sodium concentration of 13 mEq/L. The scala media has a positive direct current (DC) resting potential of approximately 80 mV that decreases slightly from base to apex. This endocochlear potential is produced by the heavily vascularized stria vascularis of the lateral wall of the cochlea. The sodium–potassium–adenosine triphosphatase (Na+-K+-ATPase) pumps in a number of specialized cells of the stria vascularis contribute to this potential (3).<br /> Acoustic energy enters the cochlea through the piston-like action of the stapes footplate on the oval window and is coupled directly to the perilymph of the scala vestibuli. The perilymph of the scala vestibuli communicates with the perilymph of the scala tympani through a small opening at the apex of the cochlea known as the helicotrema. The organ of Corti rests on the basilar membrane and osseous spiral lamina (Fig. 129.9). The basilar membrane is approximately 0.12 mm wide at the base and increases to approximately 0.5 mm at the apex. The major components of the organ of Corti are the outer and inner hair cells, supporting cells (Deiters, Hensen, Claudius), tectorial membrane, and the reticular lamina–cuticular plate complex (Fig. 129.10). Supporting cells provide structural and metabolic support for the organ of Corti. The phalangeal processes of the Deiters cells form tight cell junctions of the reticular lamina.<br /> Outer and inner hair cells of the organ of Corti are important in transduction of mechanical (acoustic) energy into electrical (neural) energy. Outer hair cells are radically different from inner hair cells. Figure 129.11 and Table 129.1 detail these differences (4). In addition to the morphologic differences between outer and inner hair cells, neural innervation is different (Fig. 129.12). The spiral ganglion, the cell body of the auditory nerve, sends axons to the cochlear nucleus of the brainstem, whereas the dendrite projects through the osseous spiral lamina. Of the 50,000 neurons that innervate the cochlea, 90% to 95% synapse directly on inner hair cells. These are called type I neurons. Each inner hair cell is innervated by approximately 15 to 20 type I neurons. In contrast, 5% to 10% of the 50,000 neurons innervate the outer hair cells (type II neurons). Each type II neuron branches to innervate approximately 10 outer hair cells. In addition to the afferent innervation pattern of the cochlea, approximately 1,800 efferent fibers, originating from the ipsilateral and contralateral superior olivary complex, project to the cochlea (Fig. 129.13).<br /> Transduction is initiated by displacement of the basilar membrane in response to displacement of the stapes due to acoustic energy. The displacement pattern of the basilar membrane is a traveling wave (Fig. 129.14). The basilar membrane is stiffer at the base than in the apex. The stiffness component is distributed continuously. Therefore, the traveling wave always progresses from base to apex. The maximal amplitude of basilar membrane displacement varies as a function of stimulus frequency. Traveling waves produced by high-frequency sounds (10 kHz) have maximal displacement near the base of the cochlea, whereas the waves to low-frequency sounds (125 Hz) have the maximum toward the apical region. Traveling waves generated by high-frequency sounds do not reach the apical region of the cochlea, whereas waves to low-frequency sounds can travel the entire length of the basilar membrane.<br />In the past, the mechanical traveling wave was considered a broadly tuned response, with finer tuning introduced subsequently by transduction, the auditory nerve, and the CNS. Data obtained with sensitive recording and detection methods, however, have shown that the traveling wave has an extremely sharply tuned response (Fig. 129.15) and that many of the remarkable frequency-selective abilities of the ear can be explained by the mechanical properties of the cochlea<br /> The mechanism by which the sharply tuned peak is generated within the mechanical traveling wave involves an enhancement known as the cochlear modifier. This is an activity of the outer hair cells that enhances the motion of the basilar membrane at frequencies near the best frequency of the particular cochlear location. This enhancement contributes to the fine frequency-selective abilities of the ear and to the sensitivity of the ear and ability to detect extremely faint sounds. The notion of an active process in the cochlea, the cochlear amplifier, is supported by the phenomenon of otoacoustic emissions. That is, when a short-duration signal is presented to the ear, an echo emanating from the cochlea can be recorded in the external auditory meatus. Because the energy of the echo can be greater than the energy of the short-duration signal, an active process, the cochlear amplifier, is assumed. Factors that may contribute to the cochlear amplifier include motility of outer hair cells and the mechanical properties of the stereocilia and tectorial membrane.<br /> The stereocilia–hair cell complex is critical to transduction. Stereocilia are bundles of actin filaments that form tubes and are inserted into the cuticular plate. They also are cross-linked between themselves. Stereocilia of inner hair cells probably do not contact the tectorial membrane, but those of outer hair cells are in direct contact. Deflection of the stereocilia by the traveling wave opens and closes nonspecific ion channels at the tips of the stereocilia, resulting in current flow (potassium) into the sensory cell. The flow of potassium ions into the sensory cell is modulated by the opening and closing of ion channels of the stereocilia. The potassium flux is caused by the endocochlear potential of +80 mV added to the negative intracellular potentials of hair cells. The resulting intracellular depolarization causes an enzyme cascade involving calcium. This ultimately leads to the release of chemical transmitters, and the subsequent activation of the afferent nerve fibers.<br /> Although the notion of the cochlea as an active rather than a passive organ is no longer debated, specific details of the cochlear amplifier and the biologic basis of its operation are under active investigation. One point of view attributes the cochlear amplifier to the ability of hair cells to contract and lengthen in response to electrical signals, a property called somatic electromotility. A protein named prestin has been identified in outer hair cells and is considered to be the motor protein of outer hair cells and the driving force of electromotility of hair cells (5). Another point of view focuses on rapidly acting potassium and calcium ion channels presumed to be the basis of the cochlear amplifier and its regulation (6). A third approach suggests that a collection of motor proteins within a hair cell can generate oscillations that depend on the elastic properties of the cell (7). The foregoing approaches are nonlinear models that involve rapidly acting calcium channels. Specification of the biologic basis of the cochlear amplifier (nonlinearity) is important inasmuch as many forms of hearing loss involve loss of the cochlear amplifier.<br /> The neurotransmitters of the afferent and efferent systems are the subject of intense study. In regard to the afferent system, analysis of excitatory amino acid receptor expression by the techniques of reverse transcriptase–polymerase chain reaction, in situ hybridization, and immunochemical analysis indicates that glutamate is the afferent neurotransmitter. Glutamate has been detected in both spiral ganglion cells and sensory cells (8). The principal transmitter substance of cochlear efferent fibers is acetylcholine. It is possible that the organ of Corti is mechanically modified by means of motility changes of outer hair cells under the influence of the efferent system. Acetylcholine acts on receptors to produce hyperpolarization of the cell membrane and doubling of the input conductance of the cell. The acetylcholine receptor has both muscarinic and nicotinic features. In addition to acetylcholine, γ-aminobutyric acid and several neuroactive peptides are neurotransmitters for the efferent system (9,10).<br /><br /><span style="font-weight:bold;">Gross Cochlear Potentials</span><br /> Four gross (extracellular) potentials can be recorded in the cochlea (11)—endolymphatic (endocochlear) potential, cochlear microphonic, summating potential, and whole-nerve action potential (Fig. 129.16). Unlike the other cochlear potentials, the endolymphatic potential is not generated in response to acoustic stimulation; rather, it is a DC potential of 80 to 100 mV recorded in the scala media. It arises from the stria vascularis of the lateral wall of the cochlea. The stria vascularis is considered to be the energy source, or “battery,â€� of the cochlea, crucial for transduction. The nature of the energy source is related to the heavy vasculature of the stria vascularis and to the Na+-K+-adenosine triphosphatase (ATPase). This pump has been localized to several types of cochlear cells, including marginal cells of the stria vascularis, outer sulcus cells, and fibrocytes near the attachment of the Reissner membrane and in the spiral ligament. Whereas Na+-K+-ATPase must play a significant role in ion transport in the cochlea, the nature of the energy source and the details of the ion exchange remain active research issues (3).<br /> Malfunctioning of the mechanisms involved in production of endolymph and the endolymphatic potential can produce hearing loss, sometimes called metabolic presbycusis. When the flow of endolymph through the ductus reuniens is blocked, endolymphatic pressure increases, and hydrops occurs.<br /> The cochlear microphonic is an alternating current (AC) voltage usually recorded within the cochlea or near the round window. It represents the potassium ion current flow through mainly the outer hair cells; that is, the electrical resistance of outer hair cells is altered by the motion of the basilar membrane. When stereocilia are bent away from the modiolus, the resistance of the hair cells decreases. The result is an increase in current flow and a small decrease in endolymphatic potential. When stereocilia are bent toward the modiolus, resistance increases and current flow decreases with an accompanying increase in the endolymphatic potential. The corresponding voltage fluctuations, the cochlear microphonic, depend on the presence of outer hair cells. Unlike neural potentials, the waveform of the cochlear microphonic mirrors the motion of the basilar membrane. The summating potential is a DC potential recorded in the cochlea in response to sound. It follows the envelope of the stimulating sound. Recordings of this DC potential can be made in the scala tympani, media, or vestibuli and in some circumstances from a gross electrode in the human ear canal. The potential can be positive or negative, and it can reverse polarity, depending on electrode location or stimulus frequency and level. The summating potential probably has several origins, but it largely reflects the DC shifts caused by stimulus-driven intracellular potentials of outer hair cells. Inner hair cells contribute to these to a lesser extent.<br /> The whole-nerve or compound action potential arises from the all-or-none discharge of auditory nerve fibers. The compound action potential is recorded most effectively with a gross electrode placed near the round window or auditory nerve and with high-frequency signals with rapid onsets. Such signals produce synchronous neural activity, which is summed to become the compound action potential waveform. The amplitude of the compound action potential increases with stimulus intensity over a 40- to 50-dB range, whereas latency decreases as stimulus intensity is increased. At high levels, a second peak sometimes is observed that probably reflects activity of the cochlear nucleus. The compound action potential can be clinically recorded with scalp electrodes or electrodes in the external meatus or by means of a transtympanic approach in which an electrode is placed near the round window niche. The ratio of the amplitude of the summating potential to the amplitude of the compound action potential has been used as an indicator of perilymphatic fistula, but the validity of this indicator is doubtful.<br /><span style="font-weight:bold;"><br />Eighth Nerve Physiology</span><br /> The auditory nerve has approximately 30,000 fibers in humans and approximately 50,000 in cats. Perhaps one of the most important research findings in recent years was the observation that 90% to 95% of neurons (type I, radial fibers) innervate inner hair cells, whereas 5% to 10% (type II, outer spiral fibers) innervate to the outer hair cells (Fig. 129.12). Most, if not all, recordings from auditory nerve fibers are from the larger type I fibers in contact with inner hair cells. These radial fibers have bipolar cell bodies in the spiral ganglion. Outer spiral fibers are monopolar and unmyelinated. Most recordings of single units of the auditory nerve are obtained by means of inserting a microelectrode into the auditory nerve where it exits the internal auditory meatus. The most basic measures of auditory nerve function are spontaneous rates, tuning curves, and intensity (rate-level) functions.<br /> Most auditory nerve fibers in mammals discharge in the absence of acoustic stimulation. The nerve fibers have been classified into three categories on the basis of rate of spontaneous discharge—high (18 to 120 spikes per second), medium (0.5 to 18 spikes per second), and low (0 to 0.5 spikes per second). Fibers with high rates of spontaneous activity respond to auditory signals at lower levels than do fibers with medium or low rates of spontaneous activity. In other words, the most-sensitive fibers have the most-spontaneous activity. Fibers with high spontaneous rates have thick dendrites that tend to terminate on the side of inner hair cells facing outer hair cells. Fibers with low and medium spontaneous rates have thin dendrites that terminate on the side of the inner hair cell facing the modiolus. Ongoing studies indicate that fibers with high rates of spontaneous activity have different terminations in the auditory CNS (cochlear nucleus) than do fibers with low rates of spontaneous activity. In other words, spontaneous activity of nerve fibers is not random but is proving to be anatomically and functionally significant (12,13,14,15). The tuning curve of a single auditory nerve fiber is perhaps the most basic measure of auditory nerve function. A tone burst controlled in frequency and level is presented. The level is adjusted until a criterion change (one or two spikes per second) in firing rate is detected. Tone bursts covering a wide range of frequencies are used, and the lowest level of signal is recorded for a given frequency that produces a specific rate of discharge. The resulting isoresponse curve is called a tuning curve. Figure 129.17 shows tuning curves for six different fibers. The sharp tip of the tuning curve identifies the best, or characteristic, frequency of the fiber. Units with low characteristic frequency are fibers that innervate inner hair cells in the apical region of the cochlea, fibers with high characteristic frequency innervate inner hair cells from the basal region, and so on. Tuning curves are described according to the frequency of the tip or characteristic frequency, the high- and low-frequency side, and the tail. Fibers with a characteristic frequency less than 1 kHz are roughly V shaped. Fibers with a higher characteristic frequency have an obvious tip at the characteristic frequency and a tail that extends to the low frequencies. The high side of a tuning curve is the frequency region greater than characteristic frequency. As characteristic frequency increases, the high side of the tuning curve becomes steeper with a slope or rejection rate that can exceed 500 dB per octave. The characteristics of tuning curves of auditory nerve fibers are strikingly similar to isoamplitude curves of a mechanical traveling wave (Fig. 129.15).<br /> Injury or damage to sensory cells, including stereocilia, can alter the shape of tuning curves dramatically (Fig. 129.18). The lower right portion of the figure shows that when outer hair cells are destroyed, the tuning curve of auditory nerve fibers from normal inner hair cells is changed in several ways. The sensitive tip region is missing; that is, the threshold of the fiber is elevated by approximately 40 to 45 dB. The high-frequency side no longer has a steep slope, and the low-frequency side becomes slightly more sensitive, or hypersensitive. The characteristic frequency of the fiber appears to be much lower in frequency, and the band width of the fiber appears broader. The upper left portion of Figure 129.18 shows the consequences of partial injury to the stereocilia of outer hair cells. A threshold shift of approximately 30 dB occurs, but a short, sharply tuned tip remains, and the low-frequency tail is again hypersensitive. Irregularities in this tuning curve may explain monaural diplacusis; that is, a tone in one ear (800 Hz) has two pitches, for example, one at 800 Hz and a second at approximately 2.8 kHz.<br />The upper left portion of Figure 129.18 shows a tuning curve in which stereocilia of inner hair cells are damaged or in disarray, whereas most of the stereocilia of outer hair cells appear normal or nearly so. The threshold of the unit is elevated approximately 30 dB, but the tuning curve is approximately normal. The lower left portion of the figure shows responses to signals in a narrow range of frequencies only at sound levels greater than 90 dB SPL. In this case, sensory cells are present, but stereocilia of inner hair cells are destroyed, and those of outer hair cells are destroyed or in disarray. Thus normal neural activity, including sensitivity (detection of faint sounds) and frequency-resolving power, depends on intact outer hair cells and normal stereocilia.<br /> Although thresholds of auditory nerve fibers are related to the rate of spontaneous discharge, most afferent nerve fibers (60%) have high spontaneous rates and thresholds within 20 dB greater than the thresholds for the animal. The remaining low-spontaneous fibers have thresholds that cover approximately 60 dB. The dynamic range of most auditory nerve fibers is approximately 30 dB from threshold to saturation (Fig. 129.19), although some low-spontaneous fibers have a much wider dynamic range. Given the dynamic range of human hearing (0 dB SPL to ≥100 dB SPL), the auditory system must have neurons the thresholds of which cover a wide range and have firing rates that also cover a wide range of intensities. The ability of the human ear to respond appropriately to sounds over a 120-dB range (10,12) is remarkable. One way is with low-spontaneous fibers; another is recruitment of fibers of characteristic frequency.<br /> One of the most common features of sensorineural hearing loss is recruitment of loudness. Figure 129.20 gives an explanation. It is assumed that loudness depends on the total activity of the auditory nerve. As Figure 129.20A shows, the number of fibers activated increases slowly as intensity is increased, and only the tips of tuning curves are activated. As the intensity increases further, the tails of the tuning curves are encountered, and the number of fibers activated increases rapidly. In the case of sensorineural hearing loss, the tips of the tuning curves are missing, and the fibers are not activated until the level of the signal is sufficient to reach the tails of the tuning curves. Abruptly, many fibers then are abruptly activated simultaneously.<br /><br /><span style="font-weight:bold;">Nonlinear Properties of the Ear</span><br /> Some of the outstanding features of the middle ear transformer are its linear properties, but the outstanding features of the cochlea and auditory nerve are the nonlinear characteristics. Perhaps the most studied nonlinearities are combination tones, described herein in relation to cochlear emissions, and two-tone rate suppression, as recorded in auditory nerve fibers.<br /> Two-tone rate suppression is the reduction in firing rate produced by one tone when a second tone is introduced. Figure 129.21 shows a tuning curve with a suppression area outlined above the characteristic frequency of the nerve fiber and an area below the characteristic frequency of the fiber. Tones presented in the dotted or suppression areas in the figure reduce the firing rate caused by the probe tone. Both the excitor and suppressor tones are presented simultaneously, and because little or no time lag is associated with this phenomenon nor is any evidence available that it is neurally produced, the effect is called suppression rather than inhibition. Two-tone suppression in single units is reflected in the compound action potential. Figure 129.21 (right) shows tuning curves of the compound action potential with suppression areas shown in the dotted areas. In this case, the amplitude of the compound action potential is altered by the suppressing signal, whereas in the single-unit case (left), the firing rate of a neuron is reduced by an arbitrary amount (20%). The single-unit and compound action potential suppression areas are similar. Inasmuch as two-tone suppression can be observed in the DC intracellular response of inner hair cells, it is probable that two-tone suppression originates in the active nature of cochlear mechanics and before the inner hair cells.In the presence of sensorineural hearing loss caused by exposure to noise or to ototoxic drugs, two-tone rate suppression is severely affected, if at all measurable. Two-tone rate suppression appears normal or nearly so in cases of cochlear hearing loss in which the sensory cells, including stereocilia, are normal or nearly so, but the stria vascularis is affected. The latter scenario leads to presbycusis (16).<br /> Otoacoustic emissions (OAEs) are sounds that are detected in the ear canal when the tympanum receives vibrations transmitted through the middle ear from the cochlea. OAEs provide support for the notion that the cochlea is not just a passive receiver of acoustic energy but can also generate or amplify sounds. Several different types of OAEs are found (17). Spontaneous OAEs occur in the absence of acoustic stimulation and are typically highly stable pure tones of -10 to 30 dB SPL, which are found in 30% to 40% of healthy young ears (18,19). The precise frequency of a spontaneous OAE does not imply an origin at a precise place in the cochlea, but only a particular coincidence of travel time and reflection from an ill-defined region of high outer cell activity. Spontaneous OAEs can be recorded over long periods with only minor but seemingly systematic variations in frequency and amplitude.A second class of OAEs are produced after exposure to an acoustic signal. Transient-evoked OAEs (TEOAE) are made via a probe placed in the ear canal. The oscillatory sound pressure waveform seen in TEOAE responses actually corresponds to the motion of the eardrum resulting from pressure fluctuations generated within the cochlea (Fig. 129.22). Although stimulatory clicks excite the entire cochlea, TEOAE responses can be used to give frequency-specific information about the cochlea through splitting of the responses into different frequency bands. TEOAEs are highly sensitive to cochlear pathology in frequency-specific manner. Frequencies at which hearing thresholds exceed 20 to 30 dB hearing loss (HL) are typically absent in the TEOAE response (20,21). Because of their sensitivity to cochlear dysfunction, TEOAEs have found widespread application in newborn hearing screening programs (22).<br />Distortion-product OAEs also are used widely in clinical situations. The TEOAE and DPOAE techniques complement each other. DPOAEs offer a wider frequency range of observation with less sensitivity to minor and subclinical conditions in adults. When two primary tones, F1 and F2, are presented to the cochlea, several distortion products are produced. The most prominent of all these intermodulation distortion products is the cubic distortion tone, 2F1-F2. Measurement of DPOAEs at multiple stimulus levels can establish the OAE “growth rate.â€� Healthy ears tend to exhibit a DPOAE growth rate of 1 dB of OAE per 1 dB of stimulus or less. Ears with some impairment show steeper growth. Single DPOAE results can be misleading, and results must be averaged across a range of frequencies. The DPOAE is easily recordable in patients with a normal middle ear system (23).Auditory Central Nervous System<br /> The ascending and descending auditory pathways are described briefly herein in relation to auditory evoked potentials. Schematics of the afferent and efferent pathways are shown in Figs. 129.23 and 129.13, respectively. These diagrams oversimplify the system but provide a rough introduction to the auditory CNS and its complexity. All eighth-nerve afferent fibers stop at the level of the cochlear nucleus. Five major cell types are found within the cochlear nucleus, each with distinct cell morphologic and physiologic features, such as response to stimulus onset, stimulus offset, and frequency modulation. From the cochlear nucleus, most fibers cross the brainstem to the contralateral superior olivary complex; a much smaller number of fibers run to the ipsilateral superior olivary complex.<br />The superior olivary complex is considered the first center in the ascending auditory system, where inputs from both ears converge. Auditory nuclei above the superior olivary complex can be excitatory or inhibitory with inputs from each ear. Stimulation of the contralateral ear typically is excitatory to cell bodies of the auditory CNS, whereas stimulation of the ipsilateral ear is inhibitory. As shown in Figure 129.13, the medial superior olivary complex is the origin of the crossed efferent fibers that terminate on outer hair cells, whereas the lateral superior olivary complex is the origin for the uncrossed efferent fibers that terminate on inner hair cells. Although many functions have been attributed to the efferent auditory system, especially protecting the cochlea from loud sounds, the functions of the system are unknown; those that have been proposed are easily debated <br />The inferior colliculus is a complex nucleus with at least 18 major cell types and at least five areas of specialization. It is involved in probably all forms of auditory behavior, including differential sensitivity for frequency and intensity, loudness, and binaural hearing. The inferior colliculus is clearly more than a relay center. The medial geniculate body of the thalamus sends projections to the auditory cortex, but its specific functions are unknown.<br /> The auditory cortex is located in the sylvian fissure of the temporal lobe; many secondary auditory areas are clustered around the primary area. In each area, the cells are tonotopically organized in a columnar manner, each column having a special attribute. The cells in one column can have different tuning at a similar characteristic frequency, whereas another column can be associated with intensity encoding, another with providing inhibitory responses to stimulation of one ear and excitatory responses of the other ear, and so on. As is common for thalamic connections with the cortex, nuclei within the medial geniculate body that send fibers to the auditory cortex also receive fibers from the same area of the cortex. Bilateral lesions of the temporal lobe have been shown to produce wide-ranging effects (cortical deafness, in which several auditory behaviors are severely affected, including speech discrimination, localization of sound, temporal processing of information, and the detection of faint, short-duration signals) (25). Another important feature of the auditory system is its tonotopic nature. From the basilar membrane to the auditory cortex, the system is organized spatially with respect to frequency. Each place on the basilar membrane responds best to a specific frequency—high-frequency sounds are localized to the base, and low-frequency sounds, to the apex. The tonotopic organization of the cochlea is preserved at the cochlear nucleus. Figure 129.24 shows that as an electrode penetrates the cochlear nucleus, fibers with different characteristic frequencies are contacted, and the characteristic frequencies form an orderly progression. Similar data exist at all nuclei of the auditory CNS, including the auditory cortex<br /> The most obvious clinical application of basic information on the auditory CNS involves interpretation of evoked potentials. The auditory brainstem response (ABR) is one component of auditory evoked potentials. The existence of the ABR was first reported by Sohmer and Feinmesser in 1967 (26). The ABR is recorded from electrodes attached to various positions on the head. The ABR consists of a series of seven waves occurring within about 10 milliseconds after stimulus onset. The convention in the United States is to label wave peaks with Roman numerals. It is generally accepted that the ABR is generated by the auditory nerve and subsequent fiber tracts and nuclei within the auditory brainstem pathways. It is widely believed that each wave is generated as follows: wave I and II are the eighth nerve, III is cochlear nucleus, IV is superior olive/lateral lemniscus, and V is lateral leminiscus/inferior colliculus.<br /> The ABR is generated by a click stimulus because it yields the clearest response. The ABR is used clinically both in the estimation of auditory sensitivity and in otoneurologic assessment. In this way, it can be used to detect lesions along the auditory nerve and brainstem pathways. The study can be performed regardless of state of wakefulness, and the result is unaffected by most medications. As a result, children are often tested while under sedation or during sleep.<br />The field of clinical objective audiometry has recently gained an additional technique in the auditory evoked response battery. The auditory steady-state response (ASSR) promises to be a valuable study in the workup of auditory dysfunction. Unlike ABRs, which are obtained through the use of transient stimuli, ASSRs are evoked by using sustained continuous tones. The tones are frequency specific because the continuous tones do not have spectral distortion problems as do brief tone bursts or click (27). Of note, ASSR also can be performed regardless of the state of wakefulness.<br /> There are several advantages of ASSR over ABR. First, ASSR is a better technique for evaluating hearing aid performance because hearing aids and cochlear implants process continuous stimuli with less signal distortion than transient stimuli. Furthermore, ASSR can provide threshold information in a frequency-specific manner at intensity levels of 120 dB or greater (28,29). This allows differentiation of severe and profound hearing loss, which cannot be accomplished with ABR. This characteristic of ASSR may allow it to be used in assessing pediatric patients for cochlear implant candidacy (30). Last, ASSR has been shown to be more time efficient by determining more thresholds in a shorter time compared with ABR (31). Future research and clinical use are likely to solidify the status of ASSR in the audiologic armamentarium.<br /> The neuroanatomic features of the system are complicated. Processing of neural information probably involves both parallel and serial processing. The former is anatomically described by a single fiber with ramifications to many target areas. Serial processing involves a fiber going to one target, which in turn goes to another target, and so forth. In the auditory CNS, both serial and parallel processing are involved. Because the auditory CNS is a highly redundant, complicated, and extremely powerful system, interpretation of evoked-potential data, and of other CNS neural data, is not straightforward.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-78430510545316016902008-11-26T13:33:00.001-08:002008-11-26T13:35:18.195-08:00Pathophysiology of GlaucomaThe major mechanism of visual loss in glaucoma is retinal ganglion cell atrophy, leading to thinning of the inner nuclear and nerve fiber layers of the retina and axonal loss in the optic nerve. The optic disk becomes atrophic, with enlargement of the optic cup (see below). The iris and ciliary body also become atrophic, and the ciliary processes show hyaline degeneration.<br /><br />The pathophysiology of intraocular pressure elevation—whether due to open-angle or to angle-closure mechanisms—will be discussed as each disease entity is considered (see below). The effects of raised intraocular pressure are influenced by the time course and magnitude of the rise in intraocular pressure. In acute angle-closure glaucoma, the intraocular pressure reaches 60–80 mm Hg, resulting in acute ischemic damage to the iris with associated corneal edema and optic nerve damage. In primary open-angle glaucoma, the intraocular pressure does not usually rise above 30 mm Hg and retinal ganglion cell damage develops over a prolonged period, often many years. In normal-tension glaucoma, retinal ganglion cells may be susceptible to damage from intraocular pressures in the normal range or the major mechanism of damage may be optic nerve head ischemiaNurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-59142177916614010402008-08-04T06:26:00.000-07:002009-02-04T05:46:55.254-08:00Mycrobiology of sinusitis<span style="font-weight:bold;">A.Acute sinusitis</span><br />The most commonly identified organisms in children with acute sinusitis are Streptococcus pneumoniae in 30% to 40%, Haemophilus influenzae in 20% to 25%, and Moraxella catarrhalis in 20%. In adults, S. pneumoniae and H. influenzae are the two leading causes of acute sinusitis, whereas Moraxella is unusual. Anaerobic organisms are primarily identified in cases of acute sinusitis originating from dental root infections, but are otherwise uncommon. Hospital-acquired sinusitis is most often seen as a complication of nasogastric tube placement, and is typically caused by gram-negative enteric organisms, such as Pseudomonas and Klebsiella species.<br /><span style="font-weight:bold;"><br />B.Chronic sinusitis </span><br />1.<span style="font-weight:bold;">Bacteria</span> cultured from children with persistent symptoms are usually the same as those seen in acute disease. In children with more severe and protracted symptoms, anaerobic species (such as Bacteroides) and staphylococci are cultured more frequently. In adults with refractory symptoms, Staphylococcus epidermidis is frequently cultured from intraoperative specimens. The exact role of this species in the pathogenesis of chronic sinusitis is unclear. Although anaerobic organisms were once implicated in adults with chronic sinus disease, more recent evidence casts doubt upon those data.<br /><br />2.<span style="font-weight:bold;">Fungi</span>, such as Aspergillus species, are a common cause of sinus disease in immunocompromised hosts, including diabetics and patients who have defective cell-mediated immunity. Increasingly, fungi have been identified as causes of sinusitis in patients who are otherwise healthy and should, therefore, be considered in cases of refractory sinusitis. Allergic fungal sinusitis is a syndrome that occurs in adults with asthma and has been attributed to Aspergillus, Bipolaris, and Curvularia species. It is characterized by severe, hyperplastic sinusitis and nasal polyposis, and is associated with significant eosinophilia of sinus tissue and blood.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-86575128820657167122008-07-11T06:15:00.000-07:002009-02-04T05:50:24.162-08:00Indications for Anticoagulation in Patients With Prosthetic Heart ValvesAll patients with mechanical valves require warfarin therapy. The risk of embolism is greater with a valve in the mitral position (mechanical or biological) than in the aortic position. With either type of prosthesis or valve location, the risk of emboli is higher in the first few days and months after valve insertion. Low-dose aspirin is recommended for all patients with prosthetic valves (see Table 1. For patients with mechanical valves, the addition of low-dose aspirin (80 to 100 mg/d) to warfarin therapy (INR 2.0 to 3.5) not only further decreases the risk thromboembolism but also decreases mortality due to other cardiovascular diseases. A slight increase in risk of bleeding with this combination should be kept in mind.<br /><span style="font-weight:bold;">Recommendations for Antithrombotic Therapy in Patients With Prosthetic Heart Valves <br />Class I <span style="font-weight:bold;"></span></span><br />1.First 3 months after valve replacement: Warfarin- INR 2.5 to 3.5 <br />2.3 or more months after valve replacement:<br /><span style="font-weight:bold;">A. Mechanical valve</span><br />AVR and no risk factor*: <br />Bileaflet valve or Medtronic Hall valve, Warfarin- INR 2 to 3 <br />Other disk valves or Starr-Edwards valve, Warfarin- INR 2.5 to 3.5 <br />AVR and risk factor,* Warfarin- INR 2.5 to 3.5 <br />MVR, Warfarin- INR 2.5 to 3.5 <br /><span style="font-weight:bold;"><br />B. Bioprosthesis</span><br />AVR and no risk factor,* Aspirin- 80 to 100 mg/d <br />AVR and risk factor,* Warfarin- INR 2 to 3 <br />MVR and no risk factor,* Aspirin- 80 to 100 mg/d <br />MVR and risk factor,* Warfarin- INR 2.5 to 3.5 <br /><br /><span style="font-weight:bold;">Class IIa</span> <br />1.Addition of aspirin to warfarin: Aspirin- 80 to 100 mg daily <br />2.High-risk patients for whom aspirin cannot be used: Warfarin- INR 3.5 to 4.5 <br />Class IIb <br />Starr-Edwards AVR and no risk factor,* Warfarin, INR 2 to 3 <br /><br /><span style="font-weight:bold;">Class III </span><br />1.Mechanical valve, no warfarin therapy. <br />2.Mechanical valve, aspirin therapy only. <br />3.Bioprosthesis, no warfarin and no aspirin therapy.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-48978280026304763832008-07-10T06:23:00.000-07:002009-02-04T05:51:54.203-08:00Symptom and Sign Diabetes<span style="font-weight:bold;">SYMPTOMS AND SIGNS</span><br /><br /><span style="font-weight:bold;">Type 1 diabetes</span><br />Increased urination is a consequence of osmotic diuresis secondary to sustained hyperglycemia. This results in a loss of glucose as well as free water and electrolytes in the urine. Thirst is a consequence of the hyperosmolar state, as is blurred vision, which often develops as the lenses are exposed to hyperosmolar fluids.<br />Weight loss despite normal or increased appetite is a common feature of type 1 when it develops subacutely. The weight loss is initially due to depletion of water, glycogen, and triglycerides; thereafter, reduced muscle mass occurs as amino acids are diverted to form glucose and ketone bodies.<br />Lowered plasma volume produces symptoms of postural hypotension. Total body potassium loss and the general catabolism of muscle protein contribute to the weakness.<br />Paresthesias may be present at the time of diagnosis, particularly when the onset is subacute. They reflect a temporary dysfunction of peripheral sensory nerves, which clears as insulin replacement restores glycemic levels closer to normal, suggesting neurotoxicity from sustained hyperglycemia.<br />When absolute insulin deficiency is of acute onset, the above symptoms develop abruptly. Ketoacidosis exacerbates the dehydration and hyperosmolality by producing anorexia and nausea and vomiting, interfering with oral fluid replacement.<br />The patient's level of consciousness can vary depending on the degree of hyperosmolality. When insulin deficiency develops relatively slowly and sufficient water intake is maintained, patients remain relatively alert and physical findings may be minimal. When vomiting occurs in response to worsening ketoacidosis, dehydration progresses and compensatory mechanisms become inadequate to keep serum osmolality below 320–330 mosm/L. Under these circumstances, stupor or even coma may occur. The fruity breath odor of acetone further suggests the diagnosis of diabetic ketoacidosis.<br />Hypotension in the recumbent position is a serious prognostic sign. Loss of subcutaneous fat and muscle wasting are features of more slowly developing insulin deficiency. In occasional patients with slow, insidious onset of insulin deficiency, subcutaneous fat may be considerably depleted.<br /><br /><span style="font-weight:bold;">Type 2 diabetes</span><br />While many patients with type 2 diabetes present with increased urination and thirst, many others have an insidious onset of hyperglycemia and are asymptomatic initially. This is particularly true in obese patients, whose diabetes may be detected only after glycosuria or hyperglycemia is noted during routine laboratory studies. Occasionally, type 2 patients may present with evidence of neuropathic or cardiovascular complications because of occult disease present for some time prior to diagnosis. Chronic skin infections are common. Generalized pruritus and symptoms of vaginitis are frequently the initial complaints of women. Diabetes should be suspected in women with chronic candidal vulvovaginitis as well as in those who have delivered large babies (> 9 lb, or 4.1 kg) or have had polyhydramnios, preeclampsia, or unexplained fetal losses.<br />Obese diabetics may have any variety of fat distribution; however, diabetes seems to be more often associated in both men and women with localization of fat deposits on the upper segment of the body (particularly the abdomen, chest, neck, and face) and relatively less fat on the appendages, which may be quite muscular. Standardized tables of waist-to-hip ratio indicate that ratios of "greater than 0.9" in men and "greater than 0.8" in women are associated with an increased risk of diabetes in obese subjects. Mild hypertension is often present in obese diabetics. Eruptive xanthomas on the flexor surface of the limbs and on the buttocks and lipemia retinalis due to hyperchylomicronemia can occur in patients with uncontrolled type 2 diabetes who also have a familial form of hypertriglyceridemia.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0tag:blogger.com,1999:blog-5658461710957833796.post-66402615357952658372008-07-07T07:18:00.001-07:002009-02-04T05:53:31.664-08:00PATHOLOGY OF ACUTE PANCREATITIS<span style="font-weight:bold;">PATHOLOGY</span><br />Detailed histological studies of pancreatic tissue are available from a limited number of cases of human acute pancreatitis. A histological spectrum of acute pancreatitis is recognized ranging from mild, interstitial disease to coagulation necrosis. 3 Interstitial pancreatitis may lead to local and systemic complications but is rarely fatal; necrotizing pancreatitis may be fatal in up to 30% of cases.<br /><span style="font-weight:bold;"></span><br />Interstitial<br />In interstitial pancreatitis the gland is edematous, but its gross architecture is preserved. Parenchymal inflammatory cells are present together with interstitial edema. Disruption of the normal acinar cell architecture is common and may contribute to the reduced enzyme secretion characteristic of acute pancreatitis. Zymogen granules are displaced from their fusion site in the apical domain of the cell and become dispersed throughout the cell, and the apical membrane appears contracted and microvilli disappear. 4 Zymogen granules fuse with each other instead of the apical membrane. Similar to animal models of pancreatitis, a distinct form of cell necrosis is observed in which the apical domain of the acinar cell is shed into the lumen, resulting in intact zymogen granules within the lumen. This pattern of partial cell necrosis may allow the acinus to regenerate rapidly after injury.<br /><span style="font-weight:bold;"><br />Necrotizing</span><br />Macroscopically, marked tissue necrosis and hemorrhage are apparent. Surrounding areas of fat necrosis are also prominent. These chalky areas of dead adipose tissue are found within the peripancreatic tissue and throughout the abdomen. Large hematomas often are located in the retroperitoneal space. The microscopic appearance of the pancreas parallels the gross changes, with marked fat and pancreatic necrosis. Vascular inflammation and thrombosis are common.Nurhasanhttp://www.blogger.com/profile/12275817960004550026noreply@blogger.com0