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The electrocardiographic tracing below illustrates a normal sinus rhythm in which there is a repetitive and coordinated activation of the entire heart generic 850mg glucophage amex. One conducted sinoatrial impulse enter- ing the ventricle from the atrioventricular node distributes over the His-Purkinje system to elicit one QRS complex indicating depolarization of the ventricular myocardium buy glucophage 500 mg visa. As in the previous figure, antegrade con- duction occurs in a normal manner over the proximal Purkinje system (P1) and in the distal Purkinje network on the left of the diagram. The intracellular recordings from the respective electrodes indicate that the resting membrane potential from P2 is decreased due to the presence of injury at this site. Therefore, the impulse conducts slowly and decrementally, and finally is blocked in the area of injury (unidirectional block). The ventricular myocardium, however, has been depolarized from nor- mally conducting Purkinje fibers at remote insertion sites. The excitatory impulses traversing within the ventricular myocardium will reenter the distal portion of the Purkinje network (right side of diagram) and conduct slowly in the retrograde direction through the area of unidirectional block. The appropriate conditions are established by the conduction velocities and refractory pe- riods in the respective tissues. The retrograde impulse can reenter the proximal Purkinje system and initiate reexcitation of the proximal and distal Purkinje network as well as the ventricular myocardium if each of these sites has recovered its excitability from the previous depolarization. The reentry impulse may give rise to a premature coupled ventricular complex in which the nor- mally conducted impulse (V1) is followed with precise timing by a reentry ventricular complex (V2). The reentry impulses could occur more frequently so that the cardiac rhythm becomes domi- nated by the activity in the reentry pathway, thus leading to a rapid, repetitive series of ventricu- lar complexes (ventricular tachycardia) in which the ventricular rate becomes rapid ( 100 beats min) and may degenerate into ventricular fibrillation. The object of antiarrhythmic drug therapy is to reduce the frequency of hemodynamically disturbing premature ventricular impulses and to prevent the establishment of a sustained and rapidly conducting reentrant rhythm capable of be- coming lethal. In the undamaged myocardium, cardiac impulses the terminal segments of the Purkinje fibers within the travel rapidly antegrade through the Purkinje fibers to affected region may be activated by impulses passing deliver the excitatory electrical impulse to the ventricu- from the ventricular myocardium to conduct in a retro- lar myocardium. In some situations, the retrograde cardium to the conducting fibers is prevented by the impulse will enter an area of normal myocardium suffi- longer duration of the membrane action potential and ciently repolarized that it is no longer refractory, and a thus the refractory period in the Purkinje fibers. The generation In the presence of myocardial ischemia, propaga- of an action potential may produce an increased rate of tion of cardiac impulses may be interfered with and a ventricular activation and may become self-sustaining.

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Additional terms • Signs and symptoms may be found in the glossary at the back of volume 2 discount glucophage 850mg on-line. The • Resources appendix contains an extensive list of organizations arranged in alphabetical order discount glucophage 500mg overnight delivery. INCLUSION CRITERIA A preliminary list of diseases and disorders was GRAPHICS compiled from a wide variety of sources, including pro- fessional medical guides and textbooks, as well as con- The Gale Encyclopedia of Genetic Disorders con- sumer guides and encyclopedias. The advisory board, tains over 200 full color illustrations, including photos GALE ENCYCLOPEDIA OF GENETIC DISORDERS ix and pedigree charts. Corneal dystrophy © Gilman/Custom Medical The editor would like to thank the following individ- Stock Photo. Cystic fibrosis uals for their assistance with the Gale Encyclopedia of © 1992 Michael English, M. Depression © NIH/ MS, and Jennifer Neil, MS CGC, for the creation of the Science Source, National Audubon Society Collection/ pedigree charts found in entries throughout the main Photo Researchers, Inc. Lee and Brenda Lerner for their assistance in Diabetes mellitus © 1992 Science Photo Library/ compiling and reviewing most of the non-disorder entries Custom Medical Stock Photo. Sieveing/Petit Kalasky, Beth Kapes, Monique Laberge, PhD, and Lisa Format/Photo Researchers, Inc. Reproduced by permis- Nielsen for their extensive assistance with the final phase sion. Fragile X syndrome reproduced by permission from the source noted in each © Siebert/Custom Medical Stock Photo. Hollyman, Science Source/ x GALE ENCYCLOPEDIA OF GENETIC DISORDERS Photo Researchers.

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Some multifactorial conditions the standard manner safe glucophage 500 mg, removal by surgery and possible occur because of the interplay of many genetic factors treatment with radiation or cancer-killing medication and limited environmental factors buy generic glucophage 500mg online. Others occur because of limited genetic factors and significant environmental (chemotherapy). The number of genetic and environmental factors before colon cancer develops is an option with HNPCC vary, as does the amount of impact of each factor on the and may be considered for individuals with Muir-Torre presence or severity of disease. Prognosis Examples of congenital malformations following a The cancers associated wth Muir-Torre syndrome multifactorial pattern of inheritance include cleft lip and are usually diagnosed at earlier ages than typically seen. Adult onset For instance, the average age at diagnosis of colorectal diseases that follow multifactorial inheritance include cancer is 10 years earlier than in the general population. For instance, height, intelligence, and blood pressure are all may be better for a person with colon cancer due to Muir- determined in part by genetic factors, but are influenced Torre syndrome than colon cancer in the general popula- by environmental factors. Resources Continuous and discontinuous traits BOOKS Some multifactorial traits are considered continuous Flanders, Tamar et al. In because there is bell shaped distribution of those traits in Inherited Susceptibility: Clinical, predictive and ethical the population. Other traits are discontinuous because there is a Hodgson, Cambridge University Press, 1998. An exam- ple would be a malformation like a cleft lip, in which the KEY TERMS person is either affected or unaffected. In both cases, the genetic and environmental factors that are involved in the Candidate gene—A gene that encodes proteins occurrence of the condition are referred to as liability. Pyloric stenosis Genetic heterogeneity—The occurrence of the An example of a discontinuous multifactorial trait same or similar disease, caused by different genes that follows the threshold model is pyloric stenosis. Pyloric stenosis is a narrowing of the pylorus, the con- Loci—The physical location of a gene on a chro- nection between the stomach and the intestine. Symptoms of pyloric stenosis include vomiting, consti- Phenotype—The physical expression of an indi- pation, and weight loss. The condition is five Polymorphism—A change in the base pair times more common in males.

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