U Urachus Vestigial remnant of the allantois from the ventral surface of the urogenital sinus to the umbilicus that normally regresses to a fibrous cord gastritis grapes order 10 mg metoclopramide with mastercard, forming the median umbilical ligament gastritis diet cheap metoclopramide 10mg visa. Urogenital ridge Bilateral epithelial-covered elevation of intermediate mesoderm that lies in the lower thoracic and lumbar regions and that forms the mesonephric kidneys and the gonads gastritis symptoms fatigue metoclopramide 10mg online. Urorectal septum Wedge of mesoderm that grows down between the hindgut and primitive urogenital sinus gastritis untreated order 10mg metoclopramide free shipping, partially separating these two structures gastritis diet eggs discount metoclopramide 10 mg without prescription. Ventral mesentery Double layer of peritoneum derived from the septum transversum and extending from the liver to the ventral body wall (the falciform ligament) and from the liver to the stomach and duodenum (lesser omentum) gastritis medscape buy 10 mg metoclopramide with visa. Ventral primary ramus Ventral branch of a spinal nerve that innervates limb and trunk muscles except the intrinsic ("true") back muscles gastritis attack buy 10mg metoclopramide visa, which are innervated by dorsal primary rami gastritis in english purchase metoclopramide 10 mg without a prescription. Ventral root Motor fibers passing from ventral horn cells in the spinal cord to a spinal nerve. Viscerocranium Part of the skull that comprises the bones of the face (the other part of the skull is the neurocranium). Vitelline duct Connection between the yolk sac and the primary intestinal loop of the midgut through the connecting stalk. W White rami communicantes Connections carrying preganglionic sympathetic fibers from spinal nerves to the sympathetic trunks. Y Yolk sac Structure located ventral to the bilaminar germ disc derived from the hypoblast. It is the site of origin of the first blood cells and remains attached to the midgut via the vitelline (yolk sac) duct until late in development. I N D E X Page numbers in italics denote figures; those followed by a b denote boxes; those followed by a t denote tables. See Rhombencephalon Hindgut, 229, 229 abnormalities, 230b Hip dislocation, 161b Hippocampus, 305, 306 Hirschsprung disease, 230b. See Organogenesis Organ of Corti, 322 380 Index Organic mercury, 120t, 124 Organogenesis. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. We are privileged to work with Dick and are grateful to him for his steadfast counsel and guidance. Nelson Professor and Chairman, Department of Pediatrics, Temple University School of Medicine, Philadelphia, Pennsylvania Cryptococcus neoformans; Histoplasmosis (Histoplasma capsulatum); Paracoccidioides brasiliensis; Sporotrichosis (Sporothrix schenckii); Zygomycosis (Mucormycosis); Primary Amebic Meningoencephalitis; Nonbacterial Food Poisoning David M. Food and Drug Administration, Rockville, Maryland Transmissible Spongiform Encephalopathies Barbara L. Dixon Professor of Pediatrics; Director, Division of Neonatology, University of Alabama, Birmingham Hospital, Birmingham, Alabama Overview of Mortality and Morbidity; the Newborn Infant; High-Risk Pregnancies; the Fetus; the High-Risk Infant; Clinical Manifestations of Diseases in the Newborn Period; Nervous System Disorders; Delivery Room Emergencies; Respiratory Tract Disorders; Digestive System Disorders; Blood Disorders; Genitourinary System; the Umbilicus; Metabolic Disturbances Ira M. Louis, Missouri Pulmonary Alveolar Proteinosis; Inherited Disorders of Surfactant Metabolism Doctoral Candidate, Clinical Psychology, Virginia Polytechnic Institute and State University, Cincinnati, Ohio Attention-Deficit/Hyperactivity Disorder Steven J. Peterson Professor, Vice Chair for Clinical Research, Pediatrics Director, Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University, Nashville, Tennessee Hemoglobinopathies Guenet H. McKusick Professor of Medicine and Genetics, Department of Pediatrics, Institute of Genetic Medicine; Investigator, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland Marfan Syndrome Nirupama K. Gilliam, PhD Associate Professor in Child Psychiatry and Psychology, Yale School of Medicine, Child Study Center, New Haven, Connecticut Child Care: How Pediatricians Can Support Children and Families Jane M. Kelch Research Professor and Director, Pediatric Infectious Diseases, University of Michigan Medical Center, Ann Arbor, Michigan Neisseria meningitidis (Meningococcus) Attending Physician/Hospital Epidemiologist/Assistant Professor of Pediatrics, Pediatrics/Section of Infectious Diseases, Drexel University School of Medicine/St. Louis, Missouri Pulmonary Alveolar Proteinosis; Inherited Disorders of Surfactant Metabolism James C. Guth Chair for Complementary and Integrative Medicine; Professor, Pediatrics and Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina Herbs, Complementary Therapies, and Integrative Medicine Charles H. Louis, Missouri Neoplasms and Adolescent Screening for Human Papilloma Virus Patrick M. Odell Professor, Pediatrics, Medicine and Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin Blastomycosis (Blastomyces dermatitidis) Pr C op D ont ert o e y N nt of ot N E D ot ls is F ev tri in ie bu al r the Stephan A. Davison Distinguished Professor of Pediatrics; Professor of Neurobiology; Chief, Division of Pediatric Neurology, Duke University Medical Center, Durham, North Carolina Seizures in Childhood; Conditions That Mimic Seizures Joseph G. DuPont Hospital for Children: Nemours Foundation, Wilmington, Delaware Phenylalanine Diane F. Murphy, PhD Professor, Department of Pediatrics, University of Texas Health Science Center, Houston, Texas Campylobacter; Yersinia; Aeromonas and Plesiomonas Timothy F. Natale, PsyD Ali and John Pierce Professor of Pediatric Hematology/Oncology; Vice Chair for Research, Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts Neutrophils; Eosinophils; Disorders of Phagocyte Function; Leukopenia; Leukocytosis Katherine A. Dick van Soolingen Head of the Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Department of Pulmonary Diseases and Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands Nontuberculous Mycobacteria Associate Professor of Pediatrics, Division of Infectious Diseases, University of Virginia, Charlottesville, Virginia Child Care and Communicable Diseases Steven G. Mortimer Newlin Professor of Pediatric Otolaryngology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Tonsils and Adenoids Director, the Pediatric Sleep Center, Fairfax Neonatal Associates, Fairfax, Virginia Emphysema and Overinflation; 1Antitrypsin Deficiency and Emphysema; Pleurisy, Pleural Effusions, and Empyema; Pneumothorax; Pneumomediastinum; Hydrothorax; Hemothorax; Chylothorax Paul H. Epstein Professor of Human Genetics and Pediatrics; Chief, Division of Medical Genetics, Department of Pediatrics and Institute of Human Genetics, University of California, San Francisco, School of Medicine, San Francisco, California Dysmorphology Anita K. Sultan Jamal Professor of Pediatrics and Child Health, and Microbiology; Chair, Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan Diagnostic Microbiology Joseph L. Wright, PhD Associate Professor, Pediatrics and Microbiology and Immunology, University of Rochester School of Medicine, Rochester, New York Pneumocystis jirovecii. Zile, PhD Professor, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan Vitamin A Deficiencies and Excess Prof. The 19th edition continues to represent the "state of the art" on the care of the normal and ill neonate, child, or adolescent by presenting both evidence-based medicine and astute clinical experiences from leading international authors. The promise that translational medicine will improve the lives of all children is greater than ever. Knowledge of human development, behavior, and diseases from the molecular to sociologic levels is increasing at fantastic rates. This has led to greater understanding of health and illness in children, as well as to substantial improvements in health quality for those who have access to health care. These exciting scientific advances also provide hope to effectively address new and emerging diseases threatening children and their families. Unfortunately, many children throughout the world have not benefited from the significant advances in the prevention and treatment of health-related problems, primarily because of a lack of political will and misplaced priorities. Additionally, many children are at substantial risk from the adverse effects of poverty, war, and bioterrorism. In order for our increasing knowledge to benefit all children and youth, medical advances and good clinical practice must always be coupled with effective advocacy. This new edition of Nelson Textbook of Pediatrics attempts to provide the essential information that practitioners, house staff, medical students, and other care providers involved in pediatric health care throughout the world need to understand to effectively address the enormous range of biologic, psychologic, and social problems that our children and youth may face. Our goal is to be comprehensive yet concise and reader friendly, embracing both the new advances in science as well as the timehonored art of pediatric practice. There are the additions of new diseases and new chapters, as well as substantial expansion or significant modification of others. In addition, many more tables, photographs, imaging studies, and illustrative figures, as well as up-to-date references, have been added. Every subject has been scrutinized for updating and improvement in its exposition and usefulness to pediatric health care providers. Although to an ill child and his or her family and physician, even the rarest disorder is of central importance, all health problems cannot possibly be covered with the same degree of detail in one general textbook of pediatrics. Thus, leading articles and subspecialty texts are referenced and should be consulted when more information is desired. In addition, to include as much information as possible and to take advantage of advances in providing background, pathophysiology, and literature citations, we have placed even more material on the website accompanying the printed text. This permits an unlimited ability to provide more detailed and updated information through our associated electronic media. Text vital to the care of children remains printed, but additional material will be provided to the reader at The outstanding value of the 19th edition of the textbook is due to its expert and authoritative contributors. We are all indebted to these dedicated authors for their hard work, knowledge, thoughtfulness, and good judgment. Our sincere appreciation also goes to Judy Fletcher and Jennifer Shreiner at Elsevier and to Carolyn Redman at the Pediatric Department of the Medical College of Wisconsin. In this edition we have had informal assistance from many faculty and house staff of the departments of pediatrics at the Medical College of Wisconsin, Wayne State University School of Medicine, Duke University School of Medicine, and University of Rochester School of Medicine. The help of these individuals and of the many practicing pediatricians from around the world who have taken the time to offer thoughtful feedback and suggestions is always greatly appreciated and helpful. Last and certainly not least, we especially wish to thank our families for their patience and understanding without which this textbook would not have been possible. DeMaso Overview of Pediatrics Assessment and Interviewing 56 Chapter 2 Quality and Safety in Health Care for Children Ramesh C. Sachdeva 13 13 13 Chapter 19 Psychologic Treatment of Children and Adolescents David R. Walter 60 60 65 66 67 Chapter 3 Chapter 4 Chapter 5 Eric Kodish and Kathryn Weise Ethics in Pediatric Care Cultural Issues in Pediatric Care 19. DeMaso Growth, Development, and Behavior Chapter 6 Overview and Assessment of Variability Susan Feigelman Susan Feigelman 21. DeMaso Habit and Tic Disorders Anxiety Disorders Mood Disorders Susan Feigelman the Second Year 31 Chapter 23 Chapter 10 Chapter 11 Chapter 12 Susan Feigelman the Preschool Years Middle Childhood 33 36 39 39 David R. Kreipe Suicide and Attempted Suicide Eating Disorders Disruptive Behavioral Disorders 45 45 46 Chapter 26 Chapter 27 90 96 99 xxxv Chapter 16 Chapter 17 Loss, Separation, and Bereavement Sleep Medicine Heather J. DeMaso Christina Ullrich, Janet Duncan, Marsha Joselow, and Joanne Wolfe Giuseppe Raviola, Gary J. Stallings 160 Chapter 29 Neurodevelopmental Function and Dysfunction in the School-Aged Child Desmond P. Natale Chapter 43 Chapter 44 Chapter 45 108 Harold Alderman and Meera Shekar Sheila Gahagan Nutrition, Food Security, and Health Overweight and Obesity Vitamin A Deficiencies and Excess 170 179 188 Chapter 30 Chapter 31 Natoshia Raishevich Cunningham and Peter Jensen Attention-Deficit/Hyperactivity Disorder Dyslexia 108 G. Sachdev and Dheeraj Shah 191 191 192 193 195 196 196 197 198 200 209 209 211 114 46. Eleoff Foster and Kinship Care Impact of Violence on Children Chapter 47 Chapter 48 Chapter 49 Chapter 50 Chapter 51 Dheeraj Shah and H. Greenbaum Vitamin C (Ascorbic Acid) Rickets and Hypervitaminosis D Vitamin E Deficiency Vitamin K Deficiency Micronutrient Mineral Deficiencies Marilyn Augustyn and Barry Zuckerman Douglas Vanderbilt and Marilyn Augustyn Isaiah D. Greenbaum Chapter 66 Acute Care of the Victim of Multiple Trauma Chapter 54 Larry A. Donovan Pediatric Pharmacogenetics, Pharmacogenomics, and Pharmacoproteomics Kathleen A. Wetzel Chapter 59 Herbs, Complementary Therapies, and Integrative Medicine Paula Gardiner and Kathi J. Gorelick 275 Human Genetics Practice Chapter 72 Integration of Genetics into Pediatric 376 377 379 Brendan Lee Brendan Lee 72. Scott and Brendan Lee Patterns of Genetic Transmission Cytogenetics 383 394 394 Iraj Rezvani and Marc Yudkoff Iraj Rezvani 79. Carlo Overview of Mortality and Morbidity the Newborn Infant 532 532 Iraj Rezvani Iraj Rezvani and K. Carlo Delivery Room Emergencies Respiratory Tract Disorders Chapter 89 Chapter 90 Waldemar A. Carlo 564 Chapter 96 Chapter 92 Clinical Manifestations of Diseases in the Newborn Period Waldemar A. Burstein 663 664 665 667 667 667 671 678 679 680 681 682 683 683 684 685 685 685 686 688 690 691 692 694 694 696 696 698 699 Chapter 98 Chapter 99 Waldemar A. Felice Adolescent Pregnancy Adolescent Rape 699 702 705 714 Chapter 126 Section 4 Laurence A. Buckley Pr C op D ont ert o e y N nt of ot N E D ot ls is F ev tri in ie bu al r the 722 Evaluation of Suspected Immunodeficiency Chapter 116 Richard B. Boxer Chapter 137 Chapter 138 Chapter 139 Chapter 140 Chapter 141 Henry Milgrom and Donald Y. Egla Rabinovich Treatment of Rheumatic Diseases Juvenile Idiopathic Arthritis Pr C op D ont ert o e y N nt of ot N E D ot ls is F ev tri in ie bu al r the Miscellaneous Conditions Associated with Arthritis Chapter 163 Angela Byun Robinson and Leonard D. Goldmann 829 Chapter 150 Ankylosing Spondylitis and Other Spondyloarthritides James Birmingham and Robert A. Schanberg Reactive and Postinfectious Arthritis Systemic Lupus Erythematosus 839 Walter A. Waggoner-Fountain 895 Scleroderma and Raynaud Phenomenon Chapter 155 Chapter 156 Chapter 157 Chapter 158 Chapter 159 Chapter 160 Chapter 161 Abraham Gedalia Heather A. Egla Rabinovich 850 Health Advice for Children Traveling Internationally Chapter 168 Jessica K. Nield and Deepak Kamat Fever without a Focus Infections in Immunocompromised Abraham Gedalia Persons Marian G. Todd 903 903 904 908 909 Chapter 191 Chapter 192 Chapter 193 Chapter 194 Chapter 195 Theresa J. Murphy Aeromonas and Plesiomonas 974 974 974 Chapter 180 Diphtheria (Corynebacterium diphtheriae) E. Jacobs Tularemia (Francisella tularensis) Brucella Chapter 185 Chapter 186 Chapter 187 Chapter 188 Chapter 189 Toni Darville Neisseria gonorrhoeae (Gonococcus) Haemophilus influenzae Chancroid (Haemophilus ducreyi) Moraxella catarrhalis Gordon E. Arnon Tetanus (Clostridium tetani) Clostridium difficile Infection Other Anaerobic Infections Margaret R. Stephen Dumler Chapter 207 Pr C op D ont ert o e y N nt of ot N E D ot ls is F ev tri in ie bu al r the Tuberculosis (Mycobacterium tuberculosis) Jeffrey R. Stephen Dumler 1038 996 leprae) Chapter 208 Hansen Disease (Mycobacterium Nontuberculous Mycobacteria Megan E. Stephen Dumler 1045 1046 1046 1047 1048 1051 1053 1053 1016 Chapter 222 Typhus Group Rickettsioses Chapter 211 Nonvenereal Treponemal Infections 1023 Megan E. Aronoff Cryptococcus neoformans Malassezia Aspergillus Chlamydia trachomatis Martin E. Steinbach Respiratory Syncytial Virus Human Metapneumovirus Adenoviruses Rhinoviruses Chapter 230 Histoplasmosis (Histoplasma capsulatum) Jane M. Denison Chapter 256 Coronaviruses Species) Chapter 232 Coccidioidomycosis (Coccidioides 1065 1068 Martin B. Denison 1134 Pr C op D ont ert o e y N nt of ot N E D ot ls is F ev tri in ie bu al r the Chapter 233 Chapter 234 Chapter 235 Chapter 236 Section 13 Paracoccidioides brasiliensis David M. Aronoff Sporotrichosis (Sporothrix schenckii) Zygomycosis (Mucormycosis) Pneumocystis jirovecii 1068 Chapter 257 Rotaviruses, Caliciviruses, and Astroviruses Dorsey M. Halstead 1141 1069 Chapter 260 Arboviral Encephalitis outside North America Scott B. Halstead 1144 1144 1145 1146 Chapter 238 Chapter 239 Chapter 240 Chapter 241 Chapter 242 Chapter 243 Chapter 244 Chapter 245 Chapter 246 Chapter 247 Chapter 248 Wilbert H. Abzug Nonpolio Enteroviruses Parvovirus B19 Herpes Simplex Virus 1088 Chapter 262 Chapter 263 Chapter 264 Chapter 265 Chapter 266 Chapter 267 William C. Halstead Yellow Fever Other Viral Hemorrhagic Fevers Lymphocytic Choriomeningitis Virus Hantavirus Pulmonary Syndrome Rabies Scott B. LaRussa and Mona Marin Varicella-Zoster Virus Infections Epstein-Barr Virus Cytomegalovirus Roseola (Human Herpes Viruses 6 Daniel J. Wright Human Herpesvirus 8 Influenza Viruses Chapter 268 Acquired Immunodeficiency Syndrome (Human Immunodeficiency Virus) Ram Yogev and Ellen Gould Chadwick 1157 (1 and 2) Chapter 269 Human T-Lymphotropic Viruses 1177 Hal B. Asher 1177 1177 1177 1178 1178 1178 1180 1180 1183 Chapter 288 Lymphatic Filariasis (Brugia malayi, Brugia timori, and Wuchereria bancrofti) Arlene E. Kazura 1227 1229 1230 1231 1232 1234 Chapter 291 Chapter 292 Chapter 293 Chapter 294 Chapter 295 Chapter 273 Edsel Maurice T. Kazura Trichinosis (Trichinella spiralis) Schistosomiasis (Schistosoma) Flukes (Liver, Lung, and Intestinal) Adult Tapeworm Infections Cysticercosis Chapter 274 Giardiasis 274. King and Amaya Lopez Bustinduy Cryptosporidium, Isospora, Cyclospora, and Microsporidia Chapter 275 Patricia M. Flynn Pr C op D ont ert o e y N nt of ot N E D ot ls is F ev tri in ie bu al r the 1183 Ronald Blanton 274. Liacouras 1240 1240 African Trypanosomiasis (Sleeping Sickness; Trypanosoma brucei Complex) Edsel Maurice T. Salata 1190 American Trypanosomiasis (Chagas Disease; Trypanosoma cruzi) Chapter 279 Edsel Maurice T. Krause 1193 Chapter 298 Major Symptoms and Signs of Digestive Tract Disorders Raman Sreedharan and Chris A. Liacouras 1240 1249 1249 Chapter 280 Chapter 281 Chapter 282 Section 16 Malaria (Plasmodium) Babesiosis (Babesia) 1198 Peter J. Kazura Disorders of the Oral Cavity Associated with Other Conditions Chapter 300 Norman Tinanoff 1251 1252 1252 1253 1254 1257 1258 1217 1217 Chapter 301 Chapter 302 Norman Tinanoff Malocclusion Cleft Lip and Palate Syndromes with Oral Manifestations Dental Caries Periodontal Diseases Dental Trauma Common Lesions of the Oral Soft Chapter 284 Hookworms (Necator americanus and Ancylostoma spp. Kazura Trichuriasis (Trichuris trichiura) Norman Tinanoff Enterobiasis (Enterobius vermicularis) Arlene E. Kazura Norman Tinanoff 1222 Chapter 306 Chapter 307 Norman Tinanoff Chapter 287 stercoralis) Strongyloidiasis (Strongyloides 1223 Arlene E. Orenstein Dysmotility 1264 Motility Disorders and Hirschsprung Disease Chapter 324 Kristin N. Orenstein 1271 Chapter 325 Ileus, Adhesions, Intussusception, and Closed-Loop Obstructions 325.
The default pathway is transport to the cell membrane and secretion from the cell by exocytosis for proteins lacking M6P gastritis y colitis nerviosa sintomas purchase metoclopramide 10 mg on line. Lysosomal enzymes are secreted into the bloodstream gastritis sintomas purchase 10 mg metoclopramide otc, and undigested substrates build up within the cells gastritis diet juice buy 10mg metoclopramide fast delivery. A newborn boy is born with first arch congenital malformations classified as Treacher-Collins syndrome gastritis symptoms pain in back discount 10mg metoclopramide with mastercard, which is an autosomal dominant inherited disorder gastritis diet pregnancy buy metoclopramide 10 mg with visa. Treacle is localized to the structure labeled with the arrows in the accompanying transmission electron micrograph gastritis diet or exercise 10 mg metoclopramide free shipping. Which of the following is true for the process that the dividing cell shown in the electron micrograph below is undergoing A 29-year-old woman presents with a 101oF fever granulomatous gastritis symptoms cheap 10 mg metoclopramide fast delivery, pericardial effusions and Libman-Sacks endocarditis gastritis diet 7 hari generic metoclopramide 10 mg without prescription, arthralgias, rash across the malar region of the face ("butterfly rash") that is accentuated by sun exposure; creatinine is 1. Which of the following is most likely to be directly affected by the disruption of nucleosomes in this patient. A middle aged anatomy professor went to the hottest Indianapolis 500 race in decades and sat with the sun facing him; there was no breeze. When he became dehydrated at the race, it triggered the uric acid crystal formation in his foot. The foot became sore, red, hot and swollen; he could not walk on that foot or even fit into a regular pair of shoes. The race was great and he drank about 2 L of water and soda at the race and another couple of liters when he arrived home. A metaphase-blocking dose of colchicine functions through which of the following mechanisms Depolymerization of actin Depolymerization of myosin Enhancement of tubulin polymerization Inhibition of tubulin polymerization Binding to and stabilizing microtubules 142 Anatomy, Histology, and Cell Biology 66. The structure labeled A in the accompanying electron micrograph is which of the following Which of the following mechanisms may be involved in the loss of cell cycle control that occurs in prostate carcinoma Increased CdkI activity Decreased transcription of G1/S cyclin Decreased expression of bcl-2 Increased transcription of gene regulatory proteins such as E2F Dephosphorylation of Rb 68. Decreased recombination is associated with the production of aneuploid sperm in humans. An obese 18-year-old man presents with small firm testes, a small penis, little axillary and facial hair, azoospermia, gynecomastia, and elevated levels of plasma gonadotropins. He has had difficulty in social adjustment throughout high school, but this has worsened and he has been referred for genetic and endocrine screening. The karyotype from peripheral blood leukocytes would most likely show how many Barr body/bodies He experienced normal fetal and early postnatal development, but now shows severe failure to thrive, some lipoatrophy, bony abnormalities, a small, beaked nose and receding mandible, hair loss, and speckled hypopigmentation with some areas of tight hard skin. Which of the following would you most likely expect to be directly affected in cells obtained in a biopsy from this patient He has craniosynostosis, hypoplasia of the middle part of his face with retrusion of the eyes, and syndactyly that includes fusion of the skin, connective tissue, and muscle of the first, middle, and ring fingers with moderate fusion of the bones of those digits. Which of the following were most likely decreased in cells in the inter-digital region of the developing hand of this newborn child A 25-year-old man presents with Triple A (Allgrove) syndrome including the clinical triad of adrenal failure, achalasia, and alacrima. Expression of treacle is critical during early embryonic development in structures that form bones and other facial structures. Treacle is active in the nucleolus, the structure labeled in the transmission electron micrograph. Ribosomal synthesis occurs in the nucleolus, but the complete assembly and maturation of ribosomes requires transport to the cytoplasm (answer a). Ribosomal proteins as well as all proteins that function in the nucleus are synthesized in the cytosol and transported into the nucleus (answer b). Cytosolic proteins are synthesized on isolated ribosomes compared with most protein synthesis that occurs on polyribosomes. Cytokinesis requires the action of the contractile ring composed of actin and myosin. The force for cytokinesis is generated by the action of actin and myosin, which may be inhibited by 146 Cell Biology: Nucleus Answers 147 treatment with antimyosin antibodies in vitro. The contractile ring pulls the plasma membrane of the telophase cell into the cleavage furrow. Kinetochore microtubules, which attach the kinetochores to the spindle apparatus, shorten and pull the chromatids to opposite poles in anaphase A (answer a). Growth of polar microtubules results in the separation of the spindle poles in anaphase B (answer c). The events that occur during each stage of the cell cycle are shown in the table below. Chromatin strands that have been treated to unpack the chromatin structure have the appearance of beads on a string in electron micrographs. The nuclear pores are perforations in the nuclear envelope, each composed of a nuclear pore complex (answer c). The nuclear matrix is the intranuclear cytoskeleton and forms the scaffolding for nuclear structures (answer d). The G1-phase cell is quickly pulled or driven into mitosis as the chromosomes condense. The lamins are a subclass of intermediate filaments including three nuclear proteins: lamins A, B, and C. Phosphorylation of intermediate filaments leads to disassembly, as occurs with the lamins. The disassembly of lamins results in the dissolution of the nuclear envelope in prometaphase of the cell cycle. A re-replication block cannot occur in the G1 cell because it has not gone through S (answer e). The lamins differ from other intermediate filament proteins in the presence of a nuclear import signal. The lamins form the core of the nuclear lamina, interact with nuclear envelope proteins, and play a role in the maintenance of the shape of the nucleus. Dephosphorylation of the lamins is associated with the reassembly of the nuclear envelope in telophase. The colchicine-tubulin complex is added at the positive end of the kinetochore, but it inhibits further addition of tubulin (answer c). The result is a biochemical capping of the tubulin at the growth end, preventing further tubulin addition. Cells are blocked in metaphase and cannot escape because microtubule motors are unable to function in generating the forces required for anaphase. Actin and myosin are involved in cytokinesis [the division of cytoplasm (answers a and b)], whereas tubulin and the microtubules regulate separation of the daughter nuclei and their contents. Taxol binds and stabilizes microtubules (answer e), causing a disruption of microtubule dynamics and inhibition of mitosis. Taxol and colchicine are similar in binding only to ,-tubulin dimers and microtubules. It is transcriptionally inactive during the interphase stage of the cell cycle, when the genetic material is normally duplicated. Heterochromatin is one of two subclassifications of chromatin on a morphologic basis. Euchromatin (B) is actively transcribed chromatin and is visible only with the use of electron microscopy. The nuclear envelope (C) shields the nucleus from the cytoplasm, which allows the sequestration of the genetic material from mechanical cytoplasmic forces. The separate nuclear compartment also allows for separation of the cellular processes of transcription and translation. The inner nuclear membrane is associated with a lamina of fibrous proteins including intermediate filament proteins, known as lamins, that regulate the assembly and disassembly of the nuclear membrane during mitosis. Nuclear pores (D) are interruptions in the nuclear envelope that function as aqueous channels for the passage of soluble molecules from the nucleus to the cytoplasm (ribosomal subunits) and from the cytoplasm to the nucleus (nuclear proteins synthesized in the cytoplasm and transported to the nucleus). E2F is regulated through phosphorylation and dephosphorylation of Retinoblastoma protein (Rb), a key "negative" regulator of the cell cycle. Cells that enter G1 have dephosphorylated Rb protein that is subsequently phosphorylated, allowing passage of cells from G1 to "S. Accumulation of 150 Anatomy, Histology, and Cell Biology bcl-2 has been associated with the increased incidence and severity of prostate carcinoma in African-American males. At each point where crossover has occurred between two chromatids of the homologous chromosomes, an attachment point known as a chiasma forms. Meiosis is the mechanism used by the reproductive organs to generate gametes-cells with the haploid number of chromosomes. During meiotic prophase I, maternal and paternal chromosomes are precisely paired, and recombination occurs in each pair of homologous chromosomes. The first meiotic prophase consists of five substages: leptotene, zygotene, pachytene, diplotene, and diakinesis. During metaphase I, there is random segregation of maternal and paternal chromosomes. Homologous chromosomes are aligned on the metaphase plate of the meiotic spindle in metaphase I. The second meiotic division is responsible for the reduction in the chromosome content of the cell by 50%. In zygotene (answer b), the synaptonemal complex begins to form, which initiates the close association between chromosomes known as synapsis. The bivalent is formed between the two sets of homologous chromosomes (one set maternal and one set paternal equals a pair of maternal chromatids and a pair of paternal chromatids). The formation of chiasmata and desynapsing (separation of the axes of the synaptonemal complex) occurs in the diplotene stage (answer d). Diakinesis (answer e) Cell Biology: Nucleus Answers 151 is an intermediate phase between diplotene and metaphase of the first meiotic division. The formula is the number of Barr bodies equals the number of X chromosomes minus one. The nondisjunction is more frequent in oogenesis than in spermatogenesis, and increased occurrence is directly proportional to increasing maternal age. A combination of abnormal and normal genotype occurs in mosaic individuals who generally have less severe symptoms. Only one of the X chromosomes is active in the somatic, diploid cells of the female; the other X chromosome remains inactive and is visible in appropriately stained interphase cells as a mass of heterochromatin. Detection of the Barr body (sex chromatin) has been an efficient method for the determination of chromosomal sex and abnormalities of X-chromosome number; however, it is not definitive proof of maleness or femaleness. Buccal scrapings for Barr body analysis are being used less-chromosomal analysis is the standard test now. The lamins are intermediate filament proteins that regulate the nuclear envelope, maintain its stability, and are phosphorylated (prometaphase) and dephosphorylated (telophase) during the cell cycle. Laminin binds to integrins on the cell surface to facilitate attachment of cells to the basement membrane (answer d). Bax is a proapoptotic member of that protein family and inhibits the antiapoptotic actions of bcl-2. Bax would be down-regulated and bcl-2 up-regulated in syndactyly where apoptosis has failed (answer d). The immediate effect of mutations in the nucleoporins is decreased import of macromolecules from the cytoplasm. Phosphorylation (breakdown) and dephosphorylation (reconstitution) of the lamins regulates nuclear envelope stability during the cell cycle (answers b and c). A male child is born with an absence of the normal structure labeled between the arrows; inclusions of that structure are found within the cells in the photomicrograph. He presents with refractory diarrhea and is chronically dependent on parenteral nutrition. What is the primary function of the structure labeled between the arrows in the photomicrograph below The mechanism for tube formation as occurs during development of the neural tube could best be explained by which of the following Contraction of microfilament bundles associated with the zonula adherens Increased condensation of the transmembrane linkers of the desmosomes Expansion of the sealing strands in the zonulae occludentes Condensation of the gap junctions Contraction of tonofilaments associated with desmosomes Epithelium 155 75. In the figure below, A is a transmission electron micrograph, and B is a freeze-fracture preparation of a specific cellular structure. Mutations in the proteins that constitute the intramembranous particles labeled in the freeze-fracture image below occur in humans. Which of the following would one expect to occur in the presence of such mutations Faster conduction of nerve impulses Increased peristalsis in the small intestine Cardiac arrhythmias More rapid mobilization of glycogen to glucose in response to low blood sugar levels Decreased adherence of epithelial cells to the basement membrane 76. Molecular filtering Contractility Excitability Modification of secreted protein Active ion transport 156 Anatomy, Histology, and Cell Biology 77. In which specific layer of the accompanying electron micrograph would you expect to see the disruption A 54-year-old woman presents to the oral surgeon on referral by her general dentist. Her dentist observes a firm mass in the anterior right side of the floor of the mouth. Her dentures were made by a denturist to save money and her general dentist indicates they fit very poorly. The calcification blocks the submandibular duct leading to atrophy of the acini and ducts with reduced secretory function. One would expect which of the following functional changes to occur in association with the basal folds of the striated duct cells Per-Lennart Westesson and Xiang Liu, University of Rochester, Case #98. Increased lipid transport Increased absorption of carbohydrate Decreased active transport Decreased secretion of the primary saliva Decreased lysosomal activity 158 Anatomy, Histology, and Cell Biology 80. In the electron micrograph below, the structure labeled D primarily does which of the following Forms a spot weld between cells Interacts with actin in the cytoplasm of the apical cytosol Facilitates communication between adjacent cells Seals membranes between cells Moves microvilli Epithelium 159 81. An 11-year-old boy presents with ciliary dyskinesia, sinusitis, and bronchiectasis. In the cross-section of the cilium shown below, which of the following is primarily affected in this disorder The conversion of sliding to bending in the cilium is accomplished by which of the following Restriction of movement by dynein binding of the central microtubules to each other b. Restriction of the microtubule doublets by radial spokes, nexin, and basal bodies 160 Anatomy, Histology, and Cell Biology 83. The structure responsible for the linkage of the intermediate filament network of cells to the basal lamina is which of the following Macula adherens Zonula adherens Hemidesmosomes Focal contacts Zonula occludens 84. A 42-year-old woman, of Mediterranean descent, presents with multiple oral blisters (see photograph), which she says have been present for several months, and a few cutaneous blisters on her back and buttocks that she just noticed over the past week. The bullae are fairly superficial, with the site of skin disruption clearly in the epidermis. Analysis of her sera indicates autoantibodies to a subfamily of cadherins with the distribution shown in the immunofluorescence image (see photomicrograph). Hemidesmosome Zonula adherens Macula adherens Gap junctions Lamina densa of the basal lamina 85. Centrioles Cytoplasmic microtubules Flagellae Axonemes Stereocilia Epithelium Answers 73. Microvilli increase surface area for specialized uptake of molecules by pinocytosis, receptor-mediated endocytosis, and phagocytosis. The microvilli also contain the brush border enzymes such as lactase and alkaline phosphatase. Microvilli are supported by a core of microfilaments and are capable of movement; however, cilia (answer a) function in the movement of substances, such as mucus and foreign material, over the surface. Cell movement is controlled by interactions between the cytoskeleton and the extracellular matrix (answer c), while microtubules facilitate organellar movement within the cytoplasm (answer d). Transitional epithelium characteristic of the urinary system facilitates distensibility and stretch (answer e). Tubular structures form from flat sheets by contraction of the microfilament bundles associated with the adhesion belt junctions (zonula adherens). In the apical part of the cells, the actin filament bundles contract, narrowing the cells at their apical ends. The position of the zonula adherens, forming a contractile ring around the circumference of the cell, coupled with the contractile nature of the actin microfilament bundles is ideal for regulating morphogenetic changes. Desmosomes (answers b and e) are involved in resisting shear forces and are not directly involved in this process. See table in answer for question 83 for detailed summary of function of components of the junctional complex. The action potential is transmitted from cell to cell through the heart, providing the rhythmic contraction of the heartbeat. Abnormalities in the spatial distribution of gap junctions or the proteins (connexins) that compose the connexons will lead to arrhythmias and play a role in obstructive coronary heart disease.
Selective increase in specific alternative splice variants of tyrosinase in murine melanomas: a projected basis for immunotherapy gastritis colitis diet cheap metoclopramide 10 mg without a prescription. Alteration of tyrosinase activity in human melanocytes and melanoma cells by histamine H2 and H3 ligands gastritis kiwi purchase 10 mg metoclopramide with mastercard. Human keratinocyte line HaCaT metabolizes 1alpha-hydroxyvitamin D3 and vitamin D3 to 1alpha gastritis diet 4 believers buy generic metoclopramide 10 mg online,25-dihydroxyvitamin D3 (calcitriol) gastritis caused by diet order metoclopramide 10mg overnight delivery. LePoole C gastritis attack diet metoclopramide 10mg cheap, Boissy R gastritis onions purchase metoclopramide 10mg free shipping, Sarangarajan R gastritis symptoms empty stomach order metoclopramide 10mg with mastercard, Chen J healthy liquid diet gastritis generic metoclopramide 10mg on line, Forristal J, Sheth P, Westerhof W, Babcock G, Das P, and Saelinger C. Effect of alpha- and beta-melanocyte stimulating hormones on the skin color of mean. Melanocytes are potential immunocompetent cells: evidence from recognition of immunological characteristics of cultured human melanocytes. Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus. Proc Advisory Group Meeting Intern Atomic Energy Agency Vienna Switzerland 1976, p. Lupetti R, Pisarra P, Verrecchia A, Farina C, Nicolini G, Anichini A, Bordignon C, Sensi M, Parmiani G, and Traversari C. Stimulation of the adenylate cyclase of A B16 melanoma cell line by pro-opiocortin-related peptides-a structure-activity study. Mislocalization of melanosomal proteins in melanocytes from mice with oculocutaneous albinism type 2. Mutational analysis of the modulation of tyrosinase by tyrosinase-related proteins 1 and 2 in vitro. Interaction of melanin with proteins-the importance of an acidic intramelanosomal pH. Vitamin D, its precursors, and metabolites do not affect melanization of cultured human melanocytes. Tyrosine hydroxylase isoenzyme I is present in human melanosomes: a possible novel function in pigmentation. Transforming growth factor beta1 mediates hypopigmentation of B16 mouse melanoma cells by inhibition of melanin formation and melanosome maturation. Mechanisms of melanogenesis inhibition by tumor necrosis factor-alpha in B16/F10 mouse melanoma cells. Growth-inhibitory effects of 1,25-dihydroxyvitamin D3 on normal human keratinocytes cultured in serum-free medium. Inhibition of melanization in human melanoma cells by a serotonin uptake inhibitor. Regulation of tyrosinase expression and activity in human melanoma cells via histamine receptors. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Receptors for B-melanocyte-stimulating hormone exhibit positive cooperativity in synchronized melanoma cells. Chronic growth stimulation of human adult melanocytes by inflammatory mediators in vitro: implications for nevus formation and initial steps in melanocyte oncogenesis. The rat melanin-concentrating hormone messenger ribonucleic acid encodes multiple putative neuropeptides coexpressed in the dorsolateral hypothalamus. Immunocytochemical identification of melanin-concentrating hormone in the brain and pituitary gland of the teleost fishes Oncorhynchus keta and Salmo gairdneri. Allosteric regulation of tyrosine hydroxylase activity by its cofactor tetrahydrobiopterin. Pertussis toxin-sensitive melatonin receptors negatively coupled to adenylate cyclase associated with cultured human and rat retinal pigment epithelial cells. Nishikawa S, Kusakabe M, Yoshinaga K, Ogawa M, Hayashi S, Kunisada T, Era T, and Sakakura T. In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit-dependency during melanocyte development. The effects of oral melatonin on skin color and on the release of pituitary hormones. The expression of the c-kit receptor by epidermal melanocytes may be reduced in vitiligo. Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated. Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Catecholamine effects on lipolysis and blood flow in human abdominal and femoral adipose tissue. Harding-passey mouse-melanoma tyrosinase inactivation by reaction products and activation by L-epinephrine. Evidence for specific complex formation between alpha-melanocyte stimulating hormone and 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin using near infrared Fourier transform Raman spectroscopy. Leukotrienes C4 and D4 as potent mitogens for cultured human neonatal melanocytes. Mori M, Harada M, Terao Y, Sugo T, Watanabe T, Shimomura Y, Abe M, Shintani Y, Onda H, Nishimura O, and Fujino M. Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci. Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. Isolation of a new tautomerase monitored by the conversion of D-dopachrome to 5,6-dihydroxyindole. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Glucocorticoid receptors in cultured human skin fibroblasts: evidence for down-regulation of receptor by glucocorticoid hormone. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Subcellular distribution of tyrosinase and tyrosinase-related protein-1: implications for melanosomal biogenesis. The pink-eyed dilution locus controls the biogenesis of melanosomes and levels of melanosomal proteins in the eye. Inhibition of induced melanogenesis in Cloudman melanoma cells by four phenotypic modifiers. Retinoic acid is a potent inhibitor of inducible pigmentation in murine and hamster melanoma cell lines. High-molecular-weight forms of tyrosinase and the tyrosinase-related proteins: evidence for a melanogenic complex. Muscarinic acetylcholine receptor-mediated phosphoinositide turnover in cultured human retinal pigment epithelium cells. Human thermoregulatory responses during heat exposure after artificially induced sunburn. Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain. Alpha-melanocyte stimulating hormone-induced pigmentation is blocked by depletion of protein kinase C. The beta isoform of protein kinase C stimulates human melanogenesis by activating tyrosinase in pigment cells. A possible role for melanin precursors in regulating both pigmentation and proliferation of melanocytes. Corticoids and cultured human epidermal keratinocytes: specific intracellular binding and clinical efficacy. Tyrosine transport into melanosomes is increased following stimulation of melanocyte differentiation. Characterization of a melanosomal transport system in murine melanocytes mediating entry of the melanogenic substrate tyrosine. Latanoprost stimulates eumelanogenesis in iridial melanocytes of cynomolgus monkeys. Effect of the dose of ultraviolet radiation on the pigment formation by human melanocytes in vitro. Effects of melanin-induced free radicals on the isolated rat peritoneal mast cells. Human melanocytes as a target tissue for hormones: in vitro studies with 1 alpha-25, dihydroxyvitamin D3, alpha-melanocyte stimulating hormone, and betaestradiol. Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells. Melanoma cells resistant to inhibition of growth by melanocyte stimulating hormone. Genetic control of melanization: isolation and analysis of amelanotic variants from cultured melanotic melanoma cells. Migration of melanoblasts into the developing murine hair follicle is accompanied by transient c-Kit expression. Proopiomelanocortin-related peptides, prohormone convertases 1 and 2 and the regulatory peptide 7B2 are present in melanosomes of human melanocytes. Pisarra P, Lupetti R, Palumbo A, Napolitano A, Prota G, Parmiani G, Anichini A, and Sensi M. Multiple roles for endothelin in melanocyte development: regulation of progenitor number and stimulation of differentiation. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. In vitro effect of histamine and histamine H1 and H2 receptor antagonists on cellular proliferation of human malignant melanoma cell lines. Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Tyrosinase kinetics: a semi-quantitative model of the mechanism of oxidation of monohydric and dihydric phenolic substrates. Rios M, Habecker B, Sasaoka T, Eisenhofer G, Tian H, Landis S, Chikaraishi D, and Roffler-Tarlov S. Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase. Identification and characterization of glucocorticoid receptors in B16 mouse melanoma cells. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Melanosomal defects in melanocytes from mice lacking expression of the pink-eyed dilution gene: correction by culture in the presence of excess tyrosine. Studies on the role of leukotrienes in murine allergic and irritant contact dermatitis. Regulation of protein kinase C gene expression by retinoic acid in B16 mouse melanoma cells. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing. Saito H, Yasumoto K, Takeda K, Takahashi K, Fukuzaki A, Orikasa S, and Shibahara S. Melanocyte-specific microphthalmia-associated transcription factor isoform activates its own gene promoter through physical interaction with lymphoid-enhancing factor 1. Defective tetrahydrobiopterin and catecholamine biosynthesis in the depigmentation disorder vitiligo. Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes. Retinal dopamine D1 and D2 receptors: characterization by binding or pharmacological studies and physiological functions. Tyrosine levels regulate the melanogenic response to alpha-melanocyte-stimulating hormone in human melanocytes: implications for pigmentation and proliferation. Eumelanins and phaeomelanins: characterization by electron spin resonance spectroscopy. The family of subtilisin/ kexin like pro-protein and pro-hormone convertases: divergent or shared functions. Sorting and targeting of melanosomal membrane proteins: signals, pathways, and mechanisms. Induction of melanogenesis during the various melanoma growth phases and the role of tyrosinase, lysosome-associated membrane proteins, and p90 calnexin in the melanogenesis cascade. Interferon-beta from melanoma cells suppresses the proliferations of melanoma cells in an autocrine manner. The induction of the alpha-1-adrenoceptor signal transduction system on human melanocytes. Thioredoxin reductase induction coincides with melanin biosynthesis in brown and black guinea pigs and in murine melanoma cells. Downregulation of tyrosinase activity in human melanocyte cell cultures by yohimbine. The importance of L-phenylalanine transport and its autocrine turnover to L-tyrosine for melanogenesis in human epidermal melanocytes. Fas and c-kit are involved in the control of hair follicle melanocyte apoptosis and migration in chemotherapy-induced hair loss. Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation. Malignant melanoma: influence of site of lesion and age of patient in the female superiority in survival. Structural organization of the pigment cell-specific gene located at the brown locus in mouse. Identification of a cis-acting element that enhances the pigment cell-specific expression of the human tyrosinase gene. Downstream region of the human tyrosinase-related protein gene enhances its promoter activity. Human malignant melanoma cells express high-affinity receptors for melatonin: antiproliferative effects of melatonin and 6-chloromelatonin. Ultraweak photon emission in model reactions of the in vitro formation of eumelanins and pheomelanins. Some properties of Bomirski Ab amelanotic melanoma cells, which underwent spontaneous melanization in primary cell culture. Molecular mechanisms governing melanogenesis in hamster melanomas: relative abundance of tyrosinase and catalase-B (gp 75). L-Tyrosine, Ldopa and tyrosinase as positive regulators of the subcellular apparatus of melanogenesis in Bomirski Ab amelanotic melanoma. Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway: L-tyrosine and L-dopa. Bomirski melanomas: a versatile and powerful model for pigment cell and melanoma research. Melanogenesis is coupled to murine anagen: toward new concepts for the role of melanocytes and the Expression of hypothalamic-pituitary-thyroid axis related genes in the human skin. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Detection of the proopiomelanocortinderived antigens in normal and pathologic human skin. Smit N, Tilgmann C, Karhunen T, Slingerland R, Ulmanen I, Westerhof W, and Pavel S. O-methylation of L-dopa in melanin metabolism and the presence of catechol-O-methyltransferase in melanocytes. Multi-hormonal regulation of tyrosinase expression in B16/C3 melanoma cells in culture. Retinoic acid blockade of imidazole-induced tyrosinase expression in B16 melanoma cultures: similar effects of the active retinoid and triiodothyronine. The pigmentary changes occurring in the breast skin during pregnancy and following estrogen treatment. New insights on the structure of the mouse silver locus and on the function of the silver protein. Multi-organellar disorders of pigmentation: intracellular traffic jams in mammals, flies and yeast. Differential expression and activity of melanogenesis-related proteins during induced hair growth in mice. Inhibition of melanogenesis as an adjuvant strategy in the treatment of melanotic melanomas: selective review and hypothesis. Pharmacological disruption of hair follicle pigmentation as a model for studying the melanocyte response to and recovery from cytotoxic damage in situ. Slominski A, Paus R, Plonka P, Maurer M, Chakraborty A, Pruski D, and Lukiewicz S. Melanogenesis during the anagencatagen-telogen transformation of the murine hair cycle. Slominski A, Pisarchik A, Johansson O, Jing C, Semak I, Slugocki G, and Wortsman J. Functional activity of serotoninergic and melatoninergic systems expressed in the skin.
Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults granulomatous gastritis symptoms buy discount metoclopramide 10mg on line, children and in pregnancy gastritis diet 50 order metoclopramide 10mg with amex. Recent advances in the treatment of chronic refractory immune thrombocytopenic purpura symptoms of gastritis flare up 10 mg metoclopramide visa. For Eosinophilic Asthma: the patient has responded to Nucala therapy as determined by the prescribing physician gastritis diet buy metoclopramide 10 mg free shipping. Members ages 10-17 will be given coverage for the initial titrating doses as well viral gastritis diet discount metoclopramide 10mg with mastercard. Jenkins A gastritis diet buy 10 mg metoclopramide fast delivery, Wang-Smith L gastritis diet what to eat cheap 10 mg metoclopramide overnight delivery, Marbury T gastritis journal pdf generic metoclopramide 10mg on-line, et al: Pharmacokinetics of treprostinil diolamine in subjects with end-stage renal disease on or off dialysis. Provider attests that the patient has achieved a clinically meaningful response while on Orkambi therapy to one of the following: a. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung function. Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: A 190ulticente, double blind, placebo controlled 190ulticenter trial. Intra-articular hyaluronan injections for the treatment osteoarthritis of the knee: a randomized, double blind, placebo controlled study. Only for use by physicians experienced in antimetabolite therapy o Embryo-fetal toxicity: Exclude pregnancy before treatment. Advise males to avoid pregnancy for a minimum of three months after therapy and females to avoid pregnancy for at least one ovulatory cycle after therapy o Risks from improper dosing: Mistaken daily use has led to fatal toxicity o Patients with impaired renal function, ascites, or pleural effusions: Elimination is reduced Dizziness and fatigue: May impair ability to drive or operate machinery Monitoring: o Effects on reproduction: May cause impairment of fertility, oligospermia and menstrual dysfunction o Laboratory tests: Monitor complete blood counts, renal function and liver function tests Contraindication: o Pregnancy; Avoid pregnancy if either partner is receiving Otrexup. One of the following: o T score at the lumbar spine, total hip, or femoral neck of less than -1. Usual dose: 60mg subcutaneously administered by a healthcare professional once every 6 months. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 5. Pediatric Vulvovaginal Disorders: A Diagnostic Approach and Review of the Literature. A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebocontrolled study. Modafinil in children and adolescents with attention-deficit/hyperactivity disorder: a preliminary 8-week, open-label study. Efficacy and safety of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, doubleblind, placebo-controlled, flexible-dose study. A randomized, double-blind, placebo-controlled study of modaf inil filmcoated tablets in children and adolescents with attention-deficit/hyperactivity disorder. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep/apnea/hypopnea syndrome. Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study. Modafinil film-coated tablets in children and adolescents with attentiondeficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Must be 5 years of age or older for capsule use or 3 years of age or older for solution use. Members who have failed previous therapy with Victrelis or Incivek-based regimens 6. Decompensated liver disease Coverage of ribavirin is not recommended in the following circumstances: Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 1. Update on the management and treatment of hepatitis C virus infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 16. The effect of interferon alfa and ribavirin combination therapy in naive patients with chronic hepatitis C. Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 37. Must be clinically diagnosed with chronic anal fissures and have moderate to severe pain associated with it. Increased intracranial pressure Known hypersensitivity to nitroglycerin, other nitrates, or any components of the ointment. If this dose cannot be tolerated because of systemic effects, the infusion rate should be reduced to 0. Rich S, Calcium channel blockers and anticoagulants in the therapy of pulmonary hypertension. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension. Efficacy and safety of treprostinil: an Epoprostenol analog for primary pulmonary hypertension. References Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 1) Virginia Premier. Member has a record of 1 month trial of and inadequate response or intolerance to 2 of any of the following oral medications: Antidepressants. For women of childbearing age; the member continued to be monitored for pregnancy status 5. For use in children clinically diagnosed with hepatitis C with compensated liver disease previously untreated with alpha interferon; relapsed following alpha interferon therapy. Members who have failed previous therapy with Victrelis or Incivek-based regimens Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 6. Decompensated liver disease Coverage of ribavirin is not recommended in the following circumstances: 1. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 15. Combination treatment with interferon alfa-2b and ribavirin for chronic hepatitis C in patients who have failed to achieve sustained response to interferon alone: Swedish experience. Randomised, double -blind, placebo-controlled trial of interferon -2b with and without ribavirin f or chronic hepatitis C. The effect of interferon alfa and ribav irin combination therapy in naive patients with chronic hepatitis C. Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 36. The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C. American College of Rheumatology 2008 Recommendations for the Use of Nonbiological and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Practice Parameter update: Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): Teratogenesis Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 2. Report of the Quality Standards Subcommittee and T herapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile Seizures: Clinical proactive guideline for the long -term management of the child with simple febrile seizures. Vasopressin v(2) receptor blockade with tolvaptan versus fluid restriction in the treatment of hyponatremia. Gabapentin in the treatment of fibromyalgia: A randomized, double-blind, placebo-controlled, multicenter trial. Psychological interven tions for major depression in primary care: a meta-analytic review of randomized controlled trials. Guideline for the management of fibromyalgia syndrome pain in adults and children. Comparative efficacy and acceptability of 12 newgeneration antidepressants: a multiple-treatments meta-analysis. Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial. Comparative Effectiveness of Second Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative benefits and harms of second generation antidepressants: background paper for the American College of Physicians. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 11. A double blind comparison of the efficacy and safety of milnacipran and fluoxetine in depressed inpatients. Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants. A double-blind six months comparative study of milnacipran and clomipramine in major depressive disorder. Sechter D, Vandel P, Weiller E, Pezous N, Cabanac F, Tournoux A; study co -coordinators. A comparative study of milnacipran and paroxetine in outpatients with major depression. Double-blind study of the efficacy and safety of milnacipran and imipramine in elderly patients with major depressive episode. Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: systematic review and metaanalysis. Member has had a trial and failure, intolerance, or contraindication to at least one (1) of the following: a. Member has lost at least 4% or baseline bodyweight Approval Duration: 4 months Notes: Change in body weight with Saxenda should be evaluated every 16 weeks after initiation of medication. If the patient has not lost 4% of baseline body weight, Saxenda should be discontinued because it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. If the patient cannot tolerate an increased dose during dose escalation, consider delaying dose escalation for one week. If the 3 mg daily dose is not tolerated, discontinue use as efficacy has not been established at lower doses. Tertiary hyperparathyroidism in post-kidney transplant patients not receiving dialysis All other indications are considered experimental/investigational and are not a covered benefit. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval B. Primary Hyperparathyroidism Authorization of 12 months may be granted for the treatment of primary hyperparathyroidism in a member who is not able to undergo parathyroidectomy and has a serum calcium level (corrected for albumin) greater than or equal to 8. Tertiary Hyperparathyroidism in Post-Kidney Transplant Patients Not Receiving Dialysis Authorization of 12 months may be granted for the treatment of tertiary hyperparathyroidism in a member who has had a kidney transplant, is not receiving dialysis, and has a serum calcium level (corrected for albumin) greater than or equal to 8. Parathyroid Carcinoma Authorization of 12 months may be granted for the treatment of parathyroid carcinoma in a member who has a serum calcium level (corrected for albumin) greater than or equal to 8. A randomized study evaluating cinacalcet to treat hypercalcemia in renal transplant recipients with persistent hyperparathyroidism. The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism. Combination therapy with two biologic agents is not recommended due to a higher rate of adverse effects with combinations and lack of additive efficacy. Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval 2. Golimumab has been studied in patients with psoriatic arthritis who had plaque psoriasis. Prospective, controlled trials are needed to determine safety and efficacy in plaque psoriasis. In a double-blind trial, 309 patients with uncontrolled, severe asthma despite high -dose inhaled corticosteroids and long-acting beta-2 agonists were randomized to golimumab 50, 100, or 200 mg or to placebo for 52 weeks. Unfavorable risk-benefit profile led to early discontinuation of study agent administration after the week 24 database lock. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Golimumab: a tumor necrosis factor alpha inhibitor for the treatment of rheumatoid arthritis. For patients who require antibiotic treatment generic minocycline is a less expensive option. Duration of Therapy: 12 weeks (safety beyond this point has not been established). Improvement or maintenance of previous improvement of at least a 3 point increase in score from pretreatment baseline Requests for continuing therapy that were approved by a previous Health Plan will be honored for at least 30 days upon receipt of documentation demonstrating that approval ii. Improvement or maintenance of previous improvement of at least a 2 point increase in score from pretreatment baseline ii. Improvement or maintenance of previous improvement of at least a 4 point increase in score from pretreatment baseline ii. Spinraza is not proven or medically necessary for spinal muscular atrophy without chromosome 5q mutations or deletions.
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