Vitamin D

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Mai 2011



Vitamin D, a steroid hormone, has mainly been known for its effects on bone and osteoporosis. The current therapeutic practices expand into such markets as cancer research, pediatrics, nephrology, dermatology, immunology, and genetics. This 3e includes over 100 chapters covering everything from chemistry and metabolism to mechanisms of action, diagnosis and management, new analogs, and emerging therapies. This complete reference works is a must-have resource for anyone working in endocrinology, osteology, bone biology, or cancer research.*Most comprehensive, up-to-date two-volume set on Vitamin D*Initial chapters cover the chemistry and metabolism of vitamin D, role in mineralization, other target organs, and general physiological effects*Second volume is more clinically oriented addressing deficiency problems (including diagnosis, interactions in the endocrine system, and involvement in malignancies)*Further sections on emerging uses for treatments of auto-immune diseases and diabetes*New chapters on squamous cell cancer, brain cancer, thyroid cancer and many more*Over 600 illustrations and figures available on CD


1;e9780123819789v1.pdf;1 1.1;Front Cover;1 1.2;Vitamin D;4 1.3;Copyright;5 1.4;Contents;6 1.5;Preface to the 3rd Edition;10 1.6;Preface to the 2nd Edition;12 1.7;Preface to the 1st Edition;14 1.8;Contributors;16 1.9;Introduction;22 1.10;Abbreviations;24 1.11;Relevant Lab Values in Adults and Children;30 1.11.1;Criteria for Vitamin D Deficiency: 25(OH)D Serum Levels;30 1.11.2;Approximate normal ranges for serum values in adultsaaNormal ranges differ in various laboratories and these values are pro ...;31 1.11.3;Approximate normal ranges for serum values in childrena;31 1.11.4;Useful equivalencies of different units;31 1.12;Section I -Chemistry, Metabolism, Circulation;32 1.12.1;Chapter 1 - Historical Overview of Vitamin D;34;Discovery of the Vitamins;34;Discovery that Vitamin D is not a Vitamin;35;Isolation and Identification of Nutritional Forms of Vitamin D;36;Discovery of the Physiological Functions of Vitamin D;36;Discovery of the Hormonal Form of Vitamin D;37;Acknowledgments;40;References;40 1.12.2;Chapter 2 - Photobiology of Vitamin D;44;Introduction;44;Historical Perspective;44;Photobiology of Vitamin D;45;Role of Sunlight and Dietary Vitamin D in Bone Health, Overall Health, and Well-Being;48;Sunlight, Vitamin D, and Skin Cancer;49;Conclusion;51;Acknowledgment;51;References;51 1.12.3;Chapter 3 - The Activating Enzymes of Vitamin D Metabolism (25- and 1a-Hydroxylases);54;Introduction;54;General Information Regarding Vitamin D Hydroxylases;54;Vitamin D3-25-Hydroxylases;57;25-Hydroxyvitamin D-1a-Hydroxylase;62;Additional Topics;65;References;69 1.12.4;Chapter 4 - CYP24A1: Structure, Function, and Physiological Role;74;Overview;74;CYP24A1-Catalyzed Pathways;74;StructureFunction Relationships;77;Putative CYP24A1 Involvement in Nonclassical Sys
tems;79;Perspectives;82;References;83 1.12.5;Chapter 5 - The Vitamin D Binding Protein DBP;88;Introduction;88;Vitamin D Binding Protein: Protein and Gene Structure;88;Functions of DBP;91;Conclusions and Perspectives;98;References;99 1.12.6;Chapter 6 - Industrial Aspects of Vitamin D;104;History of Vitamin D Leading To Commercialization;104;Manufacture of the Provitamins;105;Irradiation of 7-Dehydrocholesterol and Ergosterol;110;Metabolite Manufacture;114;Analytical;115;Dietary Requirements;118;Economic Aspects;119;Storage and Shipping;121;References;122 1.13;Section II -Mechanisms of Action;126 1.13.1;Chapter 7 - The Vitamin D Receptor: Biochemical, Molecular, Biological, and Genomic Era Investigations;128;Introduction;128;Vitamin D Biology;129;Discovery of the Vitamin D Receptor;130;VDR Research: The Biochemical Era;130;VDR Research: The Molecular Biological Era;132;VDR Research: The Genomic Era;141;VDR Chromosomal Gene: Structure and Molecular Regulation;149;Concluding Comments;155;Acknowledgment;156;References;156 1.13.2;Chapter 8 - Nuclear Vitamin D Receptor: Natural Ligands, Molecular StructureFunction, and Transcriptional Control of Vital ...;168;Ligands, Gene Targets, and Biological Actions of Vdr;168;VDR as a Member of the Nuclear Receptor Superfamily;175;Molecular StructureFunction Of VDR;178;Mechanisms of VDR-Mediated Control of Gene Expression;181;VDR-Mediated Control of Vital Genes in Healthful Aging and Disease Prevention;185;Conclusions and Perspectives;188;Acknowledgment;193;References;193 1.13.3;Chapter 9 - Structural Basis for Ligand Activity in VDR;202;Introduction;202;Crystal Structure of hvdr. Bound to 1,25(Oh)2d3;203;
Crystal Structure of zVDR Wild-Type LBD Bound to 1,25(OH)2D3;206;Structure of VDR LBD Complexed to Superagonist Ligands;206;Structures of VDR Complexed to 2a-Substituted Analogs;210;Structures of VDR With Nonsteroidal Ligands;212;Structures of VDR With Analogs that Induce Structural Rearrangements;213;Structural Basis for Vitamin D Receptor Antagonism;215;Structure-based Design of Novel Superagonist Analogs;218;Conclusion;219;References;220 1.13.4;Chapter 10 - Coregulators of VDR-mediated Gene Expression;224;Introduction;224;Coactivators of VDR;226;Corepressors;232;Conclusion Integrated Model of Coregulator Activity;234;References;235 1.13.5;Chapter 11 - Target Genes of Vitamin D: Spatio-temporal Interaction of Chromatin, VDR, and Response Elements;242;Introduction;242;Transcriptional Regulation by 1,25(OH)2D3;244;Genomic VDR-Binding sites;245;VDR Target Genes;249;VDR Target Gene Analysis;250;Transcriptional Cycling;251;Conclusion;253;Acknowledgments;253;References;253 1.13.6;Chapter 12 - Epigenetic Modifications in Vitamin D Receptor-mediated Transrepression;258;Introduction;258;WINAC: A Novel VDR-Associating ATP-Dependent Chromatin Remodeling Complex;258;E-Box Motif Negative VDRE Mediates 1,25(OH)2D3-Induced Transrepression;259;Coregulator Switching at E-Box nVdres in Ligand-Dependent Transrepression by VDR;260;WINAC Mediates Ligand-Induced Transrepression by VDR;260;1,25(OH)2D3-Dependent VDR Transrepression Involves CpG Site Methylation in the CYP27B1 Promoter;261;Cell-Cycle-Independent DNA Demethylation During CYP27B1 Transcriptional Derepression;262;MBD4 Mediates Active DNA Demethylation;263;MBD4 is a Downstream Mediator in PTH Signaling-Induced Transcriptional Derepression;263 1.13.6.
10;Conclusion;264;References;264 1.13.7;Chapter 13 - Vitamin D and Wnt/ß-Catenin Signaling;266;Introduction;266;WNT Signaling;266;Antagonism of Wnt/ß-Catenin Pathway by 1,25(OH)2D3 in Colon Cancer;269;Wnt and 1,25(OH)2D3 in the Bone;273;Wnt and 1,25(OH)2D3 in the Skin;275;Conclusions;276;References;276 1.13.8;Chapter 14 - Vitamin D Response Element-binding Protein;282;Introduction;282;Current View of Steroid/Sterol Hormone Action;282;New World Primates;284;New World Primate-Like VItamin D Resistance in Man;286;Heterogeneous Nuclear Ribonucleoproteins (hnRNPs);289;hnRNPs as Multi-Level, Multi-Site, cis-Binding Regulators of Gene Expression;293;The Estrogen Response Element Binding Protein (ERE-BP) and the Intracellular Estrogen Binding Protein (IEBP);295;Compensation for the Dominant-Negative Acting, Response Element-Binding Proteins;296;Conclusion;298;References;298 1.13.9;Chapter 15 - Vitamin D Sterol/VDR Conformational Dynamics and Nongenomic Actions;302;1a,25(OH)2-Vitamin D3 (1,25(OH)2D3) Regulation of Genomic Versus Nongenomic Signaling;302;Vitamin D3 Sterol (VDS) Chemistry;302;1,25(OH)2D3 Mediated Rapid, Nongenomic Responses;308;The Plasma Membrane Vitamin D Receptor;314;The VDR Conformational Ensemble Model;315;VDR Ligand Specificity: Does an Unliganded VDR Ever Exist in Vivo?;322;References;322 1.14;Section III -Mineral and Bone Homeostasis;330 1.14.1;Chapter 16 - Genetic and Epigenetic Control of the Regulatory Machinery for Skeletal Development and Bone Formation: Contrib ...;332;Programs of Bone Formation;332;Nuclear Organization of the Regulatory Machinery for Bone Formation;337;Epigenetic Mechanism for Lineage Commitment;340;Gene Expression within the Three-Dimensional Context of Nuclear Architec
ture;340;Chromatin Remodeling Facilitates Bone-Specific and Vitamin-D-Mediated Promoter Accessibility and Integration of Regulatory ...;342;Scaffolding of Regulatory Components for Combinatorial Control of Gene Expression;344;Closing Remarks;346;Acknowledgments;346;References;346 1.14.2;Chapter 17 - Vitamin D Regulation of Osteoblast Function;352;Introduction;352;Properties of Mature Osteoblasts and Osteocytes;352;Major Regulatory Functions of Osteoblasts and Osteocytes and Control by the Vitamin D Endocrine System;354;Effects of 1,25(OH)2D3 on Osteoblast Differentiation;357;Regulation of Intracellular Signaling Pathways by 1,25(OH)2D3;359;Summary and Conclusions;361;Acknowledgments;361;References;361 1.14.3;Chapter 18 - Osteoclasts;366;Introduction;366;References;373 1.14.4;Chapter 19 - Molecular Mechanisms for Regulation of Intestinal Calcium and Phosphate Absorption by Vitamin D;380;An Overview of Intestinal Calcium Absorption;380;Critical Role of VDR in Control of Intestinal Ca Absorption;382;Can High Vitamin D Status Increase Intestinal Calcium Absorption?;382;An Overview of Intestinal Phosphate Absorption;387;Acknowledgments;389;References;389 1.14.5;Chapter 20 - The Calbindins: Calbindin-D28K and Calbindin-D9K and the Epithelial Calcium Channels TRPV5 and TRPV6;394;Introduction and General Considerations, The Calbindins;394;Localization and Proposed Functional Significance of the Calbindins;395;Regulation of Calbindin Gene Expression;401;Epithelial Calcium Channels;403;Conclusion;404;References;405 1.14.6;Chapter 21 - Mineralization;412;Introduction;412;Conclusions;427;References;427 1.14.7;Chapter 22 - Vitamin D Regulation of Type I Collagen Expression in Bone;434;Introduction;434 1.1
4.7.2;Regulation of Bone Collagen Synthesis;435;Molecular Mechanisms of Regulation;436;Conclusions and Perspectives;437;References;438 1.14.8;Chapter 23 - Target Genes: Bone Proteins;442;Vitamin D and Skeletal Homeostasis;442;Exogenous and Endogenous Sources of 1,25(OH)2D3;443;Direct Actions of Vitamin D in Bone;445;Concluding Remarks;450;References;450 1.14.9;Chapter 24 - Vitamin D and the Calcium-Sensing Receptor;456;Introduction;456;What is the CaSR?;456;Overview of Roles of CaSR and VDR in Maintaining Ca2+O Homeostasis;458;The CaSR and VDR in Tissues Participating in Ca2+O Homeostasis;461;The CaSR and VDR in Tissues Uninvolved in Ca2+O Homeostasis;474;Polymorphisms of the CaSR and VDR and Calcium and Bone Homeostasis;477;Summary and Perspectives;478;References;480 1.14.10;Chapter 25 - Effects of 1,25-Dihydroxyvitamin D3 on Voltage-Sensitive Calcium Channels in Osteoblast Differentiation and Mor ...;488;Systemic and Intracellular Ca2+ Homeostasis;488;Voltage-Sensitive Calcium Channels;488;1,25-Dihydroxyvitamin D3 Actions on Voltage-Sensitive Ca2+ Channels;491;1,25-Dihydroxyvitamin D3-Regulated Osteoblast Differentiation;493;Influence of 1,25(OH)2D3 on Osteoblast Cell Survival;494;Acknowledgments;495;References;495 1.15;Section IV -Targets;500 1.15.1;Chapter 26 - Vitamin D and the Kidney;502;Introduction;502;Role of the Kidney in the Metabolism of 25(OH)D;503;Effects of vitamin D, 25(OH)D3 and 1,25(OH)2D3 on the Renal Handling of Calcium and Phosphorus;504;Distribution and Regulation of Vitamin-D-Dependent Proteins in the Kidney;506;Conclusion;513;References;513 1.15.2;Chapter 27 - Vitamin D and the Parathyroids;524;Introduction;524;Parathyroid Hormone Biosynthesis;524;The P
arathyroid Hormone Gene;524;Development of the Parathyroid and Tissue-Specific Expression of The PTH Gene;525;Promoter Sequences;525;Regulation Of Pth Gene Expression;526;Conclusion;533;References;534 1.15.3;Chapter 28 - Cartilage;538;Chondrogenesis, Endochondral Ossification, and Vitamin D;538;Separate Roles for 24,25(OH)2D3 and 1,25(OH)2D3 in Cartilage;540;Rapid Actions of Vitamin D and Nongenomic Mechanisms;542;Physiologic Relevance of Nongenomic Regulation of Matrix Vesicles;544;Conclusion;546;References;547 1.15.4;Chapter 29 - Vitamin D and Oral Health;552;Introduction: The Dento-Maxillofacial Skeleton;552;Dental Rare Diseases and Molecular Determinants of Dental Rickets;553;Experimental Analysis of Dental Pathway in Experimental Models of Vitamin D Bioactivation;555;Specificity of Oral Bone: Potential Vitamin D Impact in Development, Periodontal Disease, and JAW Osteonecrosis;557;Conclusions: Facts and Hypothesis;560;References;561 1.15.5;Chapter 30 - The Role of Vitamin D and its Receptor in Skin and Hair Follicle Biology;564;Introduction;564;Keratinocyte Differentiation;564;Coactivators;565;Barrier Function;565;Hair Cycle;565;Keratinocyte Stem Cells;567;Pathways Important for Keratinocyte Stem Cell Function;567;Conclusions;568;References;569 1.15.6;Chapter 31 - Vitamin D and the Cardiovascular System;572;Introduction;572;Vitamin D and the Vasculature;572;Vitamin D and the Heart;581;Clinical Epidemiological Considerations of Vitamin D Deficiency;585;Conclusion;588;Acknowledgments;589;References;589 1.15.7;Chapter 32 - Vitamin D: A Neurosteroid Affecting Brain Development and Function; Implications for Neurological and Psychiatr ...;596;Introduction;596 1.15.7
.2;Vitamin D Signaling in the Brain;596;Vitamin D Deficiency, Brain Development, and Function;598;Vitamin D and Neurological Disorders;601;Possible Neuroprotective Mechanisms of Vitamin D;603;Vitamin D and Neuropsychiatric Disorders;604;Conclusions;606;References;608 1.15.8;Chapter 33 - Contributions of Genetically Modified Mouse Models to Understanding the Physiology and Pathophysiology of the 2 ...;614;Introduction;614;Mouse Models;615;1,25(OH)2D/VDR System and Skeletal and Mineral Homeostasis;615;Extraskeletal Actions of 1,25(OH)2D;619;Conclusion;627;References;628 1.16;Section V -Human Physiology;636 1.16.1;Chapter 34 -Vitamin D: Role in the Calcium and Phosphorus Economies;638;Introduction;638;Overview of the Calcium Economy;638;Overview of the Phosphorus Economy;643;Calcium and Phosphorus Absorptive Inputs;644;Physiological Sources of Vitamin D Activity;650;Optimal Vitamin D Status;651;Summary and Conclusions;653;References;653 1.16.2;Chapter 35 -Fetus, Neonate and Infant;656;Overview of Calcium Metabolism in the Fetus;656;Animal Data Relevant to Vitamin D and the Fetus;658;Human Data Relevant to Vitamin D and the Fetus;659;Overview of Calcium Metabolism in the Neonate and Infant;663;Animal Data Relevant to Vitamin D and the Neonate and Infant;664;Human Data Relevant to Vitamin D and the Neonate and Infant;666;Conclusions;671;References;671 1.16.3;Chapter 36 -Vitamin D Deficiency and Calcium Absorption during Childhood;678;Introduction;678;Premature Infants;679;Full-Term Infants Calcium;680;Vitamin D in Full-Term Infants;681;Toddlers and Prepubertal Children;682;Special Issues;683;References;685 1.16.4;Chapter 37 -Adolescence and Acquisition of Peak B
one Mass;688;Introduction;688;Pubertal Bone Acquisition;688;Vitamin D in Children and Adolescents;690;Vitamin D and Intermediate Endpoints of Vitamin D and Bone Metabolism;693;Vitamin D and Other Predictors of Calcium Retention;697;Vitamin D and Bone;698;Vitamin D and Muscle;700;Sex and Racial Differences;700;Vitamin D and Diabetes;702;Vitamin D, Asthma, and Influenza;702;Vitamin D Requirements in Adolescents;702;Summary and Conclusions;703;References;704 1.16.5;Chapter 38 -Vitamin D Metabolism in Pregnancy and Lactation;710;Introduction;710;Adaptations in Vitamin D and Calcium Metabolism;710;Changes in Bone Mineral Content and Density;713;Low Maternal Vitamin D During Pregnancy;715;Effect of Low Maternal Vitamin D During Lactation on the Infant;719;Potential Risk of High Maternal Vitamin D During Pregnancy;720;Conclusions;720;References;720 1.16.6;Chapter 39 -Vitamin D: Relevance in Reproductive Biology and Pathophysiological Implications in Reproductive Dysfunction;726;Introduction;726;Procreative Relevance Animal Models;726;Vitamin D Relevance in Human Reproductive Physiology;727;References;734 1.16.7;Chapter 40 -Vitamin D and the Renin-Angiotensin System;738;Introduction;738;The Renin-Angiotensin System;738;Vitamin D Regulation of the Renin-Angiotensin System;742;Vitamin D, Blood Pressure and Heart Disease;746;Vitamin D and Chronic Kidney Disease;747;Conclusion;749;References;750 1.16.8;Chapter 41 -Parathyroid Hormone, Parathyroid Hormone-Related Protein, and Calcitonin;756;Parathyroid Hormone;756;Parathyroid-Hormone-Related Protein;764;Calcitonin;768;References;771 1.16.9;Chapter 42 -FGF23/Klotho New Regulators of Vitamin D Metabolism;778;Introduction;778;Regulation of Vitamin D Metabolism;778;PTHVitamin D Axis: Key Regulator of Calcium Homeostasis;779;FGF23 Klotho Bone Kidney Axis: A Pathway Coordinating Phosphate and Vitamin D Homeostasis with Bone Mineralization;780;Relationship Beween FGF23 and PTH;784;Role of FGF23 in Phosphate Homeostasis;784;Hormonal Actions of klotho?;785;How Knowledge of FGF23 Regulation and Function Changes Concepts, Treatments, and Clinical Practice;786;Conclusion;786;References;788 1.16.10;Chapter 43 -The Role of the Vitamin D Receptor in Bile Acid Homeostasis;794;Introduction;794;Bile Acids in Physiology and Disease;794;VDR as a Bile Acid Receptor;795;Regulation of Bile Acid Synthesis by VDR;795;Evolution of VDR: From Bile Acid Metabolism to Mineral Homeostasis;796;References;797 1.16.11;Chapter 44 -Vitamin D and Fat;800;Introduction;800;Vitamin D Metabolism and Mechanism of Action;800;Vitamin D Deficiency and Adiposity;801;Vitamin D and Obesity: Clinical Implication;804;References;805 1.16.12;Chapter 45 -Extrarenal 1a-Hydroxylase;808;Introduction;808;Vitamin D and Granuloma-Forming Disease: a Historical Perspective;808;Human Diseases With Extrarenal Overproduction of Active Vitamin D Metabolites;810;Extrarenal Synthesis of 1,25(OH)2D in Normal Physiology and Cancer;813;Mechanisms for the Regulation of Extrarenal 1a-Hydroxylase;817;Diagnosis, Prevention, and Treatment of the Patient with Endogenous Vitamin D Intoxication;825;Conclusions and Future Prospects;827;References;827 1.17;Section VI -Diagnosis and Management;836 1.17.1;Chapter 46 -Approach to the Patient with Metabolic Bone Disease;838;Introduction;838;Diagnostic Evaluation;838;Treatment;849;Conclusio
n;853;References;853 1.17.2;Chapter 47 -Detection of Vitamin D and Its Major Metabolites;854;Introduction;854;Detection of Vitamin D;856;Detection of 25(OH)D;858;Detection of 24,25(OH)2D;863;Detection of 1,25(OH)2D;864;Clinical Interpretation and Relevance of Antirachitic Sterol Measurements;870;Stability of 25(OH)D and 1,25(OH)2D in Serum or Plasma;872;Assessment of Assay Performance;872;References;873 1.17.3;Chapter 48 -Bone Histomorphometry;876;Introduction;876;Bone Biopsy;876;Histomorphometry;877;Assessment of Mineralization;879;Histological Diagnosis of Osteomalacia;882;Assessment of Bone Turnover;883;Assessment of Remodeling Balance;884;Assessment of Bone Structure;886;Future Developments;888;References;888 1.17.4;Chapter 49 -Radiology of Rickets and Osteomalacia;892;Introduction and Historical Aspects;892;Vitamin D Deficiency;893;Renal Osteodystrophy;900;Renal Tubular Defects and Hypophosphatemia;906;Acidemia;911;Differential Diagnoses;911;Vitamin D Intoxication;911;Technical Aspects of Imaging;911;Conclusions;915;References;915 1.17.5;Chapter 50 -High-Resolution Imaging Techniques for Bone Quality Assessment;922;Introduction;922;X-ray Computed Tomography (CT);922;Magnetic Resonance Imaging (MRI);936;References;947 1.17.6;Chapter 51 -The Role of Vitamin D in Orthopedic Surgery;958;Introduction;958;Impact on Orthopedic Trauma;958;Impact on Pediatric Orthopedics;962;Impact on Total Joint Arthroplasty;965;Impact on Muscle Strength and Rehabilitation;966;Prevention and Treatment in Orthopedic Patients;968;References;969 1.18;Section VII -Nutrition, Sunlight, Genetics and Vitamin D Deficiency;976 1.1
8.1;Chapter 52 -Worldwide Vitamin D Status;978;Introduction;978;Vitamin D Status in North America (Including Canada and Mexico);978;Vitamin D Status in South America;981;Vitamin D Status in Europe;981;Vitamin D Status in the Middle East;985;Vitamin D Status in Asia;986;Vitamin D Status in Africa;986;Vitamin D Status in Oceania;988;Multicenter and Global Studies using a Central Laboratory Facility;988;Ethnicity/Migration;988;Nutrition;990;Risk Groups;990;Implications;990;Conclusions;990;References;991 1.18.2;Chapter 53 -Sunlight, Vitamin D and Prostate Cancer Epidemiology;996;Introduction;996;Types of Epidemiologic Studies;996;Subclinical Prostate Cancer is Prevalent and May Dilute Effects in Epidemiologic Studies;997;Prostate Cancer and the Vitamin D Hypothesis;997;1,25(OH)2D is Synthesized by Normal Prostate Epithelial Cells and its Synthesis is Reduced in Prostate Cancer Cells;998;Ecologic Studies of Sunlight and Prostate Cancer;1000;Studies of Prostate Cancer and VDR Polymorphisms;1000;Serological Studies of the Vitamin D Deficiency Hypothesis;1001;Epidemiologic Studies of Sun Exposure and Prostate Cancer;1003;Epidemiologic Studies of Calcium and Prostate Cancer;1005;Conclusions;1006;References;1006 1.18.3;Chapter 54 -Nutrition and Lifestyle Effects on Vitamin D Status;1010;Introduction;1010;Determinants of Vitamin D Status;1011;Factors Influencing Skin Synthesis Supplying Vitamin D;1014;Nutrient Intake as Determinant of Vitamin D Status;1022;Lifestyle Strategies to Improve Vitamin D Status;1033;References;1035 1.18.4;Chapter 55 -Bone Loss, Vitamin D and Bariatric Surgery: Nutrition and Obesity;1040;Background;1040;Epidemiology of Bariatric Surg
ery;1040;Indications for Bariatric Surgery;1041;Classification of Bariatric Surgery;1042;Surgical Complications of Bariatric Surgery;1045;Health Benefits of Bariatric Surgery;1046;Medical Complications of Bariatric Surgery;1046;Bone Loss After Gastric Bypass;1047;Vitamin D Status;1049;Calcium Malabsorption after Gastric Bypass Surgery;1050;Evidence of Efficacy of Supplemental Vitamin D;1051;Conclusion;1052;References;1052 1.18.5;Chapter 56 -Genetics of the Vitamin D Endocrine System;1056;Introduction;1056;Genetic Studies;1057;Candidate Genes;1061;Genome-wide Association Studies;1065;Future Developments;1068;References;1068 1.18.6;Chapter 57 -The Pharmacology of Vitamin D;1072;Introduction;1072;Overview of the System of Vitamin D Metabolism and its Regulation;1073;Placebo-Controlled Clinical-Trial Justification for an Optimal Serum 25(Oh)D Level;1079;Dosage Considerations;1081;Pharmacokinetic Principles, Volume of Distribution, Turnover and Half-Life as it Pertains to Vitamin D;1085;Vitamin D Toxicity and Safety Issues;1087;The Concept of a Loading Dose;1089;Summary and Conclusions;1091;References;1092 1.18.7;Chapter 58 -How to Define Optimal Vitamin D Status;1098;Introduction;1098;Vitamin D Status and Bone Health in Adults and The Elderly;1100;Vitamin D and Extra-Skeletal Health;1107;Vitamin D and Human Health: What is The Optimal Vitamin D Status;1113;References;1114 1.19;Color Plates;1120 2;e9780123819789v2;1158 2.1;Front Cover;1158 2.2;Vitamin D;1161 2.3;Copyright;1162 2.4;Contents;1163 2.5;Preface to the 3rd Edition;1167 2.6;Preface to the 2nd Edition;1169 2.7;Preface to the 1st Edition;1171 2.8;Contributors;1173 2.9;Introduction;1179 2.10;Abbreviations;1181 2.11;Relevant Lab Values i
n Adults and Children;1187 2.11.1;Criteria for Vitamin D Deficiency: 25(OH)D Serum Levels;1187 2.11.2;Approximate normal ranges for serum values in adultsaaNormal ranges differ in various laboratories and these values are pro ...;1188 2.11.3;Approximate normal ranges for serum values in childrena;1188 2.11.4;Useful equivalencies of different units;1188 2.12;Section VIII -Disorders;1189 2.12.1;Chapter 59 -The Hypocalcemic Disorders: Differential Diagnosis and Therapeutic Use of Vitamin D;1191;Physiology;1191;Differential Diagnosis of Hypocalcemia;1194;Therapy for Hypocalcemia;1200;References;1203 2.12.2;Chapter 60 -Vitamin D Deficiency and Nutritional Rickets in Children;1207;Introduction;1207;Historical Perspective;1207;The Epidemiology of Vitamin D Deficiency and Nutritional Rickets;1208;Clinical Presentation;1210;Biochemical Abnormalities;1211;Radiologic Changes;1213;The Growth Plate in Rickets;1214;Treatment and Prevention;1215;Dietary Calcium Deficiency;1217;The Pathogenetic Spectrum of Nutritional Rickets;1220;Conclusions;1221;References;1221 2.12.3;Chapter 61 -Vitamin D and Osteoporosis;1229;Effects of Vitamin D on the Skeleton;1229;The Role of Vitamin D Genetic Factors in Osteoporosis and Possible Interactions with Vitamin D Therapy;1230;Primary Fracture Prevention with Vitamin D or Calcium and Vitamin D;1234;Secondary Fracture Prevention with Vitamin D or Calcium and Vitamin D;1239;Effects of Active Vitamin D Analogs on Fractures;1240;Future Directions for Vitamin D in Osteoporosis;1240;References;1241 2.12.4;Chapter 62 -Relevance of Vitamin D Deficiency in Adult Fracture and Fall Prevention;1245;Muscle Effects of Vitamin D;1245;Vitamin D Modulates Fracture Risk in Two Ways: By Increasing Bone Density and Decreasing Falls;1245 2.12.4.
3;Anti-fall and Fracture Efficacy of Vitamin D;1246;Desirable 25(OH)D Status for Optimal Musculoskeletal Health;1248;Dosing Interval of Vitamin D and Musculoskeletal Health;1248;How to Achieve a Serum Concentration of at Least 75nmol/l for Musculoskeletal Health;1250;Summary;1250;References;1250 2.12.5;Chapter 63 -Clinical Disorders of Phosphate Homeostasis;1255;Introduction;1255;Disorders of Phosphate Homeostasis;1259;Disorders Related to an Altered Phosphate Load;1273;Concluding remarks;1278;REFERENCES;1279 2.12.6;Chapter 64 -Pseudo-vitamin D Deficiency;1287;Introduction;1287;Clinical Manifestations;1287;Biochemical Findings;1289;Genetic and Molecular Studies;1289;Treatment;1291;Evolution of Pddr Under Treatment from Childhood to Adulthood;1292;Conclusion;1294;References;1294 2.12.7;Chapter 65 -Hereditary 1,25-Dihydroxyvitamin-D-Resistant Rickets;1297;Introduction;1297;The Clinical Features of HVDRR;1298;Mechanism of 1,25(OH)2D Action;1301;Cellular Basis of HVDRR;1303;Molecular Basis for HVDRR;1309;Therapy of HVDRR;1319;Alopecia;1323;Concluding Remarks;1324;References;1325 2.12.8;Chapter 66 -Glucocorticoids and Vitamin D;1333;Mechanisms of GlucocorticoId Osteoporosis;1333;Steroid Receptors and Actions in Bone;1334;Glucocorticoids, Vitamin D, and Inflammation;1335;Effect of Glucocorticoids on Vitamin D Metabolism;1336;Vitamin D as Treatment for Gio;1338;Summary;1341;References;1342 2.12.9;Chapter 67 -Drug and Hormone Effects on Vitamin D Metabolism;1345;Introduction;1345;Hormone Effects on Vitamin D Metabolism;1345;Drug Effects on Vitamin D Metabolism;1357;Conclusion;1369;References;1369 2.12.10;Chapter 68 -Vitamin D and
Organ Transplantation;1391;Introduction;1391;Effects of Vitamin D on Immunity and Graft Rejection;1391;Vitamin D Deficiency Prior to Organ Transplant;1392;Vitamin D Deficiency Following Organ Transplant;1393;Treatment of Post-Transplant Bone Loss with Vitamin D and Analogs;1394;Conclusions;1396;References;1396 2.12.11;Chapter 69 -Vitamin D and Bone Mineral Metabolism in Hepatogastrointestinal Diseases;1399;Physiologic Considerations;1399;Gastrointestinal Diseases;1402;Pancreatic Diseases;1408;Hepatic Diseases;1409;Total Parenteral Nutrition;1414;References;1415 2.12.12;Chapter 70 -Vitamin D and Renal Disease;1425;Introduction;1425;Renal Maintenance of the Vitamin D Endocrine System;1427;Contribution of the low 25(OH)D and 1,25(OH)2D Levels and Abnormal VDR Actions to Mineral and Skeletal Abnormalities, Renal ...;1437;Safety and Efficacy of Vitamin D And 1,25(OH)2D Therapy to Improve Outcomes in Chronic Renal Failure;1446;Adequacy of Current Recommendations to Correct Vitamin D Deficiency;1447;Summary;1448;References;1449 2.12.13;Chapter 71 -Idiopathic Hypercalciuria and Nephrolithiasis;1459;Introduction;1459;Idiopathic Hypercalciuria;1459;Genetic Hypercalciuric Rats;1469;Current View of Human Genetic Hypercalciuria;1474;Therapeutics of Idiopathic Hypercalciuria and Effects on Calcium Metabolism;1474;Risk of Stone Formation Using Vitamin D Analogs;1475;Summary;1475;References;1476 2.12.14;Chapter 72 -Hypercalcemia Due to Vitamin D Toxicity;1481;Introduction;1481;Forms of Exogenous Vitamin D Toxicity;1481;Forms of Endogenous Vitamin D Toxicity;1485;Mechanisms of Vitamin D Toxicity;1489;Clinical Manifestations;1492;Diagnosis of Vitami
n D Toxicity;1493;Treatment of Vitamin D Toxicity;1494;Summary and Conclusions;1495;References;1495 2.12.15;Chapter 73 -Vitamin D: Cardiovascular Effects and Vascular Calcification;1503;Introduction;1503;Vitamin D Signaling In Cardiovascular Remodeling And Myocardial Function;1504;Vitamin D Actions In Atherosclerosis And Arteriosclerosis;1506;Vitamin D And Human Cardiovascular Disease: Compelling Epidemiology And Physiology, Emerging But Less Compelling Evidence O ...;1508;Vitamin D Intoxication And Cardiovascular Calcification: Pharmacological Considerations;1509;The Impact Of Calcium, Phosphate, And Vitamin D Excesses On Smooth Muscle Matrix Vesicle Physiology And Vascular Calcification;1511;The Fgf23/Klotho/Vitamin D Axis, Nephrocalcinosis, And Cardiovascular Calcification;1513;Vitamin D, Vascular Pth Receptor Signaling And Arteriosclerotic Calcium Accrual: Lessons Learned From Preclinical Models An ...;1514;Defining Cardiovascular Toxicity Thresholds For Vitamin D: Critical Clues From The Clinical Literature;1515;Vitamin D, The Calcium-Sensing Receptor (Casr), And Cardiovascular Disease;1516;Summary, Conclusions, And Future Directions;1518;REFERENCES;1519 2.13;Section IX -Analogs;1527 2.13.1;Chapter 74 -Alterations in 1,25-Dihydroxyvitamin D3 Structure that Produce Profound Changes in in Vivo Activity;1529;Introduction;1529;The Non-Calcemic Holy Grail of Vitamin D Analogs;1529;Analogs Directed to Specific Structures;1530;Summary;1533;References;1533 2.13.2;Chapter 75 -Mechanisms for the Selective Actions of Vitamin D Analogs;1537;Introduction;1537;Identification of Selective Vitamin D Analogs;1537;The IN VIVO Selectivity of Vitamin D Analogs is Determined by Multiple Protein Interactions;1540;Concluding Remarks;1551;Referen
ces;1552 2.13.3;Chapter 76 -Analogs of Calcitriol;1561;Introduction;1561;14-epi Analogs of 1,25(OH)2D3;1562;Decalin Analogs;1565;C- and D-ring Analogs;1565;CF-ring Analogs;1577;E-ring Analogs;1578;Acyclic Analogs;1579;Non-Secosteroidal Compounds;1581;Conclusion;1584;References;1585 2.13.4;Chapter 77 -Analogs for the Treatment of Osteoporosis*;1589;Introduction;1589;Alfacalcidol;1589;Eldecalcitol;1592;Clinical Comparison Between Alfacalcidol and Eldecalcitol;1593;Conclusion;1595;References;1595 2.13.5;Chapter 78 -Non-secosteroidal Ligands and Modulators;1597;Introduction;1597;Diarylmethane Ligands;1598;C/D-Ring Modified Ligands;1602;Bis- and Tris-Aromatic Triols;1603;Miscellaneous non-Secosteroids;1605;Perspectives;1607;References;1608 2.13.6;Chapter 79 -The Bile Acid Derivatives Lithocholic Acid Acetate and Lithocholic Acid Propionate are Functionally Selective V ...;1609;The Vitamin D Receptor is a Dual-Functional Receptor for Vitamin D and Bile Acids;1609;Bile Acids and Nuclear Receptors;1611;Development of Bile Acid Derivatives;1614;X-Ray Crystal Structures of VDR in Complex with LCA Derivatives;1617;Perspectives;1620;References;1621 2.13.7;Chapter 80 -CYP24A1 Regulation in Health and Disease;1625;Introduction;1625;CYP24A1: Properties, Function and Expression;1625;Regulation of CYP24A1 mRNA Expression and Stability;1629;Dysregulation of CYP24A1 and Role in the Pathogenesis of Human Disease;1634;CYP24A1 Inhibitors;1639;Conclusion and Future Directions;1643;References;1643 2.13.8;Chapter 81 -Calcitriol and Analogs in the Treatment of Chronic Kidney Disease;1655;Introduction;1655;Analogs of Vitamin D Used in CKD;1656;Ana
logs in Animal Models of Uremia;1656;CKD Stages 34;1659;ESRD;1660;Cardiovascular Disease in CKD and Different Forms of Vitamin D;1663;Conclusions;1663;References;1664 2.14;Section X -Cancer;1667 2.14.1;Chapter 82 -The Epidemiology of Vitamin D and Cancer Risk;1669;Introduction;1669;Overview of Epidemiologic Study Designs for the Study of Vitamin D and Cancer;1670;Studies of 25(OH)D, Predicted 25(OH)D, Vitamin D intake and Cancer Risk by Cancer Site;1672;Studies of Sun Exposure;1678;Randomized Controlled Trials;1680;Mortality/Survival;1681;Summary and Synthesis of The Epidemiology of Vitamin D and Cancer;1684;References;1686 2.14.2;Chapter 83 -Vitamin D: Cancer and Differentiation;1691;Introduction;1691;Vitamin D and Cancer;1691;Vitamin D Effects on Tumor Cells;1698;Combination Therapy;1705;Resistance and Vitamin D Metabolism;1706;Stimulation of Proliferation;1708;Conclusions;1709;References;1709 2.14.3;Chapter 84 -Vitamin D Effects on Differentiation and Cell Cycle;1725;Introduction;1725;Induction of Differentiation by 1,25(OH)2D3 and its Analogs;1725;Cell Cycle Consequences of Vitamin-D-Induced Differentiation;1731;Cell-Type Specificity of Inhibition of Cell Proliferation by Vitamin D and Analogs Without Evidence of Differentiation;1742;Conclusions;1743;References;1743 2.14.4;Chapter 85 -Vitamin D Actions in Mammary Gland and Breast Cancer;1757;Introduction;1757;Vitamin D Actions on Breast Cancer Cells in Vitro;1758;Determinants of Breast Cancer Sensitivity to Vitamin D;1762;Vitamin D Metabolites and Analogs: Preclinical and Clinical Trials;1764;Vitamin D and Prevention of Breast Cancer;1765;Summary and Outstanding Research Questions;1768;References;1768 2.14.5;Cha
pter 86 -Vitamin D and Prostate Cancer;1775;Introduction;1775;Prostate as a Target for Vitamin D;1777;Vitamin D and Inhibition of Prostate Cancer Growth;1778;Vitamin D Analogs and Prostate Cancer;1783;Mechanisms of the Anti-Cancer Actions of Calcitriol;1784;The Role of Calcitriol in Prostate Cancer Chemoprevention;1789;Calcitriol in Combination with other Agents;1791;Clinical Trials;1794;Summary and Conclusions;1796;References;1797 2.14.6;Chapter 87 -The Vitamin D System and Colorectal Cancer Prevention;1811;Colorectal Cancer Epidemiology and Pathogenesis;1811;Vitamin D and Colorectal Cancer Pathogenesis;1813;Colonic Synthesis of 1,25(OH)2D3;1815;Regulation of CYP27b1 and of CYP24a1 Expression by Nutrition;1819;References;1824 2.14.7;Chapter 88 -Hematological Malignancy;1831;Introduction;1831;Overview of Hematopoiesis;1831;Effects of Vitamin D Compounds on Normal Hematopoiesis;1834;Effects of Vitamin D Compounds in Leukemic Cells;1835;Vitamin D Analogs Activity Against Leukemic Cells;1841;Conclusions;1844;References;1844 2.14.8;Chapter 89 -Vitamin D and Skin Cancer;1851;Two Sources of Vitamin D: Diet or Sunlight;1851;Vitamin D and Indoor Tanning;1852;UV Exposure Contributes to NMSC and Melanoma Development;1853;Vitamin D and Visceral Cancer Risk and its Potential Role in Reducing Skin Cancer Risk;1854;Role of Vitamin D in Keratinocytes;1855;Role of Vitamin D in Squamous Cell Carcinomas (SCC);1855;Role of Vitamin D in Basal Cell Carcinomas (BCC);1856;Role of Vitamin D in Melanomas;1857;Photoprotection and Vitamin D Levels;1858;Conclusions;1859;References;1859 2.14.9;Chapter 90 -The Anti-tumor Effects of Vitamin D in Other Cancers;1863;Introduction;1863;Th
yroid Cancer;1863;Bone and Soft Tissue Sarcomas;1864;Melanoma;1864;Gastro-Esophageal Cancers;1864;Lung Cancers;1864;Hepatocellular Carcinoma (HCC);1865;Bladder Cancer;1865;Gliomas;1866;Head and Neck;1866;Renal Cell Carcinoma;1867;Pancreatic Cancer;1867;Conclusions;1868;References;1868 2.15;Section XI -Immunity, Inflammation, and Disease;1875 2.15.1;Chapter 91 -Vitamin D and Innate Immunity;1877;Introduction and Historical Background;1877;VDR Gene Polymorphisms and Infectious Diseases;1879;Molecular Events Underlying Innate Immune Regulation by Vitamin D;1880;Physiological and Pathophysiological Ramifications of 1,25(OH)2D3-Regulated Camp Expression;1883;Conclusions and Future Directions;1884;References;1884 2.15.2;Chapter 92 -Control of Adaptive Immunity by Vitamin D Receptor Agonists;1889;Introduction;1889;Vitamin D Receptor Agonists as Immunoregulatory Agents;1889;Dendritic Cells as Targets for Immunoregulation by VDR Agonists;1890;Induction of Tolerogenic Dendritic Cells by VDR Agonists;1892;Modulation of T and B Lymphocytes by VDR Agonists;1896;Vitamin D Deficiency in Autoimmune Diseases;1899;Mechanisms For The Immunomodulatory Effects Of Vdr Agonists In Autoimmune Diseases;1899;References;1903 2.15.3;Chapter 93 -The Role of Vitamin D in Innate Immunity: Antimicrobial Activity, Oxidative Stress and Barrier Function;1911;Innate Immunity;1911;Immune Activity of 1,25-Dihydroxyvitamin D;1913;Vitamin D Pathway and Tuberculosis;1916;History of Vitamin D, Sunshine, and Tuberculosis;1918;References;1918 2.15.4;Chapter 94 -Vitamin D and Diabetes;1925;Introduction;1925;Vitamin D and the Beta Cell;1925;Vitamin D and the Immune System in Type 1 Diabetes;1929;V
itamin D and Genetic Predisposition to Diabetes;1935;Clinical Perspectives;1936;References;1937 2.15.5;Chapter 95 -Vitamin D and Multiple Sclerosis;1943;The Vitamin DMultiple Sclerosis Hypothesis;1943;Original Evidence Underlying the Vitamin DMultiple Sclerosis Hypothesis;1943;Multiple Sclerosis Etiology and the Association with Vitamin D;1944;Genetic Evidence Linking Vitamin D and Multiple Sclerosis;1950;Experimental Autoimmune Encephalomyelitis, A Multiple Sclerosis Model;1953;Vitamin D and Prevention of EAE;1954;Mechanisms of EAE Prevention;1956;Vitamin D Amelioration of Established EAE;1961;Mechanisms of EAE Amelioration;1961;Multiple Sclerosis, Pregnancy, and Immune Tolerance;1963;Vitamin D, Estrogen, EAE, and Multiple Sclerosis;1963;Vitamin-D-Based Therapy of Multiple Sclerosis;1965;Conclusions and Future Research Directions;1966;References;1968 2.15.6;Chapter 96 -Vitamin D and Inflammatory Bowel Disease;1979;Introduction;1979;What is IBD?;1979;Who Gets IBD?;1980;The Hygiene Hypothesis;1981;The Vitamin D Hypothesis;1981;The Immune Response and IBD;1982;Vitamin D Regulates T Cell Responsiveness;1983;Experimental Models of IBD;1984;Current Treatments for IBD;1985;Vitamin D as a Treatment Option for IBD;1986;References;1986 2.15.7;Chapter 97 -Psoriasis and Other Skin Diseases;1991;Introduction/Historical Overview;1991;Pathogenesis of Psoriasis;1991;The Vitamin D System in Normal and Psoriatic Skin;1992;Physiological and Pharmacological Actions of Vitamin D Analogs in Normal and Psoriatic Skin;1994;Clinical use of Calcitriol in Psoriasis;1995;Vitamin D Analog Therapy in Other Skin Diseases;1997;Conclusion;2000;References;2000 2.16;Section XII -Ther
apeutic Applications and New Advances;2005 2.16.1;Chapter 98 -The Role of Vitamin D in Type 2 Diabetes and Hypertension;2007;Epidemiology and Burden of Type 2 Diabetes and Hypertension;2007;Biologic Plausibility of an Association Between Vitamin D and Type 2 Diabetes and Hypertension;2008;Evidence from Human Studies for a Link Between Vitamin D and Type 2 Diabetes;2010;Evidence from Human Studies for a Link Between Vitamin D and Hypertension;2021;Summary of Evidence from Human Studies on Type 2 Diabetes and Hypertension and Limitations in the Study of Vitamin D;2023;Optimal Intake of Vitamin D in Relation to Type 2 Diabetes and Hypertension;2024;Conclusions;2024;References;2024 2.16.2;Chapter 99 -Vitamin D Receptor Agonists in the Treatment of Benign Prostatic Hyperplasia;2031;Benign Prostatic Hyperplasia: an Introduction;2031;Pathogenesis of BPH;2031;Medical Treatment for BPH;2033;Vitamin D Receptor Agonists Control Prostate Cell Growth;2033;Vitamin D Receptor Agonists and BPH-Related Luts;2034;Vitamin D Receptor Agonists Inhibit Intraprostatic Inflammation;2035;Vitamin D Receptor Agonists Modulate Prostatic Urethra Dysfunction;2036;Concluding Remarks;2037;References;2038 2.16.3;Chapter 100 -Sunlight Protection by Vitamin D Compounds;2043;Introduction;2043;UV-Induced DNA Damage and Repair;2043;UV-Induced Immune Suppression;2044;Photocarcinogenesis;2044;Local Production of Vitamin D Metabolites in Skin;2045;Vitamin D Compounds and Photoprotection;2045;Mechanisms of Photoprotection;2047;Perspectives on Future Use of Vitamin D Compounds for Sun Protection;2049;References;2050 2.16.4;Chapter 101 -The Role of Vitamin D in Osteoarthritis and Rheumatic Disease;2055;Osteoarthritis;2055;Hyaline Cartilage in OA;2055;Bo
ne Health and OA;2056;The Synovium;2057;Vitamin D Receptor (VDR) Genotype and OA Progression;2058;Vitamin D Status and OA Progression;2058;Rheumatoid Arthritis;2060;Systemic Lupus Erythematosus (SLE);2062;Psoriatic Arthritis (PsA);2066;Conclusions;2066;References;2066 2.16.5;Chapter 102 -Vitamin D and Cardiovascular Disease;2073;Introduction;2073;Components of Direct Cardiovascular Effects;2074;Components of Indirect Cardiovascular Effects;2079;Cardio- and Cerebrovascular Mortality as Endpoint in Observational and Interventional Studies;2084;Clinical Cardiovascular Outcomes in Observational and Randomized Interventional Studies;2087;Situation in Patients With Chronic Kidney Disease or on Hemodialysis;2089;Summary and Conclusions;2090;References;2091 2.16.6;Chapter 103 -Vitamin D, Childhood Wheezing, Asthma, and Chronic Obstructive Pulmonary Disease;2099;Introduction;2099;Common Respiratory Disorders;2100;Vitamin D and Respiratory Infection;2102;Vitamin D and Asthma;2106;Vitamin D and COPD;2110;Potential Mechanisms;2111;Future Research on Vitamin D and Respiratory/Allergic Disorders;2114;Summary;2115;References;2116 2.16.7;Chapter 104 -Vitamin D and Skeletal Muscle Function;2123;Introduction;2123;Myopathy;2124;Physical Performance;2125;Falls;2128;Muscle Morphology;2129;Molecular Mechanisms of Action;2130;VDR Knockout Mouse Model;2134;VDR Polymorphisms;2135;PTH;2135;Conclusion;2135;References;2136 2.16.8;Chapter 105 -The VITamin D and OmegA-3 TriaL (VITAL): Rationale and Design of a Large-Scale Randomized Controlled Trial;2143;Introduction;2143;Biology of Vitamin D and Proposed Mechanisms for Lowering Cancer and CVD Risk;2143 2.
16.8.3;Current Evidence on Vitamin D and Risk of Cancer and CVD;2144;Rationale for VITAL;2146;Rationale for the Selected Vitamin D Dose in VITAL;2146;Core Aspects of Trial Design;2147;Trial Eligibility;2148;Recruitment, Enrollment, Run-in and Randomization;2148;Characteristics of Participants in VITAL;2149;Detailed Assessment of Dietary and Supplement Intake in VITAL;2149;Blood Collections in VITAL;2150;Follow-up and Enpoint Determination Procedures;2150;Monitoring of Compliance;2151;Trial Monitoring and Safety;2151;Statistical Power;2152;Vital Value: Ancillary Studies and Establishment of a Clinical and Translational Science Center Sub-Cohort;2152;Key Points;2153;References;2153 2.17;Index;2157 2.18;Color Plates;2183

EAN: 9780123819796
Untertitel: Two-Volume Set. 200:Adobe eBook. Sprache: Englisch.
Verlag: Elsevier Science
Erscheinungsdatum: Mai 2011
Seitenanzahl: 2144 Seiten
Format: epub eBook
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