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Tietz Textbook of Clinical Chemistry and Molecular Diagnostics - E-Book

Tietz Textbook of Clinical Chemistry and Molecular Diagnostics - E-Book

Nader Rifai

(2017)

Additional Information

Book Details

Abstract

The Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 6th Edition provides the most current and authoritative guidance on selecting, performing, and evaluating the results of new and established laboratory tests. This classic clinical chemistry reference offers encyclopedic coverage detailing everything you need to know, including: analytical criteria for the medical usefulness of laboratory tests, variables that affect tests and results, laboratory medicine, applications of statistical methods, and most importantly clinical utility and interpretation of laboratory tests. It is THE definitive reference in clinical chemistry and molecular diagnostics, now fully searchable and with quarterly content updates, podcasts, clinical cases, animations, and extended content online through Expert Consult.

  • Analytical criteria focus on the medical usefulness of laboratory procedures. 
  • Reference ranges show new approaches for establishing these ranges — and provide the latest information on this topic.
  • Lab management and costs gives students and chemists the practical information they need to assess costs, allowing them to do their job more efficiently and effectively.
  • Statistical methods coverage provides you with information critical to the practice of clinical chemistry. 
  • Internationally recognized chapter authors are considered among the best in their field.
  • Two-color design highlights important features, illustrations, and content to help you find information easier and faster.
  • NEW! Internationally recognized chapter authors are considered among the best in their field.
  • NEW! Expert Consult features fully searchable text, quarterly content updates, clinical case studies, animations, podcasts, atlases, biochemical calculations, multiple-choice questions, links to Medline, an image collection, and audio interviews. You will now enjoy an online version making utility of this book even greater.
  • UPDATED! Expanded Molecular Diagnostics section with 12 chapters that focus on emerging issues and techniques in the rapidly evolving and important field of molecular diagnostics and genetics ensures this text is on the cutting edge and of the most value.
  • NEW! Comprehensive list of Reference Intervals for children and adults with graphic displays developed using contemporary instrumentation.
  • NEW! Standard and international units of measure make this text appropriate for any user — anywhere in the world.
  • NEW! 22 new chapters that focus on applications of mass spectrometry, hematology, transfusion medicine, microbiology, biobanking, biomarker utility in the pharmaceutical industry and more!
  • NEW! Expert senior editors, Nader Rifai, Carl Wittwer and Rita Horvath, bring fresh perspectives and help ensure the most current information is presented.
  • UPDATED! Thoroughly revised and peer-reviewed chapters provide you with the most current information possible.

Table of Contents

Section Title Page Action Price
Front Cover cover
Inside Front Cover ifc1
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics i
Copyright Page ii
Dedication iii
Associate Editors iv
Reviewers v
Contributors vii
Contributors to Expert Consult xvi
Foreword xvii
Preface xviii
Table Of Contents xix
I Basics of Laboratory Medicine 1
1 Clinical Chemistry and Molecular Diagnostics 2
Abstract 2
Background 2
Content 2
Introduction 2
Looking Back 3
Training in Clinical Chemistry 3
Expanding Boundaries Defined by Technology 3
How Is Clinical Chemistry Practiced? 5
Guiding Principles of Practicing the Profession 6
Confidentiality of Genetic Information 6
Confidentiality of Patient Medical Information 6
Allocation of Resources 6
Codes of Conduct 6
Publishing Issues 7
Conflicts of Interest 8
What Is in This Textbook? 8
References 8
2 Statistical Methodologies in Laboratory Medicine 10
Abstract 10
Background 10
Content 10
Assay Selection Overview 10
Medical Need and Quality Goals 10
Analytical Performance Criteria 11
Other Criteria 11
Basic Statistics 13
Frequency Distribution 13
Population and Sample 13
Probability and Probability Distributions 13
Parameters: Descriptive Measures of a Population 14
Statistics: Descriptive Measures of the Sample 14
Random Sampling 14
The Gaussian Probability Distribution 14
Student t Probability Distribution 15
Nonparametric Statistics 15
Categorical Variables 16
Technical Validity of Analytical Assays 16
Calibration 16
Trueness and Accuracy 17
Precision 18
Example 18
Precision Profile 18
Linearity 19
Analytical Measurement Range and Limits of Quantification 20
Analytical Sensitivity 20
Analytical Specificity and Interference 20
Qualitative Methods 20
Diagnostic Accuracy Measures 20
Agreement Between Qualitative Tests 21
Example 21
Assay Comparison 22
Basic Error Model 22
Measured Value, Target Value, Modified Target Value, and True Value 22
Calibration Bias and Random Bias 23
Assay Comparison Data Model 24
Comparison of a Routine Assay With a Reference Measurement Procedure 24
Comparison of Two Routine Assays 24
Preliminary Practical Work in Relation to a Method Comparison Study 24
Planning a Method Comparison Study 24
Distribution of Differences Plot (DoD Plot) 25
Nonparametric Approach 25
Parametric Approach 26
Relative Distribution of Differences Plot (Rel DoD Plot) 27
Verification of Distribution of Differences in Relation to Specified Limits 29
Difference (Bland-Altman) Plot 29
A Caution Against Incorrect Interpretation of Paired t-Tests in Method Comparison Studies 30
Regression Analysis 31
Error Models in Regression Analysis 31
Deming Regression Analysis and Ordinary Least-Squares Regression Analysis (Constant Standard Deviations) 32
Computation Procedures for Ordinary Least-Squares Regression and Deming Regression 34
Evaluation of the Random Error Around an Estimated Regression Line 34
Interpreting SDy·x (SD21) With Random Errors in Both x1 and x2 34
Assessment of Outliers 34
The Correlation Coefficient 35
Regression Analysis in Cases of Proportional Random Error 36
Testing for Linearity 36
Nonparametric Regression Analysis (Passing-Bablok Procedure) 37
Interpretation of Systematic Differences Between Methods Obtained on the Basis of Regression Analysis 37
Example of Application of Regression Analysis (Weighted Deming Analysis) 37
Discussion of Application of Regression Analysis 38
Monitoring Serial Results 39
Traceability and Measurement Uncertainty 40
Traceability 40
The Uncertainty Concept 41
The Standard Uncertainty (ust) 41
Example of Direct Assessment of Uncertainty on the Basis of Measurements of a Commutable Certified Reference Material 41
Example of Direct Assessment of Uncertainty on the Basis of a Method Comparison Study With a Reference Measurement Procedure Using Patient Samples 42
Indirect Evaluation of Uncertainty by Quantification of Individual Error Source Components 43
Example. 44
Uncertainty in Relation to Traditional Systematic and Random Error Classifications 44
Diagnostic Accuracy of Laboratory Tests 45
Diagnostic Accuracy of a Test in Isolation 45
Diagnostic Accuracy, Sensitivity, and Specificity 45
Confidence Intervals of Diagnostic Accuracy, Sensitivity, and Specificity 45
Clinical Example: Accuracy of d-Dimer Test in Diagnosis of Deep Venous Thrombosis 46
Receiver Operating Characteristic Curves 46
Selection of Cutoff Value in Case of Quantitative Index Tests 47
Posterior Probabilities (Predictive Values) 48
Likelihood Ratios and Odds Ratios 48
Comparison of Diagnostic Accuracy of Two Tests in Isolation 48
Shortcomings of Diagnostic Accuracy Studies of Tests in Isolation 49
Diagnostic Accuracy of a Test in the Clinical Context 50
Clinical Example: Added Value of d-Dimer Testing in the Diagnosis of Suspected Deep Venous Thrombosis 50
Diagnostic Accuracy of Combinations of Diagnostic Tests: Receiver Operating Characteristic Area 53
Reclassification Measures 54
Predictiveness Curve 55
Decision Curve Analysis 55
Test Evaluation Beyond Diagnostic Accuracy 57
How Does Testing Yield Health(care) Benefits? 57
The Working Pathway 57
Comparative Tests: Treatment Studies to Quantify the Impact of Tests 58
Linked-Evidence Approaches to Quantify the Impact of Tests 59
Selected References 59
References 60.e1
3 Quality Management in the Medical Laboratory 61
Abstract 61
Background 61
Content 61
Introduction 61.e1
Purpose and Scope of a Medical Laboratory 61.e1
Defining Quality in the Medical Laboratory 61.e1
Evolution of the Approach to Quality Management 61.e1
Quality Management Systems 61.e2
Standards and Guidelines for the Medical Laboratory 61.e2
ISO and the Development of ISO 15189 61.e2
CLSI-QMS Guidelines 61.e2
Quality Management Systems and the Process Model 61.e3
ISO 15189 and CLSI-QSE Compared 61.e3
The Key Components of Quality Management Systems for Medical Laboratories 61.e4
Management Responsibility 61.e4
Quality Management System 61.e5
Resource Management 61.e6
Examination Processes 61.e6
Evaluation and Continual Improvement 61.e6
Accreditation and Regulation 61.e6
Accreditation or Certification? 61.e6
Accreditation and Regulation of Medical Laboratories 61.e6
An International Model 61.e6
Alternative Models 61.e8
Approaches to Quality Management 61.e8
Principles of Quality Management 61.e8
Customer Focus 61.e9
Leadership 61.e9
Involvement of People 61.e9
Process Approach 61.e10
System Approach to Management 61.e11
Continual Improvement 61.e12
Factual Approach to Decision Making 61.e12
Measures and Quality Indicators. 61.e12
Understanding Variation. 61.e14
Cost of Quality (Including Waste). 61.e14
Nonconforming Events and Risk Management. 61.e15
Mutually Beneficial Supplier Relationships. 61.e15
Summary of Useful Quality Management Tools and Resources 61.e15
Organizational Quality and Business Excellence Frameworks 61.e17
References 61.e18
4 Specimen Collection and Processing 62
Abstract 62
Background 62
Content 62
Introduction 62
Patient Identification 62
Types of Specimens 62
Blood 63
Venipuncture 63
Preliminary Steps. 63
Location. 64
Preparation of the Site. 65
Timing. 65
Venous Occlusion. 65
Order of Draw for Multiple Blood Specimens. 65
Collection With Evacuated Blood Tubes. 65
Blood Collection With a Syringe. 66
Completion of Collection. 67
Venipuncture in Children. 68
Skin Puncture 68
Arterial Puncture 69
Anticoagulants and Preservatives for Blood 70
Heparin. 70
Ethylenediaminetetraacetic Acid. 70
Sodium Fluoride. 71
Citrate. 71
Acid Citrate Dextrose. 71
Oxalates. 71
Iodoacetate. 71
Influence of Site of Collection on Blood Composition 71
Collection of Blood From Intravenous or Arterial Lines 72
Hemolysis 72
Urine 72
Timed Urine Specimens 73
Collection of Urine From Children 74
Urine Preservatives 74
Feces 74
Other Body Fluids 75
Bronchoalveolar Lavage 75
Chorionic Villus Sampling 75
Buccal Cells 75
Solid Tissue 76
Hair and Nails 76
Handling of Specimens for Analysis 76
Maintenance of Specimen Identification 76
Preservation of Specimens 77
Add-on Requests 77
Separation and Storage of Specimens 78
Transport of Specimens 78
Conclusion 79
Multiple Choice Questions 80.e1
Answers 80.e1
References 80
5 Preanalytical Variation and Preexamination Processes 81
Abstract 81
Background 81
Content 81
Introduction 81
Historical Perspective 81
The Preanalytical Phase Today 82
Influencing and Interference Factors 82
II Analytical Techniques and Applications 198
12 Principles of Basic Techniques and Laboratory Safety 199
Abstract 199
Background 199
Content 199
Concept of Solute and Solvent 199.e1
Expressing Concentrations of Solutions 199.e1
Units of Measurement 199.e1
International System of Units 199.e1
Standardized Reporting of Test Results 199.e2
Laboratory Logical Observation Identifiers, Names, and Codes System 199.e2
Nomenclature, Properties, and Units 199.e2
Applications 199.e3
Chemicals 199.e3
Reagent Grade Water 199.e3
Preparation of Reagent Grade Water 199.e3
Distillation. 199.e3
Ion Exchange. 199.e3
Reverse Osmosis. 199.e3
Ultraviolet Oxidation. 199.e4
Quality, Use, and Storage of Purified Water 199.e4
Testing for Water Purity 199.e4
Reagent-Grade or Analytical Reagent-Grade Chemicals 199.e4
Ultrapure Reagents 199.e4
Reference Materials 199.e4
Primary Reference Materials 199.e4
Secondary Reference Materials 199.e4
Standard Reference Materials 199.e5
Certified Reference Materials 199.e5
Basic Techniques and Procedures 199.e6
Volumetric Sampling and Dispensing 199.e6
Pipettes 199.e6
Transfer and Measuring Pipettes. 199.e6
Transfer Pipettes. 199.e7
Measuring Pipettes. 199.e7
Pipetting Technique. 199.e7
Micropipettes. 199.e7
Semiautomatic and Automatic Pipettes and Dispensers. 199.e7
Volumetric Flasks 199.e8
Centrifugation 199.e10
Types of Centrifuges 199.e10
Principles of Centrifugation 199.e10
Operation of the Centrifuge 199.e10
Operating Practice 199.e10
Measurement of Radioactivity 199.e11
Basic Concepts 199.e11
Radioactive Decay. 199.e11
Alpha Decay. 199.e11
Beta Decay. 199.e11
Electron Capture. 199.e12
Gamma Radiation and Internal Conversion. 199.e12
Activity and Half-Life. 199.e12
Units of Radioactivity 199.e12
Specific Activity 199.e12
Detection and Measurement of Radioactivity 199.e12
Autoradiography. 199.e12
Gas-Filled Detectors. 199.e12
Scintillation Counting. 199.e12
Crystal Scintillation Detector. 199.e12
Liquid Scintillation Detector. 199.e13
Gravimetry 199.e13
Principles of Weighing 199.e13
Types of Balances 199.e13
Double-Pan Balance. 199.e13
Single-Pan Balance. 199.e13
Electronic Balance. 199.e13
Analytical Weights 199.e13
Thermometry 199.e14
Controlling Hydrogen Ion Concentration 199.e14
Procedures for Processing Solutions 199.e14
Dilution 199.e14
Evaporation 199.e15
Lyophilization 199.e15
Filtration 199.e15
Safety 199.e15
Safety Program 199.e15
Safety Equipment 199.e16
Safety Inspections 199.e16
Plans for the Clinical Laboratory 199.e16
Chemical Hygiene Plan 199.e16
Exposure Control Plan 199.e17
Tuberculosis Control Plan 199.e17
Pandemic Plan 199.e17
Ergonomics Program 199.e17
Hazards in the Laboratory 199.e18
Identification of Hazards 199.e18
Biological Hazards 199.e18
Chemical Hazards 199.e20
Hazards From Volatiles. 199.e20
Hazards From Compressed Gases. 199.e21
Electrical Hazards 199.e21
Fire Hazards 199.e21
References 199.e22
13 Optical Techniques 200
Abstract 200
Background 200
Content 200
Nature of Light 200
Spectrophotometry 201
Basic Concepts 201
Beer’s Law: Relationship Among Transmittance, Absorbance, and Concentration 202
Application of Beer’s Law 202
Instrumentation 203
Components 203
Light Sources. 203
Incandescent, Arc, and Cathode Lamps. 203
Laser Sources. 204
Spectral Isolation. 204
Filters. 204
Prisms and Gratings. 205
Selection of a Wavelength Isolation Device. 205
Cuvets. 205
Photodetectors. 206
Photomultiplier Tubes. 206
Photodiodes. 206
Readout Devices. 206
Performance Parameters 207
Wavelength Calibration. 207
Spectral Bandwidth. 207
Stray Light. 208
Photometric Accuracy. 208
Multiple-Wavelength Readings. 208
Reflectance Photometry 208
Flame Emission and Inductively Coupled Plasma Spectrophotometry 208
Atomic Absorption Spectrophotometry 209
Basic Concepts 209
Instrumentation 209
Interferences in Atomic Absorption Spectrophotometry 210
Spectral Interferences 210
Nonspectral Interferences 210
Fluorometry 210
Basic Concepts 210
Time Relationships of Fluorescence Emission 211
Relationship of Concentration and Fluorescence Intensity 211
Fluorescence Polarization 212
Instrumentation 212
Components 213
Excitation Source. 213
Xenon Lamp. 213
Lasers. 213
Light-Emitting Diode. 213
Excitation and Emission Monochromators. 213
Cuvet. 213
Photodetectors. 214
Visual Observation. 214
Photomultiplier Tube. 214
Charge-Coupled Detector. 215
Performance Verification 215
Types of Fluorometers and Spectrofluorometers 215
Ratio-Referencing Spectrofluorometer. 215
Time-Resolved Fluorometer. 215
Flow Cytometer. 216
Hematofluorometer. 217
Limitations of Fluorescence Measurements 217
Inner Filter Effects 217
Concentration Quenching 217
Light Scattering 217
Cuvet Material and Solvent Effects 218
Sample Matrix Effects 218
Temperature Effects 218
Photodecomposition 218
Phosphorescence 218
Chemiluminescence, Bioluminescence, and Electrochemiluminescence 219
III Analytes 372
28 Amino Acids, Peptides, and Proteins 373
Abstract 373
Background 373
Content 373
Introduction 373
Amino Acids 374
Basic Biochemistry 374
Amino Acid Supply and Transport 376
Amino Acid Metabolism 377
Amino Acid Concentrations 379
Analysis of Amino Acids 379
Peptides 380
Peptide Bond 380
Peptide Heterogeneity and Analysis 380
Clinically Relevant Peptide Systems 381
Pro-Opiomelanocortin System 381
Natriuretic Peptides 381
Hepcidin 381
Angiotensins 381
Endothelins 382
Vasopressin 382
Glutathione 382
Proteins 382
Physical Properties of Proteins 383
Protein Formation 384
Folding 384
Targeting 384
Posttranslational Modifications 385
Fatty Acylation 385
Phosphorylation 385
Prenylation 385
Glycosylphosphatidylinositol Anchor 385
γ-Carboxylation 385
Glycosylation 385
Sulfation 386
Hydroxylation 386
Nitrosylation 386
Protein Catabolism 386
Protease Families 386
Serine Proteases. 386
Cysteinyl Proteases. 386
Aspartyl Proteases. 386
Metalloproteases. 387
The Ubiquitin-Proteasome System 387
Proteins in Human Serum and Plasma 388
Abundant Components of the Circulating Proteome 389
Prealbumin (Transthyretin) 389
Albumin 389
α1-Antitrypsin 389
Ceruloplasmin 390
Haptoglobin 390
Transferrin 390
β2-Microglobulin 390
C-Reactive Protein 391
Complement 391
Immunoglobulins 392
Individual Immunoglobulins and Light Chains 393
Immunoglobulin G. 393
Immunoglobulin M. 393
Immunoglobulin A. 393
Immunoglobulin D. 393
Immunoglobulin E. 393
Free Immunoglobulin Light Chains. 394
Clinical Utility of Immunoglobulin Measurement. 394
Immunoglobulin Deficiency. 394
Polyclonal Hyperimmunoglobulinemia. 394
Monoclonal Immunoglobulins (Paraproteins). 395
Acute Phase Response 395
Methods for Analyzing Proteins 395
Determination of Total Protein 395
Kjeldahl Method. 396
Biuret Method. 396
Direct Optical Methods. 396
Dye-Binding Methods. 396
Lowry (Folin-Ciocalteu) Method. 397
Refractometry. 397
Light-Scattering Methods. 397
Variables Affecting Measured Protein Concentrations. 397
Immunochemical Techniques for Specific Proteins 397
Electrophoresis 397
Serum Protein Electrophoresis. 397
Immunofixation Electrophoresis. 399
Capillary Electrophoresis. 399
Western Blotting. 399
Mass Spectrometry. 400
Proteins in Other Body Fluids 400
Saliva 400
Cerebrospinal Fluid 400
Total Protein in Cerebrospinal Fluid. 401
Permeability of the Blood–Brain Barrier. 401
Intrathecal Protein Synthesis. 401
Peritoneal and Pleural Fluids 402
Fecal Material 402
Selected References 403
References 403.e1
29 Serum Enzymes 404
Abstract 404
Background 404
Content 404
Introduction 404
Diagnostic Enzymology 404
Factors Affecting Enzyme Concentrations in Blood 404
Leakage of Enzymes From Cells 404
Efflux of Enzymes From Damaged Cells 405
Altered Enzyme Production 406
Clearance of Enzymes 406
Selection of Enzyme Tests 406
Muscle Enzymes 408
Creatine Kinase 408
Clinical Significance 409
Methods for Determination of Creatine Kinase Activity 410
Reference Intervals 411
Methods for Separation and Quantification of Creatine Kinase Isoenzymes 411
Aldolase 411
Clinical Significance 411
Methods for Measurement of Aldolase Activity 411
Reference Intervals 412
Liver Enzymes 412
Aminotransferases 412
Clinical Significance 412
Methods for Measurement of Transaminase Activity 414
Reference Intervals 414
Glutamate Dehydrogenase 415
Clinical Significance 415
Methods for Determination of Glutamate Dehydrogenase Activity 415
Reference Intervals 415
Alkaline Phosphatase 415
Clinical Significance 416
Methods for Determination of Alkaline Phosphatase Activity 417
Reference Intervals 417
Methods for Separation and Quantification of Alkaline Phosphatase Isoenzymes 417
5′-Nucleotidase 419
Clinical Significance 419
Methods for Determination of 5′-Nucleotidase Activity 419
Reference Interval 419
γ-Glutamyltransferase 419
Clinical Significance 420
Methods for Determination of γ-Glutamyltransferase Activity 420
Reference Intervals 421
Glutathione S-Transferase 421
Clinical Significance 421
Methods for Determination of Glutathione S-Transferase 421
Reference Interval 421
Pancreatic Enzymes 421
Lipase 421
Clinical Significance 422
Methods for Measuring Lipase Activity 422
Reference Intervals 424
Amylase 424
Clinical Significance 424
Methods for Determination of α-Amylase Activity 425
Reference Interval 426
Analytical Methods and Reference Intervals for Amylase Isoenzymes 426
Trypsin 426
Clinical Significance 427
Trypsin-1 (Cationic Trypsin). 427
Trypsin-2 (Anionic Trypsin). 427
Methods for Determination of Trypsin 427
Bone Enzymes 427
Alkaline Phosphatase (Bone Isoform) 427
Clinical Significance in Bone Disease 428
Methods for Determination of Bone Alkaline Phosphatase 428
Reference Intervals 428
Acid Phosphatase (Tartrate-Resistant 5b Isoform) 428
Clinical Significance 429
Methods for Determination of Tartrate-Resistant Acid Phosphatase 429
Reference Intervals 429
Miscellaneous Enzymes 429
Lactate Dehydrogenase 429
Clinical Significance 430
Methods for Determination of Lactate Dehydrogenase Activity 430
Reference Intervals 431
Methods for Separation and Quantification of Lactate Dehydrogenase Isoenzymes 431
Cholinesterase 431
Clinical Significance 431
Methods for Determination of Serum Cholinesterase Activity 432
Reference Intervals 432
Lipoprotein-Associated Phospholipase A2 433
Clinical Significance 433
Methods for Determination of Lipoprotein-Associated Phospholipase A2 433
Selected References 433
References 434.e1
30 Enzymes of the Red Blood Cell 435
Abstract 435
Background 435
Content 435
Introduction 435.e1
Embden-Meyerhof Pathway 435.e1
Hexokinase 435.e1
Glucose-6-Phosphate Isomerase 435.e5
Phosphofructokinase 435.e5
Aldolase 435.e5
Triosephosphate Isomerase 435.e6
Phosphoglycerate Kinase 435.e6
Pyruvate Kinase 435.e6
Lactate Dehydrogenase 435.e7
Hexose Monophosphate Pathway 435.e7
Glucose-6-Phosphate Dehydrogenase 435.e7
6-Phosphogluconate Dehydrogenase (Decarboxylating) (EC 1.1.1.44) 435.e8
Transketolase 435.e8
Rapoport-Luebering Shunt 435.e8
Glutathione Pathway 435.e9
Glutamate Cysteine Ligase 435.e9
Glutathione Synthetase 435.e9
Glutathione Reductase 435.e9
Glutathione Peroxidase 435.e10
Purine–Pyrimidine Metabolism 435.e10
Pyrimidine-5′-Nucleotidase-1 435.e10
Adenylate Kinase 435.e10
Adenosine Deaminase 435.e11
Methemoglobin Reduction 435.e11
Cytochrome B5 Reductase 435.e11
Detection of Hereditary Red Blood Cell Enzyme Deficiencies 435.e11
Methods 435.e12
Method Summary for Determination of Glucose-6-Phosphate Dehydrogenase 435.e12
IV Molecular Diagnostics 926
44 Principles of Molecular Biology 927
Abstract 927
Background 927
Content 927
Historical Developments in Genetics and Molecular Biology 927
Molecular Biology Essentials 928
Nucleic Acid Structure and Function 929
Structure of Deoxyribonucleic Acid 929
Types of Deoxyribonucleic Acid 931
Molecular Composition of Ribonucleic Acid 931
Structure of Ribonucleic Acid 931
Ribonucleic Acids Associated With Protein Production 931
Human Chromosome 931
Central Dogma of Molecular Biology 932
Deoxyribonucleic Acid Replication 932
Deoxyribonucleic Acid Repair 933
Mechanisms 933
Deoxyribonucleic Acid Modification Enzymes 934
Gene Structure 934
Ribonucleic Acid Transcription and Splicing 934
Translation 935
Epigenetics 938
Deoxyribonucleic Acid Methylation 938
Chromatin Conformation Regulation 938
Noncoding Ribonucleic Acids 939
Understanding Our Genome 939
Selected References 940
References 941.e1
45 Genomes and Variants 942
Abstract 942
Background 942
Content 942
Introduction 942
Human Genome 942
Variations in Specific Populations 943
Nonhuman Genomes 944
Primates 944
Rodents 945
Fungi 946
Bacteria 946
Viruses 947
DNA That Codes for RNA but Not Protein 948
Variation in the Human Genome 948
Single Nucleotide Variants 949
Copy Number Variation (Gains and Losses) 949
Fusions 950
Short Tandem Repeats 950
Transposable Elements and Their Genetic Fossils 950
Human Epigenetic Alterations 950
ENCODE Project 951
Nomenclature 952
Small Variants 952
Large Structural Variants 953
Naming Genes 954
Databases 954
Informatics 955
Selected References 957
References 957.e1
46 Nucleic Acid Isolation 958
Abstract 958
Background 958
Content 958
History of Nucleic Acid Preparation Tools 958.e1
Steps Involved in NA Preparation 958.e1
Lysis 958.e1
Protein Removal 958.e2
Separation Techniques 958.e2
Concentration 958.e4
Storage 958.e5
Impact of Sample Matrix on Nucleic Acid Preparation 958.e5
Human Sample Complexity 958.e5
Blood 958.e5
Paraffin Embedded Tissue With Fixatives 958.e5
DNA Versus RNA 958.e6
Processing Throughput 958.e6
Batch Size 958.e6
Speed 958.e6
Specific Applications 958.e6
Inherited Disorders and Pharmacogenetics 958.e6
Oncology 958.e7
Pathogens 958.e7
Low Concentration 958.e7
Flexibility for Different Matrices 958.e7
RNA 958.e7
Integrated Nucleic Acid Preparation 958.e7
Microfluidics 958.e7
Nucleic Acid Quality and Quantity 958.e7
Purity 958.e7
Inhibitors 958.e7
Yield 958.e7
Methods to Measure Nucleic Acid Quality and Quantity 958.e8
Ultraviolet Absorbance 958.e8
Fluorescent Staining of Nucleic Acids 958.e8
Summary of Methods 958.e8
Conclusion 958.e8
References 958.e10
47 Nucleic Acid Techniques 959
Abstract 959
Background 959
Content 959
Introduction 959
Nucleic Acid Preparation 960
Nucleic Acid Fragmentation 962
Bisulfite Treatment for Methylation Analysis 962
Amplification Techniques 962
Polymerase Chain Reaction—Target Amplification 963
Details of the PCR Process 963
Polymerase Chain Reaction Kinetics 964
Polymerase Chain Reaction Optimization 966
Primer Design 966
Polymerase Chain Reaction Contamination, Inhibition, and Controls 967
Multiplex Polymerase Chain Reaction and Nested Polymerase Chain Reaction 967
Asymmetric Polymerase Chain Reaction 967
Selective Amplification of Sequence Variants by Polymerase Chain Reaction 968
Detection Limits of Polymerase Chain Reaction 968
Digital Polymerase Chain Reaction 968
Additional Target Amplification Methods 969
Transcription-Based Amplification Methods 969
Loop-Mediated Amplification Methods 970
Strand Displacement Amplification 970
Variants of Polymerase Chain Reaction That Do Not Require Heat Denaturation 970
Whole-Genome and Whole-Transcriptome Amplification 970
Signal and Probe Amplification Methods 970
Branched-Chain DNA: Signal Amplification 970
Serial Invasive Amplification: Signal Amplification 970
Rolling Circle Amplification: Probe Amplification 971
Endpoint Quantification in Amplification Assays 971
Detection Techniques 971
Nucleic Acid Probes 971
Indirect Detection of Hybridized Probes 971
Fluorescent Labels 971
Electrochemical Detection 972
Discrimination Techniques 972
Electrophoresis 972
Polymerase Chain Reaction Product Length 973
Restriction Fragment Length Polymorphism 973
Polymerase Chain Reaction/Restriction Fragment Length Polymorphisms 973
Conformation-Sensitive Scanning Techniques 974
Dideoxy-Termination Sequencing (Sanger Sequencing) 974
Single Nucleotide Extension 975
Oligonucleotide Ligation 975
Multiplex Ligation-Dependent Probe Amplification 975
Alternatives to Electrophoresis 976
Pyrosequencing 976
Mass Spectrometry 976
High-Performance Liquid Chromatography 978
Hybridization Assays 978
Thermodynamics 978
Kinetics 979
Probes 979
Cloned Probes. 979
Polymerase Chain Reaction–Generated Probes. 979
Oligonucleotide Probes. 979
Estimating Melting Temperature of Oligonucleotide Probes. 980
Purity of Labeled Oligonucleotide Probes. 980
Examples of Hybridization Assays 980
Solid Phase Hybridization 980
Dot Blot and Line Probe Assays. 980
Medium-Density Arrays. 980
Microarrays. 980
In Situ Hybridization. 982
Single-Copy Visualization. 983
Solution Phase Hybridization: Real-Time Polymerase Chain Reaction and Melting Analysis 983
Dyes and Probes. 983
Detection and Quantification in Real-Time PCR 985
Detection. 985
Quantification. 985
Accuracy and Precision. 986
Melting Analysis 987
Homogeneous Single Nucleotide Variant Typing 987
High-Resolution Melting Analysis 989
Massively Parallel Sequencing 990
Sequencing From Clones 990
Emulsion Polymerase Chain Reaction. 990
Bridge Amplification. 991
Sequencing by Synthesis 991
Pyrosequencing. 991
Semiconductor Sequencing. 992
Reversible Terminators. 992
Sequencing by Ligation 992
Single-Molecule Sequencing 993
Real-Time Single Molecule Sequencing With Fluorescent Nucleotides. 994
Nanopore Sequencing. 994
Selected References 994
References 994.e1
48 Molecular Microbiology 995
Abstract 995
Background 995
Content 995
Introduction 995
Viral Syndromes 995
Human Immunodeficiency Virus 1 995
Hepatitis 998
Hepatitis C Virus 998
Hepatitis B Virus 1001
Transplant Recipients 1003
Cytomegalovirus 1003
Epstein-Barr Virus 1004
BK Virus 1005
Sexually Transmitted Infections 1006
Chlamydia trachomatis and Neisseria gonorrhoeae 1006
Trichomonas vaginalis 1008
Herpes Simplex Virus 1009
Human Papillomavirus 1009
Respiratory Tract Infections 1011
Viruses 1011
Mycobacterium tuberculosis 1013
Bordetella pertussis 1014
Bloodstream Infections 1015
Positive Blood Culture Identification 1015
Direct Pathogen Detection 1017
Central Nervous System 1017
Herpes Simplex Virus 1017
Enterovirus 1018
Gastroenteritis 1019
Clostridium difficile 1019
Gastrointestinal Pathogen Panels 1020
Antibacterial Drug Resistance 1021
Human Microbiome and Metagenomics 1022
Future Directions 1023
Selected References 1023
References 1024.e1
49 Genetics 1025
Abstract 1025
Background 1025
Content 1025
Diseases With Mendelian Inheritance 1025
Autosomal Recessive Disorders 1025
Cystic Fibrosis 1025
Spinal Muscular Atrophy 1030
Nonsyndromic Hearing Loss and Deafness 1031
Autosomal Dominant Diseases 1032
Huntington Disease 1032
Marfan Syndrome 1036
Multiple Endocrine Neoplasia 1037
X-Linked Diseases 1039
Duchenne Muscular Dystrophy 1039
Fragile X Syndrome 1042
Rett Syndrome 1046
Complex Diseases 1046
Thrombophilia 1047
Hereditary Pancreatitis 1049
Hereditary Breast and Ovarian Cancer 1050
Inherited Colon Cancer 1053
Lynch Syndrome 1054
Familial Adenomatous Polyposis 1057
Mitochondrial DNA Diseases 1058
Leber Hereditary Optic Neuropathy 1060
Leigh Syndrome 1060
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes 1060
Myoclonic Epilepsy Associated With Ragged Red Fibers 1061
Kearns-Sayre Syndrome 1061
Imprinting 1061
Prader-Willi and Angelman Syndromes 1061
Expanded Carrier Screening 1063
Massively Parallel Sequencing 1064
Whole-Exome Sequencing 1065
Cytogenomics 1066
Reporting of Test Results 1067
Laboratory Regulation 1070
Selected References 1070
References 1071.e1
50 Solid Tumor Genomics 1072
Abstract 1072
Background 1072
Content 1072
Considerations for Solid Tumor Genomics 1072
Sampling and Preservation Methods 1072
Staining and Selection of Tumor Cells 1073
Genomic Analysis of Solid Tumors 1074
Background 1074
Large-Scale Discovery Efforts 1074
Pre-Massively Parallel Sequencing Approaches to “Hotspot” Characterization 1075
RNA-Based Approaches 1075
Massive Parallel Sequencing of Solid Tumor Samples 1075
Whole Genome Sequencing 1076
Selective Enrichment by Hybridization Capture 1077
Multiplex Polymerase Chain Reaction Approach 1077
RNA Sequencing of Solid Tumor Isolates 1077
Detection of Cancer Mutations in Body Fluids 1078
Interpreting Somatic Alterations in a Clinical Context 1079
Prognostic Interpretation 1079
Diagnostic Interpretation 1079
Challenges of Variants of Unknown Significance 1079
Challenges of Off-Label Indications 1080
Importance of Tissue Biology 1080
Summary and Concluding Remarks 1080
Selected References 1080
References 1081.e1
51 Genetic Aspects of Hematopoietic Malignancies 1082
Abstract 1082
Background 1082
Content 1082
Recurrent Translocations and Structural Chromosomal Abnormalities 1082
Lymphoid Disorders 1083
B-Lymphoblastic Leukemia/Lymphoma 1083
T-Lymphoblastic Leukemia/Lymphoma 1085
Burkitt Lymphoma 1085
Follicular Lymphoma 1085
Diffuse Large B-Cell Lymphoma 1086
Mantle Cell Lymphoma 1086
Extranodal Marginal Zone Lymphoma (MALT Lymphoma) 1086
Multiple Myeloma 1086
Anaplastic Large Cell Lymphoma 1087
Myeloid Disorders 1087
Acute Myeloid Leukemias 1087
Chronic Myelogeneous Leukemia 1090
Myelodysplastic Syndromes 1090
Myeloid and Lymphoid Neoplasms With Eosinophilia and Abnormalities of PDGFRA, PDGFRB, or FGFR1 1090
Test Applications 1091
Cytogenetics 1091
Fluorescence in Situ Hybridization 1092
Single Nucleotide Polymorphism Array 1092
Polymerase Chain Reaction 1092
Gene Mutations in Hematopoietic Malignancies 1093
Mechanisms 1093
Myeloid Diseases 1093
Signal Transduction Pathways: Disease-Specific Signaling Mutations 1094
JAK2 1095
KIT 1095
CSF3R 1096
FLT3 1096
CALR 1096
Mutations in Epigenetic Regulators 1097
DNMT3A 1097
TET2 1098
IDH1 and IDH2 1098
Mutations in the RNA Spliceosome 1098
Mutations in the Cohesin Complex 1099
Mutations in Myeloid Transcription Factors and Chromatin Modifiers 1099
TP53 1100
NPM1 1100
Lymphoid Diseases 1100
Mature B-Cell Lymphoproliferative Disorders 1100
Hairy Cell Leukemia 1101
Lymphoplasmacytic Lymphoma 1101
Diffuse Large B Cell Lymphoma 1101
Chronic Lymphocytic Leukemia 1101
Mature T and NK Cell Lymphoproliferative Disorders 1102
B/T Lymphoblastic Leukemia/Lymphoma 1102
Acquired Drug Resistance Mutations 1102
Laboratory Techniques for the Detection of Single-Gene Variants 1103
Massively Parallel Sequencing for Somatic Variants in Hematopoietic Malignancies 1103
Role of Genetic Regulatory Mechanisms in Hematopoietic Malignancies 1104
Methylation Patterns 1104
Micro RNA Expression Patterns 1104
Gene Expression Profiling 1104
Clonality Testing in Hematopoietic Malignancies 1105
Lymphoid Clonality Testing 1105
V(D)J Recombination in Normal B- and T-Lymphocytes 1106
Identification of Clonal Rearrangements in the Workup of Lymphoid Malignancies 1107
Myeloid Clonality Testing 1107
Test Applications 1108
Southern Blotting 1108
Polymerase Chain Reaction 1108
Massively Parallel Sequencing 1108
Conclusion 1110
Selected References 1110
References 1110.e1
52 Circulating Tumor Cells and Circulating Tumor DNA 1111
Abstract 1111
Background 1111
Content 1111
Circulating Tumor Cells 1113
Circulating Tumor Cells: Historical Background 1113
Circulating Tumor Cells: Analytical Techniques 1113
General Overview 1113
The CellSearch System 1114
Isolation/Enrichment Systems for CTC Analysis 1117
Label-Dependent CTC Isolation/Enrichment Systems 1117
Positive Selection. 1117
Negative Selection. 1118
Flow Cytometry–Based Technologies. 1118
Label-Independent CTC Isolation/Enrichment Systems 1118
Systems Based on Density. 1118
Systems Based on CTC Size. 1118
Separation Based on the Electric Charge of CTCs. 1119
Microfluidic Systems for CTC Isolation/Enrichment. 1119
In Vivo Systems for CTC Isolation/Enrichment. 1120
CTC Analysis: Detection and Molecular Characterization 1123
Image-Based Approaches. 1123
Molecular Assays. 1124
PCR-Based Assays. 1125
Fluorescence in Situ Hybridization and RNA in Situ Hybridization. 1125
Protein Analyses on CTCs (EPISPOT Assay). 1125
Single-Cell Analysis of CTCs. 1126
CTCs: “A Window to Metastasis” 1127
Epithelial and Mesenchymal Transitions of CTCs 1127
CTCs and Cancer Stem Cells 1128
CTCs: Clinical Significance, Molecular Characterization, and Its Impact on Individualized Treatment of Cancer Patients 1129
Breast Cancer 1129
Clinical Significance of CTCs in Metastatic Breast Cancer. 1129
Clinical Significance of CTCs in Early Breast Cancer. 1129
Molecular Characterization of CTCs in Breast Cancer and Its Impact on Individualized Treatment. 1130
HER-2. 1130
Endocrine Treatment. 1130
EMT and Stem Cell Markers on CTCs. 1130
Apoptosis and Clinical Dormancy on CTCs. 1130
DNA Methylation in CTCs. 1130
Prostate Cancer. 1131
Clinical Significance of CTCs in Metastatic Prostate Cancer. 1131
Clinical Significance of CTCs in Early Prostate Cancer. 1131
Molecular Characterization of CTCs in Prostate Cancer and Its Impact on Individualized Treatment. 1131
Colorectal Cancer 1132
Clinical Significance of CTCs in Metastatic Colorectal Cancer. 1132
Clinical Significance of CTCs in Early Colorectal Cancer. 1132
Molecular Characterization of CTCs in Colorectal Cancer and Its Impact on Individualized Treatment. 1132
Lung Cancer 1132
Clinical Significance of CTCs in Non–Small Cell Lung Cancer. 1132
Clinical Significance of CTCs in Small Cell Lung Cancer. 1132
Molecular Characterization of CTCs in Lung Cancer and Its Impact on Individualized Treatment. 1133
Cutaneous Melanoma 1133
Clinical Significance of CTCs in Cutaneous Melanoma. 1133
Molecular Characterization of Isolated CTCs From Melanoma Patients. 1133
Ovarian Cancer 1134
Pancreatic Cancer 1134
Head and Neck Cancer 1134
Hepatocellular Carcinoma 1134
Bladder Cancer 1134
Circulating Tumor DNA 1135
Origin and Function of ctDNA 1135
Types of ctDNA 1135
Isolation of ctDNA 1135
Quantification of ctDNA 1135
Massive Parallel Sequencing 1136
Plasma Versus Serum for ctDNA 1136
Tumor-Specific ctDNA Mutations 1137
Gene Amplification in ctDNA 1138
Copy Number Variation in ctDNA 1138
Microsatellite Instability and Loss of Heterozygosity in ctDNA 1138
Methylated ctDNA 1138
Noncoding ctDNA 1140
Viral ctDNA 1140
ctDNA Integrity 1141
Half-Life of ctDNA 1141
ctDNA Detection by Single-Marker Versus Multimarker Approach Assays 1141
ctDNA in Clinical Oncology Trials 1142
Future Challenges for ctDNA Analysis 1142
Combined Discussion of CTC and ctDNA 1142
Comparison Between CTCs and ctDNA 1142
Quality Control and Logistic Issues of CTCs and ctDNA 1142
Liquid Biopsy Versus Tumor Biopsy 1143
CTCs and ctDNA Combined as Companion Blood Biomarkers 1143
Conclusions 1144
Selected References 1144
References 1144.e1
53 Circulating Nucleic Acids for Prenatal Diagnostics 1145
Abstract 1145
Background 1145
Content 1145
Brief Overview of the Early Developments of Prenatal Genetic Diagnostics 1145
Strategies to Mitigate Risks of Invasive Prenatal Diagnosis 1145
Maternal Age 1145
Serum Biochemistry Screening 1146
First Trimester Screening 1146
Noninvasive Fetal DNA Analysis 1146
Fetal Cells in Maternal Blood 1146
Cell-Free Fetal DNA in Maternal Plasma 1146
The Biology of Circulating Cell-Free Fetal Nucleic Acids in Maternal Plasma 1146
Diagnostic Applications of Circulating cffDNA 1147
Fetal Sex Assessment for Sex-Associated Disorders 1147
Fetal Rhesus D Status Determination 1148
Fetal Chromosomal Aneuploidy Screening 1148
Methodological Approaches 1148
Clinical Implementation 1150
Discordant Results 1150
Single-Gene Diseases 1151
Noninvasive Fetal ‘Omics 1151
Analytical Aspects 1152
Maternal Blood Sample Collection and Processing 1152
Circulating Cell-Free Fetal DNA Analysis 1153
Measuring the Fetal DNA Fraction 1153
Massively Parallel Maternal Plasma DNA Sequencing 1154
Conclusion 1154
Selected References 1154
References 1155.e1
54 Pharmacogenetics 1156
Abstract 1156
Background 1156
Content 1156
Principles of Pharmacogenetics 1156.e1
Drug Response 1156.e1
Pharmacokinetics 1156.e2
Pharmacodynamics 1156.e4
Implementation of Pharmacogenetics 1156.e4
Logistics of Pharmacogenetics in a Clinical Setting 1156.e5
Specimens 1156.e5
Analytical Strategies 1156.e7
Targeted Testing 1156.e7
Whole Exome/Genome 1156.e7
Genome-Wide Association Studies 1156.e8
Gene Dose (Copy Number) 1156.e8
Haplotyping 1156.e8
Reporting 1156.e8
Clinical Interpretation 1156.e8
Specific Examples of Pharmacogene Associations 1156.e9
Associations With Pharmacokinetics 1156.e9
Drug Metabolizing Enzymes 1156.e9
Cytochrome P450 2D6 (CYP2D6). 1156.e11
Tamoxifen Application. 1156.e11
Codeine Application. 1156.e13
Antidepressant Application. 1156.e13
Cytochrome P450 2C9 (CYP2C9). 1156.e13
Cytochrome P450 2C19 (CYP2C19). 1156.e14
Clopidogrel Application. 1156.e15
Antidepressant Application. 1156.e15
Cytochrome P4503A Family. 1156.e15
Tacrolimus Application. 1156.e15
Dihydropyrimidine Dehydrogenase. 1156.e15
Fluoropyrimidine Application. 1156.e16
N-Acetyltransferases (NAT1 and NAT2). 1156.e16
Clinical Applications. 1156.e18
Rasburicase Application. 1156.e19
Thiopurine S-Methyltransferase. 1156.e19
Thiopurine Application. 1156.e19
UDP-Glucuronyltransferase 1A1. 1156.e19
Irinotecan Application. 1156.e20
Drug Transporters 1156.e20
Adenosine Triphosphate (ATP)-Binding Cassette Transporters. 1156.e20
Solute Carrier Organic Anion-Transporters. 1156.e20
Simvastatin Application. 1156.e21
Associations With Pharmacodynamics 1156.e21
Vitamin K Epoxide Reductase Complex 1 1156.e21
Warfarin Application. 1156.e21
Cystic Fibrosis Transmembrane Conductance Regulator 1156.e22
Ivacaftor Application. 1156.e23
Human Leukocyte Antigen Complex 1156.e23
Clinical Applications. 1156.e23
Future Directions 1156.e24
References 1156.e24
55 Identity Testing 1157
Abstract 1157
Background 1157
Content 1157
Short Tandem Repeats and Amelogenin 1157.e1
The Analytical Process 1157.e2
Sample Collection 1157.e2
Extraction 1157.e2
Quantification 1157.e3
Polymerase Chain Reaction Amplification 1157.e3
Capillary Electrophoresis and Data Analysis 1157.e3
Y–Short Tandem Repeats 1157.e4
Mitochondrial DNA 1157.e4
Touch Samples and DNA Mixtures 1157.e6
Single Nucleotide Polymorphisms 1157.e6
Quality Assurance 1157.e7
Statistical Interpretation 1157.e7
Rapid DNA 1157.e8
Massively Parallel Sequencing 1157.e9
Short Tandem Repeats 1157.e9
Mitochondrial DNA 1157.e9
Single-Nucleotide Polymorphisms 1157.e9
Legal Issues 1157.e9
Parentage and Kinship 1157.e10
Other Clinical Applications of DNA Identity Markers 1157.e11
Verification of Sample 1157.e11
Prenatal Testing 1157.e11
Bone Marrow Transplantation (Chimerism) 1157.e11
Loss of Heterozygosity 1157.e11
References 1157.e12
V Pathophysiology 1158
56 Nutrition 1159
Abstract 1159
Background 1159
Content 1159
Introduction: The Scope of Clinical Nutrition 1159.e1
Nutrient Requirements 1159.e1
A Classification of Nutrients 1159.e1
Macronutrients 1159.e3
Carbohydrate 1159.e3
Function and Sources 1159.e3
Homeostasis 1159.e3
Deficiency 1159.e3
Excess 1159.e3
Assessment of Status 1159.e3
Dietary Fiber 1159.e4
Fat 1159.e4
Function and Sources 1159.e4
Homeostasis 1159.e4
Deficiency 1159.e4
Excess 1159.e4
Assessment of Status 1159.e4
Essential Fatty Acids 1159.e4
Other Fats 1159.e5
Protein 1159.e5
Function and Sources 1159.e5
Homeostasis 1159.e5
Deficiency 1159.e5
Excess 1159.e5
VI Hematology and Coagulation 1731
71 Hemostasis 1732
Abstract 1732
Background 1732
Content 1732
Hemostasis 1732.e1
Platelets 1732.e1
Plasma Components 1732.e1
Coagulation 1732.e1
Regulation of Coagulation 1732.e2
Fibrinolysis 1732.e4
von Willebrand Factor 1732.e4
Blood Vessels and Endothelium 1732.e5
Test Methods for Evaluation of Primary Hemostasis 1732.e6
Automated Platelet Counting 1732.e6
Manual Platelet Counting and Platelet Light Microscopy 1732.e7
Platelet Structure by Platelet Transmission Electron Microscopy 1732.e8
Global Platelet and Vascular Function 1732.e9
Bleeding Time. 1732.e9
Platelet Function Analyzer (PFA-100 and PFA-200). 1732.e9
Platelet Aggregation and Secretion 1732.e9
Platelet Aggregation Studies. 1732.e9
Platelet Secretion Studies. 1732.e10
Platelet Support of Plasma Coagulation 1732.e11
Platelet Contractile Function 1732.e11
Platelet Receptors and Function Using Flow Cytometry 1732.e11
Platelet Adhesion and von Willebrand Factor 1732.e11
Ristocetin-Induced Platelet Aggregation Assay. 1732.e11
von Willebrand Factor and Ristocetin Cofactor Assay. 1732.e11
von Willebrand Factor–Collagen-Binding Assay. 1732.e11
von Willebrand Factor GPIb Binding Assays (VWF:Ab, VWF: GPlbR, VWF:GPIbM). 1732.e11
von Willebrand Factor–Factor VIII Binding Activity. 1732.e12
von Willebrand Factor Antigen Assays (VWF:Ag). 1732.e12
von Willebrand Factor Multimer Assay. 1732.e12
Evaluation of Antiplatelet Medication 1732.e13
Platelet Aggregation. 1732.e13
PFA-100. 1732.e13
VerifyNow. 1732.e13
Clinical Application of Tests for Platelet Disorders 1732.e13
Inherited Platelet Disorders 1732.e13
Congenital Thrombocytopenia. 1732.e13
Surface Receptor Deficiency. 1732.e13
Signal Transduction Deficiency. 1732.e13
Storage-Pool Deficiency. 1732.e14
Acquired Platelet Disorders 1732.e14
Medication Effects. 1732.e14
Renal Failure. 1732.e15
Paraproteinemia. 1732.e15
Primary Bone Marrow Disorder. 1732.e15
von Willebrand Disease and Acquired von Willebrand Syndrome 1732.e15
Initial von Willebrand Disease Laboratory Testing. 1732.e16
Supplementary Testing. 1732.e16
General Considerations for Coagulation Testing 1732.e17
Preanalytic Variables for Coagulation-Based Assays 1732.e17
Optical Versus Mechanical End Point Detection 1732.e18
Chromogenic Assays 1732.e18
Test Methods for Secondary Hemostasis (Coagulation) 1732.e18
Prothrombin Time 1732.e18
Activated Partial Thromboplastin Time 1732.e20
Fibrinogen (Clauss and Derived Method) 1732.e21
Mixing Studies 1732.e21
Factor Assays 1732.e23
Factor Inhibitor Assays 1732.e24
Factor XIII Assays 1732.e25
Thrombin Time 1732.e26
Clinical Application of Laboratory Tests for Coagulation Disorders 1732.e28
Inherited Coagulation Disorders 1732.e29
Factor VIII Deficiency (Hemophilia A). 1732.e30
Factor IX Deficiency (Hemophilia B). 1732.e31
Monitoring Factor Concentrate Therapy (Hemophilia A and B). 1732.e31
Factor XI Deficiency (Hemophilia C). 1732.e32
Factor XIII Deficiency. 1732.e32
Acquired Coagulation Disorders 1732.e32
Liver Disease. 1732.e33
Vitamin K Deficiency. 1732.e33
Disseminated Intravascular Coagulation. 1732.e33
Test Methods and Their Clinical Application for Fibrinolysis 1732.e34
Thrombin Time 1732.e34
Fibrin and Fibrinogen Degradation Product Assays 1732.e34
d-Dimer Assays 1732.e34
Plasminogen Activator Inhibitor Type 1 Assays 1732.e35
α2-Antiplasmin 1732.e35
Plasminogen 1732.e35
Test Methods for Thrombosis 1732.e35
d-Dimer for Exclusion of Venous Thromboembolism 1732.e36
Test Methods and Their Clinical Application for Thrombotic Risk 1732.e36
Thrombophilia Testing 1732.e36
Activated Protein C Resistance Assays 1732.e36
Factor V Leiden Mutation Detection 1732.e37
Protein C Assays 1732.e37
Protein S 1732.e38
Antithrombin Assays 1732.e38
Prothrombin G20210A Detection 1732.e39
Factor VIII and von Willebrand Factor 1732.e39
Fibrinogen 1732.e39
Clinicopathologic Diagnosis of Other Thrombotic Disorders 1732.e39
Heparin-Induced Thrombocytopenia 1732.e39
Antiphospholipid Antibodies and Lupus Anticoagulant 1732.e41
ADAMTS13 Assay 1732.e42
Monitoring Anticoagulant Therapy 1732.e42
Unfractionated Heparin 1732.e42
aPTT for Monitoring Unfractionated Heparin. 1732.e43
Heparin Assays for Monitoring Unfractionated Heparin. 1732.e44
Thrombin Time for Monitoring Unfractionated Heparin. 1732.e44
Activated Clotting Time for Monitoring Unfractionated Heparin. 1732.e44
Low Molecular Weight Heparin 1732.e44
Fondaparinux 1732.e45
Parenteral Direct Thrombin Inhibitors 1732.e45
Direct Oral Anticoagulants 1732.e45
Direct Xa Inhibitor Assays. 1732.e45
Direct IIa Inhibitor Assays. 1732.e46
Therapy With Vitamin K Antagonists 1732.e46
Point of Care for Monitoring Vitamin K Antagonist Therapy. 1732.e47
Additional Readings 1732.e48
References 1732.e48
72 Red Blood Cell Morphology and Indices With Clinical Chemistry Interface 1733
Abstract 1733
Background 1733
Content 1733
Automated Blood Counting Instruments: Historical Perspective 1733.e1
Peripheral Blood Smear Chemistry–Related Changes: Alterations in Blood Analytes Associated With or Causing Blood Count and Smear Abnormalities 1733.e1
Basophilic Stippling 1733.e5
Clinical Chemistry Laboratory Testing to Establish the Cause of Anemia 1733.e6
Interferences 1733.e8
Substances and Conditions That May Lead to Spurious Complete Blood Cell Results 1733.e9
Lipids 1733.e9
Ethylenediaminetetraacetic Acid 1733.e9
Clotted Sample 1733.e9
Overfilling the Test Tube 1733.e9
Cryoglobulins and Immunoglobulins 1733.e9
Hemolysis 1733.e9
Bilirubin 1733.e9
Glucose 1733.e9
Sodium 1733.e9
White Blood Cells 1733.e9
Hematology-Related Conditions or Diseases That May Lead to Spurious Chemistry Laboratory Findings 1733.e9
Immunoglobulins (Including Paraproteins and Polyclonal Immunoglobulins) 1733.e9
Hemolysis 1733.e10
Posttransfusion Blood Samples 1733.e10
Increased Blood Cell Counts (Leukocytosis, Erythrocytosis, and Thrombocytosis) 1733.e10
Acknowledgment 1733.e10
References 1733.e10
73 Automated Hematology 1734
Abstract 1734
Background 1734
Content 1734
Introduction 1734.e1
Manual Methods 1734.e1
Wintrobe Calculations 1734.e1
Coulter Principle 1734.e1
Multichannel Instruments 1734.e1
Red Blood Cells 1734.e2
Manual Counting Methods 1734.e2
Automated Counting Methods 1734.e2
Red Blood Cell Parameters 1734.e3
Red Blood Cell Count 1734.e3
Hemoglobin 1734.e3
Hematocrit 1734.e3
Mean Corpuscular Volume 1734.e3
Mean Corpuscular Hemoglobin 1734.e4
Mean Corpuscular Hemoglobin Concentration 1734.e4
Red Cell Distribution Width 1734.e4
Nucleated Red Blood Cells 1734.e4
Red Blood Cell Fragments 1734.e4
Reticulocytes 1734.e4
Methods 1734.e4
Reticulocyte Parameters 1734.e4
Reticulocyte Count 1734.e4
Immature Reticulocyte Fraction 1734.e5
Reticulocyte Hemoglobin Content 1734.e5
Platelets 1734.e6
Methods 1734.e6
Impedance 1734.e6
Optical Scatter 1734.e6
Immunologic Techniques 1734.e6
Platelet Parameters 1734.e6
Platelet Count 1734.e6
Mean Platelet Volume 1734.e6
Platelet Distribution Width 1734.e7
Immature Platelet Fraction 1734.e7
White Blood Cells 1734.e7
Methods 1734.e7
Electrical Impedance 1734.e7
Radiofrequency Conductivity 1734.e7
Light Scatter 1734.e7
Cytochemistry 1734.e7
Fluorescent Labeling 1734.e8
Monoclonal Antibodies 1734.e8
Image Analysis 1734.e8
White Blood Cell Parameters and Flagging 1734.e8
Large Unstained Cells 1734.e8
Immature Granulocytes 1734.e8
Hematopoietic Progenitor Cells 1734.e8
Granularity Index 1734.e8
Lymphocyte Index 1734.e9
Leukocyte Viability 1734.e9
Selected Automated Hematology Analyzers 1734.e9
Sources of Error in Automated Hematology Instruments 1734.e9
Spurious Results in Red Blood Cells Indices 1734.e9
Red Blood Cell Count 1734.e9
Hemoglobin 1734.e9
Mean Corpuscular Hemoglobin Concentration 1734.e10
Mean Corpuscular Volume 1734.e10
Reticulocytes 1734.e10
Leukocyte Count 1734.e10
Platelet Count 1734.e10
References 1734.e11
VII Microbiology 1735
74 Bacteriology 1736
Abstract 1736
Background 1736
Content 1736
Overview of the Laboratory’s Role in the Diagnosis of Bacterial Infections 1736.e1
Road to Bacterial Identification 1736.e3
Sequencing 1736.e5
Sequencing Basics 1736.e10
Basic Gene Structure and Sequencing Targets for Bacterial Identification 1736.e10
Overview of Chain-Termination DNA Sequencing 1736.e10
Potential Pitfalls of Sequence-Based Identification 1736.e12
Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for Bacterial Identification 1736.e13
Basics of Bacterial Identification by MALDI-TOF MS 1736.e13
Bacterial Identification by MALDI-TOF MS 1736.e14
Overview of MALDI-TOF MS Performance 1736.e14
Gram-Positive Cocci 1736.e15
Gram-Positive Rods 1736.e15
Gram-Negative Bacilli and Coccobacilli 1736.e15
Enterobacteriaceae. 1736.e15
Glucose Non-Fermenting Organisms. 1736.e15
Fastidious Gram-Negative Bacilli. 1736.e17
Gram-Negative Diplococci 1736.e18
Anaerobes 1736.e18
Clinical Syndromes 1736.e19
Urinary Tract Infection 1736.e19
General Considerations 1736.e19
Resident Flora 1736.e20
Types of Infections 1736.e20
Etiology and Epidemiology 1736.e20
Laboratory Diagnosis 1736.e20
Specimen Collection and Transport 1736.e20
Blood Stream Infection (BSI) 1736.e21
General Considerations 1736.e21
Resident Flora 1736.e21
Types of Infections 1736.e21
Etiology and Epidemiology 1736.e21
Laboratory Diagnosis 1736.e22
Specimen Collection and Transport 1736.e23
Upper Respiratory Tract Infection 1736.e23
General Considerations 1736.e23
Resident Flora 1736.e23
Types of Infections 1736.e24
Etiology and Epidemiology 1736.e24
Laboratory Diagnosis 1736.e24
Specimen Collection and Transport 1736.e25
Lower Respiratory Tract Infection 1736.e25
General Considerations 1736.e25
Resident Flora 1736.e25
Types of Infections 1736.e25
Etiology and Epidemiology 1736.e25
Laboratory Diagnosis 1736.e26
Specimen Collection and Transport 1736.e26
Central Nervous System Infection 1736.e26
General Considerations 1736.e26
Resident Flora 1736.e27
Types of Infections 1736.e27
Etiology and Epidemiology 1736.e27
Laboratory Diagnosis 1736.e28
Specimen Collection and Transport 1736.e28
Ear Infections 1736.e28
General Considerations 1736.e28
Resident Flora 1736.e28
VIII Transfusion Medicine 1742
80 Blood Groups, Pretransfusion Testing, and Red Blood Cell Transfusion 1743
Abstract 1743
Background 1743
Content 1743
ABO Blood Groups 1743.e1
Rh System 1743.e2
Kell, Kidd, Duffy, and MNSs Systems 1743.e3
Lewis, I/i, and P Antigens 1743.e4
Techniques for Blood Grouping and Antibody Identification 1743.e5
Serologic Techniques 1743.e5
Direct Antiglobulin Test (DAT or Direct Coombs Test) 1743.e6
Cross-Matching 1743.e6
Molecular Techniques 1743.e7
Immunohematologic Testing in the Prenatal Patient 1743.e7
Red Blood Cell Transfusion and Blood Management 1743.e9
Factors and Thresholds to Guide Allogeneic Transfusion Therapy 1743.e9
Preoperative Assessment of the Surgical Patient 1743.e10
Intraoperative and Postoperative Strategies to Reduce Allogeneic Transfusion 1743.e10
Transfusion in Sickle Cell Disease 1743.e12
Autoimmune Hemolytic Anemia and the “Incompatible Cross-Match” 1743.e12
Warm Autoantibodies and Warm Autoimmune Hemolytic Anemia (WAIHA) 1743.e12
The Direct Antiglobulin Test in AIHA 1743.e13
Transfusion Management of Warm Autoimmune Hemolytic Anemia 1743.e13
Drug-Induced Immune Hemolytic Anemia 1743.e13
References 1743.e14
81 Blood Components, Blood Donor Screening, and Transfusion Reactions 1744
Abstract 1744
Volunteer Blood Donation 1744.e1
Ensuring Blood Safety 1744.e1
Reducing Infectious Risks 1744.e1
Bacteria 1744.e1
Infectious Disease Testing 1744.e2
Viral Agents 1744.e3
Human Immunodeficiency Virus 1744.e3
Human T-Lymphotropic Virus 1744.e3
Viral Hepatitis 1744.e3
Flavivirus 1744.e4
Cytomegalovirus 1744.e4
Parasitic Diseases 1744.e4
Malaria 1744.e4
Chagas Disease 1744.e4
Syphilis 1744.e5
Babesiosis 1744.e5
Prion Disease 1744.e5
Live Vaccines 1744.e5
Bacterial Contamination 1744.e5
Pathogen Inactivation 1744.e6
Reducing NonInfectious Risks 1744.e6
Malignancy 1744.e6
Medications 1744.e6
Anticoagulants 1744.e6
Aspirin and Antiplatelet Agents 1744.e6
Female Donors 1744.e6
Donor Reactions and Complications 1744.e7
Autologous Donation 1744.e9
Directed Donations 1744.e9
Blood Components 1744.e10
Whole-Blood Collection and Component Manufacturing 1744.e10
Anticoagulant/Preservative Solutions 1744.e10
Whole-Blood Collection 1744.e10
Component Manufacturing 1744.e11
Red Cells 1744.e11
Platelets 1744.e12
Plasma 1744.e12
Cryoprecipitate and Cryoprecipitate-Reduced Plasma Collection 1744.e12
Granulocyte Collection 1744.e12
Product Modifications 1744.e12
Washing and Volume Reduction 1744.e13
Irradiation 1744.e13
Leukoreduction 1744.e13
Transfusion Reactions 1744.e13
Acute Transfusion Reactions 1744.e13
Acute Hemolytic Transfusion Reaction 1744.e13
Transfusion-Related Acute Lung Injury 1744.e15
Transfusion-Associated Circulatory Overload 1744.e15
Transfusion-Transmitted Bacterial Infection 1744.e15
Febrile Nonhemolytic Transfusion Reactions 1744.e16
Urticarial Transfusion Reactions 1744.e16
Anaphylactic Transfusion Reactions 1744.e16
IgA Deficiency 1744.e16
Hypotensive Transfusion Reactions 1744.e17
Posttransfusion Purpura 1744.e17
Delayed Hemolytic Transfusion Reactions 1744.e17
Transfusion Associated Graft versus Host Disease 1744.e17
Red Cell Storage Lesion 1744.e17
Potassium 1744.e17
Storage Time and Outcomes 1744.e18
Other Complications of Transfusion 1744.e18
Hypothermia 1744.e18
Iron Overload 1744.e18
References 1744.e18
Appendix Reference Information for the Clinical Laboratory 1745
Abstract 1745
Background 1745
Content 1745
Overview 1745
Reference Information Tables and Figures 1745
Reference Value Distributions Across Pediatric Age†CALIPER Cohort. Canadian Laboratory Initiative on Pediatric Reference Intervals. CALIPER Publications: Colantonio et al. Clin Chem 2012 May;58(5):854–68; Konforte et al. Clin Chem 2013;59(8): 1215–27; Bailey et al. Clin Chem 2013;59(9):1393–405; Bevilacqua et al. Clin Chem 2014;60(12):1532–42; Raizman et al. Clin Chem Lab Med 2015;53(10):e239–43; Kelly et al. Clin Chim Acta 2015; 450:196–202. 1818.e1
Reference Value Distributions Across Pediatric, Adult, and Geriatric Age 1818.e27
Biochemical Markers‡Canadian Health Measures Survey. Adeli K et al. Clin Chem 2015;61(8);1049–1062; Adeli K et al. Clin Chem 2015;61(8); 1063–1074. 1818.e27
Hematological Markers§Canadian Health Measures Survey. Biochemical Markers. Adeli K et al. Clin Chem 2015;61(8);1049–1062; Adeli K et al. Clin Chem 2015;61(8);1063–1074. 1818.e39
Chapter Outline 1790
References 1816
Abbreviations 1817
Tietz Atlas of Biochemical Genetics: e1
Case 1 Propionic Acidemia 1 e2
Clinical History and Background e2
Diagnosis and Case Discussion e3
Case 2 Propionic Acidemia 2 e5
Clinical History and Background e5
Diagnosis and Case Discussion e6
Case 3 Methylmalonic Acidemia, mut Type e8
Clinical History and Background e8
Diagnosis and Case Discussion e9
Case 4 Methylmalonic Aciduria, cblA Type e11
Clinical History and Background e11
Diagnosis and Case Discussion e12
Case 5 Methylmalonic Acidemia, cblC Type e14
Clinical History and Background e14
Diagnosis and Case Discussion e15
Case 6 Succinyl-CoA Ligase Deficiency e17
Clinical History and Background e17
Diagnosis and Case Discussion e18
Case 7 Isovaleric Acidemia e20
Clinical History and Background e20
Diagnosis and Case Discussion e21
Case 8 3-Methylcrotonyl-CoA Carboxylase Deficiency e23
Clinical History and Background e23
Diagnosis and Case Discussion e24
Case 9 Short-Chain Acyl-CoA Dehydrogenase Deficiency e26
Clinical History and Background e26
Diagnosis and Case Discussion e27
Case 10 Glutaric Aciduria Type I e29
Clinical History and Background e29
Diagnosis and Case Discussion e30
Case 11 Glutaric Aciduria Type I (Low Excretor) e32
Clinical History and Background e32
Diagnosis and Case Discussion e33
Case 12 Glutaric Aciduria Type II e34
Clinical History and Background e34
Diagnosis and Case Discussion e35
Case 13 Ethylmalonic-adipic Aciduria e37
Clinical History and Background e37
Diagnosis and Case Discussion e38
Case 14 2-Hydroxyglutaric Aciduria e40
Clinical History and Background e40
Diagnosis and Case Discussion e41
Case 15 Tyrosinemia Type I e43
Clinical History and Background e43
Diagnosis and Case Discussion e44
Case 16 Alkaptonuria e46
Clinical History and Background e46
Diagnosis and Case Discussion e47
Case 17 Beta-Ketothiolase Deficiency e49
Clinical History and Background e49
Diagnosis and Case Discussion e50
Case 18 HMG-CoA Lyase Deficiency e52
Clinical History and Background e52
Diagnosis and Case Discussion e53
Case 19 Malonic Aciduria e55
Clinical History and Background e55
Diagnosis and Case Discussion e56
Case 20 Medium-Chain Acyl-CoA Dehydrogenase Deficiency e58
Clinical History and Background e58
Diagnosis and Case Discussion e59
Tietz Atlas of Electrophoretic Patterns e61
Case 1 Background e62
Interpretation and Learning Points e63
Acknowledgment e63
Case 2 Background e64
Interpretation and Learning Points e65
Acknowledgment e65
Case 3 Background e66
Interpretation and Learning Points e67
Acknowledgment e67
Case 4 Background e68
Interpretation and Learning Points e69
Acknowledgment e69
Case 5 Background e70
Interpretation and Learning Points e71
Acknowledgment e71
Case 6 Background e72
Interpretation and Learning Points e73
Acknowledgment e73
Case 7 Background e74
Interpretation and Learning Points e75
Acknowledgment e75
Case 8 Background e76
Interpretation and Learning Points e77
Acknowledgment e77
Case 9 Background e78
Interpretation and Learning Points e79
Acknowledgment e79
Case 10 Background e80
Interpretation and Learning Points e81
Acknowledgment e81
Case 11 Background e82
Interpretation and Learning Points e83
Acknowledgment e83
Case 12 Background e84
Interpretation and Learning Points e85
Acknowledgment e85
Case 13 Background e86
Interpretation and Learning Points e87
Acknowledgment e87
Case 14 Background e88
Interpretation and Learning Points e89
Acknowledgment e89
Case 15 Background e90
Interpretation and Learning Points e92
Acknowledgment e92
Case 16 Background e93
Interpretation and Learning Points e95
Acknowledgment e95
Case 17 Background e96
Interpretation and Learning Points e97
Acknowledgment e97
Case 18 Background e98
Interpretation and Learning Points e99
Acknowledgment e99
Cases 19 to 22 Background e100
Interpretation and Learning Points e101
Acknowledgment e101
References e101
Case 23 Background e102
Interpretation and Learning Points e103
Acknowledgment e103
Reference e103
Case 24 Background e104
Interpretation and Learning Points e105
Acknowledgment e105
Reference e105
Case 25 Background e106
Interpretation and Learning Points e107
Acknowledgment e107
Reference e107
Case 26 Background e108
Interpretation and Learning Points e109
Acknowledgment e109
Reference e109
Case 27 Background e110
Interpretation and Learning Points e111
Acknowledgment e111
Reference e111
Case 28 Background e112
Interpretation and Learning Points e113
Acknowledgment e113
Reference e113
Case 29 Background e114
Interpretation and Learning Points e115
Acknowledgment e115
Reference e115
Case 30 Background e116
Interpretation and Learning Points e117
Acknowledgment e117
Reference e117
Case 31 Background e118
Interpretation and Learning Points e119
Acknowledgment e119
Case 32 Background e120
Interpretation and Learning Points e121
Acknowledgment e121
Methods e121
References e121
Case 33 Background e122
Interpretation and Learning Points e123
Acknowledgment e123
Methods e123
References e123
Case 34 Background e124
Interpretation and Learning Points e125
Acknowledgment e125
Methods e125
References e125
Case 35 Background e126
Interpretation and Learning Points e127
Acknowledgment e127
Methods e127
References e127
Case 36 Background e128
Interpretation and Learning Points e129
Acknowledgment e129
Methods e129
Reference e129
Case 37 Background e130
Interpretation and Learning Points e131
Acknowledgment e131
Methods e131
References e131
Case 38 Background e132
Interpretation and Learning Points e133
Acknowledgment e133
Methods e133
Case 39 Background e134
Interpretation and Learning Points e136
Acknowledgment e136
Methods e136
Case 40 Background e137
Interpretation and Learning Points e138
Acknowledgment e138
Methods e138
Case 41 Background e139
Interpretation and Learning Points e140
Acknowledgment e140
Methods e140
Cases 42 to 44 Background e141
Case 42 e141
Case 43 e142
Case 44 e142
Interpretation and Learning Points e143
Acknowledgment e143
Methods e143
Reference e143
Case 45 Background e144
Interpretation and Learning Points e145
Method e145
Acknowledgment e145
Case 46 Background e146
Interpretation and Learning Points e148
Acknowledgment e148
Method e148
Case 47 Background e149
Interpretation and Learning Points e150
Acknowledgment e150
Method e150
Case 48 Background e151
Interpretation and Learning Points e152
Acknowledgment e152
Method e152
Case 49 Background e153
Interpretation and Learning Points e154
Acknowledgment e154
Method e154
Case 50 Background e155
Interpretation and Learning Points e156
Acknowledgment e156
Method e156
References e156
Case 51 Background e157
Interpretation and Learning Points e158
Acknowledgment e158
Method e158
Case 52 Background e159
Interpretation and Learning Points e160
Acknowledgment e160
Method e160
Case 53 Background e161
Interpretation and Learning Points e162
Acknowledgment e162
Method e162
Case 54 Background e163
Interpretation and Learning Points e164
Acknowledgment e164
Method e164
Case 55 Background e165
Interpretation and Learning Points e166
Method e166
Acknowledgment e166
Case 56 Background e167
Interpretation and Learning Points e168
Method e168
Acknowledgment e168
Case 57 Background e169
Interpretation and Learning Points e170
Method e170
Acknowledgment e170
Case 58 Background e171
Interpretation and Learning Points e172
Method e172
Acknowledgment e172
Case 59 Background e173
Interpretation and Learning Points e174
Method e174
Acknowledgment e174
Case 60 Background e175
Interpretation and Learning Points e176
Method e176
Acknowledgment e176
Case 61 Background e177
Interpretation and Learning Points e178
Method e178
Acknowledgment e178
Case 62 Background e179
Interpretation and Learning Points e180
Method e180
Acknowledgment e180
Case 63 Background e181
Interpretation and Learning Points e183
Acknowledgment e183
Case 64 Background e184
Interpretation and Learning Points e186
Acknowledgment e186
Case 65 Background e187
Interpretation and Learning Points e189
Acknowledgment e189
Case 66 Background e190
Interpretation and Learning Points e192
Acknowledgment e192
Case 67 Background e193
Interpretation and Learning Points e195
Acknowledgment e195
Case 68 Background e196
Interpretation and Learning Points e198
Acknowledgment e198
Case 69 Background e199
Interpretation and Learning Points e201
Acknowledgment e201
Case 70 Background e202
Interpretation and Learning Points e203
Acknowledgment e203
Case 71 Background e204
Interpretation and Learning Points e206
Case 72 Background e207
Interpretation and Learning Points e209
Methods e209
Acknowledgment e209
Case 73 Background e210
Interpretation and Learning Points e212
Methods e212
Acknowledgments e212
Case 74 Background e213
Interpretation and Learning Points e215
Methods e215
Acknowledgment e215
Case 75 Background e216
Interpretation and Learning Points e218
Methods e218
Acknowledgment e218
Case 76 Background e219
Interpretation and Learning Points e221
Methods e221
Acknowledgment e221
Case 77 Background e222
Interpretation and Learning Points e224
Methods e224
Acknowledgment e224
Case 78 Background e225
Interpretation and Learning Points e227
Methods e227
Acknowledgment e227
Case 79 Background e228
Interpretation and Learning Points e230
Methods e230
Acknowledgment e230
Case 80 Background e231
Interpretation and Learning Points e233
Methods e233
Acknowledgment e233
Case 81 Background e234
Interpretation and Learning Points e236
Methods e236
Acknowledgment e236
Case 82 Background e237
Interpretation and Learning Points e239
Methods e239
Acknowledgment e239
Case 83 Background e240
Interpretation and Learning Points e242
Methods e242
Acknowledgment e242
Case 84 Background e243
Interpretation and Learning Points e245
Methods e245
Acknowledgment e245
Case 85 Background e246
Interpretation and Learning Points e248
Methods e248
Acknowledgment e248
Case 86 Background e249
Interpretation and Learning Points e251
Methods e251
Acknowledgment e251
Case 87 Background e252
Interpretation and Learning Points e254
Methods e254
Acknowledgment e254
Case 88 Background e255
Interpretation and Learning Points e257
Methods e257
Acknowledgment e257
Case 89 Background e258
Interpretation and Learning Points e260
Methods e260
Acknowledgment e260
Case 90 Background e261
Interpretation and Learning Points e263
Methods e263
Acknowledgment e263
Case 91 Background e264
Interpretation and Learning Points e266
Methods e266
Acknowledgment e266
Case 92 Background e267
Interpretation and Learning Points e269
Methods e269
Acknowledgment e269
Case 93 Background e270
Interpretation and Learning Points e272
Methods e272
Acknowledgment e272
Case 94 Background e273
Interpretation and Learning Points e275
Methods e275
Acknowledgment e275
Case 95 Background e276
Interpretation and Learning Points e278
Methods e278
Acknowledgment e278
Case 96 Background e279
Interpretation and Learning Points e281
Methods e281
Acknowledgment e281
Case 97 Background e282
Interpretation and Learning Points e284
Methods e284
Acknowledgment e284
Case 98 Background e285
Interpretation and Learning Points e287
Methods e287
Acknowledgment e287
Tietz Clinical Vignettes: e288
Chapter 4 e289
Case 1 e289
Clinical History and Background e289
Diagnosis and Case Discussion e290
Case 2 e291
Clinical History and Background e291
Diagnosis and Case Discussion e292
Case 3 e293
Clinical History and Background e293
Diagnosis and Case Discussion e294
Case 4 e295
Clinical History and Background e295
Diagnosis and Case Discussion e296
Case 5 e297
Clinical History and Background e297
Diagnosis and Case Discussion e298
Case 6 e299
Clinical History and Background e299
Diagnosis and Case Discussion e300
Case 7 e301
Clinical History and Background e301
Diagnosis and Case Discussion e302
Case 8 e303
Clinical History and Background e303
Diagnosis and Case Discussion e304
Case 9 e305
Clinical History and Background e305
Diagnosis and Case Discussion e306
Case 10 e307
Clinical History and Background e307
Diagnosis and Case Discussion e308
Case 11 e309
Clinical History and Background e309
Diagnosis and Case Discussion e310
Case 12 e311
Clinical History and Background e311
Diagnosis and Case Discussion e312
Case 13 e313
Clinical History and Background e313
Diagnosis and Case Discussion e314
Case 14 e315
Clinical History and Background e315
Diagnosis and Case Discussion e316
Case 15 e317
Clinical History and Background e317
Diagnosis and Case Discussion e318
Chapter 14 e319
Case 1 e319
Clinical History and Background e319
Diagnosis and Case Discussion e320
Case 2 e321
Clinical History and Background e321
Diagnosis and Case Discussion e322
Case 3 e323
Clinical History and Background e323
Diagnosis and Case Discussion e324
Chapter 29 e325
Case 1 e325
Clinical History and Background e325
Diagnosis and Case Discussion e326
Case 2 e327
Clinical History and Background e327
Diagnosis and Case Discussion e328
Case 3 e329
Clinical History and Background e329
Diagnosis and Case Discussion e330
Case 4 e331
Clinical History and Background e331
Diagnosis and Case Discussion e332
Case 5 e333
Clinical History and Background e333
Diagnosis and Case Discussion e334
Case 6 e335
Clinical History and Background e335
Diagnosis and Case Discussion e336
Case 7 e337
Clinical History and Background e337
Diagnosis and Case Discussion e338
Case 8 e339
Diagnosis and Case Discussion e340
Case 9 e341
Diagnosis and Case Discussion e342
Case 10 e343
Diagnosis and Case Discussion e344
Case 11 e345
Diagnosis and Case Discussion e346
Case 12 e347
Clinical History and Background e347
Diagnosis and Case Discussion e348
Case 13 e349
Clinical History and Background e349
Diagnosis and Case Discussion e350
Case 14 e351
Clinical History and Background e351
Diagnosis and Case Discussion e352
Case 15 e353
Clinical History and Background e353
Diagnosis and Case Discussion e354
Case 16 e355
Clinical History and Background e355
Diagnosis and Case Discussion e356
Chapter 31 e357
Case 1 e357
Clinical History and Background e357
Diagnosis and Case Discussion e358
Case 2 e359
Clinical History and Background e359
Diagnosis and Case Discussion e360
Case 3 e361
Clinical History and Background e361
Diagnosis and Case Discussion e362
Case 4 e363
Clinical History and Background e363
Diagnosis and Case Discussion e364
Chapter 32 e365
Case 1 e365
Clinical History and Background e365
Diagnosis and Case Discussion e366
Case 2 e367
Clinical History and Background e367
Diagnosis and Case Discussion e368
Case 3 e369
Clinical History and Background e369
Diagnosis and Case Discussion e370
Case 4 e371
Clinical History and Background e371
Diagnosis and Case Discussion e372
Case 5 e373
Clinical History and Background e373
Diagnosis and Case Discussion e374
Case 6 e375
Clinical History and Background e375
Diagnosis and Case Discussion e376
Case 7 e377
Clinical History and Background e377
Diagnosis and Case Discussion e378
Case 8 e379
Clinical History and Background e379
Diagnosis and Case Discussion e380
Case 9 e381
Clinical History and Background e381
Diagnosis and Case Discussion e382
Case 10 e383
Clinical History and Background e383
Diagnosis and Case Discussion e384
Chapter 34 e385
Case 1 e385
Clinical History and Background e385
Diagnosis and Case Discussion e386
Case 2 e387
Clinical History and Background e387
Diagnosis and Case Discussion e388
Case 3 e389
Clinical History and Background e389
Diagnosis and Case Discussion e390
Case 4 e391
Clinical History and Background e391
Diagnosis and Case Discussion e392
Case 5 e393
Clinical History and Background e393
Diagnosis and Case Discussion e394
Case 6 e395
Clinical History and Background e395
Diagnosis and Case Discussion e396
Case 7 e397
Clinical History and Background e397
Diagnosis and Case Discussion e398
Case 8 e399
Clinical History and Background e399
Diagnosis and Case Discussion e400
Chapter 37 e401
Case 1 e401
Clinical History and Background e401
Diagnosis and Case Discussion e402
Case 2 e403
Clinical History and Background e403
Diagnosis and Case Discussion e404
Chapter 40 e405
Case 1 e405
Clinical History and Background e405
Diagnosis and Case Discussion e406
Case 2 e407
Clinical History and Background e407
Diagnosis and Case Discussion e408
Case 3 e409
Clinical History and Background e409
Diagnosis and Case Discussion e410
Case 4 e411
Clinical History and Background e411
Diagnosis and Case Discussion e412
Chapter 41 e413
Case 1 e413
Clinical History and Background e413
Diagnosis and Case Discussion e414
Case 2 e415
Clinical History and Background e415
Diagnosis and Case Discussion e416
Case 3 e417
Clinical History and Background e417
Diagnosis and Case Discussion e418
Case 4 e419
Clinical History and Background e419
Diagnosis and Case Discussion e420
Case 5 e421
Clinical History and Background e421
Diagnosis and Case Discussion e422
Chapter 57 e423
Case 1 e423
Clinical History and Background e423
Diagnosis and Case Discussion e424
Case 2 e425
Clinical History and Background e425
Diagnosis and Case Discussion e426
Case 3 e427
Clinical History and Background e427
Diagnosis and Case Discussion e428
Case 4 e429
Clinical History and Background e429
Diagnosis and Case Discussion e430
Case 5 e431
Clinical History and Background e431
Diagnosis and Case Discussion e432
Case 6 e433
Clinical History and Background e433
Diagnosis and Case Discussion e434
Chapter 59 e435
Case 1 e435
Clinical History and Background e435
Diagnosis and Case Discussion e436
Case 2 e437
Clinical History and Background e437
Diagnosis and Case Discussion e438
Case 3 e439
Clinical History and Background e439
Diagnosis and Case Discussion e440
Case 4 e441
Clinical History and Background e441
Diagnosis and Case Discussion e442
Case 5 e443
Clinical History and Background e443
Diagnosis and Case Discussion e444
Case 6 e445
Clinical History and Background e445
Diagnosis and Case Discussion e446
Case 7 e447
Clinical History and Background e447
Diagnosis and Case Discussion e448
Case 8 e449
Clinical History and Background e449
Diagnosis and Case Discussion e450
Case 9 e451
Clinical History and Background e451
Diagnosis and Case Discussion e452
Case 10 e453
Clinical History and Background e453
Diagnosis and Case Discussion e454
Case 11 e455
Clinical History and Background e455
Diagnosis and Case Discussion e456
Case 12 e457
Clinical History and Background e457
Diagnosis and Case Discussion e458
Case 13 e459
Clinical History and Background e459
Diagnosis and Case Discussion e460
Case 14 e461
Clinical History and Background e461
Diagnosis and Case Discussion e462
Case 15 e463
Diagnosis and Case Discussion e464
Case 16 e465
Clinical History and Background e465
Diagnosis and Case Discussion e466
Case 17 e467
Clinical History and Background e467
Diagnosis and Case Discussion e468
Case 18 e469
Clinical History and Background e469
Diagnosis and Case Discussion e470
Case 19 e471
Clinical History and Background e471
Diagnosis and Case Discussion e472
Case 20 e473
Clinical History and Background e473
Diagnosis and Case Discussion e474
Case 21 e475
Clinical History and Background e475
Diagnosis and Case Discussion e476
Case 22 e477
Clinical History and Background e477
Diagnosis and Case Discussion e478
Case 23 e479
Clinical History and Background e479
Diagnosis and Case Discussion e480
Chapter 60 e481
Case 1 e481
Clinical History and Background e481
Diagnosis and Case Discussion e482
Case 2 e483
Clinical History and Background e483
Diagnosis and Case Discussion e484
Case 3 e485
Clinical History and Background e485
Diagnosis and Case Discussion e486
Case 4 e487
Clinical History and Background e487
Diagnosis and Case Discussion e488
Case 5 e489
Clinical History and Background e489
Diagnosis and Case Discussion e490
Case 6 e491
Clinical History and Background e491
Diagnosis and Case Discussion e492
Case 7 e493
Clinical History and Background e493
Diagnosis and Case Discussion e494
Case 8 e495
Clinical History and Background e495
Diagnosis and Case Discussion e496
Case 9 e497
Clinical History and Background e497
Diagnosis and Case Discussion e498
Case 10 e499
Clinical History and Background e499
Diagnosis and Case Discussion e500
Case 11 e501
Clinical History and Background e501
Diagnosis and Case Discussion e502
Case 12 e503
Clinical History and Background e503
Diagnosis and Case Discussion e504
Case 13 e505
Clinical History and Background e505
Diagnosis and Case Discussion e506
Case 14 e507
Clinical History and Background e507
Diagnosis and Case Discussion e508
Case 15 e509
Clinical History and Background e509
Diagnosis and Case Discussion e510
Case 16 e511
Clinical History and Background e511
Diagnosis and Case Discussion e512
Case 17 e513
Clinical History and Background e513
Diagnosis and Case Discussion e514
Case 18 e515
Clinical History and Background e515
Diagnosis and Case Discussion e516
Case 19 e517
Clinical History and Background e517
Diagnosis and Case Discussion e518
Case 20 e519
Clinical History and Background e519
Diagnosis and Case Discussion e520
Case 21 e521
Clinical History and Background e521
Diagnosis and Case Discussion e522
Case 22 e523
Clinical History and Background e523
Diagnosis and Case Discussion e524
Case 23 e525
Clinical History and Background e525
Diagnosis and Case Discussion e526
Case 24 e527
Clinical History and Background e527
Diagnosis and Case Discussion e528
Case 25 e529
Clinical History and Background e529
Diagnosis and Case Discussion e530
Case 26 e531
Clinical History and Background e531
Diagnosis and Case Discussion e532
Case 27 e533
Clinical History and Background e533
Diagnosis and Case Discussion e534
Case 28 e535
Clinical History and Background e535
Diagnosis and Case Discussion e536
Case 29 e537
Clinical History and Background e537
Diagnosis and Case Discussion e538
Case 30 e539
Clinical History and Background e539
Diagnosis and Case Discussion e540
Case 31 e541
Clinical History and Background e541
Diagnosis and Case Discussion e542
Case 32 e543
Clinical History and Background e543
Diagnosis and Case Discussion e544
Case 33 e545
Clinical History and Background e545
Diagnosis and Case Discussion e546
Case 34 e547
Clinical History and Background e547
Diagnosis and Case Discussion e548
Case 35 e549
Clinical History and Background e549
Diagnosis and Case Discussion e550
Case 36 e551
Clinical History and Background e551
Diagnosis and Case Discussion e552
Case 37 e553
Clinical History and Background e553
Diagnosis and Case Discussion e554
Case 38 e555
Clinical History and Background e555
Diagnosis and Case Discussion e556
Case 39 e557
Clinical History and Background e557
Diagnosis and Case Discussion e558
Chapter 61 e559
Case 1 e559
Clinical History and Background e559
Diagnosis and Case Discussion e560
Case 2 e561
Clinical History and Background e561
Diagnosis and Case Discussion e562
Case 3 e563
Clinical History and Background e563
Diagnosis and Case Discussion e564
Case 4 e565
Clinical History and Background e565
Diagnosis and Case Discussion e566
Case 5 e567
Clinical History and Background e567
Diagnosis and Case Discussion e568
Case 6 e569
Clinical History and Background e569
Diagnosis and Case Discussion e570
Case 7 e571
Clinical History and Background e571
Diagnosis and Case Discussion e572
Case 8 e573
Clinical History and Background e573
Diagnosis and Case Discussion e574
Case 9 e575
Clinical History and Background e575
Diagnosis and Case Discussion e576
Case 10 e577
Diagnosis and Case Discussion e578
Case 11 e579
Diagnosis and Case Discussion e580
Case 12 e581
Clinical History and Background e581
Diagnosis and Case Discussion e582
Case 13 e583
Clinical History and Background e583
Diagnosis and Case Discussion e584
Case 14 e585
Clinical History and Background e585
Diagnosis and Case Discussion e586
Case 15 e587
Clinical History and Background e587
Diagnosis and Case Discussion e588
Case 16 e589
Clinical History and Background e589
Diagnosis and Case Discussion e590
Case 17 e591
Clinical History and Background e591
Diagnosis and Case Discussion e592
Chapter 62 e593
Case 1 e593
Clinical History and Background e593
Diagnosis and Case Discussion e594
Case 2 e595
Clinical History and Background e595
Diagnosis and Case Discussion e596
Chapter 63 e597
Case 1 e597
Clinical History and Background e597
Diagnosis and Case Discussion e598
Case 2 e599
Clinical History and Background e599
Diagnosis and Case Discussion e600
Case 3 e601
Clinical History and Background e601
Diagnosis and Case Discussion e602
Case 4 e603
Clinical History and Background e603
Diagnosis and Case Discussion e604
Case 5 e605
Diagnosis and Case Discussion e606
Case 6 e607
Clinical History and Background e607
Diagnosis and Case Discussion e608
Chapter 64 e609
Case 1 e609
Clinical History and Background e609
Diagnosis and Case Discussion e610
Case 2 e611
Clinical History and Background e611
Diagnosis and Case Discussion e612
Case 3 e613
Clinical History and Background e613
Diagnosis and Case Discussion e614
Case 4 e615
Clinical History and Background e615
Diagnosis and Case Discussion e616
Case 5 e617
Clinical History and Background e617
Diagnosis and Case Discussion e618
Case 6 e619
Clinical History and Background e619
Diagnosis and Case Discussion e620
Case 7 e621
Clinical History and Background e621
Diagnosis and Case Discussion e622
Case 8 e623
Clinical History and Background e623
Diagnosis and Case Discussion e624
Case 9 e625
Clinical History and Background e625
Diagnosis and Case Discussion e626
Case 10 e627
Clinical History and Background e627
Diagnosis and Case Discussion e628
Case 11 e629
Clinical History and Background e629
Diagnosis and Case Discussion e630
Case 12 e631
Clinical History and Background e631
Diagnosis and Case Discussion e632
Case 13 e633
Clinical History and Background e633
Diagnosis and Case Discussion e634
Case 14 e635
Clinical History and Background e635
Diagnosis and Case Discussion e636
Case 15 e637
Clinical History and Background e637
Diagnosis and Case Discussion e638
Case 16 e639
Clinical History and Background e639
Diagnosis and Case Discussion e640
Case 17 e641
Clinical History and Background e641
Diagnosis and Case Discussion e642
Case 18 e643
Clinical History and Background e643
Diagnosis and Case Discussion e644
Case 19 e645
Clinical History and Background e645
Diagnosis and Case Discussion e646
Case 20 e647
Clinical History and Background e647
Diagnosis and Case Discussion e648
Case 21 e649
Clinical History and Background e649
Diagnosis and Case Discussion e650
Case 22 e651
Clinical History and Background e651
Diagnosis and Case Discussion e652
Case 23 e653
Clinical History and Background e653
Diagnosis and Case Discussion e654
Case 24 e655
Clinical History and Background e655
Diagnosis and Case Discussion e656
Case 25 e657
Clinical History and Background e657
Diagnosis and Case Discussion e658
Case 26 e659
Clinical History and Background e659
Diagnosis and Case Discussion e660
Chapter 65 e661
Case 1 e661
Clinical History and Background e661
Diagnosis and Case Discussion e662
Case 2 e663
Clinical History and Background e663
Diagnosis and Case Discussion e664
Case 3 e665
Clinical History and Background e665
Diagnosis and Case Discussion e666
Case 4 e667
Clinical History and Background e667
Diagnosis and Case Discussion e668
Case 5 e669
Clinical History and Background e669
Diagnosis and Case Discussion e670
Case 6 e671
Clinical History and Background e671
Diagnosis and Case Discussion e672
Case 7 e673
Clinical History and Background e673
Diagnosis and Case Discussion e674
Case 8 e675
Clinical History and Background e675
Diagnosis and Case Discussion e676
Case 9 e677
Clinical History and Background e677
Diagnosis and Case Discussion e678
Case 10 e679
Clinical History and Background e679
Diagnosis and Case Discussion e680
Chapter 66 e681
Case 1 e681
Clinical History and Background e681
Diagnosis and Case Discussion e682
Case 2 e683
Clinical History and Background e683
Diagnosis and Case Discussion e684
Case 3 e685
Clinical History and Background e685
Diagnosis and Case Discussion e686
Case 4 e687
Clinical History and Background e687
Diagnosis and Case Discussion e688
Case 5 e689
Clinical History and Background e689
Diagnosis and Case Discussion e690
Case 6 e691
Clinical History and Background e691
Diagnosis and Case Discussion e692
Case 7 e693
Clinical History and Background e693
Diagnosis and Case Discussion e694
Case 8 e695
Clinical History and Background e695
Diagnosis and Case Discussion e696
Case 9 e697
Clinical History and Background e697
Diagnosis and Case Discussion e698
Case 10 e699
Clinical History and Background e699
Diagnosis and Case Discussion e700
Case 11 e701
Clinical History and Background e701
Diagnosis and Case Discussion e702
Chapter 67 e703
Case 1 e703
Clinical History and Background e703
Diagnosis and Case Discussion e704
Case 2 e705
Clinical History and Background e705
Diagnosis and Case Discussion e706
Case 3 e707
Clinical History and Background e707
Diagnosis and Case Discussion e708
Case 4 e709
Clinical History and Background e709
Diagnosis and Case Discussion e710
Case 5 e711
Clinical History and Background e711
Diagnosis and Case Discussion e712
Case 6 e713
Clinical History and Background e713
Diagnosis and Case Discussion e714
Case 7 e715
Clinical History and Background e715
Diagnosis and Case Discussion e716
Case 8 e717
Clinical History and Background e717
Diagnosis and Case Discussion e718
Case 9 e719
Clinical History and Background e719
Diagnosis and Case Discussion e720
Case 10 e721
Clinical History and Background e721
Diagnosis and Case Discussion e722
Case 11 e723
Clinical History and Background e723
Diagnosis and Case Discussion e724
Case 12 e725
Clinical History and Background e725
Diagnosis and Case Discussion e726
Chapter 68 e727
Case 1 e727
Clinical History and Background e727
Diagnosis and Case Discussion e728
Case 2 e729
Clinical History and Background e729
Diagnosis and Case Discussion e730
Case 3 e731
Clinical History and Background e731
Diagnosis and Case Discussion e732
Case 4 e733
Clinical History and Background e733
Diagnosis and Case Discussion e734
Case 5 e735
Clinical History and Background e735
Diagnosis and Case Discussion e736
Case 6 e737
Clinical History and Background e737
Diagnosis and Case Discussion e738
Chapter 70 e739
Case 1 e739
Clinical History and Background e739
Diagnosis and Case Discussion e740
Case 2 e741
Clinical History and Background e741
Diagnosis and Case Discussion e742
Case 3 e743
Clinical History and Background e743
Diagnosis and Case Discussion e744
Case 4 e745
Clinical History and Background e745
Diagnosis and Case Discussion e746
Case 5 e747
Clinical History and Background e747
Diagnosis and Case Discussion e748
Case 6 e749
Clinical History and Background e749
Diagnosis and Case Discussion e750
Case 7 e751
Clinical History and Background e751
Diagnosis and Case Discussion e752
Case 8 e753
Clinical History and Background e753
Diagnosis and Case Discussion e754
Case 9 e755
Clinical History and Background e755
Diagnosis and Case Discussion e756
Case 10 e757
Clinical History and Background e757
Diagnosis and Case Discussion e758
Case 11 e759
Clinical History and Background e759
Diagnosis and Case Discussion e760
Case 12 e761
Clinical History and Background e761
Diagnosis and Case Discussion e762
Tietz Biochemical Calculations e763
Question 1 e763
Answer e764
Question 2 e765
Answer e766
Question 3 e767
Answer e768
Question 4 e769
Answer e770
Question 5 e771
Answer e772
Question 6 e773
Answer e774
Question 7 e775
Answer e776
Question 8 e777
Answer e778
Question 9 e779
Answer e780
Question 10 e781
Answer e782
Question 11 e783
Answer e784
Question 12 e785
Answer e786
Question 13 e787
Answer e788
Question 14 e789
Answer e790
Question 15 e792
Answer e793
Question 16 e794
Answer e795
Question 17 e797
Answer e798
Question 18 e800
Answer e801
Notes: e801
Question 19 e802
Answer e803
Question 20 e804
Answer e805
Question 21 e806
Answer e807
Question 22 e808
Answer e809
Question 23 e810
Answer e811
Question 24 e812
Answer e813
Question 25 e814
Answer e815
Question 26 e816
Answer e817
Question 27 e818
Answer e819
Question 28 e820
Answer e821
Question 29 e822
Answer e823
Question 30 e824
Answer e825
Question 31 e826
Answer e827
Question 32 e828
Answer e829
Question 33 e830
Answer e831
Question 34 e832
Answer e833
Question 35 e834
Answer e835
Question 36 e837
Answer e838
Question 37 e839
Answer e840
Question 38 e842
Answer e843
Question 39 e844
Answer e845
Notes e846
Question 40 e847
Answer e848
Question 41 e850
Answer e851
Question 42 e852
Answer e853
Question 43 e854
Answer e855
Question 44 e856
Answer e857
Alternative Approach: e858
Question 45 e859
Answer e860
Question 46 e861
Answer e862
Question 47 e863
Answer e864
Question 48 e865
Answer e866
Question 49 e867
Answer e868
Question 50 e869
Answer e870
Question 51 e871
Answer e872
Question 52 e873
Answer e874
Question 53 e875
Answer e876
Question 54 e877
Answer e878
Question 55 e879
Answer e880
Question 56 e881
Answer e882
Question 57 e883
Answer e884
Question 58 e885
Answer e886
Question 59 e887
Answer e888
Question 60 e889
Answer e890
Question 61 e891
Answer e892
Question 62 e893
Answer e894
Question 63 e895
Answer e896
Question 64 e898
Answer e899
Question 65 e900
Answer e901
Question 66 e903
Answer e904
Question 67 e905
Answer e906
Glucose e906
Creatinine e906
Blood Urea Nitrogen (BUN) e906
Albumin : Creatinine Ratio e906
Question 68 e907
Answer e908
Question 69 e909
Immunoassay Method for Peptide-X e909
Answer e910
Question 70 e911
Answer e912
Question 71 e913
Answer e914
Question 72 e915
Answer e916
Question 73 e917
Answer e918
Question 74 e919
Answer e920
Question 75 e921
Answer e922
Question 76 e923
Answer e924
Question 77 e925
Answer e926
Question 78 e927
Answer e928
Question 79 e929
Answer e930
Question 80 e931
Answer e932
Question 81 e933
Answer e934
Question 82 e935
Answer e936
Question 83 e937
Answer e938
Abbreviations: e938
Method 1 e938
Method 2 e939
Question 84 e940
Method Details e940
Answer e941
Question 85 e942
Answer e943
Question 86 e944
Method e944
Result e944
Answer e945
Question 87 e946
Answer e947
Question 88 e948
Answer e949
Question 89 e950
Answer e951
Question 90 e952
Answer e953
Question 91 e954
Answer e955
Question 92 e956
Answer e957
Question 93 e958
Answer e959
Question 94 e960
Answer e961
Question 95 e962
Answer e963
Question 96 e964
Answer e965
Question 97 e966
Answer e967
Question 98 e968
Answer e969
Question 99 e970
Answer e971
Question 100 e972
Answer e973
Question 101 e974
Answer e975
Question 102 e977
Answer e978
Question 103 e979
Answer e980
Question 104 e981
Answer e982
Question 105 e983
Answer e984
Question 106 e985
Answer e986
Question 107 e987
Answer e988
Question 108 e989
Answer e990
Question 109 e991
Answer e992
Question 110 e993
Answer e994
Question 111 e995
Answer e996
Question 112 e998
Answer e999
Question 113 e1000
Answer e1001
Question 114 e1003
Answer e1004
Reference e1005
Question 115 e1006
Answer e1007
Question 116 e1008
Answer e1009
Question 117 e1010
Answer e1011
Question 118 e1012
Answer e1013
Question 119 e1014
Answer e1015
Question 120 e1016
Answer e1017
Question 121 e1018
Answer e1019
Question 122 e1020
Answer e1021
Method 1 e1021
Method 2 e1021
Method 3 e1021
Question 123 e1023
Answer e1024
Question 124 e1025
Answer e1026
Method 1 e1026
Method 2 e1026
Method 3 e1026
Question 125 e1028
Answer e1029
Question 126 e1030
Answer e1031
Question 127 e1032
Answer e1033
Question 128 e1034
Answer e1035
Question 129 e1036
Answer e1037
Question 130 e1039
Answer e1040
Question 131 e1041
Answer e1042
Question 132 e1043
Answer e1044
Question 133 e1045
Answer e1046
Question 134 e1048
Answer e1049
Question 135 e1050
Answer e1051
Question 136 e1052
Answer e1053
Tietz Teasers in Parasitology: The Bobbi Pritt Collection e1055
Question 1 e1055
Answer and Explanation e1056
Question 2 e1057
Background e1057
Answer and Explanation e1058
Question 3 e1059
Background e1059
Answer and Explanation e1060
Question 4 e1061
Background e1061
Answer and Explanation e1062
Question 5 e1063
Answer and Explanation e1064
Question 8 e1065
Answer and Explanation e1066
Question 9 e1067
Background e1067
Answer and Explanation e1068
Question 10 e1069
Answer and Explanation e1070
Question 11 e1071
Answer and Explanation e1072
Question 12 e1073
Answer and Explanation e1074
Question 13 e1075
Background e1075
Answer and Explanation e1076
Question 14 e1077
Background e1077
Answer and Explanation e1078
Question 15 e1079
Background e1079
Answer and Explanation e1080
Question 16 e1081
Background e1081
Answer and Explanation e1082
Question 17 e1083
Background e1083
Answer and Explanation e1084
Question 18 e1085
Background e1085
Answer and Explanation e1086
Question 19 e1087
Background e1087
Answer and Explanation e1088
Question 20 e1089
Background e1089
Answer and Explanation e1090
Question 22 e1091
Background e1091
Answer and Explanation e1092
Question 23 e1093
Background e1093
Answer and Explanation e1094
Question 25 e1095
Background e1095
Answer and Explanation e1096
Question 26 e1097
Background e1097
Answer and Explanation e1098
Question 27 e1099
Background e1099
Answer and Explanation e1100
Question 28 e1101
Background e1101
Answer and Explanation e1102
Question 29 e1103
Background e1103
Answer and Explanation e1104
Question 30 e1105
Background e1105
Answer and Explanation e1106
Question 32 e1107
Background e1107
Answer and Explanation e1108
Question 33 e1109
Answer and Explanation e1110
Question 34 e1111
Background e1111
Answer and Explanation e1112
Question 35 e1113
Answer and Explanation e1114
Question 36 e1115
Background e1115
Answer and Explanation e1116
Question 37 e1117
Background e1117
Answer and Explanation e1118
Question 38 e1119
Background e1119
Answer and Explanation e1120
Question 39 e1121
Background e1121
Answer and Explanation e1122
Question 40 e1123
Background e1123
Answer and Explanation e1124
Question 41 e1125
Background e1125
Answer and Explanation e1126
Question 42 e1127
Answer and Explanation e1128
Question 43 e1129
Background e1129
Answer and Explanation e1130
Question 44 e1131
Background e1131
Answer and Explanation e1132
Question 45 e1133
Background e1133
Answer and Explanation e1134
Question 46 e1135
Background e1135
Answer and Explanation e1136
Question 47 e1137
Background e1137
Answer and Explanation e1138
Question 48 e1139
Background e1139
Answer and Explanation e1140
Question 50 e1141
Background e1141
Answer and Explanation e1142
Question 51 e1143
Background e1143
Answer and Explanation e1144
Question 52 e1145
Background e1145
Answer and Explanation e1146
Question 53 e1147
Background e1147
Answer and Explanation e1148
Question 54 e1149
Background e1149
Answer and Explanation e1150
Question 55 e1151
Background e1151
Answer and Explanation e1152
Question 56 e1153
Background e1153
Answer and Explanation e1154
Question 57 e1155
Background e1155
Answer and Explanation e1156
Question 58 e1157
Background e1157
Answer and Explanation e1158
Question 59 e1159
Background e1159
Answer and Explanation e1160
Question 60 e1161
Background e1161
Answer and Explanation e1162
Question 62 e1163
Background e1163
Answer and Explanation e1164
Question 63 e1165
Background e1165
Answer and Explanation e1166
Question 64 e1167
Answer and Explanation e1168
Question 67 e1169
Background e1169
Answer and Explanation e1170
Question 68 e1171
Background e1171
Answer and Explanation e1172
Question 69 e1173
Background e1173
Answer and Explanation e1174
Question 70 e1175
Background e1175
Answer and Explanation e1176
Question 71 e1177
Background e1177
Answer and Explanation e1178
Question 72 e1179
Background e1179
Answer and Explanation e1180
Question 73 e1181
Background e1181
Answer and Explanation e1182
Question 74 e1183
Background e1183
Answer and Explanation e1184
Question 75 e1185
Background e1185
Answer and Explanation e1186
Question 76 e1187
Background e1187
Answer and Explanation e1188
Question 77 e1189
Background e1189
Answer and Explanation e1190
Question 78 e1191
Background e1191
Answer and Explanation e1192
Question 79 e1193
Background e1193
Answer and Explanation e1194
Question 82 e1195
Background e1195
Answer and Explanation e1196
Question 84 e1197
Background e1197
Answer and Explanation e1198
Question 85 e1200
Background e1200
Answer and Explanation e1201
Question 86 e1202
Background e1202
Answer and Explanation e1203
Question 88 e1204
Background e1204
Answer and Explanation e1205
Question 89 e1206
Background e1206
Answer and Explanation e1207
Question 90 e1208
Background e1208
Answer and Explanation e1209
Question 91 e1210
Background e1210
Answer and Explanation e1211
Question 92 e1212
Background e1212
Answer and Explanation e1213
Question 93 e1214
Background e1214
Answer and Explanation e1216
Question 95 e1217
Background e1217
Answer and Explanation e1218
Question 96 e1219
Background e1219
Answer and Explanation e1220
Question 97 e1221
Background e1221
Answer and Explanation e1222
Question 98 e1223
Background e1223
Answer and Explanation e1224
Question 99 e1225
Background e1225
Answer and Explanation e1226
Question 100 e1227
Background e1227
Answer and Explanation e1228
Question 102 e1229
Background e1229
Answer and Explanation e1230
Question 103 e1231
Background e1231
Answer and Explanation e1232
Question 104 e1233
Background e1233
Answer and Explanation e1234
Question 107 e1235
Background e1235
Answer and Explanation e1236
Question 110 e1237
Background e1237
Answer and Explanation e1238
Question 111 e1239
Background e1239
Answer and Explanation e1240
Question 112 e1241
Background e1241
Answer and Explanation e1242
Question 113 e1243
Background e1243
Answer and Explanation e1244
Question 114 e1245
Answer and Explanation e1246
Question 115 e1247
Answer and Explanation e1248
1 Free-Living Amebae: Acanthamoeba species/Balamuthia mandrillaris e1250
Case 1 e1250
Case 2 e1250
Case 3 e1252
2 Acanthocephalans e1253
Case 1 e1253
3 Ascaris lumbricoides e1254
Case 1 e1254
4 Babesia species e1255
Case 1 e1255
5 Balantidium coli e1257
Case 1 e1257
Case 2 e1257
6 Blastocystis hominis e1260
Case 1 e1260
7 Brugia malayi e1261
Case 1 e1261
8 Capillaria species e1262
Case 1 e1262
9 Non-Parasitic Stool Objects e1263
Case 1 e1263
Case 2 e1264
10 Clonorchis sinensis e1265
Case 1 e1265
Case 2 e1265
11 Cyclospora cayetanensis e1266
Case 1 e1266
12 Demodex species e1267
Case 1 e1267
13 Bot Flies e1268
Case 1 e1268
Case 2 e1268
14 Diphyllobothrium species e1269
Case 1 e1269
Case 2 e1270
15 Dipylidium caninum e1271
Case 1 e1271
Case 2 e1272
Case 3 e1273
16 Echinococcus species e1274
Case 1 e1274
Case 2 e1275
Case 3 e1275
17 Entamoeba coli e1276
Case 1 e1276
18 Entamoeba histolytica/Entamoeba dispar e1277
Case 1 e1277
Case 2 e1277
19 Enterobius vermicularis (Pinworm) e1278
Case 1 e1278
Case 2 e1278
20 Fasciola hepatica e1279
Case 1 e1279
21 Giardia duodenalis (a.k.a., G. lamblia, G. intestinalis) e1280
Case 1 e1280
22 Gordian Worm e1281
Case 1 e1281
23 Hard Ticks e1283
Case 1 e1283
Case 2 e1283
Case 3 e1284
24 Hookworm e1285
Case 1 e1285
Case 2 e1285
25 Howell-Jolly Bodies e1286
Case 1 e1286
26 Hymenolepis nana e1288
Case 1 e1288
27 Iodamoeba buetschlii e1289
Case 1 e1289
28 Leishmania species e1290
Case 1 e1290
Case 2 e1291
29 Microsporidia e1292
Case 1 e1292
30 Mosquitoes e1293
Case 1 e1293
Case 2 e1293
31 Onchocerca volvulus e1294
Case 1 e1294
32 Paragonimus species e1296
Case 1 e1296
33 Pediculus humanus e1298
Case 1 e1298
Case 2 e1298
34 Plasmodium species (Malaria) e1299
Case 1 e1299
Case 2 e1300
Case 3 e1300
Case 4 e1301
Case 5 e1302
Case 6 e1302
Case 7 e1304
Case 8 e1305
Case 9 e1306
35 Pthirus pubis (Pubic Louse) e1307
Case 1 e1307
36 Sarcocystis species e1358
Case 1 e1358
37 Sarcoptes scabei e1309
Case 1 e1309
Case 2 e1310
Case 3 e1310
38 Schistosoma species e1312
Case 1 e1312
Case 2 e1312
Case 3 e1313
Case 4 e1314
Case 5 e1314
39 Strongyloides stercoralis e1316
Case 1 e1316
Case 2 e1317
40 Taenia species e1318
Case 1 e1318
Case 2 e1319
41 Toxocara species e1320
Case 1 e1320
42 Toxoplasma gondii e1322
Case 1 e1322
Case 2 e1322
43 Trichinella species e1324
Case 1 e1324
Case 2 e1324
44 Trichuris trichiura (whipworm) e1326
Case 1 e1326
Case 2 e1326
Case 3 e1328
45 Trypanosomes e1329
Case 1 e1329
Case 2 e1329
Case 3 e1330
46 Tunga penetrans e1331
Case 1 e1331
47 Wuchereria bancrofti e1332
Case 1 e1332
48 Zoonotic Mite e1334
Case 1 e1334
Index 1819
A 1819
B 1823
C 1825
D 1830
E 1832
F 1834
G 1836
H 1838
I 1841
J 1843
K 1843
L 1843
M 1845
N 1848
O 1849
P 1850
Q 1856
R 1856
S 1858
T 1861
U 1864
V 1865
W 1867
X 1867
Y 1867
Z 1867