Tietz Textbook of Clinical Chemistry and Molecular Diagnostics

by Burtis, Ashwood & Bruns

• ISBN13: 9780721601892
• ISBN10: 0721601898
• Edition: 4th
• Format: Hardcover
• Copyright: 2005-07-08
• Publisher: Saunders

Summary

"This classic resource provides the necessary guidance for selecting, performing, and evaluating the results of new and established laboratory tests. By relating pathophysiology to analytical results in health and disease, it effectively bridges the gap between the clinical laboratory and medical management."--BOOK JACKET.

Table of Contents

SECTION I LABORATORY PRINCIPLES
Introduction to Principles of Laboratory Analyses and Safety	3	(38)
Edward W. Bermes, Jr.
Stephen E. Kahn
Donald S. Young
Concept of Solute and Solvent	3	(2)
Definitions	3	(1)
Expressing Concentrations of Solutions	3	(2)
Units of Measurement	5	(5)
International System of Units	5	(1)
Decimal Multiples and Submultiples of SI Units	6	(1)
Applications of SI in Laboratory Medicine	6	(2)
Problem Areas in the Use of SI Units	8	(1)
Conversion Rules	9	(1)
Standardized Reporting of Test Results	9	(1)
Chemicals and Reference Materials	10	(2)
Reagent Grade Water	10	(2)
Reagent Grade or Analytical Reagent Grade (AR) Chemicals	12	(1)
Ultrapure Reagents	12	(1)
Reference Materials	12	(1)
Basic Techniques and Procedures	12	(15)
Volumetric Sampling and Dispensing	12	(7)
Centrifugation	19	(2)
Measurement of Radioactivity	21	(2)
Gravimetry	23	(2)
Thermometry	25	(1)
Buffer Solutions	25	(1)
Procedures for Processing Solutions	26	(1)
Safety	27	(14)
Safety Program	28	(1)
Safety Equipment	28	(1)
Safety Inspections	28	(1)
Mandated Plans	29	(1)
Ergonomics Program	30	(1)
Hazards in the Laboratory	30	(11)
Specimen Collection and Processing	41	(20)
Donald S. Young
Edward W. Bermes, Jr.
Doris M. Haverstick
Specimen Collection	41	(13)
Blood	41	(8)
Urine	49	(3)
Feces	52	(1)
Spinal Fluid	52	(1)
Synovial Fluid	52	(1)
Amniotic Fluid (Amniocentesis)	53	(1)
Pleural, Pericardial, and Ascitic Fluids	53	(1)
Saliva	53	(1)
Swabs	53	(1)
Solid Tissue	53	(1)
Hair and Finger Nails	54	(1)
Handling of Specimens for Testing	54	(7)
Maintenance of Specimen Identification	54	(1)
Preservation of Specimens in Transit	54	(2)
Separation and Storage of Specimens	56	(1)
Transport of Specimens	56	(5)
SECTION II ANALYTICAL TECHNIQUES AND INSTRUMENTATION
Optical Techniques	61	(32)
L.J. Kricka
Nature of Light	61	(1)
Spectrophotometry	62	(10)
Basic Concepts	62	(2)
Instrumentation	64	(8)
Reflectance Photometry	72	(1)
Flame Emission Spectrophotometry	73	(1)
Atomic Absorption Spectrophotometry	73	(2)
Basic Concepts	73	(1)
Instrumentation	73	(1)
Interferences in Atomic Absorption Spectrophotometry	74	(1)
Fluorometry	75	(9)
Basic Concepts	75	(2)
Instrumentation	77	(6)
Limitations of Fluorescence Measurements	83	(1)
Phosphorescence	84	(1)
Chemiluminescence, Bioluminescence, and Electrochemiluminescence	84	(1)
Basic Concepts	84	(1)
Instrumentation	85	(1)
Limitations of Chemiluminescence and Electrochemiluminescence Measurements	85	(1)
Nephelometry and Turbidimetry	85	(8)
Basic Concepts	85	(2)
Measurement of Scattered Light	87	(1)
Instrumentation	88	(1)
Limitations of Light-Scattering Measurements	88	(5)
Electrochemistry and Chemical Sensors	93	(28)
Paul D'Orazio
Mark E. Meyerhoff
Potentiometry and Ion-Selective Electrodes	93	(8)
Basic Concepts	93	(1)
Types of Electrodes	94	(6)
Direct Potentiometry by ISE---Units of Measure and Reporting for Clinical Applications	100	(1)
Voltammetry/Amperometry	101	(4)
Basic Concepts	101	(2)
Applications	103	(2)
Conductometry	105	(1)
Coulometry	106	(1)
Optical Chemical Sensors	106	(2)
Basic Concepts	107	(1)
Applications	107	(1)
Biosensors	108	(5)
Enzyme-Based Biosensors With Amperometric Detection	108	(2)
Enzyme-Based Biosensors With Potentiometric and Conductometric Detection	110	(1)
Enzyme-Based Biosensors With Optical Detection	111	(1)
Affinity Sensors	112	(1)
In Vivo and Minimally Invasive Sensors	113	(8)
Electrophoresis	121	(20)
Raymond Karcher
James P. Landers
Basic Concepts and Definitions	121	(1)
Theory of Electrophoresis	121	(1)
Conventional Electrophoresis	122	(8)
Instrumentation	122	(3)
General Operations	125	(1)
Technical and Practical Considerations	126	(2)
Types of Electrophoresis	128	(2)
Capillary Electrophoresis	130	(5)
Instrumentation	131	(2)
Technical Considerations	133	(1)
Modes of Operation	134	(1)
Microchip Electrophoresis	135	(6)
Instrumentation	135	(1)
Fabrication of Microchips	136	(1)
Molecular Diagnostics Using Microchips	137	(4)
Chromatography	141	(24)
M. David Ullman
Carl A. Burtis
Basic Concepts	141	(1)
Separation Mechanisms	142	(3)
Ion-Exchange Chromatography	142	(1)
Partition Chromatography	143	(1)
Adsorption Chromatography	144	(1)
Affinity Chromatography	144	(1)
Size-Exclusion Chromatography	144	(1)
Resolution	145	(3)
Retention Factor (k')	146	(1)
Efficiency (N)	147	(1)
Planar Chromatography	148	(1)
Column Chromatography	149	(12)
Gas Chromatography	149	(6)
Liquid Chromatography	155	(6)
Qualitative and Quantitative Analyses	161	(4)
Analyte Identification	161	(1)
Analyte Quantification	161	(4)
Mass Spectrometry	165	(26)
Thomas Annesley
Alan L. Rockwood
Nicholas E. Sherman
Basic Concepts and Definitions	165	(2)
Instrumentation	167	(14)
Ion Source	167	(4)
Vacuum System	171	(1)
Mass Analyzers, Ion Detectors, and Tandem Mass Spectrometers	171	(9)
Detectors	180	(1)
Computer and Software	181	(1)
Clinical Applications	181	(4)
Gas Chromatography-Mass Spectrometry	182	(1)
Liquid Chromatography-Mass Spectrometry	182	(1)
Maldi-TOF Mass Spectrometry	183	(1)
SELDI Mass Spectrometry	184	(1)
ICP Mass Spectrometry	184	(1)
Proteomics	184	(1)
Analytical Problem of Ion Suppression	185	(6)
Principles of Clinical Enzymology	191	(28)
Renze Bais
Mauro Panteghini
Basic Principles	191	(7)
Enzyme Nomenclature	191	(1)
Enzymes as Proteins	192	(6)
Enzymes as Catalysts	198	(1)
Enzyme Kinetics	198	(9)
The Enzyme-Substrate Complex	198	(1)
Factors Governing the Rate of Enzyme-Catalyzed Reactions	199	(8)
Analytical Enzymology	207	(7)
Measurement of Reaction Rates	207	(2)
Units for Expressing Enzyme Activity	209	(1)
Measurement of Substrates	209	(1)
Optimization, Standardization, and Quality Control	210	(1)
Measurement of Enzyme Mass Concentration	211	(1)
Enzymes as Analytical Reagents	211	(2)
Analytical Applications of Immobilized Enzymes	213	(1)
Measurement of Isoenzymes and Isoforms	213	(1)
Diagnostic Enzymology	214	(5)
Factors Affecting Enzyme Levels in Plasma or Serum	214	(2)
Selection of Enzyme Tests	216	(3)
Principles of Immunochemical Techniques	219	(26)
I.J. Kricka
Basic Concepts	219	(2)
Antibodies	219	(1)
Immunogens	220	(1)
Antigen Antibody Binding	221	(3)
Binding Forces	221	(1)
Reaction Mechanism	222	(1)
Factors Influencing Binding	222	(1)
Types of Reactions	223	(1)
Qualitative Methods	224	(5)
Passive Gel Diffusion	224	(1)
Immunoelectrophoresis (IEP)	225	(2)
Western Blotting	227	(1)
Dot Blotting	228	(1)
Quantitative Methods	229	(10)
Radial Immunodiffusion and Electroimmunoassay	229	(1)
Turbidimetric and Nephelometric Assays	230	(1)
Labeled Immunochemical Assays	230	(9)
Interferences in Immunoassays	239	(1)
Other Immunochemical Techniques	239	(6)
Immunocytochemistry	239	(1)
Agglutination Assays	240	(5)
Nanotechnology and Microfabrication	245	(20)
Peter Wilding
Background	246	(1)
Fabrication and Materials	247	(3)
Manufacturing Techniques	247	(2)
Drilling	249	(1)
Bonding and Sealing	249	(1)
Microfluidics	250	(1)
Valving Sytems	250	(2)
Applications	252	(4)
Genomics	252	(1)
Hybridization Arrays	253	(1)
Nucleic Acid Sequencing	254	(1)
Drug Detection and Assay	254	(1)
Protein Chips	254	(1)
Immunoassay for Antibodies and Peptides	255	(1)
Enzymology	255	(1)
Metabolites	255	(1)
Cell Handling and Cell Culture	256	(1)
Other Applications	256	(1)
Surface Chemistry Issues	256	(1)
Limitations of Microtechnology	257	(1)
The Future	257	(8)
Automation in the Clinical Laboratory	265	(34)
James C. Boyd
Charles D. Hawker
Historical Overview	265	(2)
Processes Used in Automation	266	(1)
Laboratory Information Systems	266	(1)
Robotics	267	(1)
Types of Automation	267	(1)
Individual Steps in the Analytical Processes	267	(13)
Specimen Acquisition	268	(1)
Specimen Identification	268	(2)
Specimen Delivery to Laboratory	270	(1)
Specimen Preparation	271	(1)
Specimen Loading and Aspiration	271	(1)
On-Analyzer Specimen Delivery	272	(1)
Reagent Handling and Storage	273	(1)
Reagent Delivery	274	(1)
Chemical Reaction Phase	274	(2)
Measurement Approaches	276	(4)
Integrated Automation for the Clinical Laboratory	280	(9)
Workstations	281	(1)
Instrument Clusters	281	(1)
Workcells	282	(1)
Automated Specimen Transport	282	(2)
Automated Specimen Processing	284	(4)
Automated Specimen Sorting	288	(1)
Automated Specimen Storage and Retrieval	289	(1)
Practical Considerations	289	(3)
Evaluation of Requirements	289	(1)
Problems of Integration	290	(2)
Measuring the Impact of Automation	292	(1)
Development of Standards for Laboratory Automation	292	(1)
Other Areas of Automation	292	(7)
Urine Analyzers	292	(1)
Flow Cytometers	293	(1)
Hematology Cell Counters	293	(1)
Nucleic Acid Analyzers	293	(1)
Microtiter Plate Systems	294	(1)
Automated Pipetting Stations	294	(1)
POCT Analyzers	294	(1)
Remote Automated Laboratory System	294	(5)
Point-of-Care Testing	299	(24)
Christopher P. Price
Andrew St. John
Analytical and Technological Considerations	299	(11)
Requirements	299	(2)
Design	301	(2)
Examples of POCT Devices	303	(5)
Informatics and POCT	308	(2)
Implementation and Management Considerations	310	(5)
Establishment of Need	310	(1)
Organizing and Implementation of a Coordination Committee	311	(1)
POCT Policy and Accountability	311	(1)
Equipment Procurement and Evaluation	311	(1)
Training and Certification	312	(1)
Quality Control, Quality Assurance, and Audit	312	(1)
Maintenance and Inventory Control	313	(1)
Documentation	314	(1)
Accreditation and Regulation of POCT	315	(1)
Future of POCT	315	(8)
SECTION III PRINCIPLES OF LABORATORY MEDICINE
Introduction to Laboratory Medicine and Evidence-Based Laboratory Medicine	323	(30)
Christopher P. Price
Patrick M.M. Bossuyt
David E. Bruns
Concepts, Definitions, and Relationships	323	(1)
What Is Laboratory Medicine?	323	(1)
Clinical Chemistry and Laboratory Medicine	324	(1)
Clinical Chemistry, Laboratory Medicine, and Evidence-Based Laboratory Medicine	324	(1)
Evidence-Based Medicine---What Is It?	324	(1)
Definition and Goals of Evidence-Based Medicine	324	(1)
The Practice of Evidence-Based Medicine	325	(1)
Evidence-Based Medicine and Laboratory Medicine	325	(3)
What is Evidence-Based Laboratory Medicine?	325	(1)
Types of Diagnostic Questions Addressed in Laboratory Medicine	326	(1)
Test Results Alone Do Not Produce Clinical Outcomes	326	(2)
Using the Test Result	328	(1)
The Clinical Setting of an Outcome Study	328	(1)
Characterization of Diagnostic Accuracy of Tests	328	(2)
Study Design	328	(1)
The Reporting of Studies of Diagnostic Accuracy and the Role of the STARD Initiative	329	(1)
Outcomes Studies	330	(6)
What Are Outcomes Studies?	330	(2)
Why Outcomes Studies?	332	(1)
Design of Studies of Medical Outcomes	333	(3)
Systematic Reviews of Diagnostic Tests	336	(2)
Why Systematic Reviews?	336	(1)
Conducting a Systematic Review	336	(2)
Economic Evaluations of Diagnostic Testing	338	(3)
A Hierarchy of Evidence	338	(1)
Methodologies for Economic Evaluations	338	(2)
Quality of Economic Evaluations	340	(1)
Perspectives of Economic Evaluations	340	(1)
Choice of Outcome Measures	340	(1)
Use of Economic Evaluations in Decision Making	341	(1)
Clinical Practice Guidelines	341	(4)
What Is a Clinical Practice Guideline?	341	(1)
A Transparent Process Must Be Used in the Development of Guidelines	341	(1)
Steps in the Development of Guidelines	342	(3)
Obtaining External Review and Updating the Guidelines	345	(1)
Clinical Audit	345	(2)
Audit to Help Solve Problems	346	(1)
Monitoring Workload and Demand	346	(1)
Monitoring the Introduction of a New Test	346	(1)
Monitoring Adherence to Best Practice	347	(1)
Applying the Principles of Evidence-Based Laboratory Medicine in Routine Practice	347	(6)
Selection and Analytical Evaluation of Methods---With Statistical Techniques	353	(56)
Kristian Linnet
James C. Boyd
Method Selection	353	(2)
Medical Criteria	353	(1)
Analytical Performance Criteria	354	(1)
Other Criteria	354	(1)
Basic Concepts in Relation to Analytical Methods	355	(7)
Calibration	355	(1)
Trueness and Accuracy	356	(1)
Precision	357	(1)
Precision Profile	358	(1)
Linearity	359	(1)
Analytical Measurement Range	359	(1)
Limit of Detection	359	(2)
Analytical Sensitivity	361	(1)
Limit of Quantitation	361	(1)
Analytical Specificity and Interference	361	(1)
Analytical Goals	362	(6)
Qualitative Methods	363	(5)
Method Comparison	368	(28)
Basic Error Model	368	(2)
Method Comparison Data Model	370	(1)
Preliminary Practical Work in Relation to a Method Comparison Study	371	(1)
Planning a Method Comparison Study	371	(1)
Distribution of Differences Plot (DoD plot)	371	(5)
Verification of Distribution of Differences in Relation to Specified Limits	376	(1)
Difference (Bland-Altman) Plot	376	(1)
A Caution Against Incorrect Interpretation of Paired t-Tests in Method Comparison Studies	377	(1)
Regression Analysis	378	(17)
Discussion of Application of Regression Analysis	395	(1)
Discussion of Method Comparison Approaches	395	(1)
Monitoring Serial Results	396	(1)
Traceability and Measurement Uncertainty	397	(5)
Traceability	397	(1)
The Uncertainty Concept	398	(4)
Guidelines, Regulatory Demands, and Accreditation	402	(1)
Software Packages	403	(6)
Clinical Evaluation of Methods	409	(16)
Edward K. Shultz
Constantin Aliferis
Dominik Aronsky
Spectrum	409	(1)
Classification Bias	410	(1)
Sensitivity and Specificity	411	(1)
Receiver Operating Characteristic Curves	412	(1)
Interpreting a Test	413	(7)
Odds Ratio	413	(1)
Likelihood Ratio	413	(1)
Bayes' Theorem	414	(1)
Combination Testing	415	(1)
Multivariate Data Analysis	416	(2)
Data Analysis Methods for Very Large Numbers of Variables	418	(1)
Clinical Examples	419	(1)
Model Validation	420	(1)
Cost Effectiveness and Outcomes Research	420	(5)
Establishment and Use of Reference Values	425	(24)
Helge Erik Solberg
The Concept of Reference Values	425	(2)
Interpretation by Comparison	425	(1)
Normal Values---An Obsolete Term	425	(1)
Terminology	426	(1)
Types of Reference Values	426	(1)
Requirements	427	(1)
Selection of Reference Individuals	427	(3)
Concept of Health in Relation to Reference Values	427	(1)
Strategies for Selection of Reference Individuals	427	(3)
Selection Criteria and Evaluation of Subjects	430	(1)
Partitioning of the Reference Group	430	(1)
Specimen Collection	430	(2)
Two Philosophies of Standardization	431	(1)
Standardization Schemes	431	(1)
The Necessity for Additional Information	431	(1)
Analytical Procedures and Quality Control	432	(1)
Statistical Treatment of Reference Values	433	(9)
Statistical Concepts	433	(1)
Determination of Reference Limits: General Considerations	434	(2)
Partitioning of Reference Values	436	(1)
Inspection of Distribution	436	(1)
Identification and Handling of Erroneous Values	437	(1)
Methods for Determining Reference Values	437	(5)
Presentation of an Observed Value in Relation to Reference Values	442	(1)
Additional Topics	443	(6)
Transferability of Reference Values	443	(1)
Multivariate, Population-Based Reference Regions	443	(2)
Subject-Based Reference Values	445	(1)
Dynamic Versus Static Interpretation of Clinical Chemistry Data	446	(3)
Preanalytical Variables and Biological Variation	449	(26)
Donald S. Young
Edward W. Bermes, Jr.
Preanalytical Variables	449	(18)
Controllable Variables	449	(10)
Noncontrollable Variables	459	(8)
Biological Variability	467	(8)
Overview	467	(1)
Delta Check	468	(1)
Calculating Total Variation	469	(1)
Reference Change Values	469	(1)
Index of Individuality	469	(1)
Index of Heterogeneity	470	(1)
Reliability Coefficient	470	(1)
Quality Specifications for Total Error Allowable	470	(1)
Assessment of Mode of Reporting Test Results	471	(4)
Clinical Laboratory Informatics	475	(10)
Kent A. Spackman
Computing Fundamentals	475	(3)
Computer Basics	475	(1)
Hardware	476	(1)
Rate of Change of Computing Capacity	477	(1)
Computer Networks	478	(1)
Laboratory Information Systems	478	(4)
LIS Modules	478	(3)
Life Cycle of Information Systems	481	(1)
Regulatory Issues	482	(1)
Security and Confidentiality	482	(1)
Pathology Informatics Resources	482	(3)
Quality Management	485	(48)
James O. Westgard
George G. Klee
Fundamentals of Total Quality Management	485	(2)
Fundamental Concepts	485	(1)
Fundamental Principles	486	(1)
Total Quality Management of the Clinical Laboratory	487	(1)
Laboratory Error and the Six Sigma Process	488	(2)
Number of Errors Made in the Clinical Laboratory	488	(1)
Six Sigma Principles and Metrics	488	(2)
Elements of a Quality Assurance Program	490	(1)
Commitment	491	(1)
Facilities and Resources	491	(1)
Technical Competence	491	(1)
Technical Procedures	491	(1)
Problem-Solving Mechanism	491	(1)
Control of Preanalytical Variables	491	(3)
Systems Analysis	491	(1)
Types of Preanalytical Variables	492	(2)
Control of Analytical Variables	494	(3)
Choice of Analytical Methodology	495	(1)
Reference Materials and Calibration	495	(1)
Documentation of Analytical Protocols	496	(1)
Establishment of Reference Intervals	496	(1)
Monitoring Technical Competence	496	(1)
Inventory Control of Materials	496	(1)
Input Control of Materials	497	(1)
Monitoring Method Changes	497	(1)
Control of Analytical Quality Using Stable Control Materials and Control Charts	497	(13)
Control Materials	497	(1)
General Principles of Control Charts	498	(1)
Performance Characteristics of a Control Procedure	498	(12)
Control of Analytical Quality Using Patient Data	510	(5)
Individual Patient Results	510	(2)
Multiple Patients	512	(3)
External Quality Assessment and Proficiency Testing Programs	515	(4)
External Quality Assessment	515	(1)
Proficiency Testing and Laboratory Accreditation	516	(3)
Identifying the Sources of Analytical Errors	519	(1)
Physical Inspection	519	(1)
Relationship of Type and Source of Error	519	(1)
Method Evaluation Experiments	520	(1)
Optimization Techniques	520	(1)
Quality Initiatives	520	(13)
Joint Committee for Traceability in Laboratory Medicine (JCTLM)	520	(1)
International Organization for Standardization	521	(2)
Malcolm Baldridge National Quality Award	523	(10)
SECTION IV ANALYTES
Amino Acids, Peptides, and Proteins	533	(64)
A. Myron Johnson
Amino Acids	533	(8)
Basic Biochemistry	533	(6)
Clinical Implications	539	(1)
Analysis of Amino Acids	540	(1)
Peptides and Proteins	541	(56)
Basic Biochemistry	541	(2)
Plasma Proteins	543	(21)
Complement Proteins	564	(5)
Immunoglobulins	569	(6)
Proteins in Other Body Fluids	575	(5)
Miscellaneous Proteins	580	(2)
Analysis of Proteins	582	(15)
Enzymes	597	(48)
Mauro Panteghini
Renze Bais
Wouter W. van Solinge
Muscle Enzymes	597	(7)
Creatine Kinase	598	(3)
Lactate Dehydrogenase	601	(2)
Aldolase	603	(1)
Glycogen Phosphorylase	603	(1)
Liver Enzymes	604	(12)
Aminotransferases	604	(3)
Glutamate Dehydrogenase	607	(1)
Alkaline Phosphatase	607	(4)
5'-Nucleotidase	611	(1)
Gamma-Glutamyl Transferase	612	(1)
Glutathione S-Transferase	613	(1)
Cholinesterase	614	(2)
Pancreatic Enzymes	616	(7)
Amylase	616	(3)
Lipase	619	(3)
Trypsin	622	(1)
Chymotrypsin	623	(1)
Elastase-1	623	(1)
Bone Enzymes	623	(2)
Alkaline Phosphatase (Bone Isoform)	624	(1)
Acid Phosphatase (Tartrate-Resistant)	624	(1)
Red Cell Enzymes	625	(20)
The Embden-Meyerhof Pathway	626	(4)
Hexose Monophosphate Pathway	630	(1)
Rapoport-Luebering Cycle	631	(1)
Glutathione Pathway	631	(1)
Purine-Pyrimidine Metabolism	632	(1)
Methemoglobin Reduction	633	(1)
Detection of Hereditary Red Cell Enzyme Deficiencies	633	(1)
Methodology	634	(11)
Cytokines	645	(100)
Manuel Santos Rosa
Anabela Mota Pinto
Background Information	645	(10)
History	645	(1)
Rationale for Measurement	645	(1)
General Characteristics	646	(1)
Nomenclature	646	(1)
Classification	646	(1)
Biochemistry	647	(2)
Cytokine Receptors	649	(1)
Clinical Significance	649	(6)
Individual Cytokines	655	(65)
Interleukin-1	655	(5)
Interleukin-2	660	(4)
Interleukin-3	664	(2)
Interleukin-4	666	(3)
Interleukin-5	669	(2)
Interleukin-6	671	(4)
Interleukin-7	675	(1)
Interleukin-8	676	(1)
Interleukin-9	676	(2)
Interleukin-10	678	(2)
Interleukin-11	680	(2)
Interleukin-12	682	(4)
Interleukin-13	686	(2)
Interleukin-14	688	(1)
Interleukin-15	689	(2)
Interleukin-16	691	(2)
Interleukin-17	693	(1)
Interleukin-18	694	(1)
Interferons	695	(7)
Tumor Necrosis Factors	702	(6)
Chemokines	708	(12)
Measurements of Cytokines	720	(25)
Requirements	720	(1)
Sample Collection and Storage	721	(1)
Principles of Cytokine Assays	721	(24)
Tumor Markers	745	(52)
Daniel W. Chan
Ronald A. Booth
Eleftherios P. Diamandis
Cancer	745	(1)
Historical Background	746	(1)
Clinical Applications	747	(2)
Evaluating Clinical Utility	749	(3)
Reference Values	749	(1)
Predictive Value Model	749	(1)
Distribution of Marker Values	750	(1)
Disease Management	750	(2)
Clinical Guidelines	752	(1)
Analytical Methodology	752	(2)
Mass Spectrometry	752	(2)
Microarrays	754	(1)
Enzymes	754	(11)
Alkaline Phosphatase	755	(1)
Creatine Kinase	756	(1)
Lactate Dehydrogenase	756	(1)
Neuron-Specific Enolase	756	(1)
Prostatic Acid Phosphatase	756	(1)
Kallikreins	756	(1)
Prostate-Specific Antigen	757	(4)
Human Glandular Kallikrein 2	761	(1)
The Urokinase-Plasminogen Activator System	761	(1)
Cathepsins	762	(1)
Matrix Metalloproteinases	763	(1)
Tumor-Associated Trypsin Inhibitor	763	(1)
Telomerase	764	(1)
Hormones	765	(1)
Adrenocorticotropic Hormone	765	(1)
Calcitonin	765	(1)
Human Chorionic Gonadotropin	766	(1)
Oncofetal Antigens	766	(3)
Alpha Fetoprotein	767	(1)
Carcinoembryonic Antigen	768	(1)
Cytokeratins	769	(1)
Tissue Polypeptide Antigen	769	(1)
Tissue Polypeptide-Specific Antigen	769	(1)
Cytokeratin 19 Fragments	769	(1)
Squamous Cell Carcinoma Antigen	769	(1)
Carbohydrate Markers	770	(3)
CA 15-3	770	(1)
CA 549	771	(1)
CA 27.29	771	(1)
Mucinlike Carcinoma-Associated Antigen	771	(1)
CA 125	771	(1)
Other Ovarian Cancer Biomarkers	772	(1)
DU-PAN-2	772	(1)
Blood Group Antigens	773	(1)
CA 19-9	773	(1)
CA 50	773	(1)
CA 72-4	773	(1)
CA 242	774	(1)
Proteins	774	(3)
Immunoglobulin	774	(1)
Bladder Cancer Markers	775	(1)
Heat Shock Proteins	776	(1)
S-100 Proteins	776	(1)
Autoantibodies	776	(1)
Thyroglobulin and Antibodies	777	(1)
Chromogranins	777	(1)
Receptors and Other Markers	777	(3)
Estrogen and Progesterone Receptors	777	(2)
Androgen Receptor	779	(1)
Hepatocyte Growth Factor Receptor (c-Met)	779	(1)
Epidermal Growth Factor Receptor	779	(1)
Genetic Markers	780	(6)
Oncogenes	780	(3)
Tumor Suppressor Genes	783	(2)
Single Nucleotide Polymorphisms	785	(1)
Miscellaneous Markers	786	(11)
Markers of Angiogenesis	786	(1)
Cell-Free Nucleic Acids	786	(1)
Circulating Cancer Cells	786	(11)
Kidney Function Tests	797	(40)
Edmund Lamb
David J. Newman
Christopher P. Price
Creatinine	797	(4)
Biochemistry and Physiology	797	(1)
Clinical Significance	798	(1)
Analytical Methodology	798	(3)
Urea	801	(2)
Biochemistry and Physiology	801	(1)
Clinical Significance	802	(1)
Analytical Methodology	802	(1)
Uric Acid	803	(5)
Biochemistry and Physiology	803	(2)
Clinical Significance	805	(2)
Analytical Methodology	807	(1)
Screeening for Kidney Disease	808	(4)
Urinalysis	808	(3)
Microscopic Examination of Urine	811	(1)
New Instrumental Techniques	812	(1)
Quantitative Assessment of Glomerular Permeability: Proteinuria	812	(6)
Clinical Significance	812	(1)
Sample Collection for Total Protein and Albumin Measurement	812	(1)
Measurement of Total Protein	813	(1)
Measurement of Individual Proteins	813	(4)
Characterization of Proteinuria	817	(1)
Assessment of Kidney Function: Estimation of Glomerular Filtration Rate	818	(19)
The Concept of Clearance	818	(1)
Markers Used	818	(6)
Glomerular Filtration Rate at the Extremes of Age	824	(1)
Recommendations and Reference Intervals	825	(12)
Carbohydrates	837	(66)
David B. Sacks
Chemistry of Carbohydrates	837	(4)
Monosaccharides	837	(2)
Disaccharides	839	(1)
Polysaccharides	839	(1)
Glycoproteins	840	(1)
Metabolism of Carbohydrates	841	(12)
Digestion and Absorption	841	(1)
Intermediary Metabolism	841	(1)
Regulation of Blood Glucose Concentration	841	(12)
Diabetes Mellitus	853	(11)
Classification	854	(1)
Pathogenesis of Type 1 Diabetes Mellitus	855	(1)
Pathogenesis of Type 2 Diabetes Mellitus	856	(3)
Diagnosis	859	(2)
Gestational Diabetes Mellitus	861	(1)
Chronic Complications of Diabetes Mellitus	862	(1)
Role of the Clinical Laboratory in Diabetes Mellitus	863	(1)
Hypoglycemia	864	(4)
Hypoglycemia in Neonates and Infants	865	(1)
Fasting Hypoglycemia in Adults	865	(1)
Postprandial Hypoglycemia	866	(1)
Hypoglycemia in Diabetes Mellitus	867	(1)
Tolbutamide Tolerance Test	867	(1)
Determination of Glucose in Body Fluids	868	(7)
Specimen Collection and Storage	868	(1)
Methods	869	(2)
Reference Intervals	871	(1)
Measurement of Glucose in Urine	872	(1)
Self-Monitoring of Blood Glucose	873	(2)
Minimally Invasive Monitoring of Blood Glucose	875	(1)
Ketone Bodies	875	(2)
Clinical Significance	876	(1)
Determination of Ketone Bodies in Body Fluids	876	(1)
Lactate and Pyruvate	877	(1)
Clinical Significance	877	(1)
Methods for Measuring Lactate and Pyruvate in Body Fluids	878	(1)
Glycated Proteins	878	(8)
Glycated Hemoglobin	879	(5)
Fructosamine	884	(2)
Advanced Glycation End Products	886	(1)
Urinary Albumin Excretion	886	(2)
Clinical Significance	886	(1)
Methods for Measuring Urinary Albumin Excretion	887	(1)
Inborn Errors of Carbohydrate Metabolism	888	(2)
Disorders of Galactose Metabolism	888	(1)
Disorders of Fructose Metabolism	889	(1)
Disorders of Pentose Metabolism	889	(1)
Other Urinary Sugars	889	(1)
Methods for Measuring Individual Sugars	889	(1)
Glycogen Storage Disease	890	(13)
Type I (Glucose-6-Phosphatase Deficiency)	890	(1)
Type II (Acid α-Glucosidase Deficiency)	891	(1)
Type III (Amylo-1,6-Glucosidase Deficiency)	891	(1)
Type IV (Branching Enzyme Deficiency)	891	(1)
Type V (Muscle Phosphorylase Deficiency)	891	(1)
Type VI (Liver Phosphorylase or Phosphorylase Kinase Deficiency)	891	(1)
Type VII (Muscle Phosphofructokinase Deficiency)	891	(12)
Lipids, Lipoproteins, Apolipoproteins, and Other Cardiovascular Risk Factors	903	(80)
Nader Rifai
G. Russell Warnick
Basic Biochemistry	903	(21)
Basic Lipids	903	(12)
Lipoproteins	915	(1)
Apolipoproteins	916	(2)
Lipoprotein Metabolism	918	(4)
Reference Lipid, Lipoprotein Cholesterol, and Apolipoprotein Levels	922	(2)
Clinical Significance	924	(14)
Association With Coronary Heart Disease	924	(4)
Disorders of Lipoprotein Metabolism	928	(4)
Diagnosis of Lipoprotein Disorders	932	(2)
Management of Lipoprotein Disorders	934	(4)
Measurement of Lipids, Lipoproteins, and Apolipoproteins	938	(24)
Historical Perspective and Background	938	(2)
Lipids and Lipoproteins	940	(14)
Sources of Variation in Lipid and Lipoprotein Measurements	954	(4)
Apolipoproteins	958	(2)
Lipoprotein(a)	960	(1)
Apolipoprotein E	961	(1)
Other Cardiac Risk Factors	962	(21)
High-Sensitivity C-Reactive Protein	962	(5)
Homocysteine	967	(16)
Electrolytes and Blood Gases	983	(36)
Mitchell G. Scott
Vicky A. LeGrys
James Stacey Klutts
Electrolytes	983	(9)
Specimens for Electrolyte Determinations	983	(1)
Sodium	984	(1)
Potassium	984	(3)
Electrolyte Exclusion Effect	987	(2)
Chloride	989	(1)
Bicarbonate (Total Carbon Dioxide)	990	(2)
Plasma and Urine Osmolality	992	(2)
Principles of Osmotic Pressure and Osmosis	992	(2)
Sweat Testing	994	(4)
Qualitative Screening Tests	995	(1)
Quantitative Confirmatory Tests	995	(1)
Reference Intervals for Sweat Chloride	996	(1)
Sweat Stimulation and Collection	996	(2)
Sources of Error in Sweat Testing	998	(1)
Sweat Testing Quality Assurance	998	(1)
Blood Gases and pH	998	(21)
Behavior of Gases	999	(2)
Application of the Henderson-Hasselbalch Equation in Blood Gas Measurements	1001	(1)
Oxygen in Blood	1002	(4)
Tonometry	1006	(1)
Determination of PCO2, PO2, and pH	1006	(7)
Temperature Correction of Measured pH, PCO2, and PO2	1013	(1)
Continuous and Noninvasive Monitoring of Blood Gases	1014	(5)
Hormones	1019	(14)
Michael Kleerekoper
Classification	1019	(1)
Polypeptide or Protein Hormones	1019	(1)
Steroid Hormones	1019	(1)
Amino Acid-Related Hormones	1019	(1)
Release and Action of Hormones	1019	(7)
Growth and Development	1025	(1)
Homeostatic Control of Metabolic Pathways	1025	(1)
Regulation of the Production, Use, and Storage of Energy	1026	(1)
Role of Hormone Receptors	1026	(1)
Cell-Surface Receptors	1026	(1)
Intracellular Receptors	1027	(1)
Postreceptor Actions of Hormones	1027	(3)
Cell-Surface Receptors	1027	(2)
Intracellular Receptors	1029	(1)
Clinical Disorders of Hormones	1030	(1)
Measurements of Hormones and Related Analytes	1030	(3)
Bioassay Techniques	1030	(1)
Receptor-Based Assays	1030	(1)
Immunoassay Techniques	1030	(1)
Instrumental Techniques	1031	(2)
Catecholamines and Serotonin	1033	(42)
Thomas G. Rosano
Graeme Eisenhofer
Ronald J. Whitley
Chemical Structure	1033	(1)
Biosynthesis, Release, and Metabolism	1033	(6)
Biosynthesis	1034	(1)
Storage and Release	1035	(1)
Uptake and Metabolism	1036	(3)
Physiology of Catecholamine and Serotonin Systems	1039	(6)
Central Nervous System	1040	(1)
Sympathetic Nervous System	1041	(2)
Adrenal Medullary System	1043	(1)
Peripheral Dopaminergic System	1044	(1)
Enteric Nervous System	1045	(1)
Clinical Applications	1045	(9)
Pheochromocytoma	1045	(4)
Neuroblastoma	1049	(1)
Dysautonomias and Genetic Disorders	1050	(2)
Carcinoid	1052	(2)
Analytical Methodology	1054	(21)
Catecholamines and Metabolites	1054	(8)
Serotonin and Metabolites	1062	(13)
Vitamins and Trace Elements	1075	(90)
Alan Shenkin
Malcolm Baines
Gordon S. Fell
T.D.G. Lyon
Nutritional Assessment and Monitoring	1076	(3)
Protein-Energy Status	1076	(1)
Vitamin and Trace Element Status	1077	(1)
Enzymes or Metabolites	1077	(1)
Markers of Antioxidant Status	1077	(1)
Analytical Factors	1078	(1)
Vitamins	1079	(39)
Vitamin A	1079	(5)
Vitamin D	1084	(1)
Vitamin E	1084	(3)
Vitamin K	1087	(3)
Vitamin B1---Thiamine	1090	(4)
Vitamin B2---Riboflavin	1094	(3)
Vitamin B6---Pyridoxine, Pyridoxamine, and Pyridoxal	1097	(3)
Vitamin B12---Cyanocobalamin	1100	(5)
Vitamin C---Ascorbic Acid	1105	(2)
Biotin	1107	(2)
Folic Acid	1109	(5)
Niacin and Niacinamide	1114	(2)
Pantothenic Acid	1116	(2)
Trace Elements	1118	(47)
Classification	1118	(1)
Dose-Effect Relationships	1118	(1)
Chemistry	1119	(1)
Biochemistry/Homeostasis	1119	(1)
Inborn Errors	1119	(1)
Interactions	1119	(1)
Laboratory Assessment of Trace Element Status	1120	(1)
Analytical Considerations	1120	(2)
Individual Trace Elements	1122	(19)
Other Possibly Essential Elements	1141	(24)
Hemoglobin, Iron, and Bilirubin	1165	(44)
Trefor Higgins
Ernest Beutler
Basil T. Doumas
Hemoglobin	1165	(21)
Biochemistry	1165	(4)
Physiological Role	1169	(1)
Analytical Methodology	1170	(8)
Clinical Significance	1178	(8)
Iron	1186	(7)
Biochemistry	1186	(2)
Analytical Methodology	1188	(4)
Clinical Significance	1192	(1)
Bilirubin	1193	(16)
Chemistry	1193	(1)
Biochemistry	1194	(1)
Analytical Methodology	1195	(3)
Clinical Significance	1198	(11)
Porphyrins and Disorders of Porphyrin Metabolism	1209	(28)
Allan C. Deacon
Sharon D. Whatley
George H. Elder
Porphyrin Chemistry	1209	(2)
Structure and Nomenclature	1209	(1)
Chelation of Metals	1209	(1)
Spectral Properties	1209	(1)
Solubility	1210	(1)
Heme Biosynthesis	1211	(2)
Enzymes of Heme Biosynthesis	1211	(2)
Excretion of Heme Precursors	1213	(1)
Regulation of Heme Biosynthesis	1213	(1)
Abnormalities of Porphyrin Metabolism	1214	(7)
The Porphyrias	1214	(6)
Abnormalities of Porphyrin Metabolism Not Caused by Porphyria	1220	(1)
Pseudoporphyria	1221	(1)
Laboratory Diagnosis of Porphyria	1221	(2)
Patients With Symptoms of Porphyria	1221	(2)
Relatives of Patients With Porphyria	1223	(1)
Analytical Methods	1223	(14)
Methods for Metabolites	1223	(3)
Methods for Blood Porphyrins	1226	(1)
Analysis of Plasma Porphyrins	1226	(1)
Enzyme Measurements	1226	(3)
DNA Analysis	1229	(8)
Therapeutic Drugs and Their Management	1237	(50)
Thomas P. Mayer
Leslie M. Shaw
Definitions	1238	(1)
Basic Concepts	1238	(10)
Mechanism of Action	1238	(2)
Pharmacokinetics	1240	(3)
Drug Disposition	1243	(4)
Clinical Utility	1247	(1)
Analytical Considerations	1248	(1)
Analytical Techniques	1248	(1)
Issues of Concern	1249	(1)
Specific Drug Groups	1249	(31)
Antiepileptic Drugs	1249	(7)
Cardioactive Drugs	1256	(5)
Bronchodilators	1261	(1)
Antibiotics	1262	(7)
Antiretrovirals	1269	(1)
Antipsychotic Drugs	1269	(3)
Antimetabolites	1272	(2)
Immunosuppressants	1274	(6)
Clinical Applications	1280	(7)
Clinical Toxicology	1287	(84)
William H. Porter
Basic Information	1287	(5)
Clinical Considerations	1288	(1)
Analytical Considerations	1289	(1)
Toxic Syndromes	1289	(3)
Abstinence Syndromes	1292	(1)
Screening Procedures for Detection of Drugs	1292	(4)
Spot Tests	1292	(1)
Determination of Volatiles by Serum Osmol Gap	1292	(1)
Immunoassay	1293	(1)
Planar Chromatography	1293	(1)
Gas Chromatography	1294	(2)
High-Performance Liquid Chromatography	1296	(1)
Pharmacology and Analysis of Specific Drugs and Toxic Agents	1296	(54)
Agents That Cause Cellular Hypoxia	1296	(4)
Alcohols	1300	(4)
Analgesics (Nonprescription)	1304	(4)
Drugs Related to the Anticholinergic Toxidrome	1308	(5)
Ethylene Glycol	1313	(1)
Toxic Metals/Iron	1314	(1)
Organophosphate and Carbamate Insecticides	1315	(2)
Drugs of Abuse	1317	(33)
On-Site Drug Testing	1350	(21)
Sequential Competitive Binding Microparticle Capture Immunoassay	1350	(1)
Homogenous Microparticle Capture Immunochromatography	1351	(1)
Solid Phase Competitive Sequential Enzyme Immunoassay	1351	(1)
Latex-Agglutination-Inhibition Immunoassay	1351	(20)
Toxic Metals	1371	(22)
Thomas P. Moyer
Mary F. Burritt
John Butz
Basic Concepts	1371	(3)
Prevalence of Metal-Based Toxicity	1371	(1)
Diagnosing Toxicity	1372	(1)
Classification of Metals	1372	(1)
Occupational Monitoring	1373	(1)
Analytical Methods	1373	(1)
Specific Metals	1374	(19)
Aluminum	1374	(1)
Antimony	1375	(1)
Arsenic	1376	(1)
Beryllium	1377	(1)
Cadmium	1377	(1)
Chromium	1378	(1)
Cobalt	1378	(1)
Copper	1378	(1)
Iron	1379	(1)
Lead	1379	(2)
Manganese	1381	(1)
Mercury	1381	(2)
Nickel	1383	(1)
Platinum	1383	(1)
Selenium	1383	(1)
Silicon	1384	(1)
Silver	1384	(1)
Thallium	1384	(9)
SECTION V MOLECULAR DIAGNOSTICS AND GENETICS
Principles of Molecular Biology and Approaches to Nucleic Acid Isolation	1393	(14)
Y.M. Dennis Lo
Rossa W.K. Chiu
Landmark Developments in Genetics and Molecular Diagnostics	1393	(1)
Nucleic Acid Chemistry, Biochemistry, and Biology	1394	(6)
Molecular Compositions and Structures of DNA and RNA	1394	(1)
Chromosome Structure	1395	(1)
Replication, Transcription, and Translation	1396	(1)
Genetics and Epigenetics	1397	(1)
Nuclear and Mitochondrial Genomes	1398	(1)
Circulating Nucleic Acids	1399	(1)
Nucleic Acid Isolation	1400	(1)
DNA Isolation	1400	(1)
RNA Isolation	1401	(1)
Assessment of Nucleic Acid Yield and Quality	1401	(1)
The Human Genome Project	1401	(6)
Nucleic Acid Techniques	1407	(44)
Carl T. Wittwer
Noriko Kusukawa
Genomes and Nucleic Acid Alterations	1407	(3)
Human Genome	1407	(3)
Bacterial Genomes and Sequence Alterations	1410	(1)
Viral Genomes and Sequence Alterations	1410	(1)
Nucleic Acid Enzymes	1410	(1)
Amplification Techniques	1411	(8)
Polymerase Chain Reaction (PCR)---Target Amplification	1412	(4)
Other Forms of Target Amplification	1416	(2)
Other Approaches to Amplification	1418	(1)
Endpoint Quantification in Amplification Assays	1419	(1)
Detection Techniques	1419	(2)
Generic Measurement and Visualization of Nucleic Acids	1419	(1)
Reporter Molecules and Labeled Probes	1419	(2)
Discrimination Techniques	1421	(24)
Electrophoresis	1421	(6)
Alternatives to Electrophoresis	1427	(2)
Hybridization Assays---Principles	1429	(3)
Hybridization Assays---Examples	1432	(4)
Real-Time PCR	1436	(5)
Melting Analysis	1441	(3)
Comparison of Closed-Tube SNP Genotyping Methods	1444	(1)
Conclusion	1445	(6)
Design and Operation of the Molecular Diagnostics Laboratory	1451	(6)
Anthony A. Killeen
Introduction	1451	(1)
Centralization or Decentralization?	1451	(1)
Choosing a Test Menu	1451	(1)
Space and Design Considerations	1452	(1)
Operational Considerations	1452	(3)
Documents, Records, Sample Retention	1452	(1)
Personnel	1453	(1)
Result Reporting	1453	(1)
Quality Assurance and Quality Improvement	1454	(1)
Proficiency Testing	1455	(1)
Summary	1455	(2)
Molecular Genetics and Diagnosis of Hematopoietic Neoplasms	1457	(26)
Kojo S.J. Elenitoba-Johnson
Antigen-Receptor Gene Rearrangements for Determination of Clonality	1458	(5)
Molecular Genetic Basis for Immunoglobulin-Gene Rearrangements	1458	(2)
Molecular Genetic Basis for T-Cell Receptor Gene Rearrangements	1460	(1)
Southern Blot Hybridization Analysis for Antigen-Receptor (Ig or TCR) Gene Rearrangements	1461	(1)
Polymerase Chain Reaction Analysis of Antigen-Receptor Gene Rearrangements	1462	(1)
Lymphoma-Specific Recurrent Chromosomal Translocations	1463	(3)
Southern Blot Hybridization Analysis for the Detection of Chromosomal Translocations	1464	(1)
Polymerase Chain Reaction Analysis for Detection of Chromosomal Translocations	1464	(2)
Molecular Genetics of Leukemias	1466	(6)
Acute Myeloid Leukemias	1466	(3)
Chronic Leukemias of Myeloid/Monocytic Lineage	1469	(2)
Use of Reverse-Transcription Polymerase Chain Reaction in Chromosomal Translocations	1471	(1)
Oncogene and Tumor Suppressor Gene Mutations in Hematopoietic Malignancies	1472	(2)
Minimal Residual Disease Detection and Monitoring	1474	(1)
Detection of Viral Genomes	1475	(1)
Epstein-Barr Virus	1475	(1)
In Situ Hybridization	1476	(1)
Potential of Microarrays in Molecular Diagnostics of Hematological Malignancies	1476	(1)
Conclusions	1476	(7)
Inherited Diseases	1483	(56)
Cindy L. Vnencak-Jones
Diseases with Mendelian Inheritance	1483	(19)
Autosomal Recessive Diseases	1483	(8)
Autosomal Dominant Diseases	1491	(5)
X-Linked Diseases	1496	(6)
Diseases with Nonmendelian Inheritance	1502	(11)
Mitochondrial DNA Diseases	1502	(2)
Imprinting	1504	(2)
Complex Diseases	1506	(7)
Reporting of Test Results	1513	(26)
Identity Assessment	1539	(16)
Thomas M. Williams
Victor W. Weedn
Malek Kamoun
Variation in the Human Genome	1539	(2)
Genetic Variation Useful in Identity Testing	1539	(1)
Exclusion of Tested Individuals	1540	(1)
Likelihood of Inclusion of Tested Individuals	1541	(1)
Samples Employed for Identity Testing	1541	(1)
Forensic DNA Typing	1541	(4)
Forensic Applications	1541	(1)
Genetic Systems Used in Forensic Identification	1542	(2)
Instrumentation Used in Forensic Laboratories	1544	(1)
Quality Assurance and Accreditation in Forensic DNA Analysis	1544	(1)
Statistical Interpretation	1545	(1)
Convicted Offender Databases	1545	(1)
Legal Issues	1545	(1)
Use of DNA Testing for the Identification of Clinical Specimens	1545	(1)
Transplantation Testing	1546	(3)
Genetic Features of HLA Genes	1546	(1)
Historical Applications of HLA Typing	1547	(1)
Transplantation	1547	(1)
DNA-Based HLA Allele Identification	1548	(1)
Interpretation of HLA Test Results	1548	(1)
Quality Assurance and Quality Control Issues	1549	(1)
Proficiency Testing	1549	(1)
Accreditation and Certification of Laboratories and Professionals	1549	(1)
Chimerism and Hematopoietic Cell Engraftment Analysis	1549	(2)
Methods for Performing Engraftment Analysis	1549	(1)
Selection and Interpretation of Short Tandem Repeat Loci	1550	(1)
Applications of Microsatellite Locus Testing to Engraftment Analysis	1550	(1)
Proficiency Testing	1551	(1)
Quality Assurance and Quality Control	1551	(1)
Accreditation	1551	(1)
Parentage Testing	1551	(4)
Methods, Instrumentation, and Sample Requirements	1551	(1)
Reporting of Test Results	1551	(1)
Quality Assurance and Quality Control	1552	(1)
Policy and Procedures for Resolution of Complaints	1553	(1)
Accreditation	1553	(2)
Molecular Methods in Diagnosis and Monitoring of Infectious Diseases	1555	(34)
Andrea Ferreira-Gonzalez
Angela M. Caliendo
Development of Molecular Assays for Infectious Diseases	1555	(3)
Analyte-Specific Reagents	1556	(1)
When to Use a Molecular Test for an Infectious Disease	1556	(1)
Choice of Specimen to Test and Analytical Approach	1556	(1)
Test Development	1557	(1)
Preanalytical Variables	1557	(1)
Internal Controls	1557	(1)
Nucleic Acid Extraction	1557	(1)
Quantitative Molecular LDTs	1558	(1)
Test Verification	1558	(3)
Analytical Verification	1558	(2)
Clinical Verification	1560	(1)
Quality Control and Quality Assurance	1561	(1)
Interpretation of Results	1562	(1)
Reporting of Results	1563	(1)
Specific Pathogens	1563	(26)
Chlamydia Trachomatis and Neisseria Gonorrhoeae	1563	(2)
Human Papillomavirus	1565	(2)
Human Immunodeficiency Virus Type 1	1567	(3)
Herpes Simplex Virus	1570	(1)
Enterovirus	1571	(1)
Perinatal Group B Streptococcal Disease	1572	(1)
Cytomegalovirus	1573	(2)
Mycobacterium tuberculosis	1575	(1)
Hepatitis C Virus	1576	(13)
Pharmacogenetics	1589	(30)
Gwendolyn A. McMillin
Mark W. Linder
Bonny Lewis Bukaveckas
Defining Pharmacogenetic Targets and What Testing to Consider	1589	(1)
Approaches to Pharmacogenetic Testing	1590	(2)
Clinical Application of Pharmacogenetic Testing	1592	(1)
Best Examples of Clinically Relevant Pharmacogenetic Targets	1592	(27)
Thiopurine S-Methyltransferase	1592	(3)
Cytochrome P450 2D6 (CYP2D6)	1595	(5)
Cytochrome P450 2C19 (CYP2C19)	1600	(2)
Cytochrome P450 2C9 (CYP2C9)	1602	(1)
N-Acetyl Transferases (NAT1 and NAT2)	1603	(6)
Other Pharmacogenetic Targets and Future Directions	1609	(10)
SECTION VI PATHOPHYSIOLOGY
Cardiac Function	1619	(52)
Fred S. Apple
Allan S. Jaffe
Basic Anatomy	1619	(2)
Physiology	1621	(1)
Cardiac Cycle	1621	(1)
Cardiac Conducting System	1621	(1)
Cardiac Disease	1622	(7)
Congestive Heart Failure	1622	(1)
Acute Coronary Syndromes	1623	(6)
Cardiac Biomarkers	1629	(6)
Cardiac Troponin I and T	1629	(1)
Brain Natriuretic Peptide	1629	(2)
Creatine Kinase Isoenzymes and Isoforms	1631	(1)
Myoglobin	1632	(1)
Lactate Dehydrogenase Isoenzymes	1632	(1)
C-Reactive Protein	1633	(1)
Serum Amyloid	1633	(1)
sCD40 Ligand	1633	(1)
Cytokines	1633	(1)
Myeloperoxidase	1634	(1)
Phospholipase A2	1634	(1)
Pregnancy Associated Plasma Protein A	1634	(1)
Oxidized LDL	1634	(1)
Matrix Metalloproteinases	1634	(1)
Monocyte Chemotactic Protein	1634	(1)
Tumor Necrosis Factor Alpha	1634	(1)
Tissue Plasminogen Activator Antigen	1634	(1)
Secreted Platelet Granular Substances	1634	(1)
Isoprostanes	1635	(1)
Urinary Thromboxane	1635	(1)
Adhesion Molecules	1635	(1)
Other Proposed Markers	1635	(1)
Analytical Measurement of Cardiac Proteins	1635	(8)
Cardiac Troponin	1635	(5)
Brain Natriuretic Peptide	1640	(2)
Creatine Kinase-2 and Isoforms	1642	(1)
Myoglobin	1643	(1)
Lactate Dehydrogenase Isoenzymes	1643	(1)
Clinical Utility	1643	(2)
General Biomarker Observations	1645	(8)
Cardiac Troponin	1645	(1)
Brain Natriuretic Peptide	1645	(7)
CK-2	1652	(1)
Myoglobin	1653	(1)
Lactate Dehydrogenase	1653	(1)
General Clinical Practice	1653	(18)
Strategies for the Role of Cardiac Troponin for Risk Assessment	1654	(5)
Clinical Utility of Cardiac Markers in Monitoring Reperfusion Following Thrombolytic Therapy	1659	(1)
Use of Multimarkers	1660	(1)
Estimation of Infarct Size	1660	(11)
Kidney Disease	1671	(76)
Michael P. Delaney
Christopher P. Price
David J. Newman
Edmund Lamb
Anatomy	1671	(6)
Blood Supply	1671	(1)
Nephron	1672	(4)
Juxtaglomerular Apparatus	1676	(1)
Renal Interstitium	1677	(1)
Kidney Function and Physiology	1677	(11)
Excretory and Reabsorptive Functions	1677	(2)
Regulatory Function	1679	(4)
Endocrine Function	1683	(1)
Glomerular Filtration Rate	1683	(3)
Glomerular Permeability and Filtration	1686	(1)
Proteinuria	1687	(1)
Pathophysiology of Kidney Disease	1688	(3)
Diagnosis and Screening for Kidney Disease	1689	(1)
Classification of Kidney Failure	1689	(2)
Diseases of the Kidney	1691	(27)
The Uremic Syndrome	1691	(2)
Chronic Kidney Disease	1693	(4)
End-Stage Renal Disease	1697	(2)
Diabetic Nephropathy	1699	(3)
Hypertensive Nephropathy	1702	(1)
Glomerular Diseases	1702	(4)
Interstitial Nephritis	1706	(1)
Polycystic Kidney Disease	1706	(1)
Toxic Nephropathy	1707	(1)
Obstructive Uropathy	1707	(1)
Tubular Diseases	1707	(4)
Diabetes Insipidus	1711	(1)
Renal Calculi	1711	(4)
Cystinuria	1715	(1)
Prostaglandins and NSAIDs in Kidney Disease	1716	(1)
Monoclonal Light Chains and Kidney Disease	1716	(2)
Assessment of Renal Concentrating Ability: Urinary Osmolality	1718	(1)
Renal Replacement Therapy	1718	(29)
Background	1719	(1)
Dialysis	1719	(6)
Kidney Transplantation	1725	(22)
Physiology and Disorders of Water, Electrolyte, and Acid-Base Metabolism	1747	(30)
James Stacey Klutts
Mitchell G. Scott
Total Body Water---Volume and Distribution	1747	(1)
Water and Electrolytes---Composition of Body Fluids	1748	(2)
Extracellular and Intracellular Compartments	1749	(1)
Reasons for Composition Differences of Body Fluids	1750	(1)
Distribution of Ions by Active and Passive Transport	1750	(1)
Electrolytes	1750	(7)
Sodium	1750	(4)
Potassium	1754	(3)
Chloride	1757	(1)
Bicarbonate	1757	(1)
Acid-Base Physiology	1757	(10)
Acid-Base Balance and Acid-Base Status	1757	(2)
Buffer Systems and Their Role in Regulating the pH of Body Fluids	1759	(3)
Respiratory Mechanism in the Regulation of Acid-Base Balance	1762	(1)
Renal Mechanisms in the Regulation of Acid-Base Balance	1763	(4)
Conditions Associated With Abnormal Acid-Base Status and Abnormal Electrolyte Composition of the Blood	1767	(10)
Metabolic Acidosis (Primary Bicarbonate Deficit)	1768	(4)
Metabolic Alkalosis (Primary Bicarbonate Excess)	1772	(2)
Respiratory Acidosis	1774	(1)
Respiratory Alkalosis	1775	(2)
Liver Disease	1777	(72)
D. Robert Dufour
Anatomy of the Liver	1777	(3)
Gross Anatomy	1777	(2)
Microscopic Anatomy	1779	(1)
Ultrastructure of the Hepatocyte	1780	(1)
Biochemical Functions of the Liver	1780	(12)
Hepatic Excretory Function	1781	(6)
Hepatic Synthetic Function	1787	(2)
Hepatic Metabolic Function	1789	(3)
Hepatic Storage Function	1792	(1)
Clinical Manifestations of Liver Disease	1792	(6)
Jaundice	1792	(1)
Portal Hypertension	1792	(4)
Hepatorenal Syndrome	1796	(1)
Altered Drug Metabolism	1796	(1)
Nutritional and Metabolic Abnormalities	1796	(1)
Disordered Hemostasis in Liver Disease	1796	(1)
Enzymes Released from Diseased Liver Tissue	1797	(1)
Diseases of the Liver	1798	(27)
Mechanisms and Patterns of Injury	1798	(1)
Disorders of Bilirubin Metabolism	1798	(1)
Hepatic Viral Infection	1798	(6)
Acute Hepatitis	1804	(5)
Chronic Hepatitis	1809	(8)
Alcoholic Liver Disease	1817	(2)
Cirrhosis	1819	(1)
Hepatic Glycogenoses	1820	(1)
Cholestatic Liver Diseases	1820	(3)
Hepatic Tumors	1823	(2)
Diagnostic Strategy	1825	(24)
Plasma Enzymes	1826	(1)
Plasma Albumin	1826	(1)
Prothrombin Time	1827	(1)
Plasma Bilirubin	1827	(22)
Gastric, Pancreatic, and Intestinal Function	1849	(42)
Peter G. Hill
Introduction to Anatomy and Physiology of the Gastrointestinal Tract	1849	(2)
Anatomy	1849	(1)
Phases of Digestion	1850	(1)
Processes of Digestion and Absorption	1851	(5)
Digestion and Absorption of Carbohydrates	1852	(2)
Digestion and Absorption of Lipids	1854	(1)
Digestion and Absorption of Proteins	1854	(2)
Stomach: Diseases and Laboratory Investigations	1856	(3)
Peptic Ulcer Disease and Helicobacter pylori	1856	(1)
Diagnostic Tests for H. pylori	1856	(2)
Determination of Basal Acid Output	1858	(1)
Intestinal Disorders and Their Laboratory Investigation	1859	(8)
Celiac Disease (Celiac Sprue, Gluten-Sensitive Enteropathy)	1859	(3)
Disaccharidase Deficiencies	1862	(2)
Bacterial Overgrowth	1864	(1)
Bile Salt Malabsorption	1865	(1)
Protein-Losing Enteropathy	1866	(1)
The Pancreas: Diseases and Assessment of Exocrine Pancreatic Function	1867	(6)
Pediatric Disorders of the Exocrine Pancreas	1867	(1)
Adult Disorders of the Exocrine Pancreas	1867	(1)
Tests of Exocrine Function of the Pancreas	1868	(5)
Gastrointestinal Regulatory Peptides	1873	(4)
Cholecystokinin	1873	(1)
Gastrin	1874	(1)
Secretin	1875	(1)
Vasoactive Intestinal Polypeptide	1876	(1)
Glucose-Dependent Insulinotropic Peptide (GIP, Gastric Inhibitory Polypeptide)	1876	(1)
Other Regulatory Peptides	1876	(1)
Neuroendocrine Tumors	1877	(1)
Gastrinoma and the Zollinger-Ellison Syndrome	1877	(1)
The Watery Diarrhea Hypokalemia Achlorhydria Syndrome (Werner-Morrison Syndrome, WDHA Syndrome, VIPoma)	1877	(1)
Other Gastrointestinal Neuroendocrine Tumors and Tumor Markers	1877	(1)
Investigation of Maldigestion/Malabsorption	1878	(3)
Evaluation of Fat Absorption	1878	(3)
Investigation of Chronic Diarrhea	1881	(10)
Laxative Abuse	1881	(2)
Fecal Osmotic (Osmolal) Gap	1883	(8)
Mineral and Bone Metabolism	1891	(76)
David B. Endres
Robert K. Rude
Overview of Bone and Mineral	1891	(1)
Calcium	1892	(13)
Biochemistry and Physiology	1892	(1)
Clinical Significance	1893	(3)
Measurement of Calcium	1896	(6)
Patient Preparation and Sources of Preanalytical Error for Total and Free Calcium Measurements	1902	(1)
Reference Intervals for Total and Free Calcium in Serum and Plasma	1903	(1)
Physiological Variation in Calcium	1903	(1)
Interpretation of Total and Free Calcium Results	1903	(1)
Urinary Calcium	1904	(1)
Phosphate	1905	(4)
Biochemistry and Physiology	1905	(1)
Clinical Significance	1905	(2)
Measurement of Phosphate	1907	(1)
Reference Intervals	1908	(1)
Magnesium	1909	(3)
Biochemistry and Physiology	1909	(1)
Clinical Significance	1909	(2)
Measurement of Total Magnesium	1911	(1)
Measurement of Free (Ionized) Magnesium	1912	(1)
Reference Intervals for Total and Free Magnesium	1912	(1)
Hormones Regulating Mineral Metabolism	1912	(18)
Parathyroid Hormone	1912	(8)
Vitamin D and Its Metabolites	1920	(6)
Calcitonin	1926	(2)
Parathyroid Hormone-Related Protein	1928	(2)
Integrated Control of Mineral Metabolism	1930	(2)
Renal Handling of Calcium and Phosphate	1930	(1)
Intestinal Absorption of Calcium and Phosphate	1931	(1)
Bone Metabolism	1931	(1)
Magnesium	1931	(1)
Metabolic Bone Diseases	1932	(3)
Osteoporosis	1932	(1)
Osteomalacia and Rickets	1933	(1)
Paget's Disease	1934	(1)
Renal Osteodystrophy	1934	(1)
Biochemical Markers of Bone Turnover	1935	(32)
Preanalytical and Analytical Variables	1936	(1)
Markers of Bone Resorption	1936	(4)
Markers of Bone Formation	1940	(27)
Pituitary Function	1967	(36)
Laurence M. Demers
Mary Lee Vance
Anatomy	1967	(1)
Adenohypophysis	1968	(23)
Regulation of Function	1968	(1)
Growth Hormone and Insulin-like Growth Factors	1969	(7)
Prolactin	1976	(5)
Corticotropin (Adrenocorticotropin) and Related Peptides	1981	(3)
Gonadotropins (Follicle-Stimulating Hormone, Luteinizing Hormone)	1984	(4)
Thyrotropin	1988	(1)
Assessment of Anterior Pituitary Lobe Reserve	1988	(3)
Neurohypophysis	1991	(12)
Arginine Vasopressin	1991	(5)
Oxytocin	1996	(7)
The Adrenal Cortex	2003	(50)
Laurence M. Demers
General Steroid Chemistry	2003	(4)
Chemical Structure	2003	(2)
Biochemistry	2005	(2)
Adrenocortical Steroids	2007	(14)
General Biochemistry	2007	(5)
Metabolism	2012	(2)
The Hypothalamic-Pituitary-Adrenal Cortical Axis	2014	(1)
Regulation of Adrenal Hormones	2014	(2)
Testing the Functional Status of the Adrenal Cortex	2016	(5)
Disorders of the Adrenal Cortex	2021	(12)
Hypofunction of the Adrenal Cortex	2021	(3)
Hyperfunction of the Adrenal Cortex	2024	(9)
Analytical Methodology	2033	(20)
Choice of Specimen	2033	(1)
Free Versus Bound Steroids	2034	(1)
Hydrolysis, Extraction, and Separation	2034	(2)
Specific Methods	2036	(17)
The Thyroid: Pathophysiology and Thyroid Function Testing	2053	(44)
Laurence M. Demers
Carole Spencer
Thyroid Hormones	2053	(4)
Chemistry	2053	(1)
Biological Function	2054	(1)
Biochemistry	2055	(1)
Metabolism	2056	(1)
Physiology	2056	(1)
Thyroid Dysfunction	2057	(8)
Hypothyroidism	2057	(2)
Hyperthyroidism	2059	(2)
Nonthyroidal Illness	2061	(1)
Hypothyroidism Versus Euthyroid Sick Syndrome	2062	(1)
Hyperthyroid Versus Euthyroid Sick Syndrome	2063	(1)
Effect of Drugs	2063	(1)
Diagnosis of Thyroid Dysfunction	2063	(2)
Analytical Methods	2065	(32)
Determination of Thyroid-Stimulating Hormone in Blood	2066	(2)
Determination of Thyroxine in Serum	2068	(3)
Determination of Triiodothyronine in Serum	2071	(2)
Determination of Reverse Triiodothyronine (rT3) Using Radioimmunoassay	2073	(1)
Determination of Free Thyroid Hormones	2073	(9)
Determination of Thyroxine-Binding Globulin and Other Thyroid Hormone--Binding Proteins	2082	(1)
Determination of Thyroglobulin	2083	(1)
Determination of Antithyroid Antibodies	2084	(13)
Reproductive Related Disorders	2097	(56)
Shannon Haymond
Ann M. Gronowski
Male Reproductive Biology	2097	(7)
Anatomy	2097	(1)
Hypothalamic-Pituitary-Gonadal Axis	2097	(1)
Androgens	2098	(1)
Male Reproductive Development	2099	(3)
Male Reproductive Abnormalities	2102	(2)
Female Reproductive Biology	2104	(16)
Anatomy	2104	(1)
Hypothalamic-Pituitary-Gonadal Axis	2105	(1)
Estrogens	2105	(3)
Progesterone	2108	(1)
Female Reproductive Development	2109	(1)
Female Reproductive Abnormalities	2110	(2)
Normal Menstrual Cycle	2112	(2)
Ovulation	2114	(1)
Irregular Menses	2114	(6)
Infertility	2120	(7)
Male Infertility	2120	(4)
Female Infertility	2124	(3)
Assisted Reproduction	2127	(1)
Analytical Methodology	2127	(26)
Measurement of Total Testosterone in Blood	2127	(2)
Measurement of Free and Weakly Bound Testosterone in Blood	2129	(2)
Measurement of Testosterone in Saliva	2131	(1)
Measurement of Testosterone Precursors and Metabolites in Blood	2131	(1)
Measurement of Dehydroepiandrosterone and Its Sulfate	2132	(2)
Measurement of 17-Ketosteroids in Urine	2134	(1)
Measurement of Anabolic Steroids	2134	(1)
Measurement of Estrogens in Blood	2134	(2)
Measurement of Estriol	2136	(1)
Measurement of Estrogens in Urine	2136	(1)
Measurement of Estrogens in Saliva	2137	(1)
Measurement of Progesterone in Blood	2137	(1)
Measurement of Progesterone in Saliva	2138	(15)
Clinical Chemistry of Pregnancy	2153	(54)
Edward R. Ashwood
George J. Knight
Human Pregnancy	2153	(7)
Conception, Embryo, and Fetus	2153	(1)
Placenta	2154	(1)
Amniotic Fluid	2155	(1)
Maternal Adaptation	2156	(3)
Functional Development of the Fetus	2159	(1)
Maternal and Fetal Health Assessment	2160	(1)
Clinical Specimens	2160	(1)
Diagnosis and Dating of Pregnancy	2160	(1)
Complications of Pregnancy	2161	(6)
Abnormal Pregnancies	2161	(4)
Trophoblastic Disease	2165	(1)
Fetal Anomalies	2165	(1)
Preterm Delivery	2166	(1)
Maternal Serum Screening for Fetal Defects	2167	(12)
Clinical Application of Prenatal Screening	2168	(11)
Laboratory Tests	2179	(28)
Chorionic Gonadotropin	2179	(3)
Alpha Fetoprotein	2182	(1)
Unconjugated Estriol	2183	(3)
Dimeric Inhibin A	2186	(1)
Fetal Fibronectin	2186	(1)
Amniotic Fluid Bilirubin (ΔA450)	2187	(1)
Tests for Evaluating Fetal Lung Maturity	2188	(19)
Inborn Errors of Amino Acid, Organic Acid, and Fatty Acid Metabolism	2207	(44)
Piero Rinaldo
Sihoun Hahn
Dietrich Matern
Biochemical Diagnosis	2207	(4)
Prenatal Diagnosis	2208	(1)
Newborn Screening	2209	(1)
Evaluation of Symptomatic Patients	2209	(1)
Postmortem Screening	2210	(1)
Disorders of Amino Acid Metabolism	2211	(10)
Classic Phenylketonuria and Other Hyperphenylalaninemias	2211	(6)
Tyrosinemia Type 1	2217	(2)
Homocystinuria	2219	(1)
Maple Syrup Urine Disease	2220	(1)
Urea Cycle Defects	2220	(1)
Nonketotic Hyperglycinemia	2221	(1)
Disorders of Organic Acid Metabolism	2221	(9)
Disorders of Propionate Metabolism	2222	(1)
Isovaleric Acidemia	2222	(8)
Glutaric Acidemia Type I	2230	(1)
Ethylmalonic Encephalopathy	2230	(1)
Disorders of Fatty Acid Oxidation	2230	(7)
Very Long-Chain Acyl-CoA Dehydrogenase Deficiency	2232	(1)
Trifunctional Protein and Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiencies	2232	(4)
Medium-Chain Acyl-CoA Dehydrogenase Deficiency	2236	(1)
Short-Chain Acyl-CoA Dehydrogenase Deficiency	2236	(1)
Analytical Considerations	2237	(14)
Analysis of Amino Acids	2237	(1)
Analysis of Organic Acids	2237	(4)
Analysis of Acylcarnitines	2241	(10)
SECTION VII APPENDIX
Reference Information for the Clinical Laboratory	2251	(66)
William L. Roberts
Gwendolyn A. McMillin
Carl A. Burtis
David E. Bruns
Table 56-1 Reference Intervals and Values	2252	(51)
Table 56-2 Therapeutic and Toxic Levels of Drugs	2303	(14)
Table 56-3 Critical Values	2317