Tietz Textbook of clinical chemistry and molecular diagnostics:
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| Other Authors: | |
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| Format: | Book |
| Language: | English |
| Published: |
St. Louis, Mo.
Elsevier, Saunders
2006
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| Edition: | 4. ed. |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XXXVI, 2412 S. Ill., graph. Darst. |
| ISBN: | 0721601898 |
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| 245 | 1 | 0 | |a Tietz Textbook of clinical chemistry and molecular diagnostics |c [ed. by.] Carl A. Burtis ; Edward R. Ashwood ; David E. Bruns |
| 246 | 1 | 3 | |a Clinical chemistry and molecular diagnostics |
| 250 | |a 4. ed. | ||
| 264 | 1 | |a St. Louis, Mo. |b Elsevier, Saunders |c 2006 | |
| 300 | |a XXXVI, 2412 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
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| 700 | 1 | |a Tietz, Norbert W. |d 1926-2018 |e Begründer eines Werks |0 (DE-588)172418003 |4 oth | |
| 700 | 1 | |a Burtis, Carl A. |4 edt | |
| 700 | 1 | |a Ashwood, Edward R. |d 1953- |e Sonstige |0 (DE-588)172663741 |4 oth | |
| 700 | 1 | |a Bruns, David E. |d 1941- |e Sonstige |0 (DE-588)173821707 |4 oth | |
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Color insert follows page 1468.
SECTION I
LABORATORY PRINCIPLES
1 Introduction to Principles of Laboratory Analyses
and Safety, 3
Edward W. Bermes, Jr., Ph.D., Stephen E. Kahn, Ph.D.,
and Donald S. Young, M.B., Ph.D.
CONCEPT OF SOLUTE AND SOLVENT, 3
Definitions, 3
Expressing Concentrations of Solutions, 3
UNITS OF MEASUREMENT, 5
International System of Units, 5
Decimal Multiples and Submultiples of SI Units, 6
Applications of SI in Laboratory Medicine, 6
Problem Areas in the Use of SI Units, 8
Conversion Rules, 9
Standardized Reporting of Test Results, 9
CHEMICALS AND REFERENCE MATERIALS, 10
Reagent Grade Water, 10
Reagent Grade or Analytical Reagent Grade (AR)
Chemicals, 12
Ultrapure Reagents, 12
Reference Materials, 12
BASIC TECHNIQUES AND PROCEDURES, 12
Volumetric Sampling and Dispensing, 12
Centrifugation, 19
Measurement of Radioactivity, 21
Gravimetry, 23
Thermometry, 25
Buffer Solutions, 25
Procedures for Processing Solutions, 26
SAFETY, 27
Safety Program, 28
Safety Equipment, 28
Safety Inspections, 28
Mandated Plans, 29
Ergonomics Program, 30
Hazards in the Laboratory, 30
Contents
2 Specimen Collection and Processing, 41
Donald S. Young, M.B., Ph.D., Edward W. Bermes, Jr., Ph.D.,
and Doris M. Haverstick, Ph.D.
SPECIMEN COLLECTION, 41
Blood, 41
Urine, 49
Feces, 52
Spinal Fluid, 52
Synovial Fluid, 52
Amniotic Fluid (Amniocentesis), 53
Pleural, Pericardial, and Ascitic Fluids, 53
Saliva, 53
Swabs, 53
Solid Tissue, 53
Hair and Finger Nails, 54
HANDLING OF SPECIMENS FOR TESTING, 54
Maintenance of Specimen Identification, 54
Preservation of Specimens in Transit, 54
Separation and Storage of Specimens, 56
Transport of Specimens, 56
SECTION II
ANALYTICAL TECHNIQUES AND
INSTRUMENTATION
3 Optical Techniques, 61
L.J. Kricka, D.Phil., F.A.C.B., C.Chem., F.R.S.C, F.R.C.Path.
NATURE OF LIGHT, 61
SPECTROPHOTOMETRY, 62
Basic Concepts, 62
Instrumentation, 64
REFLECTANCE PHOTOMETRY, 72
FLAME EMISSION SPECTROPHOTOMETRY, 73
ATOMIC ABSORPTION SPECTROPHOTOMETRY, 73
Basic Concepts, 73
Instrumentation, 73
Interferences in Atomic Absorption
Spectrophotometry, 74
FLUOROMETRY, 75
Basic Concepts, 75
Instrumentation, 77
Limitations of Fluorescence Measurements, 83
PHOSPHORESCENCE, 84
CHEMILUMINESCENCE, BIOLUMINESCENCE, AND
ELECTROCHEMILUMINESCENCE, 84
Basic Concepts, 84
Instrumentation, 85
Limitations of Chemiluminescence and
Electrochemiluminescence Measurements, 85
NEPHELOMETRY AND TURBIDIMETRY, 85
Basic Concepts, 85
Measurement of Scattered Light, 87
Instrumentation, 88
Limitations of Light-Scattering Measurements, 88
4 Electrochemistry and Chemical Sensors, 93
Paul D'Orazio, Ph.D., and Mark E. Meyerhoff, Ph.D.
POTENTIOMETRY AND ION-SELECTIVE
ELECTRODES, 93
Basic Concepts, 93
Types of Electrodes, 94
Direct Potentiometry by ISE—Units of Measure and
Reporting for Clinical Applications, 100
VOLTAMMETRY/AMPEROMETRY, 101
Basic Concepts, 101
Applications, 103
CONDUCTOMETRY, 105
COULOMETRY, 106
OPTICAL CHEMICAL SENSORS, 106
Basic Concepts, 107
Applications, 107
BIOSENSORS, 108
Enzyme-Based Biosensors With Amperometric
Detection, 108
Enzyme-Based Biosensors With Potentiometric and
Conductometric Detection, 110
Enzyme-Based Biosensors With Optical Detection, 111
Affinity Sensors, 112
IN VIVO AND MINIMALLY INVASIVE SENSORS, 113
5 Electrophoresis, 121
Raymond Karcher, Ph.D., and James P. Landers, Ph.D.
BASIC CONCEPTS AND DEFINITIONS, 121
THEORY OF ELECTROPHORESIS, 121
CONVENTIONAL ELECTROPHORESIS, 122
Instrumentation, 122
General Operations, 125
Technical and Practical Considerations, 126
Types of Electrophoresis, 128
CAPILLARY ELECTROPHORESIS, 130
Instrumentation, 131
Technical Considerations, 133
Modes of Operation, 134
MICROCHIP ELECTROPHORESIS, 135
Instrumentation, 135
Fabrication of Microchips, 136
Molecular Diagnostics Using Microchips, 137
6 Chromatography, 141
M. David Ullman, Ph.D., and Carl A. Burtis, Ph.D.
BASIC CONCEPTS, 141
SEPARATION MECHANISMS, 142
Ion-Exchange Chromatography, 142
Partition Chromatography, 143
Adsorption Chromatography, 144
Affinity Chromatography, 144
Size-Exclusion Chromatography, 144
RESOLUTION, 145
Retention Factor (k'), 146
Efficiency (N), 147
PLANAR CHROMATOGRAPHY, 148
COLUMN CHROMATOGRAPHY, 149
Gas Chromatography, 149
Liquid Chromatography, 155
QUALITATIVE AND QUANTITATIVE ANALYSES, 161
Analyte Identification, 161
Analyte Quantification, 161
7 Mass Spectrometry, 165
Thomas Annesley, Ph.D., Alan L. Rockwood, Ph.D.,
and Nicholas E. Sherman, Ph.D.
BASIC CONCEPTS AND DEFINITIONS, 165
INSTRUMENTATION, 167
Ion Source, 167
Vacuum System, 171
Mass Analyzers, Ion Detectors, and Tandem Mass
Spectrometers, 171
Detectors, 180
Computer and Software, 181
CLINICAL APPLICATIONS, 181
Gas Chromatography-Mass Spectrometry, 182
Liquid Chromatography-Mass Spectrometry, 182
MALDI-TOF Mass Spectrometry, 183
SELDI Mass Spectrometry, 184
ICP Mass Spectrometry, 184
Proteomics, 184
ANALYTICAL PROBLEM OF ION SUPPRESSION, 185
8 Principles of Clinical Enzymology, 191
Renze Bais, Ph.D., and Mauro Panteghini, M.D.
BASIC PRINCIPLES, 191
Enzyme Nomenclature, 191
Enzymes as Proteins, 192
Enzymes as Catalysts, 198
ENZYME KINETICS, 198
The Enzyme-Substrate Complex, 198
Factors Governing the Rate of Enzyme-Catalyzed
Reactions, 199
ANALYTICAL ENZYMOLOGY, 207
Measurement of Reaction Rates, 207
Units for Expressing Enzyme Activity, 209
Measurement of Substrates, 209
Optimization, Standardization, and Quality
Control, 210
Measurement of Enzyme Mass Concentration, 211
Enzymes as Analytical Reagents, 211
Analytical Applications of Immobilized Enzymes, 213
Measurement of Isoenzymes and Isoforms, 213
DIAGNOSTIC ENZYMOLOGY, 214
Factors Affecting Enzyme Levels in Plasma or
Serum, 214
Selection of Enzyme Tests, 216
9 Principles of Immunochemical Techniques, 219
L.J. Kricka, D.Phil., F.A.C.B., C.Chem., F.R.S.C, ER.C.Path.
BASIC CONCEPTS, 219
Antibodies, 219
Immunogens, 220
ANTIGEN ANTIBODY BINDING, 221
Binding Forces, 221
Reaction Mechanism, 222
Factors Influencing Binding, 222
Types of Reactions, 223
QUALITATIVE METHODS, 224
Passive Gel Diffusion, 224
Immunoelectrophoresis (IEP), 225
Western Blotting, 227
Dot Blotting, 228
QUANTITATIVE METHODS, 229
Radial Immunodiffusion and Electroimmunoassay, 229
Turbidimetric and Nephelometric Assays, 230
Labeled Immunochemical Assays, 230
Interferences in Immunoassays, 239
OTHER IMMUNOCHEMICAL TECHNIQUES, 239
Immunocytochemistry, 239
Agglutination Assays, 240
10 Nanotechnology and Microfabrication, 245
Peter Wilding, Ph.D., ER.C.Path., ER.S.C, H.C.L.D.(A.B.B.)
BACKGROUND, 246
FABRICATION AND MATERIALS, 247
Manufacturing Techniques, 247
Drilling, 249
Bonding and Sealing, 249
MICROFLUIDICS, 250
VALVING SYTEMS, 250
APPLICATIONS, 252
Genomics, 252
Hybridization Arrays, 253
Nucleic Acid Sequencing, 254
Drug Detection and Assay, 254
Protein Chips, 254
Immunoassay for Antibodies and Peptides, 255
Enzymology, 255
Metabolites, 255
Cell Handling and Cell Culture, 256
Other Applications, 256
SURFACE CHEMISTRY ISSUES, 256
LIMITATIONS OF MICROTECHNOLOGY, 257
THE FUTURE, 257
11 Automation in the Clinical Laboratory, 265
lames C. Boyd, M.D., and Charles D. Hawker, Ph.D., M.B.A., F.A.C.B.
HISTORICAL OVERVIEW, 265
Processes Used in Automation, 266
Laboratory Information Systems, 266
Robotics, 267
Types of Automation, 267
INDIVIDUAL STEPS IN THE ANALYTICAL
PROCESSES, 267
Specimen Acquisition, 268
Specimen Identification, 268
Specimen Delivery to Laboratory, 270
Specimen Preparation, 271
Specimen Loading and Aspiration, 271
On-Analyzer Specimen Delivery, 272
Reagent Handling and Storage, 273
Reagent Delivery, 274
Chemical Reaction Phase, 274
Measurement Approaches, 276
INTEGRATED AUTOMATION FOR THE CLINICAL
LABORATORY, 280
Workstations, 281
Instrument Clusters, 281
Workcells, 282
Automated Specimen Transport, 282
Automated Specimen Processing, 284
Automated Specimen Sorting, 288
Automated Specimen Storage and Retrieval, 289
PRACTICAL CONSIDERATIONS, 289
Evaluation of Requirements, 289
Problems of Integration, 290
Measuring the Impact of Automation, 292
DEVELOPMENT OF STANDARDS FOR LABORATORY
AUTOMATION, 292
OTHER AREAS OF AUTOMATION, 292
Urine Analyzers, 292
Flow Cytometers, 293
Hematology Cell Counters, 293
Nucleic Acid Analyzers, 293
Microtiter Plate Systems, 294
Automated Pipetting Stations, 294
POCT Analyzers, 294
Remote Automated Laboratory System, 294
12 Point-of-Care Testing, 299
Christopher P. Price, Ph.D., and Andrew St. John, Ph.D.,
M.A.A.C.B.
ANALYTICAL AND TECHNOLOGICAL
CONSIDERATIONS, 299
Requirements, 299
Design, 301
Examples of POCT Devices, 303
Informatics and POCT, 308
IMPLEMENTATION AND MANAGEMENT
CONSIDERATIONS, 310
Establishment of Need, 310
Organizing and Implementation of a Coordination
Committee, 311
POCT Policy and Accountability, 311
Equipment Procurement and Evaluation, 31 I
Training and Certification, 312
Quality Control, Quality Assurance, and Audit, 312
Maintenance and Inventory Control, 313
Documentation, 314
Accreditation and Regulation of POCT, 315
FUTURE OF POCT, 315
SECTION III
PRINCIPLES OF LABORATORY MEDICINE
13 Introduction to Laboratory Medicine and
Evidence-Based Laboratory Medicine, 323
Christopher P. Price, Ph.D., Patrick MM. Bossuyt, Ph.D.,
and David E. Bruns, M.D.
CONCEPTS, DEFINITIONS, AND
RELATIONSHIPS, 323
What Is Laboratory Medicine?, 323
Clinical Chemistry and Laboratory Medicine, 324
Clinical Chemistry, Laboratory Medicine, and
Evidence-Based Laboratory Medicine, 324
EVIDENCE-BASED MEDICINE—WHAT IS IT?, 324
Definition and Goals of Evidence-Based
Medicine, 324
The Practice of Evidence-Based Medicine, 325
EVIDENCE-BASED MEDICINE AND LABORATORY
MEDICINE, 325
What is Evidence-Based Laboratory Medicine?, 325
Types of Diagnostic Questions Addressed in Laboratory
Medicine, 326
Test Results Alone Do Not Produce Clinical
Outcomes, 326
Using the Test Result, 328
The Clinical Setting of an Outcome Study, 328
CHARACTERIZATION OF DIAGNOSTIC ACCURACY
OF TESTS, 328
Study Design, 328
The Reporting of Studies of Diagnostic Accuracy and
the Role of the STARD Initiative, 329
OUTCOMES STUDIES, 330
What Are Outcomes Studies?, 330
Why Outcomes Studies?, 332
Design of Studies of Medical Outcomes, 333
SYSTEMATIC REVIEWS OF DIAGNOSTIC TESTS, 336
Why Systematic Reviews?, 336
Conducting a Systematic Review, 336
ECONOMIC EVALUATIONS OF DIAGNOSTIC
TESTING, 338
A Hierarchy of Evidence, 338
Methodologies for Economic Evaluations, 338
Quality of Economic Evaluations, 340
Perspectives of Economic Evaluations, 340
Choice of Outcome Measures, 340
Use of Economic Evaluations in Decision Making, 341
CLINICAL PRACTICE GUIDELINES, 341
What Is a Clinical Practice Guideline?, 341
A Transparent Process Must Be Used in the
Development of Guidelines, 341
Steps in the Development of Guidelines, 342
Obtaining External Review and Updating the
Guidelines, 345
CLINICAL AUDIT, 345
Audit to Help Solve Problems, 346
Monitoring Workload and Demand, 346
Monitoring the Introduction of a New Test, 346
Monitoring Adherence to Best Practice, 347
APPLYING THE PRINCIPLES OF EVIDENCE-BASED
LABORATORY MEDICINE IN ROUTINE
PRACTICE, 347
14 Selection and Analytical Evaluation of Methods—
With Statistical Techniques, 353
Kristian Linnet, M.D., and James C. Boyd, M.D.
METHOD SELECTION, 353
Medical Criteria, 353
Analytical Performance Criteria, 354
Other Criteria, 354
BASIC CONCEPTS IN RELATION TO ANALYTICAL
METHODS, 355
Calibration, 355
Trueness and Accuracy, 356
Precision, 357
Precision Profile, 358
Linearity, 359
Analytical Measurement Range, 359
Limit of Detection, 359
Analytical Sensitivity, 361
Limit of Quantitation, 361
Analytical Specificity and Interference, 361
ANALYTICAL GOALS, 362
Qualitative Methods, 363
METHOD COMPARISON, 368
Basic Error Model, 368
Method Comparison Data Model, 370
Preliminary Practical Work in Relation to a Method
Comparison Study, 371
Planning a Method Comparison Study, 371
Distribution of Differences Plot (DoD plot), 371
Verification of Distribution of Differences in Relation to
Specified Limits, 376
Difference (Bland-Altman) Plot, 376
A Caution Against Incorrect Interpretation of Paired
f-Tests in Method Comparison Studies, 377
Regression Analysis, 378
Discussion of Application of Regression Analysis, 395
Discussion of Method Comparison Approaches, 395
MONITORING SERIAL RESULTS, 396
TRACEABILITY AND MEASUREMENT
UNCERTAINTY, 397
Traceability, 397
The Uncertainty Concept, 398
GUIDELINES, REGULATORY DEMANDS, AND
ACCREDITATION, 402
SOFTWARE PACKAGES, 403
15 Clinical Evaluation of Methods, 409
Edward K. Shultz, M.D., M.S., Constantin Aliferis, M.D., Ph.D.,
and Dominik Aronsky, M.D., Ph.D.
SPECTRUM, 409
CLASSIFICATION BIAS, 410
SENSITIVITY AND SPECIFICITY, 411
RECEIVER OPERATING CHARACTERISTIC
CURVES, 412
INTERPRETING A TEST, 413
Odds Ratio, 413
Likelihood Ratio, 413
Bayes' Theorem, 414
Combination Testing, 415
Multivariate Data Analysis, 416
Data Analysis Methods for Very Large Numbers of
Variables, 418
Clinical Examples, 419
Model Validation, 420
COST EFFECTIVENESS AND OUTCOMES
RESEARCH, 420
16 Establishment and Use of Reference Values, 425
Helge Erik Solberg, M.D., Ph.D.
THE CONCEPT OF REFERENCE VALUES, 425
Interpretation by Comparison, 425
Normal Values—An Obsolete Term, 425
Terminology, 426
Types of Reference Values, 426
Requirements, 427
SELECTION OF REFERENCE INDIVIDUALS, 427
Concept of Health in Relation to Reference Values, 427
Strategies for Selection of Reference Individuals, 427
Selection Criteria and Evaluation of Subjects, 430
Partitioning of the Reference Group, 430
SPECIMEN COLLECTION, 430
Two Philosophies of Standardization, 431
Standardization Schemes, 431
The Necessity for Additional Information, 431
ANALYTICAL PROCEDURES AND QUALITY
CONTROL, 432
STATISTICAL TREATMENT OF REFERENCE
VALUES, 433
Statistical Concepts, 433
Determination of Reference Limits: General
Considerations, 434
Partitioning of Reference Values, 436
Inspection of Distribution, 436
Identification and Handling of Erroneous Values, 437
Methods for Determining Reference Values, 437
PRESENTATION OF AN OBSERVED VALUE IN
RELATION TO REFERENCE VALUES, 442
ADDITIONAL TOPICS, 443
Transferability of Reference Values, 443
Multivariate, Population-Based Reference Regions, 443
Subject-Based Reference Values, 445
Dynamic Versus Static Interpretation of Clinical
Chemistry Data, 446
17 Preanalytical Variables and Biological
Variation, 449
Donald S. Young, M.B., Ph.D., and Edward W. Bermes, Jr., Ph.D.
PREANALYTICAL VARIABLES, 449
Controllable Variables, 449
Noncontrollable Variables, 459
BIOLOGICAL VARIABILITY, 467
Overview, 467
Delta Check, 468
Calculating Total Variation, 469
Reference Change Values, 469
Index of Individuality, 469
Index of Heterogeneity, 470
Reliability Coefficient, 470
Quality Specifications for Total Error Allowable, 470
Assessment of Mode of Reporting Test Results, 471
18 Clinical Laboratory Informatics, 475
Kent A. Spackman, M.D., Ph.D.
COMPUTING FUNDAMENTALS, 475
Computer Basics, 475
Hardware, 476
Rate of Change of Computing Capacity, 477
Computer Networks, 478
LABORATORY INFORMATION SYSTEMS, 478
LIS Modules, 478
Life Cycle of Information Systems, 481
Regulatory Issues, 482
Security and Confidentiality, 482
PATHOLOGY INFORMATICS RESOURCES, 482
19 Quality Management, 485
fames O. Westgard, Ph.D., and George G. Klee, MM, Ph.D.
FUNDAMENTALS OF TOTAL QUALITY
MANAGEMENT, 485
Fundamental Concepts, 485
Fundamental Principles, 486
TOTAL QUALITY MANAGEMENT OF THE CLINICAL
LABORATORY, 487
LABORATORY ERROR AND THE SIX SIGMA
PROCESS, 488
Number of Errors Made in the Clinical Laboratory, 488
Six Sigma Principles and Metrics, 488
ELEMENTS OF A QUALITY ASSURANCE
PROGRAM, 490
Commitment, 491
Facilities and Resources, 491
Technical Competence, 491
Technical Procedures, 491
Problem-Solving Mechanism, 491
CONTROL OF PREANALYTICAL VARIABLES, 491
Systems Analysis, 491
Types of Preanalytical Variables, 492
CONTROL OF ANALYTICAL VARIABLES, 494
Choice of Analytical Methodology, 495
Reference Materials and Calibration, 495
Documentation of Analytical Protocols, 496
Establishment of Reference Intervals, 496
Monitoring Technical Competence, 496
Inventory Control of Materials, 496
Input Control of Materials, 497
Monitoring Method Changes, 497
CONTROL OF ANALYTICAL QUALITY USING
STABLE CONTROL MATERIALS AND CONTROL
CHARTS, 497
Control Materials, 497
General Principles of Control Charts, 498
Performance Characteristics of a Control
Procedure, 498
CONTROL OF ANALYTICAL QUALITY USING
PATIENT DATA. 510
Individual Patient Results, 510
Multiple Patients, 512
EXTERNAL QUALITY ASSESSMENT AND
PROFICIENCY TESTING PROGRAMS, 515
External Quality Assessment, 515
Proficiency Testing and Laboratory Accreditation, 516
IDENTIFYING THE SOURCES OF ANALYTICAL
ERRORS, 519
Physical Inspection, 519
Relationship of Type and Source of Error, 519
Method Evaluation Experiments, 520
Optimization Techniques, 520
QUALITY INITIATIVES, 520
Joint Committee for Traceability in Laboratory
Medicine (JCTLM), 520
International Organization for Standardization, 521
Malcolm Baldridge National Quality Award, 523
SECTION IV
ANALYTES
20 Amino Acids, Peptides, and Proteins, 533
A. Myron Johnson, M.D.
AMINO ACIDS, 533
Basic Biochemistry, 533
Clinical Implications, 539
Analysis of Amino Acids, 540
PEPTIDES AND PROTEINS, 541
Basic Biochemistry, 541
Plasma Proteins, 543
Complement Proteins, 564
Immunoglobulins, 569
Proteins in Other Body Fluids, 575
Miscellaneous Proteins, 580
Analysis of Proteins, 582
21 Enzymes, 597
Mauro Panteghini, M.D., Renze Bais, Ph.D.,
and Wouter W. van Solinge, Ph.D.
MUSCLE ENZYMES, 597
Creatine Kinase, 598
Lactate Dehydrogenase, 601
Aldolase, 603
Glycogen Phosphorylase, 603
LIVER ENZYMES, 604
Aminotransferases, 604
Glutamate Dehydrogenase, 607
Alkaline Phosphatase, 607
5'-Nucleotidase, 611
Gamma-Glutamyl Transferase'612
Glutathione S-Transferase, 613
Cholinesterase, 614
PANCREATIC ENZYMES, 616
Amylase, 616
Lipase, 619
Trypsin, 622
Chymotrypsin, 623
Elastase-1,623
BONE ENZYMES, 623
Alkaline Phosphatase (Bone Isoform), 624
Acid Phosphatase (Tartrate-Resistant), 624
RED CELL ENZYMES, 625
The Embden-Meyerhof Pathway, 626
Hexose Monophosphate Pathway, 630
Rapoport-Luebering Cycle, 631
Glutathione Pathway, 631
Purine-Pyrimidine Metabolism, 632
Methemoglobin Reduction, 633
Detection of Hereditary Red Cell Enzyme
Deficiencies, 633
Methodology, 634
22 Cytokines, 645
Manuel Santos Rosa, Ph.D., andAnabela Mota Pinto, Ph.D.
BACKGROUND INFORMATION, 645
History, 645
Rationale for Measurement, 645
General Characteristics, 646
Nomenclature, 646
Classification, 646
Biochemistry, 647
Cytokine Receptors, 649
Clinical Significance, 649
INDIVIDUAL CYTOKINES, 655
Interleukin-1, 655
Interleukin-2,660
Interleukin-3, 664
Interleukin-4, 666
Interleukin-5, 669
Interleukin-6, 671
Interleukin-7, 675
Interleukin-8, 676
Interleukin-9, 676
Interleukin-10, 678
Interleukin-11,680
Interleukin-12, 682
Interleukin-13, 686
Interleukin-14, 688
Interleukin-15, 689
Interleukin-16, 691
Interleukin-17, 693
Interleukin-18, 694
Interferons, 695
Tumor Necrosis Factors, 702
Chemokines, 708
MEASUREMENTS OF CYTOKINES, 720
Requirements, 720
Sample Collection and Storage, 721
Principles of Cytokine Assays, 721
23 Tumor Markers, 745
Daniel W. Chan, Ph.D., D.A.B.C.C, F.A.C.B.
Ronald A. Booth, Ph.D., and Eleftherios P. Diamandis, M.D., Ph.D.
CANCER, 745
HISTORICAL BACKGROUND, 746
CLINICAL APPLICATIONS, 747
EVALUATING CLINICAL UTILITY, 749
Reference Values, 749
Predictive Value Model, 749
Distribution of Marker Values, 750
Disease Management, 750
CLINICAL GUIDELINES, 752
ANALYTICAL METHODOLOGY, 752
Mass Spectrometry, 752
Microarrays, 754
ENZYMES, 754
Alkaline Phosphatase, 755
Creatine Kinase, 756
Lactate Dehydrogenase, 756
Neuron-Specific Enolase, 756
Prostatic Acid Phosphatase, 756
Kallikreins, 756
Prostate-Specific Antigen, 757
Human Glandular Kallikrein 2, 761
The Urokinase-Plasminogen Activator
System, 761
Cathepsins, 762
Matrix Metalloproteinases, 763
Tumor-Associated Trypsin Inhibitor, 763
Telomerase, 764
HORMONES, 765
Adrenocorticotropic Hormone, 765
Calcitonin, 765
Human Chorionic Gonadotropin, 766
ONCOFETAL ANTIGENS, 766
Alpha Fetoprotein, 767
Carcinoembryonic Antigen, 768
CYTOKERATINS, 769
Tissue Polypeptide Antigen, 769
Tissue Polypeptide-Specific Antigen, 769
Cytokeratin 19 Fragments, 769
Squamous Cell Carcinoma Antigen, 769
CARBOHYDRATE MARKERS, 770
CA 15-3, 770
CA 549, 771
CA 27.29, 771
Mucinlike Carcinoma-Associated Antigen, 771
CA 125, 771
Other Ovarian Cancer Biomarkers, 772
DU-PAN-2, 772
BLOOD GROUP ANTIGENS, 773
CA 19-9, 773
CA 50, 773
CA 72-4, 773
CA 242, 774
PROTEINS, 774
Immunoglobulin, 774
Bladder Cancer Markers, 775
Heat Shock Proteins, 776
S-100 Proteins, 776
Autoantibodies, 776
Thyroglobulin and Antibodies, 777
Chromogranins, 777
RECEPTORS AND OTHER MARKERS, 777
Estrogen and Progesterone Receptors, 777
Androgen Receptor, 779
Hepatocyte Growth Factor Receptor (c-Met), 779
Epidermal Growth Factor Receptor, 779
GENETIC MARKERS, 780
Oncogenes, 780
Tumor Suppressor Genes, 783
Single Nucleotide Polymorphisms, 785
MISCELLANEOUS MARKERS, 786
Markers of Angiogenesis, 786
Cell-Free Nucleic Acids, 786
Circulating Cancer Cells, 786
24 Kidney Function Tests, 797
Edmund Lamb, Ph.D., David J. Newman, Ph.D.,
and Christopher P. Price, Ph.D.
CREATININE, 797
Biochemistry and Physiology, 797
Clinical Significance, 798
Analytical Methodology, 798
UREA, 801
Biochemistry and Physiology, 801
Clinical Significance, 802
Analytical Methodology, 802
URIC ACID, 803
Biochemistry and Physiology, 803
Clinical Significance, 805
Analytical Methodology, 807
SCREEENING FOR KIDNEY DISEASE, 808
Urinalysis, 808
Microscopic Examination of Urine, 811
New Instrumental Techniques, 812
QUANTITATIVE ASSESSMENT OF GLOMERULAR
PERMEABILITY: PROTEINURIA, 812
Clinical Significance, 812
Sample Collection for Total Protein and Albumin
Measurement, 812
Measurement of Total Protein, 813
Measurement of Individual Proteins, 813
Characterization of Proteinuria, 817
ASSESSMENT OF KIDNEY FUNCTION: ESTIMATION
OF GLOMERULAR FILTRATION RATE, 818
The Concept of Clearance, 818
Markers Used, 818
Glomerular Filtration Rate at the Extremes of Age, 824
Recommendations and Reference Intervals, 825
25 Carbohydrates, 837
David B. Sacks, M.B., Ch.B., ER.C.Path.
CHEMISTRY OF CARBOHYDRATES, 837
Monosaccharides, 837
Disaccharides, 839
Polysaccharides, 839
Glycoproteins, 840
METABOLISM OF CARBOHYDRATES, 841
Digestion and Absorption, 841
Intermediary Metabolism, 841
Regulation of Blood Glucose Concentration, 841
DIABETES MELLITUS, 853
Classification, 854
Pathogenesis of Type 1 Diabetes Mellitus, 855
Pathogenesis of Type 2 Diabetes Mellitus, 856
Diagnosis, 859
Gestational Diabetes Mellitus, 861
Chronic Complications of Diabetes Mellitus, 862
Role of the Clinical Laboratory in Diabetes
Mellitus, 863
HYPOGLYCEMIA, 864
Hypoglycemia in Neonates and Infants, 865
Fasting Hypoglycemia in Adults, 865
Postprandial Hypoglycemia, 866
Hypoglycemia in Diabetes Mellitus, 867
Tolbutamide Tolerance Test, 867
DETERMINATION OF GLUCOSE IN BODY
FLUIDS, 868
Specimen Collection and Storage, 868
Methods, 869
Reference Intervals, 871
Measurement of Glucose in Urine, 872
Self-Monitoring of Blood Glucose, 873
Minimally Invasive Monitoring of Blood Glucose, 875
KETONE BODIES, 875
Clinical Significance, 876
Determination of Ketone Bodies in Body Fluids, 876
LACTATE AND PYRUVATE, 877
Clinical Significance, 877
Methods for Measuring Lactate and Pyruvate in Body
Fluids, 878
GLYCATED PROTEINS, 878
Glycated Hemoglobin, 879
Fructosamine, 884
Advanced Glycation End Products, 886
URINARY ALBUMIN EXCRETION, 886
Clinical Significance, 886
Methods for Measuring Urinary Albumin Excretion, 887
INBORN ERRORS OF CARBOHYDRATE
METABOLISM, 888
Disorders of Galactose Metabolism, 888
Disorders of Fructose Metabolism, 889
Disorders of Pentose Metabolism, 889
Other Urinary Sugars, 889
Methods for Measuring Individual Sugars, 889
GLYCOGEN STORAGE DISEASE, 890
Type I (Glucose-6-Phosphatase Deficiency), 890
Type II (Acid a-Glucosidase Deficiency), 891
Type HI (Amylo-1,6-Glucosidase Deficiency), 891
Type IV (Branching Enzyme Deficiency), 891
Type V (Muscle Phosphorylase Deficiency), 891
Type VI (Liver Phosphorylase or Phosphorylase Kinase
Deficiency), 891
Type VII (Muscle Phosphofructokinase Deficiency), 891
26 Lipids, Lipoproteins, Apolipoproteins, and Other
Cardiovascular Risk Factors, 903
Nader Rifai, Ph.D., and G. Russell Warnick, M.S., M.B.A.
BASIC BIOCHEMISTRY, 903
Basic Lipids, 903
Lipoproteins, 915
Apolipoproteins, 916
Lipoprotein Metabolism, 918
Reference Lipid, Lipoprotein Cholesterol, and
Apolipoprotein Levels, 922
CLINICAL SIGNIFICANCE, 924
Association With Coronary Heart Disease, 924
Disorders of Lipoprotein Metabolism, 928
Diagnosis of Lipoprotein Disorders, 932
Management of Lipoprotein Disorders, 934
MEASUREMENT OF LIPIDS, LIPOPROTEINS, AND
APOLIPOPROTEINS, 938
Historical Perspective and Background, 938
Lipids and Lipoproteins, 940
Sources of Variation in Lipid and Lipoprotein
Measurements, 954
Apolipoproteins, 958
Lipoprotein(a), 960
Apolipoprotein E, 961
OTHER CARDIAC RISK FACTORS, 962
High-Sensitivity C-Reactive Protein, 962
Homocysteine, 967
27 Electrolytes and Blood Gases, 983
Mitchell G. Scott, Ph.D., Vicky A. LeGrys, D.A., M.T.(A.S.C.R),
CLS.(N.CA), and James Stacey Klutts, M.D., Ph.D.
ELECTROLYTES, 983
Specimens for Electrolyte Determinations, 983
Sodium, 984
Potassium, 984
Electrolyte Exclusion Effect, 987
Chloride, 989
Bicarbonate (Total Carbon Dioxide), 990
PLASMA AND URINE OSMOLALITY, 992
Principles of Osmotic Pressure and Osmosis, 992
SWEAT TESTING, 994
Qualitative Screening Tests, 995
Quantitative Confirmatory Tests, 995
Reference Intervals for Sweat Chloride, 996
Sweat Stimulation and Collection, 996
Sources of Error in Sweat Testing, 998
Sweat Testing Quality Assurance, 998
BLOOD GASES AND pH, 998
Behavior of Gases, 999
Application of the Henderson-Hasselbalch Equation in
Blood Gas Measurements, 1001
Oxygen in Blood, 1002
Tonometry, 1006
Determination of PCO2) PO2, and pH, 1006
Temperature Correction of Measured pH, PCO2
and PO2, 1013
Continuous and Noninvasive Monitoring of Blood
Gases, 1014
28 Hormones, 1019
Michael Kleerekoper, M.D., F.A.C.E., F.A.C.B.
CLASSIFICATION, 1019
Polypeptide or Protein Hormones, 1019
Steroid Hormones, 1019
Amino Acid-Related Hormones, 1019
RELEASE AND ACTION OF HORMONES, 1019
Growth and Development, 1025
Homeostatic Control of Metabolic Pathways, 1025
Regulation of the Production, Use, and Storage of
Energy, 1026
ROLE OF HORMONE RECEPTORS, 1026
Cell-Surface Receptors, 1026
Intracellular Receptors, 1027
POSTRECEPTOR ACTIONS OF HORMONES, 1027
Cell-Surface Receptors, 1027
Intracellular Receptors, 1029
CLINICAL DISORDERS OF HORMONES, 1030
MEASUREMENTS OF HORMONES AND RELATED
ANALYTES, 1030
Bioassay Techniques, 1030
Receptor-Based Assays, 1030
Immunoassay Techniques, 1030
Instrumental Techniques, 1031
29 Catecholamines and Serotonin, 1033
Thomas G. Rosano, Ph.D., Graeme Eisenhofer, Ph.D.,
and Ronald J. Whitley, Ph.D.
CHEMICAL STRUCTURE, 1033
BIOSYNTHESIS, RELEASE, AND METABOLISM, 1033
Biosynthesis, 1034
Storage and Release, 1035
Uptake and Metabolism, 1036
PHYSIOLOGY OF CATECHOLAMINE AND
SEROTONIN SYSTEMS, 1039
Central Nervous System, 1040
Sympathetic Nervous System, 1041
Adrenal Medullary System, 1043
Peripheral Dopaminergic System, 1044
Enteric Nervous System, 1045
CLINICAL APPLICATIONS, 1045
Pheochromocytoma, 1045
Neuroblastoma, 1049
Dysautonomias and Genetic Disorders, 1050
Carcinoid, 1052
ANALYTICAL METHODOLOGY, 1054
Catecholamines and Metabolites, 1054
Serotonin and Metabolites, 1062
30 Vitamins and Trace Elements, 1075
Alan Shenkin, Ph.D., Malcolm Raines, F.R.S.C., F.R.C.Path.,
Gordon S. Fell, Ph.D., F.R.C.Path., and T.D.G. Lyon, B.Sc, Ph.D.
NUTRITIONAL ASSESSMENT AND
MONITORING, 1076
Protein-Energy Status, 1076
Vitamin and Trace Element Status, 1077
Enzymes or Metabolites, 1077
Markers of Antioxidant Status, 1077
Analytical Factors, 1078
VITAMINS, 1079
Vitamin A, 1079
Vitamin D, 1084
Vitamin E, 1084
Vitamin K, 1087
Vitamin B,—Thiamine, 1090
Vitamin B2—Riboflavin, 1094
Vitamin B6—Pyridoxine, Pyridoxamine,
and Pyridoxal, 1097
Vitamin B12—Cyanocobalamin, 1100
Vitamin C—Ascorbic Acid, 1105
Biotin, 1107
Folk Acid, 1109
Niacin and Niacinamide, 1114
Pantothenic Acid, 1116
TRACE ELEMENTS, 1118
Classification, 1118
Dose-Effect Relationships, 1118
Chemistry, 1119
Biochemistry/Homeostasis, 1119
Inborn Errors, 1119
Interactions, 1119
Laboratory Assessment of Trace Element Status, 1120
Analytical Considerations, 1120
Individual Trace Elements, 1122
Other Possibly Essential Elements, 1141
31 Hemoglobin, Iron, and Bilirubin, 1165
Trefor Higgins, M.Sc, Ernest Beutler, M.D.,
and Basil T. Doumas, Ph.D.
HEMOGLOBIN, 1165
Biochemistry, 1165
Physiological Role, 1169
Analytical Methodology, 1170
Clinical Significance, 1178
IRON, 1186
Biochemistry, 1186
Analytical Methodology, 1188
Clinical Significance, 1192
BILIRUBIN, 1193
Chemistry, 1193
Biochemistry, 1194
Analytical Methodology, 1195
Clinical Significance, 1198
32 Porphyrins and Disorders of Porphyrin
Metabolism, 1209
Allan C. Deacon, B.Sc, Ph.D., Dip.C.B., F.R.C.Path.,
Sharon D. Whatley, Ph.D., and George H. Elder, M.D.
PORPHYRIN CHEMISTRY, 1209
Structure and Nomenclature, 1209
Chelation of Metals, 1209
Spectral Properties, 1209
Solubility, 1210
HEME BIOSYNTHESIS, 1211
Enzymes of Heme Biosynthesis, 1211
EXCRETION OF HEME PRECURSORS, 1213
REGULATION OF HEME BIOSYNTHESIS, 1213
ABNORMALITIES OF PORPHYRIN
METABOLISM, 1214
The Porphyrias, 1214
Abnormalities of Porphyrin Metabolism Not Caused by
Porphyria, 1220
Pseudoporphyria, 1221
LABORATORY DIAGNOSIS OF PORPHYRIA, 1221
Patients With Symptoms of Porphyria, 1221
Relatives of Patients With Porphyria, 1223
ANALYTICAL METHODS, 1223
Methods for Metabolites, 1223
Methods for Blood Porphyrins, 1226
Analysis of Plasma Porphyrins, 1226
Enzyme Measurements, 1226
DNA Analysis, 1229
33 Therapeutic Drugs and Their Management, 1237
Thomas P. Moyer, Ph.D., and Leslie M. Shaw, Ph.D.
DEFINITIONS, 1238
BASIC CONCEPTS, 1238
Mechanism of Action, 1238
Pharmacokinetics, 1240
Drug Disposition, 1243
Clinical Utility, 1247
ANALYTICAL CONSIDERATIONS, 1248
Analytical Techniques, 1248
Issues of Concern, 1249
SPECIFIC DRUG GROUPS, 1249
Antiepileptic Drugs, 1249
Cardioactive Drugs, 1256
Bronchodilators, 1261
Antibiotics, 1262
Antiretrovirals, 1269
Antipsychotic Drugs, 1269
Antimetabolites, 1272
Immunosuppressants, 1274
CLINICAL APPLICATIONS, 1280
34 Clinical Toxicology, 1287
William H. Porter, Ph.D.
BASIC INFORMATION, 1287
Clinical Considerations, 1288
Analytical Considerations, 1289
Toxic Syndromes, 1289
Abstinence Syndromes, 1292
SCREENING PROCEDURES FOR DETECTION OF
DRUGS, 1292
Spot Tests, 1292
Determination of Volatiles by Serum Osmol Gap, 1292
Immunoassay, 1293
Planar Chromatography, 1293
Gas Chromatography, 1294
High-Performance Liquid Chromatography, 1296
PHARMACOLOGY AND ANALYSIS OF SPECIFIC
DRUGS AND TOXIC AGENTS, 1296
Agents That Cause Cellular Hypoxia, 1296
Alcohols, 1300
Analgesics (Nonprescription), 1304
Drugs Related to the Anticholinergic Toxidrome, 1308
Ethylene Glycol, 1313
Toxic Metals/Iron, 1314
Organophosphate and Carbamate Insecticides, 1315
Drugs of Abuse, 1317
ON-SITE DRUG TESTING, 1350
Sequential Competitive Binding Microparticle Capture
Immunoassay, 1350
Homogenous Microparticle Capture
Immunochromatography, 1351
Solid Phase Competitive Sequential Enzyme
Immunoassay, 1351
Latex-Agglutination-Inhibition Immunoassay, 1351
35 Toxic Metals, 1371
Thomas P. Moyer, Ph.D., Mary F. Burritt, Ph.D.,
and John Butz, B.A.
BASIC CONCEPTS, 1371
Prevalence of Metal-Based Toxicity, 1371
Diagnosing Toxicity, 1372
Classification of Metals, 1372
Occupational Monitoring, 1373
Analytical Methods, 1373
SPECIFIC METALS, 1374
Aluminum, 1374
Antimony, 1375
Beryllium, 1377
Cadmium, 1377
Chromium, 1378
Cobalt, 1378
Copper, 1378
Iron, 1379
Lead,1379
Manganese, 1381
Mercury, 1381
Nickel, 1383
Platinum, 1383
Selenium, 1383
Silicon, 1384
Silver, 1384
Thallium, 1384
SECTION V
MOLECULAR DIAGNOSTICS AND GENETICS
36 Principles of Molecular Biology and Approaches to
Nucleic Acid Isolation, 1393
Y.M. Dennis Lo, M.A., DM., D.Phil, F.R.C.P., F.R.C.Path.,
and Rossa W.K. Chiu, M.B.B.S., Ph.D., F.R.C.P.A.
LANDMARK DEVELOPMENTS IN GENETICS AND
MOLECULAR DIAGNOSTICS, 1393
NUCLEIC ACID CHEMISTRY, BIOCHEMISTRY, AND
BIOLOGY, 1394
Molecular Compositions and Structures of DNA and
RNA, 1394
Chromosome Structure, 1395
Replication, Transcription, and Translation, 1396
Genetics and Epigenetics, 1397
Nuclear and Mitochondrial Genomes, 1398
Circulating Nucleic Acids, 1399
NUCLEIC ACID ISOLATION, 1400
DNA Isolation, 1400
RNA Isolation, 1401
Assessment of Nucleic Acid Yield and Quality, 1401
THE HUMAN GENOME PROJECT, 1401
37 Nucleic Acid Techniques, 1407
Carl T. Wittwer, M.D., Ph.D., and Noriko Kusukawa, Ph.D.
GENOMES AND NUCLEIC ACID ALTERATIONS, 1407
Human Genome, 1407
Bacterial Genomes and Sequence Alterations, 1410
Viral Genomes and Sequence Alterations, 1410
NUCLEIC ACID ENZYMES, 1410
AMPLIFICATION TECHNIQUES, 1411
Polymerase Chain Reaction (PCR)—Target
Amplification, 1412
Other Forms of Target Amplification, 1416
Other Approaches to Amplification, 1418
Endpoint Quantification in Amplification Assays, 1419
DETECTION TECHNIQUES, 1419
Generic Measurement and Visualization of Nucleic
Acids, 1419
Reporter Molecules and Labeled Probes, 1419
DISCRIMINATION TECHNIQUES, 1421
Electrophoresis, 1421
Alternatives to Electrophoresis, 1427
Hybridization Assays—Principles, 1429
Hybridization Assays—Examples, 1432
Real-Time PCR, 1436
Melting Analysis, 1441
Comparison of Closed-Tube SNP Genotyping
Methods, 1444
CONCLUSION, 1445
38 Design and Operation of the Molecular
Diagnostics Laboratory, 1451
Anthony A. Killeen, M.D., Ph.D.
INTRODUCTION, 1451
Centralization or Decentralization?, 1451
Choosing a Test Menu, 1451
SPACE AND DESIGN CONSIDERATIONS, 1452
OPERATIONAL CONSIDERATIONS, 1452
Documents, Records, Sample Retention, 1452
Personnel, 1453
Result Reporting, 1453
Quality Assurance and Quality Improvement, 1454
Proficiency Testing, 1455
SUMMARY, 1455
39 Molecular Genetics and Diagnosis of
Hematopoietic Neoplasms, 1457
Kojo S.I. Elenitoba-Johnson, M.D.
ANTIGEN-RECEPTOR GENE REARRANGEMENTS FOR
DETERMINATION OF CLONALITY, 1458
Molecular Genetic Basis for Immunoglobulin-Gene
Rearrangements, 1458
Molecular Genetic Basis for T-Cell Receptor Gene
Rearrangements, 1460
Southern Blot Hybridization Analysis for
Antigen-Receptor (Ig or TCR) Gene
Rearrangements, 1461
Polymerase Chain Reaction Analysis of Antigen-
Receptor Gene Rearrangements, 1462
LYMPHOMA-SPECIFIC RECURRENT
CHROMOSOMAL TRANSLOCATIONS, 1463
Southern Blot Hybridization Analysis for the Detection
of Chromosomal Translations, 1464
Polymerase Chain Reaction Analysis for Detection of
Chromosomal Translations, 1464
MOLECULAR GENETICS OF LEUKEMIAS, 1466
Acute Myeloid Leukemias, 1466
Chronic Leukemias of Myeloid/Monocytic
Lineage, 1469
Use of Reverse-Transcription Polymerase Chain
Reaction in Chromosomal Translocations, 1471
ONCOGENE AND TUMOR SUPPRESSOR GENE
MUTATIONS IN HEMATOPOIETIC
MALIGNANCIES, 1472
MINIMAL RESIDUAL DISEASE DETECTION AND
MONITORING, 1474
DETECTION OF VIRAL GENOMES, 1475
Epstein-Barr Virus, 1475
IN SITU HYBRIDIZATION, 1476
POTENTIAL OF MICROARRAYS IN MOLECULAR
DIAGNOSTICS OF HEMATOLOGICAL
MALIGNANCIES, 1476
CONCLUSIONS, 1476
40 Inherited Diseases, 1483
Cindy /. Vnenatk-Jones, Ph.D.
DISEASES WITH MF.NDELIAN INHERITANCE, 1483
Autosomal Recessive Diseases, 1483
Autosomal Dominant Diseases, 1491
X-Linked Diseases, 1496
DISEASES WITH NONMENDELIAN
INHERITANCE, 1502
Mitochondrial DNA Diseases, 1502
Imprinting, 1504
Complex Diseases, 1506
REPORTING OF TEST RESULTS, 1513
41 Identity Assessment, 1539
Thomas M. Williams, MAX, Victor IV. Weedn, Mil, 1.11,
and Malek Kamoun, M.D., Ph.D.
VARIATION IN THE HUMAN GENOME, 1539
Genetic Variation Useful in Identity Testing, 1539
Exclusion of Tested Individuals, 1540
Likelihood of Inclusion of Tested Individuals, 1541
Samples Employed for Identity Testing, 1541
FORENSIC DNA TYPING, 1541
Forensic Applications, 1541
Genetic Systems Used in Forensic Identification, 1542
Instrumentation Used in Forensic Laboratories, 1544
Quality Assurance and Accreditation in Forensic DNA
Analysis, 1544
Statistical Interpretation, 1545
Convicted Offender Databases, 1545
Legal Issues, 1545
USE OF DNA TESTING FOR THE IDENTIFICATION
OF CLINICAL SPECIMENS, 1545
TRANSPLANTATION TESTING, 1546
Genetic Features of Hl.A Genes, 1546
Historical Applications of HLA Typing, 1547
Transplantation, 1547
DNA-Based HLA Allele Identification, 1548
Interpretation of HLA Test Results, 1548
Quality Assurance and Quality Control Issues, 1549
Proficiency Testing, 1549
Accreditation and Certification of Laboratories and
Professionals, 1549
CHIMERISM AND HEMATOPOIETIC CELL
ENGRAFTMENT ANALYSIS, 1549
Methods for Performing Engraftment Analysis, 1549
Selection and Interpretation of Short Tandem Repeat
Loci, 1550
Applications of Microsatellite Locus 'Testing to
Engraftment Analysis, 1550
Proficiency Testing, 1551
Quality Assurance and Quality ( .ontrol, I 551
Accreditation, 1551
PARENTAGE TESTING, 1551
Methods, Instrumentation, and Sample
Requirements, 1551
Reporting ot Test Results, 1551
Quality Assurance and Quality ('ontrol, 1352
Policy and Procedures lor Resolution of
Complaints, 1533
Accreditation, 1353
42 Molecular Methods in Diagnosis and Monitoring
of Infectious Diseases, 1555
Andrea Ferreim-Gonzalez, Ph.D.,
and Angela M. Caliendo, M.D., Ph.D.
DEVELOPMENT OF MOLECULAR ASSAYS FOR
INFECTIOUS DISEASES, 1555
Analyte-Specific Reagents, 1556
When to Use a Molecular Test for an Infectious
Disease, 1556
Choice of Specimen to Test and Analytical
Approach, 1556
Test Development, 1557
Preanalytical Variables, 1557
Internal Controls, 1557
Nucleic Acid Extraction, 1557
Quantitative Molecular LDTs, 1558
TEST VERIFICATION, 1558
Analytical Verification, 1558
Clinical Verification, 1560
QUALITY CONTROL AND QUALITY
ASSURANCE, 1561
INTERPRETATION OF RESULTS, 1562
REPORTING OF RESULTS, 1563
SPECIFIC PATHOGENS, 1563
Chlamydia Trachomatis and Neisseria
Gonorrhoeae, 1563
Human Papillomavirus, 1565
Human Immunodeficiency Virus Type 1,1567
Herpes Simplex Virus, 1570
Enterovirus, 1571
Perinatal Group B Streptococcal Disease, 1572
Cytomegalovirus, 1573
Mycobacterium tuberculosis, 1575
Hepatitis C Virus, 1576
43 Pharmacogenetics, 1589
Gwendolyn A. McMillin, Ph.D., D.A.B.C.C, Mark W. Under, Ph.D.,
and Bonny Lewis Bukaveckas, Ph.D.
DEFINING PHARMACOGENETIC TARGETS AND
WHAT TESTING TO CONSIDER, 1589
APPROACHES TO PHARMACOGENETIC
TESTING, 1590
CLINICAL APPLICATION OF PHARMACOGENETIC
TESTING, 1592
BEST EXAMPLES OF CLINICALLY RELEVANT
PHARMACOGENETIC TARGETS, 1592
Thiopurine S-Methyltransferase, 1592
Cytochrome P450 2D6 (CYP2D6), 1595
Cytochrome P450 2C19 (CYP2C19), 1600
Cytochrome P450 2C9 (CYP2C9), 1602
N-Acetyl Transferases (NAT1 and NAT2), 1603
Other Pharmacogenetic Targets and Future
Directions, 1609
SECTION VI
PATHOPHYSIOLOGY
44 Cardiac Function, 1619
Fred S. Apple, Ph.D., and Allan S. Jaffe, M.D.
BASIC ANATOMY, 1619
PHYSIOLOGY, 1621
Cardiac Cycle, 1621
Cardiac Conducting System, 1621
CARDIAC DISEASE, 1622
Congestive Heart Failure, 1622
Acute Coronary Syndromes, 1623
CARDIAC BIOMARKERS, 1629
Cardiac Troponin I and T, 1629
Brain Natriuretic Peptide, 1629
Creatine Kinase Isoenzymes and Isoforms, 1631
Myoglobin, 1632
Lactate Dehydrogenase Isoenzymes, 1632
C-Reactive Protein, 1633
Serum Amyloid, 1633
sCD40 Ligand, 1633
Cytokines, 1633
Myeloperoxidase, 1634
Phospholipase A2, 1634
Pregnancy Associated Plasma Protein A, 1634
Oxidized LDL, 1634
Matrix Metalloproteinases, 1634
Monocyte Chemotactic Protein, 1634
Tumor Necrosis Factor Alpha, 1634
Tissue Plasminogen Activator Antigen, 1634
Secreted Platelet Granular Substances, 1634
Isoprostanes, 1635
Urinary Thromboxane, 1635
Adhesion Molecules, 1635
Other Proposed Markers, 1635
ANALYTICAL MEASUREMENT OF CARDIAC
PROTEINS, 1635
Cardiac Troponin, 1635
Brain Natriuretic Peptide, 1640
Creatine Kinase-2 and Isoforms, 1642
Myoglobin, 1643
Lactate Dehydrogenase Isoenzymes, 1643
CLINICAL UTILITY, 1643
GENERAL BIOMARKER OBSERVATIONS, 1645
Cardiac Troponin, 1645
Brain Natriuretic Peptide, 1645
CK-2, 1652
Myoglobin, 1653
Lactate Dehydrogenase, 1653
GENERAL CLINICAL PRACTICE, 1653
Strategies for the Role of Cardiac Troponin for Risk
Assessment, 1654
Clinical Utility of Cardiac Markers in Monitoring
Reperfusion Following Thrombolytic Therapy, 1659
Use of Multimarkers, 1660
Estimation of Infarct Size, 1660
45 Kidney Disease, 1671
Michael P. Delaney, B.Sc, M.D., M.R.C.P. Christopher P. Price, Ph.D.,
David J. Newman, Ph.D., and Edmund Lamb, Ph.D.
ANATOMY, 1671
Blood Supply, 1671
Nephron, 1672
Juxtaglomerular Apparatus, 1676
Renal Interstitium, 1677
KIDNEY FUNCTION AND PHYSIOLOGY, 1677
Excretory and Reabsorptive Functions, 1677
Regulatory Function, 1679
Endocrine Function, 1683
Glomerular Filtration Rate, 1683
Glomerular Permeability and Filtration, 1686
Proteinuria, 1687
PATHOPHYSIOLOGY OF KIDNEY DISEASE, 1688
Diagnosis and Screening for Kidney Disease, 1689
Classification of Kidney Failure, 1689
DISEASES OF THE KIDNEY, 1691
The Uremic Syndrome, 1691
Chronic Kidney Disease, 1693
End-Stage Renal Disease, 1697
Diabetic Nephropathy, 1699
Hypertensive Nephropathy, 1702
Glomerular Diseases, 1702
Interstitial Nephritis, 1706
Polycystic Kidney Disease, 1706
Toxic Nephropathy, 1707
Obstructive Uropathy, 1707
Tubular Diseases, 1707
Diabetes Insipidus, 1711
Renal Calculi, 1711
Cystinuria, 1715
Prostaglandins and NSAIDs in Kidney Disease, 1716
Monoclonal Light Chains and Kidney Disease, 1716
Assessment of Renal Concentrating Ability: Urinary
Osmolality, 1718
RENAL REPLACEMENT THERAPY, 1718
Background, 1719
Dialysis, 1719
Kidney Transplantation, 1725
46 Physiology and Disorders of Water, Electrolyte, and
Acid-Base Metabolism, 1747
James Stacey Klutts, M.D., Ph.D., and Mitchell G. Scott, Ph.D.
TOTAL BODY WATER—VOLUME AND
DISTRIBUTION, 1747
WATER AND ELECTROLYTES—COMPOSITION OF
BODY FLUIDS, 1748
Extracellular and Intracellular Compartments, 1749
Reasons for Composition Differences of Body
Fluids, 1750
Distribution of Ions by Active and Passive
Transport, 1750
ELECTROLYTES, 1750
Sodium, 1750
Potassium, 1754
Chloride, 1757
Bicarbonate, 1757
ACID-BASE PHYSIOLOGY, 1757
Acid-Base Balance and Acid-Base Status, 1757
Buffer Systems and Their Role in Regulating the pH of
Body Fluids, 1759
Respiratory Mechanism in the Regulation of Acid-Base
Balance, 1762
Renal Mechanisms in the Regulation of Acid-Base
Balance, 1763
CONDITIONS ASSOCIATED WITH ABNORMAL
ACID-BASE STATUS AND ABNORMAL
ELECTROLYTE COMPOSITION OF THE
BLOOD, 1767
Metabolic Acidosis (Primary Bicarbonate Deficit), 1768
Metabolic Alkalosis (Primary Bicarbonate Excess), 1772
Respiratory Acidosis, 1774
Respiratory Alkalosis, 1775
47 Liver Disease, 1777
D. Robert Dufour, M.D.
ANATOMY OF THE LIVER, 1777
Gross Anatomy, 1777
Microscopic Anatomy, 1779
Ultrastructure of the Hepatocyte, 1780
BIOCHEMICAL FUNCTIONS OF THE LIVER, 1780
Hepatic Excretory Function, 1781
Hepatic Synthetic Function, 1787
Hepatic Metabolic Function, 1789
Hepatic Storage Function, 1792
CLINICAL MANIFESTATIONS OF LIVER
DISEASE, 1792
Jaundice, 1792
Portal Hypertension, 1792
Hepatorenal Syndrome, 1796
Altered Drug Metabolism, 1796
Nutritional and Metabolic Abnormalities, 1796
Disordered Hemostasis in Liver Disease, 1796
Enzymes Released from Diseased Liver Tissue, 1797
DISEASES OF THE LIVER, 1798
Mechanisms and Patterns of Injury, 1798
Disorders of Bilirubin Metabolism, 1798
Hepatic Viral Infection, 1798
Acute Hepatitis, 1804
Chronic Hepatitis, 1809
Alcoholic Liver Disease, 1817
Cirrhosis, 1819
Hepatic Glycogenoses, 1820
Cholestatic Liver Diseases, 1820
Hepatic Tumors, 1823
DIAGNOSTIC STRATEGY, 1825
Plasma Enzymes, 1826
Plasma Albumin, 1826
Prothrombin Time, 1827
Plasma Bilirubin, 1827
48 Gastric, Pancreatic, and Intestinal Function, 1849
Peter G. Hill, Ph.D., C.Chem., F.R.S.C, F.R.C.Path.
INTRODUCTION TO ANATOMY AND PHYSIOLOGY
OF THE GASTROINTESTINAL TRACT, 1849
Anatomy, 1849
Phases of Digestion, 1850
PROCESSES OF DIGESTION AND ABSORPTION, 1851
Digestion and Absorption of Carbohydrates, 1852
Digestion and Absorption of Lipids, 1854
Digestion and Absorption of Proteins, 1854
STOMACH: DISEASES AND LABORATORY
INVESTIGATIONS, 1856
Peptic Ulcer Disease and Helicobacter pylori, 1856
Diagnostic Tests for H. pylori, 1856
Determination of Basal Acid Output, 1858
INTESTINAL DISORDERS AND THEIR LABORATORY
INVESTIGATION, 1859
Celiac Disease (Celiac Sprue, Gluten-Sensitive
Enteropathy), 1859
Disaccharidase Deficiencies, 1862
Bacterial Overgrowth, 1864
Bile Salt Malabsorption, 1865
Protein-Losing Enteropathy, 1866
THE PANCREAS: DISEASES AND ASSESSMENT OF
EXOCRINE PANCREATIC FUNCTION, 1867
Pediatric Disorders of the Exocrine Pancreas, 1867
Adult Disorders of the Exocrine Pancreas, 1867
Tests of Exocrine Function of the Pancreas, 1868
GASTROINTESTINAL REGULATORY PEPTIDES, 1873
Cholecystokinin, 1873
Gastrin, 1874
Secretin, 1875
Vasoactive Intestinal Polypeptide, 1876
Glucose-Dependent Insulinotropic Peptide (GIP, Gastric
Inhibitory Polypeptide), 1876
Other Regulatory Peptides, 1876
NEUROENDOCRINE TUMORS, 1877
Gastrinoma and the Zollinger-Ellison Syndrome, 1877
The Watery Diarrhea Hypokalemia Achlorhydria
Syndrome (Werner-Morrison Syndrome, WDHA
Syndrome, VIPoma), 1877
Other Gastrointestinal Neuroendocrine Tumors and
Tumor Markers, 1877
INVESTIGATION OF MALDIGESTION/
MALABSORPTION, 1878
Evaluation of Fat Absorption, 1878
INVESTIGATION OF CHRONIC DIARRHEA, 1881
Laxative Abuse, 1881
Fecal Osmotic (Osmolal) Gap, 1883
49 Mineral and Bone Metabolism, 1891
David B. Endres, Ph.D., and Robert K. Rude, M.D.
OVERVIEW OF BONE AND MINERAL, 1891
CALCIUM, 1892
Biochemistry and Physiology, 1892
Clinical Significance, 1893
Measurement of Calcium, 1896
Patient Preparation and Sources of Preanalytical
Error for Total and Free Calcium
Measurements, 1902
Reference Intervals for Total and Free Calcium in Serum
and Plasma, 1903
Physiological Variation in Calcium, 1903
Interpretation of Total and Free Calcium Results, 1903
Urinary Calcium, 1904
PHOSPHATE, 1905
Biochemistry and Physiology, 1905
Clinical Significance, 1905
Measurement of Phosphate, 1907
Reference Intervals, 1908
MAGNESIUM, 1909
Biochemistry and Physiology, 1909
Clinical Significance, 1909
Measurement of Total Magnesium, 1911
Measurement of Free (Ionized) Magnesium, 1912
Reference Intervals for Total and Free Magnesium, 1912
HORMONES REGULATING MINERAL
METABOLISM, 1912
Parathyroid Hormone, 1912
Vitamin D and Its Metabolites, 1920
Calcitonin, 1926
Parathyroid Hormone-Related Protein, 1928
INTEGRATED CONTROL OF MINERAL
METABOLISM, 1930
Renal Handling of Calcium and Phosphate, 1930
Intestinal Absorption of Calcium and Phosphate, 1931
Bone Metabolism, 1931
Magnesium, 1931
METABOLIC BONE DISEASES, 1932
Osteoporosis, 1932
Osteomalacia and Rickets, 1933
Paget's Disease, 1934
Renal Osteodystrophy, 1934
BIOCHEMICAL MARKERS OF BONE TURNOVER, 1935
Preanalytical and Analytical Variables, 1936
Markers of Bone Resorption, 1936
Markers of Bone Formation, 1940
50 Pituitary Function, 1967
Laurence M. Demers, Ph.D., F.A.C.B., D.A.B.C.C,
and Mary Lee Vance, M.D.
ANATOMY, 1967
ADENOHYPOPHYSIS, 1968
Regulation of Function, 1968
Growth Hormone and Insulin-like Growth
Factors, 1969
Prolactin, 1976
Corticotropin (Adrenocorticotropin) and Related
Peptides, 1981
Gonadotropins (Follicle-Stimulating Hormone,
Luteinizing Hormone), 1984
Thyrotropin, 1988
Assessment of Anterior Pituitary Lobe Reserve, 1988
NEUROHYPOPHYSIS, 1991
Arginine Vasopressin, 1991
Oxytocin, 1996
51 The Adrenal Cortex, 2003
Laurence M. Demers, Ph.D., F.A.C.B., D.A.B.C.C.
GENERAL STEROID CHEMISTRY, 2003
Chemical Structure, 2003
Biochemistry, 2005
ADRENOCORTICAL STEROIDS, 2007
General Biochemistry, 2007
Metabolism, 2012
The Hypothalamic-Pituitary-Adrenal Cortical Axis, 2014
Regulation of Adrenal Hormones, 2014
Testing the Functional Status of the Adrenal
Cortex, 2016
DISORDERS OF THE ADRENAL CORTEX, 2021
Hypofunction of the Adrenal Cortex, 2021
Hyperfunction of the Adrenal Cortex, 2024
ANALYTICAL METHODOLOGY, 2033
Choice of Specimen, 2033
Free Versus Bound Steroids, 2034
Hydrolysis, Extraction, and Separation, 2034
Specific Methods, 2036
52 The Thyroid: Pathophysiology and Thyroid
Function Testing, 2053
Laurence M. Demers, Ph.D., F.A.C.B., D.A.B.C.C,
and Carole Spencer, Ph.D.
THYROID HORMONES, 2053
Chemistry, 2053
Biological Function, 2054
Biochemistry, 2055
Metabolism, 2056
Physiology, 2056
THYROID DYSFUNCTION, 2057
Hypothyroidism, 2057
Hyperthyroidism, 2059
Nonthyroidal Illness, 2061
Hypothyroidism Versus Euthyroid Sick Syndrome, 2062
Hyperthyroid Versus Euthyroid Sick Syndrome, 2063
Effect of Drugs, 2063
Diagnosis of Thyroid Dysfunction, 2063
ANALYTICAL METHODS, 2065
Determination of Thyroid-Stimulating Hormone in
Blood, 2066
Determination of Thyroxine in Serum, 2068
Determination of Triiodothyronine in Serum, 2071
Determination of Reverse Triiodothyronine (rT3) Using
Radioimmunoassay, 2073
Determination of Free Thyroid Hormones, 2073
Determination of Thyroxine-Binding Globulin and
Other Thyroid Hormone-Binding Proteins, 2082
Determination of Thyroglobulin, 2083
Determination of Antithyroid Antibodies, 2084
53 Reproductive Related Disorders, 2097
Shannon Haymond, Ph.D., and Ann M. Gronowski, Ph.D.
MALE REPRODUCTIVE BIOLOGY, 2097
Anatomy, 2097
Hypothalamic-Pituitary-Gonadal Axis, 2097
Androgens, 2098
Male Reproductive Development, 2099
Male Reproductive Abnormalities, 2102
FEMALE REPRODUCTIVE BIOLOGY, 2104
Anatomy, 2104
Hypothalamic-Pituitary-Gonadal Axis, 2105
Estrogens, 2105
Progesterone, 2108
Female Reproductive Development, 2109
Female Reproductive Abnormalities, 2110
Normal Menstrual Cycle, 2112
Ovulation, 2114
Irregular Menses, 2114
INFERTILITY, 2120
Male Infertility, 2120
Female Infertility, 2124
Assisted Reproduction, 2127
ANALYTICAL METHODOLOGY, 2127
Measurement of Total Testosterone in Blood, 2127
Measurement of Free and Weakly Bound Testosterone in
Blood, 2129
Measurement of Testosterone in Saliva, 2131
Measurement of Testosterone Precursors and
Metabolites in Blood, 2131
Measurement of Dehydroepiandrosterone and Its
Sulfate, 2132
Measurement of 17-Ketosteroids in Urine, 2134
Measurement of Anabolic Steroids, 2134
Measurement of Estrogens in Blood, 2134
Measurement of Estriol, 2136
Measurement of Estrogens in Urine, 2136
Measurement of Estrogens in Saliva, 2137
Measurement of Progesterone in Blood, 2137
Measurement of Progesterone in Saliva, 2138
54 Clinical Chemistry of Pregnancy, 2153
Edward R. Ashwood, M.D., and George ]. Knight, Ph.D.
HUMAN PREGNANCY, 2153
Conception, Embryo, and Fetus, 2153
Placenta, 2154
Amniotic Fluid, 2155
Maternal Adaptation, 2156
Functional Development of the Fetus, 2159
MATERNAL AND FETAL HEALTH ASSESSMENT, 2160
Clinical Specimens, 2160
Diagnosis and Dating of Pregnancy, 2160
COMPLICATIONS OF PREGNANCY, 2161
Abnormal Pregnancies, 2161
Trophoblastic Disease, 2165
Fetal Anomalies, 2165
Preterm Delivery, 2166
MATERNAL SERUM SCREENING FOR FETAL
DEFECTS, 2167
Clinical Application of Prenatal Screening, 2168
LABORATORY TESTS, 2179
Chorionic Gonadotropin, 2179
Alpha Fetoprotein, 2182
Unconjugated Estriol, 2183
Dimeric Inhibin A, 2186
Fetal Fibronectin, 2186
Amniotic Fluid Bilirubin (M4M), 2187
Tests for Evaluating Fetal Lung Maturity, 2188
55 Inborn Errors of Amino Acid, Organic Acid, and
Fatty Acid Metabolism, 2207
Piero Rinaldo, M.D., Ph.D., Sihoun Hahn, M.D., Ph.D.,
and Dietrich Matern, M.D.
BIOCHEMICAL DIAGNOSIS, 2207
Prenatal Diagnosis, 2208
Newborn Screening, 2209
Evaluation of Symptomatic Patients, 2209
Postmortem Screening, 2210
DISORDERS OF AMINO ACID METABOLISM, 2211
Classic Phenylketonuria and Other
Hyperphenylalaninemias, 2211
Tyrosinemia Type 1, 2217
Homocystinuria, 2219
Maple Syrup Urine Disease, 2220
Urea Cycle Defects, 2220
Nonketotic Hyperglycinemia, 2221
DISORDERS OF ORGANIC ACID METABOLISM, 2221
Disorders of Propionate Metabolism, 2222
Isovaleric Acidemia, 2222
Glutaric Acidemia Type I, 2230
Ethylmalonic Encephalopathy, 2230
DISORDERS OF FATTY ACID OXIDATION, 2230
Very Long-Chain Acyl-CoA Dehydrogenase
Deficiency, 2232
Trifunctional Protein and Long-Chain 3-Hydroxy
Acyl-CoA Dehydrogenase Deficiencies, 2232
Medium-Chain Acyl-CoA Dehydrogenase
Deficiency, 2236
Short-Chain Acyl-CoA Dehydrogenase Deficiency, 2236
ANALYTICAL CONSIDERATIONS, 2237
Analysis of Amino Acids, 2237
Analysis of Organic Acids, 2237
Analysis of Acylcarnitines, 2241
SECTION VII
APPENDIX
56 Reference Information for the Clinical
Laboratory, 2251
William L. Roberts, M.D., Ph.D.,
Gwendolyn A. McMillin, Ph.D., D.A.B.C.C.,
Carl A. Burtis, Ph.D., and David E. Bruns, M.D.
Table 56-1 Reference Intervals and Values, 2252
Table 56-2 Therapeutic and Toxic Levels of Drugs, 2303
Table 56-3 Critical Values, 2317 |
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| id | DE-604.BV026534158 |
| illustrated | Illustrated |
| indexdate | 2024-09-07T00:11:28Z |
| institution | BVB |
| isbn | 0721601898 |
| language | English |
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| physical | XXXVI, 2412 S. Ill., graph. Darst. |
| publishDate | 2006 |
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| publisher | Elsevier, Saunders |
| record_format | marc |
| spelling | Tietz Textbook of clinical chemistry and molecular diagnostics [ed. by.] Carl A. Burtis ; Edward R. Ashwood ; David E. Bruns Clinical chemistry and molecular diagnostics 4. ed. St. Louis, Mo. Elsevier, Saunders 2006 XXXVI, 2412 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Molekulare Diagnostik (DE-588)4589005-5 gnd rswk-swf Klinische Chemie (DE-588)4135255-5 gnd rswk-swf Klinische Chemie (DE-588)4135255-5 s Molekulare Diagnostik (DE-588)4589005-5 s DE-604 Tietz, Norbert W. 1926-2018 Begründer eines Werks (DE-588)172418003 oth Burtis, Carl A. edt Ashwood, Edward R. 1953- Sonstige (DE-588)172663741 oth Bruns, David E. 1941- Sonstige (DE-588)173821707 oth HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=022098656&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Tietz Textbook of clinical chemistry and molecular diagnostics Molekulare Diagnostik (DE-588)4589005-5 gnd Klinische Chemie (DE-588)4135255-5 gnd |
| subject_GND | (DE-588)4589005-5 (DE-588)4135255-5 |
| title | Tietz Textbook of clinical chemistry and molecular diagnostics |
| title_alt | Clinical chemistry and molecular diagnostics |
| title_auth | Tietz Textbook of clinical chemistry and molecular diagnostics |
| title_exact_search | Tietz Textbook of clinical chemistry and molecular diagnostics |
| title_full | Tietz Textbook of clinical chemistry and molecular diagnostics [ed. by.] Carl A. Burtis ; Edward R. Ashwood ; David E. Bruns |
| title_fullStr | Tietz Textbook of clinical chemistry and molecular diagnostics [ed. by.] Carl A. Burtis ; Edward R. Ashwood ; David E. Bruns |
| title_full_unstemmed | Tietz Textbook of clinical chemistry and molecular diagnostics [ed. by.] Carl A. Burtis ; Edward R. Ashwood ; David E. Bruns |
| title_short | Tietz Textbook of clinical chemistry and molecular diagnostics |
| title_sort | tietz textbook of clinical chemistry and molecular diagnostics |
| topic | Molekulare Diagnostik (DE-588)4589005-5 gnd Klinische Chemie (DE-588)4135255-5 gnd |
| topic_facet | Molekulare Diagnostik Klinische Chemie |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=022098656&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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