CONTENTS - Contributors xx Preface xxi Acknowledgements xxiv Foreword xxv
PART 1 PRINCIPLES
1 Introduction to lmmunoassay Principles Chris Dauies Immunoassay for beginners Kinetics of antibody-antigen interactions lmmunoassay design
Competitive (reagent limited) assays Single-site irnmunometric assays Two-site immunometric assays (reagent excess) Determinants of assay sensitivity Detection and quantification of antibodies Special considerations for solid-phase imrnunoassays Comparison of experimental and theoretical immunoassay performance
2 Non-Competitive lmmunoassays for Small Molecules - The Anti-Complex, Selective Antibody and Apposltlon Systems Colin H. Self, Stephen Thompson and Larry A. Winger lntroduction The anti-complex assay
--=*miry------ Multiple binding assay Selective antibody immunomeMc assay Apposition assay Conclusions
3 Ambient Analyte Assay Roger Ekins Introduction Basic theoretical principles Applications of the ambient analyte assay principle - -
Microspot assays Free (non-protein bound) hormone immunoassays Other applications of the principle
Summary and conclusion
4 Free Analyte lmmunoassay Nic D. Christofides Basic principles governing the free hormone concentration Calculation of free analyte concentration Spreadsheet for calculation of free analyte concentration Effect of serum proteins on free analyte concentration in uftm measurement of free analyte concentration
Direct equilibrium dialysis Immunoassays for free analytes Tests of validity (accuracy)
Concluding remarks
The lmmunoassay Handbook
5 The Foundations of Immunochemistry Robert F. Ritchie Introduction The immunological reaction (1895-1935)
Summary Qualification by diffusion in gel (1861-1977)
Summay Qualitative analysis - by immunoelectrophoresis (1953-1978)
Summary Quantification of antigens by in-gel immunochemistry (1963-present)
Summay Quantification of antigens by in-liquid immunochemistry (1935-present)
Changes in immunization practice Summay
Quantification of antigens by particle-enhanced immunochemistry (1972-present) Summary
Labeled immunoassay (1959-present) Summay
Comparative studies (1907-present) Summay
6 Concepts Chris Dauies Assay concepts
Assay sensitivity Accuracy and bias Precision and imprecision Cross-reactivity Interference Recovey Dilution Correlation and method comparison Assay drift
Clinical concepts Diagnosis Reference interval Bias Clinical sensitivity and specificity Positive and negative predictive values Prevalence and clinical utility Likelihood ratio Continuous measurement, ROC curves Confidence interval analysis of clinical performance Probabilistic interpretation of test results Analytical goals
Summary
7 lmmunoassay Development in the In Vitro Diagnostic Industry Doug Brandt and Steve Figard Assay design overview
The needs of the customer The capability of the technology The requirements for consistent manufaduring
Experimental design in immunoassay development Preamble The process in overview The problems assuaged by DOE The particulars
Four key assay design principles
Contents
Plan first Think from a theoretical perspective Simplify the approach Establish specifications before starting
Concluding comments
8 Antibodies E y l Liddell Introduction Antibody structure The antibody response in vfuo Antibody diversity Immunization
Immunogen Polyclonal antisera
Purification of antisera Monoclonal antibodies
Immune lymphocytes Myeloma cell lines Cell fusion Hybrid selection Antibody screening tests Cloning Storage and propagation Human monoclonal antibodies Purification of monoclonal antibodies
Antibody fragments Bispecific antibodies Chimeric and humanized antibodies Recombinant antibodies
Recombinant phage antibody library construction Selection of specific phage antibodies Altering antibody characteristics Synthetic recombinant antibodies Bivalent and bipecific recombinant antibodies
Antibody conjugates and fusion proteins in diagnostics Polyclonal, monoclonal or recombinant?
9 Standardization and Calibratlon Dauid Wild Standardization
The role of external quality assessment (proficiency testing) schemes International standards Definitive and reference methods Other reference materials Heterogeneity of standard material Method-related causes of standardization diierences Special considerations for assay of antibodies
Calibration Analyte International standards Secondaw standards Calibrators Standard and calibrator matrices Reduced and stored calibration curves Recovery and dilution
10 Separation Systems David Wild and WIad Kusnezow Liquid-phase separations
Electrophoresis
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The lmmunoassay Handbook
Gel filtration Dextran-coated charcoal Precipitation by salts, organic solvents and polyethylene glycol (PEG) Double (second) antibody precipitation PEG-assisted second antibody precipitation Aspiration and decantation methods
Surface-coated solid phases General principles of protein binding to plastic surfaces Covalent attachment of proteins to solid phases Glass and plastic particles Magnetizable particles Tubes, wells and microtitration plates Beads Common solid phase Membrane tiltration Immunochromatography Western blot
Washing Competitive assays Immunometric assays Removal of interfering substances The mechanics of washing
Microarray Immunoassay Separation Basic principles of receptor ligand interaction on microarray Solid-phase medium Protein attachment on microarrays
11 Signal Generation and Detection Systems (Excluding Homogeneous Assays) Larry J. Kricka and David Wild Radioactive labels
Radioactivity measurement Preparation of radioactive tracers
Enzyme labels Colorimetry Fluorometty Chemiluminescence Enhanced chemiluminescence
Direct fluorescence Long wavelength fluorescence
Time-resolved fluorescence Direct chemiluminescence Bioluminescence Phosphorescence Microparticle labels StreptavididAvidin-Blotin Protein A Amplification strategies Multiple analytes and miniaturization
Microarrays
12 Homogeneous lmmunoassays Edwin F. Ullman Introduction Particle agglutination
Erythrocytes and latex Gold sols
Lysis immunoassays Spin immunoassays
Contents
Fluorescent labels Fluorescence polarization immunoassay Fluorescence resonance energy transfer Fluorescence protection assays Fluorescence fluctuation
Enzyme immunoassays Enzyme-multiplied immunoassay technique (EMITm) Charge induced enzyme activation Enzyme channeling
Enzyme effector immunoassays Subsirate linked fluorescence immunoassay (SLFIA) Enzyme cofactor immunoassay Enzyme inhibitor immunoassay Enzyme complementation immunoassay
Isotopic labels Scintillation proximity assay
Electroactive labels Electrochemical detection Electrochemiluminescence
Oxygen channeling immunoassays Luminescent oxygen channeling immunoassay
Conclusion
13 Calibration Curve-fitting Bany Nix and David Wild Introduction
Dose-response metameter Response-error relationship Homo- and heteroscedasticity Linearizing transformations Normalizing transformations Outliers Empirical and theoretical curve-fitting methods Least-squares fitting procedure Weighted least-squares procedure Precision profiles
Examples of calibration curve-fitting methods Hand-plots Linear interpolation Spline fits Polynomial regression Logit-log and four-parameter log-logistic methods Five-parameter log-logistic Four-parameter law of mass action
Monitoring the quality of curve-fitting Stored calibration curves, factory master c w e s , and adjusters
Master calibration curve Adjusters Modeling calibration curve changes over shelf life Use of electronic data transmission Summary
Suitable calibration curve-fit software
14 Conjugation Methods Alastair H. Dent Categories of conjugates employed in immunoassay Protein-protein coupling
Functional chemistry of proteins Categories of protein-protein coupling reaction Common protein-protein coupling methods
The lmmunoassay Handbook
Genetic engineering approaches to protein conjugation Protein-small molecule coupling
Introduction Common protein-small molecule coupling methods
Purification of conjugates Chromatographic approaches to conjugate purification Other approaches to conjugate purification
Characterization of conjugates Conclusion
15 immunological Biosensors James K. Gimzewski, Jason Reed, Michael A. Teitell and P. Gordon Malan Overview Electrochemical sensors
Arnperometric sensors Potentiometric sensors
Nanomechanical sensors Piezoelectric mass sensors Microcantilever sensors Micromagnetic sensors
Optical sensors Fluorescent evanescent wave sensors Integrated optical sensors Quantum dots
Conclusions and future directions
16 Surface Plasmon Resonance in Kinetic, Concentration and Binding Site Analyses --
~TKarlsson~erfmWaan~a-rgFPn*----------- lntroduction
Objectives of protein studies in basic research Protein studies and therapeutics Technology demands
SPR biosensors Technology principles Sensorgrams and report points lmmobiition Surface activity and immobilization levels
Binding site analysis - epitope mapping Pair-wise epitope mapping
Kinetic analysis SPR in kinetic analysis
Concentration analysis Direct binding assays Inhibition assays
Summary
17 Lab-on-a-Chip, Micro-, and Nanoscale lmmunoassay Systems Larry J. Kricka and David Wild Fundamental Uerences due to miniaturization
Viscosity and surface tension Capillary flow Electroosmosis The effects of reduced volume on low concentration samples Effect of reduced volumes on kinetics
Immunoassay design at micro- and nanoscale Assay format Antibodies
Contents
Standardization and calibration Separation Signal generation Homogeneous immunoassay On-chip detection methods Bioelectronic chips and irnmunoassay Microarrays and irnmunoassay Atomic force microscopy
ManufacMng and business considerations Conclusions
PART 2 PRODUCT TECHNOLOGY
18 Introduction to Product Technology in Clinical Diagnostic Testing David Wild Immunoassay product technologies
Use of fluorescence-labeled antibodies Agglutination assays Radioirnmunoassay and immunoradiometric assay Heterogeneous enzyme immunoassay Homogeneous enzyme immunoassay Automated homogeneous batch analyzer Automated heterogeneous batch analyzer Non-radioactive systems with increased sensitivity Semi-automated systems Automated dual technology batch analyzer Automated, multianalyte batch analyzers Random-access analyzers with bulk reagent packs Unitized random-access systems Clinical chemistry analyzers Near-patient tests Home-use tests Other applications Future developments
19 Market Trends David Huckle and David Wild lmmunoassay market status Established trends
Market drivers Advances in technology New analytes
The future of the immunodiagnostics business Application of marketing theory to immunodiagnostics Future market requirements Changes in the customer base Potential impact of new technologies New analytes
Conclusion Summary of likely trends In immunodiagnostics and related products
20 Choosing an Automated lmmunoassay System Lori J. Sokoll and Daniel W. Chan Defining automation goals Sources of information Considerations and criteria
Laboratoty environment considerations Test menu considerations
The lmmunoassay Handbobk
Technical and clinical considerations Financial considerations Operational considerations
Summary
21 Automated System Features Alain Truchaud, Tanguy Le Neel, Murielle Cazaubiel, Bernard capolaghi and Jean-Pierre Yuert Introduction Specific requirements of immunoassays Concepts in immunoassay automation: workstations vs. integrated systems Reagent features
Infrequent calibration Traceability Multiselective testing and continuous operation
Sample features Sample integrity Biosafety Dilution and reflex testing Stat testing
Incubation and washing Measurement Total quality managemenffbaceability Maintenance Ergonomics Integrated automation Conclusion
22 Over-the-Counter Pregnancy Test Kits Michael J. Wheeler -
Introduction Evaluation of OTC kits User preferences Factors affecting the measurement of hCG in urine
Summary
23 Fluorescence Microscopy: MicroTrakm Tom Houts
24 Automated Batch Analyzers: IMX@ Kent Ford
25 Bulk Reagent Random-Access Analyzers: U ~ ~ C A P @ 100 Gareth Evans and Mats Rilven
26 Automated Panel Analyzers PRISM^" Dinesh Shah and Jim Stewart
27 Unitized Reagent Random-Access Analyzers: IMMULITE~ and IMMULITE 1000 Arthur L. Babson
28 Bulk Reagent Random-Access Analyzers: ~cS:180@' SE Ehio Gramignano
29 Bulk Reagent Random-Access Analyzers: AxSYM" Theresa Donahoe
30 Bulk Reagent Random-Access Analyzers: ~lecsys@' lmmunoassay Systems May Beth Myers
31 Bulk Reagent Random-Access Analyzers: ~itros'@ ECi David Wild
32 Bulk Reagent Random-Access Analyzers: IMMULITE@ 2000 and IMMULITE 2500 Arthur L. Babson
Contents
33 Bulk Reagent Random-Access Analyzers: ADVlA centauraP Laura Taylor and Elvio Gmmignano
34 ~ r c h i t e c t ~ R000@ and D000& Analyzers Frank A. Quinn
35 CEDIA~, a Homogeneous Enzyme lmmunoassay System William A. Coty and Rueyming Loor
36 Clinical Chemlstry Analyzers: v ITRos~~@ Immuno-Rate and ~ i c r o ~ i p ~ ~ Assays Susan J. Danielson and David A. Hilborn 418
37 Near-Patient Tests: The TRIAGE@ System Kenneth F. Buechler
38 Near-Patient Tests: stratusm CS Acute careTM Diagnostic System W.N. McLellan 43 1
39 Over-the-counter Tests: Clearblue Pregnancy TestTM, Clearblue Ovulation TestTM and ~ l e a r v i e w ~ Keith May
40 Over-the-counter Tests: Persona Keith May
PART 3 LABORATORY MANAGEMENT
41 Subject Preparation, Sample Collection and Handling CoHn Wilde Subject state and preparation
Stress Exercise Food and drink Posture Medical procedures Drugs Pregnancy Age Race
Timing Biological rhythms Dynamic tests Pathological changes Nonthyroidal illness Therapeutic drug monitoring
Blood collection by venepuncture Precautions relating to the patient Phlebotomy techniques Blood collection Preparation of serum Preparation of plasma Whole blood
Interference by tube and stopper components Interference Precautions
The use of serum separators Characteristics of separators Interference Other additives Hemolysis
Collection of blood by skin puncture
The lmmunoassay Handbook
Skin puncture sites Collection into capillary tubes
Urine collection Containers Preservative Types of collection Instructions Sample handling
Saliva Procedures for sampling saliva Special precautions
Cerebrospinal fluid Formation of cerebrospinal fluid Collection of CSF
Amniotic fluid Collection of amniotic fluid Amniocentesis Special precautions
Sweat Semen Hair Milk Storage and transportation Conclusions
42 Laboratory Quality Assurance Pierre Block and Manuella Martin Staff selection and training
F i e d volume pipettes Repeating pipettes Semi-automated instruments Manual dilutions
Equlpment maintenance and testing Laboratory water
Water-purification methods Water purity measurement Recommended water quality
Sample control Sample collection Centrifugation Storage
Reagent and control preparation Assay quality control
Within-assay precision Between-assay precision Internal QC programs QC software on automated analyzers New generation QC software programs QC parameters other than controls QC in infectious disease tests
Point-of-care tests
43 Point-of-Care Testing James H. Nichols Delivery options
Terminology Sites Operators Menu Economics
Contents
Clinical outcome Quality assurance
Components of good laboratory practice Regulations Data management
Practical management Technical validation Quality control Administration
Summary
44 lmmunoassay Troubleshooting Guide David Wild I n s ~ c t i o n s Troubleshooting guide
Control bias - consistent change in values from one period of time to another (or from one reagent lot to another) Gradual change in control values (not consistent change at one time or with change in reagent lot) Commercial controls consistently biased from target mean (not change in values across same lot of controls) Bias in proficiency testing (external quality assessment) scheme from other users of the same assay Bias in proficiency testing (external quality assessment) scheme of one method from all-laboratoy mean or reference method Poor within-assay precision Poor between-assay precision or individual control failure Assay drift Low signal level Low binding in a competitive immunoassay Low binding in an immunometric assay Increase in binding in a competitive immunoassay Reduction in EDso (estimated dose at 50% of binding at zero concentration) - competitive immunoassays only Increase in EDm (estimated dose at 50% of binding at zero concentration) competitive immunoassays only High non-specific binding Poor linearity of dilution Unexpected or inconsistent clinical classification Apparent shift in reference interval (normal range) Negative patient sample concentrations Poor recovery Poor assay sensitivity Poor correlation between two irnmunoassays
PART 4 APPLICATIONS
45 Thyroid Rhys John, Carole A. Spencer, Nic Christofides and David Wild Normal thyroid function Clinical disorders
Hypothyroidism (thyroid hormone deficiency) Hyperthyroidism Nontoxic goiter Nonthyroidal illnesdsick euthyroid syndrome L-thyroxine replacement therapy Endogenous antibodies to T3 and T4 Familial dysalbuminemic hyperthyroxinemia
Analytes Thyrotropin
The lmmunoassay Handbook
Thyroxine T3 or T uptake and calculation of free thyroxine index Free T4 Triiodothyronine Free T3 Thyroxine-binding globulin Thyrofxopin receptor antibodies Thyroid peroxidase antibodies Thyroglobulin antibodies Thyroglobulin
Thyroid testing strategies
46 The Adrenal Cortex Sami Medbak Normal adrenocortical function Clinical disorders
Hypercortisolemia Hypocortisolemia
Analytes Cortisol Adrenocorticotropic hormone
Management of patients 4 t h Cushing's syndrome Pre-admission Admission to endocrine ward (e.g. on Monday)
47 Bone Metabolism Kay W. Colston and John C. Stevenson Normal calcium metabolism Clinical disorders
Hypercalcernia Parathyroid disorders Hypocalcemia Vitamin D disorders Medullary carcinoma of the thyroid Paget's disease Osteoporosis
Analytes Vitamin D metabolites: 25-hydroxyvitamin D,1,25-dihydroxyvitamin D Parathyroid hormone Parathyroid hormone-related protein Calcitonin
Biochemical markers of bone turnover Markers of bone formation Markers of bone resorption Serum tartrate resistant acid phosphatase (TRAP)
Conditions associated with changes in bone markers
48 lnfertllity Michael J. Wheeler Clinical disorders
Primary hypogonadism in the female Secondary hypogonadism in the female Infertility and normal menstrual function Primary hypogonadiim in the male Secondary hypogonadism in the male Impaired sperm transport and sperm viability
Analytes Luteinizing hormone (lutropin) Follicle stimulating hormone (follitropin) Proladin
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Inhibin Estradiol Progesterone Testosterone Dihydrotestosterone
Test strategy for infertility in women
49 In Vitro Fertiilzation and Embryo Transfer (IVF-ET) August C. Oliuar Stage I: induction of ovulation Stage 11: oocyte retrieval Stage 111: oocyte insemination and incubation Stage IV: embryo transfer
Other assisted reproductive technology procedures Gamete intra-Fallopian tube transfer Zygote inh-Fallopian transfer
Micromanipulation of gametes Assisted hatching Intracytoplasmic sperm injection
Analytes Estradiol
50 Hirsutism and Vlriiization in the Female Michael J. Wheeler Clinical disorders
Polycystic ovarian syndrome Androgen-secreting tumors of the ovary Congenital adrenal hyperplasia Cushing's syndrome
Analytes Luteinizing hormone and follicle-stimulating hormone Testosterone Sex hormone-binding globulin Free testosterone Androstenedione Dehydroepiandrosterone sulfate 17a-Hydroxyprogesterone Dihydrotestosterone Androstanediols and their glucuronides
51 Pregnancy Tim Chard Clinical disorders
Detection of early pregnancy Threatened abortion Ectopic pregnancy Chromosome defects of the fetus Neural tube defects of the fetus Premature labor Placental insufficiency Pre-eclampsia Miscellaneous disorders
Analytes Alphafetoprotein Human chorionic gonadotropin Estriol Pregnancy-associated plasma protein-A Other analytes Screening for Down's syndrome
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52 Growth and Growth Hormone Deficiency Michael Preece and Jane Pringle Normal childhood growth Clinical disorders
Growth hormone deficiency or insufficiency Growth hormone resistance Excessive growth hormone secretion
Anal ytes Growth hormone Growth hormone binding protein Insulin-like growth factors: IGF-I (somatomedin C) and IGF-I1 Insulin-like growth factor binding proteins
General strategy
53 Diabetes Mellltus Penny Clark Analytes
Insulin, proinsulin(s) and C-peptide Glycohemoglobin (GHb) Other glycated proteins Microalbumin Autoimmune and other a s ~ ~ y s
54 Hematology Derek Dawson, Hany Waters and John Ardem Normal blood function Clinical disorders
Anemia Polycythemia Iron overload and hemochromatosis Hemostatic disorders Leukemia and lymphoma
Analytes Anemia Intrinsic factor antibody Ferritin Transferrin Transferrin receptors Erythropoietin
Thrombosis and hemostasis Thrombophilia
Proteins C and S Antithrombin
Coagulation Coagulation factors Fibrinogen
Evidence of disseminated intravascular coagulation FibrinogenIFibrin degradation products D-Dimer test
Infrequently used and research assays P-Thromboglobulin Platelet factor 4 Heparin cofactor I1 Plasminogen Tissue plasminogen activator
lmmunodetection methods Leukemia and lymphoma analytes Malarial parasites Hemoglobinopathies
Contents
55 Cardiac Markers Alan H.B. Wu Normal heart function Clinical disorders
Coronary artery disease Heart failure Hypertension
Analytes Creatine kinase and the MB isoenzyme Myoglobin Cardiac troponin (T and I) Free btty acid binding proteins and carbonic anhydrase III isoenzyme Apolipoproteins AI, AII, and B Lipoprotein (a) Homocysteine C-reactive protein Brain natriuretic peptide and NT-PRO-BNP Plasma renin Plasminogen activators and inhibitors
56 Cancer Markers Mavanur R. Suresh Introduction History and classification
Nomenclature and idiosyncrasies of glycoprotein tumor antigens New developments
Analytes Carcino-embryonic antigen a-fetoprotein Carbohydrate antigen 19-9 (sialyl Lewisa) Cancer antigen 125 (Muc-16) Cancer antigen 15-3 Estrogen receptor and progesterone receptor Fecal occult blood Prostate-specific antigen Prostatic acid phosphatase Pz-Microglobulin Neuron-specific enolase Carbohydrate antigen 50 Squatnous cell carcinoma antigen Tissue polypeptide antigen, tissue polypeptide specific antigen and Cyfra 21-1 Placental alkaline phosphatase Human chorionic gonadotropin Cathepsin D Interleukin-2 receptor C-Erb B-2 (Her-2/Neu) oncoprotein P53 Bladder tumor antigen Immunochromatography assays for tumor markers Free light chain (FLC) assays
Novel experimental and other minor markers Cancer antigen 195 (CA 195) Tumor-associated glycoprotein 72.4 (TAG 72.4)
sialyl s-lOO Lewi (SLX-I) Mucin-like carcinoma-associated antigen (MCA) Cancer-associated antigen 549 (CA 549) Bone alkaline phosphatase B/T gene rearrangement test
The lmmunoassay Handbook
BRCAl and BRCA2 P21 or RAS DR-70 9 0 W - 2 BP Ekl-2 NMP-22 MMP assays TAG-12 CA 1-18 Angiogenic factors Chromogranin A Telomerase Urinaiy bladder cancer (UBC) antigen HHV-8 antibody Nor-IMetanephrine RIA HER2/neu PML protein
57 Allergy Lars Yman Allergic disease
Diagnosis and therapy Allergens
Analytes Total serum IgE Allergenspecific IgE antibody IgG antibody assays IgA antibody assay Markers of cell activation
Standardization and evaluation Quantitative measurement of allergen-specific IgE antibodies Reference values Quality control
Clinical applications Diagnosis of atopic disease and identification of offending allergen Prediction and monitoring of the development of allergic disease
58 Autoimmune Disease David F. Keren Analytes
Anti-nuclear antibodies Anti-double-stranded (ds) DNA Anti-Sm Anti-RNF' Anti-SSA/Ro Anti-SSB/La Anti-histone Anti-DNP Anti-centromere Anti-scl-70 Rheumatoid factor Anti-cyclic citrullinated (anti-CCP) peptide Anti-neutrophil cytoplasmic antibodies (C-ANCA, P-ANCA) Anti-glomerular basement membrane (GBM) AntiJo-1 Anti-microsomal (thyroid peroxidase - TPO) Islet cell autoantibodies (ICA) Anti-adrenal cortical antibodies
Contents
Anti-parietal cell antibodies (PCA) Anti-mitochondrial antibodies (AMA, or M2) Anti-smooth muscle antibodies (SMA) Anti-liver - kidney microsomal (LKM) IgA anti-endomysium IgA anti-tissue transglutaminase (anti-tTG) IgG and IgA anti-gliadin Anti-acetylcholine receptor (ACHR) Striational antibodies Calcium channel antibodies Anti-cardiolipin antibodies Anti-myelin oligodendrocyte glycoprotein (MOG) and anti-myelin basic protein (MBP) antibodies
59 Sexually Transmitted Diseases Bruce J. Dille, Alan S. Armstrong and lsa K. Mushahwar Neisseria gonorrhoeae Chlamydia trachomatis Trichomonas uaginalis Candida albicans - vaginitis Gardnerella vaginalis Herpes simplex virus type 2 Syphilis (Treponema pallidum)
60 Congenital Diseases of Microbiological Origin Bruce J. Dille, John W. Saford Jr. and lsa K. Mushahwar Cytomegalovirus Rubella virus Toxoplasma gondli IgG avidity tests Parvovirus B19 Group B streptococci
61 Hepatitis Isa K. Mushahwar Hepatitis A virus, anti-HAV IgM, anti-HAV IgG Hepatitis B virus, HBsAg, HBcAg, HBeAg, anti-HBs, anti-HBc, anti-H& IgM, anti-HBe Hepatitis C virus Hepatitis D virus Hepatitis E virus GB viruses
GB virus C
62 Human Retroviruses George J. Dawson and lsa K. Mushahwar Etiologic agents HTLV-I/-I I HIV-11-2
63 Dengue Virus Infections Bruce J. Dille and Isa K. Mushahwar
64 Miscellaneous Diseases of Microbiological Origin Bruce J. Dille and Isa K. Mushahwar Herpes simplex virus type 1 Epstein-Barr virus Chagas' disease Candida albicans - invasive candidiasis Borrelfa burgdorferi Helicobacter pylori
The lmmunoassay Handbook
Group A streptococcus Human herpesvirus 6 Human herpesvirus 8 (Kaposi's sarcoma herpesvirus)
65 Therapeutic Drug Monitoring (TDM) Philip A. Routledge and Alun D. Hutchings lnttoduction
Assay technology Measurement of free drug concentration Practical aspects of TDM
Antiarrhythmic drugs Acecainide (N-acetylprocainamide) Disopyramide Lidocaine Procainarnide Propranolol Quinidine Arniodarone Flecainide
Antibiotics Arnikacin Kanamycin Gentamicin Tobramycin Netilmicin Chloramphenicol Vancomycin
Anticonvulsants -- -Phenm------
Phenobarbital (phenobarbitone) Primidone Carbamazepine Valproic acid Ethosuxirnide
Chemotherapeutic agents Methotrexate
Miscellaneous Acetaminophen (paracetamol) Tricyclic antidepressants Cy closporin Digoxin Digitoxin TheophyUine
66 Drugs of Abuse Brian Widdop Applications
Drug dependence treatment centers Psychiatric clinics Medical-legal applications Drug abuse in the workplace
lmmunoassays for drugs of abuse Amphetamine Methamphetamine Methylenedioxyamphetamine Methylenedioxy-methamphetamine Barbiturates Benzodiazepines Cannabis
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Contents
Cocaine Fentanyl Lysergic add diethylamide Methadone Opiates Phencyclidine Propoxyphene
Legal addictive substances Alcohol (ethyl alcohol) and the use of carbohydrate-deficient transferrin Nicotine and the use of cotinine
Steroid abuse in sport Anabolic androgenic steroids
Rapid immunoassay tests for drugs of abuse
67 Assays for Drug-screening Applications and Research Jefiey K. Horton, Stephen J. Capper, Molly J. Price Jones and Kelvin T. Hughes Assay technology
Tritium radioimmunoassays Iodine-125 radioimmunoassays Scintillation proximity assay The application of SPA technology to the measurement of protein: protein interactions using an antibody capture format Imaging technologies and instrumentation for ultra high-throughput drug-screening Enzyme immunoassays
Analytes Prostaglandins Leukotrienes Rat hormone assays Cytokines Signal transduction assays Cell proliferation immunoassay Matrii metalloproteinases (MMPs) Cardiovascular peptides Neurodegeneration assays
68 lmmunoassay Appllcatlons In Veterinary Diagnostics Erwin Workman Infectious disease diagnosis/assessment of immune status
Feline Canine Porcine Equine Bovine Avian Murine
Assessment of reproductlve/metabolic status FelineICanine Equine Bovine
Conclusion
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