Pathology for Toxicologists
Principles and Practices of Laboratory Animal Pathology for Study Personnel
Herausgeber: Mcinnes, Elizabeth
Pathology for Toxicologists
Principles and Practices of Laboratory Animal Pathology for Study Personnel
Herausgeber: Mcinnes, Elizabeth
- Gebundenes Buch
- Merkliste
- Auf die Merkliste
- Bewerten Bewerten
- Teilen
- Produkt teilen
- Produkterinnerung
- Produkterinnerung
Non-pathologists, such as toxicologists and study personnel, can find it difficult to understand the data they receive from pathologists. Toxicological pathologists write long, detailed and highly technical reports. Study personnel are under daily pressure to decide whether lesions described in pathology reports are treatment-related and thus important to the pharmaceutical company or whether the lesions are background changes and thus of little significance. Written by experienced toxicological pathologists, Pathology for Toxicologists: Principles and Practices of Laboratory Animal Pathology…mehr
- Toxicologic Pathology244,99 €
- Goat Science and Production167,99 €
- The Guide to Investigation of Mouse Pregnancy125,99 €
- Environmental Physiology of Livestock262,99 €
- MertensBluetongue120,99 €
- David BakerParasites of Lab Animals 2e229,99 €
- Larry EngelkingTextbook of Veterinary Physiological Chemistry113,99 €
-
-
-
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
- Produktdetails
- Verlag: John Wiley & Sons / Wiley
- Seitenzahl: 216
- Erscheinungstermin: 1. Mai 2017
- Englisch
- Abmessung: 246mm x 170mm x 15mm
- Gewicht: 1597g
- ISBN-13: 9781118755419
- ISBN-10: 1118755413
- Artikelnr.: 42966157
- Verlag: John Wiley & Sons / Wiley
- Seitenzahl: 216
- Erscheinungstermin: 1. Mai 2017
- Englisch
- Abmessung: 246mm x 170mm x 15mm
- Gewicht: 1597g
- ISBN-13: 9781118755419
- ISBN-10: 1118755413
- Artikelnr.: 42966157
Techniques 1 Elizabeth McInnes 1.1 Animal Considerations 2 1.2 Necropsy 2
1.3 Lung Inflation with Fixative 5 1.4 Fixation 5 1.5 Making Glass Slides 6
1.5.1 Trimming 6 1.5.2 Tissue Processing 9 1.5.3 Embedding 9 1.5.4
Microtoming 9 1.5.5 Staining 9 1.5.6 Quality Control 11 1.6 Special
Histochemical Stains 12 1.7 Decalcification 13 1.8 Immunohistochemistry 13
1.9 Tissue Crossreactivity Studies 15 1.10 Electron Microscopy 15 1.11 In
Situ Hybridisation 16 1.12 Laser Capture Microscopy 16 1.13 Confocal
Microscopy 16 1.14 Image Analysis 17 1.15 Digital Imaging 17 1.16
Spermatocyte Analysis 17 1.17 Good Laboratory Practice 17 1.18 Inhalation
Studies 18 1.19 Continuous?]Infusion Studies 18 1.20 Carcinogenicity 19
1.21 Biologicals 19 1.22 The Pathology Report 20 1.23 Conclusion 20
References 20 2 Recording Pathology Data 23 Cheryl L. Scudamore 2.1 What is
a Pathology Finding? 24 2.2 Standardisation of Pathology Findings 24 2.2.1
Semiquantitative Analysis 24 2.2.2 Nomenclature/Controlled Terminology 26
2.2.3 Ontological Approach 28 2.3 'Inconsistencies' in Pathology Recording
28 2.3.1 Diagnostic Drift 28 2.3.2 Thresholds 28 2.3.3 Lumping versus
Splitting 29 2.4 Blind Review 30 2.5 Historical Control Data: Pros and Cons
30 2.6 The Use of Peer Review in Pathology 32 References 32 3 General
Pathology and the Terminology of Basic Pathology 35 Elizabeth McInnes 3.1
Cellular Responses to Insults 35 3.2 Inflammation 41 3.3 Circulatory
Disturbances 46 3.4 Disorders of Tissue Growth 52 3.5 Tissue Repair and
Healing 53 3.6 Neoplasia 54 3.7 Immune System 55 References 57 4 Common
Spontaneous and Background Lesions in Laboratory Animals 59 Elizabeth
McInnes 4.1 Rats 62 4.2 Mice 63 4.3 Dogs 66 4.4 Minipigs 66 4.5 Non?]Human
Primates 67 4.6 Rabbits 67 4.7 Experimental Procedures 67 4.8 Causes of
Death in Rats and Mice 67 4.9 Conclusion 68 References 69 5 Target Organ
Pathology 72 Elizabeth McInnes 5.1 Skin 72 5.2 Eye 76 5.3 Gastrointestinal
Tract 78 5.4 Liver 83 5.5 Respiratory System 85 5.6 Urinary System 89 5.7
Lymphoreticular System 94 5.8 Musculoskeletal System 95 5.9 Cardiovascular
System 97 5.10 Endocrine System 99 5.11 Reproductive System 102 5.12
Central and Peripheral Nervous System 104 5.13 Ear 106 References 106 6
Clinical Pathology 112 Barbara von Beust 6.1 Clinical Pathology in Study
Phases and Good Laboratory Practice 112 6.1.1 Preanalytic Phase: Study Plan
113 6.1.2 Analytic Phase: Data Generation 114 6.1.3 Postanalytic Phase:
Data Interpretation and Reporting 114 6.1.4 Good Laboratory Practice 114
6.2 What is Measured in Clinical Pathology? 115 6.2.1 Interference by
Haemolysis, Lipaemia and Icterus 116 6.3 Haematology 117 6.3.1 Manual and
Automated Techniques in Haematology 118 6.3.2 Haematocrit and Red Blood
Cell Mass 119 6.3.3 Blood Cells 120 6.3.3.1 Red Blood Cells 120 6.3.3.2
White Blood Cells 122 6.3.3.3 Platelets 124 6.3.4 The Standard Haematology
Profile 124 6.3.5 Bone Marrow 125 6.4 Coagulation 125 6.4.1 Standard
Coagulation Profile 126 6.4.2 Prothrombin Time 127 6.4.3 Activated Partial
Thromboplastin Time 127 6.4.4 Fibrinogen 127 6.5 Clinical Chemistry 127
6.5.1 Metabolites 127 6.5.1.1 Carbohydrate Metabolism 127 6.5.1.2 Protein
Metabolism 128 6.5.1.3 Lipid Metabolism 128 6.5.1.4 Metabolism of
Haemoglobin 129 6.5.2 Enzymes 129 6.5.3 Electrolytes and Minerals 129
6.5.3.1 Potassium 130 6.5.3.2 Sodium and Chloride 130 6.5.3.3 Calcium and
Phosphorus 130 6.5.4 Standard Chemistry Profiles 130 6.5.4.1 Assessment of
Liver Function 130 6.5.4.2 Assessment of Kidney Function 130 6.5.4.3
Assessment of Gastrointestinal Function 131 6.6 Urinalysis 131 6.7
Acute?]Phase Proteins 131 6.8 The Biomarker Concept 132 6.9 Reference
Intervals 133 6.10 Instrumentation, Validation and Quality Control 133 6.11
Data Analysis and Interpretation 134 6.12 Reporting 135 6.13 Food
Consumption and Body Weight (Gain) 136 6.14 Organ Weights 136 6.15 Examples
of Typical Clinical Pathology Profile Changes in Toxicologic Clinical
Pathology 136 6.15.1 Reduced Red Blood Cell Mass due to Chronic Disease 138
6.15.2 Stress Response 139 6.15.3 Reduced Red Blood Cell Mass due to
Excessive Blood Sampling 139 6.15.4 Common Artefacts 139 6.15.4.1
Coagulation 140 6.15.4.2 Haemolysis and Increased Potassium Concentration
140 6.15.4.3 Blood in Urine 140 6.16 Microsampling 140 6.17 Conclusion 141
Acknowledgments 141 References 141 7 Adversity: A Pathologist's Perspective
145 Bhanu Singh 7.1 LOAEL, NOEL and NOAEL: Definition 146 7.2 Adversity 147
7.3 Determining Adversity using Pathology Findings: Factors to Consider 149
7.3.1 Severity 149 7.3.2 Functional Effect 150 7.3.3 Primary versus
Secondary Effects 151 7.3.4 Physiological Adaptability 152 7.3.5
Reversibility of the Lesion 152 7.3.6 Pharmacological Effect 153 7.4
Communicating NOAEL in Toxicity Studies 153 7.5 Conclusion 154 References
154 8 Limitations of Pathology and Animal Models 157 Natasha Neef 8.1
Limitations of In Vivo Animal Models 157 8.1.1 Traditional Laboratory
Species Used as General Toxicology Models 157 8.1.2 The Test Article May
Not have Sufficient Pharmacological Activity in Routine Toxicology Species
158 8.1.3 The Model May Not Identify Hazards Related to Causation or
Exacerbation of Pathology that is Unique to Humans or Undetectable in
Animals 159 8.1.4 The Model May Not Identify Hazards with Low Incidence/Low
Severity 159 8.1.5 Potential for Misinterpretation of
Reversibility/Recovery for Low?]Incidence Findings 160 8.1.6 Potential for
Over?] or Underestimation of the Relationship to Test Article of Findings
that have High Spontaneous Incidence in Laboratory Species, but are
Relatively Rare in Humans 160 8.1.7 Exclusive Use of Young, Healthy Animals
Kept in Ideal Conditions Gives Limited Predictivity for Aged/Diseased Human
Populations 161 8.2 Efficacy/Disease Models as Toxicology Models 162 8.3
Limitations of Efficacy/Disease Models as Toxicology Models 164 8.3.1 Lack
of Validation as Safety/Toxicology Models 164 8.3.2 Disease Models Rarely
Have All the Elements of the Equivalent Human Disease 165 8.3.3 Limited
Sensitivity Produced by Increased Interanimal Variability amongst Diseased
Animals and/or Low Animal Numbers 165 8.3.4 Lack of Historical Data 166
8.3.5 Risk Associated with Nonregulated Laboratory Conditions 166 8.4
Limitations of Pathology within In Vivo Toxicology Models 167 8.4.1
Anatomic Pathology Evaluation Will Not Identify Hazards with No
Morphological Correlates 167 8.4.2 Limitations of Pathology when Evaluating
Moribund Animals or Animals Found Dead on Study 168 8.4.3 Limitations of
Anatomic and/or Clinical Pathology End Points within other Types of In Vivo
Preclinical Safety Study 168 8.4.4 Limitations of Histopathology Related to
Sampling Error 169 8.4.5 Limitations of Quantitative Anatomic Pathology 170
8.4.6 Limitations of Pathology Related to Subjectivity and Pathologist
Error 173 8.4.7 Anatomic Pathology Error/Missed Findings 173 8.4.8
Subjectivity and Pathologist Variability 175 8.5 Managing Risk Associated
with Subjectivity and the Potential for Pathologist Error 176 8.5.1 Choice
of Study Pathologist 176 8.5.2 Peer Review 176 8.5.3 Review of the Anatomic
Pathology Data 177 8.5.4 Review of Anatomic Pathology Data Interpretation
177 References 179 Glossary 184 Index 187
Techniques 1 Elizabeth McInnes 1.1 Animal Considerations 2 1.2 Necropsy 2
1.3 Lung Inflation with Fixative 5 1.4 Fixation 5 1.5 Making Glass Slides 6
1.5.1 Trimming 6 1.5.2 Tissue Processing 9 1.5.3 Embedding 9 1.5.4
Microtoming 9 1.5.5 Staining 9 1.5.6 Quality Control 11 1.6 Special
Histochemical Stains 12 1.7 Decalcification 13 1.8 Immunohistochemistry 13
1.9 Tissue Crossreactivity Studies 15 1.10 Electron Microscopy 15 1.11 In
Situ Hybridisation 16 1.12 Laser Capture Microscopy 16 1.13 Confocal
Microscopy 16 1.14 Image Analysis 17 1.15 Digital Imaging 17 1.16
Spermatocyte Analysis 17 1.17 Good Laboratory Practice 17 1.18 Inhalation
Studies 18 1.19 Continuous?]Infusion Studies 18 1.20 Carcinogenicity 19
1.21 Biologicals 19 1.22 The Pathology Report 20 1.23 Conclusion 20
References 20 2 Recording Pathology Data 23 Cheryl L. Scudamore 2.1 What is
a Pathology Finding? 24 2.2 Standardisation of Pathology Findings 24 2.2.1
Semiquantitative Analysis 24 2.2.2 Nomenclature/Controlled Terminology 26
2.2.3 Ontological Approach 28 2.3 'Inconsistencies' in Pathology Recording
28 2.3.1 Diagnostic Drift 28 2.3.2 Thresholds 28 2.3.3 Lumping versus
Splitting 29 2.4 Blind Review 30 2.5 Historical Control Data: Pros and Cons
30 2.6 The Use of Peer Review in Pathology 32 References 32 3 General
Pathology and the Terminology of Basic Pathology 35 Elizabeth McInnes 3.1
Cellular Responses to Insults 35 3.2 Inflammation 41 3.3 Circulatory
Disturbances 46 3.4 Disorders of Tissue Growth 52 3.5 Tissue Repair and
Healing 53 3.6 Neoplasia 54 3.7 Immune System 55 References 57 4 Common
Spontaneous and Background Lesions in Laboratory Animals 59 Elizabeth
McInnes 4.1 Rats 62 4.2 Mice 63 4.3 Dogs 66 4.4 Minipigs 66 4.5 Non?]Human
Primates 67 4.6 Rabbits 67 4.7 Experimental Procedures 67 4.8 Causes of
Death in Rats and Mice 67 4.9 Conclusion 68 References 69 5 Target Organ
Pathology 72 Elizabeth McInnes 5.1 Skin 72 5.2 Eye 76 5.3 Gastrointestinal
Tract 78 5.4 Liver 83 5.5 Respiratory System 85 5.6 Urinary System 89 5.7
Lymphoreticular System 94 5.8 Musculoskeletal System 95 5.9 Cardiovascular
System 97 5.10 Endocrine System 99 5.11 Reproductive System 102 5.12
Central and Peripheral Nervous System 104 5.13 Ear 106 References 106 6
Clinical Pathology 112 Barbara von Beust 6.1 Clinical Pathology in Study
Phases and Good Laboratory Practice 112 6.1.1 Preanalytic Phase: Study Plan
113 6.1.2 Analytic Phase: Data Generation 114 6.1.3 Postanalytic Phase:
Data Interpretation and Reporting 114 6.1.4 Good Laboratory Practice 114
6.2 What is Measured in Clinical Pathology? 115 6.2.1 Interference by
Haemolysis, Lipaemia and Icterus 116 6.3 Haematology 117 6.3.1 Manual and
Automated Techniques in Haematology 118 6.3.2 Haematocrit and Red Blood
Cell Mass 119 6.3.3 Blood Cells 120 6.3.3.1 Red Blood Cells 120 6.3.3.2
White Blood Cells 122 6.3.3.3 Platelets 124 6.3.4 The Standard Haematology
Profile 124 6.3.5 Bone Marrow 125 6.4 Coagulation 125 6.4.1 Standard
Coagulation Profile 126 6.4.2 Prothrombin Time 127 6.4.3 Activated Partial
Thromboplastin Time 127 6.4.4 Fibrinogen 127 6.5 Clinical Chemistry 127
6.5.1 Metabolites 127 6.5.1.1 Carbohydrate Metabolism 127 6.5.1.2 Protein
Metabolism 128 6.5.1.3 Lipid Metabolism 128 6.5.1.4 Metabolism of
Haemoglobin 129 6.5.2 Enzymes 129 6.5.3 Electrolytes and Minerals 129
6.5.3.1 Potassium 130 6.5.3.2 Sodium and Chloride 130 6.5.3.3 Calcium and
Phosphorus 130 6.5.4 Standard Chemistry Profiles 130 6.5.4.1 Assessment of
Liver Function 130 6.5.4.2 Assessment of Kidney Function 130 6.5.4.3
Assessment of Gastrointestinal Function 131 6.6 Urinalysis 131 6.7
Acute?]Phase Proteins 131 6.8 The Biomarker Concept 132 6.9 Reference
Intervals 133 6.10 Instrumentation, Validation and Quality Control 133 6.11
Data Analysis and Interpretation 134 6.12 Reporting 135 6.13 Food
Consumption and Body Weight (Gain) 136 6.14 Organ Weights 136 6.15 Examples
of Typical Clinical Pathology Profile Changes in Toxicologic Clinical
Pathology 136 6.15.1 Reduced Red Blood Cell Mass due to Chronic Disease 138
6.15.2 Stress Response 139 6.15.3 Reduced Red Blood Cell Mass due to
Excessive Blood Sampling 139 6.15.4 Common Artefacts 139 6.15.4.1
Coagulation 140 6.15.4.2 Haemolysis and Increased Potassium Concentration
140 6.15.4.3 Blood in Urine 140 6.16 Microsampling 140 6.17 Conclusion 141
Acknowledgments 141 References 141 7 Adversity: A Pathologist's Perspective
145 Bhanu Singh 7.1 LOAEL, NOEL and NOAEL: Definition 146 7.2 Adversity 147
7.3 Determining Adversity using Pathology Findings: Factors to Consider 149
7.3.1 Severity 149 7.3.2 Functional Effect 150 7.3.3 Primary versus
Secondary Effects 151 7.3.4 Physiological Adaptability 152 7.3.5
Reversibility of the Lesion 152 7.3.6 Pharmacological Effect 153 7.4
Communicating NOAEL in Toxicity Studies 153 7.5 Conclusion 154 References
154 8 Limitations of Pathology and Animal Models 157 Natasha Neef 8.1
Limitations of In Vivo Animal Models 157 8.1.1 Traditional Laboratory
Species Used as General Toxicology Models 157 8.1.2 The Test Article May
Not have Sufficient Pharmacological Activity in Routine Toxicology Species
158 8.1.3 The Model May Not Identify Hazards Related to Causation or
Exacerbation of Pathology that is Unique to Humans or Undetectable in
Animals 159 8.1.4 The Model May Not Identify Hazards with Low Incidence/Low
Severity 159 8.1.5 Potential for Misinterpretation of
Reversibility/Recovery for Low?]Incidence Findings 160 8.1.6 Potential for
Over?] or Underestimation of the Relationship to Test Article of Findings
that have High Spontaneous Incidence in Laboratory Species, but are
Relatively Rare in Humans 160 8.1.7 Exclusive Use of Young, Healthy Animals
Kept in Ideal Conditions Gives Limited Predictivity for Aged/Diseased Human
Populations 161 8.2 Efficacy/Disease Models as Toxicology Models 162 8.3
Limitations of Efficacy/Disease Models as Toxicology Models 164 8.3.1 Lack
of Validation as Safety/Toxicology Models 164 8.3.2 Disease Models Rarely
Have All the Elements of the Equivalent Human Disease 165 8.3.3 Limited
Sensitivity Produced by Increased Interanimal Variability amongst Diseased
Animals and/or Low Animal Numbers 165 8.3.4 Lack of Historical Data 166
8.3.5 Risk Associated with Nonregulated Laboratory Conditions 166 8.4
Limitations of Pathology within In Vivo Toxicology Models 167 8.4.1
Anatomic Pathology Evaluation Will Not Identify Hazards with No
Morphological Correlates 167 8.4.2 Limitations of Pathology when Evaluating
Moribund Animals or Animals Found Dead on Study 168 8.4.3 Limitations of
Anatomic and/or Clinical Pathology End Points within other Types of In Vivo
Preclinical Safety Study 168 8.4.4 Limitations of Histopathology Related to
Sampling Error 169 8.4.5 Limitations of Quantitative Anatomic Pathology 170
8.4.6 Limitations of Pathology Related to Subjectivity and Pathologist
Error 173 8.4.7 Anatomic Pathology Error/Missed Findings 173 8.4.8
Subjectivity and Pathologist Variability 175 8.5 Managing Risk Associated
with Subjectivity and the Potential for Pathologist Error 176 8.5.1 Choice
of Study Pathologist 176 8.5.2 Peer Review 176 8.5.3 Review of the Anatomic
Pathology Data 177 8.5.4 Review of Anatomic Pathology Data Interpretation
177 References 179 Glossary 184 Index 187