Surgical Research

Forsideomslag
Wiley W. Souba, Douglas W. Wilmore
Academic Press, 25. jan. 2001 - 1460 sider
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With the recent changes in the health care industry, surgeons face increasing pressure to devote their time to their clinical activities, thus limiting their research efforts. It is essential that young and creative individuals are encouraged to perform research and are given incentives to participate in research under the mentorship of more experienced research investigators.

Surgical Research is the first book to include all the information necessary for the surgical scientist to perform a research experiment. The editors have assembled outstanding, expert investigators in multiple surgical fields and asked them to describe how they achieve their research accomplishments. In Surgical Research, these experts in the field have outlined everything involved in preparing and conducting a research project. Some of the topics covered in the book include how to state a research question, how to review the available information, how to write research protocol, how to obtain grant money for the experiment, how to analyze the data, and how to present the findings. Also discussed are the ethics of animal and human experimentation along with the history and philosophy of surgical research.

To continue to advance technologies and surgical methods, research must continually be performed. Potentially great discoveries are being missed because would-be researchers do not know where to start or how to conduct research, and therefore do not even try. This book provides prospective researchers with all the basic steps needed to perform a research experiment in the surgical field. No student, resident, or fellow should start a research project without this book and no senior surgical scientist should be without it occupying a prominent position in the library.

Key Features
* The first complete compendium detailing the process and procedures to perform surgical research
* Provides details on and compares various methodologies
* A "must have" resource for the surgical resident, fellow, or scientist
* Includes a listing of resources and web sites to help the researcher even further

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Indhold

Getting Started
1
Assessing Available Information
3
External Measures of Quality
5
V Suggestions for the Future
7
References
8
Organizing and Preliminary Planning for Surgical Research
9
II Research Training
10
V General Preparation
11
VI Direct Compensatory Hyperplasia
707
Animal Models for the Study of Hepatocyte Transplantation
709
II Hepatocyte Isolation
710
V Human Hepatocyte Transplantation
716
References
717
Biliary Stone Formation
721
III Animal Models of Gallstones
724
IV Models for Cholesterol Crystal Nucleation
726

Writing a Protocol Animals Humans and Use of Biologic Chemical and Radiologic Agents
13
II Research Utilizing Laboratory Animals
14
III Human Subject Research
17
IV Institutional Safety Committees
19
V Summary
22
Grantsmanship
23
III Grant Preparation General Comments
24
IV Grant Preparation Specific Comments
25
V Other Considerations
27
References
28
Informed Consent and the Protection of Human Research Subjects Historical Perspectives and Guide to Current United States Regulations
29
II United States Regulations Governing Informed Consent
36
III Conclusion
43
References
44
Animal Care and Maintenance
47
III Available Resources
48
IV Surgical Facility Design
50
VI Anesthetic Recommendations by Species
52
VII Analgesia
58
VIII Resources
60
Funding Strategies and Agencies AcademicIndustrial Relationships Intellectual Property
63
III Industry
66
IV State Incubators and Local University Incubators
67
V Intellectual Property
68
Statistical Considerations
71
II Hypothesis Testing
72
III Sample Size Calculations
75
IV Summary
80
Use of Nonexperimental Studies to Evaluate Surgical Procedures and Other Interventions The Challenge of Risk Adjustment
81
II Dimensions of Risk
82
III Data Sources
86
IV Multivariate Modeling Framework
87
V Incorporating Risk in Multivariate Models
89
The Propensity Score and Instrumental Variables
90
VII Conclusions
97
Measuring Surgical Outcomes
101
III Specific Measures of Health Status
104
IV Utilities
105
V Patient Satisfaction
107
References
108
The SF36V2 Health Survey Questionnaire
111
Design of Clinical Trials
115
II Hypotheses Specific Aims and Endpoints
116
III Patient Eligibility
117
V Treatment Plan
119
VI Data Collection and Quality Assurance
120
VII Statistical Considerations in the Design of Clinical Trials
121
VIII Informed Consent
123
IX Summary
125
Using Administrative Data for Clinical Research
127
III Cautions about Using Administrative Databases for Research
132
IV Conclusions
135
References
136
Research in the Intensive Care Unit Ethical and Methodological Issues
137
II Spectrum of Research in the Intensive Care Unit
138
III Site Selection and Investigator Responsibilities
146
IV Ethical Issues
147
References
153
Research in the Operating Room
155
Problems and Solutions
156
What Works and Why
160
IV The Operating Room as Laboratory
161
V Technology Assessment
162
VI Summary and Conclusions
164
References
165
Effects of Age and Gender
167
II Age and Gender as Surrogates
168
IV Design Issues for Observational Studies
169
V Other Issues in Study Design
171
VI Animal Models
172
VII Summary
173
Strategies Principles and Techniques Using Transgenic and Knockout Mouse Models
175
III Design of Advanced Experiments
181
IV Pitfalls in Transgenic and Knockout Experiments
185
V Stepwise Analysis of Genotype Gene Expression and Phenotypes in Transgenic and Knockout Mice
187
VI Modification of Phenotype by Genetic Differences in Inbred Strains
188
VII Combinatorial Genetic Manipulations in Mice
189
VIII Conclusions
190
Tissue Culture Cell Growth and Analysis
193
III Handling of Media and Cells
194
IV Maintaining Frozen Stocks and Record Keeping
196
VI Primary Cultures
198
VII Contamination and Decontamination
200
VIII Cell Growth Analysis
201
IX Resources
203
References
205
Hematopoietic Stem Cells Basic Concepts and Applications to Surgical Research
207
II Historical Review
208
V Mesenchymal Stem Cells
210
VII Stem Cell Transplantation to Induce Tolerance
211
IX In Vivo Techniques
213
References
214
Basic Molecular Biological Methods in Surgical Research Genetic Library Construction Screening and DNA Sequencing
217
II Genetic Library Construction Screening and DNA Sequencing
218
III Conclusion
230
References
231
Transcription
233
III Methods to Identify Gene Expression
235
IV Methods of Identifying Differentially Expressed Genes
237
V Mapping a Eukaryotic Promoter
241
VI Identifying and Cloning Transcription Factors
243
References
250
Signal Transduction and Apoptosis
253
II Interactions between Signal Transduction Proteins
256
III Protein Phosphorylation Plays a Key Role in Enzyme Activity Regulation
259
IV Receptor Agonist and Antagonist with Blockade
261
Dominant Negative Proteins Elucidate the Importance of Signal Transduction Cascades
262
VI Regulation of Signal Transduction Gene Expression
264
VII Signal Transduction and Apoptosis
266
VIII Key Resources
269
References
270
Mechanisms and Regulation of Eukaryotic Protein Synthesis
271
III Methods for Studying Protein Synthesis
279
References
282
Organelle Studies Mitochondria Golgi and Endoplasmic Reticulum
285
II Surgically Relevant Questions
286
How to Study
290
References
295
Membrane Biology and Biophysics
297
II Methodology General Considerations
298
IV Cell Membrane Injury
302
V Sealing of Permeabilized Membranes
304
Molecular Epidemiology Beyond Gene Discovery to Clinical Diagnostic Tools
307
II Utility of Molecular Genetic Testing
308
III State of the Science
310
IV Recommendations to Surgical Investigators
314
References
316
Shock Models Hemorrhage
317
II Models of Hemorrhagic Shock
318
of Hemorrhage
319
V Heparin as a Possible Confounding Variable
321
VI Uncontrolled Hemorrhage Models
322
References
327
Scoring Systems for Trauma Research
331
III The New Injury Severity Score
332
VI Multiple Organ Failure Scoring
339
References
345
Blunt Trauma Models Fractures Chest Trauma Head Injury SoftTissue Trauma and Abdominal Trauma
347
II Blunt Head Injury Models
348
III Blunt Chest Trauma Models
349
IV Blunt Abdominal Trauma Models
350
V Fracture Models
351
VI SoftTissue Trauma Modeling 5
353
VIII Conclusion
354
Trauma Models for Studying the Influence of Gender and Aging
357
II Experimental Trauma Models
358
IV Conclusions
364
Animal Models of Burn Injury
367
II Animal Rights Considerations
368
V Small Animals
373
VI Conclusion
374
Wound Care Models
379
II In Vitro Models of Tissue Repair
380
III Animal Models
381
IV Impaired Healing Models
383
V Transgenic Models
386
VII Conclusion
387
Models of Adult Respiratory Distress SyndromeAspiration
393
III IschemiaReperfusion Models
394
IV Models of Hemorrhage That Induce Acute Lung Injury
395
V Models Using Intravenous Injections
396
VI AspirationInduced Models
397
VII Summary
398
Tumor Angiogenesis
401
II Models of Angiogenesis
405
Issues and Expectations
409
References
410
Approaches to Adoptive Immunotherapy
415
II Immunology Background
416
III Tumor Evasion of the Immune System
418
V Methods for Evaluation of Lymphocytes for Adoptive Immunotherapy
423
VI Conclusion
431
Metastasis Biology and Experimental Models
435
III Experimental Models for Studying the Biology of Metastasis
440
References
442
Cancer Genetics
445
II Experimental Methods
447
III Genetic Abnormalities in Human Cancer
452
IV The Future
454
References
455
Cancer Gene Therapy
457
III Cancer Gene Therapy Techniques
484
IV Summary
490
Active Immunotherapy for Cancer
497
II Methods of Antigen Identification
499
III Assays of Cytotoxic T Lymphocyte Activation and Function
502
IV Summary
505
Gastrointestinal Motility
507
III Techniques of Measuring Contractile Activity
509
IV Techniques of Measuring Gastric Emptying
514
V Techniques of Measuring Intestinal Transit
517
VI Techniques of Measuring Defecation
520
VII Models for Studying Gastrointestinal Motility
521
References
529
Models of Intestinal Secretion and Absorption
533
II In Vitro Studies
534
III In Vitro Models of Intestinal Transport
538
IV In Vivo Models
542
V Conclusion
544
Surgical Models of Inflammatory Bowel Disease
547
II Spontaneous Models
548
III Transgenic Rodent Models
550
IV Other Models
552
V Conclusions
554
Intestinal Regeneration and Adaptation Models
557
II In Vivo Models
558
III In Vitro Models
568
IV Summary
570
Minimally Invasive Surgery
573
II Models and Methodology
574
III Setup and Equipment
579
IV Funding
580
References
581
Experimental Models and Endpoints for Studies of Intestinal IschemiaReperfusion Injury
583
II Clinical Relevance
584
IV In Vivo Models of Intestinal IschemiaReperfusion Injury
585
V Considerations for Experimental Models of Intestinal IschemiaReperfusion Injury
590
VI End points for in Vivo Studies of Intestinal IschemiaReperfusion Injury
591
VII In Vitro Models of Intestinal IschemiaReperfusion Injury
593
VIII Endpoints for in Vitro Studies of Intestinal IschemiaReperfusion Injury
594
IX Summary
595
Gut Barrier Failure
599
II The Gut Barrier
600
III Models for Studying Barrier Function
601
IV Conclusion
609
References
610
Developmental Studies in the Gastrointestinal Tract
613
III Tissue and Organ Culture
616
IV Transgenic Animals in Studies of Developmental Biology
620
References
621
Animal Models of Liver Failure
623
III Toxic Liver Injury
625
IV Immune Liver Injury
627
References
633
Portal Hypertension and Portacaval Shunt
637
II PortalSystemic Shunt
656
References
685
Animal Models of Liver Regeneration
703
II Liver Regeneration
704
IV Regeneration Following Partial Hepatectomy
705
V Regeneration Following Portal Branch Ligation
706
V Models for Studying Biliary Motility
729
VI Gallbladder Mucosal Absorption
730
VII Conclusion
731
Models for the Study of Pancreatitis
733
II Acute Pancreatitis
734
III Chronic Pancreatitis
741
IV Preparations for in Vitro Study
742
V Conclusions
743
References
744
Models of Endocrine Insufficiency
747
II General Approaches to Study of Endocrine Insufficiency
748
III Methodology Considerations
749
V Pancreatic Insulin Insufficiency
750
VI Adrenal Insufficiency
753
VII Thyroid Insufficiency
754
VIII Sex Hormones
755
Animal Models in Transplantation
757
II General Techniques
758
III General Operative Procedures
762
IV Organ Transplantation
764
V Summary
769
References
770
Models to Study Surgical Nutrition and Metabolism
773
II Determining the Initial MetabolicNutritional State
774
IV MethodologyGeneral Principles
775
VII Animal Models
781
VIII Cultured Cells
784
IX Organelle Studies
785
XI Resources
786
References
787
Stable Isotopes
789
III Analysis
791
IV Calculation of Isotope Enrichment from Mass Spectrometer Data
792
VI Assumptions
794
References
795
Body Composition
797
III Methodology
798
IV Body Composition Models
806
V Practical Problems in Measuring Body Composition in Intensive Care Patients
807
VII Resources
809
Energetics
813
III Regional Methods
817
IV Cells
822
Models of Protein Metabolism
825
II Protein Synthesis
826
III Protein Degradation
831
IV Muscle
833
V Intestine
838
VI Conclusions
841
References
842
Membrane Transport of Nutrients
845
II Survey of Methods
846
IV Practical Membrane Methods to Assess Solute Transport
852
V Conclusions
854
Models of Wound Healing in Growth Factor Studies
855
II Types of WoundsAnimal Models
856
III Methods to Quantify Wound Healing
865
IV Conclusion
867
References
868
Animal Models of Sepsis and the Multiple Organ Dysfunction Syndrome
873
III The Ideal Animal Model of Sepsis
876
References
883
The ImmunoInflammatory Response
891
III Neutrophils
896
IV T Helper Cells
903
Antibiotic Trials
907
III Regulatory Considerations
908
V Current FDA Guidelines
913
VI The Clinical Investigator
914
References
915
Scoring Systems for Sepsis and the Multiple Organ Dysfunction Syndrome
919
III Scoring Systems for Sepsis
921
IV Scoring Systems for Multiple Organ Dysfunction Syndrome
923
V Limitations in the Use and Interpretation of Scores
928
Cytokine Biology
931
II Cytokine Response to Inflammation
932
III Exogenous Delivery of Cytokines
935
IV Inhibition of Cytokine Production or Action
938
V Measuring Cytokine Expression and Activities
940
VI Conclusion
942
Biology of Nitric Oxide Measurement Modulation and Models
947
IV Methods for Detection of NO and Measurement of NOS Activity
949
V Methods of Manipulating NO in Experimental Models
955
VI Conclusions
962
Endothelial Cell and Smooth Muscle cell Biology in Vascular Disease
969
III Experimental Models of Atherosclerosis Aneurysm and Restenosis
972
References
979
Coagulation Biology
987
IV BiochemicalMolecular BiologicImmunologic Evaluation Techniques
992
V Summary
996
References
997
Endovascular Research Stents
999
II Protocols
1000
III Experimental Design
1001
IV Methods
1003
V Clinical Evaluation
1006
Noninvasive Vascular Measurements
1009
II Patient Compliance Safety and Limitations
1010
V Doppler Ultrasound
1012
VI Measurements of Pressure
1014
IX Representative Studies
1017
X New Technology
1022
Techniques to Study Microcirculation
1025
III Isolated Microvessels
1028
IV Laser Doppler Flowmetry
1029
VI Indirect Techniques
1030
References
1031
Blood Substitutes in Surgery
1035
IV HemoglobinBased OxygenCarrying Solutions as Blood Substitutes
1037
References
1042
Research Models in Pediatric Surgery
1045
III Hirschsprungs Disease
1047
IV Necrotizing Enterocolitis
1049
V Cryptorchidism
1051
VI Intestinal Adaptation Following Massive Small Bowel Resection
1053
VII Abdominal Wall Defects
1056
References
1058
Research in Fetal Surgery
1063
III Preterm Labor after Fetal Surgery
1066
IV DiseaseBased Models
1069
References
1077
Research in Plastic Surgery
1079
IV Craniofacial Surgery
1085
References
1089
Research Methods in Neurosurgery
1093
II Neuropathologic Techniques for Study of Cerebral Ischemia and Related Disorders of the CNS
1094
III Neuroscience Techniques for Study of the Structure and Function of the CNS
1101
References
1102
Research in Urologic Surgery
1105
IV Tissue Engineering
1111
V Conclusion
1114
Research in Cardiac Surgery
1117
II Myocardial Stunning
1119
III Hibernating Myocardium
1123
IV Ischemic Preconditioning
1124
V Apoptosis
1128
VI Conclusion
1130
References
1131
Research in Orthopedic Surgery
1135
II Long Bones
1137
III Osteoporosis
1144
IV Immobilization and the Effects of Exercise
1149
V Spine
1152
VI Implant Coatings
1157
VII Joint Prostheses
1161
VIII Articular Cartilage
1164
IX Meniscus
1168
X Tendons and Ligaments
1170
XI Shoulder
1174
XII Miscellaneous Conditions
1177
XIII The Future Direction of Orthopedic Research
1180
References
1181
Statistical Analysis Specific Statistical Tests Indications for Use
1199
II Continuous Data
1201
III Categorical Data
1209
IV Survival Data
1210
V Correlation
1211
VI Summary
1213
Data Presentation How to Write and Submit Abstracts and Papers
1215
IV Developing the Manuscript
1219
V Formatting the Manuscript
1227
VI The Ethics of Authorship
1228
VII Choosing a Journal
1230
The Health Club Dilemma
1231
References
1233
Audiovisual Communications as a Research Skill
1235
III Timing and Speaking Style
1236
V Delivery
1237
VI Summary
1238
Organizing and Managing Meetings and Conferences
1239
II Choosing a Site
1240
III Contracts
1241
VI Audiovisual
1242
VIII Registration
1244
X Exhibits and Posters
1245
XIII Professional Management
1246
The Management and Organization of a Surgical Research Laboratory
1247
III Collaboration
1249
V Laboratory Safety
1252
Suggested Reading
1257
History and Philosophy of Surgical Research
1259
II Rules for Successful Research by Surgeons
1262
III Successful SurgeonScientists
1263
IV Surgical Science History
1266
Present and Future
1272
References
1273
The Surgical Research Program as a Business Enterprise
1277
IV Developing the Financial Plan
1279
VI Research as a Business
1282
VII Summary
1284
Nobel Laureates in Surgery
1285
II Surgical Award Winners
1286
III Summary
1294
References
1295
Surgical Education Research
1297
IV Results of Research in Surgical Education
1300
V Challenges for Surgical Education in the Future
1301
VI Future Research Opportunities
1302
Mathematical Modeling
1307
III Summary
1313
Suggested Readings References and URLs
1315
Information Resource Discovery for Surgeons Databases and the Internet
1317
II Databases
1319
III Internet Resources
1324
IV Suggested Reading
1333
How to Review a Manuscript
1336
III General Issues about Reviewing
1336
IV Conclusions
1336
Academic Surgical Mentoring
1337
Recommended Reading
1341
Ethics and Surgical Research
1343
II Guiding Principles of Ethical Surgical Research
1344
III Character as an Ethical Guide in the Research Setting
1350
Whose Paper Is It Who Decides and Who Controls Publication?
1352
VI Conclusion
1353
The National Institutes of Health Procedures and Performance
1355
II Structure of the NIH
1356
IV Funding Mechanisms
1357
V Life Cycle of an NIH Application
1360
VI Preparation of a Grant Proposal to the NIH
1364
VII Summary
1367
Measuring Performance of Surgical Research
1369
II Assessing the Performance of the Research Program
1370
III A New Research Model in Surgical Research?
1373
References
1375
Virtual Reality and Surgery
1377
II Definitions and Background
1378
IV Augmented Reality
1383
VI Telesurgery
1384
VII Conclusions and Future Research
1385
Surgeons and Health Services Research
1387
II Methods
1388
III Clinical Practice Improvement A New Approach
1392
IV Summary and Future Considerations
1395
References
1396
From Idea to Product Financing and Regulatory Issues in Product Development
1399
III Regulatory Structure for New Device Products
1402
IV Overview and Conclusion
1407
Recommended Reading
1408
Index
1409
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