Surgical ResearchWiley W. Souba, Douglas W. Wilmore Academic Press, 25. jan. 2001 - 1460 sider 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 |
Fra bogen
Resultater 1-5 af 84
Side vi
Denne sides indhold er desværre begrænset..
Denne sides indhold er desværre begrænset..
Side xvii
Denne sides indhold er desværre begrænset..
Denne sides indhold er desværre begrænset..
Side xix
Denne sides indhold er desværre begrænset..
Denne sides indhold er desværre begrænset..
Side xx
Denne sides indhold er desværre begrænset..
Denne sides indhold er desværre begrænset..
Side xxi
Denne sides indhold er desværre begrænset..
Denne sides indhold er desværre begrænset..
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 |
1402 | |
IV Overview and Conclusion | 1407 |
Recommended Reading | 1408 |
Index | 1409 |
Andre udgaver - Se alle
Almindelige termer og sætninger
acid activity adenovirus administration analysis anesthesia anesthetic angiogenesis angiogenic animal models antibody antigen apoptosis artery assay assessment Autologous tumor cells binding Biol biology blood cancer carcinoma cDNA cell lines cellular clinical trials clones colon complex culture cytokine Department of Surgery disease effects endothelial evaluation experimental function gastric gene expression gene therapy gene transfer genetic genomic growth factor healing Health human identified immune immunotherapy induced injection Institutional Review Board intestinal investigator involving kinase knockout laboratory lung injury lymphocytes marker measure Medical melanoma membrane metastasis metastatic method mice molecular molecules mouse mRNA mutant Natl Organ injury scaling outcome patients peptide phenotype potential procedures protein protocol randomized receptor response Retrovirus risk score sepsis sequence specific Surg Surgical Research target technique tion tissue transcription factor transgenic Trauma treatment variable vascular vector virus vitro vivo Autologous tumor wound