Transplantation Immunology.pdf - E-Lib FK UWKS

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Status of Liver <strong>Transplantation</strong> 35 cable approach to inducing renal allograft tolerance achieving potent and sustained antitumor effects in patients with multiple myeloma (24). 8. Donors The biggest obstacle to the continued expansion of liver transplantation is the increasing gap between waiting lists and organ availability. If localized primary liver tumors, alcoholic liver disease, and allograft failure are accepted as indications, the demand for liver transplants has been calculated to be 25 per million population (25). Using current donor criteria, no more than 80% of all donor livers can be used (25); thus, depending on donor incidence, between 30 and 80% of the patient demand can be met. In 2001, 1978 potential liver recipients died on the waiting list in the United States without receiving a graft (UNOS database). On first consideration, the prospects for the future are not encouraging. Donor numbers have decreased because of a progressive (and welcome) fall in the two leading causes of brain death in the United Kingdom: head injury from road traffic accidents and intracranial hemorrhage (26). Between 1989 and 1992, the annual number of donors in the United Kingdom resulting from road traffic accidents fell from 279 to 194, a decrease of 30%. The situation is further complicated by changes in neurosurgical practice. Improvements in imaging and shortage of intensive care beds have resulted in a more restrictive policy in the transfer of patients to regional neurosurgical units: patients with a very poor prognosis can now be identified at an early stage. For this reason many patients who would previously have been assessed in a neurosurgical intensive care unit are no longer identified as potential donors (27). A number of strategies are evolving to address the current situation. These include the use of organs from marginal donors (those outside the criteria previously used in respect to age, co-morbid condition, and cardiovascular stability), organs from NHBDs, the more extensive use of liver splitting (to obtain two transplants from one donor liver), and the transplantation of organs from living donors. Each of these potential solutions raises specific clinical and ethical issues. 9. Marginal Donors What constitutes a “marginal donor” remains controversial, and different transplant units have developed their own arbitrary policies to determine whether a liver is used or discarded based on broadly accepted guidelines. A selection of 10 major studies in the last decade on this subject includes no less than 32 separate parameters in the various definitions. These include preexisting liver damage (steatosis, obesity, alcohol, deranged liver function tests), adverse lifestyle (drug abuse, homosexual practice), age, hemodynamic instability (hypotension,
36 Friend and Imber inotrope use, cardiac arrest, NHBDs), risks of sepsis and malignancy, and others (length of stay on intensive therapy unit [ITU], malnutrition, hypernatremia). Widening the acceptance criteria in an effort to expand the donor pool has become a necessity. The use of livers from marginal donors has been shown in several studies to lead to an increased risk of primary graft dysfunction (28– 31). This term encompasses both catastrophic primary nonfunction, resulting in death or retransplantation in the first week, or impaired primary function manifest as a coagulation disturbance and increased transaminase levels and resulting in prolonged ITU stay and increased requirement for renal support (and greatly increased cost). Both primary nonfunction and impaired primary function represent the clinical manifestations of cumulative injury derived from the period of brain death within the donor, subsequent warm/cold ischemia during preservation, and reperfusion at the time of transplantation. A recent study from Birmingham suggested that the two most important independent donor variables that correlate with graft dysfunction are macrosteatosis (>30% on histopathological analysis) and donor age (32). In the study the outcome with such marginal organs could be dramatically improved if cold ischemia time was restricted to no more than 12 h. Strasberg et al. reaffirmed this association by describing cold preservation time, steatosis, and donor age as the only three parameters with a proven relationship to early graft outcome, the others having an uncertain relationship that required further evaluation (33). 10. Reduced-Size Liver <strong>Transplantation</strong> Size reduction of an adult liver was implemented initially to overcome the need for size-matched grafts in pediatric recipients. The technique was introduced clinically in 1981, and the first successful transplant of part of a liver was reported by Bismuth and Houssin, who transplanted the left lobe from an adult to a child in 1984 (34). Further experience at several centers suggested that the use of the left lateral segment (segments II and III) taken from an adult donor would provide an ideal-sized graft for a small child and that the results were comparable to whole size-matched grafts (35). An additional refinement, reported from both Europe and Australia, was the retention of the recipient vena cava, to which the venous outflow (the left hepatic vein) of the graft was anastomosed (36,37). This allowed even larger donor-to-recipient size mismatches as well as retaining a right hemi-liver with intact vena cava. This enabled the concept of liver splitting and, subsequently, living donation. 10.1. Liver Reduction Liver reduction involves transplantation of part of the liver, the remaining liver being discarded. It is a solution to size discrepancy, but does not affect the
Page 1 and 2: METHODS IN MOLECULAR BIOLOGY 333 T
Page 3 and 4: M E T H O D S I N M O L E C U L A R
Page 5 and 6: © 2006 Humana Press Inc. 999 River
Page 8 and 9: Contents Preface ..................
Page 10 and 11: Contributors PAUL J. R. BARTON •
Page 12 and 13: Current Status of Renal Transplanta
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Page 41 and 42: METHODS IN MOLECULAR BIOLOGY 333 T
Page 43 and 44: 30 Friend and Imber meaningful surv
Page 45 and 46: 32 Friend and Imber the most urgent
Page 47: 34 Friend and Imber ent population
Page 51 and 52: 38 Friend and Imber very experience
Page 53 and 54: 40 Friend and Imber 14. Auxiliary L
Page 55 and 56: 42 Friend and Imber subsequent isol
Page 57 and 58: 44 Friend and Imber 21. Heffron, T.
Page 59 and 60: 46 Friend and Imber 53. Saudubray,
Page 61 and 62: 48 Lakey et al. There are an estima
Page 63 and 64: 50 Lakey et al. diabetic to burn su
Page 65 and 66: 52 Lakey et al. ber 31, 2000, less
Page 67 and 68: 54 Lakey et al. Fig. 1. Schematic v
Page 69 and 70: 56 Lakey et al. Table 1 Effect of I
Page 71 and 72: 58 Lakey et al. from suitable donor
Page 73 and 74: 60 Lakey et al. mined by high-perfo
Page 75 and 76: 62 Lakey et al. Fig. 3. (A) Mean po
Page 77 and 78: 64 Lakey et al. Fig. 5. HbA1c at 3-
Page 79 and 80: 66 Lakey et al. All patients enjoy
Page 81 and 82: 68 Lakey et al. 6. Sirolimus-based
Page 83 and 84: 70 Lakey et al. Fig. 7. Two-layer (
Page 85 and 86: 72 Table 2 Human Islet Transplantat
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Page 89 and 90: 76 Lakey et al. difficult to isolat
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86 Lakey et al. 14. Despres, J. P.,
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88 Lakey et al. tion despite a weak
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90 Lakey et al. 77. Maffi, P., Bert
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92 Lakey et al. 108. Idezuki, Y., G
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94 Lakey et al. 138. http://www.imm
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96 Lakey et al. tory reaction trigg
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98 Lakey et al. 198. O’Neil, J. J
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100 Lakey et al. 232. Delves, P. J.
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102 Lakey et al. 259. Grewal, I. S.
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Status of Lung Transplantation 105
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Chronic Rejection in the Heart 131
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Direct and Indirect Allorecognition
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HLA Typing and Organ Transplantatio
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Gene Transfer to Solid Organs 175 8
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Gene Transfer to Solid Organs 177 t
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Gene Transfer to Solid Organs 181
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183 Adenovirs (Ad) Nonenveloped vir
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Gene Transfer to Solid Organs 185 t
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Gene Transfer to Solid Organs 187 A
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Gene Transfer to Solid Organs 189 c
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202 Collins Table 1 Advantages and
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204 Collins The advantage of these
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206 Collins have used liposomal del
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208 Table 2 Ligands Used for Recept
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210 Collins It must not be forgotte
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212 Collins Fig. 3. Receptor-mediat
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214 Collins Receptor-mediated polyl
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216 Collins there are, to date, mor
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218 Collins 29. Niculescu-Duvaz, D.
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220 Collins 59. Wolfert, M. A. and
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222 Collins 91. Simoes, S., Slepush
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224 Collins 122. Hart, S. L., Harbo
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Antibody Relevance After Transplant
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248 Graca and Waldmann 2. The Use o
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250 Graca and Waldmann Fig. 1. Indu
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252 Graca and Waldmann Despite this
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254 Graca and Waldmann transforming
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256 Graca and Waldmann The role of
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258 Graca and Waldmann Fig. 5. A re
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260 Graca and Waldmann 4. Kahan, B.
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262 Graca and Waldmann 35. Powrie,
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264 Graca and Waldmann 67. Annacker
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266 Graca and Waldmann 96. Bommired
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Immune Monitoring in Transplantatio
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283 Table 1 Current and Potential F
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Proteomics and Laser Microdissectio
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Real-Time PCR 305 14 Real-Time Quan
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Real-Time PCR 307 Table 1 Real-Time
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Real-Time PCR 309 Fig. 2. Determina
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Real-Time PCR 311 such as Applied B
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Real-Time PCR 313 Table 2 Compariso
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315 Fig. 4. Quantification of RNA u
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Real-Time PCR 317 correlate directl
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319 Table 4 Common Internal Control
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321 Table 5 Examples of Single-Nucl
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Real-Time PCR 323 3.2. Real-Time PC
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Real-Time PCR 325 3.3.2. Sources of
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Real-Time PCR 327 9. Barton, P. J.
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Real-Time PCR 329 40. Primer expres
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Organ Preservation 331 15 Organ Pre
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Organ Preservation 333 2. Managemen
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Organ Preservation 335 tal observat
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Organ Preservation 337 donors, depe
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Organ Preservation 339 Table 1 Lung
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Organ Preservation 341 obtained wit
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Organ Preservation 343 Fig. 2. Acti
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Organ Preservation 345 Fig. 3. Outl
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Organ Preservation 347 and related
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Organ Preservation 349 mic, ischemi
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Organ Preservation 351 While these
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Organ Preservation 353 experimental
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Organ Preservation 355 with inhaled
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Organ Preservation 357 cellular sol
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Organ Preservation 359 4. Rosengard
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Organ Preservation 361 35. Powner,
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Organ Preservation 363 64. Hendry,
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Organ Preservation 365 factor-media
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Organ Preservation 367 120. Bonser,
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Organ Preservation 369 150. Macdona
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Organ Preservation 371 180. Carbogn
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209. Szabo, G., Soos, P., Bahrle, S
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376 Hopkins the extent of cold isch
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378 Hopkins or sequential administr
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380 Hopkins Table 2 Current Availab
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382 Hopkins 2. Renal failure: acute
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384 Table 4 Comparison of Azathiopr
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386 Hopkins Table 6 Side-Effect Pro
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388 Hopkins baseline immunosuppress
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390 Hopkins supplement to maintenan
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392 Hopkins 3. Kauppinen, H., Soots
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394 Hopkins uline versus no inducti
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396 Hopkins 62. Mycophenolate Mofet
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398 Hopkins 89. Mentzer, R. M., Jah
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Experimental Models of Graft Arteri
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405 Fig. 1. Variation in GA severit
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