%0 Journal Article %~ PubMed %A Lam, Vincent W T %A Laurence, Jerome M %A Richardson, Arthur J %A Pleass, Henry C C %A Allen, Richard D M %T Hypothermic machine perfusion in deceased donor kidney transplantation: a systematic review. %B Journal of Surgical Research %D 2013 %C United States %I Academic Press %V 180 %N 1 %P 176-182 %@ 1095-8673 %X %Z FOR Codes: 110312 110323 %0 Journal Article %~ PubMed %A Irving, Michelle J %A Tong, Allison %A Jan, Stephen %A Cass, Alan %A Chadban, Steven %A Allen, Richard D %A Craig, Jonathan C %A Wong, Germaine %A Howard, Kirsten %T Community attitudes to deceased organ donation: a focus group study. %B Transplantation %D 2012 %C United States %I Lippincott Williams & Wilkins %V 93 %N 10 %P 1064-1069 %@ 0041-1337 %X Despite broad community support for organ donation, there is a chronic shortage of donor organs for transplantation. This study elicited community attitudes on deceased organ donation and the current Australian organ donation system. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Thwaites, Stephen E %A Gurung, Bina %A Yao, Jinna %A Kable, Kathy %A Robertson, Paul %A Ryan, Brendan J %A Lam, Vincent W T %A Pleass, Henry C %A Chapman, Jeremy R %A Hawthorne, Wayne J %A Allen, Richard D M %T Excellent Outcomes of Simultaneous Pancreas Kidney Transplantation in Patients From Rural and Urban Australia: A National Service Experience. %B Transplantation %D 2012 %C United States %I Lippincott Williams & Wilkins %V 94 %N 12 %P 1230-1235 %@ 0041-1337 %X %Z FOR Codes: 110323 110312 %0 Journal Article %~ PubMed %A Irving, Michelle J %A Tong, Allison %A Jan, Stephen %A Cass, Alan %A Rose, John %A Chadban, Steven %A Allen, Richard D %A Craig, Jonathan C %A Wong, Germaine %A Howard, Kirsten %T Factors that influence the decision to be an organ donor: a systematic review of the qualitative literature. %B Nephrology, Dialysis, Transplantation %D 2012 %C United Kingdom %I Oxford University Press %V 27 %N 6 %P 2526-2533 %@ 1460-2385 %X BACKGROUND: Transplantation is the treatment of choice for organ failure, but a worldwide shortage of suitable organs exists. We conducted a systematic review of qualitative studies that explored community attitudes towards living and deceased solid organ donation to inform strategies to improve organ donation rates.METHODS: Medline, Embase, PsycINFO and EconLIT were searched. Qualitative studies that explored community attitudes towards living and deceased solid organ donation were included. A thematic synthesis of the results and conclusions reported by primary authors was performed.RESULTS: Eighteen studies involving 1019 participants were identified. Eight themes emerged. The decision to be an organ donor was influenced by (i) relational ties; (ii) religious beliefs; (iii) cultural influences; (iv) family influences; (v) body integrity; (vi) previous interactions with the health care system-medical mistrust, validity of brain death and fear of early organ retrieval; (vii) the individual''s knowledge about the organ donation process and (viii) major reservations about the process of donation, even in those who support organ donation.CONCLUSIONS: This review of qualitative studies highlights that seemingly intractable factors, such as religion and culture, are often tied in with more complex issues such as a distrust of the medical system, misunderstandings about religious stances and ignorance about the donation process. Intervention that could be considered includes culturally appropriate strategies to engage minority groups, especially through religious or cultural leaders, and more comprehensively available information about the donation process and its positive outcomes. %Z FOR Codes: 111799 %0 Journal Article %~ PubMed %A Cubitt, Jonathan %A Pennington, Thomas %A Wang, Chuanmin %A Allen, Richard %A Bishop, Alex %A Sharland, Alexandra %T Reliable and reproducible murine models for commonly used abdominal plastic surgical flaps. %B Journal of Reconstructive Microsurgery %D 2012 %C United States %I Thieme Medical Publishers %V 28 %N 3 %P 161-166 %@ 1098-8947 %X Animal models have been used for many years in surgical research to develop different surgical techniques, improve understanding of anatomy and physiology and hone surgical skills. The benefit of such models has been particularly important in developing relatively young specialties like plastic surgery and many plastic surgical techniques are designed and studied in animals long before they are used in humans. We describe techniques for raising several reliable and reproducible abdominal flaps in rodents, including transverse rectus abdominis myocutaneous flaps in rats and mice, superficial inferior epigastric artery flaps in rats and perforator flaps in rats. The intention of this paper is to act as a point of reference for any microvascular or plastic surgeon who is planning to perform abdominal plastic surgical flap research or further microvascular skills. %Z FOR Codes: 110323 %0 Journal Article %~ PubMed %A Lucewicz, Ania %A Isaacs, Anna %A Allen, Richard D M %A Lam, Vincent W T %A Angelides, Socrates %A Pleass, Henry C C %T Torsion of intraperitoneal kidney transplant. %B ANZ Journal of Surgery %D 2012 %C Australia %I Wiley-Blackwell Publishing Asia %V 82 %N 5 %P 299–302 %@ 1445-2197 %X Background:??? Torsion of kidney transplant refers to rotation of the kidney transplant graft around its vascular pedicle resulting in vascular compromise and infarction. It is a rare complication of kidney transplantation associated with a high rate of graft loss. Clinical presentation and diagnostic imaging modalities are non-specific, and surgical exploration is therefore often delayed. Methods:??? We present a case report and review of the literature. Studies were identified by searching Medline and Embase from January 1954 to December 2010. Data was extracted regarding the clinical presentation, investigation, findings on surgical exploration, and treatment outcomes of patients with torsion of kidney transplant. Results:??? Eight manuscripts with 16 cases of kidney torsion were found. Presenting symptoms were decreased renal function (13 cases), abdominal pain (10 cases), oliguria/anuria (9 cases), nausea and vomiting (4 cases), fever (3 cases), diarrhoea (3 cases), weight gain (2 cases), oedema (3 cases), fatigue (1 case) and impalpable graft (1 case). Investigations were Doppler sonography (11 cases), grey-scale sonography (7 cases), nuclear scintigraphy (5 cases), computed tomography scan (4 cases), and magnetic resonance imaging/magnetic resonance angiography (1 case). Of the 16 published cases of torsion, seven (44%) grafts were detorted and salvaged, three (19%) grafts were detorted but subsequently lost and six (38%) patients underwent immediate nephrectomy. Conclusions:??? A prompt consideration of the diagnosis of torsion of kidney transplant is required to prevent delay in surgical intervention. We recommend urgent Doppler ultrasound be used as first-line investigation, followed by prompt surgical exploration. We recommend the use of prophylactic nephropexy to prevent torsion. %Z FOR Codes: 110323 110312 %0 Journal Article %~ PubMed %A Howard, Kirsten %A Jan, Stephen %A Rose, John %A Chadban, Steven %A Allen, Richard Dm %A Irving, Michelle %A Tong, Allison %A Wong, Germaine %A Craig, Jonathan C %A Cass, Alan %T Community Preferences for the Allocation &Donation of Organs - The PAraDOx Study. %B BMC Public Health %D 2011 %C United Kingdom %I BioMed Central Ltd. %V 11 %N %P 386 %@ 1471-2458 %X ABSTRACT: %Z FOR Codes: 110312 %0 Journal Article %~ PubMed %A Fahrtash, Farzan %A Kairaitis, Lukas %A Gruenewald, Simon %A Spicer, Tim %A Sidrak, Hannah %A Fletcher, John %A Allen, Richard %A Swinnen, Jan %T Defining a significant stenosis in an autologous radio-cephalic arteriovenous fistula for hemodialysis. %B Seminars in dialysis %D 2011 %C United States %I Wiley-Blackwell Publishing, Inc. %V 24 %N 2 %P 231-8 %@ 1525-139X %X The current definition of a significant stenosis in an autologous arteriovenous fistula (aAVF), the percentage narrowing compared with the adjacent "normal" vessel, is inaccurate. We believe a significant stenosis in the aAVF is an absolute minimal luminal diameter determined by the requirements of the hemodialysis pump. To determine what absolute diameter constitutes a hemodynamically significant stenosis in a radio-cephalic autologous arteriovenous fistula (RC aAVF), the minimal luminal diameter of dysfunctional RC aAVF was compared to that of functional RC aAVF using grayscale and color ultrasound. There were 93 fistulas in study group and 77 in control group. The mean minimum luminal diameter in study group was significantly lower than in control group (2.19 vs. 4.71 mm, p 0.001). With a cutoff value of 2.7 mm, there was 90% sensitivity and 80% specificity in distinguishing functional fistula from dysfunctional fistula. The area under the receiver-operator curve was 90% (CI 84-94%), indicating that a 2.7 mm diameter is accurate in discriminating functional from dysfunctional fistulas. An absolute minimal luminal diameter of 2.7 mm, as determined with grayscale and color ultrasound, is a useful cutoff for defining significant stenosis in a RC aAVF. %Z FOR Codes: 1103 1102 %0 Journal Article %~ PubMed %A Lucewicz, Ania %A Wong, Germaine %A Lam, Vincent W T %A Hawthorne, Wayne J %A Allen, Richard %A Craig, Jonathan C %A Pleass, Henry C C %T Management of Primary Symptomatic Lymphocele After Kidney Transplantation: A Systematic Review. %B Transplantation %D 2011 %C United States %I Lippincott Williams & Wilkins %V 92 %N 6 %P 663-73 %@ 0041-1337 %X Management of lymphoceles after kidney transplantation is highly variable. The aim of this study was to evaluate and compare the different approaches of lymphocele management among kidney transplant recipients. %Z FOR Codes: 110323 110312 %0 Journal Article %~ PubMed %A Wang, Chuanmin %A Cordoba, Shaun %A Hu, Min %A Bertolino, Patrick %A Bowen, David G %A Sharland, Alexandra F %A Allen, Richard D M %A Alexander, Stephen I %A McCaughan, Geoffrey W %A Bishop, G Alex %T Spontaneous acceptance of mouse kidney allografts is associated with increased Foxp3 expression and differences in the B and T cell compartments. %B Transplant immunology %D 2011 %C Netherlands %I Elsevier BV %V 24 %N 3 %P 149-56 %@ 1878-5492 %X Spontaneous acceptance of organ allografts can identify novel mechanisms of drug-free transplantation tolerance. Spontaneous acceptance occurs in both mouse kidney transplants and rat liver transplants however the early immune processes of mouse kidney acceptance have not been studied. Acceptance of C57BL/6 strain kidney allografts in fully MHC-incompatible B10.BR recipients was compared with rejection (REJ) of heart allografts in the same strain combination. Graft infiltrate and antibody deposition were examined by immunohistochemical staining. Expression of mRNA was measured by quantitative real-time PCR. Apoptosis was examined by TUNEL staining. The majority of kidney allografts were accepted long-term and induced tolerance (TOL) of donor-strain skin grafts, showing that acceptance was not due to immune ignorance. There was an extensive infiltrate of T cells in the TOL kidney that exceeded the level in REJ hearts but subsequently declined. The main differences were deposition of IgG2a antibody in REJ that was absent in TOL, more B cells infiltrating TOL kidneys and a progressive increase in the ratio of CD8:CD4 cells during rejection. There was also significantly greater Foxp3 mRNA expression in TOL. Kidneys from RAG-/- donors were accepted, showing that donor lymphocytes were not necessary for acceptance. Neutralising antibodies to TGF-?? administered from day 0 to day 6 did not prevent TOL. On the basis of cytokine expression and apoptosis there was no evidence for immune deviation or deletion as mechanisms of acceptance. In accord with the findings of spontaneous acceptance of liver allografts in rats, the main difference between mouse kidney TOL and heart REJ was in the B cell compartment. The major difference to rat liver allograft acceptance was that apoptosis of infiltrate did not appear to play a role. Instead, increased Foxp3 expression in TOL kidneys implies that regulatory T cells might be important. %Z FOR Codes: 1103 1107 %0 Journal Article %~ PubMed %A Wong, Germaine %A Howard, Kirsten %A Chapman, Jeremy R %A Tong, Allison %A Bourke, Michael J %A Hayen, Andrew %A Macaskill, Petra %A Hope, Richard L %A Williams, Narelle %A Kieu, Anh %A Allen, Richard %A Chadban, Steven %A Pollock, Carol %A Webster, Angela %A Roger, Simon D %A Craig, Jonathan C %T Test performance of faecal occult blood testing for the detection of bowel cancer in people with chronic kidney disease (DETECT) protocol. %B BMC Public Health %D 2011 %C United Kingdom %I BioMed Central Ltd. %V 11 %N %P 516 %@ 1471-2458 %X ABSTRACT: %Z FOR Codes: 110312 111202 111716 %0 Journal Article %~ PubMed %A Laurence, Jerome M %A Sandroussi, Charbel %A Lam, Vincent W T %A Pleass, Henry C C %A Eslick, Guy D %A Allen, Richard D M %T Utilization of Small Pediatric Donor Kidneys: A Decision Analysis. %B Transplantation %D 2011 %C United States %I Lippincott Williams & Wilkins %V 91 %N 10 %P 1110-3 %@ 0041-1337 %X Given the disparity between static supply and increasing demand for organs, the greatest challenge is broadening access to the benefits of kidney transplantation. Organs from small deceased pediatric donors are a potentially underused resource. These may be transplanted as en bloc kidney transplants (EBKTs) to one recipient or as single kidney transplants (SKTs) to two recipients, albeit with an increased risk of graft failure. %Z FOR Codes: 110323 111403 %0 Journal Article %~ PubMed %A Crane, Catherine %A Lam, Vincent W T %A Alsakran, Abdulrahman %A Vasilaras, Arthur %A Lau, Howard %A Ryan, Brendan %A Pleass, Henry C C %A Allen, Richard D M %T Are there anatomical barriers to laparoscopic donor nephrectomy? %B ANZ Journal of Surgery %D 2010 %C Australia %I Wiley-Blackwell Publishing Asia %V 80 %N 11 %P 781-785 %@ 1445-2197 %X Background:??? The aim of this study was to analyse the effect of the right donor kidney and multiple arteries, on donor and recipient outcomes in the era of laparoscopic live donor nephrectomy (LLDN). Methods:??? We retrospectively analysed the 200 donors and recipients who underwent a planned laparoscopic nephrectomy at two hospitals between September 1998 and December 2006. The impact of donor right kidney and multiple donor renal arteries on operative time, hospital stay, graft function, and donor and recipient complications were analysed. Results:??? Of the total cohort (n???=???200), 140 (70%) were classified as Simple LLDN (left live donor kidney with single renal artery). The Complex LLDN group (n???=???60) contained all right-sided kidney (n???=???28) and left-sided kidneys with multiple renal arteries (n???=???32). Baseline characteristics, extraction time, conversion to open, length of admission, overall graft function and complication rates were similar between the simple and complex groups. The second warm ischaemic time in the Simple LLDN group was slightly shorter than the Complex LLDN group (32 versus 36???min P???=???0.016). The 1-month post-operative recipient serum creatinine level was lower in the Simple LLDN group when compared with the Complex LLDN group (117 versus 125?????mol/L P???=???0.025). There was no difference in post op dialysis, acute rejection within 3 months or graft survival between the Simple and Complex LLDN groups. Conclusion:??? Laparoscopic procurements of right kidneys and kidneys with multiple arteries were safe and yielded kidneys with excellent function comparable with those of laparoscopic left donor nephrectomy with single artery. %Z FOR Codes: 110323 110312 %0 Journal Article %~ PubMed %A Chandra, Abhilash P %A Dimascio, Delfino %A Gruenewald, Simon %A Nankivell, Brian %A Allen, Richard Dm %A Swinnen, Jan %T Colour duplex ultrasound accurately identifies focal stenoses in dysfunctional autogenous arteriovenous fistulae. %B Nephrology %D 2010 %C Australia %I Wiley-Blackwell Publishing Asia %V 15 %N 3 %P 300-306 %@ 1440-1797 %X Aims: The aims of this study is to correlate colour duplex ultrasonography (US) with contrast fistulography for the detection of functional stenoses in the autogenous AVF (arterio-venous fistula) circuit. Methodology: Colour duplex US scans of 93 dialysis patients with dysfunctional AVF were compared with fistulograms performed within 6 weeks of the US. The AVF circuit was divided into six zones: inflow artery; anastomosis; distal vein; mid vein; proximal vein; and central vein. Colour duplex US and fistulogram images/reports were independently re-reported for stenoses in each fistula zone by two trained clinicians blinded to the outcomes. For each fistula, only zones examined by both modalities were included in the study. Kappa analysis of the results was performed to assess the accuracy of colour duplex US in the dysfunctional AVF circuit. Results: Most AVF studied were radio-cephalic (59%) or brachio-cephalic (22%). Stenoses identified within the AV circuit in order of frequency were: distal vein (41), mid vein (23), arterial (12), proximal vein (7) and anastomosis (3). The interval between US and fistulogram studies was 33 +/- 29 days. Congruence of results between US and fistulograms ranged from 85% to 96%, depending on the zone examined. Kappa analysis of this US versus fistulogram data was also moderate to good, ranging from 0.72 and 0.91. Conclusions: Colour duplex US provides an accurate diagnostic assessment of a dysfunctional autogneous AVF, and is an important planning tool for subsequent open or endovascular intervention. It is particularly accurate in the peri-anastomotic area of the fistula which harbours the majority of fistula problems. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Tong, Allison %A Howard, Kirsten %A Jan, Stephen %A Cass, Alan %A Rose, John %A Chadban, Steven %A Allen, Richard D %A Craig, Jonathan C %T Community preferences for the allocation of solid organs for transplantation: a systematic review. %B Transplantation %D 2010 %C United States %I Lippincott Williams & Wilkins %V 89 %N 7 %P 796-805 %@ 0041-1337 %X BACKGROUND: Organs for transplantation are a scarce community resource but community preferences and how they are incorporated into allocation policies are unclear. This systematic review aimed to ascertain community preferences for organ allocation and the principles underpinning these preferences. METHODS: Medline, Embase, PsycINFO, EconLit, and gray literature databases were searched. Quantitative data were extracted, and a qualitative textual synthesis of the results and conclusions reported in each included study was performed. RESULTS: Fifteen studies involving more than 5563 respondents were included. Seven themes describing community preferences for organ allocation were identified: (1) maximum benefit, to achieve maximum health gain in recipient survival and quality of life; (2) social valuation, to base preferences on societal gain; (3) moral deservingness, to consider the "worthiness" of recipients based on their social standing and lifestyle decisions; (4) prejudice, to make a judgement based on personal ideologic viewpoints; (5) "fair innings," to provide an organ preferentially to the younger recipient giving opportunity for a "normal" life span and to those waiting for a first organ rather than a retransplant; (6) "first come, first served," to allocate the organ to recipients wait-listed the longest; and (7) medical urgency, to allocate based on illness severity and saving life. CONCLUSIONS: Community preferences for organ allocation hinge on a complex balance of efficiency, social valuation, morality, fairness, and equity principles. Being a community-held resource, effective ways to identify and incorporate community preferences into allocation algorithms for solid organ transplantation are warranted. %Z FOR Codes: 111799 %0 Journal Article %~ PubMed %A Wang, Chuanmin %A Tay, Szun Szun %A Tran, Giang T %A Hodgkinson, Suzanne J %A Allen, Richard D M %A Hall, Bruce M %A McCaughan, Geoffrey W %A Sharland, Alexandra F %A Bishop, G Alex %T Donor IL-4 treatment induces alternatively activated liver macrophages and IDO-Expressing NK cells and promotes rat liver allograft acceptance. %B Transplant immunology %D 2010 %C Netherlands %I Elsevier BV %V 22 %N 3-4 %P 172-8 %@ 1878-5492 %X Most approaches to transplant tolerance involve treatment of the recipient to prevent rejection. This study investigates donor treatment with IL-4 for its effect on subsequent rat liver allograft survival. Rat orthotopic liver transplants were performed in rejecting (PVG donor to Lewis recipient) or spontaneously tolerant (PVG to DA) strain combinations. Donors were untreated or injected intraperitoneally with IL-4 (30,000U/day) for 5days. Tissue infiltrates and gene expression were examined by immunohistochemistry and real-time quantitative PCR. IL-4 induced a marked leukocyte infiltrate in donor livers prior to transplant. Macrophages comprised the major population, although B cells, T cells and natural killer (NK) cells also increased. IL-4-induced liver macrophages had an alternatively activated phenotype with increased expression of mannose receptor but not inducible nitric oxide synthase (NOS2). IL-4 also induced IDO and IFN-gamma expression by NK cells. Donor IL-4-treatment converted rejection to acceptance in the majority of Lewis recipients (median survival time >96days) and did not prevent acceptance in DA recipients. Acceptance in Lewis recipients was associated with increased donor cell migration to recipient spleens and increased splenic IL-2, IFN-gamma and IDO expression 24h after transplantation. Donor IL-4-treatment increased leukocytes in the donor liver including potentially immunosuppressive populations of alternatively activated macrophages and IDO-expressing NK cells. Donor treatment led to long-term acceptance of most livers in association with early immune activation in recipient lymphoid tissues. %Z FOR Codes: 110708 %0 Journal Article %~ PubMed %A Lam, Vincent W T %A Pleass, Henry C C %A Hawthorne, Wayne %A Allen, Richard D M %T Evolution of pancreas transplant surgery. %B ANZ Journal of Surgery %D 2010 %C Australia %I Wiley-Blackwell Publishing Asia %V 80 %N 6 %P 411-418 %@ 1445-2197 %X Background: Type 1 diabetes mellitus is a chronic condition often leading to disabling complications including retinopathy, neuropathy and cardiovascular disease which can be modified by intensive treatment with insulin. Such treatment, however, is associated with a restrictive lifestyle and risk of hypoglycaemic morbidity and mortality. Methods: This review examines the role of pancreas transplantation in patients with Type 1 diabetes mellitus. Results: Pancreas transplantation is currently the only proven option to achieve long-term insulin independence, resulting in an improvement or stabilization of those diabetic related complications. The hazards of pancreas transplantation as a major operation are well known. Balancing the risks of a surgical procedure, with the benefits of restoring normoglycaemia remains an important task for the pancreas transplant surgeon. Pancreas transplantation is not an emergency operation to treat poorly managed and non-compliant patients with debilitating complications. It is a highly specialized procedure which has evolved both in terms of the surgical technique, patient selection and assessment. Conclusion: Pancreas transplantation has emerged as the single most effective way to achieve normal glucose homeostasis in patients with Type 1 diabetes mellitus. %Z FOR Codes: 110323 110307 %0 Journal Article %~ PubMed %A Prakoso, Emilia %A Verran, Deborah %A Dilworth, Pamela %A Kyd, Graham %A Tang, Patrick %A Tse, Carol %A Koorey, David James %A Strasser, Simone Irene %A Stormon, Michael %A Shun, Albert %A Thomas, Gordon %A Joseph, David %A Pleass, Henry %A Gallagher, James %A Allen, Richard %A Crawford, Michael %A McCaughan, Geoffrey William %A Shackel, Nicholas Adam %T Increasing liver transplantation waiting list mortality : A report from the Australian National Liver Transplantation Unit Sydney. %B Internal Medicine Journal %D 2010 %C Australia, United Kingdom, Netherlands, United States %I Wiley-Blackwell Publishing Asia %V 40 %N 9 %P 619–625 %@ 1445-5994 %X ABSTRACT Background: We aimed to describe the demand for liver transplantation (LTx) and patient outcomes on the waiting list at the Australian National Liver Transplantation Unit Sydney over the last twenty years. Methods: We performed a retrospective analysis with the data divided into 3 eras: 1985-1993, 1994-2000, and 2001-2008. Results: The number of patients accepted for LTx increased from 320 to 372 and 548 (p < 0.001) with the number of LTx being performed increasing from 262 to 312 and 452 respectively (p < 0.001). The median adult recipient age increased from 45 to 48 and 52 years (p < 0.001) while it decreased in children from 4 to 2 and 1 years respectively (p=0.001). In parallel, the deceased donor offers decreased from 1003 to 720 and 717 (p < 0.001). Methods to improve access to donor livers have been utilised with the use of split livers, extended criteria and non-heart beating donors, resulting in increased acceptance of deceased donor offers by 65% and 115% in the second and third eras when compared to the first era (p < 0.001). However, the adult median waiting time has increased from 23 to 41 and 120 days respectively (p < 0.001). This was associated with increased adult mortality on the waiting list from 23 to 40 and 122 respectively (p < 0.001). Conclusions: Despite the increasing proportion of donor offers being utilised, the waiting list mortality is increasing. A solution to this problem is an increase in organ donation to keep pace with the escalating demand for LTx. %Z FOR Codes: 110307 111799 110323 %0 Journal Article %~ PubMed %A Lam, Vincent W T %A Laurence, Jerome M %A Robertson, Paul %A Hawthorne, Wayne %A Ryan, Brendan J %A Lau, Howard M H %A Allen, Richard D M %A Pleass, Henry C C %T En bloc paediatric kidney transplant: is this the best use of a scarce resource? %B ANZ Journal of Surgery %D 2009 %C Australia %I Blackwell Science %V 79 %N 1-2 %P 27-32 %@ 1445-1433 %X BACKGROUND: Kidney transplants using organs from paediatric cadaver donors are uncommon and technically difficult. It has become accepted practice to transplant both kidneys en bloc from donors of 5 years into a single recipient. We aim to compare outcomes of en bloc kidney (EBK) transplants versus single kidney (SK) transplants from cadaver donors of age 5 years and lesser. METHODS: Data reported to Australia and New Zealand Dialysis and Transplant Registry from 1989 to 2004 were analysed. RESULTS: From donors 5 years of age and younger, there were 33 EBK and 38 SK transplants carried out. Overall graft survival rates at 1 and 5 years were 78 and 61%, respectively, in the EBK group and 63 and 55%, respectively, in the SK group (P = 0.94). Vascular thrombosis was the most common cause of early graft loss with an incidence of 11 and 18%, respectively, in the EBK and SK groups (P = 0.5). CONCLUSION: There is a trend towards a lower vascular thrombosis rate and a better long-term graft survival in EBK transplants. These transplants will remain a technical challenge for the surgeon and EBK transplants should remain the technique of choice for donors of 5 years and lesser. %Z FOR Codes: 110323 %0 Journal Article %~ PubMed %A Laurence, Jerome M %A Allen, Richard D M %A McCaughan, Geoffrey W %A Logan, Grant J %A Alexander, Ian E %A Bishop, G Alex %A Sharland, Alexandra F %T Gene therapy in transplantation. %B Transplantation Reviews %D 2009 %C United States %I WB Saunders Co. %V 23 %N 3 %P 159-170 %@ 1557-9816 %X Gene therapy is an exciting and novel technology that offers the prospect of improving transplant outcomes beyond those achievable with current clinical protocols. This review explores both the candidate genes and ways in which they have been deployed to overcome both immune and non-immune barriers to transplantation success in experimental models. Finally, the major obstacles to implementing gene therapy in the clinic are considered. %Z FOR Codes: 100401 110708 %0 Journal Article %~ PubMed %A Laurence, Jerome M %A Wang, Chuanmin %A Zheng, Maolin %A Cunningham, Sharon %A Earl, John %A Tay, Szun Szun %A Allen, Richard D M %A McCaughan, Geoffrey W %A Alexander, Ian E %A Bishop, G Alex %A Sharland, Alexandra F %T Overexpression of indoleamine dioxygenase in rat liver allografts using a high-efficiency adeno-associated virus vector does not prevent acute rejection. %B Liver Transplantation %D 2009 %C United States %I John Wiley & Sons, Inc. %V 15 %N 2 %P 233-241 %@ 1527-6473 %X The aim of this study was to evaluate the ability of local overexpression of indoleamine dioxygenase (IDO) to abrogate rat liver transplant rejection by the use of an adeno-associated virus vector [recombinant adeno-associated virus 2/8 (rAAV2/8)] to deliver the transgene to the allograft prior to transplantation. A green fluorescent protein (GFP)-expressing vector [recombinant adeno-associated virus 2/8-liver-specific promoter 1-enhanced green fluorescent protein (rAAV2/8-LSP1-eGFP)] was used to examine the kinetics of expression and optimal dosing for transduction of Piebald Virol Glaxo (PVG) rat livers. A vector encoding the rat IDO gene (rAAV2/8-LSP1-rIDO) was constructed and tested by its ability to induce tryptophan catabolism and kynurenine production in vitro and in vivo. PVG donor rats were injected, via the portal vein, with rAAV2/8-LSP1-rIDO 2 weeks before transplantation into PVG strain isograft or Lewis (LEW) strain allograft recipients. With the enhanced GFP vector, 29.5% and 47.4% of hepatocytes were found to express GFP at 3 and 6 weeks after injection, respectively. In untransplanted PVG animals, the rAAV2/8-LSP1-rIDO vector induced, 3 weeks after administration, a 1.8-fold increase (P = 0.0161) in liver IDO activity, which was associated with a fall in serum tryptophan to 0.5 times the baseline level (P < 0.001). PVG recipients of PVG liver isografts pretreated with the IDO-expressing vector had a 45% lower level of serum tryptophan than recipients of isografts pretreated with the GFP-expressing vector (P = 0.03). LEW recipients of PVG liver allografts pretreated with the rat IDO vector had a median survival time of 12 days, whereas recipients of allografts pretreated with rAAV2/8-LSP1-eGFP had a median survival time of 13 days (P = 0.38). Both groups displayed similar histological features of acute cellular rejection. In conclusion, rAAV2/8 vectors produce highly efficient, though delayed, hepatocyte transduction in vivo and provide a useful gene delivery tool for transplantation models. However, gene delivery using IDO was unsuccessful in prolonging rat liver allograft survival. %Z FOR Codes: 110708 100401 %0 Journal Article %~ PubMed %A Suh, Nancy %A Ryan, Brendan %A Allen, Richard %A O'Connell, Philip %A Pleass, Henry %T Simultaneous pancreas and kidney transplantation from organ donation after cardiac death. %B ANZ Journal of Surgery %D 2009 %C Australia %I Wiley-Blackwell Publishing Asia %V 79 %N 4 %P 245-256 %@ 1445-1433 %X BACKGROUND: The concept of organ donation after cardiac death (DCD) historically precedes the current practice of organ procurement from heartbeating donors meeting the brainstem death criteria. DCD has not gained widespread interest, however, due partly to initial fears that transplantation of such organs leads to suboptimal outcome. METHODS: Available data on long-term outcomes following simultaneous pancreas and kidney transplant (SPK) from DCD donors were reviewed, and it was found that the long-term outcome is comparable to SPK from heartbeating donors. Australia''s first SPK from a DCD donor was performed. RESULTS: The patient received a kidney and a pancreas from a young healthy donor after cardiac death, and at the time of writing was well with functioning grafts. CONCLUSION: SPK from donation after cardiac death is safe and should continue to be available for patients in need. %Z FOR Codes: 110323 110708 %0 Journal Article %~ PubMed %A Laurence, Jerome M %A Wang, Chuanmin %A Park, Euiyoun T %A Buchanan, Alexandra %A Clouston, Andrew %A Allen, Richard D M %A Mccaughan, Geoffrey W %A Bishop, G Alex %A Sharland, Alexandra F %T Blocking indoleamine dioxygenase activity early after rat liver transplantation prevents long-term survival but does not cause acute rejection. %B Transplantation %D 2008 %C United States %I Lippincott Williams & Wilkins, Inc. %V 85 %N 9 %P 1357-1361 %@ 0041-1337 %X In a well-characterized rat model of liver transplantation, Piebald Virol Glaxo strain livers are accepted long term in fully mismatched Dark Agouti recipients (tolerance; TOL), but rejected in Lewis recipients (rejection; REJ). Spontaneous tolerance induction is associated with increased interferon-gamma expression, and we examined the role of the interferon-gamma-inducible immunomodulatory enzyme indoleamine dioxygenase (IDO) in this model. On day 3 after transplantation, IDO expression in the spleen of TOL recipients was significantly greater than in REJ. The B-cell population accounted for this early IDO increase. Intragraft expression of IDO increased to the same extent in both TOL and REJ. IDO inhibition for 7 days after transplantation reduced survival, but did not cause acute rejection of the liver in the TOL model. In conclusion, the differential IDO expression by B lymphocytes in the spleen of TOL recipients is not critical for preventing acute rejection. %Z FOR Codes: 110708 %0 Journal Article %~ PubMed %A Lam, Vincent W T %A Taylor, Claire F %A Laurence, Jerome M %A Wang, Chuanmin %A Sharland, Alexandra F %A McCaughan, Geoffrey W %A Hodgkinson, Suzanne %A Allen, Richard D M %A Hall, Bruce M %A Bishop, G Alex %T Heart allograft acceptance induced by anti-CD3 antibody in high-responder rats: Effect on foxp3 and cytokine expression and graft infiltration. %B Transplant Immunology %D 2008 %C Netherlands %I Elsevier BV %V 19 %N 1 %P 20-24 %@ 0966-3274 %X The ability of anti-T cell monoclonal antibody G4.18 and polyclonal anti-lymphocyte serum (ALS) to induce long-term graft survival was examined in a high-responder rat heart transplant model. Heterotopic heart allografts were performed from PVG rat strain donors to high-responder Lewis recipients. Immunosuppressive properties of G4.18 and ALS were investigated by immunohistochemistry and PCR analysis. Untreated graft rejection was 8.5 days while treatment with 1 ml ALS prolonged survival to 11.5 days (p=0.01). Treatment with 7 mg/kg G4.18 on days 1 and 3 prolonged survival to >100 days (p=0.002 vs. control and p=0.002 vs. ALS) but did not induce tolerance. Acceptance was associated with marked inhibition of cellular infiltration and inflammatory cytokine expression and only a brief, slight increase in Foxp3:T cell ratio in the graft and no increase in the spleen. In conclusion, G4.18 treatment led to long-term heart transplant survival associated with marked inhibition of early inflammation. Failure to develop tolerance was associated with a lack of early accumulation of Foxp3 cells in the graft or spleen. %Z FOR Codes: 110708 %0 Journal Article %~ PubMed %A Chapman, Jeremy R %A Allen, Richard D M %T Paired kidney exchange: how far and how wide? %B Transplantation %D 2008 %C United States %I Lippincott Williams & Wilkins, Inc. %V 85 %N 5 %P 673-674 %@ 0041-1337 %X %Z FOR Codes: 110708 %0 Journal Article %~ PubMed %A Horton, Peter John %A Hawthorne, Wayne J %A Walters, Stacey %A Patel, Tina %A Stewart, Graeme J %A Allen, Richard D M %A Chapman, Jeremy R %T Tolerance induction in a large-animal model using total lymphoid irradiation and intrathymic bone marrow. %B Transplantation %D 2008 %C United States %I Lippincott Williams and Wilkins %V 86 %N 12 %P 1830-1836 %@ 0041-1337 %X BACKGROUND.: Immunological unresponsiveness of T cells to alloantigen can be induced by intrathymic injection of donor-specific antigen in small-animal models. Intrathymic tolerance to vascularized grafts in large animals has not previously been reported. METHODS.: Thirty-two dogs were allocated into dog leukocyte antigen DP locus allele (class II)-matched donor-recipient pairs. Female recipients were paired with male donors. Tissue typing was based on restriction fragment length polymorphism. Recipients were given 18 Gy total lymphoid irradiation in 16 fractions (1.125 Gy each) over 4 weeks. Thoracotomy after the 6th fraction permitted perithymic (n=4) or intrathymic (n=4) injection of donor bone marrow (BM) or intrathymic injection of saline (n=5). Another group received intravenous peripheral BM infusion (n=3). Fifty days postthoracotomy recipients underwent bilateral nephrectomy and donor-specific kidney transplantation. Acute rejection, suspected when serum creatinine was more than 600 mumol/L or urea was more than 40 mmol/L, was confirmed histologically. Full-thickness skin grafts followed more than 100 days posttransplantation. Tissue samples were taken for Y-chromosome polymerase chain reaction. RESULTS.: One intrathymic (25%) and three perithymic (75%) BM recipients developed tolerance to renal allografts. Three intrathymic BM recipients rejected after 27, 32, and 54 days and one perithymic BM recipient rejected after 42 days. All recipients given peripheral BM or saline had rejected by 29 and 38 days, respectively. All recipients surviving more than 100 days posttransplantation, accepted donor specific and rejected dog leukocyte antigen-DP locus allele (class II) identical third-party skin grafts. Polymerase chain reaction detected intrathymic but not hematopoietic chimerism in sex-mismatched pairs. CONCLUSIONS.: Fractionated total lymphoid irradiation and perithymic or intrathymic donor-specific BM induced tolerance to renal and skin allografts without inducing hematopoietic chimerism. %Z FOR Codes: 110708 %0 Book Section %A Allen, Richard %T Vascular Complications After Kidney Transplantation %B Kidney Transplantation: Principles and Practice %D 2008 %C United States %I Saunders %V %N %P 439-461 %@ 978-1-4160-3343-1 %E Morris, Peter J %E Knechtle, Stuart J %X %Z FOR Codes: 110323 110312 %0 Journal Article %~ PubMed %A Nankivell, B J %A Wavamunno, M D %A Borrows, R J %A Vitalone, M %A Fung, C L-S %A Allen, R D M %A Chapman, J R %A O'Connell, P J %T Mycophenolate mofetil is associated with altered expression of chronic renal transplant histology. %B American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons %D 2007 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 7 %N 2 %P 366-376 %@ 1600-6135 %X Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking. We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry. MMF reduced acute rejection and OKT3 use (p < 0.05) compared with AZA. MMF therapy was associated with limited chronic interstitial fibrosis, striped fibrosis and periglomerular fibrosis (p < 0.05-0.001), mesangial matrix accumulation (p < 0.01), chronic glomerulopathy scores (p < 0.05) and glomerulosclerosis (p < 0.05). MMF was associated with delayed expression of CSA nephrotoxicity, reduced arteriolar hyalinosis, striped fibrosis and tubular microcalcification (p < 0.05-0.001). The beneficial effects of MMF remained in recipients without acute rejection. Retrospective analysis shows that MMF therapy was associated with substantially reduced fibrosis in the glomerular, microvascular and interstitial compartments, and a delayed expression of CSA nephrotoxicity. These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis. %Z FOR Codes: %0 Journal Article %~ PubMed %A Wavamunno, M D %A O'connell, P J %A Vitalone, M %A Fung, C L-S %A Allen, R D M %A Chapman, J R %A Nankivell, B J %T Transplant Glomerulopathy: Ultrastructural Abnormalities Occur Early in Longitudinal Analysis of Protocol Biopsies. %B American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons %D 2007 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 7 %N 12 %P 2757-68 %@ 1600-6135 %X Transplant glomerulopathy (TXG) presents a distinctive pattern of glomerular abnormalities. The aim of this study was to describe its sequential ultrastructural pathology. A paired cohort study of 228 protocol biopsies, from our longitudinal database (n = 1345), compared TXG (7 patients, 95 biopsies) and controls (8 patients, 133 biopsies). Ultrastructural morphometry and C4d immunoperoxidase were evaluated from implantation to 5 years after transplantation against sequential histology and functional changes. TXG was predated by early glomerular endothelial cell activation; typified by vacuolation, hypertrophy, serration and expansion of lamina rara interna from 39 +/- 23 days after transplantation. Endothelial cells were transformed into an activated phenotype, containing numerous mitochondria, Golgi and ribosomes. Transition from fenestrated to continuous endothelium, mesangial matrix expansion and podocyte fusion occurred late. Endothelial cell activation also occurred in peritubular capillaries (PTC) followed by basement membrane multi-lamination (p < 0.05-0.001). Light microscopy changes of TXG occurred at 2.3 years. PTC C4d deposition was intermittently expressed over time, correlating with endothelial abnormalities, glomerular C4d and donor-specific antibodies (DSA) (p < 0.05-0.001). In summary, endothelial and subendothelial ultrastructural abnormalities in glomerular and peritubular capillaries are sensitive, early markers of TXG, likely due to stimulation of endothelial cells into an activated phenotype by antibody-mediated sub-lytic complement deposition. %Z FOR Codes: