Counting Small Hypointense Spots Confounds the Quantification of Functional Islet Mass Based on Islet MRI.
Am J Transplant. 2012 Feb 2;
Authors: Kim JH, Jin SM, Oh SH, Lee S, Oh BJ, Kim SK, Suh S, Lee JH, Jung HS, Lee MS, Lee MK, Kim KW
Abstract
Iron-containing fragmented islets or free iron released from dying cells could confound the interpretation of MRI of iron nanoparticle-labeled islets. Exclusion of small hypointense spots could be a useful strategy to avoid such artifact. We investigated whether this strategy could improve the estimation of functioning islet mass after islet transplantation. Using a rat syngeneic intraportal islet transplantation model, we quantitatively assessed the relationships between total area, number of hypointense spots on MRI that belong to each size quartile and glycemic control of the recipients. The total area of hypointense spots on MRI was greater in the recipients that achieved diabetes reversal (p = 0.002), whereas the total number of hypointense spots was not different (p = 0.757). Exclusion of small hypointense spots improved the association between the number of hypointense spots and the blood glucose level of the recipients (p < 0.001). Ex-vivo imaging and histologic study confirmed that some small hypointense spots represent the phagocytosed free iron. Exclusion of small hypointense spots improved the quantification of the functional islet mass based on islet MRI. This would be a useful principle in the development of an algorithm to estimate functioning islet mass based on islet MRI.
PMID: 22299723 [PubMed - as supplied by publisher]
Endogenous Expansion of Regulatory T Cells Leads to Long-Term Islet Graft Survival in Diabetic NOD Mice.
Am J Transplant. 2012 Feb 2;
Authors: Shi Q, Lees JR, Scott DW, Farber DL, Bartlett ST
Abstract
Donor pancreatic lymph node cells (PLNC) protect islet transplants in Non-obese diabetic (NOD) mice. We hypothesized that induced FoxP3(+) regulatory T cells (Tregs) were required for long-term islet engraftment. NOD or NOD.NON mice were treated with ALS (antilymphocyte serum) and transplanted with NOR islets +/-PLNC (5 × 10(7) ). In vivo proliferation and expansion of FoxP3(+) Tregs was monitored in spleen and PLN from ALS- and ALS/PLNC-treated recipient mice. Anti-CD25 depletion was used to determine the necessity of Tregs for tolerance. FoxP3(+) numbers significantly increased in ALS/PLNC-treated recipients compared to ALS-treated mice. In ALS/PLNC-treated mice, recipient-derived Tregs localized to the transplanted islets, and this was associated with intact, insulin-producing β cells. Proliferation and expansion of FoxP3(+) Tregs was markedly increased in PLNC-treated mice with accepted islet grafts, but not in diabetic mice not receiving PLNC. Deletion of Tregs with anti-CD25 antibodies prevented islet graft tolerance and resulted in rejection. Adoptive transfer of Tregs to secondary NOD.scid recipients inhibited autoimmunity by cotransferred NOD effector T cells. Treg expansion induced by ALS/PLNC-treatment promoted long term islet graft survival. Strategies leading to Treg proliferation and localization to the transplant site represent a therapeutic approach to controlling recurrent autoimmunity.
PMID: 22299822 [PubMed - as supplied by publisher]
Multivisceral Ex Vivo Surgery for Tumors Involving Celiac and Superior Mesenteric Arteries.
Am J Transplant. 2012 Feb 2;
Authors: Kato T, Lobritto SJ, Tzakis A, Raveh Y, Sandoval PR, Martinez M, Granowetter L, Armas A, Brown Jr RS, Emond J
Abstract
Abdominal tumors involving both roots of the celiac and superior mesenteric artery are deemed unresectable by conventional surgical methods. We performed three cases of multivisceral ex vivo surgery involving temporary removal of the entire abdominal viscera followed by vascular reconstruction, ex vivo tumor resection and autotransplantation of excised organs. We achieved a complete tumor resection with negative margins in all cases. All patients have survived with no tumor recurrence to date at 17-, 27- and 38-month follow-up. Postoperative complications included diarrhea, sphincter of Oddi dysfunction and arterial stenosis; all responded to directed treatments. Multivisceral ex vivo surgery applying techniques of deceased donor multivisceral transplantation is feasible in achieving local control of otherwise unresectable abdominal tumors. This surgery is best suitable for locally invasive tumors unresectable because of location and vascular involvement.
PMID: 22300017 [PubMed - as supplied by publisher]
Lung Transplantation in Patients with Prior Cardiothoracic Surgical Procedures.
Am J Transplant. 2012 Feb 2;
Authors: Shigemura N, Bhama J, Gries CJ, Kawamura T, Crespo M, Johnson B, Zaldonis D, Pilewski J, Toyoda Y, Bermudez C
Abstract
The full spectrum of prior cardiothoracic procedures in lung transplant candidates and the impact of prior procedures on outcomes after lung transplantation (LTx) remain unknown, though the impact is considered to be large. Patients transplanted at our institution from 2004 to 2009 were identified (n = 554) and divided into two groups: patients who had undergone cardiothoracic surgical (CTS) procedures prior to LTx (n = 238) and patients who had not (non-CTS: n = 316). Our primary endpoint was survival. Secondary endpoints included allograft function and the incidence of major complications including reexploration due to bleeding, prolonged ventilation, renal insufficiency and primary graft dysfunction. Long-term survival was not significantly different between the groups whereas postoperative bleeding, nerve injury, respiratory and renal complications were higher in the CTS group. Posttransplant peak FEV1 was lower in the CTS group (73.4% vs. 86.9%, p < 0.05). In multivariate analysis, performance of a chemical pleurodesis procedure and prolonged cardiopulmonary bypass were significantly associated with mortality (OR, 1.7; CI, 1.5-2.0; p < 0.005). Our results suggest that patients with LTx and prior CTS remain technically challenging and experience worse outcomes than patients without prior CTS. A surgical strategy to minimize cardiopulmonary bypass time is critical for these challenging LTx patients.
PMID: 22300103 [PubMed - as supplied by publisher]
Early Metabolic Markers that Anticipate Loss of Insulin Independence in Type 1 Diabetic Islet Allograft Recipients.
Am J Transplant. 2012 Feb 2;
Authors: Hirsch D, Odorico J, Danobeitia JS, Alejandro R, Rickels MR, Hanson M, Radke N, Baidal D, Hullett D, Naji A, Ricordi C, Kaufman D, Fernandez L
Abstract
The objective of this study was to identify predictors of insulin independence and to establish the best clinical tools to follow patients after pancreatic islet transplantation (PIT). Sequential metabolic responses to intravenous (I.V.) glucose (I.V. glucose tolerance test [IVGTT]), arginine and glucose-potentiated arginine (glucose-potentiated arginine-induced insulin secretion [GPAIS]) were obtained from 30 patients. We determined the correlation between transplanted islet mass and islet engraftment and tested the ability of each assay to predict return to exogenous insulin therapy. We found transplanted islet mass within an average of 16 709 islet equivalents per kg body weight (IEQ/kg BW; range between 6602 and 29 614 IEQ/kg BW) to be a poor predictor of insulin independence at 1 year, having a poor correlation between transplanted islet mass and islet engraftment. Acute insulin response to IVGTT (AIR(GLU) ) and GPAIS (AIR(max) ) were the most accurate methods to determine suboptimal islet mass engraftment. AIR(GLU) performed 3 months after transplant also proved to be a robust early metabolic marker to predict return to insulin therapy and its value was positively correlated with duration of insulin independence. In conclusion, AIR(GLU) is an early metabolic assay capable of anticipating loss of insulin independence at 1 year in T1D patients undergoing PIT and constitutes a valuable, simple and reliable method to follow patients after transplant.
PMID: 22300172 [PubMed - as supplied by publisher]
Role of Lentivirus-Mediated Overexpression of Programmed Death-Ligand 1 on Corneal Allograft Survival.
Am J Transplant. 2012 Feb 2;
Authors: Nosov M, Wilk M, Morcos M, Cregg M, O’Flynn L, Treacy O, Ritter T
Abstract
To investigate the role of lentivirus-mediated overexpression of programmed death-ligand 1 (PD-L1) on rat corneal allograft survival. A fully allogeneic rat cornea transplant model was used for in vivo studies. Lentiviral (LV) vectors are efficient tools for ex vivo genetic modification of cultured corneas. LV vector encoding for PD-L1 (LV.PD-L1) and LV vector encoding for eGFP (LV.eGFP, as control) were constructed and tested. PD-L1 or eGFP expression was increased on corneal cells upon LV.PD-L1 and LV.eGFP transduction, respectively. Both allogeneic controls and allogeneic LV.eGFP transduced corneas were uniformly rejected (MST: 13.8 ± 1.7 days and 12.3 ± 1.9 days, respectively). In contrast, allogeneic LV.PD-L1 transduced corneas showed a high percentage (83%) of graft survival (MST > 30 days, n = 5, 15 days, n = 1). Graft opacity of PD-L1 transduced corneas was present but was significantly reduced compared to control or eGFP expressing corneas. Flow cytometric analysis revealed that percentages of CD3(+) CD8(+) CD161(+) and CD3(+) CD8(+) CD161(-) lymphocytes were decreased in animals receiving LV.PD-L1 transduced corneas compared to animals grafted with LV.eGFP transduced corneas. Moreover, reduced expression of proinflammatory cytokines (IFN-γ and IL-6) in PD-L1 transduced corneas compared to allogeneic controls was also observed. Local PD-L1 gene transfer in cultured corneas is a promising approach for the prolongation of corneal allograft survival and attenuation of graft rejection.
PMID: 22300371 [PubMed - as supplied by publisher]
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