Sample records for prolonged skin allograft

  1. Radiation sterilization of skin allograft

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.


    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

  2. Specific unresponsiveness to skin allografts in burns.

    Clark, G T; Moon, D J; Cunningham, P R; Johnson, T D; Thomas, J M; Thomas, F T


    We have examined the potential to provide long-term or even permanent wound coverage in a mouse model of a 30% total body surface area burn using skin allografts. Treatment of the recipient mouse with rabbit anti-mouse thymocyte serum (ATS) followed by donor bone marrow infusion induces a state of specific unresponsiveness to the skin allograft without the need for chronic immunosuppression. Specifically, a B6AF1 mouse receives a burn on Day -2 relative to grafting, ATS on Day -1, and Day +2, a skin allograft from a C3H/He mouse on Day 0, and infusion of C3H/He donor bone marrow on Day +6. We studied three groups of burned mice: Group I, allograft control (n = 5); Group II, allograft plus ATS (n = 12); and Group III, allograft plus ATS and bone marrow infusion (n = 15). Mean graft survival was compared using a one-way analysis of variance and a Student-Newman-Keuls post hoc test. There was no statistical difference in animal mortality among any of the three groups, and there was no evidence of infectious morbidity. Mean skin allograft survival was as follows: Group I, 9 days; Group II, 29 days; and Group III, 66 days (P less than 0.05 vs Group I and II). Nine animals in Group III had intact hair bearing grafts at 90 days when the study was terminated. This study suggests the potential use of induced specific unresponsiveness to skin allografts for wound coverage in thermal injury without use of chronic immunosuppression. In our animal study this was accomplished without increased mortality or apparent infectious morbidity.

  3. [The clinical use of cryopreserved human skin allografts for transplantation].

    Martínez-Flores, Francisco; Chacón-Gómez, María; Madinaveitia-Villanueva, Juan Antonio; Barrera-Lopez, Araceli; Aguirre-Cruz, Lucinda; Querevalu-Murillo, Walter


    The biological recovery of human skin allografts is the gold standard for preservation in Skin Banks. However, there is no worldwide consensus about specific allocation criteria for preserved human skin allografts with living cells. A report is presented on the results of 5 years of experience of using human skin allografts in burned patient in the Skin and Tissue Bank at the "Instituto Nacional de Rehabilitacion" The human skin allografts were obtained from multi-organ donors. processed and preserved at -80 °C for 12 months. Allocation criteria were performed according to blood type match, clinical history, and burned body surface. Up to now, the Skin and Tissue Bank at 'Instituto Nacional de Rehabilitacion" has processed and recovered 125,000 cm(2) of human skin allografts. It has performed 34 surgical implants on 21 burned patients. The average of burn body surface was 59.2%. More than two-thirds (67.7%) of recipients of skin allografts were matched of the same to type blood of the donor, and 66.6% survived after 126 days hospital stay. It is proposed to consider recipient's blood group as allocation criteria to assign tissue; and use human skin allografts on patiens affected with burns over 30% of body surface (according the "rule of the 9"). Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  4. Deceased donor skin allograft banking: Response and utilization

    Gore Madhuri


    Full Text Available Background: In the absence of xenograft and biosynthetic skin substitutes, deceased donor skin allografts is a feasible option for saving life of patient with extensive burn injury in our country. Aims: The first deceased donor skin allograft bank in India became functional at Lokmanya Tilak Municipal (LTM medical college and hospital on 24 th April 2000. The response of Indian society to this new concept of skin donation after death and the pattern of utilization of banked allografts from 2000 to 2010 has been presented in this study. Settings and Design: This allograft skin bank was established by the department of surgery. The departments of surgery and microbiology share the responsibility of smooth functioning of the bank. Materials and Methods: The response in terms of number of donations and the profile of donors was analyzed from records. Pattern and outcome of allograft utilization was studied from specially designed forms. Results: During these ten years, 262 deceased donor skin allograft donations were received. The response showed significant improvement after counselling was extended to the community. Majority of the donors were above 70 years of age and procurement was done at home for most. Skin allografts from 249 donors were used for 165 patients in ten years. The outcome was encouraging with seven deaths in 151 recipients with burn injuries. Conclusions: Our experience shows that the Indian society is ready to accept the concept of skin donation after death. Use of skin allografts is life saving for large burns. We need to prepare guidelines for the establishment of more skin banks in the country.

  5. Autologous Dendritic Cells Prolong Allograft Survival Through Tmem176b-Dependent Antigen Cross-Presentation

    Charnet, P.; Savina, A.; Tilly, G.; Gautreau, L.; Carretero-Iglesia, L.; Beriou, G.; Cebrian, I.; Cens, T.; Hepburn, L.; Chiffoleau, E.; Floto, R. A.; Anegon, I.; Amigorena, S.; Hill, M.; Cuturi, M. C.


    The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8+CD11c+ T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b−/− ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b−/− ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8+ T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8+CD11c+ T cells with regulatory properties and prolong graft survival. PMID:24731243

  6. Host-based Th2 cell therapy for prolongation of cardiac allograft viability.

    Shoba Amarnath

    Full Text Available Donor T cell transfusion, which is a long-standing approach to prevent allograft rejection, operates indirectly by alteration of host T cell immunity. We therefore hypothesized that adoptive transfer of immune regulatory host Th2 cells would represent a novel intervention to enhance cardiac allograft survival. Using a well-described rat cardiac transplant model, we first developed a method for ex vivo manufacture of rat host-type Th2 cells in rapamycin, with subsequent injection of such Th2.R cells prior to class I and class II disparate cardiac allografting. Second, we determined whether Th2.R cell transfer polarized host immunity towards a Th2 phenotype. And third, we evaluated whether Th2.R cell therapy prolonged allograft viability when used alone or in combination with a short-course of cyclosporine (CSA therapy. We found that host-type Th2.R cell therapy prior to cardiac allografting: (1 reduced the frequency of activated T cells in secondary lymphoid organs; (2 shifted post-transplant cytokines towards a Th2 phenotype; and (3 prolonged allograft viability when used in combination with short-course CSA therapy. These results provide further support for the rationale to use "direct" host T cell therapy for prolongation of allograft viability as an alternative to "indirect" therapy mediated by donor T cell infusion.

  7. The effect of pregnancy on paternal skin allograft survival

    SHOU ZhangFei; XU YiFang; XIAO HuaYing; ZHOU Qin; CAI JieRu; YANG Yi; JIANG Hong; ZHANG WenJie; CHEN JiangHua


    Elucidation of maternal-fetal tolerance mechanisms clarifies the role of regulatory T cells (Treg)in transplant tolerance.This study aim to investigate the effect of pregnancy on paternal skin allograft survival.Flow cytometry techniques,mixed lymphocytes reaction (MLR),PCR,real-time PCR and skin transplantation were key methods.Treg increased significantly from 4.2% before pregnancy to peak at 6.8% day 8 after pregnancy.Both heme oxygenase-1 (HO-1)and indoleamine 2,3-dioxygenase (IDO)mRNA express high in placenta while low in spleen (P<0.05).Although Treg increased during pregnancy,and splenocytes from the pregnant mice showed lower MLR response toward the paternal stimulator,single time pregnancy showed no significant protective effect on paternal skin allograft survival in the tested condition.

  8. The effect of pregnancy on paternal skin allograft survival


    Elucidation of maternal-fetal tolerance mechanisms clarifies the role of regulatory T cells (Treg) in transplant tolerance. This study aim to investigate the effect of pregnancy on paternal skin allograft survival. Flow cytometry techniques, mixed lymphocytes reaction (MLR), PCR, real-time PCR and skin transplantation were key methods. Treg increased significantly from 4.2% before pregnancy to peak at 6.8% day 8 after pregnancy. Both heme oxygenase-1 (HO-1) and indoleamine 2,3-dioxygenase (IDO) mRNA express high in placenta while low in spleen (P<0.05). Although Treg increased during pregnancy, and splenocytes from the pregnant mice showed lower MLR response toward the paternal stimulator, single time pregnancy showed no significant protective effect on paternal skin allograft survival in the tested condition.

  9. Prolonged cardiac allograft survival in presensitized rats after a high activity Yunnan-cobra venom factor therapy.

    Li, R; Chen, G; Guo, H; Wang, D W; Xie, L; Wang, S S; Wang, W Y; Xiong, Y L; Chen, S


    Complement-dependent antibody-mediated acute humoral rejection is the major obstacle of clinical transplantation across ABO incompatibility and human leukocyte antigen presensitization. We previously demonstrated that Yunnan-cobra venom factor (Y-CVF) could almost completely abrogate complement activity and successfully prevent hyperacute rejection in some xenotransplant models without any obvious toxicity. In this study we investigated whether depletion of complement by Y-CVF prevented acute humoral allograft rejection in presensitized rats thereby prolonging graft survival. Presensitization was achieved in Lewis rats by sequential grafting of three full-thickness skin pieces from Brown Norway rats. Serum cytotoxic alloantibody titers were determined by a modified in vitro complement-dependent microcytotoxicity assay. After presensitization, each Lewis rat received a heterotopic Brown Norway cardiac allograft. Fifteen recipients were divided into two groups: (1) no treatment control (n = 7); (2) Y-CVF therapy group (86 u/kg, IV, day -1) (n = 8). After cessation of the heart beat, allograft rejection was confirmed by pathologic as well as IgG and C3 immunohistochemical examinations. The mean graft survival time was significantly prolonged to 99.50 +/- 38.72 hours among rats that received Y-CVF vs 12.71 +/- 13.94 hours in nontreated controls (P < .001). Upon pathological and immunohistochemical examination, acute humoral rejection was mainly exhibited in the control group, whereas acute cellular rejection was mainly displayed in the Y-CVF therapy group. Our study demonstrated that complement depletion by Y-CVF significantly inhibited acute humoral allograft rejection in presensitized rats. As a therapeutic immunointervention tool for complement, Y-CVF has shown potential efficacy across ABO incompatible and positive cross-match barriers.

  10. Prolonged Small Bowel Allografts Survival by CTLA4Ig Gene Transfection in Rats

    WANGYi-fang; LAIFu-sheng; XUAi-gang; WUWen-xi


    Objective: To evaluate the local expression of CTLA4Ig gene in small intestines and its effect on prolonging survival time of the small bowel allografts. Methods:The donor small bowels were perfused ex vivo with CTLA4Ig cDNA reconstructed plasmid packaged with lipofectin vector via intra-superior mesenteric artery before transplantation. The CTLA4Ig transgene expression in the small bowel allografts was assessed by immunohistology and RT-PCR after transplantation. Results: Immunohistology and RT-PCR demonstrated expression of CTLA4Ig transgene in the allografts at least for 28 d after transplantation. Eleven cases of the 18 small bowel allografts that received CTLA4Ig gene transfection survived more than 90 d in the recipients. Conclusion: A single ex vivo intra-superior ruesenteric artery infusion of CTLA4Ig cDNA reconstructed plasmid packaged with lipofectin induced efficient transduction of the small intestine, and the transfected small bowel allografts could survivor longer in nonimmunosupression rats.

  11. CD160Ig fusion protein targets a novel costimulatory pathway and prolongs allograft survival.

    Francesca D'Addio

    Full Text Available CD160 is a cell surface molecule expressed by most NK cells and approximately 50% of CD8(+ cytotoxic T lymphocytes. Engagement of CD160 by MHC class-I directly triggers a costimulatory signal to TCR-induced proliferation, cytokine production and cytotoxic effector functions. The role of CD160 in alloimmunity is unknown. Using a newly generated CD160 fusion protein (CD160Ig we examined the role of the novel costimulatory molecule CD160 in mediating CD4(+ or CD8(+ T cell driven allograft rejection. CD160Ig inhibits alloreactive CD8(+ T cell proliferation and IFN-γ production in vitro, in particular in the absence of CD28 costimulation. Consequently CD160Ig prolongs fully mismatched cardiac allograft survival in CD4(-/-, CD28(-/- knockout and CTLA4Ig treated WT recipients, but not in WT or CD8(-/- knockout recipients. The prolonged cardiac allograft survival is associated with reduced alloreactive CD8(+ T cell proliferation, effector/memory responses and alloreactive IFN-γ production. Thus, CD160 signaling is particularly important in CD28-independent effector/memory CD8(+ alloreactive T cell activation in vivo and therefore may serve as a novel target for prevention of allograft rejection.

  12. Banking of non-viable skin allografts using high concentrations of glycerol or propylene glycol.

    Huang, Qizhi; Pegg, David E; Kearney, John N


    The aims of this study were to investigate the kinetics of the current glycerol banking method for the preservation of non-viable skin allografts; to improve it with respect to efficiency and microbial safety; and to investigate the possibility of using propylene glycol in place of glycerol to provide a more rapid process. Skin grafts were preserved in 98% v/v glycerol (GLY) according to the method used in the Sheffield Skin Bank. During the addition and removal processes, the amounts of GLY and water in the skin were determined using the Karl Fischer method and HPLC respectively. Propylene glycol (PG) was investigated as an alternative to glycerol with the object of shortening the process. To avoid the need for prolonged storage in glycerol to disinfect the tissue, and to improve the effectiveness of disinfection, exposure to peracetic acid (PAA) was included and its influence on the kinetics of the preservation process was evaluated. The histological and ultrastructural appearances of skin that had been banked by these methods was also investigated. It was found that the permeation of GLY in skin probably involves two processes: diffusion and binding; the rate of transport was attenuated as the GLY concentration in the skin increased. The current incubation time could be shortened, but an inconveniently prolonged washout process was required. The substitution of PG for GLY accelerated the whole process, particularly the removal process, making the method more convenient for the emergency use of skin grafts in the clinic. The penetration of PG also involved diffusion and binding, but there was no attenuation of transport as the concentration increased. The addition of PAA sterilisation did not alter the transport of GLY or PG. Structural integrity was also maintained with the new banking treatments. An improved banking method can now be proposed; it can be completed in only one working day and the risk of disease transmission is reduced.

  13. Rapamycin Prolongs Cardiac Allograft Survival in a Mouse Model by Inducing Myeloid-Derived Suppressor Cells.

    Nakamura, T; Nakao, T; Yoshimura, N; Ashihara, E


    Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR inhibitors induce immunosuppression is not fully understood. Myeloid-derived suppressor cells (MDSCs) maintain host immunity; however, the relationship between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine cardiac transplantation model revealed that rapamycin treatment (3 mg/kg, intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of MDSCs and increased their expression of inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed that rapamycin induced the migration of iNOS-expressing MDSCs into the subintimal space within the allograft vessels, resulting in a significant prolongation of graft survival compared with that in the untreated group (67 days vs. 7 days, respectively). These effects were counterbalanced by the administration of an anti-Gr-1, which reduced allograft survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs from rapamycin-treated recipients prolonged allograft survival; this increase was reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathways appear to play an important role in MDSC expansion.

  14. Disinfection of human skin allografts in tissue banking: a systematic review report.

    Johnston, C; Callum, J; Mohr, J; Duong, A; Garibaldi, A; Simunovic, N; Ayeni, O R


    The use of skin allografts to temporarily replace lost or damaged skin is practiced worldwide. Naturally occurring contamination can be present on skin or can be introduced at recovery or during processing. This contamination can pose a threat to allograft recipients. Bacterial culture and disinfection of allografts are mandated, but the specific practices and methodologies are not dictated by standards. A systematic review of literature from three databases found 12 research articles that evaluated bioburden reduction processes of skin grafts. The use of broad spectrum antibiotics and antifungal agents was the most frequently identified disinfection method reported demonstrating reductions in contamination rates. It was determined that the greatest reduction in the skin allograft contamination rates utilized 0.1 % peracetic acid or 25 kGy of gamma irradiation at lower temperatures.

  15. Interleukin-10 modified dendritic cells induce allo-hyporesponsiveness and prolong small intestine allograft survival

    Min Zhu; Ming-Fa Wei; Fang Liu; Hui-Fen Shi; Guo Wang


    AIM: To investigate whether TL-10-transduced dendritic cells (DCs) could induce tolerogenicity and prolong allograft survival in rat intestinal transplantation.METHODS: Spleen-derived DCs were prepared and genetically modified by hTL-10 gene. The level of IL-10 expression was quantitated by ELTSA. DC function was assessed by MTT in mixed leukocyte reaction. Allogeneic T-cell apoptosis was examined by flow cytometric analysis. Seven days before heterotopic intestinal transplantation, 2x106 donor-derived IL-10-DC were injected intravenously, then transplantation was performed between SD donor and Wistar recipient.RESULTS: Compared with untransduced DC, IL-10-DC could suppress allogeneic mixed leukocyte reaction (MLR). The inhibitory effect was the most striking with the stimulator/effector (S/F) ratio of 1:10. The inhibition rate was 33.25 %,41.19 % (P<0.01) and 22.92 % with the S/E ratio of 1:1,1:10 and 1:50 respectively. At 48 hours and 72 hours by flow cytometry counting, apoptotic T cells responded to IL-10-DC in MLR were 13.8 % and 30.1%, while untransduced group did not undergo significant apoptosis (P<0.05). IL-10-DC pretreated recipients had a moderate survival prolongation with a mean allograft survival of 19.8 days (P<0.01),compared with 7.3±2.4 days in control group and 8.3±2.9days in untransduced DC group. Rejection occurred in the control group within three days. The difference between untreated DC group and control group was not significant.CONCLUSION: IL-10-DC can induce allogenic T-cell hyporesponsiveness in vitro and apoptosis may be involved in it. IL-10-DC pretreatment can prolong intestinal allograft survival in the recipient.

  16. Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts

    Slavin, S.; Reitz, B.; Bieber, C.P.; Kaplan, H.S.; Strober, S.


    Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.

  17. Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study 

    Rezaei, Ezzatollah; Beiraghi-Toosi, Arash; Ahmadabadi, Ali; Tavousi, Seyed Hassan; Alipour Tabrizi, Arash; Fotuhi, Kazem; Jabbari Nooghabi, Mehdi; Manafi, Amir; Ahmadi Moghadam, Shokoofeh


    BACKGROUND Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. METHODS Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. RESULTS PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. CONCLUSION Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients.

  18. [Oleanolic acid synergizes with cyclosporine A to prolong renal allograft survival in rats].

    Qian, Kun; Liao, Wenting; Li, Jianjun; Jiang, Hongtao; Zhou, Hao; Long, Jianhua; Qin, Guoqing; Wang, Yi


    To investigate the synergistic effect of oleanolic acid (OA) and cyclosporine A (CsA) on the survival of renal allografts in rats. Renal allograft transplantation was performed using BN rats as donors and LEW rats as recipients. Forty male LEW rats were randomized into 4 equal groups for interventions with DMSO-PBS (control), OA, CsA, or CsA+OA, starting from 1 day before transplantation. Serum creatinine levels were regularly examined, and the survival of rats were recorded. On day 5 after transplantation, CD4(+) and CD8(+) T-cell infiltration in the renal grafts was analyzed by immunohistochemistry; the concentrations of the proinflammatory cytokines (IL-1β, IFN-γ, IL-2, IL-4, and IL-17), anti-inflammatory cytokine IL-10 and chemokines (IP-10, MCP-1, MIP, and Mig) were analyzed with Luminex; the T-cell phenotypes (IFN-γ, IL-10, IL-4, and IL-17) were analyzed using ELISpot. In OA+CsA group, renal allograft survival was markedly prolonged and CD4(+) and CD8(+) T cell infiltration in the graft significantly decreased as compared to other groups. A significant decrease in IL-2 was observed in OA group and OA+CsA group, especially the latter. Compared with the control group, all the 3 treated groups showed significantly decreased IL-1β, IP-10 and MCP-1, increased IL-10 levels, decreased percentages of T cells secreting IFN-γ, IL-4 and IL-17, and increased percentage of T cells secreting IL-10. The increments of serum IL-10 level and T cell percentage were more prominent in OA+CsA group than in the other two intervention groups. OA and CsA synergistically ameliorate renal graft rejection and inflammation and promote allograft survival and function in rats.

  19. Effect of Blocking with Minicircle DNA of Interleukin-6 on Skin Allograft Rejection

    Doh Kyoung Chan


    Full Text Available Blocking of proinflammatory cytokine, interleukin-6 (IL-6 is effective in decreasing resistance to allogenic tolerance. In this study, we investigated whether anti-IL-6 receptor producing nonviral minicircle (MC-DNA, is competent to inhibit alloresponse-induced IL-6 in highly immunogenic murine skin allograft model. We designed MC-DNA producing IL-6R antibody and verified in vitro system. One day before skin allograft modeling, systemic MC-DNA exposed via hydrodynamic delivery of MC-DNA in vivo (50 ug of DNA, tail vein, single injection. Using GFP tagging MC-DNA, we confirmed its organ distribution. At day 5, we measured the amount of IL-6 and IL-6R antibody in serum. As functional examinations, we evaluated survival rate, morphological changes of graft, immune cell infiltration, and population of T helper 17 cells (Th17, FACS marker: CD4+/RoRγt and regulatory T cells (Treg, FACS marker: CD4+ Foxp3+. We compared its alloimmunity and graft survival efficiency with the cyclosporine A (CsA-treated group (50 mg/kg, daily administration via oral gavage. Hydrodynamic delivery of MC-DNA was mainly localized in hepatocytes. Serum IL-6 and IL-6R antibody detected in anti-IL-6R MC-DNA treated mice. At day 8.5, untreated mice completely rejected the graft confirming by daily observation of loss of skin graft and erosion. However, mice received either anti-IL-6R MC-DNA or CsA presented prolonged acceptance of graft until day 15 or 15.6, respectively. Results from morphological changes and immune cell infiltration in the graft were also consistent with survival rate. FACS results showed that anti-IL-6R MC-DNA treatment markedly suppressed Th17 population compared with the untreated mice. However, there was no effect on Treg population. On the other hand, administration of CsA showed the increased Th17 and decreased Treg population compared with untreated group. We found that single injection of nonviral minicircle DNA targeting IL-6R is effective in both

  20. Clinical application and viability of cryopreserved cadaveric skin allografts in severe burn: a retrospective analysis.

    Cleland, Heather; Wasiak, Jason; Dobson, Hannah; Paul, Michelle; Pratt, George; Paul, Eldho; Herson, Marisa; Akbarzadeh, Shiva


    Cadaveric cutaneous allografts are used in burns surgery both as a temporary bio-dressing and occasionally as definitive management of partial thickness burns. Nonetheless, limitations in the understanding of the biology of these grafts have meant that their role in burns surgery continues to be controversial. A review of all patients suffering 20% or greater total body surface area (TBSA) burns over an eight year period that received cadaveric allografts were identified. To investigate whether tissue viability plays a role in engraftment success, five samples of cryopreserved cadaveric cutaneous allograft processed at the Donor Tissue Bank of Victoria (DTBV) were submitted to our laboratory for viability analysis using two methods of Trypan Blue Exclusion and tetrazolium salt (MTT) assays. During the study period, 36 patients received cadaveric allograft at our institution. The average total burn surface area (TBSA) for this group of patients was 40% and all patients received cadaveric skin as a temporizing measure prior to definitive grafting. Cadaveric allograft was used in complicated cases such as wound contamination, where synthetic dressings had failed. Viability tests showed fewer than 30% viability in processed allografts when compared to fresh skin following the thawing process. However, the skin structure in the frozen allografts was histologically well preserved. Cryopreserved cutaneous cadaveric allograft has a positive and definite role as an adjunct to conventional dressing and grafting where available, particularly in patients with large TBSA burns. The low viability of cryopreserved specimens processed at DTBV suggests that cell viability in cadaveric allograft may not be essential for its clinical function as a wound dressing or even as permanent dermal substitute. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  1. Immature CD4+ dendritic cells conditioned with donor kidney antigen prolong renal allograft survival in rats

    WANG Tao; XU Lin; LI Heng; HUANG Zheng-yu; ZHANG Sheng-ping; MIAO Bin; NA Ning


    Background AIIogeneic transplant rejection is currently a major problem encountered during organ transplantation.The dendritic cell (DC) is the most effective powerful known professional antigen-presenting cell,and recent studies have found that DCs can also induce immune tolerance,and avoid or reduce the degree of transplant rejection.The aim of this study was to evaluate the effect of transfused immature CD4+ DCs on renal allografts in the rat model.Methods In this study,we induced CD4+ immature DCs from rat bone marrow cells by a cytokine cocktail.The immature CD4+ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo.Results Immature CD4+ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo.Conclusions Our study provides new information on efficacious renal transplantation,which might be useful for understanding the function of immature CD4+ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.

  2. HLA-G Dimers in the Prolongation of Kidney Allograft Survival

    Maureen Ezeakile


    Full Text Available Human leukocyte antigen-G (HLA-G contributes to acceptance of allografts in solid organ/tissue transplantation. Most studies have determined that soluble HLA-G isoforms are systematically detected in serum/plasma of transplanted patients with significantly fewer episodes of acute and/or chronic rejection of allogeneic tissue/organ. Current models of the interactions of HLA-G and its specific receptors explain it as functioning in a monomeric form. However, in recent years, new data has revealed the ability of HLA-G to form disulfide-linked dimeric complexes with high preferential binding and functional activities. Limited data are available on the role of soluble HLA-G dimers in clinical pathological conditions. We describe here the presence of soluble HLA-G dimers in kidney transplant patients. Our study showed that a high level of HLA-G dimers in plasma and increased expression of the membrane-bound form of HLA-G on monocytes are associated with prolongation of kidney allograft survival. We also determined that the presence of soluble HLA-G dimers links to the lower levels of proinflammatory cytokines, suggesting a potential role of HLA-G dimers in controlling the accompanying inflammatory state.

  3. Prolongation of liver allograft survival by dendritic cells modified with NF-κB decoy oligodeoxynucleotides

    Ming-Qing Xu; Yu-Ping Suo; Jian-Ping Gong; Ming-Man Zhang; Lü-Nan Yan


    significant allocostimulatory activity. NF-κB decoy ODNs completely abrogated IL-4-induced DC maturation and allocostimulatory activity as well as LPS-induced NF-κB activation and IL-12protein expression in DCs. GM-CSF+NF-κB decoy ODNspropagated DCs promoted apoptosis of liver allograftinfiltrating cells within portal areas, and significantly decreased the expression of IL-2 and IFN-γ mRNA but markedly elevated IL-4 mRNA expression both in liver allograft and in recipient spleen, and consequently suppressed liver allograft rejection, and promoted liver allograft survival.CONCLUSION: NF-κB decoy ODNs-modified DCs can prolong liver allograft survival by promoting apoptosis of graft-infiltrating cells within portal areas as well as downregulating IL-2 and IFN-γ mRNA and up-regulating IL-4 mRNA expression both in liver graft and in recipient spleen.

  4. Histological and immunohistochemical study of cutaneous angiogenesis process in experimental third-degree skin burns treated with allograft.

    Busuioc, Cristina Jana; Popescu, Florina Carmen; Mogoşanu, G D; Pârvănescu, H; Streba, Liliana; Mogoantă, L


    Skin burns are a rather high incidence lesions which, depending on their depth and extension, can severely affect not only the skin but the entire organism. Third-degree skin burns extended on over 20% of the body surface often require skin graft. Skin allograft is a therapeutic alternative when autograft cannot be used. We investigated the allograft influence on the angiogenesis process in third-degree skin burns, using an experimental model. We noticed that the allograft induces a stronger inflammatory reaction associated with intense angiogenesis process by about 10-15% compared to control group.

  5. Prolonged renal allograft survival by donor interleukin-6 deficiency: association with decreased alloantibodies and increased intragraft T regulatory cells.

    Wang, Hao; Guan, Qiunong; Lan, Zhu; Li, Shuyuan; Ge, Wei; Chen, Huifang; Nguan, Christopher Y C; Du, Caigan


    Both humoral and cellular immune responses are involved in renal allograft rejection. Interleukin (IL)-6 is a regulatory cytokine for both B and Foxp3 (forkhead box P3)-expressing regulatory T (Treg) cells. This study was designed to investigate the impact of donor IL-6 production on renal allograft survival. Donor kidneys from IL-6 knockout (KO) vs. wild-type (WT) C57BL/6 mice (H-2(b)) were orthotopically transplanted to nephrotomized BALB/c mice (H-2(d)). Alloantibodies and Treg cells were examined by fluorescence-activated cell sorting analysis. Graft survival was determined by the time to graft failure. Here, we showed that a deficiency in IL-6 expression in donor kidneys significantly prolonged renal allograft survival compared with WT controls. IL-6 protein was upregulated in renal tubules and endothelium of renal allografts following rejection, which correlated with an increase in serum IL-6 compared with that in those receiving KO grafts or naive controls. The absence of graft-producing IL-6 or lower levels of serum IL-6 in the recipients receiving IL-6 KO allografts was associated with decreased circulating anti-graft alloantibodies and increased the percentage of intragraft CD4(+)CD25(+)Foxp3(+) Treg cells compared with those with WT allografts. In conclusion, the lack of graft-producing IL-6 significantly prolongs renal allograft survival, which is associated with reduced alloantibody production and/or increased intragraft Treg cell population, implying that targeting donor IL-6 may effectively prevent both humoral and cellular rejection of kidney transplants.

  6. Triptolide inhibits CD4(+) memory T cell-mediated acute rejection and prolongs cardiac allograft survival in mice.

    Qiu, Shuiwei; Lv, Dingliang


    There have been numerous investigations into the immunosuppressive effects of triptolide; however, its inhibitory effects on memory T cells remain to be elucidated. Using a cluster of differentiation (CD)4(+) memory T-cell transfer model, the aim of the present study was to determine the inhibitory effects of triptolide on CD4(+) memory T cell-mediated acute rejection and to determine the potential underlying mechanisms. At 4 weeks after skin transplantation, mouse cervical heart transplantation was performed following the transfer of CD4(+) memory T cells. Mice were divided into two groups: A Control [normal saline, 30 ml/kg/day; intraperitoneal injection (ip)] and a triptolide group (triptolide, 3 mg/kg/day; ip). Graft survival, pathological examination and the corresponding International Society for Heart & Lung Transplantation (ISHLT) scores were assessed 5 days following heart transplantation, and levels of interleukin (IL)-2, interferon-γ (IFN-γ), IL-10 and transforming growth factor β1 (TGF-β1) in cardiac grafts and peripheral blood were assessed using reverse transcription-quantitative polymerase chain reaction and ELISA. The duration of cardiac graft survival in the triptolide group was significantly increased compared with the control group (14.3±0.4 vs. 5.3±0.2 days; PT cell-mediated acute rejection and prolongs cardiac allograft survival in mice. This effect may be mediated by the inhibition of cytokine secretion by type 1 T helper cells and promotion of regulatory T cell proliferation.

  7. Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival

    Xiaofei Shen


    Full Text Available The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation, which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts such as skin, kidney and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed. To improve current mixed chimerism induction protocols for future clinical application, we developed a new protocol using donor-specific regulatory T (Treg cells from mice with heart allograft tolerance, clinically available immunosuppressive drugs, and low doses of irradiation. Our results demonstrated that donor-specific Treg cells acquired from tolerant mice after in vitro expansion generate stable chimerism and lead to acceptance of intestinal allograft. Increased intragraft Treg cells and clonal deletion both contribute to the development of small bowel transplantation tolerance.

  8. Role of tacrolimus prolonged release in the prevention of allograft rejection

    Peter Abrams


    Full Text Available Peter Abrams, Abhinav Humar, Henkie P TanDepartment of Surgery, Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Successful management of the solid-organ transplant recipient begins with prevention of rejection and achieving a balance between insufficient and excessive immunosuppression. Standard tacrolimus therapy for prevention of solid-organ transplant rejection consists of 2 divided doses per day. In an effort to simplify tacrolimus dosing to once daily, a new formulation (tacrolimus prolonged release [PR] was chosen for its combination of a similar extent of bioavailability and a substantially reduced rate of clearance. Several clinical conversion studies have now been completed using PR to clarify its pharmacokinetics, efficacy at prevention of allograft rejection, and safety profiles in solid-organ transplant patients. A cohort of 67 stable kidney transplant recipients was converted from standard tacrolimus to PR in an open-label, multicenter study in the United States and Canada. A second open-label, multicenter study was performed in liver transplant recipients with stable graft function on standard tacrolimus therapy converted to PR. A third conversion study was performed as an open-label study at 5 centers in the United States in stable pediatric liver transplant recipients. As medication noncompliance can significantly contribute to the incidence of graft rejection and graft loss in transplant recipients, a potentially significant advance in the transplant community’s ongoing mission to optimize prevention of rejection occurred with the development of a once-daily tacrolimus PR. The results of these preliminary studies suggest that select solid-organ transplant recipients converted to PR can be safely maintained using the same monitoring and patient care techniques historically used for standard tacrolimus therapy.Keywords: immunosuppression, tacrolimus allograft

  9. [Skin and tissue bank: Operational model for the recovery and preservation of tissues and skin allografts].

    Martínez-Flores, Francisco; Sandoval-Zamora, Hugo; Machuca-Rodriguez, Catalina; Barrera-López, Araceli; García-Cavazos, Ricardo; Madinaveitia-Villanueva, Juan Antonio


    Tissue storage is a medical process that is in the regulation and homogenisation phase in the scientific world. The international standards require the need to ensure safety and efficacy of human allografts such as skin and other tissues. The activities of skin and tissues banks currently involve their recovery, processing, storage and distribution, which are positively correlated with technological and scientific advances present in current biomedical sciences. A description is presented of the operational model of Skin and Tissue Bank at INR as successful case for procurement, recovery and preservation of skin and tissues for therapeutic uses, with high safety and biological quality. The essential and standard guidelines are presented as keystones for a tissue recovery program based on scientific evidence, and within an ethical and legal framework, as well as to propose a model for complete overview of the donation of tissues and organ programs in Mexico. Finally, it concludes with essential proposals for improving the efficacy of transplantation of organs and tissue programs. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  10. sCD200 present in mice receiving cardiac and skin allografts causes immunosuppression in vitro and induces Tregs.

    Gorczynski, Reginald; Chen, Zhiqi; Khatri, Ismat; Yu, Kai


    CD200 overexpression in transgenic mice increases skin, cardiac, and renal allograft survival. Elevated levels of soluble CD200 (sCD200) are found in the serum of cancer individuals. We investigated whether sCD200 levels increase in mice with prolonged graft survival. Control or CD200 BL/6 recipients of BALB/c cardiac or skin grafts received low-dose rapamycin (0.5 mg/kg) at 36-hr intervals, a dose shown previously not to augment the survival of control grafts or alter the host antigraft immunity or graft gene expression profiles. Separate groups received high-dose rapamycin (1.5 mg/kg). Serum was obtained at 8, 15, and 80 days after grafting and assayed for sCD200 (enzyme-linked immunosorbent assay), for the suppression of immunity in mixed leukocyte cultures (MLCs), for the induction of regulatory T cells able to suppress cytotoxic T lymphocyte induction in MLCs, and for the ability to transfer graft survival to naïve recipients. Both CD200 and conventional mice with early enhanced graft survival had increased levels of sCD200 in serum, which induced Tr1 able to suppress MLCs. Suppression was abolished after passage of serum over a CD200 immunoadsorbent column. Dendritic cells maturing in the presence of sCD200 serum could induce populations of Foxp3 regulatory T cells able to suppress MLCs in vitro. In CD200 mice with long-term surviving cardiac (skin) allografts in the absence of continued transgene induction (>80 days [>35 days]), sCD200 levels returned to baseline, with no loss of grafts, but sera were unable to suppress MLCs in vitro. sCD200 serum adoptively transferred increased graft survival to naïve mice. We conclude that monitoring sCD200 at early times after engraftment may predict allograft survival.

  11. Donor dopamine treatment limits pulmonary oedema and inflammation in lung allografts subjected to prolonged hypothermia

    Hanusch, Christine; Nowak, Kai; Toerlitz, Patrizia; Gill, Ishar S.; Song, Hui; Rafat, Neysan; Brinkkoetter, Paul T.; Leuvenink, Henri G.; Van Ackern, Klaus C.; Yard, Benito A.; Beck, Grietje C.


    Background. Endothelial barrier dysfunction severely compromises organ function after reperfusion. Because dopamine pretreatment improves hypothermia mediated barrier dysfunction, we tested the hypothesis that dopamine treatment of lung allografts positively affects tissue damage associated with hyp

  12. Donor bone marrow-derived dendritic cells prolong corneal allograft survival and promote an intragraft immunoregulatory milieu.

    O'Flynn, Lisa; Treacy, Oliver; Ryan, Aideen E; Morcos, Maurice; Cregg, Marese; Gerlach, Jared; Joshi, Lokesh; Nosov, Mikhail; Ritter, Thomas


    Investigations into cell therapies for application in organ transplantation have grown. Here, we describe the ex vivo generation of donor bone marrow-derived dendritic cells (BMDCs) and glucocorticoid-treated BMDCs with potent immunomodulatory properties for application in allogeneic transplantation. BMDCs were treated with dexamethasone (Dexa) to induce an immature, maturation-resistant phenotype. BMDC and Dexa BMDC phenotype, antigen presenting cell function, and immunomodulatory properties were fully characterized. Both populations display significant immunomodulatory properties, including, but not limited to, a significant increase in mRNA expression of programmed death-ligand 1 and indoleamine 2,3-dioxygenase. BMDCs and Dexa BMDCs display a profound impaired capacity to stimulate allogeneic lymphocytes. Moreover, in a fully MHC I/II mismatched rat corneal transplantation model, injection of donor-derived, untreated BMDC or Dexa BMDCs (1 × 10(6) cells, day -7) significantly prolonged corneal allograft survival without the need for additional immunosuppression. Although neovascularization was not reduced and evidence of donor-specific alloantibody response was detected, a significant reduction in allograft cellular infiltration combined with a significant increase in the ratio of intragraft FoxP3-expressing regulatory cells was observed. Our comprehensive analysis demonstrates the novel cellular therapeutic approach and significant effect of donor-derived, untreated BMDCs and Dexa BMDCs in preventing corneal allograft rejection.

  13. Consecutive Low Doses of Cyclosporine A Induce Pro-Inflammatory Cytokines and Accelerate Allograft Skin Rejection

    Luis I. Terrazas


    Full Text Available Cyclosporine A (CsA is a fungus-derived molecule with potent immunosuppressive activity that has been largely used to downregulate cell-mediated immune responses during transplantation. However, previous data have indicated that CsA shows immunomodulatory activity that relays on the antigen concentration and the dose of CsA used. To test the hypothesis that minimal doses of CsA may show different outcomes on grafts, we used an experimental model for skin transplants in mice. ICR outbred mice received skin allografts and were either treated daily with different doses of CsA or left untreated. Untreated mice showed allograft rejection within 14 days, with graft necrosis, infiltration of neutrophils and macrophages and displayed high percentages of CD8+ T cells in the spleens, which were associated with high serum levels of IL-12, IFN-g and TNF-α. As expected, mice treated with therapeutic doses of CsA (15 mg/kg did not show allograft rejection within the follow-up period of 30 days and displayed the lowest levels of IL-12, IFN-g and TNF-α as well as a reduction in CD8+ lymphocytes. In contrast, mice treated with consecutive minimal doses of CsA (5 × 10−55 mg/kg displayed an acute graft rejection as early as one to five days after skin allograft; they also displayed necrosis and strong inflammatory infiltration that was associated with high levels of IL-12, IFN-g and TNF-α. Moreover, the CD4+ CD25hiFoxP3+ subpopulation of cells in the spleens of these mice was significantly inhibited compared with animals that received the therapeutic treatment of CsA and those treated with placebo. Our data suggest that consecutive, minimal doses of CsA may affect Treg cells and may stimulate innate immunity.

  14. Identiifcation of the miniature pig inbred line by skin allograft

    MU Yu-lian; WEI Jing-liang; TANG Fang; YANG Shu-lin; WU Zhi-gu; XIA Ying; SUN Tong-zhu; LIU Lan; FENG Shu-tang; WU Tian-wen; LI Kui; LI Jun-you; HE Wei; GAO Qian; ZHOU Wen-fang


    Skin grafting has been used as one of the most reliable tests to determine the genetic stability of laboratory animal such as mice and rats inbred line, but no identiifcation of swine inbred lines by skin grafting has been reported. At present, Wuzhishan miniature pig (WZSP) inbred line has acquired the F24 individuals in China. In order to verify whether WZSP inbred line had been cultivated successful y, al ogeneic skin grafts and related research were performed on F20 individuals of WZSP inbreeding population, compared with a control group of autologous transplantation. We observed the transplant recipients’ wounds, detected peripheral blood-related indicators interleukin-2, 4 and 10, CD4+and CD8+lymphocytes, and conducted hematoxylin-eosin (HE) and Masson’s staining of skin to judge whether the immune rejection reactions occurred within 28 days after transplantation. Chr. 7 genomic heterozygosity of 48 WZSP individuals from F20 to F22 was analyzed by high-density single nucleotide polymorphism (SNP) chips (60 000 SNPs). The result showed that there were no signiifcant differences in graft skin, the plasma interleukin-2, 4, 10, CD4+and CD8+, HE and Masson’s staining results between the al ograft and autograft groups, and no immune rejection occurred on the al ograft group. We found that 11 genes in Chr. 7 of major histocompatibility complex (MHC) I and MHC II were homozygous which conifrmed that immune antibody of the al ograft and autograft groups were highly identical and also provided a theoretical basis to no immune rejection occurred on the al ograft in the inbred WZSP. The result proved that the WZSP inbred line had been cultivated successful y for the ifrst time in the world. The test methods also provide a scientiifc basis for the identiifcation of swine and mammal inbred lines.

  15. The versatility of a glycerol-preserved skin allograft as an adjunctive treatment to free flap reconstruction

    Mat Saad A


    Full Text Available Skin allografts have been used in medical practice for over a century owing to their unique composition as a biological dressing. Skin allografts can be obtained in several preparations such as cryopreserved, glycerol-preserved, and fresh allograft. A glycerol-preserved allograft (GPA was introduced in the early 1980s. It has several advantages compared with other dressings such as ease of processing, storage and transport, lower cost, less antigenicity, antimicrobial properties, and neo-vascularisation promoting properties. Skin allografts are mainly used in the management of severe burn injuries, chronic ulcers, and complex, traumatic wounds. Published reports of the use of skin allografts in association with free flap surgery are few or non existent. We would like to share our experience of several cases of free tissue transfer that utilised GPA as a temporary wound dressing in multiple scenarios. On the basis of this case series, we would like to recommend that a GPA be used as a temporary dressing in conjunction with free flap surgery when required to protect the flap pedicle, allowing time for the edema to subside and the wound can then be closed for a better aesthetic outcome.

  16. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion.

    Cordoba, F; Wieczorek, G; Audet, M; Roth, L; Schneider, M A; Kunkler, A; Stuber, N; Erard, M; Ceci, M; Baumgartner, R; Apolloni, R; Cattini, A; Robert, G; Ristig, D; Munz, J; Haeberli, L; Grau, R; Sickert, D; Heusser, C; Espie, P; Bruns, C; Patel, D; Rush, J S


    CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.

  17. Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands

    Jean Kanitakis


    Full Text Available Recipients of solid organ transplants (RSOT have a highly increased risk for developing cutaneous premalignant and malignant lesions, favored by the lifelong immunosuppression. Vascularized composite tissue allografts (VCA have been introduced recently, and relevant data are sparse. Two patients with skin cancers (one with basal cell carcinoma and one with squamous cell carcinomas have been so far reported in this patient group. Since 2000 we have been following 9 recipients of VCA (3 face, 6 bilateral hands for the development of rejection and complications of the immunosuppressive treatment. Among the 9 patients, one face-grafted recipient was diagnosed with nodular-pigmented basal cell carcinoma of her own facial skin 6 years after graft, and one patient with double hand allografts developed disseminated superficial actinic porokeratosis, a potentially premalignant dermatosis, on her skin of the arm and legs. Similar to RSOT, recipients of VCA are prone to develop cutaneous premalignant and malignant lesions. Prevention should be applied through sun-protective measures, regular skin examination, and early treatment of premalignant lesions.

  18. Short- and long-term outcomes of small auto- and cryopreserved allograft skin grafting in those with >60%TBSA deep burn wounds.

    Shizhao, Ji; Yongjun, Zheng; Lisen, Zhang; Pengfei, Luo; Xiaopeng, Zheng; Guangyi, Wang; Shihui, Zhu; Xiaoyan, Hu; Shichu, Xiao; Zhaofan, Xia


    The shortage of autologous skin sources not only adds difficulty to the repair of extremely large-area deep burn wounds but affects the healing quality. The aim of the present study is to explore an ideal method for repairing large-areas burn wounds with low scar formation. Between 2002 and 2014, we used grafting of small auto- and cryopreserved allo-skin to repair large-area residual burn wounds in wounds after 21 days 21 patients, and after early excision in 17 patients. The wound healing rate and quality were observed. The skin expansion rate was 1:9-1:16, and the mean area of wounds repaired after three weeks was 64.8±7.3%TBSA, the wound healing rate was 91.8±3.7%. The mean area of the early excision group was 65.9±9.8 TBSA, where the healing rate was 94.5±5.6%. After small auto- and cryopreserved allograft skin grafting, the epidermis of the auto-skin gradually replaced the allo-epidermis, and the allo-dermis persisted for a prolonged period. The dermal collagen fibers at the allo-skin grafting sites were well arranged. At 1-2-year follow-up, observation showed that the Vancouver Scar Scale total score was 4·304±2·363, and we did not discern significant contracture and dysfunction in the large joints of the four extremities. Small auto- and cryopreserved allograft skin grafting of small auto- and allo-skin not only raised the graft expansion rate but offers a stable wound healing rate. This new technique may provide an option for repair of large-area deep burn wounds. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  19. FTY720 in combination with cyclosporine--an analysis of skin allograft survival and renal function.

    Silva, Francieli Ruiz; Silva, Lea Bueno Lucas; Cury, Patricia Maluf; Burdmann, Emmanuel Almeida; Bueno, Valquiria


    Acute and chronic nephrotoxicity caused by CsA continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation. FTY720 is a new compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens. In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney. Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose could prevent graft rejection and avoid nephrotoxicity.

  20. Down-regulating cyclin-dependent kinase 9 of alloreactive CD4+ T cells prolongs allograft survival

    Zhan, Yang; Han, Yeming; Sun, Hukui; Liang, Ting; Zhang, Chao; Song, Jing; Hou, Guihua


    CDK9 (Cyclin-dependent kinase 9)/Cyclin T1/RNA polymerase II pathway has been demonstrated to promote the development of several inflammatory diseases, such as arthritis or atherosclerosis, however, its roles in allotransplantation rejection have not been addressed. Here, we found that CDK9/Cyclin T1 were apparently up-regulated in the allogeneic group, which was positively correlated with allograft damage. CDK9 was inhibited obviously in naive splenic CD4+ T cells treated 6 h with 3 μM PHA767491 (a CDK9 inhibitor), and adoptive transfer of these CD4+ T cells into allografted SCID mice resulted in prolonged survival compared with the group without PHA767491 pretreated. Decelerated rejection was correlated with enhanced IL-4 and IL-10 production and with decreased IFN-γ production by alloreactive T cells. More interestingly, we found that CDK942, not CDK955, was high expressed in allorejection group, which could be prominently dampened with PHA767491 treatment. The expression of CDK942 was consistent with its downstream molecule RNA polymerase II. Altogether, our findings revealed the crucial role of CDK9/Cyclin T1/Pol II pathway in promoting allorejection at multiple levels and may provide a new approach for transplantation tolerance induction through targeting CDK9. PMID:27102157

  1. Prolongation of islet allograft survival in mice by combined treatment with pravastatin and low-dose cyclosporine.

    Arita, S; Kasraie, A; Une, S; Ohtsuka, S; Smith, C V; Mullen, Y


    Pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is known to have suppressive effects on immune and inflammatory cells. We have previously shown in mice and dogs that this agent prevents primary nonfunction of islet iso- and autografts by reducing inflammation at the graft site. The present study was designed to further investigate whether pravastatin has a synergistic effect with cyclosporine (Cs) to prolong islet allograft survival in mice. Unpurified 3000 BALB/c newborn islets were transplanted under the renal capsule of a streptozotocin-diabetic C57BL/6 mouse. Pravastatin and Cs were administered for 10 days starting on the day of grafting (day 0). Five groups were set up based on the treatment protocol: group 1, treatment with 40 mg/kg pravastatin; group 2, 30 mg/kg Cs; group 3, 50 mg/kg Cs; group 4, 40 mg/kg pravastatin and 30 mg/kg Cs; group 5, vehicle alone. Graft survival was indicated by blood glucose levels sustained at 250 mg/dl for 2 consecutive days. Hyperglycemia persisted in six of the eight (75%) mice and grafts were rejected in 3.6 +/- 0.5 days (mean +/- SD) in group 5. In group 1, grafts were also rejected in 3.8 +/- 0.8 days, but blood glucose was transiently 60 days, the other rejected the graft on day 15, and the remaining four died with functioning grafts between 9 and 13 days due to Cs toxicity. A combination of a low dose of Cs and pravastatin (group 4) prolonged graft survival for >19 days in five of the eight mice, and for 7-13 days in the remaining three mice. Histological examination of the grafts in this group showed significantly reduced local inflammation. Results indicate a synergistic effect of pravastatin and Cs on prevention of islet allograft rejection.

  2. Live sibling skin allografts for severe burns in a paediatric patient: A viable option in developing countries

    Basil Leodoro


    Full Text Available Severe burns in the paediatric population are associated with high mortality and morbidity in any developing countries. Children with more than 40% total body surface area burns in Fiji will succumb from complications and as a direct result of inadequate treatment and lack of resources. The surgical treatment of any severely burnt patient is not only laborious but very costly to the Fiji health system and depletes existing resources with few options for skin coverage. This is the first case report of live sibling skin allograft for severe paediatric burns and one of only few patients to have survived more than 50% burns in Fiji. We describe the technique and the role of using live sibling skin allograft as an option to improve survival in patients with severe burns in a developing country.

  3. Regulatory T cell expressed MyD88 is critical for prolongation of allograft survival.

    Borges, Christopher M; Reichenbach, Dawn K; Kim, Beom Seok; Misra, Aditya; Blazar, Bruce R; Turka, Laurence A


    MyD88 signaling directly promotes T-cell survival and is required for optimal T-cell responses to pathogens. To examine the role of T-cell-intrinsic MyD88 signals in transplantation, we studied mice with targeted T-cell-specific MyD88 deletion. Contrary to expectations, we found that these mice were relatively resistant to prolongation of graft survival with anti-CD154 plus rapamycin in a class II-mismatched system. To specifically examine the role of MyD88 in Tregs, we created a Treg-specific MyD88-deficient mouse. Transplant studies in these animals replicated the findings observed with a global T-cell MyD88 knockout. Surprisingly, given the role of MyD88 in conventional T-cell survival, we found no defect in the survival of MyD88-deficient Tregs in vitro or in the transplant recipients and also observed intact cell homing and expression of Treg effector molecules. MyD88-deficient Tregs also fail to protect allogeneic bone marrow transplant recipients from chronic graft-versus-host disease, confirming the observations of defective regulation seen in a solid organ transplant system. Together, our data define MyD88 as having a divergent requirement for cell survival in non-Tregs and Tregs, and a yet-to-be defined survival-independent requirement for Treg function during the response to alloantigen.

  4. Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells.

    Uchiyama, Masateru; Jin, Xiangyuan; Zhang, Qi; Hirai, Toshihito; Amano, Atsushi; Bashuda, Hisashi; Niimi, Masanori


    Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. Naïve CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were exposed to one of three types of music--opera (La Traviata), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to that from splenocytes of

  5. Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

    Uchiyama Masateru


    Full Text Available Abstract Background Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. Methods Naïve CBA mice (H2k underwent transplantation of a C57BL/6 (B6, H2b heart and were exposed to one of three types of music--opera (La Traviata, classical (Mozart, and New Age (Enya--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed. Results CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively, whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively. Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively. Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively. Proliferation of splenocytes, interleukin (IL-2 and interferon (IFN-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased

  6. Characterization of ionizing radiation effects on human skin allografts; Caracterizacao dos efeitos da radiacao ionizante em pele humana para aloenxerto

    Bourroul, Selma Cecilia


    The skin has a fundamental role in the viability of the human body. In the cases of extensive wounds, allograft skin provides an alternative to cover temporarily the damaged areas. After donor screening and preservation in glycerol (above 85%), the skin can be stored in the Skin Banks. The glycerol at this concentration has a bacteriostatic effect after certain time of preservation. On the other hand, skin sterilization by ionizing radiation may reduces the quarantine period for transplantation in patients and its safety is considered excellent. The objectives of this work were to establish procedures using two sources of ionizing radiation for sterilization of human skin allograft, and to evaluate the skin after gamma and electron beam irradiation. The analysis of stress-strain intended to verify possible effects of the radiation on the structure of preserved grafts. Skin samples were submitted to doses of 25 kGy and 50 kGy in an irradiator of {sup 60}Co and in an electron beam accelerator. Morphology and ultra-structure studies were also accomplished. The samples irradiated with a dose of 25 kGy seemed to maintain the bio mechanic characteristics. The gamma irradiated samples with a dose of 50 kGy and submitted to an electron beam at doses of 25 kGy and 50 kGy presented significant differences in the values of the elasticity modulus, in relation to the control. The analysis of the ultramicrographies revealed modifications in the structure and alterations in the pattern of collagen fibrils periodicity of the irradiated samples. (author)

  7. The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft rejection in mice: cholinergic pathway modulates alloreactivity.

    Claude Sadis

    Full Text Available Activation of innate immunity through Toll-like receptors (TLR can abrogate transplantation tolerance by revealing hidden T cell alloreactivity. Separately, the cholinergic anti-inflammatory pathway has the capacity to dampen macrophage activation and cytokine release during endotoxemia and ischemia reperfusion injury. However, the relevance of the α7 nicotinic acetylcholine receptor (α7nAChR-dependent anti-inflammatory pathway in the process of allograft rejection or maintenance of tolerance remains unknown. The aim of our study is to investigate whether the cholinergic pathway could impact T cell alloreactivity and transplant outcome in mice. For this purpose, we performed minor-mismatched skin allografts using donor/recipient combinations genetically deficient for the α7nAChR. Minor-mismatched skin grafts were not rejected unless the mice were housed in an environment with endogenous pathogen exposure or the graft was treated with direct application of imiquimod (a TLR7 ligand. The α7nAChR-deficient recipient mice showed accelerated rejection compared to wild type recipient mice under these conditions of TLR activation. The accelerated rejection was associated with enhanced IL-17 and IFN-γ production by alloreactive T cells. An α7nAChR-deficiency in the donor tissue facilitated allograft rejection but not in recipient mice. In addition, adoptive T cell transfer experiments in skin-grafted lymphopenic animals revealed a direct regulatory role for the α7nAChR on T cells. Taken together, our data demonstrate that the cholinergic pathway regulates alloreactivity and transplantation tolerance at multiple levels. One implication suggested by our work is that, in an organ transplant setting, deliberate α7nAChR stimulation of brain dead donors might be a valuable approach for preventing donor tissue inflammation prior to transplant.

  8. The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft rejection in mice: cholinergic pathway modulates alloreactivity.

    Sadis, Claude; Detienne, Sophie; Vokaer, Benoît; Charbonnier, Louis-Marie; Lemaître, Philippe; Spilleboudt, Chloé; Delbauve, Sandrine; Kubjak, Carole; Flamand, Véronique; Field, Kenneth A; Goldman, Michel; Benghiat, Fleur S; Le Moine, Alain


    Activation of innate immunity through Toll-like receptors (TLR) can abrogate transplantation tolerance by revealing hidden T cell alloreactivity. Separately, the cholinergic anti-inflammatory pathway has the capacity to dampen macrophage activation and cytokine release during endotoxemia and ischemia reperfusion injury. However, the relevance of the α7 nicotinic acetylcholine receptor (α7nAChR)-dependent anti-inflammatory pathway in the process of allograft rejection or maintenance of tolerance remains unknown. The aim of our study is to investigate whether the cholinergic pathway could impact T cell alloreactivity and transplant outcome in mice. For this purpose, we performed minor-mismatched skin allografts using donor/recipient combinations genetically deficient for the α7nAChR. Minor-mismatched skin grafts were not rejected unless the mice were housed in an environment with endogenous pathogen exposure or the graft was treated with direct application of imiquimod (a TLR7 ligand). The α7nAChR-deficient recipient mice showed accelerated rejection compared to wild type recipient mice under these conditions of TLR activation. The accelerated rejection was associated with enhanced IL-17 and IFN-γ production by alloreactive T cells. An α7nAChR-deficiency in the donor tissue facilitated allograft rejection but not in recipient mice. In addition, adoptive T cell transfer experiments in skin-grafted lymphopenic animals revealed a direct regulatory role for the α7nAChR on T cells. Taken together, our data demonstrate that the cholinergic pathway regulates alloreactivity and transplantation tolerance at multiple levels. One implication suggested by our work is that, in an organ transplant setting, deliberate α7nAChR stimulation of brain dead donors might be a valuable approach for preventing donor tissue inflammation prior to transplant.

  9. Composite mandibular allografts in canines


    Objective: To evaluate the feasibility of transplanting composite mandibular allografts to repair large mandibular defects. Methods: Three composite mandibular transplantation models were established. The first model consisted of hemimandible with the attached teeth, muscle and skin, and oral mucosa. The second model was transplanted in the same way with the first one excluding oral mucosa and some teeth, and third one excluding the oral mucosa and all dental crowns. Fourteen transplanting operations were performed in canines. Cyclosporine A and methylprednisone were given for immunosuppression. Results: The composite mandibular organs had an effective and closed return circuit. Transplantation of vascularized allograft of mandibular compound organs was feasible. Two longest time survivors of 67 d and 76 d were in the third model group. Cyclosporine A was successful in suppressing rejection of transplanted composite allograft and prolonging survival time of transplantation models. Conclusions: The composite mandibular allografts were available with large block of living composite tissue,and helpful in restoration of appearance and function for severe mandibular defects.

  10. FTY720 treatment prolongs skin graft survival in a completely incompatible strain combination.

    Lima, R S M; Nogueira-Martins, M F; Silva, H T; Pestana, J O M; Bueno, V


    FTY720 has shown potent immunomodulatory activity in a variety of animal organ transplant models. However, the in vivo immunosuppressive mechanism of FTY720 is still not fully understood. It has been suggested that the marked decrease in the number of peripheral blood lymphocytes during FTY720 administration could be responsible for its immunosuppressive effects. Our aims were: (1) to study the effects of FTY720 treatment on skin graft survival using a fully mismatched strain combination and (2) to evaluate lymphocyte numbers in different sites at 5 days after skin transplant. C57BL/6 mice and BALB/c mice were the donors and recipients respectively. BALB/c mice received FTY720 (1 mg/kg/d) orally for 4 consecutive days. Drug administration started 1 day before skin transplants. A small segment of tail skin was affixed on the right dorsal side of the mouse via sutures. The administration of FTY720 (4 mg/kg) prolonged skin graft survival from 12.6 +/- 2.2 days (no treatment) to 16.6 +/- 4.2 days. The histologic findings of rejection were similar for all groups. Five days after transplant, lymphocyte numbers were significantly increased in lymph nodes compared with nontransplanted or isogenic graft mice. FTY720 decreased lymphocyte numbers only in the spleen. In conclusion, FTY720 prolonged skin graft survival in a fully mismatched strain combination when administered for 4 days (day -1 to day +2) at a dose of 1 mg/kg/d. The decreased number of lymphocytes in the spleen suggests that the spleen may be a target of FTY720 activity, during the early posttransplant period.

  11. Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts.

    Hautz, Theresa; Zelger, Bettina G; Nasr, Isam W; Mundinger, Gerhard S; Barth, Rolf N; Rodriguez, Eduardo D; Brandacher, Gerald; Weissenbacher, Annemarie; Zelger, Bernhard; Cavadas, Pedro; Margreiter, Raimund; Lee, W P Andrew; Pratschke, Johann; Lakkis, Fadi G; Schneeberger, Stefan


    The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T- and B-cell infiltration.

  12. Semi-mature MyD88-silenced bone marrow dendritic cells prolong the allograft survival in a rat model of intestinal transplantation

    YANG Xiao-jun; MENG Song; Zhu Chun-fu; JIANG Hong; WU Wen-xi


    Background Semi-mature dendritic cells (DCs) may induce tolerance rather than immunity.However,little is known about the regulatory mechanism by which these DCs induce transplant tolerance.Myeloid differentiation factor 88 (MyD88) is a key adaptor of Toil-like receptor signaling,which plays a critical role in DC maturation.Activation of MyD88-silenced immature DCs results in the generation of semi-mature DCs.We explored the possibility of using these DCs to induce intestinal transplant tolerance in rats.Methods MyD88 expression was silenced in bone marrow DCs (F344 rats) using small interfering RNAs for 24 hours,at which point,lipopolysaccharide (LPS) was added to the culture for another 48 hours.These cells were analyzed for their in vitro and in vivo tolerizing capacities.Results Semi-mature DCs expressing moderate levels of MHC class Ⅱ and low levels of co-stimulatory molecules were found to produce interleukin (IL)-10,while IL-12 production was decreased.In vitro co-culture with completely allogeneic T cells from Wistar rats led to a significant decrease in alloreactive T-cell responses.In vivo,the transfer of semi-mature DCs (1×106 ceils) followed by the transplantation of fully mismatched intestinal grafts (F344 rats) led to significantly prolonged survival compared to rats receiving immature and mature DCs.Serum from semi-mature DC-treated rats contained lower concentrations of the pro-inflammatory cytokines IL-2 and interferon-Y 5 days after transplantation.Conclusion Semi-mature DCs may promote inducible allograft tolerance and this study suggests a new strategy by which to facilitate the induction of transplant tolerance.

  13. Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response.

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Kanno, Emi; Suzuki, Aiko; Takagi, Naoyuki; Yamamoto, Hideki; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro


    The wound-healing process consists of the inflammation, proliferation, and remodeling phases. In chronic wounds, the inflammation phase is prolonged with persistent neutrophil infiltration. The inflammatory response is critically regulated by cytokines and chemokines that are secreted from various immune cells. Recently, we showed that skin wound healing was delayed and the healing process was impaired under conditions lacking invariant natural killer T (iNKT) cells, an innate immune lymphocyte with potent immuno-regulatory activity. In the present study, we investigated the effect of iNKT cell deficiency on the neutrophilic inflammatory response during the wound healing process. Neutrophil infiltration was prolonged in wound tissue in mice genetically lacking iNKT cells (Jα18KO mice) compared with wild-type (WT) control mice on days 1 and 3 after wounding. MIP-2, KC, and IL-17A were produced at a significantly higher level in Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO mice compared with WT mice. Treatment with either anti-IL-17A mAb, anti-Gr-1 mAb, or neutrophil elastase inhibitor reversed the impaired wound healing in Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils. This article is protected by copyright. All rights reserved. © 2017 by the Wound Healing Society.

  14. Glycerol-Preserved Arterial Allografts Evaluated in the Infrarenal Rat Aorta

    Fahner, P.J; Idu, M.M; van Gulik, T.M; van Wijk, B; van der Wal, A.C; Legemate, D.A


    .... Since glycerol preservation proved effective for the storage of skin allografts, this preservation method was investigated for vascular allografts using a rat aortic transplantation model. Methods...

  15. A biodegradable, sustained-released, prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model.

    Yu-Chi Liu

    Full Text Available Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA-loaded poly (d,l-lactide-co-ε-caprolactone (PLC microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK using a rat model. The drug release profiles of the microfilms were characterized (group 1. Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2, allogeneic control grafts (group 3, allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4, and allogeneic grafts with PA eye drops (group 5; n = 12 in each. PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006-0.009 mg/day, with a consistent aqueous drug concentration of 207-209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3. Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001. There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  16. The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+25(+Foxp3+ regulatory T cells on skin allograft rejection.

    Jung Ho Lee

    Full Text Available Mesenchymal stromal cells (MSCs are seen as an ideal source of cells to induce graft acceptance; however, some reports have shown that MSCs can be immunogenic rather than immunosuppressive. We speculate that the immunomodulatory effects of regulatory T cells (Tregs can aid the maintenance of immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy can have synergistic immunomodulatory effects on allograft rejection. After preconditioning with Fludarabine, followed by total body irradiation and anti-asialo-GM-1(ASGM-1, tail skin grafts from C57BL/6 (H-2k(b mice were grafted onto the lateral thoracic wall of BALB/c (H-2k(d mice. Group A mice (control group, n = 9 did not receive any further treatment after preconditioning, whereas groups B and C (n = 9 received cell therapy with MSCs or Tregs, respectively, on days -1, +6 and +13 relative to the skin transplantation. Group D (n = 10 received cell therapy with MSCs and Tregs on days -1, +6 and +13. Cell suspensions were obtained from the spleens of five randomly chosen mice from each group on day +7, and the immunomodulatory effects of the cell therapy were evaluated by flow cytometry and real-time PCR. Our results show that allograft survival was significantly longer in group D compared to the control group (group A. Flow cytometric analysis and real-time PCR for splenocytes revealed that the Th2 subpopulation in group D increased significantly compared to the group B. Also, the expression of Foxp3 and STAT 5 increased significantly in group D compared to the conventional cell therapy groups (B and C. Taken together, these data suggest that a combined cell therapy approach with MSCs and Tregs has a synergistic effect on immunoregulatory function in vivo, and might provide a novel strategy for improving survival in allograft transplantation.

  17. How Long Will I Be Blue? Prolonged Skin Staining Following Sentinel Lymph Node Biopsy Using Intradermal Patent Blue Dye

    Gumus, Metehan; Gumus, Hatice; Jones, Sue E; Jones, Peter A; Sever, Ali R; Weeks, Jennifer


    Summary Background Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. Patients and Methods 236 consecutive patients who had undergone breast conserving surgery and SLNB for breast cancer were reviewed prospectively from January 2007 to December 2009. Results Of the 236 patients, 2 had undergone bilateral surgery, and 41 had been examined in consecutive yearly reviews. Blue discoloration remained visible at the injection site after 12, 24, and > 36 months in 36.5, 23.6, and 8.6% of the patients, respectively. Conclusion The use of patent blue for identification of the sentinel lymph node in patients undergoing breast cancer surgery may result in prolonged discoloration of the skin at the injection site. PMID:24415970

  18. Ambulatory assessment of skin conductivity during first thesis presentation: lower self-confidence predicts prolonged stress response.

    Elfering, Achim; Grebner, Simone


    In this field study self-confidence was tested to predict the course of galvanic electrodermal stress response prior, during and after public speaking. Ten graduate students initially rated their self-confidence and afterwards presented their thesis proposals orally in a 10-min presentation to their supervisor and peers. Galvanic skin response level was measured throughout and analysed for 10 min prior to, during, and 10 min after the presentation. Two major galvanic electrodermal stress response types were observed. Five students showed a 'healthy response', i.e. an anticipatory increase in electrodermal conductance, followed by a decrease after termination of the presentation. The other five students showed a steady increase of skin conductance during and after their presentation ('prolonged response'). In line with the allostatic load model the 'prolonged response' group reported significantly lower self-confidence before presentation than the 'healthy response' group (p Self-confidence is a resource in novices facing an unfamiliar stressor.

  19. Estudo comparativo dos efeitos da talidomida, da ciclosporina e do diclofenaco na sobrevida de aloenxertos cutâneos em coelho Assessment of immunossupresion induced by thalidomide, cyclosporine and diclofenac on skin allograft survival in rabbits

    Diva Novy Barbosa Chaves


    Full Text Available OBJETIVO: Verificar se a talidomida é capaz de evitar a rejeição de aloenxertos de pele em coelhos, como droga isolada, ou melhorar a eficácia de doses subterapêuticas de ciclosporina, comparando seu efeito ao de doses terapêuticas da ciclosporina e também ao papel antiinflamatório do diclofenaco de sódio. MÉTODOS: Foram estudados 42 coelhos, distribuídos nos seguintes grupos (n=6: Grupo 1 - controle com auto-enxerto; Grupo 2 - controle com aloenxerto; Grupo 3 - aloenxerto sob o efeito de talidomida (100 mg/kg/dia; Grupo 4 - aloenxerto sob o efeito de diclofenaco de sódio (2 mg/kg/dia; Grupo 5 - aloenxerto sob o efeito de ciclosporina (10 mg/kg/dia; Grupo 6 - aloenxerto sob o efeito de ciclosporina (5 mg/kg/dia; Grupo 7 - aloenxerto sob o efeito de ciclosporina (5 mg/kg/dia associada a talidomida (100 mg/kg/dia. Foram retirados enxertos circulares de pele total do dorso de uma das orelhas do animal. Os medicamentos foram administrados por cateter orogástrico, a partir do dia anterior ao transplante. Os enxertos foram trocados entre coelhos de raças diferentes. RESULTADOS: A ciclosporina a 10 mg/kg/dia prolongou a sobrevida dos enxertos de pele, sendo seu efeito comparável ao obtido com a ciclosporina em dose subterapêutica (5 mg/kg/dia associada a talidomida a 100 mg/kg/dia. A talidomida isoladamente, mesmo em concentração de 100 mg/kg/dia, e o diclofenaco tiveram efeito mínimo na sobrevida média dos aloenxertos cutâneos. O número de eosinófilos no infiltrado inflamatório circunjacente à necrose foi maior nos grupos tratados com diclofenaco e com ciclosporina a 5 mg/kg/dia e menor no grupo em que se associou ciclosporina com talidomida. CONCLUSÃO: A talidomida pode ser uma droga útil para associar-se a baixas doses de ciclosporina no tratamento de aloenxertos cutâneos.OBJECTIVE: Allografting is one of the therapeutic alternatives for extensive burn victims without sufficient skin donor areas. This research studied the

  20. Skin lesions simulating blue toe syndrome caused by prolonged contact with a millipede

    Augusto Scardazan Heeren Neto


    Full Text Available Venomous animals are those that, by means of a hunting and defense mechanism, are able to inject their prey with a toxic substance produced in their bodies, directly from specialized glands (e.g., tooth, sting, spur through which the poison passes. Millipedes are poisonous animals; they can be harmful to humans, and their effects usually manifest as erythematous, purpuric, and cyanotic lesions; local pain; and paresthesia. Here, we report a case of skin contact with a millipede for 6h resulting in skin lesions similar to blue toe syndrome.

  1. Agonistic CD200R1 DNA Aptamers Are Potent Immunosuppressants That Prolong Allogeneic Skin Graft Survival

    Aaron Prodeus


    Full Text Available CD200R1 expressed on the surface of myeloid and lymphoid cells delivers immune inhibitory signals to modulate inflammation when engaged with its ligand CD200. Signalling through CD200/CD200R1 has been implicated in a number of immune-related diseases including allergy, infection, cancer and transplantation, as well as several autoimmune disorders including arthritis, systemic lupus erythematosus, and multiple sclerosis. We report the development and characterization of DNA aptamers, which bind to murine CD200R1 and act as potent signalling molecules in the absence of exogenous CD200. These agonistic aptamers suppress cytotoxic T-lymphocyte induction in 5-day allogeneic mixed leukocyte culture and induce rapid phosphorylation of the CD200R1 cytoplasmic tail thereby initiating immune inhibitory signalling. PEGylated conjugates of these aptamers show significant in vivo immunosuppression and enhance survival of allogeneic skin grafts as effectively as soluble CD200Fc. As DNA aptamers exhibit inherent advantages over conventional protein-based therapeutics including low immunogenicity, ease of synthesis, low cost, and long shelf life, such CD200R1 agonistic aptamers may emerge as useful and safe nonsteroidal anti-inflammatory therapeutic agents.

  2. Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

    Khan, Tapan K; Wender, Paul A; Alkon, Daniel L


    Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

  3. Hyaluronate nanoparticles included in polymer films for the prolonged release of vitamin E for the management of skin wounds.

    Pereira, Gabriela Garrastazu; Detoni, Cassia Britto; Balducci, Anna Giulia; Rondelli, Valeria; Colombo, Paolo; Guterres, Silvia Stanisçuaski; Sonvico, Fabio


    Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration.

  4. Pregnancy estrogen drives the changes of T-lymphocyte subsets and cytokines and prolongs the survival of H-Y skin graft in murine model

    LIN Xing-guang; ZHOU Qi; WANG Li; GAO Ying; ZHANG Wei-na; LUO Zhen-long; CHEN Bi-cheng; CHEN Zhong-hua; CHANG Sheng


    Background Estrogen as well as CD4+Foxp3+ regulatory T cells were shown to have a protective role not only in maintaining maternal-fetal tolerance but also against autoimmune diseases. We aimed to investigate whether the pregnancy levels of estrogen are enough to induce transplant tolerance as to maintain fetal-maternal tolerance.Methods We established H-Y skin graft transplantation in C57BL/6 ovariectomized mice that reconstituted with estrogen. Subsequently, consecutive daily estrogen injection was administrated. Tregs and the cytokines in the peripheral blood were detected by flow cytometry and ELISA pre- and post-transplant.Results The results indicated that pregnancy levels of estrogen could promote Tregs in secondary lymphoid organs and peripheral blood (P0.05). The estrogen-treated recipients accepted H-Y skin grafts for more than 35 days (median survival time (MST): (44.0±1.2) days) compared with estrogen-untreated mice (MST:(23.0±1.6) days) (P <0.05). It was also observed that estrogen up-regulated the expression of Foxp3, but did not affect CD3+CD8+ effector T-cells in non-transplant mice. While in the presence of H-Y antigens, the expression of Foxp3 was more significant and CD3+CD8+ effector T cells were decreased significantly (P <0.05). Meanwhile, the up-regulated IL-10 and IL-4, and down-regulated IFN-Y could be observed (P <0.05).Conclusions Pregnancy levels of estrogen may promote the conversion of peripheral Tregs in secondary lymphoid organs, but show no effect on the natural Tregs production, differentiation and maturity in central lymphoid organs.Furthermore, pregnancy levels of estrogen could significantly prolong the survivals of H-Y skin grafts by the expansion of Tregs, suppression of CD3+CD8+ effector T-cells and immune shift towards Th2 cytokines.

  5. miR-125b can enhance skin tumor initiation and promote malignant progression by repressing differentiation and prolonging cell survival.

    Zhang, Liang; Ge, Yejing; Fuchs, Elaine


    Previously, we identified miR-125b as a key regulator of the undifferentiated state of hair follicle stem cells. Here, we show that in both mice and humans, miR-125b is abundantly expressed, particularly at early stages of malignant progression to squamous cell carcinoma (SCC), the second most prevalent cancer worldwide. Moreover, when elevated in normal murine epidermis, miR-125b promotes tumor initiation and contributes to malignant progression. We further show that miR-125b can confer "oncomiR addiction" in early stage malignant progenitors by delaying their differentiation and favoring an SCC cancer stem cell (CSC)-like transcriptional program. To understand how, we systematically identified and validated miR125b targets that are specifically associated with tumors that are dependent on miR-125b. Through molecular and genetic analysis of these targets, we uncovered new insights underlying miR-125b's oncogenic function. Specifically, we show that, on the one hand, mir-125b directly represses stress-responsive MAP kinase genes and associated signaling. On the other hand, it indirectly prolongs activated (phosphorylated) EGFR signaling by repressing Vps4b (vacuolar protein-sorting 4 homolog B), encoding a protein implicated in negatively regulating the endosomal sorting complexes that are necessary for the recycling of active EGFR. Together, these findings illuminate miR-125b as an important microRNA regulator that is shared between normal skin progenitors and their early malignant counterparts.

  6. Uremic escape of renal allograft rejection

    van Schilfgaarde, R. (Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis); van Breda Vriesman, P.J.C. (Rijksuniversiteit Limburg Maastricht (Netherlands). Dept. of Immunopathology)


    It is demonstrated in rats that, in the presence of early postoperative severe but transient uremia, the survival of first set Brown-Norway (BN) renal allografts in Lewis (LEW) recipients is at least three times prolonged when compared to non-uremic controls. This phenomenon is called 'uremic escape of renal allograft rejection'. By means of lethal X-irradiation of donors of BN kidneys transplanted into transiently uremic and non-uremic LEW recipients, the presence of passenger lymphocyte immunocompetence is demonstrated to be obilgatory for this phenomenon to occur. As a result of mobile passenger lymphocyte immunocompetence, a graft-versus-host (GVH) reaction is elicited in the spleens of LEW recipients of BN kidneys which amplifies the host response. The splenomegaly observed in LEW recipients of BN kidneys is caused not only by this GVH reaction, which is shown to be exquisitely sensitive to even mild uremia. It is also contributed to by a proliferative response of the host against the graft (which latter response is equated with an in vivo equivalent of a unilateral mixed lymphocyte reaction (MLR)), since the reduction in spleen weights caused by abrogation of mobile passenger lymphocyte immunocompetence brought about by lethal donor X-irradiation is increased significantly by early postoperative severe but transient uremia. It is concluded that in uremic escape of renal allograft rejection both reactions are suppressed by uremia during the early post-operative period.

  7. Rare presentations of cytomegalovirus infection in renal allograft recipients.

    Ardalan, Mohammadreza


    Cytomegalovirus is the most common viral infection after kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. Most symptomatic infections manifest as fever and cytopenia. The gastrointestinal tract is the most common site of tissue-invasive infection, often presenting as diarrhea or gastrointestinal bleeding. Gastrointestinal obstruction, perforation, thrombosis of large gastrointestinal veins, splenic artery thrombosis, and pancreatitis are rare gastrointestinal presentations of cytomegalovirus infection. Renal-allograft ureteral stricture and skin involvement are other rare presentations of cytomegalovirus infection. hemophagocytic syndrome, thrombotic microangiopathy, adrenal insufficiency, and renal allograft artery stenosis are other rare symptoms of cytomegalovirus infection.

  8. Chronic allograft nephropathy.

    Vadivel, Nidyanandh; Tullius, Stefan G; Chandraker, Anil


    Chronic allograft nephropathy (CAN) remains the Achilles heel of renal transplantation. In spite of the significant strides achieved in one-year renal allograft survival with newer immunosuppressant strategies, the fate of long-term renal allograft survival remains unchanged. The number of renal transplant recipients returning to dialysis has doubled in the past decade. This is especially important since these patients pose a significantly increased likelihood of dying while on the waiting list for retransplantation, due to increasing disparity between donor organ availability versus demand and longer waiting time secondary to heightened immunologic sensitization from their prior transplants. In this review we analyze the latest literature in detail and discuss the definition, natural history, pathophysiology, alloantigen dependent and independent factors that play a crucial role in CAN and the potential newer therapeutic targets on the horizon. This article highlights the importance of early identification and careful management of all the potential contributing factors with particular emphasis on prevention rather than cure of CAN as the core management strategy.

  9. 术前输注供者CD80low/CD86low树突状细胞延长小鼠同种异体移植心脏存活%Donor dendritic cells treated with B7- 1, B7- 2 antisense oligonucleotide prolonged mouse cardiac allograft survival

    梁晓燕; 陈宗佑; 钱诗光; 李树浓


    AIM:To investigate the effect of donor bone marrow derived dentritic cell (DC) treated with B7 - 1, B7 - 2 antisense oligonucleotide on mouse heart allografe survival time and its mechanism. METHODS: There were 7 groups of C57BL/10J (B10) mouse bone marrow DCs which were treated by 400 nM antisense oligonucleotide target to B7 -1, B7 -2 mRNA (AS B7- 1/2), B7- 1 mismatch oligo control ,B7- 2 mismatch control(mASB7- 1/2), lipofeetamine only and non-treatment, respectively. Each group of DC were named as ASB7- 1 DC, ASB7- 2 DC, mASB7 - 1 DC, mAS B7 - 2DC, and Lipo DC, respectively. RESULTS: Flow cytometer results shown that AS B7- 1/2 can inhibit B7- 1 (CD80)and B7- 2 (CD86) molecule express on DC surface, while control groups have no effects. To observe their tolerogenicity in mouse cardiac allograft model, B10→C3H heterotopic heart transplantation were performed. Recepients were received 2 x 106 of DC injection 7 days before transplantation. Results showed that both AS B7 - 1 DC and AS B7 - 2 DC can prolong mouse cardiac allograft survival time to (18.6 + 0.89) days and (23.67 + 10.73) days, respectively, compared with IL - 4 DC [ (6.22 + 0.97) days ( P < 0.01 ) ]. Two mismatch control groups can slightly prolong while oligo DC has no effect. For understanding its mechanism, each group of DC was used as stimulator to stimulated C3H spleen T cell. Results suggested that AS B7 - 1DC and AS B7 - 2 DC had less allo - stimulate function, including MLR and generation CTL and IL - 2 production than IL - 4 DC but control groups have no effect. CONCLUSION: Donor bone marrow derived DC treated with AS B7 - 1 oligo and AS B7 - 2 oligo expressed lower level of CD80 and CD86, respectively. These cells can induce allogeneic T cells anergy in vitro and markedly prolong mouse heart allograft survival time in vivo.%目的:应用B7-1和B7-2反义寡核苷酸(AS B7-1/AS B7-2 oligo)抑制CD80(B7-1)、CD86(B7-2)在供体小鼠骨髓树突状细胞(DC)上的表达,观察这类DC

  10. Morphological and functional alterations in glycerol preserved rat aortic allografts.

    Fahner, P J; Idu, M M; Legemate, D A; Vanbavel, E; Borstlap, J; Pfaffendorf, M; van Marle, J; van Gulik, T M


    Glycerol preservation is an effective method for long-term preservation of skin allografts and has a potential use in preserving arterial allografts. We evaluated the effect of glycerol concentration and incubation period on vessel-wall integrity of rat aortic allografts. No significant differences were measured in breaking strength (2.3 +/- 0.3 N) and bursting pressure (223 +/- 32 kPa) between standard glycerolized and control segments (1.7 +/- 0.3 N, 226 +/- 17 kPa). Isometric tension measurements showed complete lack of functional contraction and relaxation capacity in allograft segments prepared according to all preservation protocols. Morphologically, thickness of the vessel-wall media diminished after preservation using low (30/50/75%) or high (70/85/98%) concentrations of glycerol, as compared to control segments (i.e. 81 +/- 2.4 microm, 95 +/- 5.6 microm and 125 +/- 3.5 microm, respectively). Confocal microscopy and Fourier analysis demonstrated that vascular collagen and elastin bundle orientation had remained unaltered. Electron microscopy showed defragmentation of luminal endothelial cells. In conclusion, glycerol preservation of rat aorta resulted in an acellular tissue matrix, which maintained biomechanical integrity and extracellular matrix characteristics. The next step in the investigation will be to test the concept of glycerol preservation of arterial allografts in a vascular transplantation model.

  11. Adefovir nephrotoxicity in a renal allograft recipient

    N George


    Full Text Available Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

  12. Rho kinase inhibitor y-27632 prolongs the life span of adult human keratinocytes, enhances skin equivalent development, and facilitates lentiviral transduction.

    Bogaard, E.H.J. van den; Rodijk-Olthuis, D.; Jansen, P.A.M.; Vlijmen-Willems, I.M.J.J. van; Erp, P.E.J. van; Joosten, I.; Zeeuwen, P.L.J.M.; Schalkwijk, J.


    The use of tissue-engineered human skin equivalents (HSE) for fundamental research and industrial application requires the expansion of keratinocytes from a limited number of skin biopsies donated by adult healthy volunteers or patients. A pharmacological inhibitor of Rho-associated protein kinases,

  13. A new topical panthenol-containing emollient: skin-moisturizing effect following single and prolonged usage in healthy adults, and tolerability in healthy infants.

    Stettler, Hans; Kurka, Peter; Wagner, Christine; Sznurkowska, Katarzyna; Czernicka, Olga; Böhling, Arne; Bielfeldt, Stephan; Wilhelm, Klaus-Peter; Lenz, Holger


    Two studies were conducted with a new topical panthenol-containing emollient (NTP-CE) to investigate the skin-moisturizing effect in healthy adults and tolerability in healthy infants. In Study 1 (N = 44), a single skin application of NTP-CE was performed followed by a 4-week twice-daily application. Skin hydration and stratum corneum (SC) water content change (using Raman spectroscopy) were measured. In the 4-week Study 2 (N = 65, aged 3-25 months), NTP-CE tolerability was assessed using a 5-point scoring system; skin hydration was determined in a subset (N = 21). In Study 1, mean AUC0 - 24 h for skin capacitance change from baseline was 302.03 i.u. with NTP-CE and -15.90 i.u. in control areas (p water content within the upper SC part was reduced (-45.10 vs. -13.39 g/cm(2), p = .013) and the water gradient increased (0.51 vs. 0.11 g/cm(4), p = .036), indicating relocation of water into deeper layers. In Study 2, there was no statistically significant change from baseline in mean cutaneous tolerability scores. At days 7, 14, and 28, skin hydration had increased by 42%, 54%, and 49%, respectively (all p usage is associated with sustained and deep skin moisturization. NTP-CE is well tolerated by healthy infants.

  14. Hypertension in Renal Allograft Recipients

    Waiser Johannes


    Full Text Available Hypertension is a frequent complication after renal transplantation. It contributes to the considerable cardiovascular morbidity and mortality in renal allograft recipients. Additionally, it has a major impact on long-term allograft survival. The pathogenesis of post transplant hypertension is multifactorial. Besides common risk factors, renal allograft recipients accumulate specific risk factors related to the original renal disease, renal transplantation per se and the immunosuppressive regimen. Chronic allograft dysfunction is the main cause of post transplant hypertension. The introduction of calcineurin inhibitors, such as cyclosporine, has increased the prevalence of hypertension. At present, the growing manual of diagnostic and therapeutic tools enables us to adapt better antihypertensive therapy. Tight monitoring, individualization of the immunosuppressive protocol, inclusion of non-pharmacological measures and aggressive antihypertensive treatment should help to minimize the negative implications of post transplant hypertension. Probably, this goal can only be reached by "normalization" of systolic and diastolic blood pressure to below 135/85 mmHg.

  15. Radionuclide diagnosis of allograft rejection

    George, E.A.


    Interaction with one or more anatomical and physiopathological characteristics of the rejecting renal allograft is suggested by those radioagents utilized specifically for the diagnosis of allograft rejection. Rejection, the most common cause of declining allograft function, is frequently mimicked clinically or masked by other immediate or long term post transplant complications. Understanding of the anatomical pathological features and kinetics of rejection and their modification by immunosuppressive maintenance and therapy are important for the proper clinical utilization of these radioagents. Furthermore, in selecting these radionuclides, one has to consider the comparative availability, preparatory and procedural simplicity, acquisition and display techniques and the possibility of timely report. The clinical utilities of radiofibrinogen, /sup 99m/Tc sulfur colloid and /sup 67/Ga in the diagnosis of allograft rejection have been evaluated to a variable extent in the past. The potential usefulness of the recently developed preparations of /sup 111/In labeled autologous leukocytes and platelets are presently under investigation.

  16. Characteristics of changes in the number of yH2AX and Rad51 protein foci in human skin fibroblasts after prolonged exposure to low-dose rate X-ray radiation

    Ozerov I.V.


    Full Text Available Aim: to compare the repair process of DNA double-strand breaks in mammalian cells after acute versus prolonged exposure to X-ray irradiation with different dose rates. Material and methods. Studies were performed on primary human fibroblasts isolated from skin biopsies of healthy volunteers (women, 29 and 30 years. Cells were irradiated using an X-ray machine RUB RUST-M1 (JSC "Ruselectronics", Moscow, Russia at 37°C temperature with a dose rate of 400 mGy/min (200 kV, 2*2.4 mA, a filter of 1.5mm AI or 4 mGy/min (50 kV, 2*0.4 mA, a filter of 1.5 mm AI. Immuno-cytochemical protein staining was utilized for yH2AX and Rad51 foci analysis. Results. Phosphorylated histone H2AX (yH2AX and the key protein of homologous recombination Rad51 foci formation and disappearance kinetics were investigated simultaneously in primary human dermal fibroblasts after acute and prolonged exposure to X-ray radiation at a same dose. It was shown that the relative yield of yH2AX foci per dose reduces with decrease in dose rate, while the relative yield of Rad51 foci conversely increases. Conclusion. Our findings suggest the fundamental differences in the ratio of non-homologous end joining and homologous recombination DNA repair in acute versus prolonged irradiated cells.

  17. Efficacy of prophylactic irradiation in altering renal allograft survival

    Faber, R.; Johnson, H.K.; Braren, H.V.; Richie, R.E.


    Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids.

  18. Systemic vasculitis with prolonged pyrexia, recurrent facial urticaria, skin nodules, pleural effusions and venous thrombosis: an unusual presentation of an uncommon disease

    Dar, Javeed


    Full Text Available Classically presenting with multiple or single peripheral cytopenias of variable severity, the myelodysplastic syndromes may occasionally present with bizarre manifestations that confuse the clinical picture and result in significant delays in making the correct diagnosis. We describe the case of an elderly male patient whose presentation with prolonged unexplained fever coupled with cutaneous, pulmonary and other systemic features of inflammation was finally diagnosed as having a primary myelodysplastic syndrome with associated vasculitis after a delay of 4 years.

  19. Effect of spirulina on the levels of zinc, vitamin E and linoleic acid in the palm skin extracts of people with prolonged exposure to arsenic

    Mir Misbahuddin


    Full Text Available Spirulina, a dietary supplement, improves the symptoms of arsenical palmer keratosis. To understand its mechanism of action, palm skin extracts of moderate palmer arsenical keratosis (n=10, arsenic exposed controls (n=10 and healthy volunteers (n=10 were collected before and after treatment with spirulina powder 10 g/day orally for 12 weeks. The mean (±SD amount of zinc in the palm skin of healthy volunteers was 13.1 ± 5.7 ng/cm2, which was not changed significantly in patients (11.3 ± 5.3 ng/cm2. The amount of vitamin E in healthy volunteers was 6.0 ± 0.3 ng/cm2 which was severely reduced in patients (3.5 ± 0.6 ng/cm2. The amount of linoleic acid was lowered in patient (26.7 ± 17.1 ng/cm2 which was statistically significant in comparison to healthy volunteers (p=0.029. After supplementation of spirulina, zinc level in the palm skin of arsenic exposed controls was increased but it was not statistically significant (p=0.068. The vitamin E and linoleic acid levels were not changed significantly in the skin of palm. In conclusion, arsenical keratosis showed significantly low levels of vitamin E and linoleic acid without any significant change in zinc level. After supplementation of spirulina, low levels of these three compounds were not returned towards the normal levels.

  20. Inhibition of chemokine-glycosaminoglycan interactions in donor tissue reduces mouse allograft vasculopathy and transplant rejection.

    Erbin Dai

    Full Text Available BACKGROUND: Binding of chemokines to glycosaminoglycans (GAGs is classically described as initiating inflammatory cell migration and creating tissue chemokine gradients that direct local leukocyte chemotaxis into damaged or transplanted tissues. While chemokine-receptor binding has been extensively studied during allograft transplantation, effects of glycosaminoglycan (GAG interactions with chemokines on transplant longevity are less well known. Here we examine the impact of interrupting chemokine-GAG interactions and chemokine-receptor interactions, both locally and systemically, on vascular disease in allografts. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of GAG or CC chemokine receptor 2 (CCR2 deficiency were coupled with the infusion of viral chemokine modulating proteins (CMPs in mouse aortic allograft transplants (n = 239 mice. Inflammatory cell invasion and neointimal hyperplasia were significantly reduced in N-deacetylase-N-sulfotransferase-1 (Ndst1(f/fTekCre(+ heparan sulfate (GAG-deficient (Ndst1(-/-, p<0.044 and CCR2-deficient (Ccr2(-/-, p<0.04 donor transplants. Donor tissue GAG or CCR2 deficiency markedly reduced inflammation and vasculopathy, whereas recipient deficiencies did not. Treatment with three CMPs was also investigated; Poxviral M-T1 blocks CC chemokine receptor binding, M-T7 blocks C, CC, and CXC GAG binding, and herpesviral M3 binds receptor and GAG binding for all classes. M-T7 reduced intimal hyperplasia in wild type (WT (Ccr2(+/+, p< or =0.003 and Ccr2(-/-, pallografts, but not in Ndst1(-/- aortic allografts (p = 0.933. M-T1 and M3 inhibited WT (Ccr2(+/+ and Ndst1(+/+, p< or =0.006 allograft vasculopathy, but did not block vasculopathy in Ccr2(-/- (p = 0.61. M-T7 treatment alone, even without immunosuppressive drugs, also significantly prolonged survival of renal allograft transplants (p< or =0.001. CONCLUSIONS/SIGNIFICANCE: Interruption of chemokine-GAG interactions, even in the absence of chemokine

  1. T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model

    Pilat, Nina; Farkas, Andreas M.; Mahr, Benedikt; Schwarz, Christoph; Unger, Lukas; Hock, Karin; Oberhuber, Rupert; Aumayr, Klaus; Wrba, Fritz; Wekerle, Thomas


    Background The mixed chimerism approach induces donor-specific tolerance in both pre-clinical models and clinical pilot trials. However, chronic rejection of heart allografts and acute rejection of skin allografts were observed in some chimeric animals despite persistent hematopoietic chimerism and tolerance toward donor antigens in vitro. We tested whether additional cell therapy with regulatory T cells (Tregs) is able to induce full immunologic tolerance and prevent chronic rejection. Metho...

  2. Emphysema in the renal allograft

    Potter, J.L.; Sullivan, B.M.; Fluornoy, J.G.; Gerza, C.


    Two diabetic patients in whom emphysematous pyelonephritis developed after renal transplantation are described. Clinical recognition of this unusual and serious infection is masked by the effects of immunosuppression. Abdominal radiographic, ultrasound, and computed tomography findings are discussed. The clinical presentation includes urinary tract infection, sepsis, and acute tubular malfunction of the allograft in insulin-dependent diabetics.

  3. Rho Kinase Inhibitor Y-27632 Prolongs the Life Span of Adult Human Keratinocytes, Enhances Skin Equivalent Development, and Facilitates Lentiviral Transduction

    Rodijk-Olthuis, Diana; Jansen, Patrick A.M.; van Vlijmen-Willems, Ivonne M.J.J.; van Erp, Piet E.; Joosten, Irma; Zeeuwen, Patrick L.J.M.


    The use of tissue-engineered human skin equivalents (HSE) for fundamental research and industrial application requires the expansion of keratinocytes from a limited number of skin biopsies donated by adult healthy volunteers or patients. A pharmacological inhibitor of Rho-associated protein kinases, Y-27632, was recently reported to immortalize neonatal human foreskin keratinocytes. Here, we investigated the potential use of Y-27632 to expand human adult keratinocytes and evaluated its effects on HSE development and in vitro gene delivery assays. Y-27632 was found to significantly increase the life span of human adult keratinocytes (up to five to eight passages). The epidermal morphology of HSEs generated from high-passage, Y-27632-treated keratinocytes resembled the native epidermis and was improved by supplementing Y-27632 during the submerged phase of HSE development. In addition, Y-27632-treated keratinocytes responded normally to inflammatory stimuli, and could be used to generate HSEs with a psoriatic phenotype, upon stimulation with relevant cytokines. Furthermore, Y-27632 significantly enhanced both lentiviral transduction efficiency of primary adult keratinocytes and epidermal morphology of HSEs generated thereof. Our study indicates that Y-27632 is a potentially powerful tool that is used for a variety of applications of adult human keratinocytes. PMID:22519508

  4. A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice

    Tripathi, Deepak; Venkatasubramanian, Sambasivan; Cheekatla, Satyanarayana S.; Paidipally, Padmaja; Welch, Elwyn; Tvinnereim, Amy R.; Vankayalapati, Ramakrishna


    Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1+ cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1+ cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1+ cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts. Vaccination of T1D mice with a CpG oligonucleotide TLR9 agonist (ODN 1585) enhances expansion of IL-22-producing CD3-NK1.1+ cells in the liver and prolongs allograft survival. Our study identifies a role for liver NK1.1+ cells, IL-22 and CpG oligonucleotides in the induction of tolerance to islet allografts in the liver parenchyma. PMID:27982034

  5. The Impact of Ventricular Assist Device Prior to Transplantation on Morphological Parameters in Cardiac Allografts

    Wassilew, Katharina


    Due to the shortage of donor organs, mechanical circulatory support systems (MCS) are now widely used as a treatment option to bridge the failing heart to transplantation. There are limited data, suggesting that prolonged use of ventricular assist device (VAD) therapy may result in cardiac...... of the level of macrophages on the degree of IF in right ventricular endomyocardial biopsies (EMBs) of cardiac allografts. Methods: We evaluated all consecutive EMBs of cardiac allografts from 254 patients taken between 01/2011 and 12/2012.With regard to pre-transplant MCS treatment, patients were divided....... The Cochran-Mantel-Haenzsel test was applied to assess significance of the differences in interactions between groups. To evaluate the impact of bridge- to- transplant mechanical circulatory support on development on transplant vasculopathy in cardiac allografts, the intramyocardial terminal arterial network...

  6. Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

    Sun, E.; Gao, Y.; Chen, J.; Roberts, A. I.; Wang, X.; Chen, Z.; Shi, Y.


    Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

  7. Prolonged Negative Pressure Wound Therapy Followed by Split-Thickness Skin Graft Placement for Wide Dehiscence of Clamshell Incision After Bilateral Lung Transplantation: A Case Report.

    Suzuki, H; Watanabe, T; Okazaki, T; Notsuda, H; Niikawa, H; Matsuda, Y; Noda, M; Sakurada, A; Hoshikawa, Y; Aizawa, T; Miura, T; Okada, Y


    Clamshell incision is a standard approach for bilateral lung transplantation, providing a good operative field; however, once wide dehiscence occurs, its management is sometimes difficult because of intense immunosuppression and malnutrition of the recipient. A 22-year-old man with idiopathic pulmonary arterial hypertension underwent cadaveric bilateral lung transplantation through a clamshell incision using standard cardiopulmonary bypass. He developed wound dehiscence on postoperative day (POD) 20 that resulted in exposure of the bilateral fifth ribs and open pneumothorax. Considering the extreme malnutrition and emaciation of the recipient, we avoided initial closure of the dehiscence. After the debridement of necrotic tissue, negative pressure wound therapy was initiated on POD 25 and was continued for approximately 6 months with trafermin spray application. Eventually, the wound, including the fifth ribs, was completely covered with granulation tissue except for the wire tying the sternum. On POD 217, the patient underwent removal of the sternal wire followed by split-thickness skin grafting. His wound was successfully closed and he was discharged without activity limitation on POD 265.

  8. Anterior cruciate ligament reconstruction with allograft tendons.

    Strickland, Sabrina M; MacGillivray, John D; Warren, Russell F


    Allograft tissue allows reconstruction of the ACL without the donor site morbidity that can be caused by autograft harvesting. Patients who must kneel as a part of their occupation or chosen sport are particularly good candidates for allograft reconstruction. Patients over 45 years of age and those requiring revision ACL surgery can also benefit from the use and availability of allograft tendons. In some cases, patients or surgeons may opt for allograft tendons to maximize the result or morbidity ratio. Despite advances in cadaver screening and graft preparation, there remain risks of disease transmission and joint infection after allograft implantation. Detailed explanation and informed consent is vitally important in cases in which allograft tissue is used.


    Cetrulo, Curtis L.; Torabi, Radbeh; Scalea, Joseph R.; Shimizu, Akira; Leto Barone, Angelo A.; Gillon, Brad C.; Tasaki, Masayuki; Leonard, David A.; Cormack, Taylor A.; Villani, Vincenzo; Randolph, Mark A.; Sachs, David H.; Yamada, Kazuhiko


    Background We have previously reported that MGH miniature swine which had accepted class-I mismatched kidneys long-term (LT) following 12 days of high dose Cyclosporine (CyA), uniformly accepted donor-MHC matched kidneys without immunosuppression but rejected donor-MHC matched split-thickness skin grafts (STSG) by day 25, without changes in renal graft function or anti-donor in vitro responses. We have now tested whether this “split tolerance” would also be observed for the primarily-vascularized skin of vascularized composite allografts (VCAs). Methods Group 1 animals (n=3) received donor-MHC matched VCAs transplant (KTx). Group 2 animals (n=3) received a second donor-matched t KTx followed by a donor-matched VCA >200 days after primary KTx. Results Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of 3 recipients of VCAs including epidermis in Group 2 accepted all components of the VCAs (>200 days). The other two recipients lost only the epidermis at day 45 and 85, with survival of the remainder of the VCA long-term. Conclusions All tissues of a VCA are accepted long-term on animals tolerant of class-I mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared to STSG, but not indefinite. Exposure of tolerant animals to second donor-matched kidneys prior to VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney. PMID:24056624

  10. Mucormycosis (zygomycosis) of renal allograft.

    Gupta, Krishan L; Joshi, Kusum; Kohli, Harbir S; Jha, Vivekanand; Sakhuja, Vinay


    Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients.

  11. Leiomyoma in a Renal Allograft

    Yan Jun Li


    Full Text Available Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year.

  12. Comparison of different skin preservation methods with gamma irradiation.

    Guerrero, Linda; Camacho, Bernardo


    Allografts are in constant demand, not only for burn victims, but also for all open wounds as "biological dressings". Tissue quality and security are two of the major concerns of Tissue Banks. There are limited studies published. There has been extensive discussion on the subject of preservation methods for cadaver skin. Most literature available comes from clinical reports. In this research, the authors compared 85% glycerolized non irradiated skin allografts with three glycerolized irradiated skin allografts (using different glycerol concentrations 50%, 70% and 85%). The evaluation of allograft quality was done by measuring physical and biological properties of such prepared human tissue grafts. In the histological structure evaluation changes were minimal and did not alter the skin structure. The clinical function of their behavior as temporal dressings was tested. They proved to have similar capabilities for improving granulating tissue and contributing to wound beds closure (Hickerson et al. (1994) [1]). Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  13. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    Xiaojie Wang


    Full Text Available Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1 or fibroblasts (FB, group 2 under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P<0.001 without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

  14. Hair follicle dermal sheath derived cells improve islet allograft survival without systemic immunosuppression.

    Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L; Shapiro, Jerry; McElwee, Kevin J


    Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

  15. Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

    Sonoda, Kazuhiko (Yamato Seiwa Hospital, Kanagawa (Japan)); Rapaport, F.T.


    With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author).

  16. Demand for human allograft tissue in Canada.

    Lakey, Jonathan R T; Mirbolooki, Mohammadreza; Rogers, Christina; Mohr, Jim


    There is relatively little known about the demand for allograft tissues in Canada. The Canadian Council for Donation and Transplantation (CCDT) is a national advisory body that undertook a comprehensive "market survey" to estimate surgical demand for human allograft tissues in Canada. The report "Demand for Human Allograft Tissue in Canada" reflects survey results sent to 5 prominent User Groups. User Groups were identified as orthopaedic surgeons; neurosurgeons; corneal transplant surgeons; plastic surgeons, specifically those at Canadian Burn Units; and cardiac surgeons (adult and paediatric surgery). The demand for allograft grafts was determined and then extrapolated across the total User Group and then increases in allograft tissue use over the next 1-2 years across User Groups were predicted. The overall response rate for the survey was 21.4%. It varied from a low of 19.6% for the orthopaedic survey to a high of 40.5% for the corneal survey. The estimated current demand for allograft tissue in Canada ranges from a low of 34,442 grafts per year to a high of 62,098 grafts per year. The predicted increase in use of allograft tissue over the next 1-2 year period would suggest that annual demand could rise to somewhere in the range of 42,589-72,210 grafts. The highest rated preferences (98% and 94%) were for accredited and Canadian tissue banks, respectively. This study represents a key step in addressing the paucity of information concerning the demand for allograft tissue in Canada.

  17. Optimization and Implementation of Long Nerve Allografts


    nerve tissue requires a graft to restore continuity and promote nerve regeneration and recovery of function. Presently, there is no acceptable nerve ...for nerve regeneration and meaningful recovering of nerve function that, in several cases was better than autografting. Other decellularized allografts... nerve graft, allograft, nerve regeneration , rehabilitation 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME

  18. Acellular nerve allograft promotes selective regeneration

    Haili Xin; Guanjun Wang; Xinrong He; Jiang Peng; Quanyi Guo; Wenjing Xu


    Acellular nerve allograft preserves the basilar membrane tube and extracellular matrix, which pro-motes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve was utilized to prepare acellular nerve allografts through the use of the chemical extraction method. Subsequently, the allograft was transplanted into a 10-mm sciatic nerve defect in Wistar rats, while autologous nerve grafts from Wistar rats served as controls. Compared with autologous nerve grafts, the acellular nerve allografts induced a greater number of degenerated nerve fibers from sural nerves, as well as a reduced misconnect rate in motor fibers, fewer acetyl-choline esterase-positive sural nerves, and a greater number of carbonic anhydrase-positive senso-ry nerve fibers. Results demonstrated that the acellular nerve allograft exhibited significant neural selective regeneration in the process of bridging nerve defects.

  19. Study of the immunoisolating effects of barium-alginate microencapsulation on rat islets allograft survival

    Mei Zhang; Chao Liu; Cuiping Liu; Youwen Qin; Zhaosun Zhen


    Objective: To evaluate the immunoisolating effects of barium-alginate microencapsulation on islets allograft survival. Methods: The nonmicroencapsulated and microencapsulated islets were transplanted under the kidney capsule or intraperitoneally into Wistar rat with STZ-induced diabetes. The blood glucose and insulin secretion of grafts were observed. Graft function was tested by oral rats was associated with normal glucose and insulin profiles in response to OGTT. Conclusion: Microencapsulation with barium-alginate membrane can prolong islet survival and protect islets against allorejection.

  20. Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection.

    Loupy, A; Toquet, C; Rouvier, P; Beuscart, T; Bories, M C; Varnous, S; Guillemain, R; Pattier, S; Suberbielle, C; Leprince, P; Lefaucheur, C; Jouven, X; Bruneval, P; Duong Van Huyen, J P


    In heart transplantation, there is a lack of robust evidence of the specific causes of late allograft failure. We hypothesized that a substantial fraction of failing heart allografts may be associated with antibody-mediated injury and immune-mediated coronary arteriosclerosis. We included all patients undergoing a retransplantation for late terminal heart allograft failure in three referral centers. We performed an integrative strategy of heart allograft phenotyping by assessing the heart vascular tree including histopathology and immunohistochemistry together with circulating donor-specific antibodies. The main analysis included 40 explanted heart allografts patients and 402 endomyocardial biopsies performed before allograft loss. Overall, antibody-mediated rejection was observed in 19 (47.5%) failing heart allografts including 16 patients (40%) in whom unrecognized previous episodes of subclinical antibody-mediated rejection occurred 4.5 ± 3.5 years before allograft loss. Explanted allografts with evidence of antibody-mediated rejection demonstrated higher endothelitis and microvascular inflammation scores (0.89 ± 0.26 and 2.25 ± 0.28, respectively) compared with explanted allografts without antibody-mediated rejection (0.42 ± 0.11 and 0.36 ± 0.09, p = 0.046 and p < 0.0001, respectively). Antibody-mediated injury was observed in 62.1% of failing allografts with pure coronary arteriosclerosis and mixed (arteriosclerosis and atherosclerosis) pattern, while it was not observed in patients with pure coronary atherosclerosis (p = 0.0076). We demonstrate that antibody-mediated rejection is operating in a substantial fraction of failing heart allografts and is associated with severe coronary arteriosclerosis. Unrecognized subclinical antibody-mediated rejection episodes may be observed years before allograft failure.

  1. Changes in lymphocyte phenotype and increased skin allograft survival after FTY720+FK506 therapy Modificação do fenótipo linfocitário e aumento da sobrevida do enxerto de pele após a terapia com FTY720 + FK506

    Camila T. Lopes


    Full Text Available The development of new drugs to be associated with calcineurin inhibitors and promote additional immunosuppression with fewer side effects is the goal in transplantation. FTY720 is a new synthetic compound which presents immunomodulatory properties which are not fully understood. It has been reported that the main mechanism of action of FTY720 is to reduce the peripheral lymphocyte count by redirecting these cells toward secondary lymphoid organs. Skin allograft transplantation in a fully mismatched strain combination was used to investigate the potential of FTY720 alone or in combination with a calcineurin inhibitor - FK506 - in preventing rejection. The number and phenotype of immune system cells was also evaluated. FTY720 alone or in combination with FK506 provided significant skin allograft survival. FTY720+FK506 therapy was associated with decreases of total lymphocyte numbers in spleen and blood, and increases in apoptosis levels in splenocytes. In FTY720 isolated treatment, a significant decrease in the CD4 expression and significantly lower expressions of MHC II and ICAM-1 molecules were observed in spleen lymphocytes. Despite of allograft survival being the same in both FTY720 and FTY720+FK506 treated groups, the association of drugs was associated with the absence of macroscopic skin necrosis for a longer period than the other treatments (FTY720, FK506 and histology showed less cell infiltration. Our results suggest that a decrease of effector T cells due to elevated levels of apoptosis and impairment in the appearance of antigens were events associated with FTY720+FK506 administration.O objetivo na área dos transplantes é o desenvolvimento de novas drogas que possam ser associadas a inibidores da calcineurina para evitar o processo de rejeição e causar menos efeitos colaterais. FTY720 é um novo composto sintético que apresenta propriedades imunomoduladoras não completamente elucidadas. Foi relatado que o principal mecanismo de

  2. Treatment with alpha-melanocyte stimulating hormone preserves calcium regulatory proteins in rat heart allografts.

    Colombo, Gualtiero; Sordi, Andrea; Lonati, Caterina; Carlin, Andrea; Turcatti, Flavia; Leonardi, Patrizia; Gatti, Stefano; Catania, Anna


    Prevention of graft dysfunction is a major objective in transplantation medicine. Previous research on experimental heart transplantation indicated that treatment with the immunomodulatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) improves histopathology, prolongs allograft survival, and reduces expression of the main tissue injury mediators. Because calcium-handling is critical in heart graft function, we determined the effects of transplantation injury and influences of alpha-MSH treatment on representative calcium regulatory proteins in rat heart allografts. Hearts from Brown Norway rats were transplanted heterotopically into MHC incompatible Lewis rats. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), protein kinase C epsilon (PKC epsilon), sarcoplasmic/endoplasmic reticulum calcium-ATPase 2 (SERCA2a), arrestin-beta1 (Arrb1), cholinergic receptor M2 (Chrm2), and inositol 1,4,5-triphosphate receptor 1 (InsP(3)R1) were examined in: (1) non-transplanted donor hearts; (2) allografts from saline-treated rats; and (3) allografts from rats treated with the synthetic alpha-MSH analog Nle4-DPhe7-alpha-MSH (NDP-alpha-MSH) (100 microg i.p. every 12h). Transplantation injury was associated with severe reduction in calcium regulatory protein transcription and expression level. NDP-alpha-MSH administration partly reversed inhibition of protein transcription and almost completely prevented protein loss. Finally, because certain effects of cyclic 3'-5'-adenosine monophosphate (cAMP) signaling on calcium handling in cardiac myocytes depend on activation of exchange protein directly activated by cAMP 1 (Epac1), we determined Epac1 mRNA and protein expression in heart allografts. Transplantation injury markedly reduced Epac1. NDP-alpha-MSH treatment significantly preserved both Epac1 protein and mRNA in the allografts. Administration of alpha-MSH or related melanocortins could reduce transplantation-induced dysfunction through protection of heart calcium

  3. Comparison between cryopreserved and glycerol-preserved allografts in a partial-thickness porcine wound model.

    Yoon, Cheonjae; Lim, Kihwan; Lee, Sungjun; Choi, Yanghwan; Choi, Youngwhan; Lee, Jungsuk


    Human skin allografts are one of the best temporary biological coverings for severely burned patients. Cryopreserved (CPA) and glycerol-preserved (GPA) allografts are the most widely used types. This study compared the allograft efficiency of both preservation methods under the same conditions. To simulate actual clinical conditions, we used a porcine wound model. In addition, we evaluated the macroscopic and microscopic scoring of graft performance for each method. Porcine cadaver skin 1 mm thick was obtained from one pig. Cryopreserved skin cell viability was 20.8 %, glycerol-preserved skin was 9.08 %, and fresh skin was 58.6 %. We made ten partial-thickness wounds each in two pigs. The take rates on day 2 were 96.23 and 82.65 % in the GPA and CPA group (both n = 9), respectively. After 1 week, the take rates of both groups were nearly equal. The removal rate at week 5 was 98.87 and 94.41 % in the GPA and CPA group, respectively. On microscopic findings at week 2, inflammation was greater in the CPA group. Other findings such as fibroblast hyperplasia and neovascularization were not significantly different between both groups. At week 5, the score of collagen fiber synthesis was 2.67 ± 0.47 and 2.33 ± 0.47 in the GPA and CPA group, respectively. The epidermal-dermal junction was 2.22 ± 0.79 and 2.00 ± 0.47 in the GPA and CPA group, respectively. These findings suggest that wound healing takes longer in the CPA group. The preservation method of allografts is not a absolute factor in the wound healing process in this wound model.

  4. Allograft safety in anterior cruciate ligament reconstruction.

    Cohen, Steven B; Sekiya, Jon K


    Allograft tissue seems to provide an excellent option for reconstruction of the ACL in the primary and revision setting. Although in general the risks of using allograft tissue in ACL reconstruction are low, the consequences of complications associated with disease or infection transmission or of recurrent instability secondary to graft failure are large. Surgeons should provide patients with the information available regarding allograft risks and should have thorough knowledge of the source and preparation of the grafts by their tissue bank before implantation for ACL reconstruction.

  5. Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

    Rotta, Marcello; Patriarca, Francesca; Mattei, Daniele; Allione, Bernardino; Carnevale-Schianca, Fabrizio; Sorasio, Roberto; Rambaldi, Alessandro; Casini, Marco; Parma, Matteo; Bavaro, Pasqua; Onida, Francesco; Busca, Alessandro; Castagna, Luca; Benedetti, Edoardo; Iori, Anna Paola; Giaccone, Luisa; Palumbo, Antonio; Corradini, Paolo; Fanin, Renato; Maloney, David; Storb, Rainer; Baldi, Ileana; Ricardi, Umberto; Boccadoro, Mario


    Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)–based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m2) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)–identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of “new drugs” in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (; NCT-00702247.) PMID:19064724

  6. Hyperlipidemia Promotes Anti-Donor Th17 Responses That Accelerate Allograft Rejection.

    Yuan, J; Bagley, J; Iacomini, J


    Hyperlipidemia occurs in 95% of organ transplant recipients, however its effect on organ allograft rejection has not been investigated. We found that induction of hyperlipidemia in mice caused a significant acceleration of rejection of cardiac allografts. Accelerated rejection was associated with an aggressive T cell infiltrate that mediated significant tissue damage as well as increased serum levels of the proinflammatory cytokines IL-2, IL-6, and IL-17. Hyperlipidemic mice had an increased number of Th17 cells in their periphery and rejecting allografts from hyperlipidemic mice contained significant numbers of IL-17 producing T cells that were not detectable in transplants harvested from controls. Neutralization or genetic ablation of IL-17 prolonged survival of cardiac allografts transplanted into hyperlipidemic recipients, suggesting that IL-17 production promotes accelerated rejection. Analysis of alloreactive T cell frequencies directly ex vivo in naïve mice revealed that the frequency of donor reactive IL-17 producing cells in hyperlipidemic was increased prior to antigen exposure, suggesting that hyperlipidemia was sufficient to alter T cell alloreactivity and promote anti-donor Th17 responses on first exposure to antigen. Together, our data suggest that hyperlipidemia alters rejection by altering the types of T cell subsets that respond to donor antigen by promoting Th17 biased anti-donor reactivity.

  7. Effect of blood transfusions on canine renal allograft survival

    Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.


    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  8. Effect of blood transfusions on canine renal allograft survival

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.


    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  9. Renal allograft rejection: sonography and scintigraphy

    Singh, A.; Cohen, W.N.


    A total of 30 renal allograft patients who had sonographic B scanning and radionuclide studies of the transplant was studied as to whether: (1) the allograft rejection was associated with any consistent and reliable sonographic features and (2) the sonograms complemented the radionuclide studies. Focal areas of decreased parenchymal echogenicity were the most striking and consistent sonographic finding in chymal echogenicity were the most striking and consistens sonographic finding in allograft rejection. This was observed in most of the patients exhibiting moderate or severe rejection, but was frequently absent with mild rejection. Areas of decreased parenchymal echogenicity were not seen during episodes of acute tubular necrosis. Therefore, sonography showing zones of decreased parenchymal echogenicity was complementary to radionuclide studies in the diagnosis of allograft rejection versus acute tubular necrosis. Corticomedullary demarcation was difficult to interpret because of technical variables, and was inconsistently related to rejection in this series.

  10. Computational Biology: Modeling Chronic Renal Allograft Injury.

    Stegall, Mark D; Borrows, Richard


    New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical and experimental data and how we plan to expand this approach to investigate specific mechanisms of chronic renal allograft injury.

  11. A small molecule beta2 integrin agonist improves chronic kidney allograft survival by reducing leukocyte recruitment and accompanying vasculopathy

    Vineet eGupta


    Full Text Available Kidney allograft rejection is associated with infiltration of inflammatory CD11b+ leukocytes. A CD11b agonist leukadherin-1 (LA1 increases leukocyte adhesion, preventing transmigration and tissue recruitment in vivo. Here we test the extent to which LA1 mediated activation of CD11b/CD18 enhances kidney allograft survival in a mouse model of fully MHC-mismatched orthotopic kidney transplantation, where C57BL/6J (H-2b recipients received kidney allografts from Balb/c mice (H-2d. Isograft control recipients received a kidney from a littermate. Control isograft and allograft recipients were treated daily with cyclosporine (CsA for 2 weeks, while the test group received CsA therapy and daily LA1 injections during week 1 and alternate days during weeks 2-8. LA1 treatment reduced interstitial leukocyte infiltration in the allograft, reduced neointimal hyperplasia and glomerular damage, and prolonged graft survival from 48.5% (CsA only to 100% (CsA and LA1 on day 60. Serum creatinine levels showed significantly improved kidney function in LA1 treated mice compared to CsA treated allograft controls (0.52 ± 0.18 mg/dL v/s 0.24 ± 0.07 mg/dL (n=5, respectively. Furthermore, combination therapy reduced macrophage infiltration and increased the frequency of FoxP3+ Tregs in the allograft. These findings indicate a crucial role for CD11b/CD18 in the control of leukocyte migration to the transplanted kidney and identify integrin agonist LA1 as a novel potential therapeutic agent for kidney transplantation.

  12. Critical role for CD8 T cells in allograft acceptance induced by DST and CD40/CD154 costimulatory blockade.

    Gao, Donghong; Lunsford, Keri E; Eiring, Anna M; Bumgardner, Ginny L


    Donor-specific transfusion (DST) and CD40/CD154 costimulation blockade is a powerful immunosuppressive strategy which prolongs survival of many allografts. The efficacy of DST and anti-CD154 mAb for prolongation of hepatocellular allograft survival was only realized in C57BL/6 mice that have both CD4- and CD8-dependent pathways available (median survival time, MST, 82 days). Hepatocyte rejection in CD8 KO mice which is CD4-dependent was not suppressed by DST and anti-CD154 mAb treatment (MST, 7 days); unexpectedly DST abrogated the beneficial effects of anti-CD154 mAb for suppression of hepatocyte rejection (MST, 42 days) and on donor-reactive alloantibody production. Hepatocyte rejection in CD4 KO mice which is CD8-dependent was suppressed by treatment with DST and anti-CD154 mAb therapy (MST, 35 days) but did not differ significantly from immunotherapy with anti-CD154 mAb alone (MST, 32 days). Induction of hepatocellular allograft acceptance by DST and anti-CD154 mAb immunotherapy was dependent on host CD8(+) T cells, as demonstrated by CD8 depletion studies in C57BL/6 mice (MST, 14 days) and CD8 reconstitution of CD8 KO mice (MST, 56 days). These studies demonstrate that both CD4(+) and CD8(+) T-cell subsets contribute to induction of hepatocellular allograft acceptance by this immunotherapeutic strategy.

  13. Evaluation of new antibiotic cocktails against contaminating bacteria found in allograft tissues.

    Serafini, Agnese; Riello, Erika; Trojan, Diletta; Cogliati, Elisa; Palù, Giorgio; Manganelli, Riccardo; Paolin, Adolfo


    Contamination of retrieved tissues is a major problem for allograft safety. Consequently, tissue banks have implemented decontamination protocols to eliminate microorganisms from tissues. Despite the widespread adoption of these protocols, few comprehensive studies validating such methods have been published. In this manuscript we compare the bactericidal activity of different antibiotic cocktails at different temperatures against a panel of bacterial species frequently isolated in allograft tissues collected at the Treviso Tissue Bank Foundation, a reference organization of the Veneto Region in Italy that was instituted to select, recover, process, store and distribute human tissues. We were able to identify at least two different formulations capable of killing most of the bacteria during prolonged incubation at 4 °C.

  14. The Impact of Ventricular Assist Device Prior to Transplantation on Morphological Parameters in Cardiac Allografts

    Wassilew, Katharina


    Due to the shortage of donor organs, mechanical circulatory support systems (MCS) are now widely used as a treatment option to bridge the failing heart to transplantation. There are limited data, suggesting that prolonged use of ventricular assist device (VAD) therapy may result in cardiac...... of the level of macrophages on the degree of IF in right ventricular endomyocardial biopsies (EMBs) of cardiac allografts. Methods: We evaluated all consecutive EMBs of cardiac allografts from 254 patients taken between 01/2011 and 12/2012.With regard to pre-transplant MCS treatment, patients were divided...... into two groups (MCS group n=82 patients, non-MCS group n=138 patients). The MCS patients were subdivided into groups regarding the device used (HeartMate II, HeartWare, Novacor, Incor, Excor). Patients were excluded from the analysis if they had an MCS system that was used in fewer than five of the study...

  15. Zinc finger protein A20 protects rats against chronic liver allograft dysfunction

    Jie Yang; Ming-Qing Xu; Lu-Nan Yan; Xiao-Bo Chen; Jiao Liu


    AIM:To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats.METHODS:Allogeneic liver transplantation from DA rats to Lewis rats was performed.Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day (POD) 5.Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer administered intravenously every 10 d starting from POD 10.The recipient rats were injected with physiological saline,rAdEasy-A20 (1 x 109 pfu/30 g weight) or rAdEasy (1 x 109 pfu/30 g weight) every 10 d through the tail vein for 3 mo starting from POD 10.Liver tissue samples were harvested on POD 30 and POD 60.RESULTS:Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis.A20 overexpression ameliorated the effects on liver function,attenuated liver allograft fibrosis and prolonged the survival of the recipient rats.Treatment with A20 suppressed hepatic protein production of tumor growth factor (TGF)-β1,interleukin1β,caspase-8,CD40,CD40L,intercellular adhesion molecule-1,vascular cell adhesion molecule-1 and E-selectin.A20 treatment suppressed liver cell apoptosis and inhibited nuclear factor-κB activation of Kupffer cells (KCs),liver sinusoidal endothelial cells (LSECs)and hepatic stellate cells (HSCs),and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs.CONCLUSION:A20 might prevent chronic liver allograft dysfunction by re-establishing functional homeostasis of KCs,LSECs and HSCs.

  16. Effect of lymph leakage on renal allograft outcome from living donors

    Abolfazl Bohlouli


    Full Text Available Lymph leakage is a cause of prolonged fluid discharge in renal transplant patients. Lymph leakage during early post-transplantation is responsible for extracting immune substances; therefore, it may play a role in prognosis of the transplanted kidney. In this study, we aimed to investigate the effects of lymph leakage on different factors that play significant roles in renal allograft outcome. During the present case-control study, we evaluated 62 renal allograft recipients in which 31 subjects were complicated with lymph leakage and enrolled as the study group. The other 31 subjects were included in the control group who did not experience any lymph leakage during their post-transplantation period. All kidneys were transplanted from living donors. We investigated and compared the renal allograft rejection rate, hospitalization duration, serum urea, creatinine (Cr and cyclosporine (CsA levels, antithymoglobin (ATG administration and treatment duration between the study and the control groups. There were no significant difference in the urea and Cr levels between the two groups (P >0.05. Early (one week and late (one month serum CsA levels of the study group were significantly higher than in the control group (P = 0.005 and P = 0.006. The number of days in which ATG receivers responded to therapy was significantly lower for the control group (P = 0.008. 21.93% of the study group subjects experienced allograft rejection, while this rejection probability was 28.38% for the control group (P = 0.799. Lymph leakage has no prominent role in renal function, which is estimated by Cr and urea levels in patients′ serum during the days after transplantation. CsA level was higher in patients with lymph leakage, and all cases of allograft rejection were in the subjects with lymph leakage.

  17. Scintigraphy of lower extremity cadaveric bone allografts in osteosarcoma patients.

    Bar-Sever, Z; Connolly, L P; Gebhardt, M C; Treves, S T


    To describe scintigraphic characteristics of bone allografts used in limb salvage reconstruction after resection of lower extremity osteosarcoma. The authors reviewed 85 skeletal scintigrams of 20 pediatric patients followed up for 0.5-5.7 years after resection of lower extremity osteosarcoma and allograft reconstruction. Uptake in the allograft and adjacent host tissues was assessed visually. Lack of tracer uptake in the allografts was seen in 99% of the studies and a faint rim of tracer localization outlining the allograft's periphery was seen in 95% of the studies. Increased uptake was noted at the allograft-host bone junction in 78% of the studies. Uptake was increased in the joint surfaces of native bones articulating with allografts (97% of studies), including the patella (93% of studies) when the knee was involved. These findings were stabilized as time passed. Cadaveric bone allografts have a characteristic scintigraphic appearance in this selected patient group that reflects the physiology of their incorporation process.

  18. Sagging Skin

    ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ...

  19. Genetics and Epigenetics of Chronic Allograft Dysfunction in Kidney Transplants.

    Zununi Vahed, Sepideh; Samadi, Nasser; Mostafidi, Elmira; Ardalan, Mohammad Reza; Omidi, Yadollah


    Chronic allograft dysfunction is the most common cause of allograft lost. Chronic allograft dysfunction happens as a result of complex interactions at the molecular and cellular levels. Genetic and environmental factors both influence the evolution and progression of the chronic allograft dysfunction. Epigenetic modification could be considered as a therapeutically modifiable element to pause the fibrosis process through novel strategies. In this review, the PubMed database was searched for English-language articles on these new areas.

  20. Long-term outcome of free fibula osteocutaneous flap and massive allograft in the reconstruction of long bone defect.

    Halim, Ahmad Sukari; Chai, Siew Cheng; Wan Ismail, Wan Faisham; Wan Azman, Wan Sulaiman; Mat Saad, Arman Zaharil; Wan, Zulmi


    Reconstruction of massive bone defects in bone tumors with allografts has been shown to have significant complications including infection, delayed or nonunion of allograft, and allograft fracture. Resection compounded with soft tissue defects requires skin coverage. A composite osteocutaneous free fibula offers an optimal solution where the allografts can be augmented mechanically and achieve biological incorporation. Following resection, the cutaneous component of the free osteocutaneous fibula flaps covers the massive soft tissue defect. In this retrospective study, the long-term outcome of 12 patients, who underwent single-stage limb reconstruction with massive allograft and free fibula osteocutaneous flaps instead of free fibula osteal flaps only, was evaluated. This study included 12 consecutive patients who had primary bone tumors and had follow-up for a minimum of 24 months. The mean age at the time of surgery was 19.8 years. A total of eight patients had primary malignant bone tumors (five osteosarcomas, two chondrosarcomas and one synovial sarcoma), and four patients had benign bone tumors (two giant-cell tumors, one aneurysmal bone cyst, and one neurofibromatosis). The mean follow-up for the 12 patients was 63 months (range 24-124 months). Out of the 10 patients, nine underwent lower-limb reconstruction and ambulated with partial weight bearing and full weight bearing at an average of 4.2 months and 8.2 months, respectively. In conclusion, augmentation of a massive allograft with free fibula osteocutaneous flap is an excellent alternative for reducing the long-term complication of massive allograft and concurrently addresses the soft tissue coverage.

  1. Immediate retransplantation for pancreas allograft thrombosis.

    Hollinger, E F; Powelson, J A; Mangus, R S; Kazimi, M M; Taber, T E; Goble, M L; Fridell, J A


    Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1-16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin-induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76-1137 days (mean 572 days). One-year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first-time pancreas transplantation.

  2. Radionuclide surveillance of the allografted pancreas

    George, E.A.; Salimi, Z.; Carney, K.; Castaneda, M.; Garvin, P.J.


    To determine the value of scintigraphy to detect posttransplantation complications of the allografted pancreas, we retrospectively reviewed 209 scintigrams obtained with /sup 99m/Tc-sulfur colloid (/sup 99m/Tc-SC) and /sup 99m/Tc-glucoheptonate (/sup 99m/Tc-GH). The scintigraphic studies were performed in 37 recipients of simultaneous renal and pancreatic allografts harvested from the same donor. /sup 99m/Tc-SC was used as an indicator of thrombotic vasculitis; pancreatic perfusion and blood-pool parameters were monitored with /sup 99m/Tc-GH. In 11 of the 37 recipients, scintigraphic abnormalities suggested posttransplantation infarction. Recurrent episodes of acute rejection of the pancreatic allograft, which always coincided with acute rejection of the renal allograft, were monitored in 24 recipients. Rejection-induced ischemic pancreatitis was suggested in 12 of the 24 recipients and persisted in 10 recipients for several weeks after improvement of renal allograft rejection. Pancreatic atrophy was suggested scintigraphically in 16 of the 24 recipients with recurrent episodes of rejection. Spontaneous pancreatic-duct obstruction and obstructive pancreatitis were associated with a scintigraphic pattern similar to that of rejection-induced ischemic pancreatitis. We concluded that the specific radionuclides used in this series are useful for the surveillance and assessment of posttransplantation pancreatic infarction, acute rejection, pancreatitis, and atrophy

  3. Active haemorrhage of a renal allograft detected on portable ultrasound

    Ricketts, James; Pang, Chun Lap; Dissanayake, Prageeth; Hutchinson, Rachel; Gutteridge, Catherine


    Function of a renal allograft relies on the integrity of its vascular anatomy. Renal biochemistry, ultrasound and percutaneous biopsy are used in combination to determine allograft function. Biopsy is not without risk, and in this case study we demonstrate a rare but a potentially life-threatening complication of renal allograft biopsy.

  4. Calprotectin - A novel noninvasive marker for intestinal allograft monitoring

    Sudan, Debra; Vargas, Luciano; Sun, Yimin; Bok, Lisette; Dijkstra, Gerard; Langnas, Alan


    Objective: To identify a noninvasive screening test for intestinal allograft monitoring. Summary Background Data: Intestinal allograft rejection is difficult to distinguish from other causes of diarrhea and can rapidly lead to severe exfoliation or death. Protocol biopsies are standard for allograft

  5. Chronic Kidney Isograft and Allograft Rejection

    严群; 张鹏; 杨传永


    Summary: In this study antigen-independent factor in the pathogenesis of chronic rejection of organ transplants was examined. Kidney isografts and allografts were transplanted orthotopically into bilaterally nephroectomized rat recipients and studied functionally, morphologically and immunohistologically, at serial intervals up to 52 weeks after transplantation. Allograft recipients developed progressive proteinuria after 12 weeks, with gradual renal failure ultimately leading to death. At the same time, morphological changes, including progressive arteriosclerosis and glomerulosclerosis, tubular atrophy and interstitial fibrosis, developed. Immunohistologically, macrophages infiltrated glomeruli during this period and cytokines became unregulated. Our resuits showed that antigen-independent functional and morphological changes occurred in long-term kidney isografts and mimicked those appearing much earlier in allografts that reject chronically.Initial injury and extent of functioning renal mass is suggested to be important factor for such late changes.

  6. Urinary calprotectin and posttransplant renal allograft injury

    Tepel, Martin; Borst, Christoffer; Bistrup, Claus


    OBJECTIVE: Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. METHODS: In a multicenter, prospective-cohort study of 144...... incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. RESULTS: We observed a significant inverse association of urinary calprotectin...... regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. CONCLUSIONS: Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation....

  7. Risk factors of cardiac allograft vasculopathy.

    Szyguła-Jurkiewicz, Bożena; Szczurek, Wioletta; Gąsior, Mariusz; Zembala, Marian


    Despite advances in prevention and treatment of heart transplant rejection, development of cardiac allograft vasculopathy (CAV) remains the leading factor limiting long-term survival of the graft. Cardiac allograft vasculopathy etiopathogenesis is not fully understood, but a significant role is attributed to endothelial cell damage, caused by immunological and non-immunological mechanisms. Immunological factors include the differences between the recipient's and the donor's HLA systems, the presence of alloreactive antibodies and episodes of acute rejection. Among the non-immunological factors the most important are the age of the donor, ischemia-reperfusion injury and cytomegalovirus infection. The classical cardiovascular risk factors (diabetes, hypertension, obesity and hyperlipidemia) are also important. This study presents an up-to-date overview of current knowledge on the vasculopathy etiopathogenesis and the role played by endothelium and inflammatory processes in CAV, and it also investigates the factors which may serve as risk markers of cardiac allograft vasculopathy.

  8. Live Skin Allograft in the Management of Severe Burns

    disease, the eventual rejection by the host and its handling ... Methods. Patients with severe burns of more than 40% surface area admitted at the Nyeri Provincial General Hospital .... of donors and patients it can have a wide acceptance.

  9. [Dopplerometry at prolonged pregnancy].

    Salii-Prenichi, L; Milchev, N; Markova, D; Apiosjan, Zh


    Prolonged pregnancy, associated with low amniotic fluid is a reason for the increase of fetal mortality and morbidity. There is no a define test at prolonged pregnancy which can determine which pregnancy are at a risk for adverse outcome and complications. Dopplerometry as a noninvasive method for examination of blood circulation, and especially a. cerebri media and a. umbilicalis can be used for the prediction of the outcome of prolonged pregnancy.

  10. [Kidney allograft: a target for systemic disease].

    Canaud, Guillaume; Legendre, Christophe


    Recurrence of disease after transplantation is frequent and represents the third cause of allograft loss. Recurrence of lupus nephritis after transplantation is rare. Kidney transplantation in patients with antiphospholipid syndrome or lupus anticoagulant is challenging due to the high risk of immediate post-transplant thrombosis and bleeding risk associated to the subsequent anticoagulation. Moreover, vascular changes associated to the presence of antiphospholipid antibodies negatively impact allograft rate survival. Recurrence of pauci immune glomerulonephritis or Goodpasture syndrome is exceptional. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. Clinical evaluation of an acellular dermal allograft for increasing the zone of attached gingiva.

    Shulman, J


    Grafting with autogenous tissue or freeze-dried skin is the generally accepted method for increasing and/or restoring the width of attached gingiva. This article describes the periodontal use of an acellular dermal allograft previously available for treating burn patients. When used as a gingival graft, this new dermal allograft has major potential advantages over the previously available periodontal graft materials, including improved color and contour match, elimination of multiple surgeries, and unlimited availability. The technique and results of acellular dermal grafting are presented and discussed. The learning objective of this article is to describe the principles and the clinical procedure of this technique. Several cases are used to illustrate this technique.

  12. Renal Allograft in a Professional Boxer

    Einollahi Behzad


    Full Text Available Significant health benefits result from regular physical activity for kidney transplant recipients. Nevertheless, some adverse effects also have been shown to be associated with highly intensive exercises. We report a kidney transplant professional boxer whose kidney allograft has remained in good health, despite his violent sport activities.

  13. Renal Structural Changes after Kidney Allograft Transplantation

    Bakker, R.C.


    In vitro studies done on human proximal tubular epithelial cells showed no direct cytotoxicity of cyclosporine A. The 15-year results of an open randomized trial comparing cyclosporine withdrawal and conversion to azathioprine with continued cyclosporine treatment after kidney allograft transplantat

  14. Ultrastructural basis of acute renal allograft rejection

    V.D. Vuzevski (Vojislav)


    textabstractAn attempt was made: I. to demonstrate the evolution and the time of onset of the ultrastructural morphological changes in the renal parenchyma and blood vessels, as well as the ultrastructural feature of the interstitial cellular infiltration in acute rejection of kidney allografts; 2.

  15. Renal allograft rejection. Unusual scintigraphic findings

    Desai, A.G.; Park, C.H.


    During sequential renal imagining for evaluation of clinically suspected rejection, focal areas of functioning renal tissue were seen in two cases of renal transplant in the midst of severe and irreversible renal allograft rejection. A probable explanation for this histopathologically confirmed and previously unreported finding is discussed.

  16. Donor liver natural killer cells alleviate liver allograft acute rejection in rats

    Jian-Dong Yu; Tian-Zhu Long; Guo-Lin Li; Li-Hong Lv; Hao-Ming Lin; Yong-Heng Huang; Ya-Jin Chen; Yun-Le Wan


    BACKGROUND: Liver enriched natural killer (NK) cells are of high immune activity. However, the function of donor liver NK cells in allogeneic liver transplantation (LTx) remains unclear. METHODS: Ten Gy of whole body gamma-irradiation (WBI) from a 60Co source at 0.6 Gy/min was used for depleting donor-derived leukocytes, and transfusion of purified liver NK cells isolated from the same type rat as donor (donor type liver NK cells, dtlNKs) through portal vein was performed immediately after grafting the irradiated liver. Post-transplant survival observation on recipients and histopathological detection of liver grafts were adoptive to evaluate the biological impact of donor liver NK cells on recipients' survival in rat LTx. RESULTS: Transfusion of dtlNKs did not shorten the survival time among the recipients of spontaneous tolerance model (BN to LEW rat) after rat LTx, but prolonged the liver graft survival among the recipients depleted of donor-derived leukocytes in the acute rejection model (LEW to BN rat). Compared to the recipients in the groups which received the graft depleted of donor-derived leukocytes, better survival and less damage in the allografts were also found among the recipients in the two different strain combinations of liver allograft due to transfusion of dtlNKs. CONCLUSIONS: Donor liver NK cells alone do not exacerbate liver allograft acute rejection. Conversely, they can alleviate it, and improve the recipients' survival.


    肖毅; 朱预; 陈力真; 王树蕙; 何小东


    The activation of T cells to differentiate and to proliferate is an essential step in the immune response to antigen, especially in cell-mediated acute allograft rejection. Besides the interaction of CD3/TCR complex with Ag/MHC complex presented on antigen-presenting cells, a complete T-cell activation and proliferation requires a second costimulatory signal. The interaction of CD28/CTLA-4 and B7 is a major costim-ulatory pathway for T Cell activation. Inhibition of this pathway results in development of antigen-specific unresponsiveness and clonal anergy. In present study, the biologic function of anti-CD28 monoclonsl anti-body and its Fab fragment were investigated in vitro and in viro. The results indicate that mAbCD28 and its Fab fragments could promote the functional recovery of allografts and prolong the graft suvival, but could not reverse the acute rejection or induce transplantation tolerance in the rat PTG allograft model. We also found that peripheral TNF-α level and NK-cell activity were suppressed in the presence of mAbCD28 and its Yab fragments for s relatively long time after PTG transplantation.

  18. Arthroscopic meniscal allograft transplantation without bone plugs.

    Alentorn-Geli, Eduard; Seijas Vázquez, Roberto; García Balletbó, Montserrat; Álvarez Díaz, Pedro; Steinbacher, Gilbert; Cuscó Segarra, Xavier; Rius Vilarrubia, Marta; Cugat Bertomeu, Ramón


    Partial or total meniscectomy are common procedures performed at Orthopedic Surgery departments. Despite providing a great relief of pain, it has been related to early onset knee osteoarthritis. Meniscal allograft transplantation has been proposed as an alternative to meniscectomy. The purposes of this study were to describe an arthroscopic meniscal allograft transplantation without bone plugs technique and to report the preliminary results. All meniscal allograft transplantations performed between 2001 and 2006 were approached for eligibility, and a total of 35 patients (involving 37 menisci) were finally engaged in the study. Patients were excluded if they had ipsilateral knee ligament reconstruction or cartilage repair surgery before meniscal transplantation or other knee surgeries after the meniscal transplantation. Scores on Lysholm, Subjective IKDC Form, and Visual Analogue Scale (VAS) scale for pain were obtained at a mean follow-up of 38.6 months and compared to pre-operative data. Data on chondral lesions were obtained during the arthroscopic procedure and through imaging (radiographs and MRI) studies pre-operatively. Two graft failures out of 59 transplants (3.4%) were found. Daily life accidents were responsible for all graft failures. Significant improvements for Lysholm, Subjective IKDC Form, and VAS for pain scores following the meniscal allograft transplantation were found (P lesion, there was no significant interactions for Lysholm (n.s.), Subjective IKDC Form (n.s.), and VAS for pain scores (n.s.). This study demonstrated that an arthroscopic meniscal allograft transplantation without bone plugs improved knee function and symptoms after a total meniscectomy. Improvements were observed independently of the degree of chondral lesion.

  19. Advances in Skin Regeneration Using Tissue Engineering

    Vig, Komal; Chaudhari, Atul; Tripathi, Shweta; Dixit, Saurabh; Sahu, Rajnish; Pillai, Shreekumar; Dennis, Vida A.; Singh, Shree R.


    Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application. PMID:28387714

  20. Adenoviral-mediated localized CTLA-4Ig gene expression induces long-term allograft pancreas survival and donor-specific immune tolerance in rats


    T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody (CTLA-4Ig), is known to induce to T-cell into "anergy" by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-41g resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ transplantation, we targeted on immunosuppression through a local expression of CTLA-4Ig via adenoviral-mediated gene transfer into pancreatic allografts.

  1. Evaluation of kidney allograft status using novel ultrasonic technologies

    Cheng Yang


    Full Text Available Early diagnosis of kidney allograft injury contributes to proper decisions regarding treatment strategy and promotes the long-term survival of both the recipients and the allografts. Although biopsy remains the gold standard, non-invasive methods of kidney allograft evaluation are required for clinical practice. Recently, novel ultrasonic technologies have been applied in the evaluation and diagnosis of kidney allograft status, including tissue elasticity quantification using acoustic radiation force impulse (ARFI and contrast-enhanced ultrasonography (CEUS. In this review, we discuss current opinions on the application of ARFI and CEUS for evaluating kidney allograft function and their possible influencing factors, advantages and limitations. We also compare these two technologies with other non-invasive diagnostic methods, including nuclear medicine and radiology. While the role of novel non-invasive ultrasonic technologies in the assessment of kidney allografts requires further investigation, the use of such technologies remains highly promising.

  2. Immunosuppression of canine renal allograft recipients by CD4 and CD8 monoclonal antibodies

    Watson, C.J.E.; Davies, H.S.; Rebello, P.R.U.B.; McNair, R.; Rasmussen, A.; Calne, R.Y.; Metcalfe, S.M. (Department of Surgery, University of Cambridge (United Kingdom)); Cobbold, S.P.; Thiru, S.; Waldmann, H. (Department of Pathology, University of Cambridge (United Kingdom))


    A state of tolerance to MHC mismatched allografts can be generated in rodents by treatment with CD4 and CD8 monoclonal antibodies (mAb). In order to transpose this type of therapy to large animals and ultimately to the clinic, a suitable model is required. To this end we have generated a series of mAb to the canine CD4, CD8, and Thy-l antigens and have tested their ability to prevent rejection of renal allografts. Donor-recipient pairs were selected from a colony of mongrel dogs in which untreated rejection of two haplotype-mismatched kidneys occurred by day 7 (defined as a serum creatinine > 300 [mu]mol/l). Therapy with either the CD4 or the CD8 mAb, using no other immunosuppression, did not prolong graft survival. Depletion of T cells by a Thy-l mAb prior to surgery only extended graft survival to day 9. However, treating with combinations of mAb up to day 10 (CD4 plus Thy-l; CD4 plus CD8; or CD4 plus CD8 plus Thy-l) prolonged renal allograft function up to 25 days. Combination of the triple mAb therapy with a sub-therapeutic immunosuppressive drug regimen (cyclosporin A plus azathioprine that alone gave a median survival of 15 days) favored survival to a median of 38 days. This protocol also inhibited the antiglobulin response that had curtailed the effects of mAb treatment, opening the way to more extended, and potentially tolerizing, mAb plus drug regimens. (au) (23 refs.).

  3. [Tubulointerstitial rejection of renal allografts].

    Malušková, Jana; Honsová, Eva


    Tubulo-intersticial rejection represents T-cell mediated rejection of kidney allografts with the morphology of immune-mediated interstitial nephritis. Diagnosis is dependent on the histopathological evaluation of a graft biopsy sample. The key morphological features are interstitial inflammatory infiltrate and damage to tubular epithelial cell which in severe cases can result in the ruptures of the tubular basement membranes. The differential diagnosis of tubulo-interstitial rejection includes acute interstitial nephritis and viral inflammatory kidney diseases, mainly polyomavirus nephropathy.

  4. Urinary calprotectin and posttransplant renal allograft injury.

    Martin Tepel

    Full Text Available OBJECTIVE: Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. METHODS: In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR after 4 weeks, 6 months, and 12 months. RESULTS: We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r =  -0.33; P<0.001. Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m(2 four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66. Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. CONCLUSIONS: Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation.

  5. Late de novo minimal change disease in a renal allograft

    Madhan Krishan


    Full Text Available Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by deterioration of allograft function. Treatment with mycophenolate mofetil was successful in inducing remission and stabilizing allograft function.

  6. Late de novo minimal change disease in a renal allograft.

    Madhan, Krishan K; Temple-Camp, Cynric R E


    Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by deterioration of allograft function. Treatment with mycophenolate mofetil was successful in inducing remission and stabilizing allograft function.

  7. Cytomegalovirus and chronic allograft rejection in liver transplantation

    Liang-Hui Gao; Shu-Sen Zheng


    Cytomegalovirus (CMV) remains one of the most frequent viral infections and the most common cause of death after liver transplantation (LT). Chronic allograft liver rejection remains the major obstacle to long-term allograft survival and CMV infection is one of the suggested risk factors for chronic allograft rejection. The precise relationship between cytomegalovirus and chronic rejection remains uncertain.This review addresses the morbidity of cytomegalovirus infection and the risk factors associated with it, the relationship between cytomegalovirus and chronic allograft liver rejection and the potential mechanisms of it.

  8. Rabbit trochlear model of osteochondral allograft transplantation.

    To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A


    Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft-host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host-graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host-graft bone interface available for analysis.

  9. Extensor mechanism allograft in total knee arthroplasty

    Helito, Camilo Partezani; Gobbi, Riccardo Gomes; Tozi, Mateus Ramos; Félix, Alessandro Monterroso; Angelini, Fábio Janson; Pécora, José Ricardo


    Objective To analyze the experience with allograft transplantation of the extensor mechanism in total knee arthroplasty and compare results with the international experience. Methods We retrospectively evaluated three cases of extensor mechanism allograft after total knee arthroplasty performed in our hospital with the aid of one of the few tissue banks in Brazil and attempt to establish whether our experiences were similar to others reported in the world literature regarding patient indication, techniques, and outcomes. Results Two cases went well with the adopted procedure, and one case showed bad results and progressed to amputation. As shown in the literature, the adequate tension of the graft, appropriate tibial fixation and especially the adequate patient selection are the better predictors of good outcomes. Previous chronic infection can be an unfavorable predictor. Conclusion This surgical procedure has precise indication, albeit uncommon, either because of the rarity of the problem or because of the low availability of allografts, due to the scarcity of tissue banks in Brazil. Level of Evidence IV, Case Series. PMID:24453688

  10. Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction

    Yan Qiang


    Full Text Available Abstract Objective To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Methods Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5 years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0 were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. Results The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. Conclusion There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. Virtual slides The virtual slide(s for this article can be found here: http

  11. Exhaustion from prolonged gambling

    Fatimah Lateef


    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  12. Exhaustion from prolonged gambling

    Fatimah Lateef


    Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities.Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion.Recently, three patients were seen at theDepartment ofEmergencyMedicine, presenting with exhaustion from prolonged involvement in gambling activities.The cases serve to highlight some of the physical consequences of prolonged gambling.

  13. Skin Diseases: Skin Health and Skin Diseases

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

  14. Deciding about treatments that prolong life

    Palliative care - treatments that prolong life; Palliative care - life support; End-of-life-treatments that prolong life; Ventilator - treatments that prolong life; Respirator - treatments that prolong life; ...

  15. Allograft Arthrodesis of the Knee in High-grade Osteosarcoma

    Teng-Le Huang


    Conclusion: Due to the high rate of complications in this study, we conclude that allograft arthrodesis should be left as a salvage or “back-up” reconstructive procedure after resection of osteosarcoma around the knee, unless there are special indications for this procedure. We found allograft fracture to be the most common complication.

  16. Veto cell suppression mechanisms in the prevention of allograft rejection

    Jacobsen, I M; Claesson, Mogens Helweg


    Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy....

  17. Use of local allograft irradiation following renal transplantation

    Halperin, E.C.; Delmonico, F.L.; Nelson, P.W.; Shipley, W.U.; Cosimi, A.B.


    Over a 10 year period, 67 recipients of 71 renal allografts received graft irradiation following the diagnosis of rejection. The majority of kidneys were treated with a total dose of 600 rad, 150 rad per fraction, in 4 daily fractions. Fifty-three kidneys were irradiated following the failure of standard systemic immunosuppression and maximally tolerated antirejection measures to reverse an episode of acute rejection. Twenty-two (42%) of these allografts were noted to have stable (i.e. no deterioration) or improved function 1 month following the treatment with irradiation. Eleven (21%) of these allografts maintained function 1 year following transplantation. Biopsies were obtained of 41 allografts. Of the 24 renal allografts with predominantly cellular rejection, 10 (42%) had the process reversed or stabilized at 1 month following irradiation. Five (21%) of these allografts were functioning at 1 year following irradiation. Rejection was reversed or stabilized in 6 of 17 (35%) allografts at 1 month when the histologic features of renal biopsy suggested predominantly vascular rejection. Local graft irradiation has helped maintain a limited number of allografts in patients whose rejection has failed to respond to systemic immunosuppression. Irradiation may also benefit patients with ongoing rejection in whom further systemic immunosuppression is contra-indicated.

  18. Asymptomatic bacteriuria and urinary tract infections among renal allograft recipients.

    Singh, Ramandeep; Geerlings, Suzanne E; Bemelman, Frederike J


    Bacteriuria is common among renal allograft recipients. It can be categorized into asymptomatic bacteriuria (ASB) and urinary tract infection (UTI). However, in medical literature, the classifications of bacteriuria are often not clear or ASB is also classified as a UTI. This contributes to difficulties in interpretation of the incidence and risk factors of these two entities. In this review, we describe the epidemiology, risk factors, management and the impact on renal allograft function of these two entities separately according to the recent literature. Risk factors for ASB are not completely comparable to the risk factors of UTIs. Persistent ASB has been associated with development of acute rejection and allograft pyelonephritis. The available data suggest that treatment of ASB is not very effective. Prophylaxis with trimethoprim-sulfamethoxazole does not prevent UTIs such as allograft pyelonephritis. Blood stream infections and emphysematous allograft pyelonephritis are associated with renal allograft loss. ASB is the most common manifestation of bacteriuria after renal transplantation. More effective interventions are needed to prevent bacteriuria. Renal allograft recipients with persistent ASB should be closely monitored since they could be at risk for developing not only UTIs, such as allograft pyelonephritis, but also acute rejection.

  19. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.


    Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979


    Guo, Zhimin; Gong, Xingxing; Li, Yanwei; Qiu, Xiaochun; Zhang, Meng; Shangguan, Tiancheng; Ao, Qingfang; Liu, Qiang


    To summarize the effectiveness of anatomical plate combined with cortical bone plate allografts in the treatment of comminuted fractures of the femoral condyles. Between January 2008 and December 2012, 18 patients with comminuted fractures of the femoral condyles were treated, including 13 males and 5 females with an average age of 45 years (range, 23-65 years). Fractures were caused by traffic accident in 11 cases, by falling from height in 4 cases, and by the other in 3 cases. The locations were the left side in 7 cases and the right side in 11 cases. Of 18 fractures, 12 were open fractures and 6 were closed fractures. The mean time from injury to operation was 6 days (range, 4-15 days). The fixation was performed by anatomical plate combined with cortical bone plate allografts, and autograft bone or allogeneic bone grafting were used. Superficial local skin necrosis occurred in 1 case, and was cured after skin graft, and other incisions achieved primary healing. All patients were followed up 12-36 months (mean, 23 months). X-ray films showed that bone union was achieved within 3-12 months (5.6 months on average). No related complication occurred, such as fixation loosening, refracture, infection, or immunological rejection. According to Merchan et al. criteria for knee joint function evaluation, the results were excellent in 7 cases, good in 9 cases, fair in 1 case, and poor in 1 case at last follow-up; the excellent and good rate was 88.9%. Anatomical plate combined with cortical bone plate allograft fixation is a good method to treat comminuted fractures of the femoral condyles. This method can effectively achieve complete cortical bone on the inside of the femur as well as provide rigid fixation.

  1. Incidence, risk factors, and the impact of allograft pyelonephritis on renal allograft function.

    Singh, R; Geerlings, S E; Peters-Sengers, H; Idu, M M; Hodiamont, C J; Ten Berge, I J M; Bemelman, F J


    The impact of allograft pyelonephritis (AGPN) on renal allograft function is controversial. In this study, we evaluated the incidence, risk factors, and the impact of AGPN on renal allograft function. Retrospective cohort study in adult renal allograft recipients with 1-year follow-up after transplantation (Tx). Renal allograft function was evaluated by estimated glomerular filtration rate (eGFR) (by Modification of Diet in Renal Disease formula) and 24-h urine protein excretion. A total of 431 renal allograft recipients were analyzed; 57 (13.2%) developed AGPN within 1 year after Tx. Median time between Tx and AGPN was 50 days. Risk factors for AGPN were the presence of a urological catheter (odds ratio [OR] = 18.93, 95% confidence interval [CI] = 8.00-44.81, P < 0.001) and preceding asymptomatic bacteriuria (ASB) (OR = 2.16, 95% CI = 1.20-3.90, P = 0.009). In 72.7%, the causative microorganism of ASB was identical to that of the succeeding AGPN episode. Multivariable linear regression analysis showed that experiencing AGPN did not decrease the eGFR (P = 0.61) nor did increased proteinuria (P = 0.29) 1 year after Tx. For the eGFR, an interaction was found between AGPN/bacteriuria (BU) and acute rejection (AR): the group experiencing BU preceding AR had significantly (P < 0.001) lower eGFR compared with the group that experienced only AR (21 mL/min/1.73 m(2) vs. 48 mL/min/1.73 m(2) ), as a result of increased prevalence of combined rejections within the BU group. Indwelling urological catheters and preceding ASB are associated with developing AGPN. An incident of AGPN itself does not impair renal allograft function 1 year after Tx. However, a relevant interaction occurs between BU and AR, in which the sequence of occurrence of these 2 events synergistically impairs the eGFR. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Preoperative preparation of high-risk, specifically hyperimmunized canine renal allograft recipients with total-lymphoid irradiation and cyclosporine

    Rapaport, F.T.; Meek, A.G.; Arnold, A.N.; Miura, S.; Hayashi, R.; Strober, S.


    Hyperimmunized subjects are a particularly high-risk and rapidly growing group in the patient population awaiting renal transplantation. In a search for methods designed to ameliorate the prognosis in such cases, dogs of defined DLA genotype were sensitized with DLA incompatible skin allografts and injections of buffy coat. Each recipient was challenged with a renal allograft bearing the same DLA incompatibilities. Five dogs received kidney transplants, without any other treatment, and rejected their transplants at 2.5, 4, 5, 6, and 6.5 days, respectively. Another four dogs were given a 9-11-week course (1760 +/- 35 cGy) of total-lymphoid irradiation (TLI), followed by rabbit antithymocyte globulin (ATG); these animals rejected their renal allografts at 7, 8, 14, and 17 days, respectively. Five other dogs were treated with TLI and received cyclosporine (CsA) and methylprednisolone (MPd) daily until graft rejection. Their renal allografts survived for 7.5, 8.5, 20, 62, and 227 days, respectively. Renal allografts placed in normal recipients under the same conditions of donor-recipient DLA incompatibility had a mean survival time of 12.4 days (range: 10-18 days). At the time of transplantation, the specific anti-DLA antibody titers in the recipients were 81 to 243 in the untreated dogs; 27 to 81 in the TLI-ATG-treated group, and 3 to 243 in the TLI-CsA/MPd-treated group. The titers fell within 24-48 hr after renal transplantation, to 3 to 81 in the untreated sensitized dogs; they were 3 to 9 in the TLI-ATG-treated group, and were 9 to 243 in the TLI-CsA/MPd treated group. The cytotoxic antibody titers reached postoperative peaks of 6500 to 200,000 in the untreated dogs; 729 to 6500 in the TLI-ATG-treated dogs, and 243 to 6500 in the TLI-CsA/MPd-treated recipients.


    Campanacci, D A; Dursky, S; Totti, F; Frenos, F; Scoccianti, G; Beltrami, G; Capanna, R


    Osteoarticular allografts represent a reconstructive option after bone tumor resection around the knee in growing children. The major advantage is the chance to preserve the growth plate of the remaining bone, but the disadvantage is the high failure rate eventually requiring definitive prosthetic replacement at skeletal maturity. We retrospectively reviewed 22 patients who underwent osteoarticular allograft reconstructions of the distal femur (16) or proximal tibia (6). There were 12 females and 10 males with an average age at surgery of 11 years (7-15). The diagnosis was osteosarcoma in 19 cases and Ewing sarcoma in 3. All patients underwent pre- and post-operative chemotherapy. At an average follow-up of 103 months (12-167), 18 patients (82%) were alive and 4 had died (18%). We observed 10 allograft failures requiring prosthetic replacement, 6 in distal femur and 4 in proximal tibia reconstructions. At last follow-up 8 allografts (36%) were still in place. Overall allograft survival was 79.6% at five and 45.8% at ten years. In distal femur, allograft survival was 86.2% at five and 59.1% at ten years. In proximal tibia, allograft survival was 62.5% at 5 years and 31.2% at 67 months. Average limb shortening was 3 cm (0- 5) in 8 patients with the allograft still in situ and 2 cm (0-4) in 10 patients after prosthetic replacement. Average MSTS functional score of the whole series was 25 (83.7%). The MSTS score of patients after revision with prosthetic replacement was 24 (80%) while patients who still had the allograft retained had an average MSTS scores of 26.8 (89.3%). In conclusion, osteoarticular allograft reconstruction of the knee after bone tumor resection in pediatric age can be considered a temporary solution with the aim to limit limb length discrepancy before definitive prosthetic replacement after skeletal maturity.

  4. Chemical sterilization of allograft dermal tissues.

    Phipps, Abigail; Vaynshteyn, Edward; Kowalski, John B; Ngo, Manh-Dan; Merritt, Karen; Osborne, Joel; Chnari, Evangelia


    Common terminal sterilization methods are known to alter the natural structure and properties of soft tissues. One approach to providing safe grafts with preserved biological properties is the combination of a validated chemical sterilization process followed by an aseptic packaging process. This combination of processes is an accepted method for production of sterile healthcare products as described in ANSI/AAMI ST67:2011. This article describes the validation of the peracetic acid and ethanol-based (PAAE) chemical sterilization process for allograft dermal tissues at the Musculoskeletal Transplant Foundation (MTF, Edison, NJ). The sterilization capability of the PAAE solution used during routine production of aseptically processed dermal tissue forms was determined based on requirements of relevant ISO standards, ISO 14161:2009 and ISO 14937:2009. The resistance of spores of Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Pseudomonas aeruginosa, Enterococcus faecium, and Staphylococcus aureus to the chemical sterilization process employed by MTF was determined. Using a worst-case scenario testing strategy, the D value was calculated for the most resistant microorganism, Bacillus. The 12D time parameter determined the minimum time required to achieve a SAL of 10(-6). Microbiological performance qualification demonstrated a complete kill of 10(6) spores at just a quarter of the full cycle time. The validation demonstrated that the PAAE sterilization process is robust, achieves sterilization of allograft dermal tissue to a SAL 10(-6), and that in combination with aseptic processing secures the microbiological safety of allograft dermal tissue while avoiding structural and biochemical tissue damage previously observed with other sterilization methods such as ionizing irradiation.

  5. Modifying cyclosporine associated renal allograft dysfunction

    Mohapatra N


    Full Text Available Transplantation is accepted therapy for chronic kidney disease. However the essential immuno-suppressive agents for graft survival have their own side-effects. Renal biopsy is a reliable tool for diagnosing cyclosporine (CsA nephrotoxicity. To present our observations on CsA toxicity in renal allograft biopsies, we studied prospectively 207 renal allograft biopsies performed for graft dysfunction as per Ahmedabad Tole-rance Induction Protocol (ATIP and compared them to 50 controls from January to October 2007. The ATIP comprised donor specific leucocyte infusions, low dose target specific irradiation; non-myeloablative condi-tioning with Anti-T ± B cell antibodies followed by intraportal administration of cultured donor bone marrow (BM ± adipose tissue derived mesenchymal stem cells. Renal transplantation was performed following nega-tive lymphocytotoxicity cross-matching. The post-transplant immunosuppressive agents included CsA 2.5 ± 0.5 mg/kg BW/day and prednisone 0.2 mg/kg BW/day. The controls were transplanted using standard triple immunosuppressive agents including CsA 5 ± 1 mg/Kg BW/day, prednisone 0.6 mg/kg BW/day, and MMF/ Azathioprine. The Institutional Review Board approved the ATIP. The biopsies were categorized into 2 groups; group A (N=97: performed < 6 months, group B (N= 160, > 6 months posttransplant. Acute CsA toxicity was observed in group A: 2.5% ATIP and 11.1% controls; group B: 16.2% ATIP and 8.8% controls. Chronic CsA toxicity was observed in group B: 10.8 % ATIP and 17.6 % controls. Acute toxicity was more in the ATIP, while chronic toxicity was more in the controls. CsA doses were reduced post-biopsy and resulted in improved graft function evaluated by serum creatinine. We conclude that CsA nephrotoxicity evaluated by allograft biopsy resulted in allograft function recovery by decreasing the cyclosporine dose, and the ATIP decreased the incidence of CsA nephrotoxicity.

  6. Prolonged labour : women's experiences

    Nystedt, Astrid


    Aim: The overall aim of this thesis was to illuminate, describe, and promote understanding of women’s experiences of prolonged labour. The thesis compromises four studies. Methods: Paper I describes a case-referent study that recruited women (n = 255) giving singleton live birth to their first child by spontaneous labour after more than 37 completed weeks’ pregnancy. Participants completed a questionnaire that investigated childbirth experiences, previous family relationships, and childhood e...

  7. ACL reconstruction with BPTB autograft and irradiated fresh frozen allograft

    Kang SUN; Shao-qi TIAN; Ji-hua ZHANG; Chang-suo XIA; Cai-long ZHANG; Teng-bo YU


    Objective: To analyze the clinical outcomes of arthroscopic anterior cruciate ligament (ACL) reconstruction with irradiated bone-patellar tendon-bone (BPTB) allograft compared with non-irradiated allograft and autograft. Methods: All BPTB allografts were obtained from a single tissue bank and the irradiated allografts were sterilized with 2.5 mrad of irradiation prior to distribution. A total of 68 patients undergoing arthroscopic ACL reconstruction were prospectively randomized consecutively into one of the two groups (autograft and irradiated allograft groups). The same surgical technique was used in all operations done by the same senior surgeon. Before surgery and at the average of 31 months of follow-up (ranging from 24 to 47 months), patients were evaluated by the same observer according to objective and subjective clinical evaluations. Results: Of these patients, 65 (autograft 33, irradiated allograft 32) were available for full evaluation. When the irradiated allograft group was compared to the autografi group at the 31-month follow-up by the Lachman test, the anterior drawer test (ADT), the pivot shift test, and KT-2000 arthrometer test, statistically significant differences were found. Most importantly, 87.8% of patients in the autograft group and just only 31.3% in the irradiated allograft group had a side-to-side difference of less than 3 mm according to KT-2000. The failure rate of the ACL reconstruction with irradiated allograft (34.4%) was higher than that with autograft (6.1%). The anterior and rotational stabilities decreased significantly in the irradiated allograft group. According to the overall International Knee Docu-mentation Committee (IKDC), functional and subjective evaluations, and activity level testing, no statistically significant dif-ferences were found between the two groups. Besides, patients in the irradiated allograft group had a shorter operation time and a longer duration of postoperative fever. When the patients had a fever

  8. Detailed examination of HLA antibody development on renal allograft failure and function.

    Zhu, Lan; Lee, Po-Chang; Everly, Matthew J; Terasaki, Paul I


    This is a long-term retrospective case-control study. Serial sera were collected over 17 years (1991-2008) from two groups comprised of 29 patients with allograft failure (250 sera) and 25 controls with functioning grafts (305 sera), each control matched by transplant date to one failure-group patient, and all patients tested with single antigen beads. The median follow-up for failure-group patients was 7.3 +/- 4.7 years and 11.8 +/- 4.4 years for controls. HLA alloantibodies appeared in 28 of the 29 failure-group patients (97%) and in 12 of the 25 controls (48%) (p failure (p = 0.001, p = 0.01). DSA against HLA-DQ antigen was found in 13 of 17 graft-failed patients who had received DQ-incompatible transplants (76%) compared with only one of 11 similarly DQ-mismatched control patients (9%) (p 5000) was higher in graft-failed patients than in graft-functioning patients. The time it took for antibodies to develop also differed between groups. HLA antibodies were formed sooner in the failure group compared with the controls (1.7 versus 3.7 years, P failure group patients developed antibodies within one year while none in the control group did. In conclusion, our study reinforces the observation that circulating de novo HLA alloantibodies predict adverse long-term kidney allograft outcomes. The significant negative impact of all alloantibodies calls for clinicians to monitor patients and implement removal therapy when alloantibody is first detected. This may prove a key step in the ongoing attempt to prevent chronic rejection and prolonging renal allograft survival.

  9. Your Skin

    ... Room? What Happens in the Operating Room? Your Skin KidsHealth > For Kids > Your Skin Print A A ... are really dead skin cells. continue Bye-Bye Skin Cells These old cells are tough and strong, ...

  10. Autograft versus allograft in anterior cruciate ligament reconstruction

    Kan, Shun-Li; Yuan, Zhi-Fang; Ning, Guang-Zhi; Yang, Bo; Li, Hai-Liang; Sun, Jing-Cheng; Feng, Shi-Qing


    Abstract Background: Anterior cruciate ligament (ACL) reconstruction is considered as the standard surgical procedure for the treatment of ACL tear. However, there is a crucial controversy in terms of whether to use autograft or allograft in ACL reconstruction. The purpose of this meta-analysis is to compare autograft with allograft for patients undergoing ACL reconstruction. Methods: PubMed, EMBASE, and the Cochrane Library were searched for randomized controlled trials that compared autograft with allograft in ACL reconstruction up to January 31, 2016. The relative risk or mean difference with 95% confidence interval was calculated using either a fixed- or random-effects model. The risk of bias for individual studies according to the Cochrane Handbook. The trial sequential analysis was used to test the robustness of our findings and get more conservative estimates. Results: Thirteen trials were included, involving 1636 participants. The results of this meta-analysis indicated that autograft brought about lower clinical failure, better overall International Knee Documentation Committee (IKDC) level, better pivot-shift test, better Lachman test, greater Tegner score, and better instrumented laxity test (P allograft. Autograft was not statistically different from allograft in Lysholm score, subjective IKDC score, and Daniel 1-leg hop test (P > 0.05). Subgroup analyses demonstrated that autograft was superior to irradiated allograft for patients undergoing ACL reconstruction in clinical failure, Lysholm score, pivot-shift test, Lachman test, Tegner score, instrumented laxity test, and subjective IKDC score (P allograft. Conclusions: Autograft is superior to irradiated allograft for patients undergoing ACL reconstruction concerning knee function and laxity, but there are no significant differences between autograft and nonirradiated allograft. However, our results should be interpreted with caution, because the blinding methods were not well used. PMID

  11. High-pressure saline washing of allografts reduces bacterial contamination.

    Hirn, M Y; Salmela, P M; Vuento, R E


    60 fresh-frozen bone allografts were contaminated on the operating room floor. No bacterial growth was detected in 5 of them after contamination. The remaining 55 grafts had positive bacterial cultures and were processed with three methods: soaking in saline, soaking in antibiotic solution or washing by high-pressure saline. After high-pressure lavage, the cultures were negative in three fourths of the contaminated allografts. The corresponding figures after soaking grafts in saline and antibiotic solution were one tenth and two tenths, respectively. High-pressure saline cleansing of allografts can be recommended because it improves safety by reducing the superficial bacterial bioburden.

  12. Percutaneous fusion of lumbar facet with bone allograft

    Félix Dolorit Verdecia


    Full Text Available OBJECTIVE: To assess the evolution of the cases treated with percutaneous facet fusion with bone allograft in lumbar facet disease. METHOD: Between 2010 and 2014, 100 patients (59 women and 41 men diagnosed with lumbar facet disease underwent surgery. RESULTS: The lumbar facet fusion with bone allograft shows good clinical results, is performed on an outpatient basis, and presents minimal complications and rapid incorporation of the patient to the activities of daily living. CONCLUSIONS: The lumbar facet fusion with bone allograft appears to be an effective treatment for lumbar facet disease.

  13. Immunological inhibition of transplanted liver allografts by adeno-associated virus vector encoding CTLA4Ig in rats

    Sen Lu; Yue Yu; Yun Gao; Guo-Qiang Li; Xue-Hao Wang


    BACKGROUND: Blockade interaction between CD28 and B7 with CTLA4Ig has been shown to induce experimental transplantation tolerance. In order to prolong the inhibitory effect of CTLA4Ig, a recombinant adeno-associated virus vector pSNAV expressing CTLA4Ig was constructed, and its effects on transplanted liver allografts were investigated. METHODS:The pSNAV-CTLA4Ig construct was infused into partial liver allografts of rats via the portal vein during transplantation. CTLA4Ig expression in the transplanted livers was detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Furthermore, real-time quantita-tive PCR was used to measure the expression of IL-2, IFN-γ, IL-4 and IL-10 in the allografts. RESULTS:The expression of CTLA4Ig in the partial allograft was detected successfully and pSNAV-CTLA4Ig improved the survival rate of rats after liver transplantation. Agarose gel analysis of RT-PCR products indicated the presence of CTLA4Ig in the pSNAV-CTLA4Ig treatment group. Cytokines expressed in allografts on day 7 after orthotopic liver transplantation showed that IL-2, IFN-γ, IL-4 and IL-10 mRNA levels decreased in transplant recipients treated with pSNAV-CTLA4Ig compared with those treated with pSNAV-LacZ (1.62±0.09, 1.52±0.11, 1.50± 0.07 and 1.43±0.07 versus 1.29±0.09, 1.32±0.07, 1.34±0.06 and 1.35±0.04, respectively). CONCLUSIONS:pSNAV-CTLA4Ig effectively expressed CTLA4Ig in liver allografts. CTLA4Ig improved the pathological ifndings after liver transplantation. CTLA4Ig induced immune tolerance of liver transplantation, and the mechanism involved induced alteration of Th1 and Th2 cytokine transcripts. The adeno-associated virus vector encoding CTLA4Ig may be useful in the clinical study of transplantation tolerance.

  14. Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model

    Ma, Ben; Yang, Jing-Yue; Song, Wen-jie; Ding, Rui; Zhang, Zhuo-chao; Ji, Hong-chen; Zhang, Xuan; Wang, Jian-lin; Yang, Xi-sheng; Tao, Kai-shan; Dou, Ke-feng; Li, Xiao


    Allograft tolerance is the ultimate goal in the field of transplantation immunology. Immature dendritic cells (imDCs) play an important role in establishing tolerance but have limitations, including potential for maturation, short lifespan in vivo and short storage times in vitro. However, exosomes (generally 30–100 nm) from imDCs (imDex) retain many source cell properties and may overcome these limitations. In previous reports, imDex prolonged the survival time of heart or intestine allografts. However, tolerance or long-term survival was not achieved unless immune suppressants were used. Regulatory T cells (Tregs) can protect allografts from immune rejection, and our previous study showed that the effects of imDex were significantly associated with Tregs. Therefore, we incorporated Tregs into the treatment protocol to further reduce or avoid suppressant use. We defined the optimal exosome dose as approximately 20 μg (per treatment before, during and after transplantation) in rat liver transplantation and the antigen-specific role of Tregs in protecting liver allografts. In the co-treatment group, recipients achieved long-term survival, and tolerance was induced. Moreover, imDex amplified Tregs, which required recipient DCs and were enhanced by IL-2. Fortunately, the expanded Tregs retained their regulatory ability and donor-specificity. Thus, imDex and donor-specific Tregs can collaboratively induce graft tolerance. PMID:27640806

  15. Cardiac allograft immune activation: current perspectives

    Chang D


    Full Text Available David Chang, Jon Kobashigawa Cedars-Sinai Heart Institute, Los Angeles, CA, USA Abstract: Heart transplant remains the most durable option for end-stage heart disease. Cardiac allograft immune activation and heart transplant rejection remain among the main complications limiting graft and recipient survival. Mediators of the immune system can cause different forms of rejection post-heart transplant. Types of heart transplant rejection include hyperacute rejection, cellular rejection, antibody-mediated rejection, and chronic rejection. In this review, we will summarize the innate and adaptive immune responses which influence the post-heart transplant recipient. Different forms of rejection and their clinical presentation, detection, and immune monitoring will be discussed. Treatment of heart transplant rejection will be examined. We will discuss potential treatment strategies for preventing rejection post-transplant in immunologically high-risk patients with antibody sensitization. Keywords: heart transplant, innate immunity, adaptive immunity, rejection, immunosuppression

  16. Multifocal bacterial osteomyelitis in a renal allograft recipient following urosepsis.

    Valson, A T; David, V G; Balaji, V; John, G T


    Non-tubercular bacterial osteomyelitis is a rare infection. We report on a renal allograft recipient with osteomyelitis complicating urosepsis, manifesting as a multifocal infection poorly responsive to appropriate antibiotics and surgical intervention and culminating in graft loss.

  17. Renalase Gene Polymorphism in Patients After Renal Allograft Transplantation

    Andrzej Pawlik


    Full Text Available Background/Aims: Renalase is a recently discovered protein, which is likely involved in regulation of blood pressure in humans and animals. Previous studies suggest that renalase reflects kidney functioning. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp has been described. In this study we examined the association between (Glu37Asp polymorphism (rs2296545 in renalase gene and kidney allograft function. Methods: The study enrolled 270 Caucasian kidney allograft recipients. SNP within the renalase was genotyped using TaqMan genotyping assays. Results: There were no statistically significant associations between renalase gene rs2296545 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction as well as creatinine serum concentrations and blood pressure values after transplantation. Conclusions: The results of this study suggest, that renalase gene rs2296545 polymorphism is not important factor determining renal allograft function.

  18. Bipolar fresh osteochondral allograft of the ankle.

    Giannini, Sandro; Buda, Roberto; Grigolo, Brunella; Bevoni, Roberto; Di Caprio, Francesco; Ruffilli, Alberto; Cavallo, Marco; Desando, Giovanna; Vannini, Francesca


    Severe post-traumatic ankle arthritis poses a reconstructive challenge in the young and active patient. Bipolar fresh osteochondral allograft (BFOA) may represent an intriguing alternative to arthrodesis and prosthetic replacement. The aim of this study was to describe a lateral trans-malleolar technique for BFOA, and to evaluate the results in a case series. From 2004 to 2006, 32 patients, mean age of 36.8 +/- 8.4 years, affected by ankle arthritis underwent BFOA with a mean followup of 31.2 months. The graft was prepared by specifically designed jigs, including the talus and the tibia with the medial malleolus. The host surfaces were prepared by the same jigs through a lateral approach. The graft was placed and fixed with twist-off screws. Patients were evaluated clinically and radiographically at 2, 4, and 6 month after operation, and at a minimum 24 months followup. A biopsy of the grafted areas was obtained from 7 patients at 1-year followup for histological and immunohistochemical examination. Preoperative AOFAS score was 33.1 +/- 10.9 and postoperatively 69.5 +/- 19.4 (p < 0.0005). Six failures occurred. Cartilage harvests showed hyaline-like histology with a normal collagen component but low proteoglycan presence and a disorganized structure. Samples were positive for MMP-1, MMP-13 and Capsase-3. The use of BFOA represents an intriguing alternative to arthrodesis or arthroplasty. We believe precise allograft sizing, stable fitting and fixation and delayed weightbearing were key factors for a successful outcome. Further research regarding the immunological behavior of transplanted cartilage is needed.

  19. The Spectrum of Renal Allograft Failure

    Chand, Sourabh; Atkinson, David; Collins, Clare; Briggs, David; Ball, Simon; Sharif, Adnan; Skordilis, Kassiani; Vydianath, Bindu; Neil, Desley; Borrows, Richard


    Background Causes of “true” late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. Methods We evaluated all unselected graft failures from 2008–2014 (n = 171; 0–36 years post-transplantation) by contemporary classification of indication biopsies “proximate” to failure, DSA assessment, clinical and biochemical data. Results The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and ‘interstitial fibrosis with tubular atrophy’ without rejection, infection or recurrent disease (“IFTA”). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). Conclusion This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and

  20. Moderate superficial hypothermia prolongs bleeding time in humans.

    Romlin, B; Petruson, K; Nilsson, K


    In vitro and in vivo studies have shown that mild systemic hypothermia influences platelet adhesion and aggregation and coagulation reactions. We wanted to test the hypothesis that mild local hypothermia in healthy volunteers with preserved core temperature increased bleeding time. A secondary aim was to evaluate if local cooling influenced whole blood coagulation measured by thrombelastograph (TEG) in the same setting. Bleeding time was measured at the left volar forearm at a baseline skin temperature of 32 degrees C and after cooling to 30 degrees C and 28 degrees C in a water bath. Skin temperature was continuously measured by contact thermistors. Measurements of coagulation by TEG were performed at baseline skin temperature before cooling and after cooling to 28 degrees C skin temperature. Tympanic membrane temperature was continuously measured. Compared with baseline, bleeding time was significantly prolonged at 30 degrees C skin temperature and further prolonged at 28 degrees C skin temperature. No significant differences were measured in any of the TEG parameters. During the procedure, tympanic membrane temperature did not change. Lowering the skin temperature from 32 degrees C to 30 degrees C and 28 degrees C with a preserved core temperature more than doubled the bleeding time. Whole blood coagulation measured by TEG was not influenced by the local cooling. In addition to core temperature, local temperature may offer information in understanding the surgical site of bleeding.

  1. Late de novo minimal change disease in a renal allograft

    Madhan Krishan; Temple-Camp Cynric


    Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by...

  2. Cortical and medullary vascularity in renal allograft biopsies


    Aim: To evaluate the relation between cortical and medullary peritubular capillaries (PTCs) and scarring. There are presently no studies about medullary PTCs in renal allograft biopsies. Materials and methods: Nonprotocol allograft biopsies were evaluated and 41 with adequate medullary and cortical tissues were selected. Vascular structures were counted separately at the medulla and cortex on anti-CD34 stained sections. Other histopathological and clinical findings were retrieved from the p...


    L. V. Shkalova


    Full Text Available We performed histological examination of 80 liver allograft biopsies, the diagnosis of acute rejection was proved in 34 cases. Histological changes in liver biopsies in different grades of acute rejection were estimated according to Banff classification 1995, 1997 and were compared with current literature data. The article deals with the question of morphological value of grading acute rejection on early and late, also we analyze changes in treat- ment tactics after morphological verification of liver allograft acute rejection. 

  4. De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

    Kanodia K


    Full Text Available Collapsing glomerulopathy (CG, characterized histologically by segmental/global glomerular capillary collapse, podocyte hypertrophy and hypercellularity and tubulo-interstitial injury; is characterized clinically by massive proteinuria and rapid progressive renal failure. CG is known to recur in renal allograft and rarely de novo. We report de novo CG 3 years post-transplant in a patient who received renal allograft from haplo-identical type donor.

  5. Proximal femur reconstruction by an allograft prosthesis composite.

    Donati, Davide; Giacomini, Stefano; Gozzi, Enrico; Mercuri, Mario


    Twenty-seven patients who had resection of the proximal femur for bone tumors and reconstruction with an allograft prosthesis composite are reported. In most of the patients, the prosthesis was a long-stem revision type, cemented in the allograft and uncemented in the femoral shaft. The abductor muscles and iliopsoas were sutured to the corresponding tendons on the allograft. Implant-related complications and functional results were evaluated and are reported. Twenty-two patients achieved a minimum followup of 36 months (range, 36-126 months; average, 58 months). The implant was removed in two patients (one for infection, one for intraoperative fracture of the allograft). One patient experienced nonunion, whereas in the remaining 24 patients, the allograft eventually united to the host bone. A frequent late complication (17 patients) was fracture of the greater trochanter of the allograft. In the whole series, only four new operations were done for implant-related complications. In 22 patients who could be evaluated, the functional evaluation according to the Musculoskeletal Tumor Society System was excellent in 16 (73%) patients, good in four (18%), and fair in two (9%). These results compare favorably with those of megaprostheses for tumor resection of the proximal femur, where a Trendelenburg gait almost always is present.

  6. Ex Situ Perfusion of Human Limb Allografts for 24 Hours.

    Werner, Nicole L; Alghanem, Fares; Rakestraw, Stephanie L; Sarver, Dylan C; Nicely, Bruce; Pietroski, Richard E; Lange, Paul; Rudich, Steven M; Mendias, Christopher L; Rojas-Pena, Alvaro; Magee, John C; Bartlett, Robert H; Ozer, Kagan


    Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL. Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury. Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.

  7. Clinical and functional outcomes of tibial intercalary allograft reconstructions

    Lucas López Millán


    Full Text Available Background The purpose of this study was to evaluate the survival, the complications and the functional outcome of intercalary tibial allografts reconstructions following tumor resections. Methods Intercalary tibia segmental allografts were implanted in 26 consecutive patients after segmental resections. Average follow-up was 6 years. Allograft survival was determined with the Kaplan-Meier method. Function was evaluated with the Musculoskeletal Tumor Society scoring system (MSTS. Results The rate of survival was 84% (CI 95%: 90%- 70% at 5 years and 79% at 10 years (CI 95%: 95%-63%. Allografts were removed in 5 patients (3 due to infections and 2 due to local recurrences. Two patients showed diaphyseal nonunion and 3 had an incomplete fracture, but it was not necessary to remove the allografts. Average MSTS functional score was 29 points (range 27 to 30. Conclusions Despite the incidence of complications, this analysis showed an acceptable survival with excellent functional scores. The use of intercalary allograft clearly has a place in the reconstruction of a segmental defect created by the resection of a tumor in the diaphyseal and/or metaphyseal portion of the tibia.

  8. Primary integumentary allograft reactivity in the American cockroach, Periplaneta americana.

    George, J F; Howcroft, T K; Karp, R D


    Previous reports have failed to demonstrate integumentary allograft rejection in insects. We realized however, that these studies may not have fully appreciated the structure of the insect exoskeleton. Since the subcuticlar epidermal layer constitutes the only living tissue associated with insect integument, its destruction would indicate that the animal recognized and responded to the foreign tissue. Thus, we investigated allograft reactivity in the American cockroach, Periplaneta americana, by observing the fate of the epidermal portion of the integument. Each animal in a pair received a 3 X 4-mm integumentary allograft from its partner, as well as a 3 X 4-mm control autograft. The transplants were then examined histologically for signs of epidermal destruction at 0, 1, 3, 5, 7, and 10-70 days (in 10-day increments) posttransplantation. The results indicated that significant rejection of the allografts began by day 3, with peak reactivity occurring by day 7 when 92% of the grafts were scored as rejected. At later periods (greater than 20 days), the graft sites showed signs of repopulation by host epidermal cells. The allograft reaction was found to lag behind the xenograft reaction, which showed peak activity after only 1 day posttransplantation. Even so, allograft rejection in this insect occurred quite rapidly (as compared with some other invertebrates), and would appear to be due to a cytotoxic reaction against the epidermal layer.

  9. Splenectomy increases the survival time of heart allograft via developing immune tolerance.

    Zhu, Jinguo; Chen, Shuzhen; Wang, Jinju; Zhang, Cheng; Zhang, Wei; Liu, Peng; Ma, Ruilian; Chen, Yanfang; Yao, Zhen


    The spleen is an active lymphoid organ. The effect of splenectomy on the immune response remains unclear. This study investigated whether splenectomy can induce immune tolerance and has a beneficial role in cardiac allograft. Wistar rats were used for heart donors. The Sprague-Dawley (SD) rats designated as the recipients of heart transplantation (HT) were randomly assigned into four groups: sham, splenectomy, HT, splenectomy + HT. The survival of transplanted hearts was assessed by daily checking of abdominal palpation. At various time points after transplantation, the transplanted hearts were collected and histologically examined; the level of CD4+CD25+ T regulatory lymphocytes (Tregs) and rate of lymphocyte apoptosis (annexin-v+ PI+ cells) in the blood were analyzed by using flow cytometric method. 1) Splenectomy significantly prolonged the mean survival time of heart allografts (7 ± 1.1 days and 27 ± 1.5 days for HT and splenectomy + HT, respectively; n = 12-14/group, HT vs. splenectomy + HT, p Tregs in the blood of splenectomized rats was significantly increased within 7 days (2.4 ± 0.5%, 4.9 ± 1.3% and 5.3 ± 1.0% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p increased the rate of lymphocyte apoptosis (day 7: 0.3 ± 0.05%, 3.9 ± 0.9% and 4.1 ± 0.9% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p Tregs in the blood. Splenectomy inhibits the development of pathology and prolongs the survival time of cardiac allograft. The responsible mechanism is associated with induction of immune tolerance via elevating CD4+CD25+ Tregs and increasing lymphocyte apoptosis.

  10. Anti-rejection effect of ethanol extract of Poria cocos wolf in rats after cardiac allograft implantation

    张国伟; 刘宏宇; 夏求明; 李君权; 吕航; 张庆华; 姚志发


    Background A living fetus within the maternal uterus provides an example of allogene tolerance in mammals. Poria cocos Wolf is the main component of many Chinese medicinal combination drugs that have therapeutic effects on recurrent spontaneous abortion and that can maintain pregnancy until delivery. It was hypothesized that this herbal medicine can also prolong allograft survival after organ transplantation. Here, in an in vivo study, we report the anti-rejection effect of the ethanol extract of Poria cocos Wolf (EEPCW) in rats after cardiac allograft implantation. Methods Ten normal rats were healthy controls. Eighty rats receiving homologous heart transplants were divided into 4 groups of 20 rats each based on type of treatment: olive oil 8 ml*kg-1*d-1, EEPCW 25 mg*kg-1*d-1, EEPCW 50 mg*kg-1*d-1 or cyclosporin A 5mg*kg-1*d-1. Allograft survival was observed in 10 rats from each group. On the seventh day post transplantation, pathological lesions and percentages of CD3+, CD4+, and CD8+ lymphocytes and the CD4+/CD8+ ratio in peripheral blood were assessed in another 10 rats from each group and in 10 normal rats. Results The survival time of donor hearts in the two EEPCW groups was significantly prolonged, to (15.9±2.4) days and (30.0±0.0) days, respectively, compared with (6.7±0.8) days in the control group. Pathological lesions in the two EEPCW groups were also less severe, and the percentages of CD3+, CD4+, and CD8+ lymphocytes and CD4+/CD8+ ratio were significantly lower in the EEPCW groups.Conclusions Acute rejection of heart transplants and cellular immune reaction can be effectively suppressed using the EEPCW. Taking advantage of novel immunosuppressants derived from Chinese medicinal herbs used to treat abnormal pregnancy provides a hopeful road for future research and treatment in organ transplantation.

  11. Statins induce immunosuppressive effect on heterotopic limb allografts in rat through inhibiting T cell activation and proliferation.

    Nie, Chunlei; Yang, Daping; Liu, Guofeng; Dong, Deli; Ma, Zhiqiang; Fu, Hailiang; Zhao, Zhengyu; Sun, Zhiyong


    Long-term use of immunosuppressive agents could bring many side effects. Recently, 3-Hydroxy-3-methyl-gutaryl coenzyme A reductase inhibitors (statins) have been reported to be immunomodulatory besides lowering serum cholesterol level. The aim of this study was to investigate the effects of statins on composite tissue allografts and T lymphocyte in vivo and in vitro. Rats were divided into 5 groups: syngeneic transplantation group (Lewis-Lewis); allogeneic control group (Brown Norway-Lewis, no treatment); low-dose statins group (15 mg /kg); high-dose statins group (30 mg /kg) and cyclosporin A group. In vivo, treatment of statins significantly prolonged allografts survival as compared to control group. Histological findings further supported these clinical results and demonstrated less extent of rejection. Immunohistochemical analysis showed that there was a remarkably reduced T cells infiltration in statins groups. Moreover, the serum levels of IL-2 and IFN-gamma were decreased after statins therapy, while these in control group increased significantly. Meanwhile, transcriptional activities of IL-2 and IFN-gamma were also dramatically down-regulated after statins treatment. In vitro, mixed lymphocyte reaction assay was performed and the results revealed lymphocyte proliferation was inhibited by statins in a dose-dependent manner. Furthermore, administration of statins exhibited inhibitory effects on CD3/CD28 mediated T cell activation and proliferation. Besides, the results demonstrated that statins significantly down-regulated mRNA expression and suppress cytokine production of IL-2 and IFN-gamma in vitro. In conclusion, our data demonstrated that application of statins could induce immunosuppressive effect and prolong allografts survival through inhibiting activation and proliferation of T cell and reducing production of IL-2 and IFN-gamma.

  12. Skin Biopsy

    ... I Help Someone Who's Being Bullied? Volunteering Skin Biopsy KidsHealth > For Teens > Skin Biopsy Print A A ... español Biopsia de piel What Is a Skin Biopsy and Who Would Need One? In a biopsy, ...

  13. Skin Conditions

    Your skin is your body's largest organ. It covers and protects your body. Your skin Holds body fluids in, preventing dehydration Keeps harmful ... it Anything that irritates, clogs, or inflames your skin can cause symptoms such as redness, swelling, burning, ...

  14. Quadriceps tendon allografts as an alternative to Achilles tendon allografts: a biomechanical comparison.

    Mabe, Isaac; Hunter, Shawn


    Quadriceps tendon with a patellar bone block may be a viable alternative to Achilles tendon for anterior cruciate ligament reconstruction (ACL-R) if it is, at a minimum, a biomechanically equivalent graft. The objective of this study was to directly compare the biomechanical properties of quadriceps tendon and Achilles tendon allografts. Quadriceps and Achilles tendon pairs from nine research-consented donors were tested. All specimens were processed to reduce bioburden and terminally sterilized by gamma irradiation. Specimens were subjected to a three phase uniaxial tension test performed in a custom environmental chamber to maintain the specimens at a physiologic temperature (37 ± 2 °C) and misted with a 0.9 % NaCl solution. There were no statistical differences in seven of eight structural and mechanical between the two tendon types. Quadriceps tendons exhibited a significantly higher displacement at maximum load and significantly lower stiffness than Achilles tendons. The results of this study indicated a biomechanical equivalence of aseptically processed, terminally sterilized quadriceps tendon grafts with bone block to Achilles tendon grafts with bone block. The significantly higher displacement at maximum load, and lower stiffness observed for quadriceps tendons may be related to the failure mode. Achilles tendons had a higher bone avulsion rate than quadriceps tendons (86 % compared to 12 %, respectively). This was likely due to observed differences in bone block density between the two tendon types. This research supports the use of quadriceps tendon allografts in lieu of Achilles tendon allografts for ACL-R.

  15. Kidney allograft offers: Predictors of turndown and the impact of late organ acceptance on allograft survival.

    Cohen, J B; Shults, J; Goldberg, D S; Abt, P L; Sawinski, D L; Reese, P P


    There is growing interest in understanding patterns of organ acceptance and reducing discard. Little is known about how donor factors, timing of procurement, and geographic location affect organ offer decisions. We performed a retrospective cohort study of 47 563 deceased donor kidney match-runs from 2007 to 2013. Several characteristics unrelated to allograft quality were independently associated with later acceptance in the match-run: Public Health Service increased-risk donor status (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 2.29-2.69), holiday or weekend procurement (aOR 1.11, 95% CI 1.07-1.16), shorter donor stature (aOR 1.53 for 180 cm, 95% CI 1.28-1.94), and procurement in an area with higher intensity of market competition (aOR 1.71, 95% CI 1.62-1.78) and with the longest waiting times (aOR 1.41, 95% CI 1.34-1.49). Later acceptance in the match-run was associated with delayed graft function but not all-cause allograft failure (adjusted hazard ratio 1.01, 95% CI 0.96-1.07). Study limitations include a lack of match-run data for discarded organs and the possibility of sequence inaccuracies for some nonlocal matches. Interventions are needed to reduce turndowns of viable organs, especially when decisions are driven by infectious risk, weekend or holiday procurement, geography, or other donor characteristics unrelated to allograft quality. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Skin abscess

    Abscess - skin; Cutaneous abscess; Subcutaneous abscess; MRSA - abscess; Staph infection - abscess ... Skin abscesses are common and affect people of all ages. They occur when an infection causes pus ...

  17. Uncemented allograft-prosthetic composite reconstruction of the proximal femur

    Li Min


    Full Text Available Background: Allograft-prosthetic composite can be divided into three groups names cemented, uncemented, and partially cemented. Previous studies have mainly reported outcomes in cemented and partially cemented allograft-prosthetic composites, but have rarely focused on the uncemented allograft-prosthetic composites. The objectives of our study were to describe a surgical technique for using proximal femoral uncemented allograft-prosthetic composite and to present the radiographic and clinical results. Materials and Methods: Twelve patients who underwent uncemented allograft-prosthetic composite reconstruction of the proximal femur after bone tumor resection were retrospectively evaluated at an average followup of 24.0 months. Clinical records and radiographs were evaluated. Results: In our series, union occurred in all the patients (100%; range 5-9 months. Until the most recent followup, there were no cases with infection, nonunion of the greater trochanter, junctional bone resorption, dislocation, allergic reaction, wear of acetabulum socket, recurrence, and metastasis. But there were three periprosthetic fractures which were fixed using cerclage wire during surgery. Five cases had bone resorption in and around the greater trochanter. The average Musculoskeletal Tumor Society (MSTS score and Harris hip score (HHS were 26.2 points (range 24-29 points and 80.6 points (range 66.2-92.7 points, respectively. Conclusions: These results showed that uncemented allograft-prosthetic composite could promote bone union through compression at the host-allograft junction and is a good choice for proximal femoral resection. Although this technology has its own merits, long term outcomes are yet not validated.

  18. Development of a Fresh Osteochondral Allograft Program Outside North America.

    Tírico, Luís Eduardo Passarelli; Demange, Marco Kawamura; Santos, Luiz Augusto Ubirajara; de Rezende, Márcia Uchoa; Helito, Camilo Partezani; Gobbi, Riccardo Gomes; Pécora, José Ricardo; Croci, Alberto Tesconi; Bugbee, William Dick


    To standardize and to develop a fresh osteochondral allograft protocol of procurement, processing and surgical utilization in Brazil. This study describes the steps recommended to make fresh osteochondral allografts a viable treatment option in a country without previous fresh allograft availability. The process involves regulatory process modification, developing and establishing procurement, and processing and surgical protocols. Legislation: Fresh osteochondral allografts were not feasible in Brazil until 2009 because the law prohibited preservation of fresh grafts at tissue banks. We approved an amendment that made it legal to preserve fresh grafts for 30 days from 2°C to 6°C in tissue banks. Procurement: We changed the protocol of procurement to decrease tissue contamination. All tissues were procured in an operating room. Processing: Processing of the grafts took place within 12 hours of tissue recovery. A serum-free culture media with antibiotics was developed to store the grafts. Surgeries: We have performed 8 fresh osteochondral allografts on 8 knees obtaining grafts from 5 donors. Mean preoperative International Knee Documentation Committee (IKDC) score was 31.99 ± 13.4, improving to 81.26 ± 14.7 at an average of 24 months' follow-up. Preoperative Knee Injury and Oseoarthritis Outcome Score (KOOS) score was 46.8 ± 20.9 and rose to 85.24 ± 13.9 after 24 months. Mean preoperative Merle D'Aubigne-Postel score was 8.75 ± 2.25 rising to 16.1 ± 2.59 at 24 months' follow-up. To our knowledge, this is the first report of fresh osteochondral allograft transplantation in South America. We believe that this experience may be of value for physicians in countries that are trying to establish an osteochondral allograft transplant program.

  19. The amelioration of composite tissue allograft rejection by TIM-3-modified dendritic cell: Regulation of the balance of regulatory and effector T cells.

    Wang, Yaojun; Zheng, Zhao; Zhu, Xiongxiang; Han, Juntao; Dong, Maolong; Tao, Ke; Wang, Hongtao; Wang, Yunchuan; Hu, Dahai


    T cell-dependent immune responses play a central role in allograft rejection. Exploring ways to disarm alloreactive T cells represents a potential strategy to promote long-term allograft acceptance and survival. T cell Ig domain and mucin domain 3 (TIM-3) has previously been demonstrated as a central regulator of T helper 1 (Th1) responses and immune tolerance. Hence, TIM-3 may be an important molecule for decreasing immunological rejection during composite tissue allotransplantation (CTA). In this study, BALB/c and C57BL/6 mice were chosen as the experimental animals. The effects of TIM-3 on allograft rejection were explored using TIM-3-modified mature dendritic cells (TIM-3 mDCs). A laser speckle blood flow (LSBF) imager was used to evaluate blood distribution of the BALB/c mice. ELISA, MTT, ELISPOT assays and flow cytometry analysis were carried out for further researches. We found that TIM-3 could obviously prolong the survival time of the transplanted limbs. And TIM-3 could mitigate the immune response and thus enhance immune tolerance after CTA. Also, TIM-3 can induce lymphocyte hyporesponsiveness, including facilitating lymphocyte apoptosis, decreasing lymphocyte proliferation, and influencing the secretion of inflammatory cytokines by CD4(+) T cells. Furthermore, TIM-3 overexpression could induce CD4(+) T cells to differentiate into regulatory T cells (Tregs), which recalibrate the effector and regulatory arms of the alloimmune response. In summary, we concluded that TIM-3 can mitigate allograft rejection and thus enhance immune tolerance by inducing lymphocyte hyporesponsiveness and increasing the number of Tregs of the alloimmune response. TIM-3 may be a potential therapeutic molecule for allograft rejection in CTA.

  20. Comparison of Clinical Outcome of Autograft and Allograft Reconstruction for Anterior Cruciate Ligament Tears

    Yu-Hua Jia


    Conclusions: In the repair of ACL tears, allograft reconstruction is as effective as the autograft reconstruction, but the allograft can lead to more tunnel widening evidently in the tibial tunnel, particularly.

  1. Transmission of infection with human allografts: essential considerations in donor screening.

    Fishman, Jay A; Greenwald, Melissa A; Grossi, Paolo A


    Transmission of infection via transplantation of allografts including solid organs, eyes, and tissues are uncommon but potentially life-threatening events. Donor-derived infections have been documented following organ, tissue, and ocular transplants. Each year, more than 70 000 organs, 100 000 corneas, and 2 million human tissue allografts are implanted worldwide. Single donors may provide allografts for >100 organ and tissue recipients; each allograft carries some, largely unquantifiable, risk of disease transmission. Protocols for screening of organ or tissue donors for infectious risk are nonuniform, varying with the type of allograft, national standards, and availability of screening assays. In the absence of routine, active surveillance, coupled with the common failure to recognize or report transmission events, few data are available on the incidence of allograft-associated disease transmission. Research is needed to define the optimal screening assays and the transmissibility of infection with allografts. Approaches are reviewed that may contribute to safety in allograft transplantation.

  2. Skin disease in paper mill workers

    Jungbauer, F.H.W.; Lensen, G.J.; Groothoff, J.W.; Coenraads, P.J.

    Background Paper mill workers have frequent and prolonged exposure to skin irritants and allergens and may have a higher risk of developing occupational dermatitis. Aims The aim of this study was to determine the extent of skin problems in a paper mill and how much was attributable to contact with

  3. Anterior cruciate ligament allograft transplantation for intraarticular ligamentous reconstruction.

    Goertzen, M; Dellmann, A; Gruber, J; Clahsen, H; Bürrig, K F


    A multiplicity of surgical operations have been developed in an attempt to achieve satisfactory function after anterior cruciate ligament (ACL) repair. None of these procedures have been able to reproduce the fiber organization anatomy of attachment site, vascularity, or function of the ACL. Twenty-nine foxhounds received a deep-frozen bone-ACL-bone allograft and a ligament augmentation device (LAD). Biomechanical, microvascular, and histological changes were evaluated 3, 6, and 12 months following implantation. The maximum loads of the allograft/LADs were 34.3% (387.2 N) after 3 months, 49.3% (556.6 N) after 6 months, and 61.1% (698.8 N) after a year. The maximum load was 69.1% (780 N). In general, after 6 months the allografts showed normal collagen orientation. The allografts demonstrated no evidence of infection or immune reaction. No bone ingrowth into the LAD was observed. Polarized light microscopy and periodic acid-schiff staining showed that the new bone-ligament substance interface had intact fiber orientation at the area of the ligament insertion. Microvascular examination using the Spalteholtz technique revealed revascularization and the importance of an infrapatellar fat pad for the nourishment of ACL allografts.

  4. The role of CD8+ T cells during allograft rejection

    Bueno V.


    Full Text Available Organ transplantation can be considered as replacement therapy for patients with end-stage organ failure. The percent of one-year allograft survival has increased due, among other factors, to a better understanding of the rejection process and new immunosuppressive drugs. Immunosuppressive therapy used in transplantation prevents activation and proliferation of alloreactive T lymphocytes, although not fully preventing chronic rejection. Recognition by recipient T cells of alloantigens expressed by donor tissues initiates immune destruction of allogeneic transplants. However, there is controversy concerning the relative contribution of CD4+ and CD8+ T cells to allograft rejection. Some animal models indicate that there is an absolute requirement for CD4+ T cells in allogeneic rejection, whereas in others CD4-depleted mice reject certain types of allografts. Moreover, there is evidence that CD8+ T cells are more resistant to immunotherapy and tolerance induction protocols. An intense focal infiltration of mainly CD8+CTLA4+ T lymphocytes during kidney rejection has been described in patients. This suggests that CD8+ T cells could escape from immunosuppression and participate in the rejection process. Our group is primarily interested in the immune mechanisms involved in allograft rejection. Thus, we believe that a better understanding of the role of CD8+ T cells in allograft rejection could indicate new targets for immunotherapy in transplantation. Therefore, the objective of the present review was to focus on the role of the CD8+ T cell population in the rejection of allogeneic tissue.

  5. Differential gene expression pattern in biopsies with renal allograft pyelonephritis and allograft rejection

    Oghumu, Steve; Nori, Uday; Bracewell, Anna; Zhang, Jianying; Bott, Cherri; Nadasdy, Gyongyi M.; Brodsky, Sergey V.; Pelletier, Ronald; Satoskar, Abhay R.; Nadasdy, Tibor; Satoskar, Anjali A.


    Differentiating acute pyelonephritis (APN) from acute rejection (AR) in renal allograft biopsies can sometimes be difficult because of overlapping clinical and histologic features, lack of positive urine cultures, and variable response to antibiotics. We wanted to study differential gene expression between AR and APN using biopsy tissue. Thirty-three biopsies were analyzed using NanoString multiplex platform and PCR (6 transplant baseline biopsies, 8 AR, 15 APN [8 culture positive, 7 culture negative], and 4 native pyelonephritis [NP]). Additional 22 biopsies were tested by PCR to validate the results. CXCL9, CXCL10, CXCL11, and IDO1 were the top differentially expressed genes, upregulated in AR. Lactoferrin (LTF) and CXCL1 were higher in APN and NP. No statistically significant difference in transcript levels was seen between culture-positive and culture-negative APN biopsies. Comparing the overall mRNA signature using Ingenuity pathway analysis, interferon-gamma emerged as the dominant upstream regulator in AR and allograft APN, but not in NP (which clustered separately). Our study suggests that chemokine pathways in graft APN may differ from NP and in fact resemble AR, due to a component of alloreactivity, resulting in variable response to antibiotic treatment. Therefore, cautious addition of steroids might help in resistant cases of graft APN. PMID:27352120

  6. Differential gene expression pattern in biopsies with renal allograft pyelonephritis and allograft rejection.

    Oghumu, Steve; Nori, Uday; Bracewell, Anna; Zhang, Jianying; Bott, Cherri; Nadasdy, Gyongyi M; Brodsky, Sergey V; Pelletier, Ronald; Satoskar, Abhay R; Nadasdy, Tibor; Satoskar, Anjali A


    Differentiating acute pyelonephritis (APN) from acute rejection (AR) in renal allograft biopsies can sometimes be difficult because of overlapping clinical and histologic features, lack of positive urine cultures,and variable response to antibiotics. We wanted to study differential gene expression between AR and APN using biopsy tissue. Thirty-three biopsies were analyzed using NanoString multiplex platform and PCR (6 transplant baseline biopsies, 8 AR, 15 APN [8 culture positive, 7 culture negative], and 4 native pyelonephritis [NP]). Additional 22 biopsies were tested by PCR to validate the results. CXCL9, CXCL10, CXCL11, and IDO1 were the top differentially expressed genes, upregulated in AR. Lactoferrin (LTF) and CXCL1 were higher in APN and NP. No statistically significant difference in transcript levels was seen between culture-positive and culture-negative APN biopsies. Comparing the overall mRNA signature using Ingenuity pathway analysis, interferon-gamma emerged as the dominant upstream regulator in AR and allograft APN, but not in NP (which clustered separately). Our study suggests that chemokine pathways in graft APN may differ from NP and in fact resemble AR, due to a component of alloreactivity, resulting in variable response to antibiotic treatment. Therefore, cautious addition of steroids might help in resistant cases of graft APN.

  7. Skin Infections

    ... Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old First Aid: Skin ... (bacterial infection of the deeper layers of the skin and tissues beneath) are typical childhood skin infections. The usual bacterial culprits in skin ...

  8. Skin Biomes.

    Fyhrquist, N; Salava, A; Auvinen, P; Lauerma, A


    The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.

  9. Assessment of cryopreserved donor skin viability: the experience of the regional tissue bank of Siena.

    Pianigiani, E; Tognetti, L; Ierardi, F; Mariotti, G; Rubegni, P; Cevenini, G; Perotti, R; Fimiani, M


    Skin allografts from cadaver donors are an important resource for treating extensive burns, slow-healing wounds and chronic ulcers. A high level of cell viability of cryopreserved allografts is often required, especially in burn surgery, in Italy. Thus, we aimed to determine which conditions enable procurement of highly viable skin in our Regional Skin Bank of Siena. For this purpose, we assessed cell viability of cryopreserved skin allografts procured between 2011 and 2013 from 127 consecutive skin donors, before and after freezing (at day 15, 180, and 365). For each skin donor, we collected data concerning clinical history (age, sex, smoking, phototype, dyslipidemia, diabetes, cause of death), donation process (multi-tissue or multi-organ) and timing of skin procurement (assessment of intervals such as death-harvesting, harvesting-banking, death-banking). All these variables were analysed in the whole case study (127 donors) and in different groups (e.g. multi-organ donors, non refrigerated multi-tissue donors, refrigerated multi-tissue donors) for correlations with cell viability. Our results indicated that cryopreserved skin allografts with higher cell viability were obtained from female, non smoker, heartbeating donors died of cerebral haemorrhage, and were harvested within 2 h of aortic clamping and banked within 12 h of harvesting (13-14 h from clamping). Age, cause of death and dyslipidaemia or diabetes did not appear to influence cell viability. To maintain acceptable cell viability, our skin bank needs to reduce the time interval between harvesting and banking, especially for refrigerated donors.

  10. Cefuroxime, rifampicin and pulse lavage in decontamination of allograft bone.

    Hirn, M; Laitinen, M; Pirkkalainen, S; Vuento, R


    The risk of bacterial infection through allogenic bone transplantation is one of the major problems facing tissue banks. Different screening methods and decontamination procedures are being used to achieve a safe surgical result. The purpose of this study was to investigate the contamination rate in fresh frozen bone allografts after treating them with different decontamination methods. The allografts were contaminated by rubbing on the operating theatre floor for 60 min, after which they were rinsed either with sterile physiological saline, cefuroxime or rifampicin solution or they were washed with low-pressure pulse lavage of sterile physiological saline. Our findings show that low-pressure pulse lavage with sterile saline solution is very effective in removing bacteria from bone allograft, when compared with the antibiotic solutions tested.

  11. Nephron-Sparing Surgery for Adenocarcinoma in a Renal Allograft

    Fernando Vázquez Alonso


    Full Text Available The incidence of malignant tumors in recipients of renal allografts is higher than in the general population. Renal cell carcinoma (RCC accounts for 4.6% of the tumors in transplanted patients; of them, only 10% are found in transplanted kidneys. Transplantectomy has always been the usual treatment. However, during the last years, nephron-sparing surgery of the allograft is more frequently done in well-selected cases, and therefore dialysis can be avoided. We report the case of a 37-year-old female patient with renal transplant, diagnosed with a 4.5 cm tumor in the lower pole of the renal allograft. The patient underwent partial nephrectomy successfully. Six years after surgery, there is no evidence of recurrence of the disease and the patient maintains an adequate renal function.

  12. Nephron-Sparing Surgery for Adenocarcinoma in a Renal Allograft

    Vázquez Alonso, Fernando; Cardozo Rodríguez, Enrique; Puche Sanz, Ignacio; Flores Martin, Jose Francisco; Molina Hernandez, Jose Miguel; Berrio Campos, Raquel; Vicente Prados, Javier; Medina Benitez, Antonio; Cózar Olmo, Jose Manuel


    The incidence of malignant tumors in recipients of renal allografts is higher than in the general population. Renal cell carcinoma (RCC) accounts for 4.6% of the tumors in transplanted patients; of them, only 10% are found in transplanted kidneys. Transplantectomy has always been the usual treatment. However, during the last years, nephron-sparing surgery of the allograft is more frequently done in well-selected cases, and therefore dialysis can be avoided. We report the case of a 37-year-old female patient with renal transplant, diagnosed with a 4.5 cm tumor in the lower pole of the renal allograft. The patient underwent partial nephrectomy successfully. Six years after surgery, there is no evidence of recurrence of the disease and the patient maintains an adequate renal function. PMID:22848857

  13. Lung transplantation: chronic allograft dysfunction and establishing immune tolerance.

    Gracon, Adam S A; Wilkes, David S


    Despite significant medical advances since the advent of lung transplantation, improvements in long-term survival have been largely unrealized. Chronic lung allograft dysfunction, in particular obliterative bronchiolitis, is the primary limiting factor. The predominant etiology of obliterative bronchiolitis involves the recipient's innate and adaptive immune response to the transplanted allograft. Current therapeutic strategies have failed to provide a definitive treatment paradigm to improve long-term outcomes. Inducing immune tolerance is an emerging therapeutic strategy that abrogates allograft rejection, avoids immunosuppression, and improves long-term graft function. The aim of this review is to discuss the key immunologic components of obliterative bronchiolitis, describe the state of establishing immune tolerance in transplantation, and highlight those strategies being evaluated in lung transplantation.

  14. Nebulized Pentamidine-Induced Acute Renal Allograft Dysfunction

    Siddhesh Prabhavalkar


    Full Text Available Acute kidney injury (AKI is a recognised complication of intravenous pentamidine therapy. A direct nephrotoxic effect leading to acute tubular necrosis has been postulated. We report a case of severe renal allograft dysfunction due to nebulised pentamidine. The patient presented with repeated episodes of AKI without obvious cause and acute tubular necrosis only on renal histology. Nebulised pentamidine was used monthly as prophylaxis for Pneumocystis jirovecii pneumonia, and administration preceded the creatinine rise on each occasion. Graft function stabilised following discontinuation of the drug. This is the first report of nebulized pentamidine-induced reversible nephrotoxicity in a kidney allograft. This diagnosis should be considered in a case of unexplained acute renal allograft dysfunction.

  15. Neuromodulators for Aging Skin

    ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ...

  16. Porous allograft bone scaffolds: doping with strontium.

    Yantao Zhao

    Full Text Available Strontium (Sr can promote the process of bone formation. To improve bioactivity, porous allograft bone scaffolds (ABS were doped with Sr and the mechanical strength and bioactivity of the scaffolds were evaluated. Sr-doped ABS were prepared using the ion exchange method. The density and distribution of Sr in bone scaffolds were investigated by inductively coupled plasma optical emission spectrometry (ICP-OES, X-ray photoelectron spectroscopy (XPS, and energy-dispersive X-ray spectroscopy (EDS. Controlled release of strontium ions was measured and mechanical strength was evaluated by a compressive strength test. The bioactivity of Sr-doped ABS was investigated by a simulated body fluid (SBF assay, cytotoxicity testing, and an in vivo implantation experiment. The Sr molar concentration [Sr/(Sr+Ca] in ABS surpassed 5% and Sr was distributed nearly evenly. XPS analyses suggest that Sr combined with oxygen and carbonate radicals. Released Sr ions were detected in the immersion solution at higher concentration than calcium ions until day 30. The compressive strength of the Sr-doped ABS did not change significantly. The bioactivity of Sr-doped material, as measured by the in vitro SBF immersion method, was superior to that of the Sr-free freeze-dried bone and the Sr-doped material did not show cytotoxicity compared with Sr-free culture medium. The rate of bone mineral deposition for Sr-doped ABS was faster than that of the control at 4 weeks (3.28 ± 0.23 µm/day vs. 2.60 ± 0.20 µm/day; p<0.05. Sr can be evenly doped into porous ABS at relevant concentrations to create highly active bone substitutes.

  17. The first experience of orthotropic implantation of decellularized mitral allograft

    P. P. Yablonsky


    Full Text Available Traditional biological and mechanical valve substitutes have some well-known limitation, such as rapid deterioration of the tissue ones in young patient and the high risk of thrombosis and anticoagulation therapy complications for the mechanical ones. At the same time the aortic and pulmonary valves can already be replaced with decellularized allografts that showed promising results in terms of both hemodynamics and reliability while anticoagulation for them is not needed. This paper describes the first orthotropic implantation of the decellularized mitral valve allograft in sheep model. The original method without stabilizing ring is described, which have shown good echocardiographic results.

  18. A Case of Intraparenchymal Pseudoaneurysms in Kidney Allograft

    Lorentz, Liam Antony; Hlabangana, Linda Tebogo; Davies, Malcolm


    Patient: Male, 31 Final Diagnosis: Intraparenchymal pseudo-aneurysms in kidney transplant Symptoms: Asymptomatic Medication: — Clinical Procedure: Percutaneous renal biopsy Specialty: Transplantology Objective: Diagnostic/therapeutic accidents Background: Percutaneous needle biopsy is routinely performed for renal allograft management. Vascular complications of the procedure include pseudoaneurysm and arterio-venous fistulae formation. Delayed diagnosis of these complications is due to their mostly asymptomatic and indolent nature. Case Report: We present a case of extensive intraparenchymal pseudoaneurysm formation within the inferior pole of the allograft, diagnosed two years following the most recent biopsy procedure. Conclusions: Renal pseudoaneurysms may only be diagnosed years after their formation as they are typically asymptomatic. PMID:27510594

  19. No effect of platelet-rich plasma with frozen or processed bone allograft around noncemented implants

    Jensen, T B; Rahbek, O; Overgaard, S


    We compared processed morselized bone allograft with fresh-frozen bone graft around noncemented titanium implants. Also, the influence of platelet-rich plasma (PRP) in combination with bone allograft was evaluated. Analysis was based on implant fixation and histomorphometry. PRP was prepared...... by isolating the buffy coat from autologous blood samples. Bone allograft was used fresh-frozen or processed by defatting, freeze drying, and irradiation. Cylindrical hydroxyapatite-coated titanium implants were inserted bilaterally in the femoral condyles of eight dogs. Each implant was surrounded by a 2.5-mm...... concentric gap, which was filled randomly according to the four treatment groups--group 1: fresh-frozen bone allograft; group 2: processed bone allograft; group 3: fresh-frozen bone allograft + PRP; group 4: processed bone allograft + PRP. Histological and mechanical evaluation demonstrated no influence...

  20. Skin Cancer

    ... are round and lie directly under squamous cells. Melanocytes are specialized skin cells that produce pigment called melanin. The melanin pigment produced by melanocytes gives skin its color. It also protects the ...

  1. Skin turgor

    ... arm or abdomen is checked. The skin is held for a few seconds then released. Skin with ... University of Washington, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  2. Skin Cancer

    Skin cancer is the most common form of cancer in the United States. The two most common types ... face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ...

  3. Skin Aging

    Your skin changes as you age. You might notice wrinkles, age spots and dryness. Your skin also becomes thinner and loses fat, making it ... heal, too. Sunlight is a major cause of skin aging. You can protect yourself by staying out ...

  4. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    Rajan Kapoor


    Full Text Available Acute Page Kidney (APK phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS. Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

  5. Recurrence of Acute Page Kidney in a Renal Transplant Allograft.

    Kapoor, Rajan; Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan


    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

  6. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan


    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  7. Pulse lavage washing in decontamination of allografts improves safety.

    Hirn, M; Laitinen, M; Vuento, R


    We analyzed the bacterial contamination rate of 140 femoral head allografts after rinsing the allografts in different decontamination solutions. Bacterial screening methods and cleansing effect of antibiotics (cefuroxime and rifampicin) and pulse lavage were compared. Swabbing and taking small pieces of bone for culture were the screening methods used. Both methods proved to be quite unreliable. Approximately one-fourth of the results were false negative. Culturing small pieces of bone gave the most accurate and reliable results and, therefore, can be recommended as a bacterial screening method. The use of antibiotics in allograft decontamination is controversial. In prophylactic use antibiotics include risks of allergic reactions and resistant development and our results in the present study show that antibiotics do not improve the decontamination any better than low-pressure pulse lavage with sterile saline solution. Therefore, pulse lavage with sterile saline solution can be recommended for allograft decontamination. Our results demonstrate that it decreases bacterial bioburden as effectively as the antibiotics without persisting the disadvantages.

  8. Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival

    Smelt, M. J.; Faas, M. M.; Melgert, B. N.; de Vos, P.; de Haan, Bart; de Haan, Aalzen


    Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats receive

  9. Urine Proteomics to Detect Biomarkers for Chronic Allograft Dysfunction

    Quintana, Luís F.; Solé-Gonzalez, Amanda; Kalko, Susana G.; Bañon-Maneus, Elisenda; Solé, Manel; Diekmann, Fritz; Gutierrez-Dalmau, Alex; Abian, Joaquin; Campistol, Josep M.


    Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction. A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life. In this proof-of-concept study, we used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction (14 with pure interstitial fibrosis and tubular atrophy and 18 with chronic active antibody-mediated rejection) and 18 control subjects (eight stable recipients and 10 healthy control subjects). Unsupervised hierarchical clustering showed good segregation of samples in groups corresponding mainly to the four biomedical conditions. Moreover, the composition of the proteome of the pure interstitial fibrosis and tubular atrophy group differed from that of the chronic active antibody-mediated rejection group, and an independent validation set confirmed these results. The 14 protein ions that best discriminated between these two groups correctly identified 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection. In summary, this study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction. PMID:19056874

  10. Left versus right deceased donor renal allograft outcome.

    Phelan, Paul J


    It has been suggested that the left kidney is easier to transplant than the right kidney because of the longer length of the left renal vein, facilitating the formation of the venous anastomosis. There are conflicting reports of differing renal allograft outcomes based on the side of donor kidney transplanted (left or right).We sought to determine the effect of side of donor kidney on early and late allograft outcome in our renal transplant population. We performed a retrospective analysis of transplanted left-right deceased donor kidney pairs in Ireland between January 1, 1998 and December 31, 2008. We used a time to death-censored graft failure approach for long-term allograft survival and also examined serum creatinine at different time points post-transplantation. All outcomes were included from day of transplant onwards. A total of 646 transplants were performed from 323 donors. The incidence of delayed graft function was 16.1% in both groups and there was no significant difference in acute rejection episodes or serum creatinine from 1 month to 8 years post-transplantation.There were 47 death-censored allograft failures in the left-sided group compared to 57 in the right-sided group (P = 0.24). These observations show no difference in renal transplant outcome between the recipients of left- and right-sided deceased donor kidneys.

  11. Noninvasive diagnosis of allograft vascular disease after heart transplantation

    Fernando Bacal


    Full Text Available OBJECTIVE: To determine the predictive values of noninvasive tests for the detection of allograft vascular disease. METHODS: We studied 39 patients with mean ages of 48±13 years and a follow-up period of 86±13 months. The diagnosis of allograft vascular disease was made by cine-coronary arteriography, and it was considered as positive if lesions existed that caused > or = 50% obstruction of the lumen. Patients underwent 24h Holter monitoring, thallium scintigraphy, a treadmill stress test, and dobutamine stress echocardiography. Sensitivity, specificity, and positive and negative predictive values were determined in percentages for each method, as compared with the cine-coronary arteriography results. RESULTS: Allograft vascular disease was found in 15 (38% patients. The Holter test showed 15.4% sensitivity, 95.5% specificity. For the treadmill stress test, sensitivity was 10%, specificity was 100%. When thallium scintigraphy was used, sensitivity was 40%, specificity 95.8%. On echocardiography with dobutamine, we found a 63.6% sensitivity, 91.3% specificity. When the dobutamine echocardiogram was associated with scintigraphy, sensitivity was 71.4%, specificity was 87%. CONCLUSION: In this group of patients, the combination of two noninvasive methods (dobutamine echocardiography and thallium scintigraphy may be a good alternative for the detection of allograft vascular disease in asymptomatic patients with normal ventricular function.

  12. Efficacy of isoniazid prophylaxis in renal allograft recipients.

    Naqvi, R; Akhtar, S; Noor, H; Saeed, T; Bhatti, S; Sheikh, R; Ahmed, E; Akhtar, F; Naqvi, A; Rizvi, A


    The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients. Occurrence of clinical tuberculosis during the initial 2 years posttransplantation was observed in the risk group and patients at no risk. Risks were defined as acute rejection episodes and exposure to antirejection therapy, past history of TB completely or incompletely treated, radiological evidence of past tuberculosis, history of tuberculosis in close contacts. Among 480 patients registered in the study, INH prophylaxis was given to 219 randomly assigned renal allograft recipients. Results were compared among patients developing TB during the initial 2 years posttransplantation in both the groups. Risk factors were analyzed for comparison in both groups. No significant difference was observed in terms of past history of TB, TB in close contacts, episodes of acute rejection during the initial 3 months, and comorbidities such as cytomegalovirus infection, hepatitis C virus infection, and posttransplant diabetes. One patient from the INH group and 10 patients from the non-INH group developed TB during the initial 2 years posttransplantation (P < .0001). None of patients required discontinuation of INH. INH was observed to be safe and effective as a chemoprophylactic agent in renal allograft recipients.

  13. Tuberculosis in a renal allograft recipient presenting with intussusception.

    Mohapatra, A; Basu, G; Sen, I; Asirvatham, R; Michael, J S; Pulimood, A B; John, G T


    Extra-pulmonary tuberculosis (TB) is more common in renal allograft recipients and may present with dissemination or an atypical features. We report a renal allograft recipient with intestinal TB presenting 3 years after transplantation with persistent fever, weight loss, diarrhea, abdominal pain and mass in the abdomen with intestinal obstruction. He was diagnosed to be having an ileocolic intussusception which on resection showed a granulomatous inflammation with presence of acid-fast bacilli (AFB) typical of Mycobacterium tuberculosis. In addition, AFB was detected in the tracheal aspirate, indicating dissemination. He received anti-TB therapy (ATT) from the fourth postoperative day. However, he developed a probable immune reconstitution inflammatory syndrome (IRIS) with multiorgan failure and died on 11(th) postoperative day. This is the first report of intestinal TB presenting as intussusception in a renal allograft recipient. The development of IRIS after starting ATT is rare in renal allograft recipients. This report highlights the need for a high index of suspicion for diagnosing TB early among renal transplant recipients and the therapeutic dilemma with overwhelming infection and development of IRIS upon reduction of immunosuppression and starting ATT.

  14. Identification and treatment of cyclosporine-associated allograft thrombosis

    Schlanger, R.E.; Henry, M.L.; Sommer, B.G.; Ferguson, R.M.


    Endothelial injury associated with cyclosporine (CSA) therapy in the absence of rejection has resulted in irreversible intrarenal allograft thrombosis and transplant loss. Indium 111 (/sup 111/In)-labeled platelet scanning is an effective way to identify those transplants that are at risk for acute loss. Two hundred prospective /sup 111/In scans were obtained (100 on allografts with normal function and 100 with transplant dysfunction of all causes). /sup 111/In scans in patients with dose-dependent CSA nephrotoxicity (N = 58) and biopsy proved acute rejection (N = 22) were negative. Grossly abnormal scans (three to eight times greater than hepatic uptake) were noted in nine recipients identified as having a hemolytic uremic-like syndrome associated with CSA use. Accelerated allograft functional loss was irreversible in six patients despite stopping CSA, systemic anticoagulation, increased steroids and antilymphocyte globulin, and infusion of fresh-frozen plasma. Three patients with grossly positive /sup 111/In scans and clinical and laboratory parameters consistent with this syndrome were treated with cessation of CSA and intra-arterial infusion of streptokinase into the renal allograft followed by systemic heparinization. Normal transplant function was regained and continues at 1, 7, and 8 months after transplant. /sup 111/In-labeled platelet scanning can noninvasively identify this syndrome of CSA-associated arteriopathy and allow for early therapy to reverse it. Intrarenal arterial streptokinase therapy is a successful way to treat acute CSA-associated arteriopathy.

  15. Effect of the Multiglycoside of Tripterygium Wilfordii Hookf.(Tii)on Cornea Allograft Rejection Model in Rabbit

    ZhijieLi; ChenLi


    Purpose:Toexamine the effect of Tii treatment of cornea graft survival in a rab-bit model.Methods:Tii was administrated orally after eccentrical corneal transplantation.Survival times were determined by biomicroscopy.Cytotoxic T lymphocytes(CTL)and delayed-type hypersensitivity(DTH)responses to donor alloantigens were assessed at ady 16after heterotopic corneal grafts.Results:Administration of Tii reduced the incidence and prologed the graft sur-vival time.Both CTLand DTH responses to donor alloantigens were severely ed-pressed in hosts treated with Tii.However,combination of Tii and cyclosporine further enhanced the immunosuppressive effects described above.Conclusions:Tii is a potent immunosuppressant with the ability to prolong allo-graft survival in the rabbit penetrating keratoplasty model and may have coordi-native effects with CsA through different mechanisms.Further studies are neces-sary to define any potentially coordinative role in the prevention of allograft rejec-tion in human keratoplasty.Eye Science 1995;11:168-172.

  16. ACL graft failure location differs between allografts and autografts

    Magnussen Robert A


    Full Text Available Abstract Background Between 5 and 20% of patients undergoing ACL reconstruction fail and require revision. Animal studies have demonstrated slower incorporation of allograft tissue, which may affect the mechanism of graft failure. The purpose of this study is to determine the location of traumatic graft failure following ACL reconstruction and investigate differences in failure patterns between autografts and allografts. Methods The medical records of 34 consecutive patients at our center undergoing revision ACL reconstruction following a documented traumatic re-injury were reviewed. Graft utilized in the primary reconstruction, time from initial reconstruction to re-injury, activity at re-injury, time to revision reconstruction, and location of ACL graft tear were recorded. Results Median patient age at primary ACL reconstruction was 18.5 years (range, 13–39 years. The primary reconstructions included 20 autografts (13 hamstrings, 6 patellar tendons, 1 iliotibial band, 12 allografts (5 patellar tendon, 5 tibialis anterior tendons, 2 achilles tendons, and 2 unknown. The median time from primary reconstruction to re-injury was 1.2 years (range, 0.4 – 17.6 years. The median time from re-injury to revision reconstruction was 10.4 weeks (range, 1 to 241 weeks. Failure location could be determined in 30 patients. In the autograft group 14 of 19 grafts failed near their femoral attachment, while in the allograft group 2 of 11 grafts failed near their femoral attachment (p  Conclusions When ACL autografts fail traumatically, they frequently fail near their femoral origin, while allograft reconstructions that fail are more likely to fail in other locations or stretch. Level of evidence Level III - Retrospective cohort study

  17. Metabolomic Profiling in Individuals with a Failing Kidney Allograft

    Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D’Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo


    Background Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. Methods To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. Results LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. Conclusions We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function. PMID:28052095

  18. Air Pollution and the skin

    Eleni eDrakaki


    Full Text Available The increase of air pollution over the years has major effects on the human skin. The skin is exposed to ultraviolet radiation (UVR and environmental air pollutants such as polycyclic aromatic hydrocarbons (PAHs, volatile organic compounds (VOCs, oxides, particulate matter (PM, ozone (O3 and cigarette smoke. Although human skin acts as a biological shield against pro-oxidative chemical and physical air pollutants, the prolonged or repetitive exposure to high levels of these pollutants may have profound negative effects on the skin. Exposure of the skin to air pollutants has been associated with skin aging and inflammatory or allergic skin conditions such as atopic dermatitis, eczema, psoriasis or acne, while skin cancer is among the most serious effects. On the other hand, some air pollutants (ie, ozone, nitrogen dioxide, and sulfur dioxide and scattering particulates (clouds and soot in the troposphere reduce the effects of shorter wavelength UVR and significant reductions in UV irradiance have been observed in polluted urban areas.

  19. Clinical Evaluation of Equine Antithymocyte Globulin in Recipients of Renal Allografts: Analysis of Survival, Renal Function, Rejection, Histocompatibility, and Complications

    Diethelm, Arnold G.; Aldrete, Joaquin S.; Shaw, June F.; Cobbs, C. Glenn; Hartley, Marshall W.; Sterling, William A.; Morgan, Jean McN


    Equine antithymocyte globulin combined with azathioprine and prednisone as immunosuppressive therapy in 50 transplant recipients prolonged allograft survival and seemed to modify the severity of rejection episodes. Although nine patients died from a variety of causes, only three kidneys were lost to rejection, one of which was hyperacute. There were no serious untoward hematologic or systemic effects caused by the ATG, and all patients completed the course of therapy. Infection, a serious and frequent complication of transplant patients, was encountered no more often than in other transplant series not using ALG. The data pertaining to the clinical value of ATG, although suggestive in terms of its immunosuppressive effects, is still not conclusive; and a definitive answer to this question awaits further evaluation in a series of cadaveric recipients in a randomized-double-blind study. ImagesFig. 1. PMID:4599406

  20. Angiosome-Based Allografts: Vascularized Composite Allotransplantation for Tailored Subunit Reconstruction with Volkmann Ischemic Contracture as a Case in Point.

    Taylor, G Ian; Sparks, David S; Gascoigne, Adam C; Corlett, Russell J; Ashton, Mark W


    As we enter an age with new approaches to tissue reconstruction, the emphasis on the adage "like for like" has become even more relevant. This study illustrates the potential for several tailored vascularized composite allotransplantation reconstructive techniques and, in particular, for the management of Volkmann contracture. Twenty fresh cadaver dissections and 30 archival lead oxide radiographic studies were examined to (1) identify potential upper limb vascularized composite allotransplantation donor sites (i.e., elbow, forearm, and flexor tendon complex) and (2) demonstrate a "mock transplant" of the vascularized volar forearm allograft for a severe Volkmann ischemia defect. They were designed without skin to reduce antigenicity. The elbow joint was supplied within the brachial angiosome and the flexor tendon complex of the flexor digitorum superficialis and flexor digitorum profundus by the superficial palmar arch of the ulnar angiosome. The forearm allograft of flexor muscles, median, ulnar, and anterior interosseous nerves, when harvested on the brachial vessels, was supplied within the radial, ulnar, and anterior interosseous angiosomes but could be based on the ulnar artery alone because of intramuscular connections with the other territories. A mock transplant was performed with a distal-to-proximal dissection of the allograft, facilitating the best and fastest technique. This application of the angiosome concept highlights the anatomical feasibility of the volar forearm vascularized composite allotransplantation donor site focusing on a complex subunit problem in the upper limb-severe Volkmann ischemic contracture. It demonstrates the potential use and immunologic advantage of subdivided and modified nonskin variations of vascularized composite allotransplantation in reconstructive transplantation surgery. Therapeutic, V.


    R. Adam


    Full Text Available Children’s skin under nappy needs special defense from irritative action of urine and faeces and, therefore, prophylaxis of nappy dermatitis is necessary. It means that disposable nappy absorbing faeces and urine and special staff for skin cleaning should be used. There are several factors conductive to dermatitis: prolonged irritation with excrements, change of skin pH or increase of its hydratation and disorders of skin micro flora. During last decades there is a significant progress in understanding of these factors, and it resulted in production of more and more perfect stuff for defense of children’s skin. Improved design of nappies and development of pH-buffer wipes for babies increased the quality of skin care. Key words: children, skin, hygienic care.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(5:90-94

  2. Multifocal Aggressive Squamous Cell Carcinomas Induced by Prolonged Voriconazole Therapy: A Case Report

    C. Morice


    Full Text Available Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of the MICR gene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring.

  3. Multifocal aggressive squamous cell carcinomas induced by prolonged voriconazole therapy: a case report.

    Morice, C; Acher, A; Soufir, N; Michel, M; Comoz, F; Leroy, D; Verneuil, L


    Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of the MICR gene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring.

  4. Prolonged unexplained fatigue in paediatrics

    Bakker, R.J.


    Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of exertio

  5. Prolongation structures for supersymmetric equations

    Roelofs, G.H.M.; Hijligenberg, van den N.W.


    The well known prolongation technique of Wahlquist and Estabrook (1975) for nonlinear evolution equations is generalized for supersymmetric equations and applied to the supersymmetric extension of the KdV equation of Manin-Radul. Using the theory of Kac-Moody Lie superalgebras, the explicit form of

  6. Effects of recombinant human interleukin-10 on Treg cells, IL-10 and TGF-β in transplantation of rabbit skin



    The current study aimed to investigate the rejection and survival time of grafted skin, and the changes of Treg cells, interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) in peripheral blood following skin transplantation with recombinant human interleukin-10 (rhIL-10) or cyclosporin A (CsA), as well as the role of IL-10 in immunological rejection mechanisms. A total of 36 rabbits were divided into two groups. The skin of a donor rabbit was transplanted onto the back of one receptor rabbit. Receptors were randomly divided into six groups, including rhIL-10 low-dose (5 μg/kg/d), rhIL-10 high-dose (10 μg/kg/d), CsA low-dose (5 mg/kg/d), CsA high-dose (10 mg/kg/d), rhIL-10 (5 μg/kg/d) and CsA (5 mg/kg/d) and negative control normal saline (NS; 1 ml/d). All groups received intramuscular drug injection for ten days, beginning one day prior to skin transplantation surgery. Following transplantation, each rabbit’s peripheral blood was collected at different times. The changes of CD4+CD25+ regulatory T cells, IL-10 and TGF-β were determined by flow cytometry and enzyme-linked immunosorbent assay. When compared with the control group, the rejection and survival times of the experimental groups were longer following skin graft. Compared with the two CsA groups and the control group, the proportion of CD4+CD25+ regulatory T cells of rhIL-10 groups was significantly upregulated on the 4th and 7th days following surgery. However, TGF-β levels were not significantly different. Data suggested that the concentration of IL-10 was positively correlated with the proportion of CD4+CD25+ regulatory T cells. In addition, IL-10 may delay the rejection time of rabbit skin transplantation and prolong the survival time. Thus, the role of IL-10 in inhibited allograft rejection may be associated with CD4+CD25+ regulatory T cells and IL-10, and may be independent of TGF-β. PMID:24270972

  7. Effects of recombinant human interleukin-10 on Treg cells, IL-10 and TGF-β in transplantation of rabbit skin.

    Liu, Kai Shan; Fan, Xiao Qin; Zhang, Lei; Wen, Qiong Na; Feng, Ji Hong; Chen, Fu Chao; Luo, Jun Min; Sun, Wan Bang


    The current study aimed to investigate the rejection and survival time of grafted skin, and the changes of Treg cells, interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) in peripheral blood following skin transplantation with recombinant human interleukin-10 (rhIL-10) or cyclosporin A (CsA), as well as the role of IL-10 in immunological rejection mechanisms. A total of 36 rabbits were divided into two groups. The skin of a donor rabbit was transplanted onto the back of one receptor rabbit. Receptors were randomly divided into six groups, including rhIL-10 low-dose (5 µg/kg/d), rhIL-10 high-dose (10 µg/kg/d), CsA low-dose (5 mg/kg/d), CsA high-dose (10 mg/kg/d), rhIL-10 (5 µg/kg/d) and CsA (5 mg/kg/d) and negative control normal saline (NS; 1 ml/d). All groups received intramuscular drug injection for ten days, beginning one day prior to skin transplantation surgery. Following transplantation, each rabbit's peripheral blood was collected at different times. The changes of CD4+CD25+ regulatory T cells, IL-10 and TGF-β were determined by flow cytometry and enzyme-linked immunosorbent assay. When compared with the control group, the rejection and survival times of the experimental groups were longer following skin graft. Compared with the two CsA groups and the control group, the proportion of CD4+CD25+ regulatory T cells of rhIL-10 groups was significantly upregulated on the 4th and 7th days following surgery. However, TGF-β levels were not significantly different. Data suggested that the concentration of IL-10 was positively correlated with the proportion of CD4+CD25+ regulatory T cells. In addition, IL-10 may delay the rejection time of rabbit skin transplantation and prolong the survival time. Thus, the role of IL-10 in inhibited allograft rejection may be associated with CD4+CD25+ regulatory T cells and IL-10, and may be independent of TGF-β.

  8. Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.

    Xu, Jin; Casas-Ferreira, Ana M; Ma, Yun; Sen, Arundhuti; Kim, Min; Proitsi, Petroula; Shkodra, Maltina; Tena, Maria; Srinivasan, Parthi; Heaton, Nigel; Jassem, Wayel; Legido-Quigley, Cristina


    Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.

  9. Micro-organisms isolated from cadaveric samples of allograft musculoskeletal tissue.

    Varettas, Kerry


    Allograft musculoskeletal tissue is commonly used in orthopaedic surgical procedures. Cadaveric donors of musculoskeletal tissue supply multiple allografts such as tendons, ligaments and bone. The microbiology laboratory of the South Eastern Area Laboratory Services (SEALS, Australia) has cultured cadaveric allograft musculoskeletal tissue samples for bacterial and fungal isolates since 2006. This study will retrospectively review the micro-organisms isolated over a 6-year period, 2006-2011. Swab and tissue samples were received for bioburden testing and were inoculated onto agar and/or broth culture media. Growth was obtained from 25.1 % of cadaveric allograft musculoskeletal tissue samples received. The predominant organisms isolated were coagulase-negative staphylococci and coliforms, with the heaviest bioburden recovered from the hemipelvis. The rate of bacterial and fungal isolates from cadaveric allograft musculoskeletal tissue samples is higher than that from living donors. The type of organism isolated may influence the suitability of the allograft for transplant.

  10. Kidney retransplantation for BK virus nephropathy with active viremia without allograft nephrectomy.

    Huang, Jingbo; Danovitch, Gabriel; Pham, Phuong-Thu; Bunnapradist, Suphamai; Huang, Edmund


    BK virus nephropathy is an important cause of kidney allograft failure. Retransplantation has been successfully performed for patients with previous allograft loss due to BK virus nephropathy; however, whether allograft nephrectomy and viral clearance are required prior to retransplantation is controversial. Some recent studies have suggested that retransplantion can be successfully achieved without allograft nephrectomy if viremia is cleared prior to retransplant. The only published experience of successful retransplantation in the presence of active viremia occurred in the presence of concomitant allograft nephrectomy of the failing kidney. In this report, we describe a case of successful repeat kidney transplant in a patient with high-grade BK viremia and fulminant hepatic failure without concomitant allograft nephrectomy performed under the setting of a simultaneous liver-kidney transplant.

  11. Immune reactivity of cells from long-term rat renal allograft survivors

    Weiss, A.; Stuart, F.P.; Fitch, F.W.


    Lewis rats receiving an LBN kidney allograft demonstrate no signs of rejection if they are pretreated with donor spleen cells and antiserum reactive with the donor alloantigen. We examined the cellular reactivity of long-term kidney allograft survivors. Normal proliferative and cytolytic responses were obtained with spleen cells from long-term survivors, in marked contrast to the diminished responses of cells from neonatally tolerant rats or the heightened cytolytic response of cells from rats that had rejected a renal allograft. Serum from long-term renal allograft survivors as well as serum obtained from rats at the time of transplantation did not suppress proliferative or cytolytic responses of normal cells. The results of this study suggest that long-term renal allograft survivors possess the precursors of those cells which are responsible for proliferative and cytolytic responses in mixed leukocyte cultures, but that they have not been sensitized to their renal allograft.

  12. Septic arthritis following anterior cruciate ligament reconstruction using tendon allografts--Florida and Louisiana, 2000.


    In the United States, approximately 50,000 knee surgeries are performed each year for repairing anterior cruciate ligament (ACL) injuries. Tissue allografts frequently are used for ACL reconstruction, and septic arthritis is a rare complication of such procedures. This report describes four patients who acquired postsurgical septic arthritis probably associated with contaminated bone-tendon-bone allografts used for ACL reconstruction. Effective sterilization methods that do not functionally alter musculoskeletal tissue are needed to prevent allograft-related infections.

  13. Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury.

    Wang, Ying-Ying; Jiang, Hong; Pan, Jun; Huang, Xiao-Ru; Wang, Yu-Cheng; Huang, Hong-Feng; To, Ka-Fai; Nikolic-Paterson, David J; Lan, Hui-Yao; Chen, Jiang-Hua


    Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers. CD68(+)/α-SMA(+) cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and α-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of α-SMA(+) myofibroblasts in renal allografts originated from recipient bone marrow-derived macrophages. Knockout of Smad3 protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in Smad3-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow-derived M2-type macrophages to myofibroblasts in the renal allograft is regulated via a Smad3-dependent mechanism.

  14. Simvastatin combined with aspirin increases the survival time of heart allograft by activating CD4(+)CD25(+) Treg cells and enhancing vascular endothelial cell protection.

    Zhu, Jinguo; Gao, Bingren


    The objective was to investigate whether the combination of simvastatin and aspirin treatment prolongs the survival time of the heart allograft in rat and its underlying mechanism. Heterotopic heart transplantation was performed using Wistar rats as donors and Sprague-Dawley (SD) rats as recipients. The SD rats were randomly divided into five groups (n=20/group): sham, HT (heart transplantation), HT+simvastatin (HT+S), HT+aspirin (HT+A), and HT+aspirin+simvastatin (HT+A+S). After transplantation, at 3, 7, 10, 15, 20, 30, and 40 days, the endothelial nitric oxide synthase (eNOS) expression was assessed by immunohistological staining; nitric oxide (NO) levels were analyzed by Griess assay; the activation of CD4(+)CD25(+) T regulatory lymphocytes (Tregs) was analyzed by flow cytometry; and pathological changes in the graft heart were determined by histology. Combined treatment of hearts with simvastatin and aspirin significantly prolonged the mean survival time of heart allografts [8 ± 1.2 days (n=18), 20 ± 3.4 days (n=19), 21 ± 2.8 days (n=19), and 39 ± 5.3 days (n=19) for HT, HT+S, HT+A, and HT+A+S group, respectively; HT vs. HT+A+S, PTreg-cell-induced immune tolerance and enhanced vascular endothelial cell protection. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Cyclosporine-pancuronium interaction in a patient with a renal allograft.

    Crosby, E; Robblee, J A


    A case is described of a 54-year-old 55 kg patient who presented for clipping of a middle cerebral aneurysm two years after a successful renal allograft. Immunosuppression was maintained with azathioprine 100 mg daily, cyclosporine 300 mg daily and prednisone 10 mg daily. The patient had chronic hypertension controlled with nifedipine 40 mg daily and furosemide 20 mg daily. The cyclosporine level taken on the morning of surgery was 166 micrograms.L-1. Induction of anaesthesia consisted of fentanyl 350 micrograms, thiopentone 125 mg and pancuronium 5.5 mg. Anaesthesia was maintained with nitrous oxide 70 per cent in oxygen and isoflurane 0.5-1.5 per cent. No additional doses of pancuronium were given during the four hour surgical procedure. At the end of surgery, four twitches were present with train-of-four stimulation, but evidence of residual muscle paralysis was present. Residual neuromuscular blockade was reversed with atropine 1.2 mg and neostigmine 2.5 mg. Residual paralysis was present in the Recovery Room and edrophonium 10 mg was given prior to extubation. Clinical testing demonstrated adequate reversal of neuromuscular blockade. Twenty minutes following extubation, increasing respiratory distress was noted. There was clinical evidence of muscle paralysis. The patient was re-intubated. It is proposed that cyclosporine potentiated the pancuronium blockade producing prolonged neuromuscular relaxation resulting in residual paralysis following surgery. The potential interactions of cyclosporine and muscle relaxants deserve further study.

  16. Histological study of fresh versus frozen semitendinous muscle tendon allografts

    Alexandre Carneiro Bitar


    Full Text Available OBJECTIVE: The purpose of this study was to histologically analyze allografts from cadaveric semitendinous muscle after cryopreservation at -80°C in comparison to a control group kept at only -4°C to test the hypothesis that the histological characteristics of the tissue are maintained when the tendons are kept at lower temperatures. METHODS: In a tissue bank, 10 semitendinous tendons from 10 cadavers were frozen at -80ºC as a storage method for tissue preservation. They were kept frozen for 40 days, and then a histological study was carried out. Another 10 tendon samples were analyzed while still "fresh". RESULTS: There was no histological difference between the fresh and frozen samples in relation to seven variables. CONCLUSIONS: Semitendinous muscle tendon allografts can be submitted to cryopreservation at -80ºC without suffering histological modifications.

  17. Mechanism of arterial remodeling in chronic allograft vasculopathy

    Qichang Zheng; Shanglong Liu; Zifang Song


    Chronic allograft vasculopathy (CAV) remains a major obstacle for long-term survival of grafts even though therapeutic strategies have improved considerably in recent years.CAV is characterized by concentric and diffuse neointimal formation,medial apoptosis,infiltration of lymphocyte or inflammatory cells,and deposition of extracellular matrix both in arteries and veins.Recent studies have shown that stem cells derived from the recipient contribute to neointimal formation under the regulation of chemokines and cytokines.Arterial remodeling in allografts eventually causes ischemic graft failure.The pathogenesis is multi-factorial with both immunologic and non-immunological factors being involved.The immunological factors have been discussed extensively in other articles.This review focuses mainly on the arterial remodeling that occurs in 3 layers of vessel walls including intimal injury,accumulation of smooth muscle-like cells in the neointimal,medial smooth muscle cell apoptosis,adventitial fibrosis,and deposition of extracellular matrix.

  18. Blockade of p38 MAPK inhibits chronic allograft vasculopathy.

    Ollinger, Robert; Thomas, Michael; Kogler, Pamela; Hermann, Martin; Weiss, Helmut; Mark, Walter; Bilban, Martin; Troppmair, Jakob; Bach, Fritz H; Margreiter, Raimund


    Long-term survival after solid-organ transplantation is hampered by chronic changes in the arteries of the grafts, called chronic allograft vasculopathy (CAV). The lesions consist mainly of proliferating vascular smooth muscle cells that cause narrowing of the vessels; these lesions can develop within a few months. There is no effective treatment to prevent CAV. We previously noted that the pharmacological inhibition of p38 mitogen-activated protein kinase (MAPK) suppresses the proliferation of vascular smooth muscle cells. We hypothesized that in vivo inhibition of p38 MAPK in mice bearing allogeneic aortic allografts would prevent CAV. We here report that blockade of p38 MAPK, a signaling molecule involved in cell division, apoptosis, and cell death, markedly suppresses CAV. Given recent data indicating that inhibition of p38 MAPK is a promising approach for the treatment of autoimmune diseases plus our present findings, p38 MAPK blockade for CAV seems a reasonable approach to consider for clinical application.

  19. [The immunologic function and role of allograft inflammatory factor-1].

    Yamamoto, Aihiro; Kawahito, Yutaka


    Allograft inflammatory factor-1 is the protein that expressed in the macrophages around the coronary arteries in rat ectopic cardiac allograft model. AIF-1 is produced mainly by macrophages and regulated by interferon-gamma (IFN-γ). There are various splicing valiants in AIF-1, and the functions are different. AIF-1 has Ca-binding EF-hand motif that induces cell proliferation and migration by structural features. Besides cell proliferation and migration, AIF-1 contributes to secretion of inflammatory cytokines and chemokines such as IL-6, IL-10, IL-12, and transforming growth factor-beta (TGF-β), insulin resistance by downregulation of GLUT4 or IRS-1, and fibrosis process by upregulation of collagen production. It has been elucidated that AIF-1 is responsible for the onset of various diseases such as rheumatoid arthritis and systemic sclerosis, atherosclerotic disease, diabetes mellitus. AIF-1 may have the therapeutic potential for chronic inflammatory diseases by elucidation of the mechanism.

  20. Late Acute Rejection Occuring in Liver Allograft Recipients

    Eric M Yoshida


    Full Text Available To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1. Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2. LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant. Mean trough CsA levels were lower in patients with LAR compared with those without (224±66 ng/mL versus 233±49 ng/mL but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5±1.6 mg/ day versus 6.5±2.9 mg/day, P=0.007 and CsA nadir values (129±60 ng/mL versus 186±40 ng/mL, P=0.03 were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83% of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8% receiving prednisone 5 mg/day or more (P=0.004. In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.

  1. Inflammatory mediators and cytotoxins in cardiac allograft rejection

    Lowry, R.P.; Powell, W.S.; Blais, D.; Marghesco, D.


    Though organ allograft rejection in rats has been linked to delayed type hypersensitivity (DTH) the pathogenesis of DTH induced tissue injury is uncertain. Accordingly, the authors have undertaken to identify the following inflammatory mediators/cytotoxins in rejecting rat cardiac allografts (WF ..-->.. LEW, day 5): phospholipase A/sub 2/(PLA/sub 2/ in cardiac homogenates assessed using /sup 14/C oleate labelled E Coli), PAF in lipid extracts of grafts measured by aggregation of rabbit platelets, arachidonic acid (AA) metabolites (HPLC analysis of products released from isolated perfused hearts and slices prelabelled with /sup 3/H-AA), lymphotoxin and/or tumor necrosis factor (LT/TNF release in vitro from infiltrating mononuclear cells assayed using cell line varies as L929. Briefly, aliquots of homogenates (10ml) of rejecting grafts demonstrated PLA/sub 2/ activity as evidenced by liberation of FFA from bacterial phospholipids (baseline 3%, 1 4%, 25 24%, 100 /sup +/l 29%, 200 39%; control hearts, 200 5%). Rejecting cardiac allografts contained approximately 10 ng PAF while PAF recovered from syngeneic grafts was less than or equal to 5 ng. Observed changes in eicosanoid biosynthesis with rejection were limited to a decrement in 6 oxo PGF/sub /sub 1/..cap alpha../ release. Infiltrating mononuclear cells recovered from rejecting grafts released greater than or equal to 64 units of cytotoxin (LT and/or TNF). The author present results, documenting a decrement in prostacyclin release by rejecting heart grafts, the presence of PLA/sub 2/ and PAF and the release of cytotoxins (LT and/or TNF) by infiltrating mononuclear cells are compatible with the thesis that allograft rejection must be viewed as a complex immune/inflammatory process. Additional studies are clearly required to define roles of these and other soluble factors in homograft destruction.

  2. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

    Ito, Hiromu; Koefoed, Mette; Tiyapatanaputi, Prarop


    Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease...... in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze...

  3. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.


    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system....

  4. Quantification of renal allograft perfusion using arterial spin labeling MRI: initial results

    Lanzman, Rotem S.; Wittsack, Hans-Joerg; Bilk, Philip; Kroepil, Patric; Blondin, Dirk [University Hospital Duesseldorf, Department of Radiology, Duesseldorf (Germany); Martirosian, Petros; Schick, Fritz [University Hospital Tuebingen, Section for Experimental Radiology, Department of Diagnostic Radiology, Tuebingen (Germany); Zgoura, Panagiota; Voiculescu, Adina [University Hospital Duesseldorf, Department of Nephrology, Duesseldorf (Germany)


    To quantify renal allograft perfusion in recipients with stable allograft function and acute decrease in allograft function using nonenhanced flow-sensitive alternating inversion recovery (FAIR)-TrueFISP arterial spin labeling (ASL) MR imaging. Following approval of the local ethics committee, 20 renal allograft recipients were included in this study. ASL perfusion measurement and an anatomical T2-weighted single-shot fast spin-echo (HASTE) sequence were performed on a 1.5-T scanner (Magnetom Avanto, Siemens, Erlangen, Germany). T2-weighted MR urography was performed in patients with suspected ureteral obstruction. Patients were assigned to three groups: group a, 6 patients with stable allograft function over the previous 4 months; group b, 7 patients with good allograft function who underwent transplantation during the previous 3 weeks; group c, 7 allograft recipients with an acute deterioration of renal function. Mean cortical perfusion values were 304.8 {+-} 34.4, 296.5 {+-} 44.1, and 181.9 {+-} 53.4 mg/100 ml/min for groups a, b and c, respectively. Reduction in cortical perfusion in group c was statistically significant. Our results indicate that ASL is a promising technique for nonenhanced quantification of cortical perfusion of renal allografts. Further studies are required to determine the clinical value of ASL for monitoring renal allograft recipients. (orig.)

  5. MR evaluation of renal allografts; Rola badania MR w ocenie nerki przeszczepionej

    Slapa, R.Z.; Jakubowski, W.; Tyminska, B. [Zaklad Diagnostyki Obrazowej, Wojewodzki Zespol Publicznych Zakladow Opieki Zdrowotnej, Warsaw (Poland)


    The paper presents state of the art in MR evaluation of renal allografts. MRI is very sensitive in diagnosis of renal allograft rejection. This diagnosis is mainly based on evaluation of cortico-medullary differentiation. MRI has potential for differential diagnosis of pathological perirental fluid collections. T2-weighted images and paramagnetic contrast agent studies diagnosis of allograft necrosis. MRA is useful for evaluation of possible vascular surgical complications. New applications of MR technique for evaluation of renal allograft as dynamic contrast agent studies and spectroscopy are under investigation. (author) 15 refs, 2 figs

  6. Impaired renal allograft function is associated with increased arterial stiffness in renal transplant recipients

    Kneifel, M; Scholze, A; Burkert, A;


    It is important whether impairment of renal allograft function may deteriorate arterial stiffness in renal transplant recipients. In a cross-sectional study, arterial vascular characteristics were non-invasively determined in 48 patients with renal allograft using applanation tonometry and digital...... of large arteries S1 and small arteries S2 in renal transplant recipients (each p renal allograft (p ...-Wallis test between groups). It is concluded that impairment of renal allograft function is associated with an increased arterial stiffness in renal transplant recipients....

  7. Oily skin

    ... keep your skin clean using warm water and soap, or a soapless cleanser. Clean your face with astringent pads if frequent face washing causes irritation. Use only water-based or oil-free cosmetics if you have oily skin. Your ...

  8. Your Skin

    ... your body. Without skin, people's muscles, bones, and organs would be hanging out all over the place. Skin holds everything together. It also: protects our bodies helps keep our bodies at just the right temperature allows us to have the sense of touch Don't Miss Your Epidermis The ...

  9. Treatment of chronic osteomyelitis with one-stage allograft

    LU Wei-ju; LI Bin; BAO Ni-rong; QIAN Hong-bo; ZENG Xiao-feng; XU Bin; CHEN Yong; ZHAO Jian-ning


    Objective: To avoid disadvantages of two-stage cancellus bone autograft, we investigated the feasibility of one-stage allograft for reconstructing the bone defect resulting from debridement of chronic osteomyelitis in limbs.Methods: Between Feb. 1999 and Apr. 2004, 35 cases of chronic osteomyelitis (8 cases of nonunion )underwent one-stage allograft after debridement in our hospital.Results: Thirty-five cases were followed up for an average period of 28 months (range, 13 to 55 months), in which 32 cases (91.43%) were found no infection, and 3cases (8.57 %) were confirmed recurrence of infection.Four out of 8 cases of bone nonunion healed in 9.5 months on average (range, 3 to 12 months), and another case also acquired union after redebridement and autograft of ilium due to infection recurrence 35 days after surgery.Renonunion occurred in 3 cases, 2 out of whom healed after secondary operation with autograft. One case of renonunion and 2 cases of infection recurrence refused further treatment.Conclusions: A high rate of infection arrest can be attained when one-stage allograft is used to reconstruct the bone defect of chronic osteomyelitis after debridement in limbs. Therefore, chronic osteomyelitis should not be regarded as a contraindication to one-stage allogeneic bone grafting. Renonuion, however, achieves a relatively high rate, especially in cases of segmental bone defect.

  10. Multidetector computed tomography findings of spontaneous renal allograft ruptures

    Basaran, C. [Department of Radiology, Baskent University Faculty of Medicine, Ankara (Turkey)], E-mail:; Donmez, F.Y.; Tarhan, N.C.; Coskun, M. [Department of Radiology, Baskent University Faculty of Medicine, Ankara (Turkey); Haberal, M. [Department of General Surgery, Baskent University Faculty of Medicine, Ankara (Turkey)


    Aim: To describe the characteristics of spontaneous renal allograft rupture using multidetector computed tomography (MDCT). Method: Five patients with spontaneous renal allograft rupture, as confirmed by pathologic examination, were referred to our institution between 1985 and 2008. The clinical records and preoperative MDCT findings of the patients were studied retrospectively. Results: Clinical and/or histological findings were consistent with acute rejection in all cases. Using MDCT, disruption of the capsular integrity and parenchymal rupture was seen in four patients. Four of the five patients showed decreased enhancement and swollen grafts. Perirenal (n = 4), subcapsular (n = 1), and intraparenchymal (n = 1) haematomas were also seen. In the patient with an intraparenchymal haematoma there was no disruption of capsular integrity, but capsular irregularities were seen near the haematoma. Conclusion: MDCT is a useful investigative tool for the evaluation of suspected spontaneous renal allograft rupture. As well as a swollen graft, disruption of the capsule, parenchyma, and/or haematoma should prompt the radiologist to consider this diagnosis.

  11. Renal allograft tuberculosis with infected lymphocele transmitted from the donor.

    Al-Nesf, Maryam Ali; Al-Ani, Omar Isam; Al-Ani, Ahmed Abdul-Rahman; Rashed, Awad Hamed


    Transmission of tuberculosis (TB) from a donor through renal transplantation is a rare incident. We are reporting a 53-year-old Qatari woman diagnosed with renal allograft TB infection. The disease was confirmed by isolation of Mycobacterium tuberculosis from fluid from the lymphocele and demonstration of caseating granuloma in graft biopsy with acid-fast bacilli seen on Ziehl-Neelsen staining. The diagnosis was made quite early post-transplantation. The presence of the granuloma, which is unusual with patients on intensive immunosuppressant medications, suggests that transmission of the infection occurred from the donor rather than from the activation of latent infection. In reviewing the literature, we found ten case reports of TB in transplanted kidney with transmission of TB infection from the donor. The presence of TB in lymphocele in association with the infected transplant by TB, to the best of our knowledge, was reported only once in the literature. Our case had unfavorable outcome and ended by renal allograft nephrectomy and hemodialysis. We are presenting this case of TB infection of renal allograft and lymphocele diagnosed early post-transplantation transmitted from the donor and pertinent review from the literature.

  12. Significance of urinary proteome pattern in renal allograft recipients.

    Suhail, Sufi M


    Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation.

  13. Prolonged fever after Infliximab infusion

    Jennifer; Katz; Michael; Frank


    Pharmacologic management for ulcerative colitis (UC) has recently been expanded to include antitumor necrosis factor (TNF) therapy for severe disease. Infliximab, a chimeric monoclonal antibody directed again TNF α was first tested in patients with Crohn’s disease. In addition to serious infections, malignancy, drug induced lupus and other autoimmune diseases, serum sickness-like reactions, neurological disease, and infusion reactions further complicate the use of Infliximab. We report a case of prolonged fever after Infliximab infusion to treat steroid refractory UC.

  14. Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival.

    Choi, Wungrak; Ji, Yong Woo; Ham, Hwa-Yong; Yeo, Areum; Noh, Hyemi; Jin, Su-Eon; Song, Jong Suk; Kim, Hyeon Chang; Kim, Eung Kwon; Lee, Hyung Keun


    We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1(+)CD11b(+) cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1(+)CD11b(+) cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1(int)CD11b(+) cells, but not Gr-1(hi)CD11b(+) cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-β, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-γ plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1(int)CD11b(+) cells. Furthermore, adoptive transfer of Gr-1(int)CD11b(+) cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1(int)CD11b(+) MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.

  15. Gluteal Compartment Syndrome After Prolonged Immobilisation

    H.L. Liu


    Full Text Available Muscles in the gluteal region are confined by distinct fascial attachments which can potentially result in compartment syndrome. A 74-year-old chronic drinker was admitted to the medical ward after being found drunk on the street. He noticed acute painful swelling of the right side of his buttock the following morning and recalled a slip and fall prior to his blackout. The whole right half of the buttock was tense with erythematous overlying skin. Examination revealed sciatic nerve palsy and myoglobinuria. Emergency fasciotomy and debridement were performed. Intra-operative pressure measurement confirmed a grossly elevated intra-compartmental pressure. Gluteal compartment syndrome is an extremely rare condition and has only been scantily documented previously in case reports. Early diagnosis is crucial but delay recognition is common from lack of knowledge of the condition and readily results in permanent sciatic nerve injury and acute renal shutdown from myoglobinuria. Awareness of the condition, early diagnosis and prompt exploration provide the only chance of avoiding these devastating consequences. Acute swelling diffusely affecting the whole or one side of the buttock, a history of trauma and prolonged local pressure impingement associated with pain out of proportion to the clinical signs should raise a suspicion of this rare condition.

  16. The value of urine cytologic examination findings in the diagnosis of the acute renal allograft rejection

    Tatomirović Željka


    Full Text Available Background. Acute rejection of allograft is one of the most serious complications of renal transplantation that requires fast and precise diagnostic approach. In this paper our experience in cytologic urinalysis as a diagnostic method of the acute renal allograft rejection was reviewed. Methods. The study group included 20 of 56 patients with transplanted kidneys who were assumed for the acute allograft rejection according to allograft dysfunction and/or urine cytology findings. Histological findings confirmed allograft rejection in 4 patients. Urine sediment obtained in cytocentrifuge was air-dried and stained with May-Grunwald-Giemsa. Acute allograft rejection was suspected if in 10 fields under high magnification 15 or more lymphocytes with renal tubular cells were found. Results. Acute transplant rejection occured in 32.1% patients. In 15 patients clinical findings of the acute renal allograft rejection corresponded with cytological and histological findings (in the cases in which it was performed. Three patients with clinical signs of the acute allograft rejection were without cytological confirmation, and in 2 patients cytological findings pointed to the acute rejection, but allograft dysfunction was of different etiology (acute tubular necrosis, cyclosporine nephrotoxicity. In patients with clinical, cytological and histological findings of the acute allograft rejection urine finding consisted of 58% lymphocytes, 34% neutrophilic leucocytes and 8% monocytes/macrophages on the average. The accuracy of cytologic urinalysis related to clinical and histological finding was 75%. Conclusion. Urine cytology as the reliable noninvasive, fast and simple method is appropriate as the a first diagnostic line of renal allograft dysfunction, as well as for monitoring of the graft function.

  17. Differentiation between Acute Skin Rejection in Allotransplantation and T-Cell Mediated Skin Inflammation Based on Gene Expression Analysis

    Dolores Wolfram


    Full Text Available Advances in microsurgical techniques and immunosuppressive medication have rendered transplantation of vascularized composite allografts possible, when autologous tissue is neither available nor sufficient for reconstruction. However, skin rejection and side effects of long-term immunosuppression still remain a major hurdle for wide adoption of this excellent reconstructive technique. Histopathologic changes during acute skin rejection in vascular composite allotransplantation often mimic inflammatory skin disorders and are hard to distinguish. Hence, the identification of diagnostic and therapeutic markers specific for skin rejection is of particular clinical need. Here we present novel markers allowing for early differentiation between rejection in hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7, Il18, and Il1b expression is most indicative of distinguishing skin rejection from skin inflammatory disorders. Gene expression levels varied significantly across skin types and regions, indicating localization specific mechanism of leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene expression levels differed significantly between rejection and inflammation, independent of the skin type. In synopsis of the RNA expression profile and previously assessed protein expression, the Il1 family appears as a promising option for accurate skin rejection diagnosis and, as a following step, for development of novel rejection treatments.

  18. Estudo da ação da estreptoquinase e do alopurinol em retalhos cutâneos em ilha submetidos à isquemia prolongada: estudo experimental em ratos Study of the effect of streptokinase and allopurinol in island skin flaps submitted to prolonged ischemia: experimental study in rats

    Tatiana de Moura


    Full Text Available OBJETIVO: Estabelecer relação entre a sobrevivência de retalhos cutâneos em ilha submetidos à isquemia prolongada e o uso da estreptoquinase e do alopurinol administrados após o período de isquemia prolongado. MÉTODOS: Foram utilizados 48 ratos machos da raça Wistar, com peso entre 300 e 350g, divididos em quatro grupos com 12 cada um, sendo; grupo controle, alopurinol, estreptoquinase e associação de alopurinol com estreptoquinase, submetidos à dissecção de retalho epigástrico em ilha, seguido de clampeamento do feixe vascular, por oito horas em isquemia mista normotérmica. Após este período, as pinças foram retiradas e cada animal recebeu o esquema terapêutico proposto através de injeção intravenosa. A análise da sobrevivência dos retalhos foi realizada no sétimo dia de pós-operatório. Foram realizadas análises descritivas (% de área necrótica e de variâncias, bem como comparações múltiplas de Dunnett T3 entre os quatro grupos e o teste da mediana. RESULTADOS: O grupo controle apresentou em média 79,88% de necrose da área total. Aqueles que receberam alopurinol apresentaram em média 64,05% de necrose e o grupo que recebeu estreptoquinase apresentou em média 55,52% de necrose. Com a associação das duas drogas, os ratos apresentaram 54,30% em média de necrose do retalho. Aplicando o teste Dunnett e o teste da mediana verificou-se de que o grupo estreptoquinase é o com menor percentual de necrose neste estudo. CONCLUSÃO: A administração sistêmica da estreptoquinase após oito horas de isquemia mista normotérmica resultou em aumento da sobrevivência de retalhos epigástricos em ilha em ratos, quando comparada à administração de alopurinol, associação do alopurinol e estreptoquinase e do grupo controle.BACKGROUND: To establish a relation between the survival rate of island skin flaps submitted to prolonged ischemia and the effect of streptokinase and allopurinol administered after the ischemic

  19. Septic arthritis with Staphylococcus lugdunensis following arthroscopic ACL revision with BPTB allograft.

    Mei-Dan, Omer; Mann, Gideon; Steinbacher, Gilbert; Ballester, Soleda J; Cugat, Ramon Bertomeu; Alvarez, Pedro Diaz


    Septic arthritis following anterior cruciate ligament reconstruction is an uncommon but a serious complication resulting in six times greater hospital costs than that of uncomplicated ACL surgery and an inferior postoperative activity level. Promptly initiating a specific antibiotic therapy is the most critical treatment, followed by open or arthroscopic joint decompression, debridement and lavage. Staphylococcus lugdunensis is a coagulase-negative staphylococcus predominantly infecting the skin and soft tissue. The few reported cases of bone and joint infections by S. lugdunensis indicate that the clinical manifestations were severe, the diagnosis elusive, and the treatment difficult. If the microbiology laboratory does not use the tube coagulase (long) test to confirm the slide coagulase test result, the organism might be misidentified as Staphylococcus aureus. S. lugdunensis is more virulent than other coagulase-negative staphylococcus; in many clinical situations it behaves like S. aureus, further increasing the confusion and worsening the expected outcome. S. lugdunensis is known to cause infective endocarditis with a worse outcome, septicemia, deep tissue infection, vascular and joint prosthesis infection, osteomyelitis, discitis, breast abscess, urine tract infections, toxic shock and osteitis pubis. We present the first case report in the literature of septic arthritis with S. lugdunensis following arthroscopic ACL revision with bone-patellar-tendon-bone allograft.

  20. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.


    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  1. Acetabular allograft reconstruction in total hip arthroplasty. Part I: Current concepts in biomechanics.

    Stiehl, J B


    Allograft reconstruction has become an essential tool for restoration of acetabular bone stock lost in failed total hip arthroplasty or resected in tumor reconstruction. This first segment of a two-part review will discuss the current status of allograft applications, together with pertinent biologic and biochemical aspects. Part II will address surgical considerations and recent clinical experience.

  2. Treatment of Steroid-Resistant Acute Renal Allograft Rejection With Alemtuzumab

    van den Hoogen, M. W. F.; Hesselink, D. A.; van Son, W. J.; Weimar, W.; Hilbrands, L. B.


    Steroid-resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid-resistant renal allograft rejection treated with alemtuzumab (1530 mg s.c. on 2 subseq

  3. Treatment of steroid-resistant acute renal allograft rejection with alemtuzumab

    Hoogen, M.W. van den; Hesselink, D.A.; Son, W.J. van; Weimar, W.; Hilbrands, L.B.


    Steroid-resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid-resistant renal allograft rejection treated with alemtuzumab (15-30 mg s.c. on 2 subse

  4. B cells assist allograft rejection in the deficiency of protein kinase c-theta.

    Yan, Wenwei; Xu, Rui; Ma, Lian Li; Han, Wei; Geevarghese, Sunil K; Williams, Phillip E; Sciammas, Roger; Chong, Anita S; Yin, Deng Ping


    We have previously shown that mice deficient in protein kinase C theta (PKCθ) have the ability to reject cardiac allografts, but are susceptible to tolerance induction. Here we tested role of B cells in assisting alloimmune responses in the absence of PKCθ. Mouse cardiac allograft transplantations were performed from Balb/c (H-2d) to PKCθ knockout (PKCθ(-/-)), PKCθ and B cell double-knockout (PBDK, H-2b) mice and wild-type (WT) C57BL/6 (H-2b) mice. PBDK mice spontaneously accepted the allografts with the inhibition of NF-κB activation in the donor cardiac allograft. Anti-B cell antibody (rituximab) significantly delayed allograft rejection in PKCθ(-/-), but not in WT mice. Co-transfer of PKCθ(-/-) T plus PKCθ(-/-) B cells or primed sera triggered allograft rejection in Rag1(-/-) mice, and only major histocompatibility complex class II-enriched B cells, but not class I-enriched B cells, were able to promote rejection. This, together with the inability of PKCθ(-/-) and CD28(-/-) double-deficient (PCDK) mice to acutely reject allografts, suggested that an effective cognate interaction between PKCθ(-/-) T and B cells for acute rejection is CD28 molecule dependent. We conclude that T-B cell interactions synergize with PKCθ(-/-) T cells to mediate acute allograft rejection.

  5. Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective.

    Demetris, Anthony J; Lunz, John G; Randhawa, Parmjeet; Wu, Tong; Nalesnik, Michael; Thomson, Angus W


    Several factors acting together have recently enabled clinicians to seriously consider whether chronic immunosuppression is needed in all solid organ allograft recipients. This has prompted a dozen or so centers throughout the world to prospectively wean immunosuppression from conventionally treated liver allograft recipients. The goal is to lessen the impact of chronic immunosuppression and empirically identify occasional recipients who show operational tolerance, defined as gross phenotype of tolerance in the presence of an immune response and/or immune deficit that has little or no significant clinical impact. Rare operationally tolerant kidney allograft recipients have also been identified, usually by single case reports, but only a couple of prospective weaning trials in conventionally treated kidney allograft recipients have been attempted and reported. Pre- and postweaning allograft biopsy monitoring of recipients adds a critical dimension to these trials, not only for patient safety but also for determining whether events in the allografts can contribute to a mechanistic understanding of allograft acceptance. The following is based on a literature review and personal experience regarding the practical and scientific aspects of biopsy monitoring of potential or actual operationally tolerant human liver and kidney allograft recipients where the goal, intended or attained, was complete withdrawal of immunosuppression.

  6. Scapular allograft reconstruction after total scapulectomy: surgical technique and functional results

    Capanna, R.; Totti, F.; Geest, I.C.M. van der; Muller, D.A.


    HYPOTHESIS: Scapular allograft reconstruction after total scapulectomy preserving the rotator cuff muscles is an oncologically safe procedure and results in good functional outcome with a low complication rate. METHODS: The data of 6 patients who underwent scapular allograft reconstruction after a

  7. The renal arterial resistive index and stage of chronic kidney disease in patients with renal allograft

    Winther, Stine O; Thiesson, Helle C; Poulsen, Lene N;


    The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft.......The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft....

  8. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat.

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J


    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague-Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation.

  9. Aging skin.

    Bolognia, J L


    Aging of the skin is a composite of actinic damage, chronologic aging, and hormonal influences. The majority of changes associated with aging, such as wrinkles and solar lentigines ("liver spots"), are due to photoaging and reflect cumulative sun exposure as well as skin pigmentation. Classically, chronologic aging includes those cutaneous changes that occur in non-sun-exposed areas, such as the buttocks, and are observed in both men and women. A clinical example would be soft tissue sagging due to elastic fiber degeneration. In women, investigations into the effect of hormones on aging of the skin have concentrated on estrogens; in men, there have been a limited number of studies on the influence of testosterone. The latter have shown an age-dependent decrease in tissue androgens in pubic skin, but not scrotal or thigh skin. To date, age has not been shown to have an effect on androgen receptor binding, although a decrease in foreskin 5 alpha-reductase activity with increasing age has been described. In fibroblast cultures from foreskins, there have been conflicting results as to whether 5 alpha-reductase activity decreases in an age-dependent manner. Some of the skin changes that have been categorized as secondary to chronologic aging, such as decreased sebaceous gland activity and decreased hair growth, may actually represent a decline in the concentration of tissue androgens with increasing age. The influence of androgens on age-related changes in keratinocyte and fibroblast function remains speculative.

  10. A strategy for skin irritation testing.

    Robinson, Michael K; Perkins, Mary A


    Skin irritation safety testing and risk assessment for new products, and the ingredients they contain, is a critical requirement before market introduction. In the past, much of this skin testing required the use of experimental animals. However, new current best approaches for skin corrosion and skin irritation testing and risk assessment are being defined, obviating the need for animal test methods. Several in vitro skin corrosion test methods have been endorsed after successful validation and are gaining acceptance by regulatory authorities. In vitro test methods for acute, cumulative (repeat exposure), and chronic (prolonged exposure) skin irritation are under development. Though not yet validated, many are being used successfully for testing and risk assessment purposes as documented through an expanding literature. Likewise, a novel acute irritation patch test in human subjects is providing a valid and ethical alternative to animal testing for prediction of chemical skin irritation potential. An array of other human test methods also have been developed and used for the prediction of cumulative/chronic skin irritation and the general skin compatibility of finished products. The development of instrumental methods (e.g., transepidermal water loss, capacitance, and so on) has provided the means for analyzing various biophysical properties of human skin and changes in these properties caused by exposure to irritants. However, these methods do not directly measure skin inflammation. A recently introduced skin surface tape sampling procedure has been shown to detect changes in skin surface cytokine recovery that correlate with inflammatory skin changes associated with chemical irritant exposures or existing dermatitis. It holds promise for more objective quantification of skin irritation events, including subclinical (sensory) irritation, in the future.

  11. Effects of ureteral stents on risk of bacteriuria in renal allograft recipients.

    Chordia, P; Schain, D; Kayler, L


    Placement of ureteral stents at the time of renal transplantation is thought to decrease the incidence of postoperative complications, such as anastomotic leakage and stenosis. However, stents may also predispose to post-transplantation urinary tract infection, which can lead to increased risks of graft dysfunction, sepsis, and death. The aim of this study was to analyze the risk of post-transplantation bacteriuria with ureteral stent placement in renal allograft recipients. A retrospective single-center analysis was conducted to investigate the incidence of bacteriuria in all renal allograft recipients transplanted between January 2007 and March 2009. Recipients were categorized as in the nonstent group (NSTG) or the stent group (STG). Stent removal was performed per protocol at 6 weeks, and all patients were followed for at least 1 year post transplantation. In the NSTG, the incidence of bacteriuria was assessed at 0-6, 6-12, and 12 weeks to 1 year post transplantation. In the STG, bacteriuria was assessed prior to stent removal, 6 weeks after stent removal, and thereafter until 1 year post transplantation. A total of 395 renal allograft recipients, 183 in the NSTG and 212 in the STG groups, were studied. The overall incidence of bacteriuria within 1 year post transplantation was similar between NSTG and STG (28.0 vs. 24.0%, P = 0.38). No difference was found in the incidence of bacteriuria when NSTG and STG were compared at 0-6 weeks or prior to stent removal (9.7% vs. 9.1%, P = 0.81), at 6-12 weeks, or 6 weeks after stent removal (6.7% vs. 5.8%, P = 0.75), and thereafter for 1 year post transplantation (13.3% vs. 10.8%, P = 0.46). The incidence of graft failure at 1 year was similar in NSTG and STG (6.2% vs. 4.9%, P = 0.6). Urinary anastomotic leakage occurred in none of the NSTG and 2 of the STG recipients. On multivariate analysis, risk factors for bacteriuria were female recipient gender (odds ratio [OR] 2.5, 95% confidence interval [CI

  12. Doppler Ultrasound in Chronic Renal Allograft Dysfunction : Can Acute Rejection be Predicted

    Kim, Eun Kyung; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Ki Whang; Park, Ki Ill; Chung, Hyun Joo [Yonsei University College of Medicine, Seoul (Korea, Republic of)


    To investigate Doppler sonographic findings valuable for detecting acute rejection in transplanted kidney with chronic allograft dysfunction. Forty-three renal allografts who underwent renal Doppler sonography and renal biopsy due to chronic allograft dysfunction were included. According to histopathologic findings, patients were classified into 2 groups: chronic component only(group 1, n=30) and acute rejection with or without chronic component 2 groups were performed. No definite difference in radio of renal size, cortical echogenecity, corticomedullary differentiation was noted between group 1 and group 2.Resistive index was 0.61{+-}0.18 in group 1 and 0.64{+-}0.22 in group 2, which showed no statistically significant difference. Characteristic Doppler sonographic findings suggesting acute rejection in cases of chronic allograft dysfunction were not found inauther's study. Therefore, minimal invasive renal biopsy to determine histopathologic status of transplanted kidney is essential in evaluation of the chronic allograft dysfunction

  13. Three-dimensional virtual bone bank system workflow for structural bone allograft selection: a technical report.

    Ritacco, Lucas Eduardo; Farfalli, German Luis; Milano, Federico Edgardo; Ayerza, Miguel Angel; Muscolo, Domingo Luis; Aponte-Tinao, Luis


    Structural bone allograft has been used in bone defect reconstruction during the last fifty years with acceptable results. However, allograft selection methods were based on 2-dimensional templates using X-rays. Thanks to preoperative planning platforms, three-dimensional (3D) CT-derived bone models were used to define size and shape comparison between host and donor. The purpose of this study was to describe the workflow of this virtual technique in order to explain how to choose the best allograft using a virtual bone bank system. We measured all bones in a 3D virtual environment determining the best match. The use of a virtual bone bank system has allowed optimizing the allograft selection in a bone bank, providing more information to the surgeons before surgery. In conclusion, 3D preoperative planning in a virtual environment for allograft selection is an important and helpful tool in order to achieve a good match between host and donor.

  14. Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure: An Observational Cohort Study.

    Naesens, Maarten; Lerut, Evelyne; Emonds, Marie-Paule; Herelixka, Albert; Evenepoel, Pieter; Claes, Kathleen; Bammens, Bert; Sprangers, Ben; Meijers, Björn; Jochmans, Ina; Monbaliu, Diethard; Pirenne, Jacques; Kuypers, Dirk R J


    Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria 3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P3 months after transplant (AUC 0.73, P1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.

  15. Clinical utility of labeled cells for detection of allograft rejection and myocardial infarction

    Fawwaz, R.A.


    The choice of a specific radiolabeled blood component for use in detection of allograft rejection depends on several factors including the immunosuppressive agents used, the type of organ allografted, and particularly the length of time the allograft resides in the host and the duration of rejection. To date, only the use of 111In-labeled platelets in renal allograft recipients immunosuppressed with azathioprine and corticosteroids has shown clinical promise in the detection of early allograft rejection. Radiolabeled blood components are unlikely to play a significant role in detection of myocardial infarction. The use of these agents for monitoring therapeutic interventions or as indicators of prognosis in patients with myocardial infarction continues to be investigated.

  16. Abdominal aortic aneurysm repair in patient with a renal allograft: a case report.

    Kim, Hyung-Kee; Ryuk, Jong-Pil; Choi, Hyang Hee; Kwon, Sang-Hwy; Huh, Seung


    Renal transplant recipients requiring aortic reconstruction due to abdominal aortic aneurysm (AAA) pose a unique clinical problem. The concern during surgery is causing ischemic injury to the renal allograft. A variety of strategies for protection of the renal allograft during AAA intervention have been described including a temporary shunt, cold renal perfusion, extracorporeal bypass, general hypothermia, and endovascular stent-grafting. In addition, some investigators have reported no remarkable complications of the renal allograft without any specific measures. We treated a case of AAA in a patient with a renal allograft using a temporary aortofemoral shunt with good result. Since this technique is safe and effective, it should be considered in similar patients with AAA and previously placed renal allografts.

  17. Skin Cancer Prevention

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Prevention (PDQ®)–Patient Version What is prevention? ... prevent cancer are being studied. General Information About Skin Cancer Key Points Skin cancer is a disease ...

  18. Skin Cancer Screening

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  19. Dry Skin Relief

    ... Advocacy priorities AADA Health System Reform Principles Drug pricing and availability CVS dermatologic formulary restrictions Access to ... Skin care for men Skin care on a budget Skin care products Skin care secrets Skin of ...

  20. The significance of cytologic examination of urine in the diagnosis of renal allograft dysfunction

    Tatomirović Željka


    Full Text Available Background. This paper presents our experience with cytologic examination of urine in diagnosing renal allograft dysfunction. Methods. The study group included 23 patients with renal allograft dysfunction, selected from 56 patients who underwent renal transplantation. Etiologic diagnosis was made according to the clinical picture, histological findings during allograft biopsy, and cytologic examination of urine. Urine sediment was obtained in cytocentrifuge and was air dried and stained with May Grunwald Giemsa. Results. Out of 23 patients with allograft dysfunction in 18 (78.3% patient it was caused by acute rejection, and in 5 (8.9% patients by allograft infarction, cyclosporine nephrotoxicity, acute tubular necrosis and chronic nephropathy. In eighteen patients (78.3% cytologic examination of urine was pathologic, while in 16 (70% clinical and histology findings coincided with urine cytology findings. Out of 18 patients with acute allograft rejection in 15 patients cytologic examination of urine coincided with acute rejection. Out of 7 patients with expressed cyclosporine nephrotoxicity, in 5 cytologic examination of urine confirmed the cause of allograft dysfunction, as well as in one of 2 patients with acute tubular necrosis. Cytologic examination of urine indicated parenchymal damage in 2 patients with reccurent disease (membranoproliferative and focal sclerosing glomerulonephritis. In 4 of 5 patients suffering from chronic rejection in a year’s monitoring period, urine sediment periodically consisted of lymphocytes, neutrophilic leucocytes, monocyte/macrophages, tubular cells and cilindres, without the predominance of any cell type. In 3 patients allograft dysfunction was caused by infective agents (bacteria, fungus cytomegalovirus. Conclusion. Cytologic examination of urine might be an alternative to histological in diagnosing acute allograft rejection and acute tubular necrosis or nephtotoxicity. Also it might indicate parenchymal

  1. Injury-induced allograft rejection: A rendezvous with evolution.

    Land, Walter G


    Modern immunology, in many ways, is based on three major paradigms: the clonal selection theory, the pattern recognition theory, and the danger/injury theory. The last theory holds that any cell stress and tissue injury, including allograft injury, via induction of damage-associated molecular patterns, induces immunity, including alloimmunity, leading to allograft rejection. On the other hand, the concept precludes that non-self per se induces immunity as proposed by the two former theories. Recently, the danger/injury model has gained considerable acceptance by immunologists, in particular as promoted by new insights into the function of the mammalian gut microbiota, representing a huge assemblage of non-self. Harboring microbiota by hosts is characterized by the fact that harmless noninjurious commensal microbes are protected by innate immunity-based tolerance, whereas intestinal injury-causing pathogenic microbes are immunologically attacked. Plausibility and validity of the danger/injury concept is stringently supported by observations of similar phenomena across the tree of life: the ability of the immune system to discriminate between harmful life-threatening non-self to induce immunity and harmless beneficial non-self to induce tolerance has apparently emerged during evolution. Immune defense responses to injuring/injured non-self (e.g., as reflected by plant resistance to biotic and abiotic stresses on one hand, and allograft rejection on the other hand) as well as immunity-controlled protection of beneficial non-self (e.g., as reflected by microbiota and the fetus of placental mammals) are processes in the interest of evolution and, thus, evolved under pressure across the phylogenetic tree.

  2. Urine Metabolite Profiles Predictive of Human Kidney Allograft Status.

    Suhre, Karsten; Schwartz, Joseph E; Sharma, Vijay K; Chen, Qiuying; Lee, John R; Muthukumar, Thangamani; Dadhania, Darshana M; Ding, Ruchuang; Ikle, David N; Bridges, Nancy D; Williams, Nikki M; Kastenmüller, Gabi; Karoly, Edward D; Mohney, Robert P; Abecassis, Michael; Friedewald, John; Knechtle, Stuart J; Becker, Yolanda T; Samstein, Benjamin; Shaked, Abraham; Gross, Steven S; Suthanthiran, Manikkam


    Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

  3. Diagnosis and management of late hepatic allograft dysfunction

    MEI Jian-min; YU Cong-hui


    Late hepatic allograft dysfunction (LHAD) is common after liver transplantation (LT) and can cause graft failure,retransplantation,or even death.A variety of etiologies including rejection,vascular complications,bile duct complications,recurrent diseases,infections,de novo diseases,neoplasms and drug toxicity can result in LHAD.The recurrent diseases have the potential to become the most serious problems facing LT in the future.It is difficult to differentiate late acute rejection from recurrent viral or autoimmune hepatitis.Accurate diagnosis of the cause of LHAD has therapeutic importance.

  4. Stem cell autograft and allograft in autoimmune diseases.

    De Cata, Angelo; Matarangolo, Angela; Inglese, Michele; Rubino, Rosa; Mazzoccoli, Gianluigi


    Autoimmune diseases are characterized by an insufficiency of immune tolerance and, although treated with a number of useful drugs, may need more unconventional therapeutic strategies for their more severe presentations. Among such unconventional therapeutic approaches, stem cell autograft and allograft have been used, with the aim of stimulating disease remission by modifying the pathogenic mechanisms that induce anomalous responses against self-antigens. Autologous transplantation is performed with the purpose of retuning autoimmune cells, whereas allogeneic transplantation is performed with the purpose of replacing anomalous immune effectors and mediators. In this article, we comprehensively review up-to-date information on the autoimmune diseases for which the transplantation of stem cells is indicated.

  5. Vascularized composite allograft-specific characteristics of immune responses.

    Issa, Fadi


    Vascularized composite allograft (VCA) transplantation, or reconstructive transplantation, has revolutionized the treatment of complex tissue and functional defects. Despite arriving during an age in which the immunology of solid organ transplant rejection has been investigated in much detail, these transplants have offered new perspectives from which to explore the immunobiology of transplantation. VCAs have a number of unique molecular, cellular, and architectural features which alter the character and intensity of the rejection response. While much is yet to be clarified, an understanding of these distinct mechanisms affords new possibilities for the control of immune responses in an effort to improve outcomes after VCA transplantation.

  6. Development of a Vascularized Skin Construct Using Adipose-Derived Stem Cells from Debrided Burned Skin

    Rodney K. Chan


    Full Text Available Large body surface area burns pose significant therapeutic challenges. Clinically, the extent and depth of burn injury may mandate the use of allograft for temporary wound coverage while autografts are serially harvested from the same donor areas. The paucity of donor sites in patients with burns involving large surface areas highlights the need for better skin substitutes that can achieve early and complete coverage and retain normal skin durability with minimal donor requirements. We have isolated autologous stem cells from the adipose layer of surgically debrided burned skin (dsASCs, using a point-of-care stem cell isolation device. These cells, in a collagen—polyethylene glycol fibrin-based bilayer hydrogel, differentiate into an epithelial layer, a vascularized dermal layer, and a hypodermal layer. All-trans-retinoic acid and fenofibrate were used to differentiate dsASCs into epithelial-like cells. Immunocytochemical analysis showed a matrix- and time-dependent change in the expression of stromal, vascular, and epithelial cell markers. These results indicate that stem cells isolated from debrided skin can be used as a single autologous cell source to develop a vascularized skin construct without culture expansion or addition of exogenous growth factors. This technique may provide an alternative approach for cutaneous coverage after extensive burn injuries.

  7. Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester ester nanovector induces donor-specific liver allograft tolerance

    Hu F


    Full Text Available Fanguo Hu,1,* Hanjie Wang,2,* Shuangnan Zhang,2 Yao Peng,2 Lin Su,2 Jin Chang,2 Gang Liu11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin, People’s Republic of China*These authors contributed equally to this workAbstract: Toll-like receptors (TLRs activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88, which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester(HGPAE nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88 (pMyD88. We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88 expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88 as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced.Keywords: immune recognition, allograft rejection, MyD88, short hairpin RNA (shRNA, gene delivery, PAE

  8. Indium-111 labelled platelet scintigraphy can predict the immunological origin of fever in patients on dialysis carrying a non-functioning renal allograft

    Fuster, D.; Lomena, F.; Piera, C.; Setoain, F.J.; Laterza, C.; Herranz, R.; Setoain, J. [Nuclear Medicine Dept., Hospital Clinic de Barcelona (Spain); Torregrosa, J.V.; Oppenheimer, F. [Renal Transplant Unit, Hospital Clinic de Barcelona (Spain)


    The purpose of this study was to evaluate the usefulness of labelled platelet scintigraphy in the differential diagnosis of a prolonged febrile syndrome (PFS) in patients on dialysis carrying a non-functioning renal allograft. We prospectively performed an indium-111 mercaptopyridine-labelled platelet scan on 91 patients (54 men, 37 women; mean age 39.6{+-}12 years). The mean duration of PFS was 35 days (range 7-122). Forty-six of the 91 patients underwent steroid therapy (2- 10 mg/day). Platelet labelling was carried out following Thakur's method. Platelet scans were performed 48 h after reinjection of labelled platelets. The platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft ROI by cpm/pixel in a mirror background ROI. The final diagnosis of PFS was established depending on the outcome after treatment. In 61/91 patients the fever had an immunological origin because it disappeared after graft embolisation or transplantectomy. In 30/91 patients the PFS disappeared after antibiotic therapy (non-immunological origin). The PUI in patients with immunological PFS was 1.80{+-}0.7, while in patients with non-immunological PFS it was 1.12{+-}0.1 (P<0.05). When a PUI of {>=}1.5 was considered as the threshold to establish PFS of immunological origin, the sensitivity of platelet scan was 76%, the specificity 100%, and the negative and positive predictive values 69% and 100%, respectively. In patients classified with immunological PFS who underwent steroid therapy, the PUI was significantly lower than in patients without steroids (P<0.05). These results suggest that {sup 111}In-labelled platelet scintigraphy can accurately predict an immunological PFS in patients on dialysis carrying a non-functioning renal allograft. Therapy with steroids could reduce the sensitivity of {sup 111}In-labelled platelet scintigraphy in detecting immunological PFS. (orig.)

  9. Treatment of postcatheterization femoral arteriovenous fistulas with simple prolonged bandaging

    ZHOU Tao; LIU Zhen-jiang; ZHOU Sheng-hua; SHEN Xiang-qian; LIU Qi-ming; FANG Zhen-fei; HU Xin-qun; LI Jiang; L(U) Xiao-lin


    Background The methods for the treatment of postcatheterization femoral arteriovenous fistulas (AVF-s) - simple observation, ultrasound guided compression, covered stents implantation and coil embolization have poor outcome.Surgery is the standard method for treatment of femoral AVFs, but it is a traumatic operation. In this study, we report the results of the treatment of postcatheterization femoral AVFs by simple prolonged compressing bandage.Methods To treat iatrogenic femoral AVFs caused by transfemoral catheterization, prolonged binding with elastic or common bandage was applied in 16 cases. Catheterization was performed in 7 cases for radiofrequency current catheter ablation, in 4 for occlusion of congenital heart disease, in 3 for percutaneous coronary intervention, in 1 for coronary angiography and in 1 for right heart catheterization.Results All iatrogenic femoral AVFs were healed after simple binding with elastic or common bandage for 4-46 days (mean (15±10) days). During the period of binding, local skins ulceration occurred at puncture site in two cases and femoral vein thrombus was found in one patient. During 6-24 months (mean (11.8±3.6) months) followup with colour Doppler ultrasonography, no recurrent arteriovenous shunting or other complications were observed.Conclusion The results suggest that simple prolonged bandaging for postcatheterization femoral AVFs is an effective and economical procedure.

  10. Hearing Benefit in Allograft Tympanoplasty Using Tutoplast Processed Malleus

    Anja Lieder


    Full Text Available Objectives. Tutoplast processed human cadaveric ossicular allografts are a safe alternative for ossicular reconstruction where there is insufficient material suitable for autograft ossiculoplasty. We present a series of 7 consecutive cases showing excellent air-bone gap closure following canal-wall-down mastoidectomy for cholesteatoma and reconstruction of the middle ear using Tutoplast processed malleus. Patients and Methods. Tympanoplasty with Tutoplast processed malleus was performed in seven patients to reconstruct the middle ear following canal-wall-down mastoidectomy in a tertiary ENT centre. Main Outcome Measures. Hearing improvement and recurrence-free period were assessed. Pre-and postoperative audiograms were performed. Results. The average pre operative hearing loss was 50 ± 13 dB, with an air-bone gap of 33 ± 7 dB. Post operative audiograms at 25 months demonstrated hearing thresholds of 29 ± 10 dB, with an air-bone gap of 14 ± 6 dB. No prosthesis extrusion was observed, which compares favourably to other commercially available prostheses. Conclusions. Tutoplast processed allografts restore conductive hearing loss in patients undergoing mastoidectomy and provide an excellent alternative when there is insufficient material suitable for autograft ossiculoplasty.

  11. A prospective study on knee proprioception after meniscal allograft transplantation.

    Thijs, Y; Witvrouw, E; Evens, B; Coorevits, P; Almqvist, F; Verdonk, R


    The meniscus plays an important role in the proprioceptive ability of the knee joint. The aim of this prospective study was to assess the short-term influence of a meniscus replacement on the proprioception of the knee. Fourteen patients who had undergone a fresh meniscal allograft transplantation between May 2001 and June 2003 were tested pre-operatively and 6 months post-operatively. Disability regarding pain, stiffness and functionality of the affected knee during daily activities was measured by the Western Ontario and McMaster Universities Arthritis (WOMAC) scale. The knee joint position sense was assessed using the Biodex System 3 isokinetic dynamometer. The results of the WOMAC scale showed no significant differences concerning pain, stiffness or knee function between the pre- and post-operative condition of the knee. Assessment of the knee joint position sense at a reference point of 70 degrees of knee flexion revealed a significant improvement of the proprioception of the operated knee at 6 months after surgery compared with the pre-operative condition. The results of this study suggest that although no significant improvement of pain and functionality of the operated knee occurred at this short-term follow-up period, a meniscal allograft transplantation seems to have a significant positive effect on the joint position sense of the previously meniscectomised knee.

  12. High-Fat Diet-Induced Obesity Enhances Allograft Rejection.

    Molinero, Luciana L; Yin, Dengping; Lei, Yuk Man; Chen, Luqiu; Wang, Ying; Chong, Anita S; Alegre, Maria-Luisa


    Obesity promotes a state of low-grade inflammation that exacerbates chronic inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation, the survival of organs transplanted into obese patients is reduced compared with allografts in lean recipients. However, whether this is due to increased alloimmunity remains to be addressed conclusively. We used a mouse model of high-fat diet (HFD)-induced obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic splenocyte immunization in vivo, and allogeneic heart transplantation. Our results indicate that HFD altered the composition and phenotype of splenic antigen-presenting cells that led to their enhanced capacity to stimulate T cells. Immunization with allogeneic splenocytes in vivo resulted in increased alloreactivity, as determined by IFNγ production. Moreover, cardiac allograft rejection in HFD mice was modestly accelerated compared to aged-matched control animals fed a low-fat diet, correlating with enhanced alloreactive T cell function. Our results highlight the increased alloresponse triggered by HFD-induced obesity and its negative impact on transplant outcome.

  13. De novo C3 glomerulonephritis in a renal allograft.

    Nahm, Ji Hae; Song, Seung Hwan; Kim, Yu Seun; Cheong, Hae-Il; Lim, Beom Jin; Kim, Beom Seok; Jeong, Hyeon Joo


    C3 glomerulonephritis (C3GN) is a recently described, rare glomerular disease characterized by predominant or sole glomerular C3 deposits. Morphologic features of C3GN are similar to those of dense deposit disease (DDD); however, ribbon-like intramembranous electron-dense deposits are absent in the former. We report a case of de novo C3GN in a renal allograft with morphologic transformation to DDD. A 6-year-old boy presented with congenital left renal agenesis and right ureteropelvic junction obstruction. The patient underwent pyeloplasty but experienced recurrent urinary tract infections. At the age of 22 years, he received a renal allograft from a living related donor. C3GN was diagnosed after 1 year of transplantation; initial histology showed minimal mesangiopathy and this progressed to mesangial proliferation and membranoproliferative features over the next 7 years. Serum creatinine levels were stabilized with anti-rejection treatments for combating repeated episodes of acute rejection; however, glomerular and tubular band-like electron-dense deposits became evident.

  14. Effects of subcutaneous implant of peripheral nerve allograft on the regeneration of defected sciatic nerve

    Mingtang Gao; Dianming Jiang; Hong An


    BACKGROUND: Some experimental studies demonstrate that subcutaneous implant of allograft can significantly decrease lymphocyte infiltration and reduce immunological reaction. However, compared with autologous nerve grafting, what is the effect of nerve regeneration after repair?OBJECTIVE: To observe the local nervous status of the detected part of sciatic nerve repaired through subcutaneously implanting peripheral nerve allograft, and compare the effect with fresh autologous nerve grafting.DESIGN: Contrast observation.SETTING: Departments of Orthopaedics of Zhengzhou Fifth People's Hospital and First Hospital Affiliated to Chongqing Medical University.MATERIALS: Totally 30 healthy adult Wistar male rats, with body mass of (200±20)g, were enrolled. Optical microscope (Olympus biological microscope BHS, Japan), Electron microscope (H-600, Japan),CM-2000 biomedical image analysis system (CM-2000,Beihang) and myoelectricity scanner (KEYPOINT,Denmark) were used in this experiment.METHODS: This experiment was carried out in the Orthopaedic Laboratory of Chongqing Medical University between October 2000 and April 2002. ① Six rats were chosen as the donors for allogenic nerve grafting,and 15 mm sciatic nerve segment was chosen as graft. The other rats were randomly divided into two groups: allogenic nerve grafting group and autologous nerve grafting group, with 12 rats in each group. In the allogenic nerve grafting group, a skin incision was made on the posterior side of right thigh, and subcutaneous blunt dissection was performed prorsally a little, then allograft was implanted. Two weeks later, sciatic nerve was exposed at the posterior side of left thigh and cut respectively at 5 mm and another 10 mm away from pelvis. The donor nerve (with connective tissue veil) implanted subcutaneously on the right thigh was taken out. Sectioned connective tissue at the proximal end was trimmed and that at the distal end as done but reserved 10 mm in length, and inosculated

  15. Long-term outcomes of allograft reconstruction of the anterior cruciate ligament.

    Lenehan, Eric A; Payne, W Barrett; Askam, Brad M; Grana, William A; Farrow, Lutul D


    Recent studies have found higher rates of failed reconstruction of the anterior cruciate ligament (ACL) with use of allograft when compared with autograft reconstruction. To evaluate the long-term outcomes of allograft ACL reconstruction, we retrospectively reviewed the cases of all patients who underwent allograft (n=99) or autograft (n=24) ACL reconstruction by 2 senior surgeons at a single institution over an 8-year period. Seventeen (17%) of the 99 allograft reconstructions required additional surgery. Reoperation and revision ACL reconstruction rates (30.8% and 20.5%, respectively) were much higher for patients 25 years of age or younger than for patients older than 25 years. In our cohort of NCAA (National Collegiate Athletic Association) Division I athletes, the revision ACL reconstruction rate was 62% for allograft ACL reconstruction and 0% for autograft reconstruction. Our study found that reoperation and revision rates for irradiated soft-tissue allograft ACL reconstruction were higher than generally quoted for autograft reconstruction. Given the extremely high graft failure rates in patients younger than 25 years, we recommend against routine use of irradiated soft-tissue allograft for ACL reconstruction in younger patients.

  16. Renal allograft loss in the first post-operative month: causes and consequences.

    Phelan, Paul J


    Early transplant failure is a devastating outcome after kidney transplantation. We report the causes and consequences of deceased donor renal transplant failure in the first 30 d at our center between January 1990 and December 2009. Controls were adult deceased donor transplant patients in the same period with an allograft that functioned >30 d. The incidence of early graft failure in our series of 2381 consecutive deceased donor transplants was 4.6% (n = 109). The causes of failure were allograft thrombosis (n = 48; 44%), acute rejection (n = 19; 17.4%), death with a functioning allograft (n = 17; 15.6%), primary non-function (n = 14;12.8%), and other causes (n = 11; 10.1%). Mean time to allograft failure was 7.3 d. There has been a decreased incidence of all-cause early failure from 7% in 1990 to <1% in 2009. Patients who developed early failure had longer cold ischemia times when compared with patients with allografts lasting >30 d (p < 0.001). Early allograft failure was strongly associated with reduced patient survival (p < 0.001). In conclusion, early renal allograft failure is associated with a survival disadvantage, but has thankfully become less common in recent years.

  17. Utility of an allograft tendon for scoliosis correction via the costo-transverse foreman.

    Sun, Dong; McCarthy, Michael; Dooley, Adam C; Ramakrishnaiah, Raghu H; Shelton, R Shane; McLaren, Sandra G; Skinner, Robert A; Suva, Larry J; McCarthy, Richard E


    Current convex tethering techniques for treatment of scoliosis have centered on anterior convex staples or polypropylene tethers. We hypothesized that an allograft tendon tether inserted via the costo-transverse foramen would correct an established spinal deformity. In the pilot study, six 8-week-old pigs underwent allograft tendon tethering via the costo-transverse foreman or sham to test the strength of the transplanted tendon to retard spine growth. After 4 months, spinal deformity in three planes was induced in all animals with allograft tendons. In the treatment study, the allograft tendon tether was used to treat established scoliosis in 11 8-week-old pigs (spinal deformity > 50°). Once the deformity was observed (4 months) animals were assigned to either no treatment group or allograft tendon tether group and progression assessed by monthly radiographs. At final follow-up, coronal Cobb angle and maximum vertebral axial rotation of the treatment group was significantly smaller than the non-treatment group, whereas sagittal kyphosis of the treatment group was significantly larger than the non-treatment group. In sum, a significant correction was achieved using a unilateral allograft tendon spinal tether, suggesting that an allograft tendon tethering approach may represent a novel fusion-less procedure to correct idiopathic scoliosis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:183-192, 2017.

  18. Tc-99m DTPA scans in renal allograft rejection and cyclosporine nephrotoxicity

    Gedroyc, W.; Taube, D.; Fogleman, I.; Neild, G.; Cameron, S.; Maisey, M.


    Renal allograft dysfunction arising from rejection or cyclosporine (CsA) nephrotoxicity can currently only be distinguished reliably by allograft biopsy. We have assessed Technetium (Tc)-99m diethylamine pentacetic acid (DTPA) scanning in 30 CsA-treated patients with allograft dysfunction. Scintigrams were performed during 20 biopsy-proved episodes of rejection and during 14 episodes of CsA nephrotoxicity. These results were compared with the scintigrams of 15 allografts showing stable function. Quantitative indices expressing allograft perfusion (flow index) and function (uptake index) derived from the DTPA scintigrams showed no significant differences between the groups of patients with rejection, CsA nephrotoxicity, or stable or improving function. Similarly, the flow and uptake indices of individual allografts obtained during periods of stable or improving function and then during episodes of dysfunction due to rejection or CsA nephrotoxicity did not significantly change. We conclude that Tc-99m DTPA scintigrams are of limited value in the management of allograft dysfunction in patients immunosuppressed with CsA.

  19. Renal Allograft Torsion: US and CT Imaging Findings of a Rare Posttransplant Complication

    Rohit Dewan


    Full Text Available Vascular torsion is a rare renal transplant complication which requires prompt diagnosis and surgery to salvage allograft function. We report here a case of renal allograft torsion with interesting imaging findings on unenhanced CT and color Doppler ultrasound. A 60-year-old woman with a history of pancreas and kidney transplant presented to the emergency room with nausea, vomiting, abdominal pain, and minimal urine output. Unenhanced CT of the abdomen demonstrated an enlarged and malrotated renal allograft with moderate hydronephrosis. Color Doppler ultrasound demonstrated lack of vascularity within the allograft. The patient was taken urgently to the operating room where the renal allograft was found twisted 360 degrees around the vascular pedicle. After the allograft was detorsed, the color of the kidney returned and the Doppler signals for arterial flow improved. Intraoperative biopsy showed no evidence of infarct or acute cellular rejection. The detorsed kidney was surgically fixed in position in its upper and lower poles. Follow-up ultrasound 1 day later demonstrated normal blood flow to the renal allograft and the serum level of creatinine returned to normal.

  20. Renal Allograft Torsion: US and CT Imaging Findings of a Rare Posttransplant Complication.

    Dewan, Rohit; Dasyam, Anil K; Tan, Henke; Furlan, Alessandro


    Vascular torsion is a rare renal transplant complication which requires prompt diagnosis and surgery to salvage allograft function. We report here a case of renal allograft torsion with interesting imaging findings on unenhanced CT and color Doppler ultrasound. A 60-year-old woman with a history of pancreas and kidney transplant presented to the emergency room with nausea, vomiting, abdominal pain, and minimal urine output. Unenhanced CT of the abdomen demonstrated an enlarged and malrotated renal allograft with moderate hydronephrosis. Color Doppler ultrasound demonstrated lack of vascularity within the allograft. The patient was taken urgently to the operating room where the renal allograft was found twisted 360 degrees around the vascular pedicle. After the allograft was detorsed, the color of the kidney returned and the Doppler signals for arterial flow improved. Intraoperative biopsy showed no evidence of infarct or acute cellular rejection. The detorsed kidney was surgically fixed in position in its upper and lower poles. Follow-up ultrasound 1 day later demonstrated normal blood flow to the renal allograft and the serum level of creatinine returned to normal.

  1. Incidence and Indications for Late Allograft Pancreatectomy While on Continued Immunosuppression.

    Parajuli, Sandesh; Odorico, Jon; Astor, Brad C; Djamali, Arjang; Sollinger, Hans; Redfield, Robert; Kaufman, Dixon; Mandelbrot, Didier A


    There are limited data about the incidence and indications for late allograft pancreatectomy while on continued immunosuppression for functional kidney allografts. We analyzed recipients of simultaneous pancreas and kidney and pancreas after kidney transplants between January 1994 and July 2013. Patients with functional kidney but failed pancreas allografts after 90 days were included. Out of 1022 simultaneous pancreas and kidney or pancreas after kidney recipients, 246 satisfied these criteria. Of these, 50 underwent allograft pancreatectomy (Px) and 196 did not (no-Px). Eleven of these pancreatectomies were performed at the time of repeat transplant and were analyzed separately. None of the basic recipient or donor characteristics differed significantly between the Px (n = 39) and no-Px groups, except for a higher proportion of females in the Px group. The most common presentation in the Px group was abdominal pain. Histopathology of the pancreas varied widely with graft thrombosis as the most common finding. In univariate and multivariate Cox regression analyses, only female recipient was associated with higher risk for allograft pancreatectomy. Px was not associated with kidney allograft survival (P = 0.16). Despite the ongoing presence of full immunosuppression for a functioning kidney allograft, the need for Px for symptoms and radiological findings is not rare (39/246, 15.8%).

  2. Allograft pretreatment for the repair of sciatic nerve defects:green tea polyphenolsversus radiation

    Sheng-hu Zhou; Ping Zhen; Shen-song Li; Xiao-yan Liang; Ming-xuan Gao; Qi Tian; Xu-sheng Li


    Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can elimi-nate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups: autograft, fresh nerve allograft, green tea polyphenol-pretreated (1 mg/mL, 4°C) nerve allograft, and irradiation-pre-treated nerve allograft (26.39 Gy/min for 12 hours; total 19 kGy). The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pre-treated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the allografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve ifbers formed, and abundant microiflaments and microtubules were present in the axoplasm. Our ifndings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to trans-planting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.

  3. Squamous cell skin cancer

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  4. Prolonged QT interval in Rett syndrome


    Rett syndrome is a severe neurodevelopmental disorder of unknown aetiology. A prolonged QT interval has been described previously in patients with Rett syndrome. To investigate QT prolongation and the presence of cardiac tachyarrhythmias in Rett syndrome electrocardiography and 24 hour Holter monitoring were performed prospectively in a cohort of 34 girls with Rett syndrome. The corrected QT value was prolonged in nine patients. Compared with a group of healthy controls of a...

  5. Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction

    Judd Fitzgerald


    Full Text Available Case. This case report describes the operative management of 16-year-old male with a symptomatic chondroblastoma of the distal femur with breach of the chondral surface. Following appropriate imaging and core needle biopsy, the diagnosis was confirmed histologically. The patient then underwent intralesional curettage and osteochondral allograft reconstruction of the defect. At one-year follow-up the patient was pain-free and has obtained excellent range of motion. There is radiographic evidence of allograft incorporation and no evidence of local recurrence. Conclusion. Osteochondral allograft reconstruction is an effective option following marginal resection and curettage of chondroblastoma involving the chondral surface of the distal femur.

  6. Biological effects of rAAV-caAlk2 coating on structural allograft healing

    Koefoed, Mette; Ito, Hiromu; Gromov, Kirill


    that 4-mm murine femoral allografts coated with rAAV-LacZ are capable of transducing adjacent inflammatory cells and osteoblasts in the fracture callus following transplantation. While this LacZ vector had no effect on allograft healing, bone morphogenetic protein signals delivered via rAAV-caAlk2......AAV-LacZ- vs rAAV-caAlk2-coated allografts after 42 days of healing demonstrated a significant increase in new bone formation (0.67 +/- 0.21 vs 2.49 +/- 0.40 mm(3); P


    A. V. Vatazin


    Full Text Available The article focuses on the results of the investigation of peripheral blood lymphocyte morphofunctional status in healthy volunteers and renal allograft recipients for early postoperative period. Working out noninvasive tests for diagnosis of acute renal allograft rejection based on the measuring of cell morphometric parameters by method of coherent phase microscopy (CPM. It was found out that the lymphocyte phase height was proportional cell image density and its geometrical thickness. Our results showed that the variations of immunocompetent cell morphometric indicants can be in advance the dynamics of blood creatine increasing and answer for early criteria of acute renal allograft rejection. 

  8. Chondroblastoma of the knee treated with resection and osteochondral allograft reconstruction.

    Fitzgerald, Judd; Broehm, Cory; Chafey, David; Treme, Gehron


    Case. This case report describes the operative management of 16-year-old male with a symptomatic chondroblastoma of the distal femur with breach of the chondral surface. Following appropriate imaging and core needle biopsy, the diagnosis was confirmed histologically. The patient then underwent intralesional curettage and osteochondral allograft reconstruction of the defect. At one-year follow-up the patient was pain-free and has obtained excellent range of motion. There is radiographic evidence of allograft incorporation and no evidence of local recurrence. Conclusion. Osteochondral allograft reconstruction is an effective option following marginal resection and curettage of chondroblastoma involving the chondral surface of the distal femur.

  9. Renal allograft accumulation of Tc-99m sulfur colloid: temporal quantitation and scintigraphic assessment

    George, E.A.; Meyerovitz, M.; Codd, J.E.; Fletcher, J.W.; Donati, R.M.


    Renal allograft accumulation of Tc-99m sulfur colloid (TSC) was studied using visual assessment of scintigraphic displays and a quantitative temporal model in 210 examinations of 56 transplant recipients. The quantitative temporal model related the immediate pool of the radioagent in the transplant to the fixed allograft accumulation of TSC at 20 minutes after administration. Examinations performed less than 3 days after grafting or steroid pulse therapy were excluded. Rejection was established by clinical and biochemical evaluation in all 84 examinations that showed acute or choronic allograft rejection. Rejection was accurately diagnosed by visual scintigraphic assessment in 82% of the established cases.

  10. Myoglobinuria masquerading as acute rejection in a renal allograft recipient with recurrent post transplant diabetic nephropathy.

    Gupta, Pallav; Sharma, Amit; Khullar, Dinesh


    Rhabdomyolysis contributes to 7-10% of total AKI cases. Myoglobinuria as a cause of acute renal allograft dysfunction is extremely uncommon. Renal allograft recipient on cyclosporine or tacrolimus can develop myoglobinuria in presence of other precipitating factors. Present case describes an interesting report of myoglobinuria in a patient with post transplant diabetic nephropathy mimicking acute graft rejection. Clinically myoglobinuria presenting as renal allograft dysfunction is diagnosis of exclusion and renal biopsy is extremely important in making a correct diagnosis and planning optimal management in such cases.

  11. Transplant graft vasculopathy: an emerging target for prevention and treatment of renal allograft dysfunction.

    Kang, Duk-Hee; Kang, Shin-Wook; Jeong, Hyeon Joo; Kim, Yu Seun; Yang, Chul Woo; Johnson, Richard J


    Maintenance of healthy endothelium is essential to vascular homeostasis, and preservation of endothelial cell function is critical for transplant allograft function. Damage of microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection and chronic allograft nephropathy, which is an important predictor of graft loss and is often associated with transplant vasculopathy. In this review, we will discuss the role of microvascular endothelium, in renal allograft dysfunction, particularly as it relates to markers of endothelial dysfunction and endothelial repair mechanisms. We also discuss the potential for therapies targeting endothelial dysfunction and transplant graft vasculopathy.

  12. Skin Cancer Treatment

    ... of Skin Cancer Skin Cancer Screening Research Skin Cancer Treatment (PDQ®)–Patient Version General Information About Skin Cancer ... clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have ...

  13. Skin Pigmentation Disorders

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  14. Skin Cancer Foundation

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the only ... Handbook A "Sunscreen Gene"? Skin Cancer Facts & Statistics Skin Cancer Treatment Glossary Information on medications and procedures The ...

  15. Skin Bleaching

    Ahmed, Samira M.


    In this project, I aim to investigate the reasoning behind the practice of skin bleaching by analyzing the documentary ”Dark Girls”, to gain a better understanding of race and colorism issues. Also this project tries to see if there is a connection with history and if this has been a part of making the european beauty ideal determine the choices black’s make in regards to beauty.

  16. Dermal absorption and skin damage following hydrofluoric acid exposure in an ex vivo human skin model.

    Dennerlein, Kathrin; Kiesewetter, Franklin; Kilo, Sonja; Jäger, Thomas; Göen, Thomas; Korinth, Gintautas; Drexler, Hans


    The wide industrial use of hydrofluoric acid (HF) poses a high risk for accidental dermal exposure. Despite local and systemic hazards associated with HF, information on percutaneous penetration and tissue damage is rare. In the present ex vivo study, the dermal absorption of HF (detected in terms of fluoride ions) was quantified and the skin damaging potential as a function of concentration and exposure duration was assessed. Percutaneous penetration of HF (c=5, 30, and 50%) at 3 exposure durations (3, 5, and 10 min) was investigated in a static diffusion cell model using freshly excised human skin. Alterations of skin were histologically evaluated. HF rapidly penetrated through skin under formation of a considerable intradermal reservoir (∼ 13-67% of total absorbed fluoride). Histologically, epidermal alterations were detected already after exposure to 5% HF for 3 min. The degree of skin damage increased with rising concentration and exposure duration leading to coagulation necrosis. For HF concentrations of ≥ 30%, skin damage progressed into deeper skin layers. Topically applied HF concentration was the principal parameter determining HF induced skin effects. The intradermal HF retention capacity associated with progression and prolongation of HF induced skin effects must be considered in the review of skin decontamination procedures.

  17. Prolonged Pregnancy: Methods, Causal Determinants and Outcome

    Olesen, Annette Wind

    Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1...

  18. Prenatal risk indicators of a prolonged pregnancy

    Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn


    BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from the Dan...

  19. Arthroscopic capsule reconstruction in the hip using iliotibial band allograft.

    Trindade, Christiano A C; Sawyer, Gregory A; Fukui, Kiyokazu; Briggs, Karen K; Philippon, Marc J


    The hip capsule has been identified as an important static stabilizer of the hip joint. Despite the intrinsic bony stability of the hip socket, the capsule plays a key role in hip stability, particularly at the extremes of motion, and the iliofemoral ligament is the most important stabilizer in extension and external rotation. Patients who do not undergo capsular closure or plication may continue to complain of hip pain and dysfunction postoperatively, likely because of microinstability or muscle invagination into the capsular defect, and high-resolution magnetic resonance imaging or magnetic resonance arthrography will identify the capsular defect. Seen primarily in the revision setting, capsular defects can cause recurrent stress at the chondrolabral junction. An attempt at secondary closure can be challenging because of capsular limb adherence to the surrounding soft tissues. Therefore reconstruction may be the only possible surgical solution for this problem. We describe our new surgical technique for arthroscopic hip capsular reconstruction using iliotibial band allograft.

  20. Amniotic membrane allografts: development and clinical utility in ophthalmology

    Rizzuti A


    Full Text Available Allison Rizzuti,1,2 Adam Goldenberg,1 Douglas R Lazzaro1,2 1SUNY Downstate Medical Center, 2Kings County Hospital Center, Brooklyn, NY, USA Abstract: Amniotic membrane, the innermost layer of the placenta, is a tissue that promotes epithelialization, while decreasing inflammation, neovascularization, and scarring. It is used in the surgical management of a wide variety of ophthalmic conditions where it functions as a graft or patch in ocular surface reconstruction. The development of new preservation techniques, as well as a sutureless amniotic membrane, has allowed for easier, in-office placement, without the disadvantages of an operating room procedure. The purpose of this review is to describe the historical development of amniotic membrane in ophthalmology and to describe its current clinical applications, particularly focusing on recent advances. Keywords: ocular surface, cornea, stem cells, prokera, allograft, patch, transplantation

  1. Amastigotes forms of Trypanosoma cruzi detected in a renal allograft

    CARVALHO Maria Fernanda C.


    Full Text Available Trypanosoma cruzi, the causative agent of Chagas?disease assumes two distinct forms in vertebrate hosts: circulating trypomastigote and tissular amastigote. This latter form infects predominantly the myocardium, smooth and skeletal muscle, and central nervous system. The present work describes for the first time the detection of amastigote forms of T. cruzi in the renal parenchyma of a kidney graft recipient one month after transplantation. The patient was serologically negative for Chagas?disease and received no blood transfusion prior to transplant. The cadaver donor was from an endemic area for Chagas?disease. The recipient developed the acute form of the disease with detection of amastigote forms of T. cruzi in the renal allograft biopsy and circulating trypomastigote forms. The present report demonstrates that T. cruzi can infect the renal parenchyma. This mode of transmission warrants in endemic areas of Chagas?disease

  2. Focal segmental glomerulosclerosis recurrence in the renal allograft.

    Leca, Nicolae


    Focal segmental glomerulosclerosis (FSGS) represents a common histologic pattern of glomerular injury associated with a multitude of disease mechanisms. The etiology of FSGS is often classified into primary (idiopathic) and secondary forms in response to genetic abnormalities, infections, toxins, and systemic disorders that lead to adaptive changes, glomerular hyperfiltration, and proteinuria. Our understanding of the pathogenic mechanisms responsible for FSGS was substantially enhanced in recent years because of major advances in the cell biology of the podocyte and parietal epithelial cell. Recurrence of FSGS occurs mainly in its primary form and is only rarely described in secondary forms. The re-enactment of pathologic mechanisms of FSGS as recurrent disease after kidney transplantation represents a biologic experiment that can provide unique insight. Nonetheless, recurrent FSGS remains a notable clinical problem that correlates with poorer renal allograft outcomes. This is the focus of this particular review, concentrating on the most recent developments.

  3. Technical aspects of mitral valve replacement with an allograft for acute bacterial endocarditis.

    Conklin, L D; Reardon, M J


    Mitral valve replacement with a mitral valve allograft is receiving a resurgence of interest. We discuss the technical aspects of this procedure as it applies to cases of acute bacterial endocarditis infecting the mitral valve.

  4. Identification of β2-microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods.

    Johnston, Olwyn


    Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals.

  5. Optimising femoral-head osteochondral allograft transplantation in a preclinical model

    Brett D. Crist


    Conclusion: These data provide initial translational and clinical evidence for large osteochondral allografts as a potential option for functional resurfacing of full-thickness cartilage defects of the femoral head.

  6. Chemokines in Chronic Liver Allograft Dysfunction Pathogenesis and Potential Therapeutic Targets

    Bin Liu


    Full Text Available Despite advances in immunosuppressive drugs, long-term success of liver transplantation is still limited by the development of chronic liver allograft dysfunction. Although the exact pathogenesis of chronic liver allograft dysfunction remains to be established, there is strong evidence that chemokines are involved in organ damage induced by inflammatory and immune responses after liver surgery. Chemokines are a group of low-molecular-weight molecules whose function includes angiogenesis, haematopoiesis, mitogenesis, organ fibrogenesis, tumour growth and metastasis, and participating in the development of the immune system and in inflammatory and immune responses. The purpose of this review is to collect all the research that has been done so far concerning chemokines and the pathogenesis of chronic liver allograft dysfunction and helpfully, to pave the way for designing therapeutic strategies and pharmaceutical agents to ameliorate chronic allograft dysfunction after liver transplantation.

  7. Localization of gallium-67 in the normally functioning allografted kidney: concise communication

    Fawwaz, R.A.; Johnson, P.M.


    Radiogallium localization in the normally functioning renal allograft is a normal finding in the immediate postoperative period. The intensity of tracer accumulation decreases with time and is no longer demonstrable by the end of the second postoperative month.

  8. Cutaneous skin tag

    Skin tag; Acrochordon; Fibroepithelial polyp ... have diabetes. They are thought to occur from skin rubbing against skin. ... The tag sticks out of the skin and may have a short, narrow stalk connecting it to the surface of the skin. Some skin tags are as long as ...

  9. Factors affecting the long-term renal allograft survival

    WANG Wei; LI Xiao-bei; YIN Hang; YANG Xiao-yong; LIU Hang; REN Liang; HU Xiao-peng; WANG Yong; ZHANG Xiao-dong


    Background In the past decades, the one-year graft survival of cadaveric renal allografts has been markedly improved,but their long-term survival has not kept pace. The attrition rate of renal allografts surviving after one year remains almost unchanged. The causes for late graft loss are multiple. The aim of this study was to analyze the predictive factors that impact long-term survival of grafts after kidney transplantation.Methods We retrospectively analyzed 524 kidney transplantation patients who were treated in our hospital between January 1991 and January 2000, including 254 patients who had lived more than 10 years with normal graft function (long survival group), and 270 cases whose renal graft had survived less than 10 years (control group). Specifically, we analyzed 10 factors that may potentially affect graft survival by both univariate and Logistic model multivariate analyses to pinpoint the independent risk factors.Results Univariate analyses showed that no significant differences existed in the age or gender of recipients, dialysis time, lymphotoxin levels, or cold ischemia time between the two groups. However, the ratio of delayed graft function and acute rejection, and the uric acid levels of patients in the long survival group were significantly lower than those in the control group (P <0.01). Furthermore, we found that the concentration of cyclosporin A at one year after transplantation and the histocompatibility antigen match of donor-recipients for patients within the long survival group were significantly higher than those in the control group (P <0.01 ). Furthermore, multivariate analyses showed that these four factors were independent risk factors that impact patient survival.Conclusions The ratios of delayed graft function and acute rejection, the concentration of cyclosporin A at one year after transplantation, and serum uric acid levels are very important factors that affect the long-term survival of renal grafts.

  10. Cyclosporine-induced renal dysfunction in human renal allograft recipients.

    Kiberd, B A


    Cyclosporine-treated renal allograft recipients frequently suffer CsA-related nephrotoxicity and hypertension. This study demonstrates that glomerular filtration rate is reduced acutely by 13% (P less than 0.02) and renal vascular resistance increased by 30% (P less than 0.05), immediately after patients take their CsA dose. The reduction in GFR is directly related to their trough CsA level (r = 0.82; P less than 0.01). The lower the trough CsA level the greater the fall in GFR after the CsA dose. Plasma renin activity does not increase after the CsA dose (pre-CsA 0.6 +/- 0.2 ng/L/sec vs. post-CsA 0.4 +/- 0.1 ng/L/sec; P = NS), and therefore cannot be responsible for the reduction in renal function. Short-term nifedipine treatment is effective in preventing the acute reduction in GFR (P less than 0.05). This occurred despite no apparent effect of nifedipine in altering trough or post-dose CsA levels. Furthermore nifedipine was effective in lowering both the mean arterial blood pressure (109 mmHg to 94 mmHg; P less than 0.01) and the elevated renal vascular resistance (25% reduction; P less than 0.02) observed in these patients. These results suggest that nifedipine may be a suitable agent for limiting acute CsA nephrotoxicity and for treating CsA-associated hypertension in renal allograft recipients.

  11. Chronic lung allograft dysfunction following lung transplantation: challenges and solutions

    Bemiss BC


    Full Text Available Bradford C Bemiss, Chad A WittDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO, USAAbstract: Chronic rejection is a major cause of death after the first year following lung transplantation. Bronchiolitis obliterans (BO is the most common pathologic finding on biopsy, characterized by fibrous granulation tissue, which obliterates the lumen of the bronchiole. Clinically, in the absence of tissue for pathology, BO syndrome refers to a progressive irreversible drop in the forced expiratory volume in 1 second. Recently, a broader definition of chronic rejection, termed "chronic lung allograft dysfunction", has been used to encompass a more inclusive definition of posttransplant dysfunction. Recently, the lung transplant community has come to realize that chronic rejection may be the final common result after repetitive epithelial insults. Acute rejection, infection, and alloreactivity to mismatched HLA antigens are a few of these insults that damage the surface of the bronchioles. Recent evidence of autoimmunity to the normally hidden structural proteins collagen V and K-α1 tubulin have been correlated with a BO phenotype as well, perhaps correlating the epithelial damage with a mechanism for developing BO lesions. Many immunomodulatory medications and treatments have been studied for effectiveness for the treatment of chronic lung allograft dysfunction. New drugs, which more precisely target the immune system, are being developed and tested. Further study is required, but recent advances have improved our understanding of the pathogenesis and potential intervention for this common and deadly complication of lung transplantation.Keywords: lung transplant, bronchiolitis obliterans syndrome, rejection

  12. Editorial Commentary: Iliotibial Band Allograft Shows Promise for Arthroscopic Hip Labral Reconstruction.

    Rossi, Michael J


    Arthroscopic hip labral reconstruction using iliotibial band allograft in a modified front-to-back technique results in improved outcomes after 2-year follow-up. The authors' reasoning for reconstruction are reminiscent of similar arguments for restoring hoop stresses in knee meniscal surgery. Results are comparable to reported outcomes of labral repair, and allograft is particularly indicated for severe labral damage when repair is not possible. Don't miss the related technical note with video in Arthroscopy Techniques.

  13. Autograft versus allograft reconstruction of acute tibial plateau fractures: a comparative study of complications and outcome.

    Bagherifard, Abolfazl; Ghandhari, Hassan; Jabalameli, Mahmoud; Rahbar, Mohammad; Hadi, Hosseinali; Moayedfar, Mehdi; Sajadi, Mohammadreza Minatour; Karimpour, Alireza


    There is no consensus regarding the use of filling agent in the re-elevation of depressed tibial plateau fracture (TPF). Although autograft is considered as the gold standard approach of such reconstructions, its limitation has led to a recent attraction toward allograft substitution. In this study, we compare the complications and outcome of autograft and allograft in TPF reconstruction, in order to address the existing controversy. A total of 81 patients with acute TPF were included in this study. Allograft and autograft were applied in 58 and 23 cases, respectively. The mean age of the patients was 40.26 years, and the mean follow-up period of patients was 19.1 months. Clinical and radiological assessment of the outcome was conducted, employing the modified Rasmussen clinical criteria. A total of three infections were observed in our patients, from which two infections occurred in allograft received patients. Articular surface collapse was seen in two cases, including one allograft and one autograft receiving patient. The mean clinical score was 18.65 and 18.55 in autograft and allograft received patients, respectively (p = 0.09). The mean radiological score was 15.65 and 15.68 in autograft and allograft received patients (p = 0.3). With respect to the comparable complication rate, clinical and radiological outcome of allogenic versus autologous reconstruction of TPF, freeze-dried allograft could be recommended as an appropriate substitute of autograft in this treatment. Nevertheless, the longer follow-up period of the patients could further extend our understanding of the clinical outcome of each component.

  14. Selection of allografts for impaction bone grafting for bone defect reconstruction on the acetabular side

    XU Zheng-jian; HE Rong-xin


    Objective To review the choices of allografts for bone defect reconstruction in acetabular revision surgery using the technique of impaction bone grafting.Data sources The data cited in this review were mainly obtained from articles listed in PubMed that were published from January 1993 to July 2009. The search terms were "impaction bone grafting", "particle size", "mechanical property"and "biological behavior".Study selection Articles relevant to the choices of allografts and their results for bone defect reconstruction on the acetabular side were selected.Results Different choices of allografts, including the particle size, process of irradiation or fat reduction, composition and particle grade, are made to improve the survival rate of a prosthesis in acetabular revision surgery. This review,which compares both mechanical and biological factors, summarizes the experimental and clinical results for different techniques.Conclusions Fresh frozen cancellous allografts with particle sizes ranging from 7 to 10 mm are a favorable choice for reconstruction of bone defects of American Academy of Orthopedic Surgeons (AAOS) types Ⅱ (cavitary defect) and Ⅲ(combined cavitary and segmental defect) on the acetabular side. A fat-reducing procedure with saline or solvent/detergent is controversial. Adding autologous marrow into irradiated allografts, which provides reliable mechanical stability and biological safety, may be a substitute for fresh frozen allografts. Cortical bone can be a supplementary material in cases of insufficiency of cancellous allografts. Cartilage should be excluded from the graft material. Further research is required to demonstrate the best particle grade, and randomized controlled trials in clinical practice are required to obtain more information about the selection of allografts.

  15. High-Throughput Proteomic Approaches to the Elucidation of Potential Biomarkers of Chronic Allograft Injury (CAI

    Hilary Cassidy


    Full Text Available This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI. CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG. The term CAI, sometimes referred to as chronic allograft nephropathy (CAN, describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection, and other non-immunological factors such as calcineurin inhibitor (CNI induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies.

  16. Antiseptic skin agents for percutaneous procedures.

    Lepor, Norman E; Madyoon, Hooman


    Infections associated with percutaneously implanted devices, such as pacemakers, internal cardiac defibrillators, and endovascular prostheses, create difficult and complex clinical scenarios because management can entail complete device removal, antibiotic therapy, and prolonged hospitalization. A source for pathogens is often thought to be the skin surface, making skin preparation at the time of the procedure a critical part of minimizing implantation of infected devices and prostheses. The most common skin preparation agents used today include products containing iodophors or chlorhexidine gluconate. Agents are further classified by whether they are aqueous-based or alcoholbased solutions. Traditional aqueous-based iodophors, such as povidone-iodine, are one of the few products that can be safely used on mucous membrane surfaces. Alcohol-based solutions are quick, sustained, and durable, with broader spectrum antimicrobial activity. These agents seem ideal for percutaneous procedures associated with prosthesis implantation, when it is critical to minimize skin colony counts to prevent hardware infection.

  17. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure.

    Loupy, Alexandre; Hill, Gary S; Jordan, Stanley C


    Despite improvements in outcomes of renal transplantation, kidney allograft loss remains substantial, and is associated with increased morbidity, mortality and costs. Identifying the pathologic pathways responsible for allograft loss, and the attendant development of therapeutic interventions, will be one of the guiding future objectives of transplant medicine. One of the most important advances of the past decade has been the demonstration of the destructive power of anti-HLA alloantibodies and their association with antibody-mediated rejection (ABMR). Compelling evidence exists to show that donor-specific anti-HLA antibodies (DSAs) are largely responsible for the chronic deterioration of allografts, a condition previously attributed to calcineurin inhibitor toxicity and chronic allograft nephropathy. The emergence of sensitive techniques to detect DSAs, together with advances in the assessment of graft pathology, have expanded the spectrum of what constitutes ABMR. Today, subtler forms of rejection--such as indolent ABMR, C4d-negative ABMR, and transplant arteriopathy--are seen in which DSAs exert a marked pathological effect. In addition, arteriosclerosis, previously thought to be a bystander lesion related to the vicissitudes of aging, is accelerated in ABMR. Advances in our understanding of the pathological significance of DSAs and ABMR show their primacy in the mediation of chronic allograft destruction. Therapies aimed at B cells, plasma cells and antibodies will be important therapeutic options to improve the length and quality of kidney allograft survival.

  18. Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection

    S. R. Alam


    Full Text Available Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO- enhanced magnetic resonance imaging (MRI can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2∗-weighted protocols. R2∗ values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2∗ values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36 versus 0.96 (0.92 to 1.04, P<0.01. R2∗ values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51 compared to native kidney (2.91 (1.11 to 6.46 P<0.05. Increased R2∗ signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.

  19. Impaction grafting with morsellised allograft and tricalcium phosphate-hydroxyapatite: incorporation within ovine metaphyseal bone defects.

    Pratt, J N J; Griffon, D J; Dunlop, D G; Smith, N; Howie, C R


    An ovine model was used to investigate the in vivo properties of impacted tricalcium phosphate-hydroxyapatite (TCP-HA) aggregates, varying in chemical composition (ratio of TCP to HA) and particle size distribution (8 versus 3 particle size ranges). All pellets were impacted to a standard compactive effort. Eight sheep underwent implantation of pellets in 4 metaphyseal defects in both rear limbs. Treatment groups consisted of: (1) allograft (clinical control). (2) 50/50 allograft/80% HA/20% TCP in 8 particle size ranges, (3) 50/50 allograft/80% TCP/20% HA in 8 sizes and (4) 50/50 allograft/80% HA/20% TCP in only 3 sizes of particles. Healing of defects was evaluated at 14 weeks with computed tomography, histology and histomorphometry. The computer tomography (CT) density measured in all defects containing synthetic agents was higher than in defects filled with allograft alone (p<0.01). Defects containing 8 sizes of 80% HA/ 20% TCP granules (group 2) achieved lower histological scores and contained less bone than the clinical control (p<0.05), whereas groups 3 and 4 did not differ from the control. Although all synthetic agents were osteoconductive, our results suggest that increasing the ratio of TCP over HA and limiting the number of particle size ranges to 3 instead of 8 improve the performance of impacted aggregates as graft expanders. Evaluation under loading conditions of morsellised allograft expanded with 80% TCP/20% HA (BoneSave) in 3 particle size ranges is warranted.

  20. Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab

    Addonizio, L.J.; Michler, R.E.; Marboe, C.; Esser, P.E.; Johnson, L.L.; Seldin, D.W.; Gersony, W.M.; Alderson, P.O.; Rose, E.A.; Cannon, P.J.


    The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities.

  1. AA amyloidosis in the renal allograft: a report of two cases and review of the literature.

    Rojas, Rebecca; Josephson, Michelle A; Chang, Anthony; Meehan, Shane M


    AA amyloidosis is a disorder characterized by the abnormal formation, accumulation and systemic deposition of fibrillary material that frequently involves the kidney. Recurrent AA amyloidosis in the renal allograft has been documented in patients with tuberculosis, familial Mediterranean fever, ankylosing spondylitis, chronic pyelonephritis and rheumatoid arthritis. De novo AA amyloidosis is rarely described. We report two cases of AA amyloidosis in the renal allograft. Our first case is a 47-year-old male with a history of ankylosing spondylitis who developed end-stage renal disease reportedly from tubulointerstitial nephritis from non-steroidal anti-inflammatory agent use. A biopsy was never performed. One year after transplantation, AA amyloidosis was identified in the femoral head and 8 years post-transplantation, AA amyloidosis was identified in the renal allograft. He was treated with colchicine and adalimumab and has stable renal function at 1 year-follow-up. Our second case is a 57-year-old male with a long history of intravenous drug use and hepatitis C infection who developed end-stage kidney disease due to AA amyloidosis. Our second patient's course was complicated by renal adenovirus, pulmonary aspergillosis and hepatitis C with AA amyloidosis subsequently being identified in the allograft 2.5 years post-transplantation. Renal allograft function remains stable 4-years post-transplantation. These reports describe clinical and pathologic features of two cases of AA amyloidosis presenting with proteinuria and focal involvement of the renal allograft.

  2. Blockade of the OX40/OX40L pathway and induction of PD-L1 synergistically protects mouse islet allografts from rejection

    Li Tao; Ma Rui; Zhu Jiye; Wang Fushun; Huang Lei; Leng Xisheng


    showed that combined OX40L-RNAi-LV/Ad-PD-L1 treatment significantly decreased proliferation in an antigen-specific mixed lymphocyte reaction.After donor DBA/2 lymphocyte stimulation,89.71% of lymphocytes from recipient combination treatment C57BL/6 mice were not split and proliferated.In contrast,after stimulation with third party Lewis rat lymphocytes,only 45.84% lymphocytes of C57BL/6 mice were not split and proliferated.Conclusions This study demonstrates the successful construction of the recombinant lentivirus vector OX40L-RNAi-LV and adenovirus vector Ad-PD-L1 for the blockade of OX40/OX40L and activation of PD-1/PD-L1 costimulatory pathways simultaneously in pancreatic islet allografts in diabetic mice.Combination therapy with these two vectors resulted in inhibition of T cell activation,synergistically prolonging the survival time of pancreatic islet allografts.

  3. Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

    J.R. Olmos-Zúãiga


    Full Text Available Various methods are available for preservation of vascular grafts for pulmonary artery (PA replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA grafts and cryopreserved (CryoPA grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP in group III increased significantly at the end of the study compared with baseline (P=0.02 and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA. Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

  4. Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

    Olmos-Zúãiga, J.R.; Jasso-Victoria, R. [Department of Experimental Surgery, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Díaz-Martínez, N.E. [Medical and Pharmaceutical Biotechnology, Center for Research and Assistance in Technology and Design of the State of Jalisco, Guadalajara, Jalisco (Mexico); Gaxiola-Gaxiola, M.O. [Laboratory of Morphology, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Sotres-Vega, A.; Heras-Romero, Y.; Baltazares-Lipp, M. [Department of Experimental Surgery, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Baltazares-Lipp, M.E. [Hemodynamics and Echocardiography Service, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Santillán-Doherty, P. [Medical Administration, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Hernández-Jiménez, C. [Department of Experimental Surgery, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico)


    Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

  5. Increased Risk of Revision after ACL Reconstruction with Soft Tissue Allograft Compared to Autograft

    Maletis, Gregory; Chen, Jason; Inacio, Maria Carolina Secorun; Love, Rebecca; Funahashi, Tadashi Ted


    Objectives: The use of allograft tissue for anterior cruciate ligament reconstruction (ACLR) remains controversial. Numerous meta-analysis and systematic reviews of small clinical studies have not found differences between autograft and allograft outcomes but large registry studies have shown an increased risk of revision with allografts. The purpose of this study was to compare the risk of aseptic revision between bone-patellar tendon-bone (BPTB) autografts, hamstring tendon autografts and soft tissue allografts. Methods: A retrospective cohort study of prospectively collected data was conducted using an US ACLR Registry. A cohort of primary unilateral ACLR cases reconstructed with BPTB autografts, hamstring autografts and soft tissue allografts (from any site) was identified. Aseptic revision was the end point of the study. Type of graft and allograft processing methods (non-processed, 1.8 Mrads irradiation with and without chemical processing, and chemical processing alone (BioCleanse)) were the exposures of interest evaluated. Time from surgery was evaluated as an effect modifier. All analyses were adjusted for age, gender, and race. Kaplan-Meier curves and Cox proportional hazard models were employed. Hazard ratios (HR), 95% confidence intervals (CI) are provided. Results: The cohort had 14015 cases, 8924 (63.7%) were male, 6397 (45.6%) were White, 4557 (32.5%) cases used BPTB autograft, 3751 (26.8%) cases used soft tissue allograft and 5707 (40.7%) cases used hamstring autograft. The median age was 34.6 years-old (IQR 24.1-43.2) for allograft cases and 24.3 years-old (IQR 17.7-33.8) for hamstring autograft cases, and 22.0 years-old (IQR 17.6-30.0) for BPTB autograft cases. Compared to hamstring tendon autografts, an increased risk of revision was found in allografts processed with >1.8Mrads without chemical processing after 2.5 years (HR: 3.88 95%CI 1.48-10.12), and >1.8Mrads with chemical processing after only 1 year (HR: 3.43 95%CI 1.58-7.47) and with Bio

  6. Late aspergilloma of a renal allograft without need for operative management: a case report and review of the literature.

    Shannon, E M; Reid, M J A; Chin-Hong, P


    Aspergillus infection localized to the renal allograft is a rare and potentially life-threatening infection and typically requires a combination of operative and medical management. We report the case of a renal allograft aspergilloma in a renal transplant patient presenting 2 years post transplant, successfully managed non-surgically. To our knowledge, this is the first report of a patient presenting with an allograft aspergilloma so long after transplantation and being successfully managed with antifungal therapy alone.

  7. Skin Keratins.

    Wang, Fengrong; Zieman, Abigail; Coulombe, Pierre A


    Keratins comprise the type I and type II intermediate filament-forming proteins and occur primarily in epithelial cells. They are encoded by 54 evolutionarily conserved genes (28 type I, 26 type II) and regulated in a pairwise and tissue type-, differentiation-, and context-dependent manner. Keratins serve multiple homeostatic and stress-enhanced mechanical and nonmechanical functions in epithelia, including the maintenance of cellular integrity, regulation of cell growth and migration, and protection from apoptosis. These functions are tightly regulated by posttranslational modifications as well as keratin-associated proteins. Genetically determined alterations in keratin-coding sequences underlie highly penetrant and rare disorders whose pathophysiology reflects cell fragility and/or altered tissue homeostasis. Moreover, keratin mutation or misregulation represents risk factors or genetic modifiers for several acute and chronic diseases. This chapter focuses on keratins that are expressed in skin epithelia, and details a number of basic protocols and assays that have proven useful for analyses being carried out in skin.

  8. Revision anterior cruciate ligament reconstruction with bone-patellar tendon-bone allograft and extra-articular iliotibial band tenodesis.

    Mascarenhas, Randy; McConkey, Mark O; Forsythe, Brian; Harner, Christopher D


    Revision anterior cruciate ligament (ACL) reconstruction is a technically demanding procedure with outcomes that generally fail to reach those seen with primary ACL reconstruction. With most index procedures using autograft tissue, it is not uncommon for allograft tissue to be required for revision ACL reconstruction. Compared with autografts, allografts take longer to incorporate and lead to more episodes of instability. In this article, we describe ipsilateral iliotibial band tenodesis performed to augment use of bone-patellar tendon-bone allograft in revision ACL reconstruction. This technique adds rotational stability to protect the allograft tissue while it incorporates.

  9. [Neurologic complications induced by the treatment of the acute renal allograft rejection with the monoclonal antibody OKT3].

    Fernández, O; Romero, F; Bravo, M; Burgos, D; Cabello, M; González-Molina, M


    The treatment of the acute renal allograft rejection with the monoclonal antibody orthoclone OKT3 produces both systemic and neurologic alterations. In a series of 21 patients with an acute renal allograft rejection treated with this monoclonal antibody, 20 with a renal allograft transplantation and one with a renal and pancreatic allograft transplantation, 29% referred headache associated with fever and vomiting, and 14.2% presented severe neurological alterations induced by the treatment. We stress the need to know these secondary effects to differentiate them from other central nervous system disorders, particularly those of infectious origin.

  10. Anterior cruciate ligament reconstruction with BPTB autograft, irradiated versus non-irradiated allograft: a prospective randomized clinical study.

    Sun, Kang; Tian, Shaoqi; Zhang, Jihua; Xia, Changsuo; Zhang, Cailong; Yu, Tengbo


    The effect of using gamma irradiation to sterilize bone-patellar tendon-bone (BPTB) allograft on the clinical outcomes of anterior cruciate ligament (ACL) reconstruction with irradiated allograft remains controversial. Our study was aimed to analyze the clinical outcomes of arthroscopic ACL reconstruction with irradiated BPTB allograft compared with non-irradiated allograft and autograft. All BPTB allografts were obtained from a single tissue bank and the irradiated allografts were sterilized with 2.5 Mrad of irradiation prior to distribution. A total of 102 patients undergoing arthroscopic ACL reconstruction were prospectively randomized consecutively into three groups. The same surgical technique was used in all operations done by the same senior surgeon. Before surgery and at the average of 31 months follow-up (range 24-47 months) patients were evaluated by the same observer according to objective and subjective clinical evaluations. Of these patients, 99 (autograft 33, non-irradiated allograft 34, irradiated allograft 32) were available for full evaluation. When compared the irradiated allograft group to non-irradiated allograft group or autograft group at 31 months follow-up by the Lachman test, ADT, pivot shift test and KT-2000 arthrometer testing, statistically significant differences were found. Most importantly, 87.8% of patients in the Auto group, 85.3% in the Non-Ir-Auto group and just only 31.3% in the Ir-Allo group had a side-to-side difference of less than 3 mm according to KT-2000. The failure rate of the ACL reconstruction with irradiated allograft (34.4%) was higher than that with autograft (6.1%) and non-irradiated allograft (8.8%). The anterior and rotational stability decreased significantly in the irradiated allograft group. According to the overall IKDC, functional, subjective evaluations and activity level testing, no statistically significant differences were found between the three groups. However, there was a trend that the functional and

  11. Gastrointestinal Bleeding and Diffuse Skin Thickening as Kaposi Sarcoma Clinical Presentation

    Querido, Sara; Sousa, Henrique Silva; Pereira, Tiago Assis; Birne, Rita; Matias, Patrícia; Jorge, Cristina; Weigert, André; Adragão, Teresa; Bruges, Margarida; Machado, Domingos


    A 56-year-old African patient received a kidney from a deceased donor with 4 HLA mismatches in April 2013. He received immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil, and prednisone. Immediate diuresis and a good allograft function were soon observed. Six months later, the serum creatinine level increased to 2.6 mg/dL. A renal allograft biopsy revealed interstitial fibrosis and tubular atrophy grade II. Toxicity of calcineurin inhibitor was assumed and, after a switch for everolimus, renal function improved. However, since March 2014, renal function progressively deteriorated. A second allograft biopsy showed no new lesions. Two months later, the patient was admitted due to anuria, haematochezia with anaemia, requiring 5 units of packed red blood cells, and diffuse skin thickening. Colonoscopy showed haemorrhagic patches in the colon and the rectum; histology diagnosis was Kaposi sarcoma (KS). A skin biopsy revealed cutaneous involvement of KS. Rapid clinical deterioration culminated in death in June 2014. This case is unusual as less than 20 cases of KS with gross gastrointestinal bleeding have been reported and only 6 cases had the referred bleeding originating in the lower gastrointestinal tract. So, KS should be considered in differential diagnosis of gastrointestinal bleeding in some kidney transplant patients. PMID:26783491

  12. QT Prolongation due to Graves’ Disease

    Zain Kulairi


    Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

  13. Hippocampal Abnormalities in Prolonged Febrile Seizures

    J Gordon Millichap


    Full Text Available Apparent diffusion coefficient (ADC measurements were used to characterize hippocampal edema within 5 days of a prolonged febrile seizure (PFS in a study at Great Ormond Street Hospital, London, UK.

  14. MRI Abnormalities After Prolonged Febrile Seizures

    J Gordon Millichap


    Full Text Available The clinical, radiologic, and laboratory findings of 17 Asian patients with encephalopathy following a prolonged febrile seizure were reviewed retrospectively at Kameda Medical Center, and other centers in Japan and San Francisco, USA.

  15. QT Prolongation due to Graves' Disease

    Deol, Nisha; Tolly, Renee; Manocha, Rohan; Naseer, Maliha


    Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status. PMID:28154763

  16. Survival without sequelae after prolonged cardiopulmonary resuscitation after electric shock.

    Motawea, Mohamad; Al-Kenany, Al-Sayed; Hosny, Mostafa; Aglan, Omar; Samy, Mohamad; Al-Abd, Mohamed


    "Electrical shock is the physiological reaction or injury caused by electric current passing through the human body. It occurs upon contact of a human body part with any source of electricity that causes a sufficient current through the skin, muscles, or hair causing undesirable effects ranging from simple burns to death." Ventricular fibrillation is believed to be the most common cause of death after electrical shock. "The ideal duration of cardiac resuscitation is unknown. Typically prolonged cardiopulmonary resuscitation is associated with poor neurologic outcomes and reduced long term survival. No consensus statement has been made and traditionally efforts are usually terminated after 15-30 minutes." The case under discussion seems worthy of the somewhat detailed description given. It is for a young man who survived after 65 minutes after electrical shock (ES) after prolonged high-quality cardiopulmonary resuscitation (CPR), multiple defibrillations, and artificial ventilation without any sequelae. Early start of adequate chest compressions and close adherence to advanced cardiac life support protocols played a vital role in successful CPR.

  17. Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation.

    Hirano, Yutaka; Sugimoto, Seiichiro; Mano, Toshifumi; Kurosaki, Takeshi; Miyoshi, Kentaroh; Otani, Shinji; Yamane, Masaomi; Kobayashi, Motomu; Miyoshi, Shinichiro; Oto, Takahiro


    BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

  18. Anyone Can Get Skin Cancer

    ... of Skin Cancer Skin Cancer Screening Research Anyone Can Get Skin Cancer Order the free Anyone Can ... rarely, younger children can develop skin cancer. How can people with dark skin get skin cancer? Although ...

  19. Repeated freeze-thaw cycles do not alter the biomechanical properties of fibular allograft bone.

    Shaw, Joshua M; Hunter, Shawn A; Gayton, J Christopher; Boivin, Gregory P; Prayson, Michael J


    Allograft tissues can undergo several freeze-thaw cycles between donor tissue recovery and final use by surgeons. However, there are currently no standards indicating the number of reasonable freeze-thaw cycles for allograft bone and it is unclear how much a graft may be degraded with multiple cycles. We therefore asked whether (1) the mechanical properties of fibular allograft bone would remain unchanged with increasing numbers of freeze-thaw cycles and (2) histologic alterations from increased numbers of freeze-thaw cycles would correspond to any mechanical changes. Fibular allograft segments were subjected to two, four, and eight freeze-thaw cycles and compared biomechanically and histologically with a control group (one freeze-thaw cycle). Two freeze-dried treatments, one after being subjected to one freeze-thaw cycle and the other after being subjected to three freeze-thaw cycles, also were compared with the control group. For all segments, the average ultimate stress was 174 MPa, average modulus was 289 MPa, average energy was 2.00 J, and the average stiffness was 1320 N/mm. The material properties of the freeze-thaw treatment groups were similar to those of the control group: ultimate stress and modulus were a maximum of 16% and 70% different, respectively. Both freeze-dried treatments showed increased stiffness (maximum 53% ± 71%) and energy to failure (maximum 117% ± 137%) but did not exhibit morphologic differences. There were no alterations in the histologic appearance of the bone sections in any group. Fibular allograft segments can be refrozen safely up to eight times without affecting the biomechanical or morphologic properties. Freeze-dried treatments require further study to determine whether the detected differences are caused by the processing. Cryopreserved cortical allografts are thawed by surgeons in preparation for procedures and then occasionally discarded when not used. Refreezing allograft tissues can result in a cost savings because of a

  20. Abnormally dark or light skin

    Hyperpigmentation; Hypopigmentation; Skin - abnormally light or dark ... Normal skin contains cells called melanocytes. These cells produce melanin , the substance that gives skin its color. Skin with ...

  1. Recent prospective of nanofiber scaffolds fabrication approaches for skin regeneration.

    Ahmadi-Aghkand, Fateme; Gholizadeh-Ghaleh Aziz, Shiva; Panahi, Yunes; Daraee, Hadis; Gorjikhah, Fateme; Gholizadeh-Ghaleh Aziz, Sara; Hsanzadeh, Arash; Akbarzadeh, Abolfazl


    The largest organ of human body is skin, which acting as a barrier with immunologic, sensorial and protective functions. It is always in exposure to the external environment, which can result many different types of damage and injury with loss of variable volumes of extracellular matrix (ECM). For the treatment of skin lesions and damages, several approaches are now accessible, such as the application of allografts, autografts, and tissue-engineered substitutes, wound dressings and nanofiber scaffolds approaches. Even though proven clinically effective, these methods are still characterized by main drawbacks such as patient inadequate vascularization, morbidity, the inability to reproduce skin appendages, low adherence to the wound bed and high manufacturing costs. Advanced approaches based on nanofiber scaffolds approaches offer a permanent, viable and effective substitute to explain the drawbacks of skin regeneration and repair by combining growth factors, cells, and biomaterials and advanced biomanufacturing methods. This review details recent advances of nanofiber scaffolds in skin regeneration and repair strategies, and describes a synthesis method of nanofiber scaffolds.

  2. Assessment of early renal allograft dysfunction with blood oxygenation level-dependent MRI and diffusion-weighted imaging

    Park, Sung Yoon [Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Chan Kyo, E-mail: [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Byung Kwan [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Sung Ju; Lee, Sanghoon [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Huh, Wooseong [Department of Nephrology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    Highlights: • R2* and ADC in renal allografts are moderately correlated with eGFR. • R2* and ADC are lower in early allograft dysfunction than normal allograft function. • No significant difference between AR and ATN was found in both R2* and ADC. - Abstract: Purpose: To investigate blood oxygenation level-dependent (BOLD) MRI and diffusion-weighted imaging (DWI) at 3 T for assessment of early renal allograft dysfunction. Materials and methods: 34 patients with a renal allograft (early dysfunction, 24; normal, 10) were prospectively enrolled. BOLD MRI and DWI were performed at 3 T. R2* and apparent diffusion coefficient (ADC) values were measured in cortex and medulla of the allografts. Correlation between R2* or ADC values and estimated glomerular filtration rate (eGFR) was investigated. R2* or ADC values were compared among acute rejection (AR), acute tubular necrosis (ATN) and normal function. Results: In all renal allografts, cortical or medullary R2* and ADC values were moderately correlated with eGFR (P < 0.05). Early dysfunction group showed lower R2* and ADC values than normal function group (P < 0.05). AR or ATN had lower R2* values than normal allografts (P < 0.05), and ARs had lower cortical ADC values than normal allografts (P < 0.05). No significant difference of R2* or ADC values was found between AR and ATN (P > 0.05). Conclusion: BOLD MRI and DWI at 3 T may demonstrate early functional state of renal allografts, but may be limited in characterizing a cause of early renal allograft dysfunction. Further studies are needed.

  3. The Origin of Neointimal Smooth Muscle Cells in Transplant Arteriosclerosis from Recipient Bone-marrow Cells in Rat Aortic Allograft

    SONG Zifang; LI Wei; ZHENG Qichang; SHANG Dan; SHU Xiaogang; GUAN Siming


    In order to investigate the origin of neointimal smooth muscle cells in transplant arteriosclerosis in rat aortic allograft, sex-mismatched bone marrow transplantation was performed from male Wistar rats to female Wistar rats. Four weeks after transplantation, the aortic transplant model was established by means of micro-surgery in rats. The recipients were divided into 4 groups: female Wistar-female Wistar aortic isografts, female SD-female Wistar aortic allografts, male SD-male Wistar aortic allografts, female SD-chimera Wistar aortic allografts. Eight weeks after transplantation, aortic grafts were removed at autopsy and processed for histological evaluation and immunohistochemistry. The results indicated that excessive accumulation of α-SMA-positive smooth muscle cells resulted in significant neointima formation and vascular lumen stricture in rat aortic allografts.Neointima assay revealed that the neointimal area and NIA/MA ratio of transplanted artery were significantly increased in all of aortic allograft groups as compared with those in aortic isograft group (P<0.01). Neointimal smooth muscle cells were harvested from cryostat sections of aortic allograft by microdissection method. The Sry gene-specific PCR was performed, and the result showed that a distinct DNA band of 225 bp emerged in the male-male aortic allograft group and chimera aortic allograft group respectively, but not in the female-female aortic allograft group. It was suggested that recipient bone-marrow cells, as the origin of neointimal smooth muscle cells, contributed to the pathological neointimal hyperplasia of aortic allograft and transplant arteriosclerosis.

  4. Quality of drug label information on QT interval prolongation

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;


    characteristics (SPC) of recently approved medicinal products. METHODS: Drug labels of products centrally approved in Europe between 2006 and 2012 were screened. Of drugs including the term 'QT' in the SPC, the message on QT-prolongation ('no prolongation'/'unclear drug-QT association'/'possibly QT......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

  5. Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

    Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.;


    Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...

  6. Skin color - patchy

    ... page: // Skin color - patchy To use the sharing features on this page, please enable JavaScript. Patchy skin color is areas where the skin color is irregular. ...

  7. Alveolar Ridge Preservation Using Xenogeneic Collagen Matrix and Bone Allograft

    Andreas O. Parashis


    Full Text Available Alveolar ridge preservation (ARP has been shown to prevent postextraction bone loss. The aim of this report is to highlight the clinical, radiographic, and histological outcomes following use of a bilayer xenogeneic collagen matrix (XCM in combination with freeze-dried bone allograft (FDBA for ARP. Nine patients were treated after extraction of 18 teeth. Following minimal flap elevation and atraumatic extraction, sockets were filled with FDBA. The XCM was adapted to cover the defect and 2-3 mm of adjacent bone and flaps were repositioned. Healing was uneventful in all cases, the XCM remained in place, and any matrix exposure was devoid of further complications. Exposed matrix portions were slowly vascularized and replaced by mature keratinized tissue within 2-3 months. Radiographic and clinical assessment indicated adequate volume of bone for implant placement, with all planned implants placed in acceptable positions. When fixed partial dentures were placed, restorations fulfilled aesthetic demands without requiring further augmentation procedures. Histological and immunohistochemical analysis from 9 sites (4 patients indicated normal mucosa with complete incorporation of the matrix and absence of inflammatory response. The XCM + FDBA combination resulted in minimal complications and desirable soft and hard tissue therapeutic outcomes, suggesting the feasibility of this approach for ARP.

  8. Liver allograft pathology in healthy pediatric liver transplant recipients.

    Briem-Richter, Andrea; Ganschow, Rainer; Sornsakrin, Marijke; Brinkert, Florian; Schirmer, Jan; Schaefer, Hansjörg; Grabhorn, Enke


    Liver transplantation offers excellent results for children with end-stage liver disease, and efforts should be directed toward maintaining long-term graft health. We evaluate graft pathology in healthy pediatric transplant recipients with low-maintenance immunosuppressive medications to assess whether protocol biopsies are helpful for adapting immunosuppression and protecting long-term graft function. Liver biopsies were performed on 60 healthy pediatric liver transplant recipients, and histological findings were correlated with laboratory, serological, and radiological results. Fourteen patients (23%) were diagnosed with acute or early chronic rejection, and immunosuppressive medications were increased in these children. Liver function tests did not correlate with histological findings. The incidence of fibrosis was 36% in transplant recipients five or more years after liver transplantation. We observed an unexpectedly high prevalence of rejection and fibrosis in children with no laboratory abnormalities, which led to changes in their immunosuppressive medications. Scheduled biopsies appear to be useful in pediatric transplant recipients with low immunosuppressive medications for early detection of morphological changes in liver transplants. Further studies are needed to evaluate whether adaption of immunosuppression helps to reduce tissue damage and the incidence of allograft dysfunction in the long term.

  9. Long-term histopathology of allografts in sensitized kidney recipients.

    Miura, Masayoshi; Harada, Hiroshi; Fukasawa, Yuichiro; Hotta, Kiyohiko; Itoh, Yosuke; Tamaki, Tohru


    Successful desensitization therapy has brought satisfying short-term outcomes in the recipients with anti-donor antibody. We analyzed the long-term pathology of the allografts in the sensitized kidney recipients. Eleven stable recipients after desensitization against positive flow cytometry T-cell crossmatch (FTXM) were included. They were divided into two groups, based on the protocol biopsies findings at three to eight yr (group 1: subclinical glomerulitis and/or peritubular capillaritis, n = 5 and group 2: no rejection, n = 6). Estimated glomerular filtration rate (eGFR), presence of donor-specific antibody (DSA), mean channel shift (MCS) of FTXM, urine protein levels, acute antibody-mediated rejection (AAMR) episodes, and protocol biopsy findings were compared. Chronic transplant glomerulopathy was found in final biopsy of all group 1 cases. DSA was positive in 60% but C4d was positive in 20% case of the group 1. The history of AAMR was only found in the group 1. There was no difference in eGFR decline or proteinuria. The MCS of FTXM was higher in the group 1. The recipients with AAMR history, high MCS in FTXM, and subclinical microvascular inflammation in the early protocol biopsies have risk for developing chronic rejection in long term.

  10. Early Cardiac Allograft Vasculopathy: Are the Viruses to Blame?

    Ashim Aggarwal


    Full Text Available This paper describes a case of early (7 months after transplant cardiac allograft vasculopathy. This-43-year-old (CMV positive, EBV negative female patient underwent an orthotopic heart transplant with a (CMV negative, EBV positive donor heart. She had a history of herpes zoster infection and postherpetic neuralgia in the past. The patient’s panel reactive antibodies had been almost undetectable on routine surveillance testing, and her surveillance endomyocardial biopsies apart from a few episodes of mild-to-moderate acute cellular rejection (treated adequately with steroids never showed any evidence of humoral rejection. The postoperative course was complicated by multiple admissions for upper respiratory symptoms, and the patient tested positive for entero, rhino, and coronaviruses serologies. During her last admission (seven months postoperatively the patient developed mild left ventricular dysfunction with an ejection fraction of 40%. The patient’s endomyocardial biopsy done at that time revealed concentric intimal proliferation and inflammation resulting in near-total luminal occlusion in the epicardial and the intramyocardial coronary vessels, suggestive of graft vasculopathy with no evidence of rejection, and the patient had a fatal ventricular arrhythmia.

  11. Laminins affect T cell trafficking and allograft fate.

    Warren, Kristi J; Iwami, Daiki; Harris, Donald G; Bromberg, Jonathan S; Burrell, Bryna E


    Lymph nodes (LNs) are integral sites for the generation of immune tolerance, migration of CD4⁺ T cells, and induction of Tregs. Despite the importance of LNs in regulation of inflammatory responses, the LN-specific factors that regulate T cell migration and the precise LN structural domains in which differentiation occurs remain undefined. Using intravital and fluorescent microscopy, we found that alloreactive T cells traffic distinctly into the tolerant LN and colocalize in exclusive regions with alloantigen-presenting cells, a process required for Treg induction. Extracellular matrix proteins, including those of the laminin family, formed regions within the LN that were permissive for colocalization of alloantigen-presenting cells, alloreactive T cells, and Tregs. We identified unique expression patterns of laminin proteins in high endothelial venule basement membranes and the cortical ridge that correlated with alloantigen-specific immunity or immune tolerance. The ratio of laminin α4 to laminin α5 was greater in domains within tolerant LNs, compared with immune LNs, and blocking laminin α4 function or inducing laminin α5 overexpression disrupted T cell and DC localization and transmigration through tolerant LNs. Furthermore, reducing α4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation.

  12. Adipose Gene Expression Profile Changes With Lung Allograft Reperfusion.

    Diamond, Joshua M; Arcasoy, Selim; McDonnough, Jamiela A; Sonett, Joshua R; Bacchetta, Matthew; D'Ovidio, Frank; Cantu, Edward; Bermudez, Christian A; McBurnie, Amika; Rushefski, Melanie; Kalman, Laurel H; Oyster, Michelle; D'Errico, Carly; Suzuki, Yoshikazu; Giles, Jon T; Ferrante, Anthony; Lippel, Matthew; Singh, Gopal; Lederer, David J; Christie, Jason D


    Obesity is a risk factor for primary graft dysfunction (PGD), a form of lung injury resulting from ischemia-reperfusion after lung transplantation, but the impact of ischemia-reperfusion on adipose tissue is unknown. We evaluated differential gene expression in thoracic visceral adipose tissue (VAT) before and after lung reperfusion. Total RNA was isolated from thoracic VAT sampled from six subjects enrolled in the Lung Transplant Body Composition study before and after allograft reperfusion and quantified using the Human Gene 2.0 ST array. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment for genes involved in complement and coagulation cascades and Jak-STAT signaling pathways. Overall, 72 genes were upregulated and 56 genes were downregulated in the postreperfusion time compared with baseline. Long pentraxin-3, a gene and plasma protein previously associated with PGD, was the most upregulated gene (19.5-fold increase, p = 0.04). Fibronectin leucine-rich transmembrane protein-3, a gene associated with cell adhesion and receptor signaling, was the most downregulated gene (4.3-fold decrease, p = 0.04). Ischemia-reperfusion has a demonstrable impact on gene expression in visceral adipose tissue in our pilot study of nonobese, non-PGD lung transplant recipients. Future evaluation will focus on differential adipose tissue gene expression and the development of PGD after transplant. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. Impact of obesity on development of chronic renal allograft dysfunction

    Jahromi Alireza


    Full Text Available Obesity in nontransplant patients has been associated with hypertension, hyperlipi-demia, diabetes, and proteinuria. To determine whether renal transplant recipients with an elevated BMI have worse long term graft survival, we prospectively studied 92 patients transplanted between April 1999 and July 2000. Weight (Wt and height of the patients were recorded prior to transplantation and two weeks, one, two and three years post transplantation. Blood urea nitrogen (BUN, creatinine (Cr and blood pressure were checked monthly, while triglyceride, cholesterol, high den-sity lipoprotein (HDL, and low density lipoprotein (LDL were obtained 3 monthly for 3 years post transplantation. Graft dysfunction was defined as serum Cr > 1.8 mg/dL. While BMI and Wt of the patients before transplantation did not show any significant correlation with chronic renal allograft dysfunction (CRAD, patients with higher Wt and BMI two weeks after transplantation showed an increased risk of developing CRAD during the three year post transplant independent of other risk factors (P< 0.05. Patients with greater Wt loss in the first two weeks post transplantation showed a decreased risk of developing CRAD in the following 3 years (P< 0.001. Our study suggests that high Wt and BMI are significantly associated with worse graft survival 3 years post renal trans-plantation.

  14. Aortic valve replacement with cryopreserved aortic allograft: ten-year experience.

    Doty, J R; Salazar, J D; Liddicoat, J R; Flores, J H; Doty, D B


    Cryopreserved aortic allograft can be used for aortic valve replacement in congenital, rheumatic, degenerative, and infected native valve conditions, as well as failed prosthetic valves. This study was conducted to determine the long-term results of aortic valve replacement with cryopreserved aortic allografts. Aortic valve replacement with cryopreserved aortic allografts was performed in 117 patients from July 1985 until August 1996. All patients requiring aortic valve replacement regardless of valve disease were considered for allograft replacement; the valve was preferentially used in patients under age 55 years and in the setting of bacterial endocarditis. Four operative techniques involving cryopreserved aortic allografts were used: freehand aortic valve replacement with 120-degree rotation, freehand aortic valve replacement with intact noncoronary sinus, aortic root enlargement with intact noncoronary sinus, and total aortic root replacement. Valve function was assessed by echocardiography during the operation in 78 patients (66%) and after the operation in 77 patients (65%). One-hundred eighteen aortic valve replacements with cryopreserved aortic allografts were performed on 117 patients; mean age was 45.6 years (range 15 to 83 years) and mean follow-up was 4.6 years (range up to 11 years). Intraoperative echocardiography disclosed no significant aortic valve incompetence. There were four operative deaths (3%) and seven late deaths; freedom from valve-related mortality at 10 years was 9:3% +/- 4.55%. New York Heart Association functional status at latest follow-up was normal in 98 (94%) patients. On postoperative echocardiography, 90% had no or trivial aortic valve incompetence. Freedom from thromboembolism at 10 years was 100% and from endocarditis, 98% +/- 2.47%. Seven (6%) patients required valve explantation, four for structural deterioration. At 10 years, freedom from reoperation for allograft-related causes was 92% +/- 3.47%. Aortic valve replacement

  15. High meniscal slope angle as a risk factor for meniscal allograft extrusion.

    Łuczkiewicz, P; Daszkiewicz, K; Chróścielewski, J; Witkowski, W; Kuik, L


    A meniscal graft extrusion is still an unresolved problem that affects most patients after a meniscal transplantation. Despite the advances in surgical techniques, together with the improved methods for a meniscal allograft sizing, success is only observed in up to 75% of patients after they experience a meniscal allograft transplantation. Because a meniscal extrusion is associated with a cartilage deterioration and the progression of osteoarthritis there is a great interest in how to prevent this phenomenon. The crucial factor for the minimisation of a meniscal allograft extrusion is by perfectly matching the implant. Most methods for a meniscal allograft sizing only focus on assessing the length and the width of the meniscus. Even though there is some evidence that there is a relationship between the shape of the meniscus in a cross-sectional plane and the meniscal extrusion, any of the planning methods do not take this factor into consideration. Although there is a large variability of meniscus shapes in cross-section, we hypothesise that by taking the meniscal slope into account during surgical planning, as well as performing the correct adjustments of this particular parameter, we can diminish the risk of a meniscal allograft extrusion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Geographic inequities in liver allograft supply and demand: does it affect patient outcomes?

    Rana, Abbas; Kaplan, Bruce; Riaz, Irbaz B; Porubsky, Marian; Habib, Shahid; Rilo, Horacio; Gruessner, Angelika C; Gruessner, Rainer W G


    Significant geographic inequities mar the distribution of liver allografts for transplantation. We analyzed the effect of geographic inequities on patient outcomes. During our study period (January 1 through December 31, 2010), 11,244 adult candidates were listed for liver transplantation: 5,285 adult liver allografts became available, and 5,471 adult recipients underwent transplantation. We obtained population data from the 2010 United States Census. To determine the effect of regional supply and demand disparities on patient outcomes, we performed linear regression and multivariate Cox regression analyses. Our proposed disparity metric, the ratio of listed candidates to liver allografts available varied from 1.3 (region 11) to 3.4 (region 1). When that ratio was used as the explanatory variable, the R(2) values for outcome measures were as follows: 1-year waitlist mortality, 0.23 and 1-year posttransplant survival, 0.27. According to our multivariate analysis, the ratio of listed candidates to liver allografts available had a significant effect on waitlist survival (hazards ratio, 1.21; 95% confidence interval, 1.04-1.40) but was not a significant risk factor for posttransplant survival. We found significant differences in liver allograft supply and demand--but these differences had only a modest effect on patient outcomes. Redistricting and allocation-sharing schemes should seek to equalize regional supply and demand rather than attempting to equalize patient outcomes.

  17. The use of bone allografts for limb salvage in high-grade extremity osteosarcoma.

    Gebhardt, M C; Flugstad, D I; Springfield, D S; Mankin, H J


    Limb preservation is increasingly being employed in the local treatment of high-grade extremity osteosarcoma. Bone allografts used to reconstruct the bony defects following tumor resection offer many advantages, including joint reconstruction and incorporation of the graft to the host bone in these relatively young patients. The results of 53 patients 30 years of age or younger were assessed to determine functional outcome. Fresh-frozen allografts were employed as osteoarticular grafts, allograft-arthrodeses, allograft-prosthesis composites, or intercalary grafts. Follow-up intervals averaged 25 months (range, two to 63 months). Life-table analysis showed that the probability of a satisfactory functional result was 73% if local tumor recurrences were excluded. Complications included 16 infections, six fractures, 12 nonunions, and six unstable joints. There were five local recurrences. Eighteen grafts ultimately failed, and in six patients, this resulted in an above-knee amputation. An additional five received a second graft. The functional "end results" of the 38 patients with two or more years of follow-up examinations were 70% satisfactory in those without a local recurrence. There was no statistically significant difference in functional outcome or local or distant relapse in those patients receiving preoperative chemotherapy. The authors conclude that allografts can be used for limb reconstruction in patients with high-grade osteosarcoma who receive aggressive adjuvant chemotherapy. The functional results are comparable to other methods of reconstruction, and once incorporated by the host, offer the advantage of longevity, compared with metallic implants.

  18. Allografts about the Knee in Young Patients with High-Grade Sarcoma.

    Brigman, Brian E; Hornicek, Francis J; Gebhardt, Mark C; Mankin, Henry J


    Reconstruction after resections for high-grade sarcomas about the knee in children and adolescents is a challenging problem because of the large soft tissue and skeletal defects, the effects of adjuvant therapy, and the potential for long-term use of the limb. One hundred sixteen patients, all 18 years or younger, with osteosarcoma or Ewing's sarcoma located between the middle femur and middle tibia, were treated with chemotherapy, resection, and allograft reconstruction. One hundred three patients with osteosarcoma and 13 patients with Ewing's sarcoma had 105 Stage II and 11 Stage III tumors. There were 72 osteoarticular grafts (39 femur, 33 tibia), 28 intercalary grafts (19 femur), seven allograft-prosthetic composites (all femur,) and nine allograft-arthrodeses (seven femur, two tibia). At latest followup, 49% of all of the allograft reconstructions were rated good or excellent, 14% were rated as fair, and 37% were failures. Sixteen percent had an infection develop. Twenty-seven percent of patients had a fracture, 34% had a nonunion, and 14 patients eventually required amputation. Reconstruction of large bone defects about the knee in young patients who are being treated with chemotherapy is difficult. Although complications significantly affect outcome, allografts are a viable option for reconstruction in children with high-grade sarcomas about the knee.

  19. Circumferential proximal femoral allografts in revision hip arthroplasty: four to 20 years follow-up.

    Roos, Bruno Dutra; Roos, Milton Valdomiro; Camisa, Antero


    The purpose of this study was to analyze the clinical and radiographic results of revision of loose total hip replacements, using proximal femoral allografts and a cemented implant. We retrospectively reviewed of 28 consecutive patients. Twenty patients were available for study. Each patient was scored using a modified Harris Hip Score. Radiographs were examined for endosteal and periosteal reabsorption, allograft-host union, trochanteric migration, component loosening and heterotrophic calcification. The mean pre-operative Harris hip Score was 34 points. At the latest follow-up, the meanscore was 80 points. Nineteen cases (95%) had combined femoral defects and one patient (5%) had a segmental defect, according to the AAOS classification. Allograft resorption was seen in eight (40%) hips. There were 18 cases (90%) of allograft union, one (5%) of partial union and one (5%) of nonunion. There was one case of trochanteric migration (more than 1 cm). All femoral components were radiographically stable. The reconstruction was considered successful in 18 patients (90%). The use of proximal femoral allografts in femoral revision of loose total hip replacements has high survival and satisfactory clinical results at an average period of eight years postoperatively.

  20. Cardiogenic shock and coronary endothelial dysfunction predict cardiac allograft vasculopathy after heart transplantation.

    Lopez-Fernandez, Silvia; Manito-Lorite, Nicolas; Gómez-Hospital, Joan Antoni; Roca, Josep; Fontanillas, Carles; Melgares-Moreno, Rafael; Azpitarte-Almagro, José; Cequier-Fillat, Angel


    Cardiac allograft vasculopathy remains one of the major causes of death post-heart transplantation. Its etiology is multifactorial and prevention is challenging. The aim of this study was to prospectively determine factors related to cardiac allograft vasculopathy after heart transplantation. This research was planned on 179 patients submitted to heart transplant. Performance of an early coronary angiography with endothelial function evaluation was scheduled at three-month post-transplant. Patients underwent a second coronary angiography after five-yr follow-up. At the 5- ± 2-yr follow-up, 43% of the patients had developed cardiac allograft vasculopathy (severe in 26% of them). Three independent predictors of cardiac allograft vasculopathy were identified: cardiogenic shock at the time of the transplant operation (OR: 6.49; 95% CI: 1.86-22.7, p = 0.003); early coronary endothelial dysfunction (OR: 3.9; 95% CI: 1.49-10.2, p = 0.006), and older donor age (OR: 1.05; 95% CI: 1.00-1.10, p = 0.044). Besides early endothelial coronary dysfunction and older donor age, a new predictor for development of cardiac allograft vasculopathy was identified: cardiogenic shock at the time of transplantation. In these high-risk patient subgroups, preventive measures (treatment of cardiovascular risk factors, use of novel immunosuppressive agents such as mTOR inhibitors) should be earlier and much more aggressive.

  1. Reconstruction of the medial patellofemoral ligament: Evaluation of the clinical results of autografts versus allografts.

    Calvo Rodríguez, R; Figueroa Poblete, D; Anastasiadis Le Roy, Z; Etchegaray Bascur, F; Vaisman Burucker, A; Calvo Mena, R


    The purpose of the study was to evaluate the functional results after medial patellofemoral ligament (MPFL) reconstruction in patients using auto- and allograft. A retrospective study was conducted on 28 patients with recurrent patellar dislocation, with 13 patients (13 knees) undergoing MPFL reconstruction with hamstring autograft, and 15 patients (16 knees) with reconstruction surgery with allograft. The total group included 13 males and 15 females, with an age range of 15 to 38 years. The graft-related morbidity was studied and a clinical assessment was performed using the pre- and postoperative Kujala score. Associated complications were reported for each group. All the patients had more than 12 months of follow up. No recurrent dislocations or graft related complications were reported in either group. The post-operative Kujala subjective knee score was 89.2 in the autograft group, and 92.6 in the allograft group (p >.05). One patient in the allograft group received a revision surgery due to poor positioning of anchors. Another patient in the allograft group had non-displaced patella fracture related to the bone tunnels and another patient had flexion deficit and needed mobilization under anesthesia. There were no significant differences between both groups, and the results were comparable. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  2. Diffusion tensor imaging and tractography for assessment of renal allograft dysfunction - initial results

    Hueper, Katja; Gutberlet, M.; Rodt, T.; Wacker, F.; Galanski, M.; Hartung, D. [Institute for Diagnostic and Interventional Radiology, Hannover Medical School - Germany, Hannover (Germany); Gwinner, W. [Clinic for Nephrology, Hannover Medical School - Germany, Hannover (Germany); Lehner, F. [Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School - Germany, Hannover (Germany)


    To evaluate MR diffusion tensor imaging (DTI) as non-invasive diagnostic tool for detection of acute and chronic allograft dysfunction and changes of organ microstructure. 15 kidney transplanted patients with allograft dysfunction and 14 healthy volunteers were examined using a fat-saturated echo-planar DTI-sequence at 1.5 T (6 diffusion directions, b = 0, 600 s/mm{sup 2}). Mean apparent diffusion coefficient (ADC) and mean fractional anisotropy (FA) were calculated separately for the cortex and for the medulla and compared between healthy and transplanted kidneys. Furthermore, the correlation between diffusion parameters and estimated GFR was determined. The ADC in the cortex and in the medulla were lower in transplanted than in healthy kidneys (p < 0.01). Differences were more distinct for FA, especially in the renal medulla, with a significant reduction in allografts (p < 0.001). Furthermore, in transplanted patients a correlation between mean FA in the medulla and estimated GFR was observed (r = 0.72, p < 0.01). Tractography visualized changes in renal microstructure in patients with impaired allograft function. Changes in allograft function and microstructure can be detected and quantified using DTI. However, to prove the value of DTI for standard clinical application especially correlation of imaging findings and biopsy results is necessary. (orig.)

  3. Current Safety of Renal Allograft Biopsy With Indication in Adult Recipients: An Observational Study.

    Tsai, Shang-Feng; Chen, Cheng-Hsu; Shu, Kuo-Hsiung; Cheng, Chi-Hung; Yu, Tung-Min; Chuang, Ya-Wen; Huang, Shih-Ting; Tsai, Jun-Li; Wu, Ming-Ju


    Renal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann-Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing "medullary tissue only" were susceptible to complications (P biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications.

  4. Broth versus solid agar culture of swab samples of cadaveric allograft musculoskeletal tissue.

    Varettas, Kerry


    As part of the donor assessment protocol, bioburden assessment must be performed on allograft musculoskeletal tissue samples collected at the time of tissue retrieval. Swab samples of musculoskeletal tissue allografts from cadaveric donors are received at the microbiology department of the South Eastern Area Laboratory Services (Australia) to determine the presence of bacteria and fungi. This study will review the isolation rate of organisms from solid agar and broth culture of swab samples of cadaveric allograft musculoskeletal tissue over a 6-year period, 2006-2011. Swabs were inoculated onto horse blood agar (anaerobic, 35 °C) and chocolate agar (CO2, 35 °C) and then placed into a cooked meat broth (aerobic, 35 °C). A total of 1,912 swabs from 389 donors were received during the study period. 557 (29.1 %) swabs were culture positive with the isolation of 713 organisms, 249 (34.9 %) from solid agar culture and an additional 464 (65.1 %) from broth culture only. This study has shown that the broth culture of cadaveric allograft musculoskeletal swab samples recovered a greater amount of organisms than solid agar culture. Isolates such as Clostridium species and Staphylococcus aureus would not have been isolated from solid agar culture alone. Broth culture is an essential part of the bioburden assessment protocol of swab samples of cadaveric allograft musculoskeletal tissue in this laboratory.

  5. A radiological evaluation of allografts (ethylene oxide sterilized cadaver bone and autografts in anterior cervical fusion.

    Parthiban J


    Full Text Available Serial roentgenograms of 40 patients who had 70 cervical intervertebral spaces grafted with ethylene oxide sterilized cadaver bone and 28 patients who received 44 iliac crest auto grafts for anterior cervical spine fusion, were studied. The radiological evaluation was made on the basis of settlement of intervertebral spaces, fusion rate, delayed union, non-union, graft collapse and extrusion of the graft. Indigenous methodologies were designed for the assessment of settlement of grafted intervertebral spaces in percentage. Disc space settlement was more common in autografts (93% cases than in allografts (80% cases. The average percentage of settlement of intervertebral disc space (S% was 22 in autografts and 28 in allografts during the first four months. By the end of eight months, allograft disc spaces settle more. No significant difference was noted in fusion rate at the end of one year viz. allografts (90% cases and autografts (93% cases. Autograft and allograft (ethylene oxide sterilized cadaver bone are equally useful in anterior cervical spine fusions.

  6. Effect of two cleaning processes for bone allografts on gentamicin impregnation and in vitro antibiotic release.

    Coraça-Huber, D C; Hausdorfer, J; Fille, M; Steidl, M; Nogler, M


    Bone allografts are a useful and sometimes indispensable tool for the surgeon to repair bone defects. Microbial contamination is a major reason for discarding allografts from bone banks. To improve the number of safe allografts, we suggest chemical cleaning of the grafts followed by antibiotic impregnation. Comparison of two chemical cleaning processes for bone allografts aiming for antibiotic impregnation and consequently delivery rates in vitro. Bone chips of 5-10 mm were prepared from human femoral heads. Two cleaning methods (cleaning A and cleaning B) based on solutions containing hydrogen peroxide, paracetic acid, ethanol and biological detergent were carried out and compared. After the cleaning processes, the bone chips were impregnated with gentamicin. Bacillus subtilis bioassay was used to determine the gentamicin release after intervals of 1-7 days. Differences were compared with non-parametric Mann-Whitney U tests. The zones of inhibition obtained from the bone grafts cleaned with both cleaning processes were similar between the groups. The concentration of the released antibiotic was decreasing gradually over time, following a similar pattern for both groups. The cleaning procedure A as well as the cleaning procedure B for bone allografts allowed the impregnation with gentamicin powder in the same concentrations in both groups. The delivery of gentamicin was similar for both groups. Both cleaning procedures were easy to be carried out, making them suitable for routine use at the bone banks.

  7. Currently available useful immunohistochemical markers of renal pathology for the diagnosis of renal allograft rejection.

    Kanzaki, Go; Shimizu, Akira


    Renal allograft dysfunction may be induced by various causes, including alloimmune rejection, viral infection, urinary tract obstruction, calcineurin inhibitor nephrotoxicity and/or recurrent renal disease. In order to determine the underlying cause, a renal biopsy is performed and the renal transplant pathology is diagnosed using the internationally consensus Banff classification. Although a progressive understanding of allograft rejection has provided numerous immunohistochemical markers, only the C4d is regarded to be a sufficiently useful marker for antibody-mediated allograft rejection according to the Banff classification. This review summarizes currently available useful immunohistochemical markers of renal transplant pathology, including C4d, with diagnostic implications for human renal allograft rejection. In particular, we discuss immunohistochemical markers in the following three categories: immunohistochemical markers of renal pathology used to (i) analyze the mechanisms of alloimmune rejection, (ii) monitor cell injury and/or inflammation associated with rejection and (iii) identify renal components in order to improve the diagnosis of rejection. In addition, recent progress in the field of renal transplant pathology includes the development of a new method for assessing molecular pathology using OMICS analyses. As the recent findings of various studies in patients undergoing renal transplantation are very encouraging, novel immunohistochemical markers must be also developed and combined with new technologies for the diagnosis of human renal allograft rejection.

  8. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M


    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.

  9. IL-12p40 is not required for islet allograft rejection

    En-guang BI; Wei SHI; Jia ZOU; Zhen-hua HAO; Zhen-hu LI; Duan CAI; Hua-qun ZHANG; Bing SUN


    Aim: To investigate whether IL-12p40 plays a crucial role in regulating islet allograft rejection in a streptozotocin (STZ)-induced diabetes mouse model. Methods: C57BL/6 and IL-12p40 gene knockout mice were selected as recipient mice, to which the diabetes was induced with a treatment of STZ (150-200 mg/kg) by a single ip injection. BALB/c mice were selected as donor mice and islet cells were isolated from the mice. The 500 islets were transplanted into recipient mice beneath the capsule of the left kidney. Following the islet transplantation the glucose from the mice sera was monitored and the rejection rate of islets was analyzed. Results: STZ could induce diabetes in the recipient mice within 1 week. After transplantation of allograft islets, the increased glucose in wild-type (WT) mice returned to normal level and was maintained for 10 d. Unexpectedly, the rejection rate of islet allograft between IL-12p40-deficient mice and WT mice was similar. Conclusion: The results suggested that, although islet allograft rejection is believed to be Th1-cell predominant, the Th1 response inducer, IL-12 and IL-23 are not essential to induce islet allograft rejection.

  10. Rescue Arterial Revascularization Using Cryopreserved Iliac Artery Allograft in Liver Transplant Patients.

    Mohkam, Kayvan; Darnis, Benjamin; Rode, Agnès; Hetsch, Nathalie; Balbo, Gregorio; Bourgeot, Jean-Paul; Mezoughi, Salim; Demian, Hassan; Ducerf, Christian; Mabrut, Jean-Yves


    Management of hepatic arterial complications after liver transplant remains challenging. The aim of our study was to assess the efficacy of rescue arterial revascularization using cryopreserved iliac artery allografts in this setting. Medical records of patients with liver transplants who underwent rescue arterial revascularization using cryopreserved iliac artery allografts at a single institution were reviewed. From 1992 to 2015, 7 patients underwent rescue arterial revascularization using cryopreserved iliac artery allografts for hepatic artery pseudoaneurysm (3 patients), thrombosis (2 patients), aneurysm (1 patient), or stenosis (1 patient). Two patients developed severe complications, comprising one biliary leakage treated percutaneously, and one acute necrotizing pancreatitis causing death on postoperative day 29. After a median follow-up of 75 months (range, 1-269 mo), 2 patients had an uneventful long-term course, whereas 4 patients developed graft thrombosis after a median period of 120 days (range, 2-488 d). Among the 4 patients who developed graft thrombosis, 1 patient developed ischemic cholangitis, 1 developed acute ischemic hepatic necrosis and was retransplanted, and 2 patients did not develop any further complications. Despite a high rate of allograft thrombosis, rescue arterial revascularization using cryopreserved iliac artery allografts after liver transplant is an effective and readily available approach, with a limited risk of infection and satisfactory long-term graft and patient survival.

  11. Simultaneous pancreas and kidney transplantation with concurrent allograft nephrectomy for recipients with prior renal transplants lost to BK virus nephropathy: two case reports.

    Kubal, S; Powelson, J A; Taber, T E; Goble, M L; Fridell, J A


    Candidacy for retransplantation after allograft loss due to BK virus-associated nephropathy (BKVN) with or without allograft nephrectomy is controversial. This report describes 2 renal transplant recipients who lost their grafts to BKVN and subsequently underwent simultaneous kidney and pancreas transplantation with allograft nephrectomy.

  12. Conversion from tacrolimus/mycophenolic acid to tacrolimus/leflunomide to treat cutaneous warts in a series of four pediatric renal allograft recipients.

    Nguyen, Lieuko; McClellan, Robert B; Chaudhuri, Abanti; Alexander, Steven R; Chen, Sharon F; Concepcion, Waldo; Grimm, Paul


    The challenge of immunosuppression in pediatric renal transplantation is to balance preventing rejection while avoiding infectious complications. A dermatological complication of immunosuppression is viral warts, which cause significant disfigurement and increase the risk of skin malignancy. We present three pediatric and adolescent renal allograft recipients with multiple, recalcitrant verrucae vulgares lesions and one patient with molluscum contagiosum who were switched from mycophenolate mofetil to leflunomide. Teriflunomide metabolite levels were carefully maintained between 50,000 and 100,000 ng/mL to balance its immunosuppressive and antiviral properties. No adverse events requiring discontinuation of leflunomide were encountered. Switching from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares and molluscum lesions in all four renal transplant patients. The ability to minimize and even resolve warts can improve quality of life by reducing risk of skin malignancies and emotional distress in solid organ transplant patients. Leflunomide is a potential therapeutic option for posttransplantation patients with skin warts because it serves both as an adjunct to the immunosuppressive regimen and an antiviral agent.

  13. Total allograft transplantation of the elbow joint after wide resection of synovial cell sarcoma: a case series.

    Hossein, E M; Ashraf, H; Peivandi, L


    Total elbow allograft transplantation is an option for patients who have extensive joint defects secondary to tumor surgery, trauma, or failed total elbow arthroplasty. This salvage procedure provides patients with a useful, painless range of motion of the elbow. We report our experience with two complete elbow allograft reconstructions after tumor resection surgery with 5 and 6 years of follow-up.

  14. Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded allograft

    J O Eniwumide


    Full Text Available Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as controls and the experimental groups comprised autologous bone marrow derived stem cell seeded allograft, biphasic calcium phosphate (BCP and tricalcium phosphate (TCP, respectively. All implants were implanted in the back muscle of adult Dutch milk goats for 12 weeks. Micro-computed tomography (µCT analysis and histomorphometry was performed to evaluate and quantify ectopic bone formation. In good agreement, both µCT and histomorphometric analysis demonstrated a significant increase in bone formation by cell-seeded calcium phosphate scaffolds as compared to the autograft, allograft and cell-seeded allograft implants. An extensive resorption of the autograft, allograft and cell-seeded allograft implants was observed by histology and confirmed by histomorphometry. Cell-seeded TCP implants also showed distinct signs of degradation with histomorphometry and µCT, while the degradation of the cell-seeded BCP implants was negligible. These results indicate that cell-seeded calcium phosphate scaffolds are superior to autograft, allograft or cell-seeded allograft in terms of bone formation at ectopic implantation sites. In addition, the usefulness of µCT for the efficient and non-destructive analysis of mineralised bone and calcium phosphate scaffold was demonstrated.

  15. Periosteal augmentation of allograft bone and its effect on implant fixation - an experimental study on 12 dogs()

    Barckman, Jeppe; Baas, Jorgen; Sørensen, Mette;


    Periosteum provides essential cellular and biological components necessary for fracture healing and bone repair. We hypothesized that augmenting allograft bone by adding fragmented autologous periosteum would improve fixation of grafted implants.......Periosteum provides essential cellular and biological components necessary for fracture healing and bone repair. We hypothesized that augmenting allograft bone by adding fragmented autologous periosteum would improve fixation of grafted implants....

  16. ICOS-Ig combined with CsA induces long term survival of cardiac allografts in mouse

    Zhang Peng; Wang Zhenmeng; Qin Qin; Tang Yi; Wang Quanxing; Shen Qian


    Objective: To study the synergistic effect of ICOS-Ig combined with cyclosporine (CsA) on mouse heart transplantation and explore its therapeutic potential. Methods: ICOS-Ig fusion protein was generated by fusing the extracellular portion of human ICOS and Fc portion of human IgG. To investigate the effect of ICOS-Ig on T-cell proliferation in vitro, ICOS-Ig or IgG was added to the primary MLR cultures (BALB/c spleen T cells as responder cells and irradiated C57BL/6 spleen cells as stimulator cells). The cells responsiveness rates were detected by 3H-TdR methods. Then the T cells of each group in primary MLR were cultured as responder cells for secondary MLR, and irradiated C57BL/6 (donor) or C3H (third party) spleen cells as stimulator cells. To study the effect of ICOS-Ig on T-cell proliferation in vivo, CFSE-labeled C57BL/6 spleen cells were transferred to irradiated BALB/c mice. Mice were then treated with IgG, ICOS-Ig or CsA. Seventy two hours after transfer, the spleen cells of the mice were harvested for the detection of CD4+CFSE+ and CD8+CFSE+ by FACS. C57BL/6 mouse underwent transplantation of the hearts of BALB/c mouse and were then randomly divided into five equal groups: no treatment group, control IgG treated group (250 μg i.p. d2, 4, 6), ICOS-Ig treated group (250 μg i.p. d2, 4, 6), CsA treated group (10 mg/kg i.p. d0-6), ICOS-Ig combined with CsA group. The cardiac allograft survival was monitored by daily palpation. Results: In primary MLR, ICOS-Ig inhibited T-cell proliferation, (inhibition ratio 58±8.2% in 50 μg/ml). In secondary MLR, ICOS-Ig specifically inhibited donor spleen cells, which suggested ICOS-Ig could induce donor-specific hyporesponsiveness. In the CFSE dye assay, CD4+CFSE+ and CD8+CFSE+ in ICOS-Ig and CsA group was stronger than those in control group, which showed ICOS-Ig and CsA could inhibit the proliferation of allo-reactive T cells in vivo. In mouse heart transplantation model, survival was significantly prolonged in

  17. Prolonged acute hepatitis A mimicking autoimmune hepatitis

    Rintaro Mikata; Osamu Yokosuka; Fumio Imazeki; Kenichi Fukai; Tatsuo Kanda; Hiromitsu Saisho


    AIM: We report a case with a prolonged course of hepatitisA, with alanine aminotransferase (ALT) higher than 500 IU/Lfor more than 2 mo.METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive arti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out.RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCAproved to be effective.

  18. Stratum corneum barrier integrity controls skin homeostasis.

    Smith, W


    The stratum corneum water barrier controls structural and functional properties of both the epidermis and the dermis. Treatments which chronically disrupt the stratum corneum water barrier can induce changes similar to those seen with 'anti-aging' treatments such as (-Hydroxy acids (AHAs) and Retin Atrade mark. Barrier disruption via daily tape stripping increases epidermal and dermal thickness, superficial and integral skin firmness, and improves skin surface texture. Modest or transitory disruption did not produce such effects. Similar results were observed with topical application of AHAs, retinoids or mild irritants after about 4-6 weeks provided such treatments resulted in prolonged elevation in TEWL (trans-epidermal water loss). Treatments that did not chronically elevate TEWL could also produce positive cosmetic effects, but such effects were in general restricted to the skin surface or epidermis. Irritation, which was observed with some treatments, was not solely responsible for the positive effects observed.

  19. Surgical treatment of infective endocarditis with aortic and tricuspid valve involvement using cryopreserved aortic and mitral valve allografts.

    Ostrovsky, Yury; Spirydonau, Siarhei; Shchatsinka, Mikalai; Shket, Aliaksandr


    Surgical treatment of infective and prosthetic endocarditis using allografts gives good results. Aortic allograft implantation is a common technique, while tricuspid valve replacement with a mitral allograft is very rare. Multiple valve disease in case of infective endocarditis is a surgical challenge as such patients are usually in a grave condition and results of surgical treatment are often unsatisfactory. In this article we describe a clinical case of successful surgical treatment in a patient with active infective endocarditis of aortic and tricuspid valve, complicated by an aortic-right ventricular fistula. The aortic valve and ascending aorta were replaced with a cryopreserved aortic allograft; the tricuspid valve was replaced with a cryopreserved mitral allograft. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  20. Determination of mechanical properties of impacted human morsellized cancellous allografts for revision joint arthroplasty.

    Tanabe, Y; Wakui, T; Kobayashi, A; Ohashi, H; Kadoya, Y; Yamano, Y


    This paper deals with the characterization of mechanical properties of impacted morsellized cancellous allograft (IMCA) produced by dynamic compaction of allograft femoral heads ground by commercially available bone mills, i.e. rotating rasp and reciprocating type bone mills. Various ranges and profiles of particle size in the graft aggregates were obtained using these bone mills, and the effect of number of compaction as well as the distribution of particle sizes on the mechanical properties of IMCA under quasistatic compression and shear loading conditions was discussed. The morsellized cancellous allograft prepared by the reciprocating type bone mill showed a broad distribution of particle sizes, and gave IMCA superior mechanical properties to the graft with a more uniform size distribution, or prepared by the rotating rasp type bone mills. The increase of number of compaction also improved the mechanical properties of IMCA in compression.

  1. Evaluation of an Osseous Allograft Membrane for Guided Tissue Regeneration in the Dog.

    Stepaniuk, Kevin S; Gingerich, Wade


    Clinical application of a demineralized freeze-dried cortical bone membrane allograft (DFBMA) for treatment of intra(infra)bony periodontal pockets in dogs was evaluated. The mean pre-treatment periodontal probing depth equaled 7.2-mm. Post-treatment probing depths in all 11 cases were normal, with a mean periodontal probing gain of 5.4-mm. Guided tissue regeneration using a commercially available veterinary canine DFBMA and canine demineralized freeze-dried bone allograft (DFDBA) resulted in clinically significant periodontal attachment gains. The gain of new periodontal tissue attachment was statistically significant (P < 0.0001). The commercially available veterinary allograft products predictably increased new periodontal attachment without any identified membrane sequelae in these 11 cases.

  2. Acute Page kidney following renal allograft biopsy: a complication requiring early recognition and treatment.

    Chung, J; Caumartin, Y; Warren, J; Luke, P P W


    The acute Page kidney phenomenon occurs as a consequence of external compression of the renal parenchyma leading to renal ischemia and hypertension. Between January 2000 and September 2007, 550 kidney transplants and 518 ultrasound-guided kidney biopsies were performed. During that time, four recipients developed acute oligo-anuria following ultrasound-guided allograft biopsy. Emergent doppler-ultrasounds were performed demonstrating absence of diastolic flow as well as a sub-capsular hematoma of the kidney. Prompt surgical exploration with allograft capsulotomy was performed in all cases. Immediately after capsulotomy, intraoperative Doppler study demonstrated robust return of diastolic flow. Three patients maintained good graft function, and one kidney was lost due to acute antibody-mediated rejection. We conclude that postbiopsy anuria associated with a subcapsular hematoma and acute absence of diastolic flow on doppler ultrasound should be considered pathognomonic of APK. All renal transplant specialists should be able to recognize this complication, because immediate surgical decompression can salvage the allograft.

  3. Anterior cruciate ligament reconstruction using the bone-posterior cruciate ligament-bone allograft

    JIAO Chen; AO Ying-fang; LIU Ping; XIE Xing; LIU Chen; MA Yong


    Background AIIografts were widely used in anterior cruciate ligament (ACL) reconstruction for patients with ACL rupture of the knee.This study was to approve the feasibility of bone-posterior cruciate ligament-bone (BPCLB) allograft transplantation in ACL reconstruction.Methods Eight patients underwent ACL reconstructions with BPCLB allografts and were followed up for an average period of 32 months after operation.Results Subjective parameters including Intemational Knee Documentation Committee (IKDC),modified Larson knee ligament,Lysholm,and Tegner rating scales were much improved and side to side KT-2000 arthrometer difference was much less postoperatively.Pivot shift test was negative in all patients.The reconstructed ACL had satisfactory shape and tension.Conclusions BPCLB allograft is an optional choice forACL reconstruction.

  4. The Use of Structural Allograft in Primary and Revision Knee Arthroplasty with Bone Loss

    Raul A. Kuchinad


    Full Text Available Bone loss around the knee in the setting of total knee arthroplasty remains a difficult and challenging problem for orthopaedic surgeons. There are a number of options for dealing with smaller and contained bone loss; however, massive segmental bone loss has fewer options. Small, contained defects can be treated with cement, morselized autograft/allograft or metal augments. Segmental bone loss cannot be dealt with through simple addition of cement, morselized autograft/allograft, or metal augments. For younger or higher demand patients, the use of allograft is a good option as it provides a durable construct with high rates of union while restoring bone stock for future revisions. Older patients, or those who are low demand, may be better candidates for a tumour prosthesis, which provides immediate ability to weight bear and mobilize.

  5. Postrenal transplant urinary leakage caused by segmental infarction of a renal allograft treated by partial nephrectomy.

    Salehipour, Mehdi; Roozbeh, Jamshid; Eshraghian, Ahad; Nikeghbalian, Saman; Salahi, Heshmatollah; Bahador, Ali; Malek-hosseini, Seyed Ali


    Kidney transplant is the final treatment for patients with end-stage renal disease. Urinary leakage is the most-common surgical complication early after transplant. Another complication in the early posttransplant period is segmental allograft infarction. We report a kidney recipient who developed urinary leakage secondary to a segmental infarction of the upper pole of the transplanted kidney 2 months after transplant. The patient was treated successfully by a partial nephrectomy of the infracted upper lobe of the kidney. Three months after the partial nephrectomy of the allograft, serum blood urea nitrogen and creatinine were normal, and the patient was able to partake in her daily activities. Partial nephrectomy in the context of infarction of a kidney allograft is safe and can be used in similar cases.

  6. Antibody-engineered nanoparticles selectively inhibit mesenchymal cells isolated from patients with chronic lung allograft dysfunction.

    Cova, Emanuela; Colombo, Miriam; Inghilleri, Simona; Morosini, Monica; Miserere, Simona; Peñaranda-Avila, Jesus; Santini, Benedetta; Piloni, Davide; Magni, Sara; Gramatica, Furio; Prosperi, Davide; Meloni, Federica


    Chronic lung allograft dysfunction represents the main cause of death after lung transplantation, and so far there is no effective therapy. Mesenchymal cells (MCs) are primarily responsible for fibrous obliteration of small airways typical of chronic lung allograft dysfunction. Here, we engineered gold nanoparticles containing a drug in the hydrophobic section to inhibit MCs, and exposing on the outer hydrophilic surface a monoclonal antibody targeting a MC-specific marker (half-chain gold nanoparticles with everolimus). Half-chain gold nanoparticles with everolimus have been synthesized and incubated with MCs to evaluate the effect on proliferation and apoptosis. Drug-loaded gold nanoparticles coated with the specific antibody were able to inhibit proliferation and induce apoptosis without stimulating an inflammatory response, as assessed by in vitro experiments. These findings demonstrate the effectiveness of our nanoparticles in inhibiting MCs and open new perspectives for a local treatment of chronic lung allograft dysfunction.

  7. Emphysematous pyelonephritis in failed renal allograft: Case report and review of literature.

    Bansal, Rahul Kumar; Lambe, Shahid; Kapoor, Anil


    Emphysematous pyelonephritis (EPN) in renal allograft is rare but potentially lethal complication and requires aggressive medical and/or surgical therapy to achieve cure. We report a case of 60-year-old diabetic male with poor cardiac function on maintenance hemodialysis, who underwent delayed allograft nephrectomy for EPN in failed renal allograft. Blood culture grew Bacteroides. He was stable in the postoperative period but passed away on day 4 due to myocardial infarction likely secondary to poor baseline cardiac function. Delay in diagnosis and treatment could have contributed to this unfavorable outcome. There is a paucity of published literature regarding EPN in the transplant population, such that management decisions (percutaneous conservative versus urgent surgical) are challenging. Further studies are required to establish treatment guidelines.

  8. Renal allograft accumulation of Tc-99m sulfur colloid: temporal quantitation and scintigraphic assessment

    George, E.A.; Meyerovitz, M.; Codd, J.E.; Fletcher, J.W.; Donati, R.M.


    Renal allograft accumulation of Tc-99m sulfur colloid (TSC) was studied using visual assessment of scintigraphic displays and a quantitative temporal model in 210 examinations of 56 transplant recipients. The quantitative temporal model related the immediate pool of the radioagent in the transplant to the fixed allograft accumulation of TSC at 20 minutes after administration. Examinations performed less than 3 days after grafting or steroid pulse therapy were excluded. Rejection was established by clinical and biochemical evaluation in all 84 examinations that showed acute or chronic allograft rejection. Rejection was accurately diagnosed by visual scintigraphic assessment in 82% of the established cases; this improved to 99% with relative temporal quantitation analysis. Sensitivity improved from 78% by visual examination to 95% with temporal quantitation and specificity improved from 83% to 100%.

  9. Safety information on QT-interval prolongation

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;


    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve......) was moderate (kappa 0.434). However, the agreement in expected clinical decisions based on the product labels was much higher (kappa 0.673). The US drug label tends to be more explicit, especially when it considers absence of QT effects....

  10. Impaired elastin deposition in Fstl1-/- lung allograft under the renal capsule.

    Yan Geng

    Full Text Available Lung alveolar development in late gestation is a process important to postnatal survival. Follistatin-like 1 (Fstl1 is a matricellular protein of the Bmp antagonist class, which is involved in the differentiation/maturation of alveolar epithelial cells during saccular stage of lung development. This study investigates the role of Fstl1 on elastin deposition in mesenchyme and subsequent secondary septation in the late gestation stage of terminal saccular formation. To this aim, we modified the renal capsule allograft model for lung organ culture by grafting diced E15.5 distal lung underneath the renal capsule of syngeneic host and cultured up to 7 days. The saccular development of the diced lung allografts, as indicated by the morphology, epithelial and vascular developments, occurred in a manner similar to that in utero. Fstl1 deficiency caused atelectatic phenotype companied by impaired epithelial differentiation in D3 Fstl1(-/- lung allografts, which is similar to that of E18.5 Fstl1(-/- lungs, supporting the role of Fstl1 during saccular stage. Inhibition of Bmp signaling by intraperitoneal injection of dorsomorphin in the host mice rescued the pulmonary atelectasis of D3 Fstl1(-/- allografts. Furthermore, a marked reduction in elastin expression and deposition was observed in walls of air sacs of E18.5 Fstl1(-/- lungs and at the tips of the developing alveolar septae of D7 Fstl1(-/- allografts. Thus, in addition to its role on alveolar epithelium, Fstl1 is crucial for elastin expression and deposition in mesenchyme during lung alveologenesis. Our data demonstrates that the modified renal capsule allograft model for lung organ culture is a robust and efficient technique to increase our understanding of saccular stage of lung development.

  11. Aortic allografts in treatment of aortic valve and ascending aorta prosthetic endocarditis

    S.V. Spiridonov


    Full Text Available The aim – to assess short- and long-term results of aortic root replacement using aortic allografts in patients with prosthetic endocarditis. Materials and methods. Since February 2009 until June 2016 aortic valve and ascending aorta replacement using aortic allografts was performed in 26 patients with prosthetic endocarditis. In 50 % of cases at initial operation aortic valve replacement was performed, in another 50 % of cases – aortic valve and ascending aorta replacement. Echocardiography was performed 10 days, 3, 6 and 12 months, 2, 3 and 5 years after surgery. Analysis of long-term results included all cases of deaths, prosthesis-related complications and recurrence of endocarditis. Results. 30-day mortality was 23.1 %. Extracorporeal membranous oxygenation (ECMO was used only in 5 patients (19.2 %. Four patients were weaned from ECMO. We did not observe any allograft-related complications. During follow-up period there were no cases of reoperation due to structural allograft failure. Relapse of infection occurred in 1 patient (3.8 % four years after the operation and led to lethal outcome. Conclusion. Reoperations using allografts are an effective surgical treatment of prosthetic endocarditis. In majority of cases prosthetic endocarditis was caused by gram-positive cocci (Staphylococcus. In 84.6 % of cases it was associated with destruction of paravalvular structures and abscesses formation. Heart failure was a causative factor of different complications in these patients, which required ECMO in 19.2 % of patients. In 80 % of cases patients were weaned from ECMO. Allografts using for the treatment of prosthetic endocarditis is associated with high resistance to infection and with a significant rate of freedom from recurrence of endocarditis within 3 years after surgery.

  12. Ankle arthrodesis fusion rates for mesenchymal stem cell bone allograft versus proximal tibia autograft.

    Anderson, John J; Boone, Joshua J; Hansen, Myron; Brady, Chad; Gough, Adam; Swayzee, Zflan


    Ankle arthrodesis is commonly used in the treatment of ankle arthritis. The present study compared mesenchymal stem cell (MSC) bone allografts and proximal tibia autografts as adjuncts in performing ankle arthrodesis. A total of 109 consecutive ankle fusions performed from 2002 to 2008 were evaluated retrospectively. Of the 109 fusions, 24 were excluded from the present study, leaving 85 patients who had undergone ankle arthrodesis. Of the 85 patients, 41 had received a proximal tibia autograft and 44, an MSC bone allograft. These 2 groups were reviewed and compared retrospectively at least 2 years postoperatively for the overall fusion rate, interval to radiographic fusion, and interval to clinical fusion. A modified and adjusted American College of Foot and Ankle Surgeons ankle scale was used to measure patient satisfaction. The overall fusion rate was 84.1% in the MSC bone allograft group and 95.1% in the proximal tibia autograft group (p = .158). The corresponding mean intervals to radiographic fusion were 13.0 ± 2.5 weeks and 11.3 ± 2.8 weeks (p ≤ .001). The interval to clinical fusion was 13.1 ± 2.1 weeks and 11.0 ± 1.5 weeks (p ≤ .001) in the MSC bone allograft and proximal tibia autograft group, respectively. No statistically significant difference was found in the fusion rates between the MSC bone allograft and proximal tibia autograft groups. Also, no statistically significant difference was found between the preoperative and postoperative scores using a modified and adjusted American College of Foot and Ankle Surgeons ankle scale between the 2 groups (p = .41 and p = .44, respectively). A statistically significant delay to radiographic and clinical fusion was present in the MSC bone allograft group compared with the proximal tibia autograft group; however, no difference was found in patient satisfaction.

  13. T2' imaging of native kidneys and renal allografts. A feasibility study

    Mathys, C.; Blondin, D.; Wittsack, H.J.; Miese, F.R.; Rybacki, K.; Walther, C.; Holstein, A.; Lanzman, R.S. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Radiologie


    Purpose: To evaluate the feasibility of T2' mapping in native kidneys and renal allografts. Materials and Methods: Following approval of the local ethics committee, 24 renal allograft recipients and 10 control subjects (healthy volunteers) were included in this study. Multi-echo T2 and T2{sup *} imaging was performed on a 1.5 Tesla scanner. Allograft recipients were assigned to two groups: group (a), 8 patients with good (glomerular filtration rate of more than 40 ml/min) allograft function and no evidence of transplant rejection, transplant renal artery stenosis or ureteral obstruction; group (b), 16 patients with deterioration of renal graft function (glomerular filtration rate (GFR) of 40 ml/min or less). Two different imaging protocols were tested. Results: The mean T2' relaxation parameters were 108.33 msec {+-} 13.34, 100.00 msec {+-} 18.89 and 124.57 msec {+-} 6.51 for groups (a), (b) and for control subjects, respectively. The reduction of T2' values in patient group (b) was not statistically significant. However, significant correlations could be demonstrated between T2' values and the glomerular filtration rate (GFR) of renal allograft function. The reproducibility was tested and the coefficients of variation of T2' values in the cortex of transplanted kidneys were 11.1 % within subjects and 11.3 % between subjects. Conclusion: Our results indicate that T2' imaging is a promising non-enhanced technique, which seems to reveal information on transplant function. Further studies are required to determine the clinical value of T2' mapping for monitoring renal allograft recipients. (orig.)

  14. Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure

    Acker Michael A


    Full Text Available Abstract Background Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated. Methods 709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%. A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function. Results Etiology of primary graft failure included transplant arteriopathy (n = 10, acute rejection (n = 3, hyperacute rejection (n = 1, and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1. Mean age at retransplantation was 45.5 ± 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 ± 12.2% at a mean follow-up of 32.6 ± 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 ± 95.7 mos post-transplant. Conclusion Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.

  15. Comparison of Clinical Outcome of Autograft and Allograft Reconstruction for Anterior Cruciate Ligament Tears

    Yu-Hua Jia; Peng-Fei Sun


    Background: Hamstring (HS) autograft and bone-patellar tendon-bone allograft are the most common choice for reconstruction of anterior cruciate ligament (ACL).There was a little report about the clinical outcome and difference of arthroscopic ACL reconstruction using allograft and autograft.This study aimed to compare the clinical outcome of autograft and allograft reconstruction for ACL tears.Methods: A total of 106 patients who underwent surgery because of ACL tear were included in this study.The patients were randomly divided into two groups, including 53 patients in each group.The patients in group Ⅰ underwent standard ACL reconstruction with HS tendon autografts, while others in group Ⅱ underwent reconstruction with bone-patellar tendon-bone allograft.All the patients were followed up and analyzed;the mean follow-up was 81 months (range: 28-86 months).Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC), Lysholm scores, physical instability tests, and patient satisfaction questionnaires.The complication rates of both groups were compared.Tibial and femoral tunnel widening were assessed using lateral and anteroposterior radiographs.Results: At the end of follow-up, no significant differences were found between the groups in terms of IKDC, Lysholm scores, physical instability tests, patient satisfaction questionnaires, and incidences of arthrofibrosis.Tibial and femoral tunnel widening was less in the HS tendon autografts.This difference was more significant on the tibial side.Conclusions: In the repair of ACL tears, allograft reconstruction is as effective as the autograft reconstruction, but the allograft can lead to more tunnel widening evidently in the tibial tunnel, particularly.

  16. Evaluation of renal allograft function early after transplantation with diffusion-weighted MR imaging

    Eisenberger, Ute; Frey, Felix J. [University Hospital of Bern, Department of Nephrology and Hypertension, Bern (Switzerland); Thoeny, Harriet C. [University Hospital of Bern, Department of Radiology, Neuroradiology and Nuclear Medicine, Bern (Switzerland); Binser, Tobias; Boesch, Chris [University Hospital of Bern, Department of Clinical Research, Bern (Switzerland); Gugger, Mathias [University Hospital of Bern, Department of Pathology, Bern (Switzerland); Vermathen, Peter [University Hospital of Bern, Department of Clinical Research, Bern (Switzerland); University Bern, Department of Clinical Research/AMSM, Pavillon 52, Inselspital, P.O. Box 35, Bern (Switzerland)


    To determine the inter-patient variability of apparent diffusion coefficients (ADC) and concurrent micro-circulation contributions from diffusion-weighted MR imaging (DW-MRI) in renal allografts early after transplantation, and to obtain initial information on whether these measures are altered in histologically proven acute allograft rejection (AR). DW-MRI was performed in 15 renal allograft recipients 5-19 days after transplantation. Four patients presented with AR and one with acute tubular necrosis (ATN). Total ADC (ADC{sub T}) was determined, which includes diffusion and micro-circulation contributions. Furthermore, diffusion and micro-circulation contributions were separated, yielding the ''perfusion fraction'' (F{sub P}), and ''perfusion-free'' diffusion (ADC{sub D}). Diffusion parameters in the ten allografts with stable function early after transplantation demonstrated low variabilities. Values for ADC{sub T} and ADC{sub D} were (x 10{sup -5} mm{sup 2}/s) 228 {+-} 14 and 203 {+-} 9, respectively, in cortex and 226 {+-} 16 and 199 {+-} 9, respectively, in medulla. F{sub P} values were 18 {+-} 5% in cortex and 19 {+-} 5% in medulla. F{sub P} values were strongly reduced to less than 12% in cortex and medulla of renal transplants with AR and ATN. F{sub P} values correlated with creatinine clearance. DW-MRI allows reliable determination of diffusion and micro-circulation contributions in renal allografts shortly after transplantation; deviations in AR indicate potential clinical utility of this method to non-invasively monitor derangements in renal allografts. (orig.)

  17. The effect of adjuvant chemotherapy on osteoarticular allografts.

    Hazan, E J; Hornicek, F J; Tomford, W; Gebhardt, M C; Mankin, H J


    Two hundred lower extremity osteoarticular allografts (in 200 patients) performed for aggressive or malignant bone tumors between 1976 and 1997 included 124 grafts of the distal femur, 46 of the proximal tibia, and 30 of the proximal femur. Seventy-four patients did not receive chemotherapy, and 126 received either adjuvant or neoadjuvant therapy. The diagnoses, mean ages, and length of followup were different for the two groups because most of the patients in the chemotherapy group had osteosarcoma, whereas the largest number in the control group had chondrosarcoma or parosteal osteosarcoma. The extent of the surgery was essentially the same for both patient groups, as is reflected by a low recurrence rate (7% for the control and 6% for the chemotherapy group). A statistical comparison of the various parameters showed that the infection, fracture, and amputation rates were the same, but the nonunion rate was markedly increased in the patients who received chemotherapy (32% versus 12%). Cox regression and Kaplan-Meier studies showed that chemotherapy had a significant effect on outcome, with the success rates for the two groups being quite different (72% versus 56%). The results for the distal femur showed a greater effect than for either the proximal tibia or the proximal femur. Analysis of these data suggest the distal femur is perhaps the most prone to healing problems, possibly based in part on the extent of the surgery. A final study supports the concept that the results improved in later years, suggesting a modification or application of the drugs used, better selection of patients, and improvements in surgical technique.

  18. Outcome of pregnancy in renal allograft recipients: SIUT experience.

    Naqvi, R; Noor, H; Ambareen, S; Khan, H; Haider, A; Jafri, N; Alam, A; Aziz, R; Manzoor, K; Aziz, T; Ahmed, E; Akhtar, F; Naqvi, A; Rizvi, A


    The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

  19. Intrapancreatic Splenule in a Pancreas Allograft: Case Report.

    Yadav, K; Serrano, O K; Kandaswamy, R


    A 16-year-old white man was involved in a motor vehicle collision and suffered head, chest, and abdominal trauma. Despite initial resuscitative efforts, he progressed to brain death and was designated to be an organ donor by his family. He had no earlier medical or surgical history and no high-risk behaviors. Blood work revealed normal creatinine, liver function tests, lipase, and amylase. Viral serologies were negative except for cytomegalovirus IgG and Epstein-Barr virus nucleic acid. Imaging revealed a right kidney contusion, a manubrial fracture, and fractures of right first rib and bilateral scapulae. No other abdominal trauma was identified, specifically to the pancreas, duodenum, or spleen. Our transplant center accepted the pancreas from this donor. During back-table inspection of the pancreas, a 1.5 × 1.5 cm dark purple rubbery mass was identified within the parenchyma of the pancreas in the tail. An incisional biopsy of the lesion was sent for frozen section, which yielded a mixed inflammatory infiltrate consisting of neutrophils and lymphocytes and an overlying fibrous capsule. The diagnosis of lymphoma or another neoplasm could not be definitely ruled out. Owing to uncertainty in diagnosis, the entire lesion was excised along with the distal pancreas with the use of a linear stapler. The staple line was oversewn with running 4-0 polypropylene suture, and the pancreas was transplanted. After surgery, the pancreas allograft functioned well with a small pancreatic leak, which had resolved by the first postoperative outpatient visit. Published by Elsevier Inc.

  20. Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

    Grupper, Avishay; Grupper, Ayelet; Daly, Richard C; Pereira, Naveen L; Hathcock, Matthew A; Kremers, Walter K; Cosio, Fernando G; Edwards, Brooks S; Kushwaha, Sudhir S


    Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m(2) at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Nasal dorsal augmentation with freeze-dried allograft bone.

    Clark, Richard P; Wong, Granger; Johnson, Loche M; Hagge, Rosalie J; Ciminello, Frank; Lee, John; Stone, Kiki I; Clark, Isabel A


    Properly prepared freeze-dried bone has been used with impunity by orthopedic surgeons since 1992 without a single report of disease transmission. The aim of this study was to evaluate freeze-dried cortical allograft bone for nasal dorsal augmentation. Freeze-dried human cortical bone was obtained from DCI Donor Services, Nashville, Tennessee. Standards recommended by the American Association of Tissue Banks, the U.S. Food and Drug Administration, and the Centers for Disease Control and Prevention were followed. Objective evaluation of the persistence of graft volume was obtained by cephalometric radiography. Vascularization and incorporation of new bone elements within the grafts were demonstrated by using fluorine-18 sodium fluoride positron emission tomographic/computed tomographic scanning. The average persistence of projection in 18 patients was 87 percent at 6 months. Thereafter, 10 patients showed 100 percent maintenance of projection at 12 to 36 months. Vascularization and incorporation of new bone elements within the grafts were demonstrated by using fluorine-18 sodium fluoride positron emission tomographic/computed tomographic scanning in four patients. The initial loss of 13 percent of projection is most likely attributable to resolution of early surgical edema. The authors postulate that there are two pathways based on whether the recipient bed allows vascular access to the graft. The revascularization or inductive pathway involves stem cell conversion to eventual osteoblasts. The scar bed barrier or noninductive pathway involves the preservation of the graft as an unchanged alloimplant. This report is the first of a series that will include a 5-year and a 10-year follow-up.

  2. Anterior cruciate ligament reconstruction with fresh-frozen patellar tendon allografts.

    Valenti, J R; Sala, D; Schweitzer, D


    A prospective study was performed on 30 patients who underwent an anterior cruciate ligament reconstruction with fresh-frozen patellar tendon allograft. An arthroscopic technique alone was used in 10 patients, and in the other 20 patients this was combined with a miniarthrotomy. After a mean follow up of 35 months, the overall functional results were satisfactory in 85%. There were no cases of infection, disease transmission or tissue rejection. Fresh-frozen patellar tendon allografts are a good method of anterior cruciate reconstruction.

  3. Donor-Derived Ip-10 Initiates Development of Acute Allograft Rejection

    Hancock, Wayne W.; Gao, Wei; Csizmadia, Vilmos; Faia, Kerrie L.; Shemmeri, Nida; Luster, Andrew D.


    An allograft is often considered an immunologically inert playing field on which host leukocytes assemble and wreak havoc. However, we demonstrate that graft-specific physiologic responses to early injury initiate and promulgate destruction of vascularized grafts. Serial analysis of allografts showed that intragraft expression of the three chemokine ligands for the CXC chemo-kine receptor CXCR3 was induced in the order of interferon (IFN)-γ–inducible protein of 10 kD (IP-10, or CXCL10), IFN-i...

  4. Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome.

    Garvey, J P


    Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN.

  5. Anatomical Glenoid Reconstruction Using Fresh Osteochondral Distal Tibia Allograft After Failed Latarjet Procedure.

    Sanchez, Anthony; Ferrari, Marcio B; Akamefula, Ramesses A; Frank, Rachel M; Sanchez, George; Provencher, Matthew T


    In the treatment of recurrent anterior glenohumeral instability, the Latarjet procedure has been shown to fail. This results in a need for viable revisional procedures for patients who present with this challenging pathology. We report our preferred technique for anatomical glenoid reconstruction using a fresh osteochondral distal tibia allograft after a failed Latarjet procedure. This bony augmentation technique employs a readily available dense, weight-bearing osseous tissue source that has excellent conformity, as well as the added benefit of a cartilaginous surface to correct chondral deficiencies. Given its effectiveness in the Latarjet revision setting and low complication rate, the distal tibia allograft is a reasonable treatment option.

  6. Experi mental Study on Preparation of Decellularized Artery Vascular Graftand Transplantation of Carotid Artery Allografts


    1 IntroductionRemoval of cells may decrease the antigenicity of artery allografts and xenografts~([1~3]). This study was to set up a new process to prepare the decellularized artery grafts. And the feasibility of small diameter decellularized artery allografts in vivo was evaluate. 2 Materials and Methods2.1 Set up a new processA four-step process, including hypotonic, hypertonic solutions and combining with 1% t-octyl-phenoxypolyethoxyethanol (Triton X-100) and 1% sodium dodecyl sulfate (SDS) detergents, w...

  7. Outcome of Kidney Allografts in Recipients With a Femoral Arteriovenous Fistula: Report of Two Cases

    Denise M.D. Özdemir-van Brunschot


    Full Text Available Two patients, who were on hemodialysis over a femoral arteriovenous fistula, were transplanted in our center. Despite adequate blood pressure, perfusion of the renal allograft remained poor after completion of the vascular anastomoses. Ligation of the femoral arteriovenous fistula (1.6 L/min led to adequate perfusion. Initial graft function was good. Although it remains unclear whether ischemia of a renal allograft is caused by venous hypertension or vascular steal due to a femoral arteriovenous fistula, it might be necessary to ligate a femoral arteriovenous fistula to obtain adequate graft perfusion.

  8. Successful treatment of verruca vulgaris with Thuja occidentalis in a renal allograft recipient

    R Joseph


    Full Text Available Human papillomavirus-driven verruca vulgaris infection is common in solid organ transplant recipients and increases the risk for squamous cell carcinoma. The available treatment modalities have limited response. We report a renal allograft recipient who presented with multiple warts not responding to cryotherapy and radiosurgery with one turning malignant, needing amputation of the finger. An extract from Thuja occidentalis (White cedar tree cured the resistant warts on the other fingers, leaving only superficial scars and without affecting allograft function. We have reviewed the pharmacological and clinical properties of T. occidentalis.

  9. Renal allograft recovery subsequent to apparent hyperacute rejection based on clinical, scintigraphic, and pathologic criteria

    Sacks, G.A.; Sandler, M.P.; Partain, C.L.


    An unusual case is described in which in spite of clinical, scintigraphic and histologic findings strongly supportive of a diagnosis of hyperacute rejection, recovery of renal function occurred. These findings are in contrast to the current literature in which it is generally accepted that a renal allograft showing neither pertechnetate transit nor hippurate concentration warrants allograft nephrectomy irrespective of the etiology. Scintigraphic evaluation included both dynamic studies after a bolus administration of /sup 99m/Tc pertechnetate and serial renogram collections after the intravenous administration of /sup 131/I Hippuran.

  10. Skin Care and Aging

    ... version of this page please turn Javascript on. Skin Care and Aging How Aging Affects Skin Your skin changes with age. It becomes thinner, ... to make it feel and look better. Dry Skin and Itching Click for more information Many older ...


    Suzanne Schneider


    Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

  12. Carotid Baroreflex Function During Prolonged Exercise

    Raven, P. B.


    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  13. Ridge preservation comparing socket allograft alone to socket allograft plus facial overlay xenograft: a clinical and histologic study in humans.

    Poulias, Evmenios; Greenwell, Henry; Hill, Margaret; Morton, Dean; Vidal, Ricardo; Shumway, Brian; Peterson, Thomas L


    Previous studies of ridge preservation showed a loss of ≈18% or 1.5 mm of crestal ridge width in spite of treatment. The primary aim of this randomized, controlled, masked clinical trial is to compare a socket graft to the same treatment plus a buccal overlay graft, both with a polylactide membrane, to determine if loss of ridge width can be prevented by use of an overlay graft. Twelve patients who served as positive controls received an intrasocket mineralized cancellous allograft (socket group), and 12 patients received the same socket graft procedure plus buccal overlay cancellous xenograft (overlay group). Horizontal ridge dimensions were measured with a digital caliper, and vertical ridge changes were measured from a stent. Before implant placement, at 4 months, a trephine core was obtained for histologic analysis. The mean horizontal ridge width at the crest for the socket group decreased from 8.7 ± 1.0 to 7.1 ± 1.5 mm for a mean loss of 1.6 ± 0.8 mm (P overlay group decreased from 8.4 ± 1.4 to 8.1 ± 1.4 mm for a mean loss of 0.3 ± 0.9 mm (P >0.05). The overlay group was significantly different from the socket group (P overlay group had 40% ± 16% (P >0.05). The overlay treatment significantly prevented loss of ridge width and preserved or augmented the buccal contour. The socket and overlay groups healed with a high percentage of vital bone.

  14. Mycophenolate mofetil and FK506 have different effects on kidney allograft fibrosis in rats that underwent chronic allograft nephropathy

    Luo Lei


    Full Text Available Abstract Background Tacrolimus (FK506 is associated with renal fibrosis in long-term use. Mycophenolatemofetil (MMF can also inhibit or attenuate the progression of renal fibrosis. This study aimed to determine the different effects of FK506 and MMF on fibrosis-associated genes in the kidney in rats that underwent chronic allograft nephropathy (CAN. Methods Fisher (F344 kidneys were orthotopically transplanted into Lewis rat recipients. All recipients were given Cyclosporin A (CsA 10 mg/kg-1.d-1 × 10 day and were then randomly divided into three oral treatment groups (n = 9 in each group: (1 the vehicle group was given vehicle orally; (2 the FK506 group was given 0.15 mg/kg-1.d-1 FK506; and (3 the MMF group was given 20 mg/kg-1.d-1 MMF. At 4, 8, and 12 weeks post-transplantation, serum creatinine (SCr, collagen deposition, Connective tissue growth factor (CTGF, alpha smooth muscle actin (α-SMA and E-cadherin expressions were determined and hematoxylin-eosin (HE and Periodic acid-Schiff (PAS stains were performed. Results Renal function progressively deteriorated and showed typical CAN morphology in the vehicle and FK506 groups, while SCr and inflammatory infiltration (Banff score showed a significant decrease in the MMF group after 8 weeks post-transplantation compared with those in the other groups (p α-SMA in the MMF group were significantly reduced, and the down-regulated expression of E-cadherin was abated (p  Conclusions MMF showed favorable effects on renal interstitial fibrosis, thus efficiently retarding the progression of CAN.

  15. Defense against dermal exposures is only skin deep

    Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm


    The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical...... or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model...... substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present...

  16. Effect of impaction on gene-modified cells seeded on granular bone allografts in vitro and in vivo

    YUAN Zhen; MAO Yuan-qing; ZHU Zhen-an


    Background While attempting to restore bone stock, impaction bone grafting employed during revision joint surgery may result in slow and limited allograft incorporation into host bone. A new approach including gene-modified bone marrow stromal cells (BMSCs) in combination with impaction bone grafting may effectively restore bone stock and improve allograft incorporation. This study aimed to investigate the effect of impaction on gene-modified BMSCs seeded on granular bone allografts in vitro and in vivo.Methods Deep-frozen, granular, cancellous bone allografts from canines were prepared to serve as cell delivery scaffolds and were seeded with green fluorescent protein (GFP) genetically-modified BMSCs to construct cell-allograft composites. The composites were impacted in a simulative, in vitro impaction model and cultured for further analysis under standard conditions. Four Beagle dogs, treated with bilateral, uncemented proximal tibial joint hemiarthroplasty with a prosthesis, were implanted with autologous GFP gene-modified cell-allograft composites to repair the bone cavity around each prosthesis.Results A significant reduction in cell viability was observed after impaction by fluorescence microscopy in vitro.However, there remained a proportion of GFP-positive cells that were viable and functionally active, as evidenced by the secretion of GFP protein in vitro and in vivo.Conclusions Gene-modified BMSCs seeded on granular allografts were able to withstand the impaction forces and to maintain their normal functions in vitro and in vivo, in spite of a partial loss in cell viability.

  17. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    Easterling, K.J.; Trumble, T.E. (Yale Univ. School of Medicine, New Haven, CT (USA))


    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

  18. Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity

    Sommerville, Laura J.; Xing, Chen; Kelemen, Sheri E.; Eguchi, Satoru; Autieri, Michael V.


    Aims Allograft inflammatory factor-1 (AIF-1) is a calcium-binding, scaffold-signalling protein expressed in vascular smooth muscle cells (VSMCs) in response to injury. The effects of AIF-1 attenuation on development of intimal hyperplasia are unknown, and the molecular mechanisms of these effects remain uncharacterized. The goals of the present study were to determine whether AIF-1 knockdown reduced VSMC proliferation, migration, and intimal hyperplasia, and determine AIF-1 effects on signal transduction in VSMCs. Methods and results Balloon angioplasty-injured rat carotid arteries transduced with adenovirus to overexpress AIF-1 (AdAIF-1) significantly increased, and adenovirus to knock down AIF-1 (AdsiRNA) expression significantly decreased neointimal formation compared with green fluorescent protein (AdGFP) and Adscrambled controls (P < 0.05 and P < 0.01, n = 6). Primary rat VSMCs transduced with AdAIF-1 displayed a significant increase in proliferation, and AdsiRNA-transduced VSMCs proliferated significantly more slowly than controls (P < 0.05). VSMCs transduced with AdAIF-1 show increased migration when compared with control VSMCs (P < 0.01). Rat VSMCs transduced with AdAIF-1 showed constitutive and prolonged activation of the mitogen-activated protein kinase p38, whereas AdsiRNA-treated VSMCs showed decreased p38 activation compared with AdGFP (P < 0.05). Immunohistochemical analysis of AdAIF-1-transduced carotid arteries showed increased staining with a phospho-specific p38 antibody compared with AdGFP-transduced arteries. A specific p38 inhibitor abrogated AIF-1-induced VSMC proliferation, but not AIF-1-induced migration. Conclusion Taken together, AIF-1 expression plays a key role in the development of neointimal hyperplasia. AIF-1 expression enhances the activation of p38 MAP kinase. AIF-1-enhanced proliferation is p38 kinase dependent, but AIF-1-enhanced VSMC migration is p38 independent. PMID:18779232

  19. Personal experience with the procurement of 32 liver allografts

    Guang-Wen Zhou; Cheng-Hong Peng; Hong-Wei Li


    AIM: To introduce the American Pittsburgh's method of rapid liver procurement under the condition of brain death and factors influencing the quality of donor liver.METHODS: To analyze 32 cases of allograft liver procurement retrospectively and observe the clinical outcome of orthotopic liver transplantation.RESULTS: Average age of donors was 38.24±12.78 years,with a male:female ratio of 23:9. The causes of brain death included 21 cases of trauma (65.63%) and nine cases of cerebrovascular accident (28.13%). Fourteen grafts (43.75%) had hepatic arterial anomalies, seven cases only right hepatic arterial anomalies (21.88%), five cases only left hepatic arterial anomalies (15.63%) and two cases of both right and left hepatic arterial anomalies (6.25%) among them. Eight cases (57.14%) of hepatic arterial anomalies required arterial reconstruction prior to transplantation. Of the 32 grafts evaluated for early function, 27 (84.38%) functioned well, whereas three (9.38%) functioned poorly and two (6.25%) failed to function at all. Only one recipient died after transplantation and thirty-one recipients recovered. Four recipients needed retransplantation. The variables associated with less than optimal function of the graft consisted of donor age (35.6±12.9 years vs 54.1±4.3 years, P<0.05), duration of donor's stay in the intensive care unit (ICU) (3.5±2.4 d vs 7.4±2.1 d, P<0.005), abnormal graft appearance (19.0% vs 100%, P<0.05), and such recipient problems as vascular thromboses during or immediately following transplantation (89.3% vs 50.0%, P<0.005).CONCLUSION: During liver procurement, complete heparization, perfusion in situ with localized low temperature and standard technique procedures are the basis ensuring the quality of the graft. The hepatic arterial anomalies should be taken care of to avoid injury. The donor age,duration of donor's staying in ICU, abnormal graft appearance and recipient problem are important factors influencing the quality of the

  20. Allograft loss from acute Page kidney secondary to trauma after kidney transplantation

    Takahashi, Kazuhiro; Prashar, Rohini; Putchakayala, Krishna G; Kane, William J; Denny, Jason E; Kim, Dean Y; Malinzak, Lauren E


    We report a rare case of allograft loss from acute Page kidney secondary to trauma that occurred 12 years after kidney transplantation. A 67-year-old Caucasian male with a past surgical history of kidney transplant presented to the emergency department at a local hospital with left lower abdominal tenderness. He recalled that his cat, which weighs 15 lbs, jumped on his abdomen 7 d prior. On physical examination, a small tender mass was noticed at the incisional site of the kidney transplant. He was producing a normal amount of urine without hematuria. His serum creatinine level was slightly elevated from his baseline. Computer tomography revealed a large subscapular hematoma around the transplant kidney. The patient was observed to have renal trauma grade II at the hospital over a period of three days, and he was finally transferred to a transplant center after his urine output significantly decreased. Doppler ultrasound demonstrated an extensive peri-allograft hypoechoic area and abnormal waveforms with absent arterial diastolic flow and a patent renal vein. Despite surgical decompression, the allograft failed to respond appropriately due to the delay in surgical intervention. This is the third reported case of allograft loss from acute Page kidney following kidney transplantation. This case reinforces that kidney care differs if the kidney is solitary or a transplant. Early recognition and aggressive treatments are mandatory, especially in a case with Doppler signs that are suggestive of compression. PMID:28280700

  1. Chronic lung allograft dysfunction after lung transplantation: novel insights into immunological mechanisms

    Budding, K.


    Lung transplantation (LTx) is the final treatment option for patients suffering from end-stage lung diseases. Survival after LTx is hampered by the development of chronic lung allograft dysfunction which presents itself in an obstructive form as the bronchiolitis obliterans syndrome (BOS). BOS is ha

  2. Partial trapeziectomy and interposition of fascia lata allograft in the operative treatment of thumb base osteoarthritis

    Spaans, Anne J.; Weijns, Marieke E.; Braakenburg, Assa; Van Minnen, Leo Paul; Mink Van Der Molen, Aebele B.


    Aim: The purpose of this retrospective cohort study was to evaluate the results of fascia lata allograft interposition after partial trapeziectomy in patients with symptomatic first carpometacarpal joint osteoarthritis. Methods and results: Twenty-one patients (22 thumbs) with Eaton-Glickel stage II

  3. Intercalary Reconstructions with Vascularised Fibula and Allograft after Tumour Resection in the Lower Limb

    Katharina Rabitsch


    Full Text Available Reconstruction with massive bone allograft and autologous vascularised fibula combines the structural strength of the allograft and the advantages of fibula’s intrinsic blood supply. We retrospectively analysed the outcome of twelve patients (4 male, 8 female who received reconstruction with massive bone allograft and autologous vascularised fibula after tumour resection in lower limb. Mean age was 17.8 years (range 11–31 years, with following primaries: Ewing’s sarcoma (n=6, osteosarcoma (n=4, liposarcoma grade 2 (n=1, and adamantinoma (n=1. Mean followup was 38.7 months (median 25.7 months; range 2–88 months. Seven tumours were located in the femur and five in the tibia. The mean length of bone defect was 18.7 cm (range 15–25 cm. None of the grafts had to be removed, but there occurred four fractures, four nonunions, and two infections. Two patients developed donor side complication, in form of flexion deformity of the big toe. The event-free survival rate was 51% at two-year followup and 39% at three- and five-year followup. As the complications were manageable, and full weight bearing was achieved in all cases, we consider the combination of massive bone allograft and autologous vascularised fibula a stable and durable reconstruction method of the diaphysis of the lower limbs.

  4. Comparing autograft, allograft, and tricalcium phosphate ceramic in a goat instrumented posterolateral fusion model

    Delawi, D.; Kruyt, M.C.; Yuan, H.; Vincken, K.L.; Bruijn, de J.D.; Oner, F.C.; Dhert, W.J.A.


    The most common application of bone grafts is spinal fusion surgery, in which the use of iliac crest autograft is the gold standard. Harvesting of autograft, however, requires an extra surgical procedure, which is associated with additional morbidity. Allograft is the well-known alternative, but it

  5. Allograft and prostatic involvement in a renal transplant recipient with disseminated tuberculosis.

    Sreejith, P; Jha, V; Kohli, H S; Rathi, M; Gupta, K L; Sakhuja, V


    Tuberculosis is a serious opportunistic infection in renal transplant recipients and is disseminated in nature in one-third of patients. Genito urinary tuberculosis is rare in renal transplant recipients. We report a patient presenting 5 years after renal transplantation with disseminated tuberculosis and allograft and prostatic involvement.

  6. Microbiological cultures of allografts of the femoral head just before transplantation.

    Pol, G.J. van de; Sturm, P.D.J.; Loon, C.J.M. van; Verhagen, C.; Schreurs, B.W.


    Allografts of bone from the femoral head are often used in orthopaedic procedures. Although the donated heads are thoroughly tested microscopically before release by the bone bank, some surgeons take additional cultures in the operating theatre before implantation. There is no consensus about the ne

  7. Distinct phenotypes of cardiac allograft vasculopathy after heart transplantation : A histopathological study

    Huibers, Manon M H; Vink, Aryan; Kaldeway, Johannes; Huisman, André; Timmermans, Kim; Leenders, Max; Schipper, Marguèrite E I; Lahpor, Jaap R.; Kirkels, Hans J H; Klöpping, Corinne; de Jonge, Nicolaas; de Weger, Roel A.


    Introduction: Long-term survival after heart transplantation (HTx) is hampered by cardiac allograft vasculopathy (CAV). Better understanding of the pathophysiological mechanisms of CAV might have considerable consequences for therapeutic approaches in the future. The aim of the present study was to

  8. Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a Rat Kidney Model.

    Zhou, Li-Na; Wang, Ning; Dong, Yang; Zhang, Yiqin; Zou, Hequn; Li, Qingqin; Shi, Yangling; Chen, Ling; Zhou, Wenying; Han, Conghui; Wang, Yuxin


    Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.

  9. Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival.

    Prasad, G V Ramesh; Ananth, Sailesh; Palepu, Sneha; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S


    Transplant tourism, a form of transplant commercialization, has resulted in serious short-term adverse outcomes that explain reduced short-term kidney allograft survival. However, the nature of longer-term outcomes in commercial kidney transplant recipients is less clear. To study this further, we identified 69 Canadian commercial transplant recipients of 72 kidney allografts transplanted during 1998 to 2013 who reported to our transplant center for follow-up care. Their outcomes to 8 years post-transplant were compared with 702 domestic living donor and 827 deceased donor transplant recipients during this period using Kaplan-Meier survival plots and multivariate Cox regression analysis. Among many complications, notable specific events included hepatitis B or C seroconversion (7 patients), active hepatitis and/or fulminant hepatic failure (4 patients), pulmonary tuberculosis (2 patients), and a type A dissecting aortic aneurysm. Commercial transplantation was independently associated with significantly reduced death-censored kidney allograft survival (hazard ratio 3.69, 95% confidence interval 1.88-7.25) along with significantly delayed graft function and eGFR 30 ml/min/1.73 m(2) or less at 3 months post-transplant. Thus, commercial transplantation represents an important risk factor for long-term kidney allograft loss. Concerted arguments and efforts using adverse recipient outcomes among the main premises are still required in order to eradicate transplant commercialization.

  10. Proliferation of CD8-positive T cells in blood vessels of rat renal allografts.

    Grau, V; Fuchs-Moll, G; Wilker, S; Weimer, R; Padberg, W


    It is still disputed in which anatomical compartments of allograft recipients T-cells proliferate. After experimental renal transplantation, host monocytes and lymphocytes accumulate in the lumina of graft blood vessels. In this study, we test the hypothesis that T lymphocytes proliferate in the vascular bed of the graft. Kidneys were transplanted in the Dark Agouti to Lewis rat strain combination, an established experimental model for acute rejection. Isogeneic transplantation was performed as a control. Cells in the S-phase of mitosis were detected in situ three days posttransplantation by pulse-labeling with BrdU and by immunohistochemical detection of the proliferating cell nuclear antigen (PCNA). More than 20% of all T-cells in the lumina of allograft blood vessels incorporated BrdU and approximately 30% of them expressed PCNA. In the blood vessels of isografts as well as in other organs of allograft recipients, only few BrdU(+) cells were detected. A majority of the BrdU(+) cells in graft blood vessels expressed CD8. In conclusion, we demonstrate that CD8(+) T lymphocytes proliferate in the lumina of the blood vessels of renal allografts during the onset of acute rejection.

  11. CT perfusion technique for assessment of early kidney allograft dysfunction: preliminary results

    Helck, A.; Notohamiprodjo, M.; Schoen, F.; Nikolaou, K.; Clevert, D.A.; Reiser, M.; Becker, C. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, University Hospitals Grosshadern, Munich (Germany); Wessely, M.; Schoenermarck, U.; Fischereder, M. [Ludwig-Maximilians-University of Munich, Department of Internal Medicine IV, Nephrology, University Hospitals Grosshadern, Munich (Germany); Klotz, E. [Siemens Healthcare, Computed Tomography, Forchheim (Germany)


    To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 {+-} 21 ml/100 ml/min) compared with those with ATN (77.5 {+-} 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 {+-} 3.1 mg/dl in AR and 5.3 {+-} 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 {+-} 5.2 mSv; the mean amount of contrast media applied was 34.5 {+-} 5.1 ml. All examinations were performed without complications. CT perfusion of kidney allografts may help to differentiate between ATN and rejection. (orig.)

  12. Subtalar Distraction Arthrodesis with Fresh Frozen Femoral Neck Allograft: A Retrospective Case Series.

    Monaco, Spencer J; Brandao, Roberto A; Manway, Jeffrey M; Burns, Patrick R


    Subtalar joint distraction arthrodesis has been well reported with use of structural iliac crest or local autologous bone graft for malunited calcaneal fractures. Early reports for structural allograft did not yield good, consistent results, leading to a subsequent lack of recommendation in previous literature. Newer studies have had promising results utilizing femoral allograft as an alternative to autogenous bone graft. We performed a retrospective chart review on 10 patients (12 feet) undergoing subtalar joint distraction arthrodesis with femoral neck allograft for malunited calcaneal fractures. The primary aim of this study was to report on successful union rates and, in addition, outline any consistent complications. Twelve of the 12 procedures (100%) yielded successful fusion with a mean final follow-up of 7.7 months (range = 2.2-35.1 months). The mean increase in talocalcaneal height was 4 mm (range = 2-6 mm). The overall complication rate was 16.6%, including one superficial wound complication that healed uneventfully and one hardware removal. In conclusion, the current study reports a 100% successful fusion rate with interpositional structural femoral neck allograft in treatment for malunited calcaneal fractures. Therapeutic, Level IV: Case series. © 2016 The Author(s).

  13. Comparison of gait parameters in distal femoral replacement using a metallic endoprosthesis versus allograft reconstruction.

    AlGheshyan, Fahad; Eltoukhy, Moataz; Zakaria, Khaled; Temple, Harry Thomas; Asfour, Shihab


    Restoration of gait mechanics after reconstruction have been associated with improved functional outcomes and increased longevity of the reconstruction. The goal of this study is to compare the gait mechanics of an allograft reconstruction of the distal femur to both metallic endoprosthetic reconstruction relative to normal control subjects. Gait parameters were captured using motion capture system, and then analyzed and compared for patients with metallic endoprosthetic reconstructions, and patients with allograft reconstructions of the distal femur following resection of malignant bone tumor, with subjects having no history of musculoskeletal disorders serving as a control group. All reconstructed distal femurs following tumor resection resulted in decreased range of motion reflected in observed flexion/extension angles compared to the normal limbs. The allograft reconstructed knees demonstrated normal patterns of rotation whereas the metal subjects had abnormal patterns of rotation and statistically significant differences in rotational moments. Allograft distal femoral reconstruction after malignant excision remains a viable option for surgeons faced with problems associated with iatrogenic muscle, bone and soft tissue defects.

  14. Renoprotective effects of the AGE-inhibitor pyridoxamine in experimental chronic allograft nephropathy in rats

    Waanders, Femke; van den Berg, Else; Nagai, Ryoji; van Veen, Ingrid; Navis, Gerjan; van Goor, Harry


    Background. Advanced glycation end products (AGEs) are involved in diabetic nephropathy (DN). The AGE formation inhibitor pyridoxamine (PM) is renoprotective in DN and in normoglycaemic obese Zucker rats. In chronic allograft nephropathy (CAN), renal AGE accumulation occurs as well. Methods. To inve

  15. Reversal of Diabetes by Islet Transplantation: Vulnerability of the Established Allograft

    Bowen, K. M.; Prowse, S. J.; Lafferty, K. J.


    Nonspecific stimulation of the immune system of CBA mice carrying a functional BALB/c islet allograft failed to trigger graft rejection. Only three of six animals rejected their graft when injected intravenously with 105, 106, and 107 peritoneal cells of BALB/c origin over a 3-month period commencing 100 days after transplantation.

  16. Effect of lateral meniscus allograft on shoulder articular contact areas and pressures.

    Creighton, R Alexander; Cole, Brian J; Nicholson, Gregory P; Romeo, Anthony A; Lorenz, Eric P


    The objective of this study was to determine the effect of a lateral meniscus allograft on the articular contact area and pressures across the glenohumeral joint under compressive loads of 220 N and 440 N. Eight fresh-frozen shoulders were used, and contact areas and pressures were determined with a Tekscan flexible tactile force sensor. Testing conditions included a normal glenohumeral joint and one interposed with a lateral meniscus allograft. Using the Tekscan sensing equipment, we evaluated the total force (in Newtons), contact area (in square millimeters), mean contact pressure (in kilograms per square centimeter), peak force (in Newtons), and peak contact pressure (in kilograms per square centimeter). The interposed lateral meniscus allograft group showed a statistically significant decrease in total force at both 220 N and 440 N, as well as a decrease in contact area for the 220-N testing condition. There were no statistically significant differences between the two groups in contact area at 440 N or in peak forces or peak contact areas for either 220-N or 440-N testing condition. Biomechanically biologic resurfacing with a lateral meniscus allograft of the glenohumeral joint is supported by decreased forces on the glenoid surface.

  17. Early peri-operative hyperglycaemia and renal allograft rejection in patients without diabetes

    Russ Graeme R


    Full Text Available Abstract Background Patients with diabetes have an increased risk for allograft rejection, possibly related to peri-operative hyperglycaemia. Hyperglycaemia is also common following transplantation in patients without diabetes. We hypothesise that exposure of allograft tissue to hyperglycaemia could influence the risk for rejection in any patient with high sugars. To investigate the relationship of peri-operative glucose control to acute rejection in renal transplant patients without diabetes, all patients receiving their first cadaveric graft in a single center were surveyed and patients without diabetes receiving cyclosporin-based immunosuppression were reviewed (n = 230. Records of the plasma blood glucose concentration following surgery and transplant variables pertaining to allograft rejection were obtained. All variables suggestive of association were entered into multivariate logistic regression analysis, their significance analysed and modeled. Results Hyperglycaemia (>8.0 mmol/L occurs in over 73% of non-diabetic patients following surgery. Glycaemic control immediately following renal transplantation independently predicted acute rejection (Odds ratio=1.08. 42% of patients with a glucose Conclusion Hyperglycaemia is associated with an increased risk for allograft rejection. This is consistent with similar findings in patients with diabetes. We hypothesise a causal link concordant with epidemiological and in vitro evidence and propose further clinical research.

  18. Renoprotective effects of the AGE-inhibitor pyridoxamine in experimental chronic allograft nephropathy in rats

    Waanders, Femke; van den Berg, Else; Nagai, Ryoji; van Veen, Ingrid; Navis, Gerjan; van Goor, Harry


    Background. Advanced glycation end products (AGEs) are involved in diabetic nephropathy (DN). The AGE formation inhibitor pyridoxamine (PM) is renoprotective in DN and in normoglycaemic obese Zucker rats. In chronic allograft nephropathy (CAN), renal AGE accumulation occurs as well. Methods. To inve

  19. The Presence of Recipient-Derived Renal Cells in Kidney Allografts

    Türkan METE


    Full Text Available OBJECTIVE: Stem cells may be involved in the repair processes of renal tissues during various disorders. We aimed to search the presence of recipient originated cells in renal allograft tissues from patients with various types of allograft dysfunction including acute rejection, acute tubular necrosis, calcineurin inhibitor toxicity, and chronic rejection. MATERIAL and METHODS: Eleven kidney transplant recipients were enrolled in the study. Seven patients who had sex-mismatched donors were regarded as the study group and the remaining were the controls (male-male, positive controls, n=2; female-female, negative controls, n=2. Histopathological examinations in the study group had revealed chronic rejection in four patients(together with calcineurin inhibitor toxicity in three and acute rejection, acute tubular necrosis, and cyclosporine toxicity in one patient each. Deparaffi nised biopsy specimens were examined using chromogenic in situ hybridization (CISH method for the XY cocktail probe. RESULTS: Renal cells of positive controls had XY, whereas those of negative controls had XX chromosomal signals. Examination of the biopsy samples from the study group showed variable ratios of recipient-derived tubular(2-76%, interstitial mesenchymal(5-83%, and endothelial cells(1-53%. CONCLUSION: The presence of recipient-derived renal cells in injured kidney allografts suggests that there is a possible dynamic interaction between allograft and stem cells of the recipient. Further studies are needed to clarify the origin and the function of these cells.

  20. Partial trapeziectomy and interposition of fascia lata allograft in the operative treatment of thumb base osteoarthritis

    Spaans, Anne J.; Weijns, Marieke E.; Braakenburg, Assa; Van Minnen, Leo Paul; Mink Van Der Molen, Aebele B.


    Aim: The purpose of this retrospective cohort study was to evaluate the results of fascia lata allograft interposition after partial trapeziectomy in patients with symptomatic first carpometacarpal joint osteoarthritis. Methods and results: Twenty-one patients (22 thumbs) with Eaton-Glickel stage II

  1. Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans

    McConnell, J.D.; Sagalowsky, A.I.; Lewis, S.E.; Gailiunas, P.; Helderman, J.H.; Dawidson, I.; Peters, P.C.


    A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.

  2. Monocyte procoagulant activity and plasminogen activator. Role in human renal allograft rejection

    Cole, E.H.; Cardella, C.J.; Schulman, J.; Levy, G.A.


    Currently the mechanism of renal allograft rejection is not well understood. This study was designed to determine whether induction of monocyte procoagulant activity (MCPA) is important in the pathogenesis of renal allograft rejection. The MPCA assay was performed utilizing a one stage clotting assay both in normal and in factor-VII-deficient plasma. There was no increase in spontaneous MPCA in 20 patients with endstage renal failure and in 10 patients following abdominal or orthopedic operation, as compared with 20 normal controls. MPCA was assessed daily in 18 patients who had received renal allografts. Rejection episodes (RE) were predicted on the basis of persistent elevation in MPCA as compared with pretransplant levels. Rejection was diagnosed clinically and treated on the basis of standard criteria. Treated RE were compared with those predicted by elevated MPCA, and 3 patients were assessed as having no RE by MPCA and by standard criteria. In 8 RE, MPCA correlated temporally with RE (same day) when compared with standard criteria. In 12 RE, MPCA was predictive of rejection preceding standard criteria by at least 24 hr. There were 7 false-positive predictions on the basis of MPCA; however, there was only 1 false negative. MPCA was shown to be a prothrombinase by its dependence only on prothrombin and fibrinogen for full activity. MPCA may be important in the pathogenesis of allograft rejection, and additionally it may be a useful adjunct in the clinical management of this disease.

  3. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)


    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

  4. Fatal Progressive Multifocal Leukoencephalopathy in a Kidney Transplant Recipient 19 Years After Successful Renal Allograft Transplantation

    Carlson, N; Hansen, Jesper Melchior


    in circumstances of extreme immunodeficiency. Development of fulminant PML is rare and treatment options are limited. CASE REPORT: We have presented a case of JCV reactivation resulting in PML 19 years after renal allograft transplantation and after recent conversion of immunosuppressive treatment. One year after...

  5. Kidney injury molecule-1 expression is closely associated with renal allograft damage.

    Song, Lianlian; Xue, Lijuan; Yu, Jinyu; Zhao, Jun; Zhang, Wenlan; Fu, Yaowen


    The aim of our study was to investigate the expression of kidney injury molecule-1 (KIM-1) in renal allograft biopsy samples and assess the clinical significance of its use as a biomarker for tissue damage. A total of 69 renal allograft biopsy samples from 17 patients with normal serum creatinine and 52 cases of increased serum creatinine were collected. They were divided into different groups according to the Banff 2007 diagnostic criteria. KIM-1 expression was detected by immunohistochemical methods and the association of KIM-1 and blood biochemical indexes was analyzed. KIM-1 expression increased as Banff 2007 classification grade increased and was positively correlated with tubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1 expression was strongly positive in the chronic active antibody-mediated rejection group. Interestingly, KIM-1 was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group, 27.3% (3/11) of the cases with normal serum creatinine level showed weakly positive KIM-1 expression in their renal tissues. KIM-1 expression level is positively correlated with renal allograft damage and tubular cell injury. KIM-1 is expressed in tubular epithelial cells before blood biochemical indexes become elevated and morphological changes occur. KIM-1 expression is an early, sensitive, and specific biomarker to determine renal tubular epithelial cell injury in renal allograft tissue.

  6. Tissue elasticity quantification by acoustic radiation force impulse for the assessment of renal allograft function.

    He, Wan-Yuan; Jin, Yun-Jie; Wang, Wen-Ping; Li, Chao-Lun; Ji, Zheng-Biao; Yang, Cheng


    Acoustic radiation force impulse (ARFI) quantification, a novel ultrasound-based elastography method, has been used to measure liver fibrosis. However, few studies have been performed on the use of ARFI quantification in kidney examinations. We evaluated renal allograft stiffness using ARFI quantification in patients with stable renal function (n = 52) and those with biopsy-proven allograft dysfunction (n = 50). ARFI quantification, given as shear wave velocity (SWV), was performed. The resistance index (RI) was calculated by pulsed-wave Doppler ultrasound, and clinical and laboratory data were collected. Morphologic changes in transplanted kidneys were diagnosed by an independent pathologist. Mean SWV was more significantly negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.657, p renal allograft dysfunction were 72.0% and 86.5% (cutoff value = 2.625), respectively. The latter values were better than those of RI, which were 62.0% and 69.2% (cutoff value = 0.625), respectively. The coefficient of variation for repeat SWV measurements of the middle part of transplanted kidney was 8.64%, and inter-observer agreement on SWV was good (Bland-Altman method, ICC = 0.890). In conclusion, tissue elasticity quantification by ARFI is more accurate than the RI in diagnosing renal allograft function.

  7. Characterization of acute renal allograft rejection by proteomic analysis of renal tissue in rat.

    Chen, Gang; Huang, Jing-Bin; Mi, Jie; He, Yun-Feng; Wu, Xiao-Hou; Luo, Chun-Li; Liang, Si-Min; Li, Jia-Bing; Tang, Ya-Xiong; Li, Jie


    Rapid and reliable biomarkers of renal allograft rejection have not been available. This study aimed to investigate biomarkers in renal allograft tissue using proteomic analysis. Orthotopic kidney transplantations were performed using Fisher (F344) or Lewis rats as donors and Lewis rats as recipients. Syngenic control group (Group I) constituted F344-to-F344 orthotopic kidney allo-transplantations (n = 8); and allogenic group (Group II) consisted of F344-to-Lewis orthotopic kidney allo-transplantations (n = 8). Renal tissues were harvested 7 days after transplantation. Samples were analyzed using 2-D electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. 6 differentially expressed proteins were identified between allogenic group and syngenic control group. A rat model of acute renal allograft rejection was successfully set up. Differentially expressed proteins in renal allograft tissue of rat were detected using proteomic analysis and might serve as novel diagnostic and therapeutic targets in human. Quantitative proteomics, using MALDL-TOF-MS methodology has the potential to provide a profiling and a deeper understanding of acute renal rejection.

  8. Total aortic arch replacement: superior ventriculo-arterial coupling with decellularized allografts compared with conventional prostheses.

    Alexander Weymann

    Full Text Available To date, no experimental or clinical study provides detailed analysis of vascular impedance changes after total aortic arch replacement. This study investigated ventriculoarterial coupling and vascular impedance after replacement of the aortic arch with conventional prostheses vs. decellularized allografts.After preparing decellularized aortic arch allografts, their mechanical, histological and biochemical properties were evaluated and compared to native aortic arches and conventional prostheses in vitro. In open-chest dogs, total aortic arch replacement was performed with conventional prostheses and compared to decellularized allografts (n = 5/group. Aortic flow and pressure were recorded continuously, left ventricular pressure-volume relations were measured by using a pressure-conductance catheter. From the hemodynamic variables end-systolic elastance (Ees, arterial elastance (Ea and ventriculoarterial coupling were calculated. Characteristic impedance (Z was assessed by Fourier analysis.While Ees did not differ between the groups and over time (4.1±1.19 vs. 4.58±1.39 mmHg/mL and 3.21±0.97 vs. 3.96±1.16 mmHg/mL, Ea showed a higher increase in the prosthesis group (4.01±0.67 vs. 6.18±0.20 mmHg/mL, P<0.05 in comparison to decellularized allografts (5.03±0.35 vs. 5.99±1.09 mmHg/mL. This led to impaired ventriculoarterial coupling in the prosthesis group, while it remained unchanged in the allograft group (62.5±50.9 vs. 3.9±23.4%. Z showed a strong increasing tendency in the prosthesis group and it was markedly higher after replacement when compared to decellularized allografts (44.6±8.3 dyn·sec·cm(-5 vs. 32.4±2.0 dyn·sec·cm(-5, P<0.05.Total aortic arch replacement leads to contractility-afterload mismatch by means of increased impedance and invert ventriculoarterial coupling ratio after implantation of conventional prostheses. Implantation of decellularized allografts preserves vascular impedance thereby improving

  9. [Sarcoidosis of the skin].

    Suga, Y; Ogawa, H


    Sarcoidosis is characterized by formation of epithelioid-cell tubercules, without caseation, of the affected organ systems. The mediastinum, peripheral lymph nodes and eyes, in addition to the skin, are most frequently affected. Between 10% and 30% of patients with systemic sarcoidosis in Japan have skin lesions. Skin sarcoidosis is morphologically classified into three basic groups, erythema nodosum, scar sarcoidosis and skin sarcoid. Skin sarcoid is characterized by specific cutaneous lesions of sarcoidosis, and may take nodular, plaque, angiolupoid, subcutaneous and some other forms. Clinical manifestations of the cutaneous lesions are usually asymptomatic and polymorphous. Skin biopsy is, however, often highly useful for confirming a diagnosis of sarcoidosis.

  10. Severe bradycardia and prolonged hypotension in ciguatera.

    Chan, Thomas Yan Keung


    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  11. An unusual case of a patient who lost his native kidneys and renal allograft from cholesterol crystal emboli.

    Ahmed, Wasim; Al Garni, Abdulkareem; Abdelgadir, Elbadri; Khamees, Khamess Obeid; Ellouly, Mohammed Ali Ahmed; Haleem, Abdul


    Cholesterol crystal emboli (CCE) syndrome involving native kidneys is an underdiagnosed condition. CCE is rare in renal allografts. It may present with acute kidney injury, but usually not acute graft loss. CCE should be considered in patients with a history of atherosclerosis and an invasive arterial procedure who present with acute or chronic renal allograft dysfunction. Therapy for CCE is mainly supportive and carries a high rate of mortality. To the best of our knowledge, this is the first reported case of a patient who lost his native kidneys and renal allograft due to CCE arising from his own vasculature.

  12. An unusual case of a patient who lost his native kidneys and renal allograft from cholesterol crystal emboli

    Wasim Ahmed


    Full Text Available Cholesterol crystal emboli (CCE syndrome involving native kidneys is an underdiagnosed condition. CCE is rare in renal allografts. It may present with acute kidney injury, but usually not acute graft loss. CCE should be considered in patients with a history of atherosclerosis and an invasive arterial procedure who present with acute or chronic renal allograft dysfunction. Therapy for CCE is mainly supportive and carries a high rate of mortality. To the best of our knowledge, this is the first reported case of a patient who lost his native kidneys and renal allograft due to CCE arising from his own vasculature.

  13. [Prolonged pain in neonates: retrospective analysis].

    Lilla, Michèle; Stadelman-Diaw, Corinne; Ramelet, Anne-Sylvie


    Infants hospitalised in neonatology are inevitably exposed to pain repeatedly. Premature infants are particularly vulnerable, because they are hypersensitive to pain and demonstrate diminished behavioural responses to pain. They are therefore at risk of developing short and long-term complications if pain remains untreated. Compared to acute pain, there is limited evidence in the literature on prolonged pain in infants. However, the prevalence is reported between 20 and 40 %. This single case study aimed to identify the bio-contextual characteristics of neonates who experienced prolonged pain. This study was carried out in the neonatal unit of a tertiary referral centre in Western Switzerland. A retrospective data analysis of seven infants' profile, who experienced prolonged pain ,was performed using five different data sources. The mean gestational age of the seven infants was 32weeks. The main diagnosis included prematurity and respiratory distress syndrome. The total observations (N=55) showed that the participants had in average 21.8 (SD 6.9) painful procedures that were estimated to be of moderate to severe intensity each day. Out of the 164 recorded pain scores (2.9 pain assessment/day/infant), 14.6 % confirmed acute pain. Out of those experiencing acute pain, analgesia was given in 16.6 % of them and 79.1 % received no analgesia. This study highlighted the difficulty in managing pain in neonates who are exposed to numerous painful procedures. Pain in this population remains underevaluated and as a result undertreated.Results of this study showed that nursing documentation related to pain assessment is not systematic.Regular assessment and documentation of acute and prolonged pain are recommended. This could be achieved with clear guidelines on the Assessment Intervention Reassessment (AIR) cyclewith validated measures adapted to neonates. The adequacy of pain assessment is a pre-requisite for appropriate pain relief in neonates.

  14. Napping and Human Functioning during Prolonged Work


    alternative to napping is prolonged wakefulness. Polyphasic sleep , with frequent naps rather than a single sleep period per 24 hours, is natural for both the...very young and for the aged. It is not practiced by most adults, perhaps because of societal demands. Possibly a polyphasic sleep schedule could be...Functioning 1.2 Scope of this Chapter 2. REVIEW OF LITERATURE 2.1 Partial Sleep Deprivation Studies 2.2 Nap Studies: Four Nap Factors Affecting Performance

  15. Prolonged grief: setting the research agenda

    Rita Rosner


    Full Text Available Background: Prolonged grief disorder is proposed for the International Classification of Diseases (ICD-11, though it was rejected as a diagnosis for DSM-5. Objective: This review outlines findings and defines important areas for future research viewed from a lifespan perspective. Results: The development and psychometric evaluation of measures for the new diagnosis is paramount, specifically for children and adolescents. Treatments need to be adapted for specific subgroups and research findings have to be disseminated into various professional settings.

  16. Development of sterilization and storage processes of Xeno-skins by gamma irradiation for the Industrialization as dressing materials

    Choi, Jong Il; Lee, Ju Woon; Kim, Jae Hun; Song, Beom Seok; Kim, Jae Kyung; Park, Jong Hum; Sung, Nak Yun; Jo, Eu Ri; Kim, Jeong Soo [KAERI, Daejeon (Korea, Republic of)


    Allografts have been increased in concerns as treatment methods to be use in replacement and reconstruction procedures of tissue. The major concern about tissue and bone transplantation is the risk of transferring bacteria, viruses from recipient to the donors, especially from different species. To avoid these risks, tissue and bone banks use many different sterilization methods such as a deep-frozenness, freeze-drying ethylene oxide-sterilization and gamma-irradiation. Among these methods, gamma-irradiation has been widely used to sterilize the tissue for allograft and xenograft safety. Gamma irradiation could be an effective method for sterilization of soft tissue for the development of xenografts. Also, this study suggests the potential of development as tissue graft with the improved mechanical property of the structural stability and protection of tissue materials by antioxidant on porcine skin irradiated for sterilization and storage process

  17. Anterior cruciate ligament reconstruction with Achilles tendon allografts in revisions and in patients older than 30.

    Grafe, Michael W; Kurzweil, Peter R


    We evaluated the results of anterior cruciate ligament (ACL) reconstruction using an Achilles tendon allograft in revisions and in patients older than 30. Results from 23 consecutive patients (mean age, 43 years) who underwent ACL reconstruction with fresh-frozen, irradiated (22/23) Achilles allografts were retrospectively reviewed. Seven cases were revisions. Patients were evaluated with physical examination, questionnaires, and x-rays. Twenty of the 23 patients were evaluated a mean of 28 months after surgery. There were 5 failures (21%); 3 acute failures were not evaluated at follow-up. One patient had an infection that required graft removal, 2 patients had mechanical failure of the grafts, and 2 had displacements of more than 5.5 mm as measured with a KT-1000 arthrometer. The 18 clinically successful cases had full motion, no thigh atrophy, and no effusion. Pivot shift scores were 55% A and 45% B on the International Knee Documentation Committee (IKDC) scale. Lachman scores were 40% A, 55% B, and 5% C on the IKDC scale. The KT-1000 difference was a mean of 2.9 mm at final follow-up. However, knees loosened a mean of 4.5 mm from the immediate postoperative measurements (Preconstructions with Achilles tendon allografts failed. Grafts deemed successful still had significant loosening at final follow-up. Allografts from donors older than 40 may have played a role in these failures. From the data in this study, it appears that surgeons should scrutinize the source of the allograft tissue and the age of the donor.

  18. RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes

    Lin, Yang; Lewallen, Eric A.; Camilleri, Emily T.; Bonin, Carolina A.; Jones, Dakota L.; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J.; Larson, Annalise N.; Dahm, Diane L.; Stuart, Michael J.; Levy, Bruce A.; Smith, Jay; Ryssman, Daniel B.; Westendorf, Jennifer J.; Im, Hee-Jeong; van Wijnen, Andre J.; Riester, Scott M.; Krych, Aaron J.


    Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. PMID:26909883

  19. Allograft arthrodesis treatment of bone tumors: a two-center study.

    Donati, D; Giacomini, S; Gozzi, E; Salphale, Y; Mercuri, M; Mankin, Henry J; Springfield, Dempsy S; Gebhardt, Mark C


    The current study consists of an outcome review of a consecutive series of 92 patients with knee arthrodesis using an allograft, done for malignant or aggressive tumors in two centers on different continents during a period of 18 years (mean followup, 5 +/- 4 years). The data were compiled by creating a computerized file using the information provided by both centers. Seventy-five of the patients (81%) had high-grade nonmetastatic tumors (Stage II), mostly osteosarcoma. In addition seven (8%) had metastases at outset (Stage III) and the remaining 10 (11%) had benign disease, mostly giant cell tumor or revision procedures for failed allograft or total joint replacement. Seventy-two patients (78%) had distal femoral lesions (78%) whereas the proximal tibia was the site of the tumor in 20 patients (22%). The average age of the patients was 23 +/- 16 years; 51 were males and 41 were females. Tumor complications were a major problem for patients in the series. Thirty-four percent of the patients died, 47% had metastases develop, and 9% had a local recurrence. Allograft complications included an infection rate of 20%, a fracture rate of 25%, and a nonunion rate of 44%. Repeat surgery was required for more than 50% of the patients with 26 requiring one additional operation, 11 requiring two, and 10 requiring three or more operations. Nineteen of the patients required an amputation (20%), only four of which were for recurrent tumor. When these data were compared with data for a control series of 880 patients with allografts other than allograft arthrodeses, the complications were greater and the outcome less successful, suggesting that other approaches should be considered unless there are special indications for this procedure.

  20. Mechanoreceptor Reinnervation of Autografts Versus Allografts After Anterior Cruciate Ligament Reconstruction

    Young, Simon W.; Valladares, Roberto D.; Loi, Florence; Dragoo, Jason L.


    Background: Loss of proprioceptive function occurs after anterior cruciate ligament (ACL) rupture. Clinical, motor, and proprioceptive function is known to improve after ACL reconstruction but does not return to normal. While histological studies of human ACL allografts have been unable to demonstrate mechanoreceptor reinnervation, animal data suggest that reinnervation may occur when an autograft is used. Purpose: To compare the presence or absence of mechanoreceptors between allograft versus autograft after ACL reconstruction in humans. Study Design: Cohort study; Level of evidence, 3. Methods: Ten patients with previous ACL reconstruction presenting for either revision ACL surgery or knee arthroscopy for other reasons were enrolled in a prospective, comparative study. Five patients had a previous autograft ACL and 5 patients had an allograft. Biopsies, either from intact or ruptured grafts, were taken from identical locations as close to the femoral and tibial insertions as possible. Specimens were stained with hematoxylin-eosin (H-E) and monoclonal antibodies against neurofilament protein (NFP), known to be present in mechanoreceptor tissue. Immunohistochemical examination was carried out, and the number of NFP+ neural tissue analogs was counted and compared with that of native ACL tissue. Results: The mean time between original graft and biopsy was 6.9 years (range, 0.5-15 years). Histological examination showed significantly less NFP+ neural analogs in allograft and autograft patients than control tissue (mean number of NFP+ analogs per high-power field, 0.7 ± 0.9 [allograft] and 0.5 ± 0.8 [autograft] vs 4.7 ± 0.9 [controls]; P proprioceptive deficits seen clinically after ACL reconstruction. PMID:27803939