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Sample records for cardiac allograft survival

  1. Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice

    OpenAIRE

    1985-01-01

    Administration of the monoclonal antibody M7/20, which binds to the murine interleukin-2 (IL) receptor, significantly prolongs cardiac allograft survival in two H-2-incompatible strain combinations of inbred mice. The results support the important role of the IL-2 receptor in the mechanism of graft rejection, and suggest its suitability as a target for immunosuppressive therapy.

  2. Trichinella spiralis infection changes immune response in mice performed abdominal heterotopic cardiac transplantation and prolongs cardiac allograft survival time.

    Science.gov (United States)

    Deng, Gengguo; Deng, Ronghai; Yao, Jianping; Liao, Bing; Chen, Yinghua; Wu, Zhongdao; Hu, Hongxing; Zhou, Xingwang; Ma, Yi

    2016-01-01

    Allograft rejection has been an obstacle for long-term survival of patients for many years. Current strategies for transplant rejection are not as optimal as we expected, especially for long-term treatments. Trichinella spiralis, a nematode parasitized in mammalian muscle and as an invader, maintains harmonious with host in the long term by evading host immune attack. To determine whether T. spiralis infection impacts on allograft rejection, we performed mice cardiac allograft transplantation model by using BALB/c (H-2(b)) mice as donors and C57BL/6 (H-2(b)) mice orally infected with 300 muscle larvae for 28 days as recipients. Graft survival was monitored by daily palpation of the abdomen; histologic change was observed by H&E stain; and CD4(+), CD8(+), CD4(+)IFN-γ(+), and CD4(+)IL-17(+) T cells and regulatory T cells were examined with the use of flow cytometry. Serum cytokine levels were measured by Luminex. Finally, we found that mean survival time of cardiac allografts in T. spiralis group was 23.40 ± 1.99 days, while the vehicle control group was 10.60 ± 0.75 days. Furthermore, we observed alleviated histological changes in the heart allograft, decreased corresponding CD8(+) T cells, suppressed Th1 and Th17 responses, and increased regulatory T cell frequency in a murine cardiac transplantation model at day 7 post-transplantation in experimental group. These data suggest that T. spiralis infection resulted in prolonged allograft survival following murine cardiac transplantation, with suppressed Th1/Th17 responses and augmented regulatory T cells. PMID:26481486

  3. Prolongation of Cardiac Allograft Survival in Rats by Treatment with Anti-Interleukin 2 Antiserum

    Directory of Open Access Journals (Sweden)

    Osaki,Toshihide

    1988-04-01

    Full Text Available Interleukin-2 (IL2 is the obligatory signal for both T cell mitogenesis and in vitro generation of alloreactive cytotoxic T lymphocytes (CTL. An investigation was made to determine whether an antibody directed against IL2 would suppress the rejection reaction of rat cardiac allografts. Rabbit anti-interleukin 2 (anti-IL2 antiserum was obtained by immunizing at 2 week intervals over a period of 8 weeks with 10(6 U of recombinant human IL2 along with complete Freund's adjuvant. The bioassay for inhibition of IL2 activity by anti-IL2 antiserum was carried out in conjunction with the IL2-dependent cytotoxic T cell (CTLL cell assay. Cardiac allografts of F344 rats were heterotopically transplanted into ACI rats. Seven daily doses of 1 ml of anti-IL2 antiserum were administered intravenously following transplantation. IL2-driven [3H]thymidine incorporation in CTLL cells was significantly inhibited by rabbit anti-IL2 antiserum. Graft survival in the anti-IL2 serum-treated group was significantly prolonged in a dose-dependent fashion compared to control groups. In conclusion, these results indicate that rabbit anti-IL2 antiserum may prove to be of significant value as an immunosuppressive agent in clinical organ transplantation.

  4. Effect of anti-interleukin 2 monoclonal antibody treatment on the survival of rat cardiac allograft

    International Nuclear Information System (INIS)

    The effect of anti-interleukin 2 monoclonal antibody (anti-IL2 MoAb) and the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb were examined in heterotopic rat cardiac allografts. Mouse anti-human recombinant IL2 MoAb was obtained by the hybridoma technique. The anti-IL2 MoAb, termed 8H-10, was an IgG2a which inhibited IL2-driven [3H]TdR incorporation in cytolytic T lymphocyte line cells at a dilution of 2(6). 8H-10 was injected iv at a dose of 200 micrograms/day for 8 consecutive days, beginning on the day of transplantation. Hearts from F344 rats (RT11v1) were transplanted into ACI recipient rats (RT1av1). The mean survival time was 7.6 +/- 0.8 days in untreated controls, 9.0 +/- 1.2 days in additional controls treated with mouse anti-sheep red blood cell monoclonal antibody, and 25.3 +/- 18.4 days in the anti-IL2 MoAb (8H-10)-treated group (P less than 0.05). Furthermore, the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb (8H-10) was specifically seen in the grafted heart. In conclusion, these results suggest that IL2 may play an important role in allograft rejection and that anti-IL2 MoAb may serve as a useful immunosuppressive agent in clinical transplantation

  5. Prolongation of Cardiac Allograft Survival in Rats by Treatment with Anti-Interleukin 2 Antiserum

    OpenAIRE

    Osaki, Toshihide; Sakagami, Kenichi; Orita,Kunzo

    1988-01-01

    Interleukin-2 (IL2) is the obligatory signal for both T cell mitogenesis and in vitro generation of alloreactive cytotoxic T lymphocytes (CTL). An investigation was made to determine whether an antibody directed against IL2 would suppress the rejection reaction of rat cardiac allografts. Rabbit anti-interleukin 2 (anti-IL2) antiserum was obtained by immunizing at 2 week intervals over a period of 8 weeks with 10(6) U of recombinant human IL2 along with complete Freund's adjuvant. The bioassay...

  6. Cyclosporine inhibits long-term survival in cardiac allografts treated with monoclonal antibody against CD45RB

    NARCIS (Netherlands)

    Parry, N; Lazarovits, AI; Wang, JJ; Garcia, B; Luke, P; Poppema, S; Zhong, R

    1999-01-01

    Background: We have previously reported that a monoclonal antibody to CD45RB is a novel immunosuppressive agent; however, the optimal regimen in cardiac allografts remains unknown. The present study was undertaken to determine the optimal protocol of this therapy and its interaction with cyclosporin

  7. ICOS-Ig combined with CsA induces long term survival of cardiac allografts in mouse

    Institute of Scientific and Technical Information of China (English)

    Zhang Peng; Wang Zhenmeng; Qin Qin; Tang Yi; Wang Quanxing; Shen Qian

    2009-01-01

    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

  8. Cardiac allograft immune activation: current perspectives

    OpenAIRE

    Chang D; Kobashigawa J

    2014-01-01

    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, antibod...

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

    Science.gov (United States)

    2012-01-01

    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 compared to

  10. Cardiac allograft immune activation: current perspectives

    Directory of Open Access Journals (Sweden)

    Chang D

    2014-12-01

    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

  11. Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis.

    Science.gov (United States)

    Booth, Adam J; Wood, Sherri C; Cornett, Ashley M; Dreffs, Alyssa A; Lu, Guanyi; Muro, Andrés F; White, Eric S; Bishop, D Keith

    2012-03-01

    Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long-term allograft survival. While initiating elements of anti-allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN-deficient (EDA(-/-)) and wild-type (WT) mice. While EDA(-/-) mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA(-/-) mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T-helper lineages. Conditions supporting regulatory T-cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient-derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft-protective, may drive production of ECM molecules which enhance

  12. Recipient–derived EDA fibronectin promotes cardiac allograft fibrosis

    Science.gov (United States)

    Booth, Adam J; Wood, Sherri C; Cornett, Ashley M; Dreffs, Alyssa A; Lu, Guanyi; Muro, Andrés F; White, Eric S; Bishop, D Keith

    2014-01-01

    Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long-term allograft survival. While initiating elements of anti-allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN-deficient (EDA−/−) and wild-type (WT) mice. While EDA−/− mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA−/− mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T-helper lineages. Conditions supporting regulatory T-cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient-derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft-protective, may drive production of ECM molecules which

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

    Directory of Open Access Journals (Sweden)

    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.

  14. New developments in the diagnosis and management of cardiac allograft vasculopathy.

    OpenAIRE

    Mehra, M. R.; Ventura, H O; Smart, F W; Stapleton, D D; Collins, T J; Ramee, S R; Murgo, J P; White, C. J.

    1995-01-01

    The major cause of late death in cardiac transplant recipients is cardiac allograft vasculopathy, also referred to as cardiac transplant atherosclerosis, which occurs in as many as 45% of transplant recipients who survive longer than 1 year. It differs from typical atherosclerosis in that intimal hyperplasia is concentric and diffuse, the internal elastic lamina remains intact, calcification is rare, and the disease tends to develop rapidly. Intravascular ultrasound and coronary angioscopy ar...

  15. Relationship between CGRP level and acute reject reaction in cardiac allograft recipient in rats

    International Nuclear Information System (INIS)

    Objective: To investigate the relationship between the calcitonin gene related peptide (CGRP) and acute reject reaction in the cardiac allograft in rat. Methods: There were 28 wistar rats with inbreeding line as donors and SD rats as recipients. Cervical heart allograft model was used. Blood was sampled from the third day after grafting to terminal reject reaction when the acceptors were killed. 32 rats without allograft were regarded as the normal controls. Results: The mean survival time of the experimental group was 7.21±2.36 days. Volume of the allografts was greatly increased with hyperemia and edema. CGRP level in the plasma of experimental rats was 180.18±69.77 ng/L, while the level of control rats was 277.41 ± 79.02 ng/L. The deference was statistically significant (P<0.05). Conclusion: In the acute reject reaction, CGRP level is greatly decreased in the plasma of cardiac allograft recipients. Further studies are therefore needed to investigate the application of CGRP measurement in the prevention and treatment of rejection reaction of cardiac allograft

  16. Association of CD14+ monocyte-derived progenitor cells with cardiac allograft vasculopathy

    OpenAIRE

    Salama, Mohamed; Andrukhova, Olena; Roedler, Susanne; Zuckermann, Andreas; Laufer, Guenther; Aharinejad, Seyedhossein

    2011-01-01

    Objective The pathogenesis of cardiac allograft vasculopathy after heart transplant remains controversial. Histologically, cardiac allograft vasculopathy is characterized by intimal hyperplasia of the coronary arteries induced by infiltrating cells. The origin of these infiltrating cells in cardiac allograft vasculopathy is unclear. Endothelial progenitor cells are reportedly involved in cardiac allograft vasculopathy; however, the role of CD14+ monocyte-derived progenitor cells in cardiac al...

  17. Sphingosine-1-phosphate receptor 1 agonist SEW2871 prolongs heterotopic heart allograft survival in mice.

    Science.gov (United States)

    Ni, Qian; Yuan, Baohong; Liu, Tao; Lan, Fang; Luo, Xiaochun; Lu, Xiaoyan; Huang, Ping; Dai, Liangcheng; Jin, Xiaobao; Yin, Hui

    2015-05-01

    Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids that is essential for immune cell trafficking. Recent studies have revealed immunomodulatory functions of S1P and its receptors (S1PR1-S1PR5) in many inflammatory conditions, such as asthma and autoimmunity. Here, we explore the efficacy of SEW2871, a selective S1PR1 agonist, in the prevention of acute allograft rejection in a murine cardiac transplantation model. Treatment of recipient mice with SEW2871 significantly prolongs cardiac allograft survival as compared to those recipients treated with control vehicle. The enhanced graft survival is associated with reduced circulating lymphocytes and allograft inflammatory cell infiltration. The cytokine analysis showed decreased allograft expression of TNF-α, IFN-γ and IL-2 in the SEW2871-treated mice. Moreover, administration of SEW2871 increases the percentage of CD4(+) T regulatory cells and FoxP3 expression in spleen of allograft recipients. Therefore, SEW2871 plays a critical role in regulation of lymphocyte trafficking and development, which directly contributes to prolongation of the allograft survival. PMID:25776899

  18. Critical Role for IL-6 in Hypertrophy and Fibrosis in Chronic Cardiac Allograft Rejection

    OpenAIRE

    Diaz, J. A.; Booth, A. J.; Lu, G.; Wood, S.C.; Pinsky, D.J.; Bishop, D. K.

    2009-01-01

    Chronic cardiac allograft rejection is the major barrier to long term graft survival. There is currently no effective treatment for chronic rejection except re-transplantation. Though neointimal development, fibrosis, and progressive deterioration of graft function are hallmarks of chronic rejection, the immunologic mechanisms driving this process are poorly understood. These experiments tested a functional role for IL-6 in chronic rejection by utilizing serial echocardiography to assess the ...

  19. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Science.gov (United States)

    2010-04-01

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

  20. The effect of pregnancy on paternal skin allograft survival

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    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.

  1. The effect of pregnancy on paternal skin allograft survival

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    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.

  2. Survival and Reoperation Rate Following Osteochondral Allograft Transplantation

    OpenAIRE

    Frank, Rachel M.; Levy, David; Scalise, Pamela Nina; Smith, Margaret Elizabeth; Cole, Brian J.

    2016-01-01

    Objectives: The purpose of this study was to quantify survival for osteochondral allograft transplantation (OAT) and report findings at reoperation. Methods: A retrospective review of a prospectively collected database of patients who underwent OAT by a single surgeon with a minimum follow-up duration of 2-years was conducted. The reoperation rate, timing of reoperation, procedure performed at reoperation, and findings at surgery were reviewed. Failure was defined by revision OAT, conversion ...

  3. Factors affecting the long-term renal allograft survival

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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.

  4. Arsenic trioxide attenuated the rejection of major histocompatibility complex fully-mismatched cardiac allografts in mice.

    Science.gov (United States)

    Yan, S; Zhang, Q Y; Zhou, B; Xue, L; Chen, H; Wang, Y; Zheng, S S

    2009-06-01

    We investigated the effects of arsenic trioxide (As(2)O(3)) on allogeneic immune response using a mouse heart transplantation model. Mice were randomly divided into 4 groups of 6 animals each. The control group received phosphate-buffered saline (PBS); the As(2)O(3)-treated group, intraperitoneal (IP) injection of As(2)O(3) (1 mg/kg) from days -3 to 10 after heart transplantation. The cyclosporine (CsA)-treated group was given a subtherapeutic dose of CsA (10 mg/kg) IP, and the As(2)O(3) plus CsA-treated group, a combined protocol of As(2)O(3) and CsA. Six days after transplantation, cardiac allografts were harvested for immunohistology and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The survival of the allografts was significantly improved among the As(2)O(3)-treated group compared with the control group (17.2 +/- 1.9 vs 8.0 +/- 0.9 days; P < .05). A marked prolongation (28.6 +/- 6.0 days) of graft survival was achieved by the combined protocol compared with the CsA-treated group (9.6 +/- 3.0 days; P < .05) or the As(2)O(3)-treated group. Allografts of As(2)O(3)-treated and As(2)O(3) plus CsA-treated mice showed a changing pattern of Th1/Th2 cytokine mRNA expression. Allograft rejection was apparently alleviated by low-dose As(2)O(3), and particularly when combined with a subtherapeutic CsA dose. PMID:19545743

  5. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-04-01

    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.

  6. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-04-01

    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.

  7. Survival and Reoperation Rate Following Osteochondral Allograft Transplantation

    Science.gov (United States)

    Frank, Rachel M.; Levy, David; Scalise, Pamela Nina; Smith, Margaret Elizabeth; Cole, Brian J.

    2016-01-01

    Objectives: The purpose of this study was to quantify survival for osteochondral allograft transplantation (OAT) and report findings at reoperation. Methods: A retrospective review of a prospectively collected database of patients who underwent OAT by a single surgeon with a minimum follow-up duration of 2-years was conducted. The reoperation rate, timing of reoperation, procedure performed at reoperation, and findings at surgery were reviewed. Failure was defined by revision OAT, conversion to knee arthroplasty, or gross appearance of graft failure at 2ndlook arthroscopy. Descriptive statistics, log-rank testing, cross-tabulation, and chi-square testing were performed, with POAT at an average follow-up of 4.9±2.5 years (range, 2.0 to 11.3) were included. Ninety-five patients (95%) underwent an average of 2.7±1.7 prior surgical procedures on the ipsilateral knee prior to OAT. The average defect size was 452.7±181.6 mm2 and was located on the medial femoral condyle in 63 patients (63%). Fifty-one percent of OATs were isolated, while 49% were performed with concomitant procedures including meniscus allograft transplantation (MAT) in 27 (27%). Fifty-three patients (53%) returned to the operating room at an average 2.8±2.7 years, with 26% of these patients (14/53) undergoing additional reoperations (range, 1-3 additional reoperations). Arthroscopic debridement was performed in 91% of the initial reoperations (48/53); 55% of reoperations (29/53) were performed within 2 years of the index OAT. Twenty patients (20%) were considered failures at an average 4.0±2.7 years following index OAT either due to revision OAT (N=6), conversion to arthroplasty (N=10), or appearance of poorly incorporated allograft at arthroscopy (N=4). Patients requiring multiple reoperations had an odds ratio of 7.25 (95% CI, 1.85 to 28.37) of OAT failure (P=0.004), while patients requiring secondary surgery within 2 years had an odds radio of 1.35 (95% CI, 0.48 to 3.82) for OAT failure (P>0

  8. Resistance of Foxp3+ regulatory T cells to Nur77-induced apoptosis promotes allograft survival.

    Directory of Open Access Journals (Sweden)

    Ran Tao

    Full Text Available The NR4A nuclear receptor family member Nur77 (NR4A1 promotes thymocyte apoptosis during negative selection of autoreactive thymocytes, but may also function in mature extrathymic T cells. We studied the effects of over-expression of Nur77 on the apoptosis of murine peripheral T cells, including thymic-derived Foxp3+ regulatory (Treg cells. Overexpression of Nur77 in the T cell lineage decreased numbers of peripheral CD4 and CD8 T cells by approximately 80% compared to wild-type (WT mice. However, the proportions of Treg cells were markedly increased in the thymus (61% of CD4+Foxp3+ singly positive thymocytes vs. 8% in WT and secondary lymphoid organs (40-50% of CD4+Foxp3+ T cells vs. 7-8% in WT of Nur77 transgenic (Nur77Tg mice, and immunoprecipitation studies showed Nur77 was associated with a recently identified HDAC7/Foxp3 transcriptional complex. Upon activation through the T cell receptor in vitro or in vivo, Nur77Tg T cells showed only marginally decreased proliferation but significantly increased apoptosis. Fully allogeneic cardiac grafts transplanted to Nur77Tg mice survived long-term with well-preserved structure, and recipient splenocytes showed markedly enhanced apoptosis and greatly reduced anti-donor recall responses. Allografts in Nur77Tg recipients had significantly increased expression of multiple Treg-associated genes, including Foxp3, Foxp1, Tip60 and HDAC9. Allograft rejection was restored by CD25 monoclonal antibody therapy, indicating that allograft acceptance was dependent upon Treg function in Nur77Tg recipients. These data show that compared to conventional CD4 and CD8 T cells, Foxp3+ Tregs are relatively resistant to Nur77-mediated apoptosis, and that tipping the balance between the numbers of Tregs and responder T cells in the early period post-transplantation can determine the fate of the allograft. Hence, induced expression of Nur77 might be a novel means to achieve long-term allograft survival.

  9. Early Cardiac Allograft Vasculopathy: Are the Viruses to Blame?

    Directory of Open Access Journals (Sweden)

    Ashim Aggarwal

    2012-01-01

    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.

  10. Cardiogenic shock and coronary endothelial dysfunction predict cardiac allograft vasculopathy after heart transplantation.

    Science.gov (United States)

    Lopez-Fernandez, Silvia; Manito-Lorite, Nicolas; Gómez-Hospital, Joan Antoni; Roca, Josep; Fontanillas, Carles; Melgares-Moreno, Rafael; Azpitarte-Almagro, José; Cequier-Fillat, Angel

    2014-12-01

    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.

  11. Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection

    OpenAIRE

    1990-01-01

    It has been a long-standing dogma that host sensitization against fully- vascularized organ allografts occurs peripherally within the graft itself. In this report we show that donor-derived MHC class II-positive (Ia+) DL migrate rapidly out of mouse cardiac allografts into the recipients' spleens where they home to the peripheral white pulp and associate predominantly with CD4+ T lymphocytes. This provides a novel route for central sensitization against fully vascularized allografts, and most...

  12. Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR and with cytomegalovirus (CMV infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score >37%  = AR and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.

  13. Adoptive transfer of mix-cultured hone marrow cells to prolong survival of cardiac allografts in mice%混合培养的供、受者骨髓细胞过继回输延长小鼠移植心脏存活时间

    Institute of Scientific and Technical Information of China (English)

    王慧; 刘世雄; 杨能; 周佩军; 邵琨; 赵菊平; 徐达; 王祥慧; 沈周俊; 路丽明

    2009-01-01

    /c abdominal cavity,and the BMC from donor and recipient was mix-cultured and adoptively transferred.The recipients were divided as follows:Ⅰ,no treatment;Ⅱ,total body irradiation (TBI) + rapamune;Ⅲ,TBI + rapamune + mix-cultured BMC;Ⅳ,treated by the same protocol as group Ⅲ except that C3H mouse served as the donor.The survival of cardiac allograft in all groups was observed.The percentage of CD4~+ CD25~+ T and donor-derived H-2K~b cells in peripheral blood of the recipient was measured by using FCM,when the allograft stopped beating.Results Mix-cultured BMC specifically downregulated lymphocyte reaction in vitro.Adoptive transfer of mix-cultured BMC significantly prolonged the allograft survival in group Ⅲ,but not in group Ⅳ.And in recipient peripheral blood of group Ⅲ,the percentage of CD4~+ CD25~+ T cells and H-2K~b cells was increased significantly.Specially,these effects were all acted as a donor antigen-specific manner.Conclusion Mix-cultured BMC can regulate immune response and prolong the cardiac allograft survival in a donor antigen-specific manner.

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

    Institute of Scientific and Technical Information of China (English)

    张国伟; 刘宏宇; 夏求明; 李君权; 吕航; 张庆华; 姚志发

    2004-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    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.

  16. Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Aparici, C.M.; Martin, J.C.; Tembl, A.; Flotats, A.; Estorch, M.; Catafau, A.M.; Berna, L.; Carrio, I. [Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Narula, J.; Puig, M.; Camprecios, M.; Ballester, M. [Cardiology Department, Sant Pau Hospital, Barcelona (Spain)

    2000-12-01

    The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. {sup 111}In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the

  17. Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy

    International Nuclear Information System (INIS)

    The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. 111In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the

  18. Reduced Progression of Cardiac Allograft Vasculopathy with Routine Use of Induction Therapy with Basiliximab

    Directory of Open Access Journals (Sweden)

    Ricardo Wang

    2015-01-01

    Full Text Available Abstract Introduction: Cardiac allograft vasculopathy (CAV is a major limitation for long-term survival of patients undergoing heart transplantation (HT. Some immunosuppressants can reduce the risk of CAV. Objectives: The primary objective was to evaluate the variation in the volumetric growth of the intimal layer measured by intracoronary ultrasound (IVUS after 1 year in patients who received basiliximab compared with that in a control group. Methods: Thirteen patients treated at a single center between 2007 and 2009 were analyzed retrospectively. Evaluations were performed with IVUS, measuring the volume of a coronary segment within the first 30 days and 1 year after HT. Vasculopathy was characterized by the volume of the intima of the vessel. Results: Thirteen patients included (7 in the basiliximab group and 6 in the control group. On IVUS assessment, the control group was found to have greater vessel volume (120–185.43 mm3 vs. 127.77–131.32 mm3; p = 0.051. Intimal layer growth (i.e., CAV was also higher in the control group (27.30–49.15 mm3 [∆80%] vs. 20.23–26.69 mm3 [∆33%]; p = 0.015. Univariate regression analysis revealed that plaque volume and prior atherosclerosis of the donor were not related to intima growth (r = 0.15, p = 0.96, whereas positive remodeling was directly proportional to the volumetric growth of the intima (r = 0.85, p < 0.001. Conclusion: Routine induction therapy with basiliximab was associated with reduced growth of the intima of the vessel during the first year after HT.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

    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. Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival.

    Science.gov (United States)

    Prasad, G V Ramesh; Ananth, Sailesh; Palepu, Sneha; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S

    2016-05-01

    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.

  1. PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

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    Dongxia Ma

    Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

  2. Prospective coronary angioscopy assessment of allograft coronary artery disease in human cardiac transplant recipients

    Science.gov (United States)

    Jain, Ashit; Ventura, Hector O.; Collins, Tyrone J.; Ramee, Stephen R.; White, Christopher J.

    1993-09-01

    Annual angiographic assessment to determine the presence or progression of allograft coronary artery disease (CAD) has been unable to modify the natural history of this disease. Coronary angioscopy is a sensitive method to detect the early presence of coronary artery disease and in a retrospective analysis severity of CAD by angioscopy correlated with the time since transplantation. The purpose of this study was to prospectively evaluate progression of coronary artery disease over a one year period in 40 cardiac transplant recipients. The progression of coronary artery disease as assessed by angioscopy is directly related to time after transplantation and therefore angioscopy may be the method of choice for detection and evaluation of therapeutic regimens to control allograft coronary artery disease.

  3. Impact of acute rejection episodes on long-term renal allograft survival

    Institute of Scientific and Technical Information of China (English)

    吴建永; 陈江华; 王逸民; 张建国; 朱琮; 寿张飞; 王苏娅; 张萍; 黄洪锋; 何强

    2003-01-01

    Objective To assess the impact of the number, and time of acute rejection (AR) and outcome of anti-rejection therapy on the long-term survival of renal allografts and the relative risk factors. Methods The Kaplan-Meier analysis and log-rank test were used to calculate the survival rates of patients and grafts in no acute rejection group (NAR, 895 patients), 1 rejection episode group (1AR, 183), 2 and more than 2 rejection episodes group (2AR, 17), acute rejection group [AR (1AR+2AR), 200], early acute rejection group (within 90 days after transplantation, EAR, 125), late acute rejection group (91 days later, LAR, 58), completely AR reversed group (CAR, 105), and incompletely AR reversed group (IAR, 68). The relative risk factors were analyzed by the Cox proportional hazards regression. Results The 5- and 10-year survival rates of renal allografts were 75.4% and 17.1% in AR and 93.2% and 86.5% in the NAR group (P<0.0001). The long-term graft survival was much lower in the 2AR group than in the NAR or 1AR groups (P<0.0001 and P=0.002, respectively). It was similar in either the NAR or CAR groups (P=0.31), but it was significantly lower (P<0.0001) in the IAR group. Multivariate Cox regression analysis revealed that the outcome of anti-rejection therapy is an important risk factor affecting the long-term survival of allografts.Conclusions AR is significantly associated with poor long-term survival of renal allografts. But the long-term graft survival of patients with one acute rejection but completely reversed is not significantly different from that of patients without acute rejection.

  4. Effects of Adoptive Transfer of Tolerogenic Dendritic Cells on Allograft Survival in Organ Transplantation Models: An Overview of Systematic Reviews

    Science.gov (United States)

    Shan, Juan; Guo, Yingjia; Li, Shengfu; Long, Dan

    2016-01-01

    Objective. To dissect the efficacy of Tol-DC therapy with or without IS in multiple animal models of transplantation. Methods and Results. PubMed, Medline, Embase, and the Cochrane Library were searched for reviews published up to April 2015. Six systematic reviews and a total of 61 articles were finally included. Data were grouped by organ transplantation models and applied to meta-analysis. Our meta-analysis shows that Tol-DC therapy successfully prolonged allograft survival to varying extents in all except the islet transplantation models and with IS drugs further prolonged the survival of heart, skin, and islet allografts in mice, but not of heart allografts in rats. Compared with IS drugs alone, Tol-DC therapy with IS extended islet allograft survival in rats but failed to influence the survival of skin, small intestine, and heart allografts in rats or of heart and skin allografts in mice. Conclusion. Tol-DC therapy significantly prolonged multiple allograft survival and further prolonged survival with IS. However, standardized protocols for modification of Tol-DC should be established before its application in clinic.

  5. Pretreatment of donor islets with papain improves allograft survival without systemic immunosuppression in mice.

    Science.gov (United States)

    Kumano, Kenjiro; Nishinakamura, Hitomi; Mera, Toshiyuki; Itoh, Takeshi; Takahashi, Hiroyuki; Fujiwara, Toshiyoshi; Kodama, Shohta

    2016-09-01

    Although current immunosuppression protocols improve the efficacy of clinical allogenic islet transplantation, T cell-mediated allorejection remains unresolved, and major histocompatibility complexes (MHCs) play a crucial role in this process. Papain, a cysteine protease, has the unique ability to cleave the extracellular domain of the MHC class I structure. We hypothesized that pretreatment of donor islets with papain would diminish the expression of MHC class I on islets, reducing allograft immunogenicity and contributing to prolongation of islet allograft survival. BALB/c islets pretreated with papain were transplanted into C57BL/6J mice as an acute allorejection model. Treatment with 1 mg/mL papain significantly prolonged islet allograft survival. In vitro, to determine the inhibitory effect on T cell-mediated alloreactions, we performed lymphocyte proliferation assays and mixed lymphocyte reactions. Host T cell activation against allogenic islet cells was remarkably suppressed by pretreatment of donor islet cells with 10 mg/mL papain. Flow cytometric analysis was also performed to investigate the effect of papain treatment on the expression of MHC class I on islets. One or 10 mg/mL papain treatment reduced MHC class I expression on the islet cell surface. Pretreatment of donor islets with papain suppresses MHC class I-mediated allograft rejection in mice and contributes to prolongation of islet allograft survival without administration of systemic immunosuppressants. These results suggest that pretreatment of human donor islets with papain may reduce the immunogenicity of the donor islets and minimize the dosage of systemic immunosuppressants required in a clinical setting. PMID:27618231

  6. New approaches to the management of acute and chronic cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Mitsuaki; Suzuki, Jun-ichi [Shinshu Univ., Matsumoto, Nagano (Japan). School of Medicine

    1998-05-01

    There are still many problems to be faced in the field of heart transplantation. Acute and chronic rejection are still the major medical obstacles. In this review, we describe recent research in this field undertaken in our laboratory. The induced intercellular adhesion molecule-1 (ICAM-1) and MHC class II antigen resulting from rejection can be visualized in vivo by radioimmunoscintigraphy. This non-invasive method is sensitive for detecting early rejection and allows quantitative assessment of rejection. Short-term administration of monoclonal antibodies to ICAM-1 and leukocyte function-associated antigen-1 (LFA-1) results in an indefinite acceptance of cardiac allografts by induction of antigen-specific tolerance, as evidenced by acceptance of the secondary skin allografts. The characteristics and possible mechanisms of this tolerance induction are discussed. Immunohistopathologic features of graft coronary arteriopathy are shown. Adhesion molecules, cytokines, and growth factors are associated with intimal hyperplasia and phenotypic transformation of smooth muscle cells in the allograft coronary arteries. Dramatic reduction in this intimal hyperplasia was demonstrated by antisense gene therapy targeting cyclin-dependent kinase 2 kinase. We hope that these investigations will contribute to the improvement of the management of patients who undergo heart transplantation. (author). 117 refs.

  7. Arsenic trioxide inhibits accelerated allograft rejection mediated by alloreactive CD8(+) memory T cells and prolongs allograft survival time.

    Science.gov (United States)

    Li, Chun; Guan, Tianjun; Gao, Chang; Lin, Yingying; Yan, Guoliang; Zhu, Maoshu; Lv, Chongshan; Xia, Junjie; Qi, Zhongquan

    2015-09-01

    CD8(+) memory T (Tm) cells are a significant barrier to transplant tolerance induction in alloantigen-primed recipients, and are insensitive to existing clinical immunosuppressants. Here, we studied the inhibition of CD8(+) Tm cells by arsenic trioxide (As2O3) for the first time. Alloantigen-primed CD8(+) Tm cells were transferred to T cell immunodeficient nude mice. The mice were subjected to heart allotransplantation, and treated with As2O3. The transplant survival time was determined, and the inhibitory effects of As2O3 on CD8(+) Tm cell-mediated immune rejection were assessed through serological studies and inspection of the transplanted heart and lymphoid organs. We found that As2O3 treatment prolonged the mean survival time of the graft and reduced the number of CD8(+) Tm cells in the spleen and lymph nodes. The expression of the genes encoding interleukin (IL)-2, and IFN-γ was reduced, while expression of IL-10 and transforming growth factor-β was increased in the transplant. Our findings show that As2O3 treatment inhibits allograft rejection mediated by alloreactive CD8(+) Tm cells in the mouse heart transplantation model.

  8. Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Laker, L.; Els, D.; Weideman, A.; Wolfe-Coote, S.; van der Merwe, E.A.

    1985-04-01

    The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/ kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversible bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 x 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 x 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 x 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 x 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients.

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

    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.

  10. Racial and ethnic disparities in pediatric renal allograft survival in the United States.

    Science.gov (United States)

    Patzer, Rachel E; Mohan, Sumit; Kutner, Nancy; McClellan, William M; Amaral, Sandra

    2015-03-01

    This study was undertaken to describe the association of patient race/ethnicity and renal allograft survival among the national cohort of pediatric renal allograft recipients. Additionally, we determined whether racial and ethnic differences in graft survival exist among individuals living in low- or high-poverty neighborhoods and those with private or public insurance. Among 6216 incident, pediatric end-stage renal disease patients in the United States Renal Data System (kidney transplant from 2000 through September, 2011), 14.4% experienced graft failure, with a median follow-up time of 4.5 years. After controlling for multiple covariates, black race, but not Hispanic ethnicity, was significantly associated with a higher rate of graft failure for both deceased and living donor transplant recipients. Disparities were particularly stark by 5 years post transplant, when black living donor transplant recipients experienced only 63.0% graft survival compared with 82.8 and 80.8% for Hispanics and whites, respectively. These disparities persisted among high- and low-poverty neighborhoods and among both privately and publicly insured patients. Notably profound declines in both deceased and living donor graft survival rates for black, compared with white and Hispanic, children preceded the 3-year mark when transplant Medicare eligibility ends. Further research is needed to identify the unique barriers to long-term graft success among black pediatric transplant recipients.

  11. Interleukin-1 receptor antagonist eye drops promoting high-risk corneal allografts survival in rats

    Institute of Scientific and Technical Information of China (English)

    接英; 张文华; 潘志强; 武宇影; 王颖

    2004-01-01

    Background Immune rejection is the main reason of grafts failure after corneal transplantation. This study was to determine whether interlerkin-1 receptor antagonist (IL-1ra) eye drops could prolong corneal allografts survival in high-risk corneal orthotopic allotransplantation in rat model and to study the effect of IL-1ra on the expression of CD1-positive cells in the grafts. Methods For all experiments, the Sprague-Dawley (SD) rats' corneas were transplanted into Wistar rats' eyes. High-risk transplants included those that had been sutured into Wistar recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 7 days earlier. All the animals were divided, in a masked fashion, into three treatment groups and one control group. Each treatment group received IL-1ra eye drops of different concentrations (1 mg/ml, 3 mg/ml, or 5 mg/ml, respectively) four times a day for 30 days. The control group received 0.9% normal saline (NS) eye drops in the same way as the treatment groups. All allografts were evaluated for signs of rejection from the first day after surgery. Ten days later, corneal specimens were processed to examine the expression of CD1-positive cells and histopathological changes. Results The survival time of the transplants was 5.80±0.79, 5.89±1.05, 6.78±0.83, and 9.00±2.36 days respectively in the control or three treatment groups. Compared with the control group, 1 mg/ml IL-1ra eye drop did not prolong the survival time of the allografts (t=0.210, P>0.05). However, 3 mg/ml and 5 mg/ml IL-1ra eye drop did prolong the survival time of the grafts (t≥2.627, P<0.05), with the latter showing more obvious effect. Immunohistochemical examinations showed a significant decrease in inflammatory cell and CD1-positive cell infiltration in IL-1ra treated groups compared with the control group. Conclusions IL-1ra can promote corneal allograft survival in a dose-dependant manner by reducing the infiltration of

  12. Pregnancy-Related Human Leukocyte Antigen Sensitization Leading to Cardiac Allograft Vasculopathy and Graft Failure in a Heart Transplant Recipient: A Case Report

    OpenAIRE

    Ginwalla, M.; Pando, M.J.; Khush, K. K.

    2013-01-01

    In this report, we present a heart transplant recipient who developed cross-reactive paternal and donor-specific human leukocyte antigen (HLA) class II antibodies during pregnancy, leading to accelerated cardiac allograft vasculopathy and severe allograft dysfunction 17 years after transplantation. This resulted in acute heart failure and ventricular arrhythmias requiring repeat heart transplantation.

  13. Pachymic acid, a novel compound for anti-rejection: effect in rats following cardiac allograft transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fan; WANG Fei; ZHANG Xue-feng; WANG Bai-chun; LIU Hong-yu; LI Chun-yu; LIU Zong-hong; ZHANG Guo-wei; L(U) Hang; CHI Chao

    2009-01-01

    Background Pachymic acid (PA), a natural triterpenoid, is known to significantly reduce cell proliferation and induce apoptosis in vitro through initiation of mitochondria dysfunction. However, its effect on immune cells and anti-rejection following organ transplantation remains unknown.Methods In this study, we investigated PA as a treatment to control acute rejection occurred in rats which had accepted cardiac transplantation. We measured apoptosis of peripheral blood lymphocyte (PBLs), and CD4~+ lymphocyte, as well as the number of CD4~+ and CD8~+ lymphocytes and the effect of PA on acute rejection in rats 7 days after cardiac transplantation.Results PA treatment might decrease allograft rejection, protect PBLs from apoptosis, and reduce the percentage of CD8~+ lymphocyte. PA neither regulated the number nor the apoptosis rate of CD4~+ lymphocyte.Conclusions Our findings indicated that PA has an anti-apoptotic effect acting on PBLs through a novel mechanism involving stabilization of the PBLs mitochondrial transmembrane potential, an anti-rejection effect in rats after cardiac transplantation and an inhibiting effect to CD8~+ lymphocyte.

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

    Science.gov (United States)

    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.

    2015-01-01

    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

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

    Science.gov (United States)

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

    2012-01-15

    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.

  16. Effect of total lymphoid irradiation and pretransplant blood transfusion on pancreatic islet allograft survival

    International Nuclear Information System (INIS)

    Total lymphoid irradiation (TLI) has been shown to have a strong immunosuppressive effect both experimentally and clinically. Pretransplant blood transfusions have also been shown to have a strong beneficial effect in the outcome of organ transplantation. A study was made of the effect of TLI and pretransplant blood transfusions, alone and in combination, as an immunosuppressive modality in the isolated pancreatic islet transplant in the rat model. Donor rats (Fischer RT1v1) were kept on a 50% DL-ethionine supplemented diet for 4-6 weeks prior to pancreas removal. Recipient rats (Lewis RT1) were made diabetics prior to transplantation by iv injection of streptozotocin (45 mg/kg). Transfusion protocol consisted of a biweekly transfusion of 2 ml of either donor specific or third party transfusions. Total lymphoid irradiation was carried out by daily administration of 200 rads during one week prior to transplantation. Transplantation of the isolated islets was performed by intraportal injection. Syngeneic transplant of one and a half donor pancreata in each recipient reverted the diabetic condition indefinitely (greater than 100 days). Untreated allogenic grafts had a mean survival time (MST) of 5.2 days. Total lymphoid irradiation in dosages of 800, 1000, and 1200 rads, as the only immunosuppressive regimen, prolonged the MST of allografts to 15.3, 16.5, and 21.8 days, respectively (P less than .05). Pretransplant third party blood transfusion had no effect on allograft survival (MST 6.0). When donor specific blood transfusions were given, the MST was prolonged to 25.3 days (P less than .05). When TLI was administered to recipients of donor specific transfusions, the MST of the allografts did not show any statistical significant difference when compared with untreated animals. This abrogation of the beneficial effect of specific blood transfusion was observed in all dosages of TLI employed: 800 rad (MST 3.0), 1000 rad (MST 8.0), 1200 rad (MST 5.18)

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    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.

  18. Blockade of both B7-H4 and CTLA-4 co-signaling pathways enhances mouse islet allograft survival

    Science.gov (United States)

    Wang, Xiaojie; Hao, Jianqiang; Metzger, Daniel L.; Mui, Alice; Lee, I-Fang; Akhoundsadegh, Noushin; Chen, C. Lieping; Ou, Dawei; Ao, Ziliang; Verchere, C. Bruce; Warnock, Garth L.

    2012-01-01

    Costimulation blockade is an effective way to prevent allograft rejection. In this study, we tested the efficacy of two negative co-signaling molecules in protecting islet allograft function. We used local expression of B7-H4 by adenoviral transduction of islets (Ad-B7-H4) and systemic administration of CTLA-4.Ig to investigate the outcomes of allograft survival. Five groups of streptozotocin-induced diabetic C57BL/6 mice received 400 islets each from BALB/c donors. The groups consisted of control (G1); CTLA-4.Ig (G2); Ad-LacZ (G3); Ad-B7-H4 (G4); and Ad-B7-H4 and CTLA-4.Ig combined (G5). G1 and G3 developed graft failure on average of two weeks. G2, G4 and G5 survived for 43.8 ± 34.8, 54.7 ± 31.2 and 77.8 ± 21.5 d, respectively. Activated T and B cells in the lymph nodes were significantly controlled by CTLA-4.Ig treatment. Significantly reduced infiltrates were also detected in the allografts of G2 compared with G1. By contrast, B7-H4 significantly inhibited Th1-associated IFN-gamma secretion in the early stage and increased Foxp3+ T cells in the long-term surviving allografts. Our study suggests that CTLA-4 and B7-H4 inhibit alloimmune responses through distinct mechanisms, and that combination therapy which activates two negative co-signaling pathways can further enhance islet allograft survival. PMID:22878670

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Maureen Ezeakile

    2014-01-01

    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.

  1. The detection of coronary stiffness in cardiac allografts using MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Kai, E-mail: kai-lin@northwestern.edu [Department of Radiology, Northwestern University, 737 N Michigan Avenue, Suite 1600, Chicago, IL 60611 (United States); Lloyd-Jones, Donald M. [Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Suite 1400, Chicago, IL 60611 (United States); Taimen, Kirsi; Liu, Ying [Department of Radiology, Northwestern University, 737 N Michigan Avenue, Suite 1600, Chicago, IL 60611 (United States); Bi, Xiaoming [Cardiovascular MR R and D, Siemens Healthcare, 737 N Michigan Avenue, Suite 1600, Chicago, IL 60611 (United States); Li, Debiao; Carr, James C. [Department of Radiology, Northwestern University, 737 N Michigan Avenue, Suite 1600, Chicago, IL 60611 (United States)

    2014-08-15

    Objective: To test the hypothesis that biomechanical changes are quantitatively related to morphological features of coronary arteries in heart transplant (HTx) recipients. Materials and methods: With IRB approval, three-dimensional (3D) magnetic resonance (MR) angiography and two-dimensional (2D) black-blood stead-state free precession (SSFP) MR imaging were performed to image coronary arteries of 36 HTx patients. Contours of coronary wall were manually drawn. For each coronary segment, coronary wall thickness, wall area, lumen area (in systole and diastole) were acquired. Coronary distensibility index (CDI) and the percent of the coronary wall occupying the vessel area (PWOV) were calculated. Results: There are totally 98 coronary segments eligible for quantitative analysis from 27 HTx patients. The CDI is 4.90 ± 2.44 mmHg{sup −1}. The mean wall thickness is 1.49 ± 0.24 mm and the PWOV is 74.6% ± 7.5%. CDI has moderate correlations with wall thickness (r = −0.531, P < 0.001) and with PWOV (R = −0.435, P < 0.001). Conclusions: Detected with coronary MR imaging, CDI is quantitatively correlated with the morphological features of the coronary artery in HTx patients. Coronary stiffness has the potential to become an alternative imaging biomarker for the quantitative assessment of the status of cardiac allografts.

  2. Donor Heart Treatment With COMP-Ang1 Limits Ischemia-Reperfusion Injury and Rejection of Cardiac Allografts.

    Science.gov (United States)

    Syrjälä, S O; Nykänen, A I; Tuuminen, R; Raissadati, A; Keränen, M A I; Arnaudova, R; Krebs, R; Koh, G Y; Alitalo, K; Lemström, K B

    2015-08-01

    The major cause of death during the first year after heart transplantation is primary graft dysfunction due to preservation and ischemia-reperfusion injury (IRI). Angiopoietin-1 is a Tie2 receptor-binding paracrine growth factor with anti-inflammatory properties and indispensable roles in vascular development and stability. We used a stable variant of angiopoietin-1 (COMP-Ang1) to test whether ex vivo intracoronary treatment with a single dose of COMP-Ang1 in donor Dark Agouti rat heart subjected to 4-h cold ischemia would prevent microvascular dysfunction and inflammatory responses in the fully allogeneic recipient Wistar Furth rat. COMP-Ang1 reduced endothelial cell-cell junction disruption of the donor heart in transmission electron microscopy during 4-h cold ischemia, improved myocardial reflow, and reduced microvascular leakage and cardiomyocyte injury of transplanted allografts during IRI. Concurrently, the treatment reduced expression of danger signals, dendritic cell maturation markers, endothelial cell adhesion molecule VCAM-1 and RhoA/Rho-associated protein kinase activation and the influx of macrophages and neutrophils. Furthermore, COMP-Ang1 treatment provided sustained anti-inflammatory effects during acute rejection and prevented the development of cardiac fibrosis and allograft vasculopathy. These results suggest donor heart treatment with COMP-Ang1 having important clinical implications in the prevention of primary and subsequent long-term injury and dysfunction in cardiac allografts. PMID:25932532

  3. Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography

    International Nuclear Information System (INIS)

    The ability of noninvasive risk stratification using dipyridamole-thallium-201 (Tl-201) imaging and radionuclide ventriculography to predict perioperative and long-term cardiac events (myocardial infarction or cardiac death) was evaluated in 36 uremic diabetic and 29 nondiabetic candidates for renal allograft surgery. Of the 35 patients who underwent renal allograft surgery 8 +/- 7 months after the study, none had transient Tl-201 defects (although 13 had depressed left ventricular ejection fraction) and none developed perioperative cardiac events. During a mean follow-up of 23 +/- 11 months, 6 (9%) patients developed cardiac events. Logistic regression analysis was used to compare the predictive value of clinical data (including age, sex, diabetes, chest pain history, allograft recipient) and radionuclide data. Presence of transient Tl-201 defect and left ventricular ejection fraction were the only significant predictors of future cardiac events (p less than 0.01). No other patient variables, including diabetes or receiving a renal allograft, had either univariate or multivariate predictive value. All 3 patients with transient Tl-201 defects had cardiac events compared with only 3 of 62 (5%) patients without transient Tl-201 defect (p less than 0.0001). Mean left ventricular ejection fraction was lower in patients with cardiac events (44 +/- 13%) compared with patients without cardiac events (57 +/- 9%, p less than 0.005). Overall, 5 of 6 patients with cardiac events had either transient Tl-201 defects or depressed left ventricular ejection fraction. Dipyridamole-Tl-201 imaging and radionuclide ventriculography may be helpful in identifying uremic candidates for renal allograft surgery who are at low risk for perioperative and long-term cardiac events

  4. Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K.A.; Rimmer, J.; Haisch, C. (Univ. of Vermont College of Medicine, Burlington (USA))

    1989-11-01

    The ability of noninvasive risk stratification using dipyridamole-thallium-201 (Tl-201) imaging and radionuclide ventriculography to predict perioperative and long-term cardiac events (myocardial infarction or cardiac death) was evaluated in 36 uremic diabetic and 29 nondiabetic candidates for renal allograft surgery. Of the 35 patients who underwent renal allograft surgery 8 +/- 7 months after the study, none had transient Tl-201 defects (although 13 had depressed left ventricular ejection fraction) and none developed perioperative cardiac events. During a mean follow-up of 23 +/- 11 months, 6 (9%) patients developed cardiac events. Logistic regression analysis was used to compare the predictive value of clinical data (including age, sex, diabetes, chest pain history, allograft recipient) and radionuclide data. Presence of transient Tl-201 defect and left ventricular ejection fraction were the only significant predictors of future cardiac events (p less than 0.01). No other patient variables, including diabetes or receiving a renal allograft, had either univariate or multivariate predictive value. All 3 patients with transient Tl-201 defects had cardiac events compared with only 3 of 62 (5%) patients without transient Tl-201 defect (p less than 0.0001). Mean left ventricular ejection fraction was lower in patients with cardiac events (44 +/- 13%) compared with patients without cardiac events (57 +/- 9%, p less than 0.005). Overall, 5 of 6 patients with cardiac events had either transient Tl-201 defects or depressed left ventricular ejection fraction. Dipyridamole-Tl-201 imaging and radionuclide ventriculography may be helpful in identifying uremic candidates for renal allograft surgery who are at low risk for perioperative and long-term cardiac events.

  5. Long-term survival of intestinal allografts induced by costimulation blockade, busulfan and donor bone marrow infusion.

    Science.gov (United States)

    Guo, Zhong; Wang, Jun; Dong, Ying; Adams, Andrew B; Shirasugi, Nozomu; Kim, Oliver; Hart, John; Newton-West, Marvin; Pearson, Thomas C; Larsen, Christian P; Newell, Kenneth A

    2003-09-01

    Tolerance-inducing strategies that infuse donor bone marrow cells in conjunction with costimulation blockade have not been applied to intestinal transplantation. Intestines from BALB/c mice were transplanted into C57BL/6 recipients treated with anti-CD40L mAb, CTLA4-Ig, donor bone marrow, and busulfan. The majority of mice transplanted after completion of this regimen developed hematopoietic macrochimerism, although the degree of chimerism varied widely between recipients, and experienced long-term allograft survival. T cells from these mice demonstrated donor-specific hyporesponsiveness in vitro. However, T cells from chimeric mice proliferated to donor alloantigen in vivo. Furthermore, chimeric mice bearing intestinal allografts were capable of rejecting subsequently placed donor-strain skin grafts. These data suggest that although long-term allograft survival occurs in the absence of acute or chronic rejection, recipient mice are not completely unresponsive to donor alloantigens. When intestinal transplantation was performed at the time of initial bone marrow infusion (initiation of the chimerism protocol), most recipients failed to develop chimerism and promptly rejected the intestinal allograft. Although this is the most effective protocol that we have tested using this stringent model of transplantation, our observations suggest that modifications will be necessary before it can be reliably applied to the transplantation of highly immunogeneic organs like the intestine. PMID:12919088

  6. Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4+ CD25+ regulatory T cells population

    Science.gov (United States)

    Zheng, Quan-you; Liang, Shen-ju; Li, Gui-qing; Lv, Yan-bo; Li, You; Tang, Ming; Zhang, Kun; Xu, Gui-lian; Zhang, Ke-qin

    2016-01-01

    Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3−/−) as skin graft donors or recipients. Compared with C3+/+ B6 allografts, C3−/− B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2bm12 B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3+/+ allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3−/− allografts. Moreover, C3−/− allografts caused attenuated Th1/Th17 responses, but increased CD4+CD25+Foxp3+ regulatory T (Treg) cell expression markedly in local intragraft and H-2bm12 recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4+ CD25+ Treg cell population expansion and attenuated Th1/Th17 response. PMID:27641978

  7. Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population.

    Science.gov (United States)

    Zheng, Quan-You; Liang, Shen-Ju; Li, Gui-Qing; Lv, Yan-Bo; Li, You; Tang, Ming; Zhang, Kun; Xu, Gui-Lian; Zhang, Ke-Qin

    2016-01-01

    Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3(-/-)) as skin graft donors or recipients. Compared with C3(+/+) B6 allografts, C3(-/-) B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2(bm12) B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3(+/+) allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3(-/-) allografts. Moreover, C3(-/-) allografts caused attenuated Th1/Th17 responses, but increased CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell expression markedly in local intragraft and H-2(bm12) recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4(+) CD25(+) Treg cell population expansion and attenuated Th1/Th17 response. PMID:27641978

  8. Dendritic Cells Transduced with SOCS1 Gene Exhibit Regulatory DC Properties and Prolong Allograft Survival

    Institute of Scientific and Technical Information of China (English)

    Hong Fu; Shaohua Song; Fang Liu; Zhijia Ni; Yi Tang; Xiaoyun Shen; Liang Xiao; Guoshan Ding; Quanxing Wang

    2009-01-01

    SOCS1 is a key regulator of cytokine signaling and is important for maintaining balance in the immune system. It is thought to participate in negative feedback loops in cytokine signaling and may be an important signal for the regulation of dendritic cell (DC) maturation. However, it remains unclear whether DCs transduced with SOCS1 exhibit characteristics of regulatory DCs and induce allogeneic T-cell hyporesponsiveness. In this study, we constructed adenoviral vector coding SOCS1 (Ad-SOCS1) that can efficiently increase SOCS1 gene expression in bone marrow-derived dendritic cells. DCs transduced with Ad-SOCS1 (DC-SOCS1) expressed low levels of costimulatory and MHC molecules, were resistant to maturation and activation stimulation, induced allogeneic T-cell hyporesponsiveness, and promoted the generation of regulatory-like T cells in vitro. DC-SOCS1 pretreatment significantly prolonged the survival of allografts and led to a substantial increase in the generation of regulatory T cells. Our data suggest that SOCS1 inhibits DC maturation and induces regulatory DC generation, therefore possessing therapeutic potential to prevent rejection in organ transplantation. Cellular & Molecular Immunology.

  9. Interruption of dendritic cell-mediated TIM-4 signaling induces regulatory T cells and promotes skin allograft survival.

    Science.gov (United States)

    Yeung, Melissa Y; McGrath, Martina M; Nakayama, Masafumi; Shimizu, Tetsunosuke; Boenisch, Olaf; Magee, Ciara N; Abdoli, Rozita; Akiba, Hisaya; Ueno, Takuya; Turka, Laurence A; Najafian, Nader

    2013-10-15

    Dendritic cells (DCs) are the central architects of the immune response, inducing inflammatory or tolerogenic immunity, dependent on their activation status. As such, DCs are highly attractive therapeutic targets and may hold the potential to control detrimental immune responses. TIM-4, expressed on APCs, has complex functions in vivo, acting both as a costimulatory molecule and a phosphatidylserine receptor. The effect of TIM-4 costimulation on T cell activation remains unclear. In this study, we demonstrate that Ab blockade of DC-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4(+) T cells, both in vitro and in vivo. iTreg induction occurs through suppression of IL-4/STAT6/Gata3-induced Th2 differentiation. In addition, blockade of TIM-4 on previously activated DCs still leads to increased iTreg induction. iTregs induced under TIM-4 blockade have equivalent potency to control and, upon adoptive transfer, significantly prolong skin allograft survival in vivo. In RAG(-/-) recipients of skin allografts adoptively transferred with CD4(+) T cells, we show that TIM-4 blockade in vivo is associated with a 3-fold prolongation in allograft survival. Furthermore, in this mouse model of skin transplantation, increased induction of allospecific iTregs and a reduction in T effector responses were observed, with decreased Th1 and Th2 responses. This enhanced allograft survival and protolerogenic skewing of the alloresponse is critically dependent on conversion of naive CD4(+) to Tregs in vivo. Collectively, these studies identify blockade of DC-expressed TIM-4 as a novel strategy that holds the capacity to induce regulatory immunity in vivo.

  10. Early inflammatory markers are independent predictors of cardiac allograft vasculopathy in heart-transplant recipients.

    Directory of Open Access Journals (Sweden)

    Carlos A Labarrere

    Full Text Available BACKGROUND: Identification of risk is essential to prevent cardiac allograft vasculopathy (CAV and graft failure due to CAV (GFDCAV in heart transplant patients, which account for 30% of all deaths. Early CAV detection involves invasive, risky, and expensive monitoring approaches. We determined whether prediction of CAV and GFDCAV improves by adding inflammatory markers to a previously validated atherothrombotic (AT model. METHODS AND FINDINGS: AT and inflammatory markers interleukin-6 (IL-6 and C-reactive protein (CRP were measured in heart biopsies and sera of 172 patients followed prospectively for 8.9±5.0 years. Models were estimated for 5- and 10-year risk using (1 the first post-transplant biopsy only, or (2 all biopsies obtained within 3 months. Multivariate models were adjusted for other covariates and cross-validated by bootstrapping. After adding IL-6 and CRP to the AT models, we evaluated the significance of odds ratios (ORs associated with the additional inflammatory variables and the degree of improvement in the area under the receiver operating characteristic curve (AUROC. When inflammatory markers were tested alone in prediction models, CRP (not IL-6 was a significant predictor of CAV and GFDCAV at 5 (CAV: p<0.0001; GFDCAV: p = 0.005 and 10 years (CAV: p<0.0001; GFDCAV: p = 0.003. Adding CRP (not IL-6 to the best AT models improved discriminatory power to identify patients destined to develop CAV (using 1st biopsy: p<0.001 and p = 0.001; using all 3-month biopsies: p<0.04 and p = 0.008 at 5- and 10-years, respectively and GFDCAV (using 1st biopsy: 0.92 vs. 0.95 and 0.86 vs. 0.89; using all 3-month biopsies: 0.94 vs. 0.96 and 0.88 vs. 0.89 at 5- and 10-years, respectively, as indicated by an increase in AUROC. CONCLUSIONS: Early inflammatory status, measured by a patient's CRP level (a non-invasive, safe and inexpensive test, independently predicts CAV and GFDCAV. Adding CRP to a previously established AT model

  11. Alefacept promotes immunosuppression-free renal allograft survival in nonhuman primates via depletion of recipient memory T cells.

    Science.gov (United States)

    Lee, S; Yamada, Y; Tonsho, M; Boskovic, S; Nadazdin, O; Schoenfeld, D; Cappetta, K; Atif, M; Smith, R-N; Cosimi, A B; Benichou, G; Kawai, T

    2013-12-01

    Renal allograft tolerance has been achieved in MHC-mismatched primates via nonmyeloablative conditioning beginning 6 days prior to planned kidney and donor bone marrow transplantation (DBMT). To extend the applicability of this approach to deceased donor transplantation, we recently developed a novel-conditioning regimen, the "delayed protocol" in which donor bone marrow (DBM) is transplanted several months after kidney transplantation. However, activation/expansion of donor-reactive CD8(+) memory T cells (TMEM) occurring during the interval between kidney and DBM transplantation impaired tolerance induction using this strategy. In the current study, we tested whether, Alefacept, a fusion protein which targets LFA-3/CD2 interactions and selectively depletes CD2(high) CD8(+) effector memory T cells (TEM) could similarly induce long-term immunosuppression-free renal allograft survival but avoid the deleterious effects of anti-CD8 mAb treatment. We found that Alefacept significantly delayed the expansion of CD2(high) cells including CD8(+) TEM while sparing naïve CD8(+) T and NK cells and achieved mixed chimerism and long-term immunosuppression-free renal allograft survival. In conclusion, elimination of CD2(high) T cells represents a promising approach to prevent electively the expansion/activation of donor-reactive TEM and promotes tolerance induction via the delayed protocol mixed chimerism approach.

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

    Science.gov (United States)

    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

    2015-11-01

    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.

  13. DIFFERENTIAL IMPACT OF HLA-A, HLA-B AND HLA-DR COMPATIBILITY ON THE RENAL ALLOGRAFT SURVIVAL

    Directory of Open Access Journals (Sweden)

    V. Y. Abramov

    2012-01-01

    Full Text Available We studied the long-term results of 532 deceased donor kidney transplantations to investigate the impact of HLA match on the survival of renal allograft. All transplants were performed in our center in 1996–2009 and moni- tored prospectively for 1–14 years. We found, the survival of 58 kidneys grafted with 0–2 mismatch for HLA- ABDR to be significantly better (Plogrank = 0,016 than the survival of the kidneys grafted with 3–6 HLA-ABDR mismatch. The full compatibility for HLA-A (n = 75 did not influence the long-term survival (Plogrank = 0,48. The absence of HLA-DR mismatch had a beneficial effect for survival of 68 kidneys (Plogrank = 0,07. Eighteen cases with the full HLA-B compatibility between graft and recipient demonstrated excellent long-term survival (Plogrank = 0,007. HLA-B compatibility influenced significantly (P = 0,042 the survival of transplanted kidney in the Cox regression model adjusted for donor and recipient age, panel-reactive antibody level, re-transplant, and immunosuppression protocol. The data obtained support the conclusion, that HLA compatibility should be one of the criteria of deceased donor kidney allocation. 

  14. Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival

    Institute of Scientific and Technical Information of China (English)

    De-Sheng Wang; Yu Li; Ke-Feng Dou; Kai-Zong Li; Zhen-Shun Song

    2006-01-01

    BACKGROUND: Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas-mediated cell death and to prolong recipient survival. METHODS: Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft. RESULTS: Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group. CONCLUSION: Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.

  15. 47. A cardiac center experience with Brugada syndrome who survived sudden cardiac death

    Directory of Open Access Journals (Sweden)

    I. Suliman

    2016-07-01

    Full Text Available Brugada syndrome is a heritable arrhythmia syndrome that is characterized by an electrocardiographic pattern consisting of coved-type ST-segment elevation (2 mm followed by a negative T wave in the right precordial leads, V1 through V3 (often referred to as type 1 Brugada electrocardiographic pattern, here we describe 3 cases of Brugada who survived sudden cardiac death (SCD cardiac center experience with survived Brugada syndrome patients – case series. First Case: The Father 45 years old male, presented in 2005 after involvement in unprovoked motor vehicle accident, the patient was the driver who lost consciousness and rushed to the hospital. On arrival to our ER and putting the patient on the bed, the ER doctor observed a brief episode of VF on the monitor. The patient was taken to the catheterization Lab , his coronaries were normal. The diagnosis of Brugada was established and the patient received a defibrillator. At That Time all family members were screened and were negative. Second Case: The Son of the first patient 5 years later his 23 years old male rushed to our ER after he lost consciousness, he was passenger in the car of his friend. Third Case: The pilot A military pilot aged a male 35 years old was in very good health when he lost consciousness and brought to the hospital after resuscitation in 2005. He had full invasive cardiac evaluation, subsequently he received a defibrillator in the same admission period, till 2015 he is doing fine. Brugada syndrome is associated with high tendency for sudden cardiac death. In our three cases the first clinical presentation was survived sudden cardiac death (SCD and all three male patients survived. We did not encounter a female patient who survived sudden cardiac death.

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    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.

  17. Overhydration, cardiac function and survival in hemodialysis patients

    OpenAIRE

    Mihai Onofriescu; Dimitrie Siriopol; Luminita Voroneanu; Simona Hogas; Ionut Nistor; Mugurel Apetrii; Laura Florea; Gabriel Veisa; Irina Mititiuc; Mehmet Kanbay; Radu Sascau; Adrian Covic

    2015-01-01

    RESEARCH ARTICLE Overhydration, Cardiac Function and Survival in Hemodialysis Patients Mihai Onofriescu1☯, Dimitrie Siriopol1☯, Luminita Voroneanu1, Simona Hogas1, Ionut Nistor1, Mugurel Apetrii1, Laura Florea1, Gabriel Veisa1, Irina Mititiuc1, Mehmet Kanbay3, Radu Sascau2, Adrian Covic1* 1 Department of Nephrology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania, 2 Department of Cardiology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania...

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

    Science.gov (United States)

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

    2016-01-01

    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

  19. Role of mobile passenger lymphocytes in the rejection of renal and cardiac allografts in the rat. A passenger lymphocyte-mediated graft-versus-host reaction amplifies the host response

    Energy Technology Data Exchange (ETDEWEB)

    van Vrieshilfgaarde, R.; Hermans, P.; Terpstra, J.L.; van Breda Viresman, P.J.

    1980-03-01

    It is demonstrated that passenger lymphocytes migrate out of rat renal allografts into host spleens in a radioresistant fashion. These mobile passenger lymphocytes within BN kidney and heart transplants are immunocompetent, since they elicit a graft-versus-host (GVH) reaction in the spleens of (LEW x BN)F2 hybrid hosts. The greater GVH reaction in (LEW x BN)F1 recipients of BN kidneys reflects the greater number of mobile passenger lymphocytes in the kidney when compared to the heart. The mobile passenger lymphocytes within BN renal allografts also cause a proliferative response in the spleens of the LEW hosts as well as an accelerated rejection of BN renal allografts when compared to BN cardiac allografts, for the differences between BN kidney and heart, both in terms of splenomegaly elicited in LEW as well as tempo of rejection, are abolished by total body x-irradiation of the donor with 900 rad. Results indicate that a mobile passenger lymphocyte mediated GVH reaction in the central lymphoid organs of the host augments the host response to allogenic kidneys and contributes materially to first-set renal allograft rejection; this GVH reaction on the other hand is not conspicuously present in LEW recipients of BN cardiac allografts and has therefore little effect on first-set cardiac allograft rejection.

  20. An infant with out-of-hospital cardiac arrest secondary to enteroviral myocarditis surviving up to cardiac transplantation.

    Science.gov (United States)

    McGovern, Eimear; Ryan, Ethel; McMahon, Colin J

    2016-01-01

    We report the case of a 13-day-old infant with enteroviral myocarditis surviving an out-of-hospital cardiac arrest. She underwent orthotopic cardiac transplantation three months later. A year after the transplantation, she is alive and well. Enteroviral infection is common in neonates with high mortality in cases of enteroviral myocarditis. Cardiac transplantation is a treatment option for infants who fail to recover and remain dependent on inotropic support. This is the first report of an infant with out-of-hospital cardiac arrest secondary to enteroviral myocarditis surviving up to cardiac transplantation.

  1. Adoptive infusion of tolerogenic dendritic cells prolongs the survival of pancreatic islet allografts: a systematic review of 13 mouse and rat studies.

    Directory of Open Access Journals (Sweden)

    Guixiang Sun

    Full Text Available OBJECTIVE: The first Phase I study of autologous tolerogenic dendritic cells (Tol-DCs in Type 1 diabetes (T1D patients was recently completed. Pancreatic islet transplantation is an effective therapy for T1D, and infusion of Tol-DCs can control diabetes development while promoting graft survival. In this study, we aim to systematically review islet allograft survival following infusion of Tol-DCs induced by different methods, to better understand the mechanisms that mediate this process. METHODS: We searched PubMed and Embase (from inception to February 29(th, 2012 for relevant publications. Data were extracted and quality was assessed by two independent reviewers. We semiquantitatively analyzed the effects of Tol-DCs on islet allograft survival using mixed leukocyte reaction, Th1/Th2 differentiation, Treg induction, and cytotoxic T lymphocyte activity as mechanisms related-outcomes. We discussed the results with respect to possible mechanisms that promote survival. RESULTS: Thirteen articles were included. The effects of Tol-DCs induced by five methods on allograft survival were different. Survival by each method was prolonged as follows: allopeptide-pulsed Tol-DCs (42.14 ± 44 days, drug intervention (39 days, mesenchymal stem cell induction (23 days, genetic modification (8.99 ± 4.75 days, and other derivation (2.61 ± 6.98 days. The results indicate that Tol-DC dose and injection influenced graft survival. Single-dose injections of 10(4 Tol-DCs were the most effective for allograft survival, and multiple injections were not superior. Tol-DCs were also synergistic with immunosuppressive drugs or costimulation inhibitors. Possible mechanisms include donor specific T cell hyporesponsiveness, Th2 differentiation, Treg induction, cytotoxicity against allograft reduction, and chimerism induction. CONCLUSIONS: Tol-DCs induced by five methods prolong MHC mismatched islet allograft survival to different degrees, but allopeptide-pulsed host DCs

  2. Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival

    Energy Technology Data Exchange (ETDEWEB)

    Burkhardt, K.; Loughnan, M.S.; Diamantstein, T.; Mandel, T.E.

    1988-11-01

    Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes.

  3. Prolonging survival in vascularized bone allograft transplantation: developing specific immune unresponsiveness

    Energy Technology Data Exchange (ETDEWEB)

    Paskert, J.P.; Yaremchuk, M.J.; Randolph, M.A.; Weiland, A.J.

    1987-04-01

    Vascularized bone allografts (VBAs) could be useful adjuncts to the clinical reconstructive surgeon's arsenal. These grafts are known experimentally to be subject to host rejection. One way to control the rejection problem would be to develop specific immune unresponsiveness via host conditioning. Using a proven reliable model in inbred rats for studying heterotopic VBA transplantation, recipient animals were conditioned preoperatively with third-party unrelated blood, donor-specific blood (DSB) alone and with cyclosporine, and ultraviolet irradiated donor-specific blood. The combination of DSB plus cyclosporine delayed rejection of grafts across a strong histocompatibility barrier for three to four weeks. However, rejection was delayed across a weak histocompatibility barrier for five to six weeks using this same host pretreatment. The implications are that specific immunosuppression, although possible, is difficult to achieve in VBA transplantation, and that such techniques will rely on tissue-matching to minimize the genetic disparity between graft and host.

  4. Blockade of γc Signals in Combination with Donor-specific Transfusion Induces Cardiac Allograft Acceptance in Murine Models

    Institute of Scientific and Technical Information of China (English)

    昌盛; 汪理; 林星光; 向芙莉; 陈必成; 陈忠华

    2010-01-01

    The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the γc in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received an...

  5. DISTURBANCE OF THE CARDIOMYOCYTE’S MACROMOLECULAR STRUCTURE IN HEART ALLOGRAFTS AS A SIGN OF CHRONIC REJECTION

    OpenAIRE

    A. G. Kupriyanova; L. V. Beletskaya; I. M. Ilyinsky; V. A. Zaidenov; N. P. Mozeiko; R. S. Saitgareev; A. Y. Kormer; A. M. Golts; V. M. Zakharevich; S. V. Gautier

    2012-01-01

    Chronic rejection, especially cardiac allograft vasculopathy, is a major limiting factor for long-term transplant survival. This process affects not only the blood vessels, but also cardiomyocytes. However, there are extremely few reports on the evaluation of their macromolecular structure state. The aim of the study was to evaluate the structural proteins of cardiomyocytes (actin, myosin, troponin I, titin, desmin, vinculin) of heart allografts in different periods after the operation (from ...

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

    Science.gov (United States)

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

    2016-08-01

    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. PMID:27112509

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

    Science.gov (United States)

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

    2016-08-01

    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.

  8. Effect of nifedipine on renal allograft function and survival beyond one year.

    Science.gov (United States)

    Shin, G T; Cheigh, J S; Riggio, R R; Suthanthiran, M; Stubenbord, W T; Serur, D; Wang, J C; Rubin, A L; Stenzel, K H

    1997-01-01

    We previously reported that a calcium channel blocker supplemented immunosuppression produced excellent patient and graft survival rates in cadaveric kidney transplantation. We report here the long term outcome of patients treated with nifedipine-supplemented triple immunosuppression as compared with those of historical controls who were treated similarly without nifedipine. Study subjects included 111 patients transplanted in 1990-1994, treated with nifedipine and triple immunosuppression and with functioning grafts for more than one year (Nifedipine group). The results of cyclosporine (CyA) dose, blood pressure (BP), serum creatinine (Cr), and actuarial graft survival rate (GSR) up to 5 years posttransplant in these patients were compared with those of 52 patients transplanted in 1985-1990, treated similarly without calcium channel blockers (Control group). Donor sources, gender ratio, age distribution, causes of end stage renal disease, incidence of hypertension prior to transplantation and incidence of rejection in the first year between the groups were comparable. Throughout the study period the Nifedipine group had significantly lower serum Cr (1.5 +/- 0.7 vs. 1.8 +/- 0.7 mg/dl) and higher GSR (93.8% vs. 88% at 5 years) than the Control group. BP was comparable despite higher CyA doses in the Nifedipine group (4.3 +/- 1.1 vs. 3.3 +/- 1.1 mg/kg/day). We conclude that nifedipine is beneficial in improving long-term graft function and survival in kidney transplant recipients by mitigating CyA associated renal injury.

  9. Current Status of Cardiac Allograft Vasculopathy Diagnosis%移植心脏冠状动脉血管病变的诊断现状

    Institute of Scientific and Technical Information of China (English)

    韩春勇

    2012-01-01

    Cardiac allograft vasculopathy ( CAV) is a complicated coronary artery disease that occurs after heart transplantation. CAV primarily contributes to the patients' high postoperative morbidites and mortality. Due to the denervation of cardiac allografts, CAV rarely presents with an ischemic syndrome. Therefore it is important to screen and diagnose CAV early. Coronary angiography remains the principal screening tool for CAV in most centers, even though its sensitivity is not high enough to detect CAV. Intravascular ultrasound is considered to be the most reliable tool for diagnosing CAV as it can directly determine the intimal thickness and the vessel wall morphology. New approaches to diagnosis include dobutamine stress echocardiography, coronary computed tomography, and cardiac MRI. These diagnostic tools require more testing in relation to CAV.%移植心脏血管病变(CAV)是一种相当复杂的心脏移植后冠状血管病变,是在心脏移植术后患者发病或死亡的首要原因,CAV患者通常无症状,因此CAV的早期筛查诊断是非常重要.大部分心脏中心每年常规行冠状动脉造影筛查CAV,而冠状动脉造影敏感性欠佳.血管内超声被认为是最敏感的早期筛查诊断CAV的方法,因为它可以直接准确测定内膜增厚程度、管壁形态.多巴酚丁胺负荷超声心动图、冠状动脉CT和心脏磁共振成像是较新的CAV诊断方法,但仍需要进一步研究.

  10. Length of time on dialysis prior to renal transplantation is a critical factor affecting patient survival after allografting.

    Science.gov (United States)

    West, J C; Bisordi, J E; Squiers, E C; Latsha, R; Miller, J; Kelley, S E

    1992-01-01

    Within the past year at our transplant center we have had the experience of performing renal allografts in two patients older than 65 years, each of whom had been on hemodialysis more than 10 years. Both resulted in patient mortality within 90 days of transplant (one due to myocardial infarction, the other due to visceral ischemia with infarction). This prompted us to review retrospectively our own data (n = 204) and the national (UNOS) data (n = 10,971) regarding transplant outcome, patient age, and length of time on dialysis prior to renal transplantation. This review revealed that patient mortality after transplant increased with the length of end-stage renal disease (dialysis, regardless of type) independent of age, the greatest mortality occurring within the first 6 months of transplant (and not thereafter); graft survival was similar for all age cohorts analyzed. Our review of the literature reveals a paucity of articles pertaining to post-transplant mortality and length of time on dialysis prior to transplant. Our results indicate the following possible conclusions. (1) The length of time of end-stage renal disease therapy prior to renal transplantation is a significant and independent risk factor for post-transplant mortality. (2) Higher priority should be given to this factor when formulating strategies for allocation of scarce resources. (3) Patients on dialysis for extended periods of time who are elderly may be at particularly high risk. (4) Patients being considered for renal transplant should be informed of their individual risk factors for mortality post-transplant based on length of ESRD therapy. (5) Renal transplantation should be considered as early as possible in patients with ESRD (or imminent ESRD). PMID:14621760

  11. Short-term azithromycin treatment promotes cornea allograft survival in the rat.

    Directory of Open Access Journals (Sweden)

    Katrin Wacker

    Full Text Available BACKGROUND: Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM following experimental keratoplasty in rats. METHODS: Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+, CD4(+, CD8(+, CD25(+, CD161(+ and CD163(+ cells were quantified via immunohistochemistry. RESULTS: AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls. CONCLUSIONS: Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

  12. 抗ICOS免疫疗法抑制鼠心脏移植的加速性和慢性排斥反应%Anti-inducible costimulator immunotherapy inhibits accelerated and chronic cardiac allograft rejections in rats

    Institute of Scientific and Technical Information of China (English)

    孙志鹏; 阿民布和; 朱斌; 宫柯; 张能维

    2010-01-01

    -stimulator(ICOS)therapy and AdCTLA-41g treatment on preventing accelerated cardiac rejection caused by donor-strain skin grafting and validate that ICOS therapy can block accelerated cardiac rejection,no matter with or without AdCTLA-41g treatment.METHODS: DA hearts were transplanted into the abdominal cavity of LEW recipients.The recipients intravenously received single dose of 109 plaque-forming units of AdCTLA-41g immediately after transplantation.Recipients with grafts surviving>50days were given a full-thickness donor-type skin graft to the lateral thoracic wall.These recipients received intravenous injection of anti-ICOS antibody(1 mg/kg)or control IgG from the 50th day,once every other day,for 2 weeks.Complete graft rejection was defined as cessation of beating and was histologically confirmed by mononuclear cell infiltration and cardiac myocyte necrosis using hematoxylin and eosin staining of graft sections.RESULTS AND CONCLUSION: Cardiac sections of AdCTLA-41g-treated recipients surviving > 100 days showed typical ICOS-positive mononuclear cell infiltration and vasculopathy.AdCTLA-41g treatment combined with anti-ICOS therapy induced stable tolerance to chronic rejection.Anti-ICOS therapy significantly reduced ICOS-positive inflammatory cell infiltration,and prevented accelerated cardiac graft rejection following secondary skin grafting.These findings identify a critical role of ICOS in chronic and accelerated cardiac ailograft rejection and suggest a novel approach to prevent chronic rejection of vascularized organ allografts.

  13. Association between prehospital physician involvement and survival after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Hamilton, Annika; Steinmetz, Jacob; Wissenberg, Mads;

    2016-01-01

    involvement and 30-day survival. METHODS: Observational study including persons registered with first-time OHCA of any cause in the Danish Cardiac Arrest Registry during 2005-2012. We used logistic regression analysis to assess the association between 30-day survival and involvement of a physician at any time......AIM: Sudden out-of-hospital cardiac arrest (OHCA) is an important public health problem. While several interventions are known to improve survival, the impact of physician-delivered advanced cardiac life support for OHCA is unclear. We aimed to assess the association between prehospital physician...

  14. Inability of donor total body irradiation to prolong survival of vascularized bone allografts: Experimental study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-07-01

    At the present time, the toxic side effects of recipient immunosuppression cannot be justified for human non-vital organ transplantation. Total body irradiation has proven effective in ablating various bone-marrow-derived and endothelial immunocompetent cellular populations, which are responsible for immune rejection against donor tissues. Irradiation at a dose of 10 Gy was given to donor rats six days prior to heterotopic transplantation of vascularized bone allografts to host animals. Another group of recipient rats also received a short-term (sixth to fourteenth day after grafting), low dose of cyclosporine. Total body irradiation was able merely to delay rejection of grafts across a strong histocompatibility barrier for one to two weeks, when compared to nonirradiated allografts. The combination of donor irradiation plus cyclosporine did not delay the immune response, and the rejection score was similar to that observed for control allografts. Consequently, allograft viability was quickly impaired, leading to irreversible bone damage. This study suggest that 10 Gy of donor total body irradiation delivered six days prior to grafting cannot circumvent the immune rejection in a vascularized allograft of bone across a strong histocompatibility barrier.

  15. MicroRNA-155 may affect allograft survival by regulating the expression of suppressor of cytokine signaling 1.

    Science.gov (United States)

    Zhang, Maomao; Zhang, Qi; Liu, Fang; Yin, Li; Yu, Bo; Wu, Jian

    2011-10-01

    Immune rejection of organ transplants has life-threatening implications. It is believed that allograft rejection is initiated by the activation of lymphocytes following recognition of donor antigens, leading to generation of effector T lymphocytes, alloantibody production, and graft infiltration by alloreactive cells. There is solid evidence that miRNAs are integral for maintaining immune homeostasis and self-tolerance. A deeper understanding of the regulation of the immune response by miRNAs could define new mechanisms for manipulating graft immunity and preventing rejection. The miRNA miR-155 is of particular interest due to its known roles in regulating the expression of genes relevant to allograft rejection and the induction of immune tolerance. Indeed, miR-155 has been shown to dramatically impact both innate and adaptive immune processes, including inflammation, antigen presentation, T-cell differentiation, cytokine production, and T regulatory cell (Treg) functions. The suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of immune cell function and an evolutionarily conserved target of miR-155 in breast cancer cells. We propose that suppression of miR-155 could enhance SOCS1 expression in immune cells and suppress allograft rejection. Further studies on the specific role of miR-155 in allograft rejection may lead to the identification of new targets for therapeutic intervention. PMID:21802214

  16. Survival after out-of-hospital cardiac arrest in relation to sex

    DEFF Research Database (Denmark)

    Wissenberg, Mads; Hansen, Carolina Malta; Folke, Fredrik;

    2014-01-01

    AIM: Crude survival has increased following an out-of-hospital cardiac arrest (OHCA). We aimed to study sex-related differences in patient characteristics and survival during a 10-year study period. METHODS: Patients≥12 years old with OHCA of a presumed cardiac cause, and in whom resuscitation...... was attempted, were identified through the Danish Cardiac Arrest Registry 2001-2010. A total of 19,372 patients were included. RESULTS: One-third were female, with a median age of 75 years (IQR 65-83). Compared to females, males were five years younger; and less likely to have severe comorbidities, e...

  17. Long-term survival after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Holler, Nana G; Mantoni, Teit; Nielsen, Søren L;

    2007-01-01

    from the Danish Causes of Death Registry and the Danish Civil Registration System. We conducted a search to find out whether patients were still alive on 31 January 2005. RESULTS: Resuscitation was indicated and attempted in 1095 cases and 95 patients (8.7%) survived to discharge. Of these 75% had...... an initial rhythm of VF, 13% had asystole, 10% had PEA and 2% were unknown. Survival was 87% after one year and survival after 10 years was 46% with a significantly lower survival for patients over 60 years. CONCLUSION: Long-term survival after out-of-hospital cardiac arrest in a physician-staffed emergency...

  18. Kidneys from donors after cardiac death provide survival benefit.

    NARCIS (Netherlands)

    Snoeijs, M.G.; Schaubel, D.E.; Hene, R.; Hoitsma, A.J.; Idu, M.M.; Ijzermans, J.N.M.; Ploeg, R.J.; Ringers, J.; Christiaans, M.H.; Buurman, W.A.; Heurn, L.W.E. van

    2010-01-01

    The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait

  19. Kidneys from donors after cardiac death provide survival benefit

    NARCIS (Netherlands)

    M.G. Snoeijs (Maarten); D.E. Schaubel (Douglas); R. Hené (Ronald); A.J. Hoitsma (Andries); M.M. Idu (Mirza); J.N.M. IJzermans (Jan); R.J. Ploeg (Rutger); J. Ringers; M.H. Christiaans (Maarten); W.A. Buurman; L.W.E. van Heurn (Ernest)

    2010-01-01

    textabstractThe continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialys

  20. Kidneys from Donors after Cardiac Death Provide Survival Benefit

    NARCIS (Netherlands)

    Snoeijs, Maarten G.; Schaubel, Douglas E.; Hene, Ronald; Hoitsma, Andries J.; Idu, Mirza M.; Ijzermans, Jan N.; Ploeg, Rutger J.; Ringers, Jan; Christiaans, Maarten H.; Buurman, Wim A.; van Heurn, L. W. Ernest

    2010-01-01

    The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait

  1. Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography

    DEFF Research Database (Denmark)

    Dankiewicz, J; Nielsen, N; Annborn, M;

    2015-01-01

    PURPOSE: To investigate whether early coronary angiography (CAG) after out-of-hospital cardiac arrest of a presumed cardiac cause is associated with improved outcomes in patients without acute ST elevation. METHODS: The target temperature management after out-of-hospital cardiac arrest (TTM) trial...... early CAG was not significantly associated with survival. CONCLUSIONS: In this post hoc observational study of a large randomized trial, early coronary angiography for patients without acute ST elevation after out-of-hospital cardiac arrest of a presumed cardiac cause was not associated with improved...... showed no difference in all-cause mortality or neurological outcome between an intervention of 33 and 36 °C. In this post hoc analysis, 544 patients where the admission electrocardiogram did not show acute ST elevation were included. Early CAG was defined as being performed on admission or within...

  2. Optimizing Neurologically Intact Survival from Sudden Cardiac Arrest: A Call to Action

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Goodloe

    2014-11-01

    Full Text Available The U.S. national out-of-hospital and in-hospital cardiac arrest survival rates, although improving recently, have remained suboptimal despite the collective efforts of individuals, communities, and professional societies. Only until very recently, and still with inconsistency, has focus been placed specifically on survival with pre-arrest neurologic function. The reality of current approaches to sudden cardiac arrest is that they are often lacking an integrative, multi-disciplinary approach, and without deserved funding and outcome analysis. In this manuscript, a multidisciplinary group of authors propose practice, process, technology, and policy initiatives to improve cardiac arrest survival with a focus on neurologic function. [West J Emerg Med. 2014;15(7:-0.

  3. DISTURBANCE OF THE CARDIOMYOCYTE’S MACROMOLECULAR STRUCTURE IN HEART ALLOGRAFTS AS A SIGN OF CHRONIC REJECTION

    Directory of Open Access Journals (Sweden)

    A. G. Kupriyanova

    2012-01-01

    Full Text Available Chronic rejection, especially cardiac allograft vasculopathy, is a major limiting factor for long-term transplant survival. This process affects not only the blood vessels, but also cardiomyocytes. However, there are extremely few reports on the evaluation of their macromolecular structure state. The aim of the study was to evaluate the structural proteins of cardiomyocytes (actin, myosin, troponin I, titin, desmin, vinculin of heart allografts in different periods after the operation (from 6 days to 15 years. Major changes of macromolecular structure were revealed in late period after transplantation (6 months – 15 years. The contribution of humoral immune response in the process of chronic cardiac allograft rejection was observed: in eight of twelve recipients episodes of acute humoral rejection had been repeatedly registered; disorders of the expression of 5 proteins out of 6 characterized were found in recipients with recurrent and persistent antibody-mediated rejection. 

  4. Survival after blunt left ventricular rupture with cardiac tamponade

    Institute of Scientific and Technical Information of China (English)

    Yu-Jang Su; Chang-Chih Chen

    2013-01-01

    A34-year-old man was drunk and drove to hit a traffic island.Cold sweating and unconscious status were found on arrival.Vital signs revealedBP42/25, and heart rate121/min.There was massive pericardial effusion with cardiac tamponade found byCT.Immediate surgical intervention and rupture of left ventricular(LV) free wall was found.He was discharged after2 d intensive care unit(ICU) observation and5-day regular ward care.There is high mortality rate in traumatic heart rupture although timely repair, over all mortality is around20%-36% in recent3 years.

  5. De novo expression of fetal ED-A(+) fibronectin and B (+) tenascin-C splicing variants in human cardiac allografts: potential impact for targeted therapy of rejection.

    Science.gov (United States)

    Franz, Marcus; Matusiak-Brückner, Monika; Richter, Petra; Grün, Katja; Ziffels, Barbara; Neri, Dario; Maschek, Hansjörg; Schulz, Uwe; Pfeil, Alexander; Jung, Christian; Figulla, Hans R; Gummert, Jan; Berndt, Alexander; Renner, André

    2014-10-01

    Management of acute and especially chronic rejection after human cardiac transplantation is still challenging. Chronic rejection, represented by allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) is known to cause severe long-term complications. Rejection associated tissue-remodelling entails the reoccurrence of fetal variants of Fibronectin (Fn) and Tenascin-C (Tn-C), which are virtually absent in adult human organs. In a rat model, an extensive re-expression could be demonstrated for ED-A(+) Fn with spatial association to CAV and CIF. Thus, it is of great interest to investigate the cardiac tissue expression and distribution in human samples. From 48 heart transplanted patients, 64 tissue specimens derived from right ventricular biopsies were available. Histopathological analysis was performed according to the International Society for Heart and Lung Transplantation (ISHLT) guidelines for the detection of acute rejection. By immunohistochemistry, protein expression of ED-A(+) Fn, B(+) Tn-C, alpha-smooth muscle actin, CD31 and CD45 was assessed and analysed semiquantitatively. Co-localisation studies were performed by means of immunofluorescence double labelling. Histopathological analysis of the 64 samples revealed different ISHLT grades (0R in 36 cases, 1R in 20 cases and 2R in 8 cases). There was a distinct and quantitatively relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C in most samples. Semi-quantitative evaluation did not show any correlation to the acute rejection grade for all markers. Interestingly, significant correlations to the extent of inflammation could be shown for ED-A(+) Fn (r = 0.442, p = 0.000) and B(+) Tn-C (r = 0.408, p = 0.001) as well as between both proteins (r = 0.663, p = 0.000). A spatial association of ED-A(+) Fn and B(+) Tn-C to CAV and CIF could be demonstrated. A relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C following human heart transplantation could be demonstrated with spatial association to

  6. 基因表达谱监测心脏移植排斥反应%Gene expression profile to monitor cardiac allograft rejection

    Institute of Scientific and Technical Information of China (English)

    陈浩; 于伟勇; 程韵枫

    2011-01-01

    @@ Introduction Despite improved immunosuppression, rejection still accounts for significant morbidity and mortality after heart transplantation[1].Any method that improves early detection and hence treatment of rejection is likely to lead to improved long-term survival.Serial surveillance endomyocardial biopsies (EMB) following cardiac transplantation have become an integral component of post-transplant management.However, EMB is invasive, expensive, variable[2] and causes low but definitemorbidity[3].

  7. SUCCESSFUL APPLICATION OF PERIPHERAL VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION FOR CARDIAC ALLOGRAFT ANTIBODY-MEDIATED REJECTION WITH SEVERE HEMODYNAMIC COMPROMISE

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2015-01-01

    Full Text Available Introduction. Acute antibody-mediated rejection (AMR is one of the severe complications of early and late period after heart transplantation (HT. Only few case reports and studies presented of mechanical circulatory support (MCS application for refractory acute rejection causing hemodynamic compromise. Aim. We report the case of a woman with cardiogenic shock caused by severe AMR that was successfully treatment by peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO. Material and methods. In december 2014, a 60-year-old woman with dilated cardiomyopathy was operated for HT. The patient had a good initial cardiac allograft function and no and was discharged from ICU on the 4th day after HT. 1st endomyocardial biopsy (EMB (the 7th day after HT showed absence of acute cellular and antibody-mediated rejection. On the 11th day after HT patient aggravated and presented clinical signs of life-threatening acute cardiac allograft dysfunction: arterial blood pressure 78/49/38 mm Hg, HR 111 in min, CVP 20 mm Hg, PAP 47/34/25 mm Hg, PCWP 25 mm Hg, CI 1.5 l/min/m2, adrenalin 110 ng/kg/min, dopamine 15 mcg/kg/min. ECG showed impairment of systolic left (LVEF 25% and right (RVEF 15% ventricle function, left and right ventricle diffuse hypokinesis, thickness of IVS, LV and RV wall 1.7, 1.4 and 0.8 cm, tricuspid and mitral valve regurgitation 2–3 degrees. EMB presented AMR. In conscience peripheral VA ECMO was installed. We used peripheral transcutaneous cannulation technique via femoral vessels – arterial cannula 15 F, venous cannula – 23 F, vascular catheter 14 G for anterograde leg’s perfusion. ACT 130–150 sec. AMR therapy included: methylprednisolon pulse-therapy (10 mg/kg for 5 day, IgG, plasmapheresis (No 7, rituximab. Results. Under MCS by VA ECMO we noted quick improvement of hemodynamic, metabolic homeostasis and organ functions. On the 6th day of VA ECMO (blood flow 1.8 l/min: arterial blood pressure 133/81/54 mm Hg, CVP 5 mm

  8. Prolonged hypoxia increases survival even in Zebrafish (Danio rerio showing cardiac arrhythmia.

    Directory of Open Access Journals (Sweden)

    Renate Kopp

    Full Text Available Tolerance towards hypoxia is highly pronounced in zebrafish. In this study even beneficial effects of hypoxia, specifically enhanced survival of zebrafish larvae, could be demonstrated. This effect was actually more pronounced in breakdance mutants, which phenotypically show cardiac arrhythmia. Breakdance mutants (bre are characterized by chronically reduced cardiac output. Despite an about 50% heart rate reduction, they become adults, but survival rate significantly drops to 40%. Normoxic bre animals demonstrate increased hypoxia inducible factor 1 a (Hif-1α expression, which indicates an activated hypoxic signaling pathway. Consequently, cardiovascular acclimation, like cardiac hypertrophy and increased erythrocyte concentration, occurs. Thus, it was hypothesized, that under hypoxic conditions survival might be even more reduced. When bre mutants were exposed to hypoxic conditions, they surprisingly showed higher survival rates than under normoxic conditions and even reached wildtype values. In hypoxic wildtype zebrafish, survival yet exceeded normoxic control values. To specify physiological acclimation, cardiovascular and metabolic parameters were measured before hypoxia started (3 dpf, when the first differences in survival rate occurred (7 dpf and when survival rate plateaued (15 dpf. Hypoxic animals expectedly demonstrated Hif-1α accumulation and consequently enhanced convective oxygen carrying capacity. Moreover, bre animals showed a significantly enhanced heart rate under hypoxic conditions, which reached normoxic wildtype values. This improvement in convective oxygen transport ensured a sufficient oxygen and nutrient supply and was also reflected in the significantly higher mitochondrial activity. The highly optimized energy metabolism observed in hypoxic zebrafish larvae might be decisive for periods of higher energy demand due to organ development, growth and increased activity. However, hypoxia increased survival only during a

  9. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Wissenberg, Mads; Lippert, Freddy K.; Folke, Fredrik;

    2013-01-01

    resuscitation was attempted were identified between 2001 and 2010 in the nationwide Danish Cardiac Arrest Registry. Of 29 111 patients with cardiac arrest, we excluded those with presumed noncardiac cause of arrest (n = 7390) and those with cardiac arrests witnessed by emergency medical services personnel (n......IMPORTANCE Out-of-hospital cardiac arrest is a major health problem associated with poor outcomes. Early recognition and intervention are critical for patient survival. Bystander cardiopulmonary resuscitation (CPR) is one factor among many associated with improved survival. OBJECTIVE To examine...... temporal changes in bystander resuscitation attempts and survival during a 10-year period in which several national initiatives were taken to increase rates of bystander resuscitation and improve advanced care. DESIGN, SETTING, AND PARTICIPANTS Patients with out-of-hospital cardiac arrest for which...

  10. Electron spin resonance analysis of heme-nitrosyl and reduced iron-sulfur centered complexes in allogeneic, heterotopic cardiac transplants: effects of treatment with pyrrolidine dithiocarbamate.

    Science.gov (United States)

    Nakanishi, A L; Roza, A M; Adams, M B; Seibel, R; Moore-Hilton, G; Kalyanaraman, B; Pieper, G M

    1998-07-15

    Inhibition of inducible nitric oxide synthase (iNOS) prolongs allograft survival suggesting a role for nitric oxide (.NO) in allograft rejection. Induction of iNOS is regulated by the oxidant-sensitive, nuclear factor kappa B (NF-kappaB) in many cell types. In the present study using electron spin resonance (ESR) spectroscopy, we evaluated whether pyrrolidine dithiocarbamate (PDTC), a metal chelator and antioxidant, might limit .NO production during the development of rejection in cardiac allografts. We performed either isogeneic (Lewis to Lewis) or allogeneic (Wistar-Furth to Lewis) heterotopic abdominal cardiac transplantation. Allograft recipients received daily injections of PDTC or aminoguanidine (a known inhibitor of iNOS). At postoperative days 4 or 6, grafted and native hearts of transplant recipients were flushed with cardioplegic solution to remove blood contamination. ESR data of allografts revealed a triplet nitrogen signal (aN=17.5 G) and centered at g=2.012 and an additional broad signal at g=2.08. This signal was not seen in either isografts or native hearts of either isograft or allograft recipients. Based upon these parameters, these signals are attributed to nitrosomyoglobin. This signal was inhibited by treatment with aminoguanidine or PDTC. Under these conditions, PDTC also prolonged graft survival from 6.6+/-0.2 to 11.7+/-0.3 days. Thus, it is conceivable that nitrosylmyoglobin formation precedes rejection in cardiac allografts and inhibition of nitrosomyoglobin with agents such as PDTC contribute to improved graft survival. PMID:9667497

  11. Survival after out-of-hospital cardiac arrest in relation to age and early identification of patients with minimal chance of long-term survival

    DEFF Research Database (Denmark)

    Wissenberg, Mads; Folke, Fredrik; Hansen, Carolina Malta;

    2015-01-01

    BACKGROUND: Survival after out-of-hospital cardiac arrest has increased during the last decade in Denmark. We aimed to study the impact of age on changes in survival and whether it was possible to identify patients with minimal chance of 30-day survival. METHODS AND RESULTS: Using data from the n...

  12. Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival

    Institute of Scientific and Technical Information of China (English)

    LI Zhao-lun; TIAN Pu-xun; XUE Wu-jun; WU Jun

    2006-01-01

    Objective: To investigate the role of simultaneous blockade of CD40/CD40L and B7/CD28 pathways in the immune tolerance via co-expression of sCD40LIg and CTLA4Ig mediated by replication-defective adenovirus. Methods: Ad-sCD40LIgIRES2-CTLA4Ig, replication-defective adenovirus co-expressing sCD40LIg and CTLA4Ig, was constructed and identified. The co-expression of sCD40LIg and CTLA4Ig was evaluated with confocal laser scanning microscope and Western blotting. Skin transplantations of C57BL/6 to BALB/c mice were performed. PBS, Ad-Shuttle-CMV and Ad-sCD40LIg-IRES2-CTLA4Ig were administered. Skin graft survival was monitored and the mRNA expression of both genes was evaluated in the skin allografts.Results: Ad-sCD40LIg-IRES2-CTLA4Ig was constructed successfully and identified. The co-expression of sCD40LIg and CTLA4Ig was identified with confocal laser scanning microscopy and Western blotting. Compared to the skin graft mean survival time (MST) of non-treated group ((5.75±0.71) d) or Ad-Shuttle-CMV-treated group ((5.50±0.53) d), the skin graft MST was dramatically prolonged in the Ad-sCD40LIg-IRES2-CTLA4Ig-treated group (( 16.38± 1.19) d, P<0.001). The mRNA expression of both genes was detected. Conclusion: Ad-sCD40LIg-IRES2-CTLA4Ig, a replication-defective adenovirus carrying genes encoding sCD40LIg and CTLA4Ig, was constructed. Simultaneous blockade of CD40/CD40L and B7/CD28 costimulatory pathway mediated by replication-defective adenovirus significantly prolonged skin allograft survival in mice.

  13. Allogeneic unresponsiveness to orthotopic cardiac transplants in DL-A-identical radiation chimeras

    International Nuclear Information System (INIS)

    Nine Cooperstown beagles of known DL-A genotypes were exposed to supralethal total-body irradiation and received bone-marrow allografts from DL-A-identical donors. Four to 5 months later, the resulting chimeras received orthotopic cardiac allografts from their corresponding donors of marrow. Six chimeras died of operative complications in the immediate postoperative period. The other 3 chimeras survived from 173 to 547 days; 1 dog died at 173 days as a result of right-sided heart failure, secondary to stenosis at the site of the pulmonary artery anastomosis. The other two recipients continue to be active and healthy at 545 and 547 days. The results indicate that dogs can be rendered specifically tolerant to orthotopic cardiac allografts by supralethal total-body irradiation and the transplantation of marrow obtained from the prospective allograft donor

  14. Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.

    Directory of Open Access Journals (Sweden)

    Yaping Sun

    Full Text Available Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na(+/K(+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na(+/K(+ ATPase α3 subunit (ATP1A3. Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.

  15. Reproducibility of the acute rejection diagnosis in human cardiac allografts. The Stanford Classification and the International Grading System

    DEFF Research Database (Denmark)

    Nielsen, H; Sørensen, Flemming Brandt; Nielsen, B;

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...... systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three...... observers evaluated 168 endomyocardial biopsy specimens according to the Stanford Classification and 100 endomyocardial biopsy specimens according to the International Grading System. The evaluation was carried out blindly. Kappa values of 54.1% and 51.5%, respectively, were obtained, both significantly...

  16. Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea

    Science.gov (United States)

    Lee, Jung Pyo; Bae, Eunjin; Kang, Eunjeong; Kim, Hack-Lyoung; Kim, Yong-Jin; Oh, Yun Kyu; Kim, Yon Su; Kim, Young Hoon; Lim, Chun Soo

    2016-01-01

    Background Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. PMID:27501048

  17. Survival to admission after out-of-hospital cardiac arrest in Seoul, South Korea

    OpenAIRE

    Kim JH; Uhm TH

    2014-01-01

    Jin-Hue Kim,1 Tai-Hwan Uhm2 1Department of Emergency Medical Technology, Sun Moon University, Asan-si, Chungnam, South Korea; 2Department of Emergency Medical Services, Eulji University, Seongnam-si, Gyeonggi-do, South Korea Purpose: Out-of-hospital cardiac arrest (OHCA) data derived according to the Utstein Style guidelines was used to try to determine factors influencing survival to admission (STA) and epidemiological rates of OHCA. Patients and methods: This was an observational study of ...

  18. Combined survival analysis of cardiac patients by a Cox PH model and a Markov chain.

    Science.gov (United States)

    Shauly, Michal; Rabinowitz, Gad; Gilutz, Harel; Parmet, Yisrael

    2011-10-01

    The control and treatment of dyslipidemia is a major public health challenge, particularly for patients with coronary heart diseases. In this paper we propose a framework for survival analysis of patients who had a major cardiac event, focusing on assessment of the effect of changing LDL-cholesterol level and statins consumption on survival. This framework includes a Cox PH model and a Markov chain, and combines their results into reinforced conclusions regarding the factors that affect survival time. We prospectively studied 2,277 cardiac patients, and the results show high congruence between the Markov model and the PH model; both evidence that diabetes, history of stroke, peripheral vascular disease and smoking significantly increase hazard rate and reduce survival time. On the other hand, statin consumption is correlated with a lower hazard rate and longer survival time in both models. The role of such a framework in understanding the therapeutic behavior of patients and implementing effective secondary and primary prevention of heart diseases is discussed here. PMID:21735134

  19. Celecoxib plays a multiple role to peripheral blood lymphocytes and allografts in acute rejection in rats after cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue-feng; ZHANG Fan; LIU Hong-yu; SUN Guo-dong; LIU Zong-hong; L(U) Hang; CHI Chao; LI Chun-yu

    2009-01-01

    Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4+ and CD8+ lymphocytes. Methods After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4+ and CD8+ lymphocytes. Results Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4+ lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8+ lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days. Conclusions The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

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

    Science.gov (United States)

    Yuan, J; Bagley, J; Iacomini, J

    2015-09-01

    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.

  1. Demand for human allograft tissue in Canada.

    Science.gov (United States)

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

    2007-01-01

    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.

  2. The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function

    OpenAIRE

    Mayfield, Audrey E.; Tilokee, Everad L.; Latham, Nicholas; McNeill, Brian; Lam, Bu-Khanh; Ruel, Marc; Suuronen, Erik J; Courtman, David W.; Stewart, Duncan J.; Davis, Darryl R.

    2013-01-01

    Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the...

  3. Surviving Sudden Cardiac Arrest: A Pilot Qualitative Survey Study of Survivors.

    Science.gov (United States)

    Sawyer, Kelly N; Brown, Frances; Christensen, Roxanne; Damino, Colleen; Newman, Mary M; Kurz, Michael C

    2016-06-01

    Research describing survivors of sudden cardiac arrest (SCA) has centered on quantifying functional ability, perceived quality of life, and neurocognitive assessment. Many gaps remain, however, regarding survivors' psychosocial perceptions of life in the aftermath of cardiac arrest. An important influence upon those perceptions is the presence of support and its role in a survivor's life. An Internet-based pilot survey study was conducted to gather data from SCA survivors and friends and/or family members (FFMs) representing their support system. The survey was distributed to members of the Sudden Cardiac Arrest Foundation (SCAF) via the Internet by SCAF leadership. Questions included both discrete multiple-choice and open-ended formats. Inductive thematic analyses were completed by three independent researchers trained in qualitative research methodology to identify primary themes consistent among study participants until thematic saturation was achieved. No statistical inferences were made. A total of 205 surveys were returned over the 5-month study period (July to November 2013); nine were received blank, leaving 196 surveys available for review. Major themes identified for survivors (N = 157) include the significance of and desire to share experiences with others; subculture identification (unique experience from those suffering a heart attack); and the need to seek a new normal, both personally and inter-personally. Major themes identified for FFMs (N = 39) include recognition of loved one's memory loss; a lack of information at discharge, including expectations after discharge; and concern for the patient experiencing another cardiac arrest. This pilot, qualitative survey study suggests several common themes important to survivors, and FFMs, of cardiac arrest. These themes may serve as a basis for future patient-centered focus groups and the development of patient-centered guidelines for patients and support persons of those surviving cardiac arrest

  4. Surviving Sudden Cardiac Arrest: A Pilot Qualitative Survey Study of Survivors.

    Science.gov (United States)

    Sawyer, Kelly N; Brown, Frances; Christensen, Roxanne; Damino, Colleen; Newman, Mary M; Kurz, Michael C

    2016-06-01

    Research describing survivors of sudden cardiac arrest (SCA) has centered on quantifying functional ability, perceived quality of life, and neurocognitive assessment. Many gaps remain, however, regarding survivors' psychosocial perceptions of life in the aftermath of cardiac arrest. An important influence upon those perceptions is the presence of support and its role in a survivor's life. An Internet-based pilot survey study was conducted to gather data from SCA survivors and friends and/or family members (FFMs) representing their support system. The survey was distributed to members of the Sudden Cardiac Arrest Foundation (SCAF) via the Internet by SCAF leadership. Questions included both discrete multiple-choice and open-ended formats. Inductive thematic analyses were completed by three independent researchers trained in qualitative research methodology to identify primary themes consistent among study participants until thematic saturation was achieved. No statistical inferences were made. A total of 205 surveys were returned over the 5-month study period (July to November 2013); nine were received blank, leaving 196 surveys available for review. Major themes identified for survivors (N = 157) include the significance of and desire to share experiences with others; subculture identification (unique experience from those suffering a heart attack); and the need to seek a new normal, both personally and inter-personally. Major themes identified for FFMs (N = 39) include recognition of loved one's memory loss; a lack of information at discharge, including expectations after discharge; and concern for the patient experiencing another cardiac arrest. This pilot, qualitative survey study suggests several common themes important to survivors, and FFMs, of cardiac arrest. These themes may serve as a basis for future patient-centered focus groups and the development of patient-centered guidelines for patients and support persons of those surviving cardiac arrest.

  5. Value of the first post-transplant biopsy for predicting long-term cardiac allograft vasculopathy (CAV and graft failure in heart transplant patients.

    Directory of Open Access Journals (Sweden)

    Carlos A Labarrere

    Full Text Available BACKGROUND: Cardiac allograft vasculopathy (CAV is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV. METHODS AND FINDINGS: In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA] and endothelial activation (intercellular adhesion molecule-1 in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years. Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00-374.77; and 3.99, p = 0.005, 95% CI = 1.53-10.40 and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08-3.03; and 1.31, p = 0.001, 95% CI = 1.12-1.55. First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years. CONCLUSIONS: Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively

  6. The risk of allograft failure and the survival benefit of kidney transplantation are complicated by delayed graft function.

    Science.gov (United States)

    Gill, Jagbir; Dong, Jianghu; Rose, Caren; Gill, John S

    2016-06-01

    Concern about the long-term impact of delayed graft function (DGF) may limit the use of high-risk organs for kidney transplantation. To understand this better, we analyzed 29,598 mate kidney transplants from the same deceased donor where only 1 transplant developed DGF. The DGF associated risk of graft failure was greatest in the first posttransplant year, and in patients with concomitant acute rejection (hazard ratio: 8.22, 95% confidence interval: 4.76-14.21). In contrast, the DGF-associated risk of graft failure after the first posttransplant year in patients without acute rejection was far lower (hazard ratio: 1.15, 95% confidence interval: 1.02-1.29). In subsequent analysis, recipients of transplants complicated by DGF still derived a survival benefit when compared with patients who received treatment with dialysis irrespective of donor quality as measured by the Kidney Donor Profile Index (KDPI). The difference in the time required to derive a survival benefit was longer in transplants with DGF than in transplants without DGF, and this difference was greatest in recipients of lower quality kidneys (difference: 250-279 days for KDPI 20%-60% vs. 809 days for the KDPI over 80%). Thus, the association of DGF with graft failure is primarily limited to the first posttransplant year. Transplants complicated by DGF provide a survival benefit compared to treatment with dialysis, but the survival benefit is lower in kidney transplants with lower KDPI. This information may increase acceptance of kidneys at high risk for DGF and inform strategies to minimize the risk of death in the setting of DGF.

  7. A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft.

    Science.gov (United States)

    Gajanayake, Thusitha; Olariu, Radu; Leclère, Franck M; Dhayani, Ashish; Yang, Zijiang; Bongoni, Anjan K; Banz, Yara; Constantinescu, Mihai A; Karp, Jeffrey M; Vemula, Praveen Kumar; Rieben, Robert; Vögelin, Esther

    2014-08-13

    Currently, systemic immunosuppression is used in vascularized composite allotransplantation (VCA). This treatment has considerable side effects and reduces the quality of life of VCA recipients. We loaded the immunosuppressive drug tacrolimus into a self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A one-time local injection of the tacrolimus-laden hydrogel significantly prolonged graft survival in a Brown Norway-to-Lewis rat hindlimb transplantation model, leading to a median graft survival of >100 days compared to 33.5 days in tacrolimus only-treated recipients. Control groups with no treatment or hydrogel only showed a graft survival of 11 days. Histopathological evaluation, including anti-graft antibodies and complement C3, revealed significantly reduced immune responses in the tacrolimus-hydrogel group compared with tacrolimus only. In conclusion, a single-dose local injection of an enzyme-responsive tacrolimus-hydrogel is capable of preventing VCA rejection for >100 days in a rat model and may offer a new approach for immunosuppression in VCA. PMID:25122638

  8. The effect of referral for cardiac rehabilitation on survival following acute myocardial infarction

    DEFF Research Database (Denmark)

    Lewinter, Christian; Bland, John M; Crouch, Simon;

    2014-01-01

    BACKGROUND: International guidelines recommend referral for cardiac rehabilitation (CR) after acute myocardial infarction (AMI). However, the impact on long-term survival after CR referral has not been adjusted by time-variance. We compared the effects of CR referral after hospitalization for AMI...... in two consecutive decades. METHODS AND RESULTS: A total of 2196 and 2055 patients were recruited in the prospective observational studies of the Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) -1 and 2 in 1995 and 2003, (1995: median age 72 years, 39% women, 74% referred vs...... 2003: median age 71 years, 36% women, 64% referred) and followed up through September 2010. Survival functions showed CR referral to be an independent predictor for survival in 2003, but not in 1995 (hazard ratio (HR), 0.90; 95% confidence interval [CI]; 0.70 to 1.17, p = 0.44 in 1995 vs HR, 0.80; 95...

  9. Population density, call-response interval, and survival of out-of-hospital cardiac arrest

    Directory of Open Access Journals (Sweden)

    Ogawa Toshio

    2011-04-01

    Full Text Available Abstract Background Little is known about the effects of geographic variation on outcomes of out-of-hospital cardiac arrest (OHCA. The present study investigated the relationship between population density, time between emergency call and ambulance arrival, and survival of OHCA, using the All-Japan Utstein-style registry database, coupled with geographic information system (GIS data. Methods We examined data from 101,287 bystander-witnessed OHCA patients who received emergency medical services (EMS through 4,729 ambulatory centers in Japan between 2005 and 2007. Latitudes and longitudes of each center were determined with address-match geocoding, and linked with the Population Census data using GIS. The endpoints were 1-month survival and neurologically favorable 1-month survival defined as Glasgow-Pittsburgh cerebral performance categories 1 or 2. Results Overall 1-month survival was 7.8%. Neurologically favorable 1-month survival was 3.6%. In very low-density (2 and very high-density (≥10,000/km2 areas, the mean call-response intervals were 9.3 and 6.2 minutes, 1-month survival rates were 5.4% and 9.1%, and neurologically favorable 1-month survival rates were 2.7% and 4.3%, respectively. After adjustment for age, sex, cause of arrest, first aid by bystander and the proportion of neighborhood elderly people ≥65 yrs, patients in very high-density areas had a significantly higher survival rate (odds ratio (OR, 1.64; 95% confidence interval (CI, 1.44 - 1.87; p Conclusion Living in a low-density area was associated with an independent risk of delay in ambulance response, and a low survival rate in cases of OHCA. Distribution of EMS centers according to population size may lead to inequality in health outcomes between urban and rural areas.

  10. Survival of male patients with spinal cord injury after cardiac arrest in Department of Veterans Affairs hospital: Pilot study

    Directory of Open Access Journals (Sweden)

    Deborah Caruso, MD

    2014-11-01

    Full Text Available Survivability characteristics after cardiopulmonary resuscitation in the population with spinal cord injury (SCI are unclear but may be useful for advanced care planning discussions with patients. Retrospective evaluation from records of all SCI patients over 10 yr at a Department of Veterans Affairs medical center who experienced in-hospital cardiac arrest was performed. Demographic data and other common measurements were recorded. Thirty-six male subjects were identified, and only two patients survived to discharge (5.5% survival rate, both of whom were admitted for nonacute issues and were asymptomatic shortly before the cardiac arrest. The mean age at the time of cardiopulmonary arrest was 62.4 yr, with a mean time from cardiac arrest to death of 3.02 d. No significant demographic parameters were identified. Overall, SCI likely portends worse outcome for acutely ill patients in the situation of a cardiac arrest. Conclusions are limited by sample size.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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.

  12. Spatial Variation and Resuscitation Process Affecting Survival after Out-of-Hospital Cardiac Arrests (OHCA.

    Directory of Open Access Journals (Sweden)

    Chien-Chou Chen

    Full Text Available Ambulance response times and resuscitation efforts are critical predictors of the survival rate after out-of-hospital cardiac arrests (OHCA. On the other hand, rural-urban differences in the OHCA survival rates are an important public health issue.We retrospectively reviewed the January 2011-December 2013 OHCA registry data of Kaohsiung City, Taiwan. With particular focus on geospatial variables, we aimed to unveil risk factors predicting the overall OHCA survival until hospital admission. Spatial analysis, network analysis, and the Kriging method by using geographic information systems were applied to analyze spatial variations and calculate the transport distance. Logistic regression was used to identify the risk factors for OHCA survival.Among the 4,957 patients, the overall OHCA survival to hospital admission was 16.5%. In the multivariate analysis, female sex (adjusted odds ratio:, AOR, 1.24 [1.06-1.45], events in public areas (AOR: 1.30 [1.05-1.61], exposure to automated external defibrillator (AED shock (AOR: 1.70 [1.30-2.23], use of laryngeal mask airway (LMA (AOR: 1.35 [1.16-1.58], non-trauma patients (AOR: 1.41 [1.04-1.90], ambulance bypassed the closest hospital (AOR: 1.28 [1.07-1.53], and OHCA within the high population density areas (AOR: 1.89 [1.55-2.32] were positively associated with improved OHCA survival. By contrast, a prolonged total emergency medical services (EMS time interval was negatively associated with OHCA survival (AOR: 0.98 [0.96-0.99].Resuscitative efforts, such as AED or LMA use, and a short total EMS time interval improved OHCA outcomes in emergency departments. The spatial heterogeneity of emergency medical resources between rural and urban areas might affect survival rate.

  13. Cardiac arrest teams and time of day: effects on surviving in-hospital resuscitation

    Directory of Open Access Journals (Sweden)

    Christ M

    2014-06-01

    Full Text Available Martin Christ, Wolfgang Dierschke, Katharina Isabel von Auenmueller, Marc van Bracht, Martin Grett, Hans-Joachim Trappe Department of Cardiology and Angiology, Marienhospital Herne, Ruhr – University Bochum, Herne, Germany Objectives: Little is known about the factors that influence survival following in-hospital resuscitation, but previous investigations have suggested that in-hospital resuscitations outside of regular working hours are associated with worse survival rates. Material and methods: In-hospital cardiac arrest teams at our hospital were instructed to complete a questionnaire following every emergency call between July 2011 and June 2013. Data on all resuscitation attempts were collected and analyzed. Results: A total of 65 in-hospital resuscitations were recorded in 42 males (64.6% and 23 females (35.4% (mean age 72.0±14.3 years. A total of 54 (83.1% cardiac arrests were witnessed; seven (10.8% showed a shockable rhythm at the time of the first ECG. Resuscitation attempts lasted 29.3±41.3 minutes, and 4.1±3.1 mg epinephrine was given. Return of spontaneous circulation could be achieved in 38 patients (58.5%; 29 (44.6% survived the first day, 23 (35.4% the seventh day, and 15 patients (23.1% were discharged alive. Significantly more in-hospital resuscitations were obtained for those performed during non-regular working hours (P<0.001, with higher neuron-specific enolase levels at 72 hours after resuscitation during nonregular working hours (P=0.04. Patients who were discharged alive were significantly younger (P=0.01, presented more often with an initial shockable rhythm (P=0.04, and had a shorter duration of resuscitation (P<0.001 with the need of a lower dose of epinephrine (P<0.001. Discussion: Survival rates following in-hospital resuscitation were poor at any time, but appear to depend less on time-dependent effects of the quality of resuscitation and more on time-dependent effects of recognition of cardiac arrests

  14. Out-of-hospital cardiac arrest (OHCA) survival in rural Northwest Ireland: 17 years' experience.

    LENUS (Irish Health Repository)

    Masterson, Siobhán

    2011-05-01

    SAVES, the name used to describe a register of survivors of out-of-hospital cardiac arrest (OHCA), was established in rural Northwest Ireland in 1992. From 1992 to 2008, 80 survivors were identified (population 239,000 (2006)). Most incidents were witnessed (69\\/70) and all were in shockable rhythm at the time of first rhythm analysis (66\\/66). Of 66 patients who could be traced, 46 were alive in December 2008. Average survival rates appeared to increase over the lifetime of the database. SAVES has also contributed to the development of a national OHCA register.

  15. Determinants of long-term renal allograft outcome

    NARCIS (Netherlands)

    Leeuwen-Artz, M.A.

    2005-01-01

    Long-term renal allograft survival is markedly affected by premature death with a functioning graft, chronic allograft nephropathy, and recurrence of the original kidney disease. To improve long-term graft survival, focus is shifting from the prevention of acute rejections to the recognition and tre

  16. Successful abdominal aortic aneurysm resection in long-term survivors of cardiac transplantation.

    OpenAIRE

    Defraigne, Jean-Olivier; SakalihasanN, Natzi; DEMOULIN, Julie; Limet, Raymond

    1995-01-01

    With the improvement of survival rates following cardiac transplantation, the probability of recipients developing extracardiac disease is increased. Three cases are reported of abdominal aortic aneurysm successfully operated on in cardiac allograft recipients 1 to 4 years after transplantation. Indications for transplantation were valvular, idiopathic and ischaemic cardiomyopathy. Post-transplant hypertension and hyperlipidaemia may have played a role in the rapid growth of the aneurysms. Ca...

  17. The composition of the microbiota modulates allograft rejection.

    Science.gov (United States)

    Lei, Yuk Man; Chen, Luqiu; Wang, Ying; Stefka, Andrew T; Molinero, Luciana L; Theriault, Betty; Aquino-Michaels, Keston; Sivan, Ayelet S; Nagler, Cathryn R; Gajewski, Thomas F; Chong, Anita S; Bartman, Caroline; Alegre, Maria-Luisa

    2016-07-01

    Transplantation is the only cure for end-stage organ failure, but without immunosuppression, T cells rapidly reject allografts. While genetic disparities between donor and recipient are major determinants of the kinetics of transplant rejection, little is known about the contribution of environmental factors. Because colonized organs have worse transplant outcome than sterile organs, we tested the influence of host and donor microbiota on skin transplant rejection. Compared with untreated conventional mice, pretreatment of donors and recipients with broad-spectrum antibiotics (Abx) or use of germ-free (GF) donors and recipients resulted in prolonged survival of minor antigen-mismatched skin grafts. Increased graft survival correlated with reduced type I IFN signaling in antigen-presenting cells (APCs) and decreased priming of alloreactive T cells. Colonization of GF mice with fecal material from untreated conventional mice, but not from Abx-pretreated mice, enhanced the ability of APCs to prime alloreactive T cells and accelerated graft rejection, suggesting that alloimmunity is modulated by the composition of microbiota rather than the quantity of bacteria. Abx pretreatment of conventional mice also delayed rejection of major antigen-mismatched skin and MHC class II-mismatched cardiac allografts. This study demonstrates that Abx pretreatment prolongs graft survival, suggesting that targeting microbial constituents is a potential therapeutic strategy for enhancing graft acceptance.

  18. The composition of the microbiota modulates allograft rejection.

    Science.gov (United States)

    Lei, Yuk Man; Chen, Luqiu; Wang, Ying; Stefka, Andrew T; Molinero, Luciana L; Theriault, Betty; Aquino-Michaels, Keston; Sivan, Ayelet S; Nagler, Cathryn R; Gajewski, Thomas F; Chong, Anita S; Bartman, Caroline; Alegre, Maria-Luisa

    2016-07-01

    Transplantation is the only cure for end-stage organ failure, but without immunosuppression, T cells rapidly reject allografts. While genetic disparities between donor and recipient are major determinants of the kinetics of transplant rejection, little is known about the contribution of environmental factors. Because colonized organs have worse transplant outcome than sterile organs, we tested the influence of host and donor microbiota on skin transplant rejection. Compared with untreated conventional mice, pretreatment of donors and recipients with broad-spectrum antibiotics (Abx) or use of germ-free (GF) donors and recipients resulted in prolonged survival of minor antigen-mismatched skin grafts. Increased graft survival correlated with reduced type I IFN signaling in antigen-presenting cells (APCs) and decreased priming of alloreactive T cells. Colonization of GF mice with fecal material from untreated conventional mice, but not from Abx-pretreated mice, enhanced the ability of APCs to prime alloreactive T cells and accelerated graft rejection, suggesting that alloimmunity is modulated by the composition of microbiota rather than the quantity of bacteria. Abx pretreatment of conventional mice also delayed rejection of major antigen-mismatched skin and MHC class II-mismatched cardiac allografts. This study demonstrates that Abx pretreatment prolongs graft survival, suggesting that targeting microbial constituents is a potential therapeutic strategy for enhancing graft acceptance. PMID:27322054

  19. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection

    International Nuclear Information System (INIS)

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-γ by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4+CD25highFoxp3+ regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  20. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

    2010-05-14

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  1. Composite mandibular allografts in canines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    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.

  2. Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies

    NARCIS (Netherlands)

    J. Berdowski; R.A. Berg; J.G.P. Tijssen; R.W. Koster

    2010-01-01

    Aim: The aim of this investigation was to estimate and contrast the global incidence and outcome of out-of-hospital cardiac arrest (OHCA) to provide a better understanding of the variability in risk and survival of OHCA. Methods: We conducted a review of published English-language articles about inc

  3. Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Ashham Mansur

    Full Text Available Genetic variants within the endothelin-1 gene (EDN1 have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint. The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy-Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T haplotype had a higher cardiac index than did non-carriers (p = 0.0008; however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery.

  4. Incidence, predisposing factors, management and survival following cardiac arrest due to subarachnoid haemorrhage: a review of the literature

    Directory of Open Access Journals (Sweden)

    Skrifvars Markus B

    2012-11-01

    Full Text Available Abstract Introduction The prevalence of cardiac arrest among patients with subarachnoid haemorrhage [SAH], and the prevalence of SAH as the cause following out-of-hospital cardiac arrest [OHCA] or in-hospital cardiac arrest [IHCA] is unknown. In addition it is unclear whether cardiopulmonary resuscitation [CPR] and post-resuscitation care management differs, and to what extent this will lead to meaningful survival following cardiac arrest [CA] due to SAH. Aim We reviewed the literature in order to describe; 1.The prevalence and predisposing factors of CA among patients with SAH 2.The prevalence of SAH as the cause of OHCA or IHCA and factors characterising CPR 3.The survival and management of SAH patients with CA. Material and methods The following sources, PubMed, CinAHL and The Cochrane DataBase were searched using the following Medical Subheadings [MeSH]; 1. OHCA, IHCA, heart arrest and 2. subarachnoid haemorrhage. Articles containing relevant data based on the abstract were reviewed in order to find results relevant to the proposed research questions. Manuscripts in other languages than English, animal studies, reviews and case reports were excluded. Results A total of 119 publications were screened for relevance and 13 papers were included. The prevalence of cardiac or respiratory arrest among all patients with SAH is between 3-11%, these patients commonly have a severe SAH with coma, large bleeds and evidence of raised intracerebral pressure on computed tomography scans compared to those who did not experience a CA. The prevalence of patients with SAH as the cause of the arrest among OHCA cases vary between 4 to 8% among those who die before hospital admission, and between 4 to 18% among those who are admitted. The prevalence of SAH as the cause following IHCA is low, around 0.5% according to one recent study. In patients with OHCA survival to hospital discharge is poor with 0 to 2% surviving. The initial rhythm is commonly asystole or

  5. Cytomegalovirus and chronic allograft rejection in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Liang-Hui Gao; Shu-Sen Zheng

    2004-01-01

    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.

  6. Prolongation of skin allograft survival in mice by HLA-derived peptide and subtherapeutic CsA%合成HLA肽延长同种小鼠移植皮肤存活时间

    Institute of Scientific and Technical Information of China (English)

    汪泽厚; 关双成; 朱锡华; 张艮甫; 杨唐俊; 曾毅; 刘素英

    2001-01-01

    Synthetic HLA-derived peptide,HLA-B*2702.75-84,was used to induce skin allograft tolerance in mice.NIH mice skin was heterotopically transplanted into the backside of Balb/c.HLA peptide therapy combined with a subtherapeutic dose of CsA was perioperatively administrated.The result shown that the HLA peptide combined CsA prolonged significantly the allogenic skin allograft survival.%目的:本实验观察人工合成HLA肽,HLA-B*270275-84,对同种小鼠移植皮肤存活时间的影响。方法:将B6小鼠皮肤移植于受者Balb/c小鼠侧背部,并于围手术期给予HLA肽和亚治疗剂量CsA。结果:HLA肽可显著延长同种异基因小鼠移植皮肤存活时间,与对照组比较,平均存活时间由6.5天延长至28.0天(P<0.01)。结论:合成HLA肽可显著延长同种移植皮肤存活时间。

  7. Protein kinase G1 α overexpression increases stem cell survival and cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    Full Text Available BACKGROUND: We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs contributing to regeneration of the ischemic heart. METHODS AND RESULTS: MSCs from male rats were transduced with adenoviral vector encoding for PKG1α ((PKG1αMSCs.Controls included native MSCs ((NatMSCs and MSCs transduced with an empty vector ((NullMSCs. PKG1α activity was increased approximately 20, 5 and 16 fold respectively in (PKG1αMSCs. (PKG1αMSCs showed improved survival under oxygen and glucose deprivation (OGD which was evidenced by lower LDH release, caspase-3/7 activity and number of positive TUNEL cells. Anti-apoptotic proteins pAkt, pGSK3β, and Bcl-2 were significantly increased in (PKG1αMSCs compared to (NatMSCs and (NullMSCs. Higher release of multiple prosurvival and angiogenic factors such as HGF, bFGF, SDF-1 and Ang-1 was observed in (PKG1αMSCs before and after OGD. In a female rat model of acute myocardial infarction, (PKG1αMSCs group showed higher survival compared with (NullMSCs group at 3 and 7 days after transplantation as determined by TUNEL staining and sry-gene quantitation by real-time PCR. Increased anti-apoptotic proteins and paracrine factors in vitro were also identified. Immunostaining for cardiac troponin I combined with GFP showed increased myogenic differentiation of (PKG1αMSCs. At 4 weeks after transplantation, compared to DMEM group and (NullMSCs group, (PKG1αMSCs group showed increased blood vessel density in infarct and peri-infarct areas (62.5±7.7; 68.8±7.3 per microscopic view, p<0.05 and attenuated infarct size (27.2±2.5%, p<0.01. Heart function indices including ejection fraction (52.1±2.2%, p<0.01 and fractional shortening (24.8%±1.3%, p<0.01 were improved significantly in (PKG1αMSCs group. CONCLUSION: Overexpression of PKG1α transgene could be a powerful approach to improve MSCs

  8. Influence of tissue culture on the survival of thyroid Allografts in rats%甲状腺组织培养条件对移植存活的影响

    Institute of Scientific and Technical Information of China (English)

    刘文革; 彭钧铮; 庞智玲; 张元芳; 谭郁彬; 丁强; 吴忠

    1997-01-01

    本文采用两个大气压氧与低pH值(5.5及6.9)相结合培养大鼠甲状腺组织48小时,将甲状腺组织块移植入受体的肾包膜下,从T3、T4均值、平均体重增长及移植组织观察四个方面评价移植物存活及排斥反应情况.结果发现,此方法可减弱排斥反应,延长移植物存活时间,培养后滤泡间过客白细胞并未完全去除,提示此方法以改变主要组织相容性抗原为主.%The thyroid allografts in rats were cultured for 48 h in the conditions of hyperbaric oxygen(a mixture of 95%O2,5%CO2pressurized at 2 atmospheres)and low pH(5.5 and 6.9).Uncultured and air cultured allografts were taken ascontrol groups.The thyroid slices were trans planted under the kidney capsulse of thyroidectomized recipients.By examining histological changes,detecting the serum T3 and T4 levels and five weeks body weight gain,the graft survival was cvaluated.Though the thyroids cultured in hyperbaric O2 were contaminated with the passenger leukocytes,the grafts had prolonged survival,suggesting this method might effectively diminish MHC immunogenicity to thyroid grafts.

  9. The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function.

    Science.gov (United States)

    Mayfield, Audrey E; Tilokee, Everad L; Latham, Nicholas; McNeill, Brian; Lam, Bu-Khanh; Ruel, Marc; Suuronen, Erik J; Courtman, David W; Stewart, Duncan J; Davis, Darryl R

    2014-01-01

    Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the integration of fibronectin and fibrinogen into a supportive intra-capsular matrix. Encapsulation maintained CSC viability under hypoxic stress conditions and, when compared to standard suspended CSC, media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, cardiac structure and function. Single cell encapsulation prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium. PMID:24099706

  10. Cardiac troponin I elevation and overall survival among cancer patients receiving investigational compounds during phase I trials

    OpenAIRE

    Hollebecque, Antoine; Lanoy, Emilie; Troallen, Frederic; Soulat-Dufour, Laurie; Massard, Christophe; Bahleda, Rastislav; VARGA, Andrea; Gazzah, Anas; Postel-Vinay, Sophie; Ribrag, Vincent; Deutsch, Eric; Angevin, Eric; Boccara, Franck; Cohen, Ariel; Soria, Jean-Charles

    2016-01-01

    Objective : To identify factors associated with troponin elevation and to measure the effect of elevated troponin on survival in cancer patients participating in phase I trials.Methods : Clinical characteristics, cardiovascular risk factors, and biological data from consecutive patients treated in phase I trials (January 2010–November 2012) were reviewed. Troponin value was measured for each patient before study-drug administration and then weekly. Cardiac troponin I was considered elevated i...

  11. Survival with good neurological outcome in a patient with prolonged ischemic cardiac arrest--utility of automated chest compression systems in the cardiac catheterization laboratory.

    Science.gov (United States)

    Psaltis, Peter J; Meredith, Ian T; Ahmar, Walid

    2014-11-15

    The management of refractory cardiac arrest during invasive coronary procedures has substantial logistical challenges and is typically associated with disappointing outcomes. We describe the case of a young woman with recalcitrant ventricular fibrillation due to acute anterior ST-elevation myocardial infarction caused by occlusion of her proximal left anterior descending artery. Survival without neurological deficit or organ failure was achieved following primary percutaneous reperfusion and a total of 52 min of intra-procedural chest compression support, made possible by the use of an automated chest compression device. PMID:24403102

  12. Clinical analysis of recipients with survival of over ten years after cardiac transplantation: a report of 13 cases%心脏移植后存活时间超过10年者的临床分析

    Institute of Scientific and Technical Information of China (English)

    黄雪珊; 廖崇先; 陈良万; 陈道中

    2011-01-01

    Objective To retrospectively analyze the clinical management and follow-up of 13 recipients with survival of over ten years after cardiac transplantation. Methods Thirteen male recipients underwent orthotopic heart transplantation between August 1995 and June 2001 in our center and received standard immunosuppressive therapy protocols (8 cases) or induction therapy protocols (5 cases). Cyclosporine, azathioprine or mycophenolate mofetil, and prednisolone were applied as maintenance immunosuppressive regimens. Six recipients switched from azathioprine to mycophenolate mofetil when mycophenolate mofetil was available. Perioperative complications were prevented and treated. After operation, the recipients were followed up regularly to set up personnel long-term follow-up files. The incidence of acute rejection (AR) and (cardiac allograft vasculopathy (CAV) was monitored. Results The 13 survived recipients accounted for 48. 1 % of the total number in the corresponding period (13/27). All survivals recovered well and had a good quality of life. The recent (1 year) complications included acute allograft rejection (3 cases), infection (4 cases), renal insufficiency (3 cases), allograft right ventricular dysfunction (5 cases), post-transplant diabetes (2 cases) and liver dysfunction (5 cases). The long-term (1 year later) complications included acute allograft rejection (2 cases), CAV (2 cases), hypercholesterolemia (5 cases), hypertension (4 cases), hyperuricemia (10 cases) and chronic renal impairment (3 cases). One hepatitis B virus carrier died of liver cancer 13 years after transplantation. Conclusion The long-term survival of cardiac allograft recipients is closely associated with psychological state, financial condition, compliance and follow-up medical system, while the sociological and environmental factors may play important roles.%目的 总结单中心13例心脏移植后存活超过10年受者的治疗及随访情况.方法 13例受者在1995年8月至2001年6

  13. Survival to admission after out-of-hospital cardiac arrest in Seoul, South Korea

    Directory of Open Access Journals (Sweden)

    Kim JH

    2014-09-01

    Full Text Available Jin-Hue Kim,1 Tai-Hwan Uhm2 1Department of Emergency Medical Technology, Sun Moon University, Asan-si, Chungnam, South Korea; 2Department of Emergency Medical Services, Eulji University, Seongnam-si, Gyeonggi-do, South Korea Purpose: Out-of-hospital cardiac arrest (OHCA data derived according to the Utstein Style guidelines was used to try to determine factors influencing survival to admission (STA and epidemiological rates of OHCA. Patients and methods: This was an observational study of all age groups based on data from prehospital care reports in Seoul, South Korea. The collected data were reported according to the Utstein Style template for OHCA and analyzed in order to compare STA with non-STA. Univariate analysis was conducted using a binomial logistic regression model to identify predictors associated with trauma patients. Results: Eighty-three (4.8% OHCA survivors were admitted to the emergency department with carotid pulse. The median time from arrest to emergency medical personnel defibrillation was statistically significantly shorter in STA cases (8.0 minutes than in non-STA cases (12.0 minutes; P<0.001. Factors independently associated with better prognosis in terms of trauma patients were female sex (odds ratio [OR]: 0.67; 95% confidence interval [95% CI]: 0.50–0.91; P=0.01, arrest at home (OR: 0.36; 95% CI: 0.27–0.49; P<0.001, and witnessed arrest (OR: 2.64; 95% CI: 1.94–3.39; P<0.001. Conclusion: Early basic life support, performed by either a layperson or emergency medical personnel, had a positive effect on STA. Male sex, arrest outside of the home, and witnessed arrest are significantly associated with trauma. Keywords: Utstein Style, prehospital, defibrillation, basic life support

  14. Enhancing the survival of grafted cardiac stem cells for long-term imaging

    Energy Technology Data Exchange (ETDEWEB)

    Le, Uyenchi N.; Tae, Seong Ho; Bom, Hee Seung; Min, Jung Joon [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-07-01

    Heat shock treatment is known to induce the protection for cells from various environmental insults. Akt (protein kinase B) - with anti-apoptotic activity - has presently been reemerged as a critical enzyme in several signal transduction pathways involved in cell proliferation and programmed cell death. We hypothesized that thermotic treatment and Akt activity in genetically modified cardiomyoblasts would improve their survival after transplantation. Embryonic rat H9c2 cardiomyoblasts were simultaneously transfected with adenovirus containing luciferase reporter gene (MOl 50) and another containing Akt gene [MOl (0 100) ]. 5x106 harvested cells were i.m. implanted into murine skeletal muscles. Bioluminescence imaging was acquired for everyday and luciferase assay was performed to validate the imaging data. For thermotic challenge, adenovirus-mediated flue expressing H9c2 cells were subjected to great heat of 42 .deg. C for 1 hr and re-cultured at 37 .deg. C for 18 hours. Expression of heat shock protein in cells was detected in vitro by Western-blotting. 5x106 normal and shocked cells were implanted into mouse thigh (n = 5) and the animals were imaged with bioluminescence imaging system. In vitro evidences showed a high level expression of Akt and HSP in transfected H9c2 cells. Animals carrying Akt expressed bioluminescence signals until day 34 of post-implantation. The Flue activity was significantly higher in the shocked H9c2 cell-implanted rats and detected over 10 days as compared with the control group. The graft cell death was reduced by 73% at day 2 (1.46+ 10-7 p/s/cm{sup 2}/sr), 51% at day 3 (1.02+10-7 p/s/cm{sup 2}/sr), and 8% at day 10 (1.62+ 10-6 p/s/cm{sup 2}/sr). We revealed here improvement of donor cell's survival induced by the anti-apoptotic means of Akt genetic therapy or heat shock. Utility of bioluminescence imaging resulted in a potential to noninvasively and repetitively monitor implanted cardiac myoblasts over time.

  15. Temporal trends in survival after out-of-hospital cardiac arrest in patients with and without underlying chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Møller, Sidsel G.; Rajan, Shahzleen; Folke, Fredrik;

    2016-01-01

    AIM: Survival after out-of-hospital cardiac arrest (OHCA) has tripled during the past decade in Denmark as a likely result of improvements in cardiac arrest management. This study analyzed whether these improvements were applicable for patients with chronic obstructive pulmonary disease (COPD). M...

  16. Temporal Differences in Out-of-Hospital Cardiac Arrest Incidence and Survival

    DEFF Research Database (Denmark)

    Bagai, Akshay; McNally, Bryan F; Al-Khatib, Sana M;

    2013-01-01

    Understanding temporal differences in the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) has important implications for developing preventative strategies and optimizing systems for OHCA care.......Understanding temporal differences in the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) has important implications for developing preventative strategies and optimizing systems for OHCA care....

  17. Near death experiences, cognitive function and psychological outcomes of surviving cardiac arrest.

    Science.gov (United States)

    Parnia, S; Spearpoint, K; Fenwick, P B

    2007-08-01

    Cardiac arrest is associated with a number of cognitive processes as well as long term psychological outcomes. Recent studies have indicated that approximately 10-20% of cardiac arrest survivors report cognitive processes, including the ability to recall specific details of their resuscitation from the period of cardiac arrest. In addition it has been demonstrated that these cognitive processes are consistent with the previously described near death experience and that those who have these experiences are left with long term positive life enhancing effects. There have also been numerous studies that have indicated that although the quality of life for cardiac arrest survivors is generally good, some are left with long term cognitive impairments as well as psychological sequelae such as post-traumatic stress disorder. This paper will review near death experiences, cognitive function and psychological outcomes in survivors of cardiac arrest.

  18. Role of anti-vimentin antibodies in allograft rejection.

    Science.gov (United States)

    Rose, Marlene L

    2013-11-01

    Production of anti-vimentin antibodies (AVA) after solid organ transplantation are common. Although classically thought to be expressed mainly within the cytosol, recent evidence demonstrates that extracellular or cell surface expression of vimentin is not unusual. This review examines the evidence to assess whether AVA contribute to allograft pathology. Clinical studies suggest that AVA are associated with cardiac allograft vasculopathy in heart transplant recipients. Studies in non-human primates confirm that production of AVA after renal and heart transplantation are not inhibited by Cyclosporine. Experimental studies have demonstrated that mice pre-immunised with vimentin undergo accelerated acute rejection and vascular intimal occlusion of cardiac allografts. Adoptive transfer of hyperimmune sera containing AVA into B-cell-knock-out mice caused accelerated rejection of allografted hearts, this is clear evidence that antibodies to vimentin accelerate rejection. AVA act in concert with the alloimmune response and AVA do not damage syngeneic or native heart allografts. Confocal microscopy of allografted organs in vimentin immunised mice shows extensive expression of vimentin on endothelial cells, apoptotic leukocytes and platelet/leukocyte conjugates, co-localising with C4d. One explanation for the ability of AVA to accelerate rejection would be fixation of complement within the graft and subsequent pro-inflammatory effects; there may also be interactions with platelets within the vasculature.

  19. Implantable Defibrillators Improve Survival in Patients With Mildly Symptomatic Heart Failure Receiving Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Gold, Michael R; Daubert, Jean-Claude; Abraham, William T;

    2013-01-01

    Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT...

  20. Effect of FTY720 and ICAM-1 mAb mono and combination therapy in cardiac allo-transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Hai-bo; HUANG Zu-fa; XIA Sui-sheng; YE Qi-fa; WEN Hao

    2005-01-01

    Objective To observe the effect of FTY720 and ICAM-1 mAb mono and combination therapy in cardiac silo-transplantation in rats. Methods Rats were randomly assigned to 9 groups, heart allo-transplantation were performed in abdominal site with micro-surgical technique. Recipients with allografts were treated with different doses of FTY720 and(or) ICAM-1 mAb. Graft survival, histopathology andlevel of serum IL-2, IFN-γ, IL-4, IL-10were investigated. Results Low doses of FTY720 (lmg/kg) combined with ICAM-1 mAb achieved synergistic effect in the prolongation of cardiac graft survival, combination index(CD =0.67. Conclusion Concomitant therapy of FTY720 and ICAM-1 mAb achieved a synergistic effect in the prolongation of heart allograft survival in rats.

  1. Reduced in-hospital survival rates of out-of-hospital cardiac arrest victims with obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Blom, M T; Warnier, M J; Bardai, A;

    2013-01-01

    AIM: Out-of-hospital cardiac arrest (OHCA) due to sustained ventricular tachycardia/fibrillation (VT/VF) is common and often lethal. Patient's co-morbidities may determine survival after OHCA, and be instrumental in post-resuscitation care, but are poorly studied. We aimed to study whether patients......, to hospital discharge, and at 30 days after OHCA, of OPD-patients and non-OPD patients, using logistic regression analysis. We also compared 30-day survival of patients who were admitted to hospital, using multivariate logistic regression analysis. RESULTS: OPD patients (n=178) and non-OPD patients (n=994...... admitted to hospital (OPD: n=100, no OPD: n=561) revealed that OPD was an independent determinant of reduced 30-day survival rate (39% vs. 59%, adjusted OR 0.6 [0.4-1.0, p=0.035]). CONCLUSION: OPD-patients had lower survival rates after OHCA than non-OPD patients. Survival to ER and to hospital admission...

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

    Science.gov (United States)

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

    2013-09-01

    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.

  3. A strategy for organ allografts without using immunosuppressants or irradiation

    OpenAIRE

    Morita, Haruo; Sugiura, Kikuya; Inaba, Muneo; Jin, Tienan; Ishikawa, Junji; Lian, Zhexiong; Adachi, Yasushi; Sogo, Shinji; Yamanishi, Kazuya; Taki, Hideo; Adachi, Masakazu; Noumi, Takato; Kamiyama, Yasuo; Good, Robert A.; Ikehara, Susumu

    1998-01-01

    A strategy to achieve regular and long lasting organ and tissue allografts without using immunosuppressants and/or irradiation has been established for mice. One hundred percent of skin allografts can be induced to survive >350 days after transplantation if spleen cells from the same donors are first injected into the portal vein of the recipients. The mechanisms underlying this long-term tolerance induction can be described as follows: (i) donor T cells from the spleen of the donor facilitat...

  4. Similar liver transplantation survival with selected cardiac death donors and brain death donors

    NARCIS (Netherlands)

    Dubbeld, J.; Hoekstra, H.; Farid, W.; Ringers, J.; Porte, R. J.; Metselaar, H. J.; Baranski, A. G.; Kazemier, G.; van den Bere, A. P.; van Hoek, B.

    2010-01-01

    Background: The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive

  5. Response interval is important for survival until admission after prehospital cardiac arrest

    DEFF Research Database (Denmark)

    Do, Hien Quoc; Nielsen, Søren Loumann; Rasmussen, Lars Simon

    2010-01-01

    An increasing distance to the nearest hospital must be expected as a result of centralization of acute care at a small number of hospitals. This may have important consequences in emergency situations, such as prehospital or out-of-hospital cardiac arrest (OHCA) where the aim is to obtain return...

  6. Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival

    Science.gov (United States)

    Volland, Cornelia; Bremer, Sebastian; Hellenkamp, Kristian; Hartmann, Nico; Dybkova, Nataliya; Khadjeh, Sara; Kutschenko, Anna; Liebetanz, David; Wagner, Stefan; Unsöld, Bernhard; Didié, Michael; Toischer, Karl; Sossalla, Samuel; Hasenfuß, Gerd; Seidler, Tim

    2016-01-01

    TBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity. PMID:27667030

  7. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy.

    Science.gov (United States)

    Defer, Nicole; Wan, Jinghong; Souktani, Richard; Escoubet, Brigitte; Perier, Magali; Caramelle, Philippe; Manin, Sylvie; Deveaux, Vanessa; Bourin, Marie-Claude; Zimmer, Andreas; Lotersztajn, Sophie; Pecker, Françoise; Pavoine, Catherine

    2009-07-01

    Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction. Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR. Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts. The infarct size was increased 24 h after IR in CB2(-/-) vs. wild-type (WT) hearts and decreased when WT hearts were injected with the CB2 agonist JWH133 (3 mg/kg) at reperfusion. Compared with WT hearts, CB2(-/-) hearts showed widespread injury 3 d after IR, with enhanced apoptosis and remodeling affecting the remote myocardium. Finally, CB2(-/-) hearts exhibited exacerbated fibrosis, associated with left ventricular dysfunction 4 wk after IR, whereas their WT counterparts recovered normal function. Cardiac myocytes and fibroblasts isolated from CB2(-/-) hearts displayed a higher H(2)O(2)-induced death than WT cells, whereas 1 microM JWH133 triggered survival effects. Furthermore, H(2)O(2)-induced myofibroblast activation was increased in CB2(-/-) fibroblasts but decreased in 1 microM JWH133-treated WT fibroblasts, compared with that in WT cells. Therefore, CB2 receptor activation may protect against post-IR heart failure through direct inhibition of cardiac myocyte and fibroblast death and prevention of myofibroblast activation.

  8. Las células T reguladoras y su influencia en la sobrevida del trasplante renal Regulatory T cells and their influence in kidney allograft survival

    Directory of Open Access Journals (Sweden)

    Sonia Y. Velásquez

    2007-10-01

    Full Text Available La respuesta inmune desencadenada frente a un trasplante alogénico conduce usualmente a una respuesta efectora que resulta en el rechazo del aloinjerto; sin embargo, algunos individuos mantienen un trasplante funcionante a largo plazo sin signos de rechazo (tolerancia operacional, aun en ausencia de inmunosupresión. Se ha sugerido que los mismos mecanismos son responsables para la tolerancia hacia antígenos propios y aloantígenos. Uno de estos mecanismos es la regulación inmune y se han identificado varias subpoblaciones de células con propiedades reguladoras. Entre ellas, la población celular mejor caracterizada corresponde a las células T reguladoras (Tregs. Aunque las Tregs en ratones son CD4+CD25+, en humanos el fenotipo de las Treg está restringida a las células T CD4 con alta expresión de CD25 (CD25high y del factor de transcripción Foxp3. El análisis fenotípico y funcional de las células T reguladoras o supresoras circulantes en pacientes trasplantados tal vez sea útil para la detección de pacientes tolerantes operacionales. Además, una futura manipulación in vitro de estas células con fines terapéuticos podría conducir a lograr la inducción de tolerancia in vivo en el trasplante clínico. Aquí, revisamos la evidencia experimental y clínica del papel de las células reguladoras en la biología del trasplante.The immune response elicited by an allogenic transplant usually leads to an effector response resulting in allograft rejection; however, some individuals maintain a long-term functioning transplant without signs of rejection (operational tolerance even in the absence of immunosuppression. It has been suggested that the same mechanisms are responsible for tolerance to self-antigens and alloantigens. One of such mechanisms is immune regulation and several cell subsets with regulatory properties have been identified. Among them, the best characterized cell populations are the regulatory T cells (Treg. Although

  9. All-trans retinoic acid attenuates cardiac allograft vasculopathy and myocardial fibrosis%全反式维甲酸减轻大鼠移植心脏血管病变及纤维化

    Institute of Scientific and Technical Information of China (English)

    张明奎; 吴清玉; 胡建国

    2009-01-01

    目的 探讨全反式维甲酸(atRA)对大鼠移植心脏血管病变(CAV)及心肌纤维化的影响及可能机制.方法 以近交系Wistar大鼠为供者,SD大鼠为受者,进行异位心脏移植,一组受者术后接受环孢素A(CsA,10 nag·kg-1·d-1)皮下注射,同时以atRA(10 mg·kg-1·d-1)灌胃(atRA治疗组),另一组受者术后接受CsA皮下注射(慢性排斥组).术后60 d,取移植心脏,行Masson染色观察心肌组织纤维化程度,Van Gieson染色分析血管狭窄程度,免疫组织化学染色(sP法)观察心肌组织中CD68+细胞浸润情况,逆转录聚合酶链反应分析心肌组织中血小板生长因子(PDGF)A mRNA的相对含量.结果 慢性排斥组和atRA治疗组心肌纤维化指数分别为64.0±11.9和34.7±6.3,慢性排斥组纤维化指数明显高于atRA治疗组(P<0.01).慢性排斥组的血管狭窄指数为62.9±17.2,atRA治疗组为40.1±8.2,二者比较,差异有统计学意义(P<0.01).慢性排斥组CD68+细胞数为(32.1±9.3)个,atRA治疗组CD68+细胞数为(17.6±4.2)个,慢性排斥组明显高于atRA治疗组(P<0.01).慢性排斥组PDGF-AmRNA的相对含量为0.94±0.11,atRA治疗组为0.46±0.08,慢性排斥组明显高于atRA治疗组(P<0.01).结论 atRA能减轻大鼠心脏移植后的CAV及心肌纤维化,机制可能与其抑制CD68+细胞浸润及PDGF A mRNA表达有关.%Objective To investigate the mechanism of albtrans retinoic acid (atRA)attenuating cardiac allograft vasculopathy and myocardial fibrosis. Methods With inbred Wistar rats as donors and Sprague Dawley (SD) rats as recipients, heterotopic heart transplantation model was rejection group received same doses of cyclosporine A for 60 days. Grafts were removed on the day 60 post-transplant. Paraffin-embedded sections of cardiac allograft were stained with Masson's trichrome and Van Gieson for examination of myocardial fibrosis and vascular stenosis. Immunohistochemistry was performed to observe CD68 positive cell infiltration. Platelet

  10. Cardiac arrest teams and time of day: effects on surviving in-hospital resuscitation

    OpenAIRE

    Christ M; Dierschke W; von Auenmueller KI; van Bracht M; Grett M; Trappe HJ

    2014-01-01

    Martin Christ, Wolfgang Dierschke, Katharina Isabel von Auenmueller, Marc van Bracht, Martin Grett, Hans-Joachim Trappe Department of Cardiology and Angiology, Marienhospital Herne, Ruhr – University Bochum, Herne, Germany Objectives: Little is known about the factors that influence survival following in-hospital resuscitation, but previous investigations have suggested that in-hospital resuscitations outside of regular working hours are associated with worse survival rates. Materi...

  11. Epidemiological and Survival Trends of Pediatric Cardiac Arrests in Emergency Departments in Korea: A Cross-sectional, Nationwide Report.

    Science.gov (United States)

    Ahn, Jae Yun; Lee, Mi Jin; Kim, Hyun; Yoon, Han Deok; Jang, Hye Young

    2015-09-01

    Cardiac arrest (CA) in children is associated with high mortality rates. In Korea, cohort studies regarding the outcomes of pediatric CAs are lacking, especially in emergency departments (EDs) or in-hospital settings. This study was conducted to examine the trends in epidemiology and survival outcomes in children with resuscitation-attempted CAs using data from a cross-sectional, national, ED-based clinical registry. We extracted cases in which cardiopulmonary resuscitation and/or manual defibrillation were performed according to treatment codes using the National Emergency Department Information System (NEDIS) from 2008 to 2012. The total number of ED visits registered in the NEDIS during the 5-yr evaluation period was 20,424,530; among these, there were 2,970 resuscitation-attempted CAs in children. The annual rates of pediatric CAs per 1,000 ED visits showed an upward trend from 2.81 in 2009 to 3.62 in 2012 (P for trend = 0.045). The median number of estimated pediatric CAs at each ED was 7.8 (25th to 75th percentile, 4 to 13) per year. The overall rates for admission survival and discharge survival were 35.2% and 12.8%, respectively. The survival outcome of adults increased substantially over the past 5 yr (11.8% in 2008, 11.7% in 2010, and 13.6% in 2012; P for trend = 0.001); however, the results for children did not improve (13.6% in 2008, 11.4% in 2010, and 13.7% in 2012; P for trend = 0.870). Conclusively, we found that the overall incidence of pediatric CAs in EDs increased substantially over the past 5 yr, but without significantly higher survival outcomes. PMID:26339179

  12. Inorganic polyphosphate in cardiac myocytes: from bioenergetics to the permeability transition pore and cell survival.

    Science.gov (United States)

    Dedkova, Elena N

    2016-02-01

    Inorganic polyphosphate (polyP) is a linear polymer of Pi residues linked together by high-energy phosphoanhydride bonds as in ATP. PolyP is present in all living organisms ranging from bacteria to human and possibly even predating life of this planet. The length of polyP chain can vary from just a few phosphates to several thousand phosphate units long, depending on the organism and the tissue in which it is synthesized. PolyP was extensively studied in prokaryotes and unicellular eukaryotes by Kulaev's group in the Russian Academy of Sciences and by the Nobel Prize Laureate Arthur Kornberg at Stanford University. Recently, we reported that mitochondria of cardiac ventricular myocytes contain significant amounts (280±60 pmol/mg of protein) of polyP with an average length of 25 Pi and that polyP is involved in Ca(2+)-dependent activation of the mitochondrial permeability transition pore (mPTP). Enzymatic polyP depletion prevented Ca(2+)-induced mPTP opening during ischaemia; however, it did not affect reactive oxygen species (ROS)-mediated mPTP opening during reperfusion and even enhanced cell death in cardiac myocytes. We found that ROS generation was actually enhanced in polyP-depleted cells demonstrating that polyP protects cardiac myocytes against enhanced ROS formation. Furthermore, polyP concentration was dynamically changed during activation of the mitochondrial respiratory chain and stress conditions such as ischaemia/reperfusion (I/R) and heart failure (HF) indicating that polyP is required for the normal heart metabolism. This review discusses the current literature on the roles of polyP in cardiovascular health and disease. PMID:26862184

  13. 黄芪注射液对小鼠同种皮肤移植存活率的影响%EFFECT OF ASTRAGALUS INJECTION ON THE SURVIVAL OF THE ALLOGRAFTS OF SKIN IN MICE

    Institute of Scientific and Technical Information of China (English)

    于新娟; 侯桂华; 朱新红; 林存智

    2011-01-01

    目的 探讨黄芪注射液对小鼠同种皮肤移植存活率的影响及对脾细胞糖皮质激素受体(GR)与血清皮质醇的调节作用.方法 建立小鼠同种皮肤移植模型,通过腹腔注射给予黄芪注射液和环磷酰胺(CTX),观察黄芪注射液对同种移植物生存期的影响;采用受体放射配基结合分析和放射免疫分析方法,观察移植后不同时间小鼠脾细胞GR及血清皮质醇的改变以及黄芪注射液和环磷酰胺对其的影响.结果 与对照组相比,黄芪组、黄芪+CTX组及CTX组移植皮片存活时间明显延长,差异有显著性(F=48.58,q=5.11~14.48,P0.05)≯黄芪与C'FX合用后逆转C'TX对GR结合位点数的影响(g=10.72,P<0.05).对照组移植后第14天血清皮质醇水平明显升高,与未移植组比较,差异有显著性(F=29.46,q=7.64,P<0.05);CTX组血清皮质醇水平降低,与对照组比较,差异有显著性(q=3.46,P<0.05);黄芪组、黄芪+CTX组血清皮质醇水平升高,与对照组比较,差异有显著性(q=4.54、5.22,P<0.05).结论 黄芪注射液可以明显抑制同种移植排斥反应,提高移植物存活率,其作用机制可能与上调 GR 数量和血清皮质醇水平,从而使内源性糖皮质激素更好地发挥作用有关.%Objective To study the effect of astragalus injection on the survival of the skin allografts in mice and its mechanism. Methods A mouse model of alloskin grafting was created. Astragalus injection and CTX were administered intraperitoneally. The effect of astragalus on survival of the graft was observed. With radioligand banding assay of receptors (RBA),the quantity of GR in the animal spleen cells at different times before and after the transplantation and after administration of astragalus injection and CTX were detected. Cortisol concentration in serum was examined via radioimmunoassay (RIA). Results Compared with that of the controls, the survival duration of the allografts in mice treated with astragalus alone

  14. S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes

    DEFF Research Database (Denmark)

    Schneider, Mikael; Kostin, Sawa; Strøm, Claes C;

    2007-01-01

    RNA expression was increased in hypertrophic rat hearts and that it has pro-cardiomyogenic effects in embryonic stem cell-derived embryoid bodies. We therefore hypothesized that S100A4 could play a supportive role in the injured heart. METHODS AND RESULTS: Here we verify by quantitative real-time PCR...... and immunoblotting that S100A4 mRNA and protein is upregulated in hypertrophic rat and human hearts and show by way of confocal microscopy that S100A4 protein, but not mRNA, appears in cardiac myocytes only in the border zone after an acute ischemic event in rat and human hearts. In normal rat and human hearts, S100...... after injury. Promisingly, recombinant S100A4 protein elicited a robust hypertrophic response and increased the number of viable cells in cardiac myocyte cultures by inhibiting apoptosis. We also found that ERK1/2 activation was necessary for both the hypertrophy and survival effects of S100A4 in vitro...

  15. Effects of Long-term Ramipril on Ventricular Remodeling, Cardiac Function and Survival in Rat Congestive Heart Failure after Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    陶则伟; 黄元伟

    2004-01-01

    Objectives The purpose of this study was to investigate the effects of long-term ramipril on ventricular remodeling, cardiac function and survival in rat congestive heart failure after myocardial infarction. Methods Myocardial infarction (MI) was caused by ligation of the left anterior descending coronary artery in rats. 7 days after the surgery, the surviving rats were randomly assigned to the following treatment protocols: 1) MI rats with no therapy, 2) MI rats treated with ramipril 3 mg/kg per day, 3) Sham-operated control rats, and 4) Sham-operated rats treated with ramipril 3 mg/kg per day. At 22 weeks, cardiac hemodynamic parameters such as MAP, LVSP, ±dP/dtmax and LVEDP were measured,and cardiac morphometric parameters such as HW,LVW and LVCA were measured, mRNA of cardiacmolecule genes, such as βMHC, BNP, collagen Ⅰ and Ⅲ, and TGF-β1, were quantified, and survival rates were calculated. Results Compared with sham-operated rats, MI rats without therapy showed significant increases in cardiac morphological parameters as well as in mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly impaired (P<0.01), and survival rate shortened (P<0.05). Compared with MI rats with no therapy, MI rats treated with ramipril showed significant attenuation of mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly impaired (P<0.01), and survival rate shortened (P<0.05). Compared with MI rats with no therapy, MI rats treated with ramipril showed significant attenuation of mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly improved (P<0.05 or P<0.01), and survival rates prolonged (P<0.05). Conclusions Treatment with long-term ramipril may improve LV remodeling, cardiac function and survival in rat congestive heart failure after MI.

  16. Chimeric Allografts Induced by Short-Term Treatment With Stem Cell Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: II, Study in Miniature Swine.

    Science.gov (United States)

    Cameron, A M; Wesson, R N; Ahmadi, A R; Singer, A L; Hu, X; Okabayashi, T; Wang, Y; Shigoka, M; Fu, Y; Gao, W; Raccusen, L C; Montgomery, R A; Williams, G M; Sun, Z

    2016-07-01

    Transplantation is now lifesaving therapy for patients with end-stage organ failure but requires lifelong immunosuppression with resultant morbidity. Current immunosuppressive strategies inhibit T cell activation and prevent donor-recipient engagement. Therefore, it is not surprising that few host cells are demonstrated in donor grafts. However, our recent small animal studies found large numbers of recipient stem cells present after transplantation and pharmacological mobilization, resulting in a chimeric, repopulated organ. We now confirm these findings in a well-characterized large animal preclinical model. Here, we show that AMD3100 and FK506 mobilization of endogenous stem cells immediately post kidney transplantation combined with repeat therapy at 1, 2, and 3 months led to drug-free long-term survival in maximally immunologically mismatched swine. Three long-term recipients have stable chimeric transplants, preserved antidonor skin graft responses, and normal serum creatinine levels despite withdrawal of all medication for 3 years. PMID:26748958

  17. Better management of out-of-hospital cardiac arrest increases survival rate and improves neurological outcome in the Swiss Canton Ticino

    OpenAIRE

    Mauri, Romano; Burkart, Roman; Benvenuti, Claudio; Caputo, Maria Luce; Moccetti, Tiziano; Del Bufalo, Alessandro; Gallino, Augusto; Casso, Carlo; Anselmi, Luciano; Cassina, Tiziano; Klersy, Catherine; Auricchio, Angelo

    2015-01-01

    Aim To determine the incidence of out-of-hospital cardiac arrest (OHCA) fulfilling Utstein criteria in the Canton Ticino, Switzerland, the survival rate of OHCA patients and their neurological outcome. Methods and results All OHCAs treated in Canton Ticino between 1 January 2005 and 31 December 2014 were followed until either death or hospital discharge. The survival and neurological outcome of those OHCA fulfilling Utstein criteria are reported. A total of 3367 OHCAs occurred in the Canton T...

  18. Prolonging rat liver allograft survival by blockade of OX40-OX40L co-stimulatory signaling%针对OX40小于扰RNA供体转染抗大鼠肝移植排斥反应

    Institute of Scientific and Technical Information of China (English)

    夏仁品; 卢实春; 赖威; 戴军; 娄金丽; 李宁

    2008-01-01

    目的 观察RNA干扰阻断OX40-OX40L共刺激通路对大鼠移植肝存活时间的影响.方法 制作DA大鼠到Lewis大鼠的原位肝脏移植模型,移植前取预先制备的5 ml含5×109pfu的pLVTHM-OX40-siRNA重组慢病毒,灌注感染移植供肝30 min,术后观察受者存活时间,移植肝脏进行组织病理学检查;采用ELISA法检测大鼠外周血IL-2,IFN-γ,的水平,并进行受者大鼠脾细胞对供者大鼠脾细胞的混合淋巴细胞反应(MLR).结果 转染组受者肝脏移植物的存活时间为(74.00±3.79)d,明显长于对照组和未转染组;转染组移植肝组织炎细胞侵润、间质水肿、肝组织坏死程度较对照组和未转染组减轻,实验组大鼠脾细胞刺激T淋巴细胞增殖的能力降低(P<0.01);移植术后的第7天,转染组血清IL-2浓度为(46.0±8.4)ng/L,IFN-γ浓度为(202.7±14.6)ng/L,均显著低于对照组和未转染组(P<0.05).结论 转染靶向OX40的siRNA,在体内可通过阻断OX40-OX40L共刺激通路,抑制大鼠肝脏移植后的排斥反应,延长大鼠移植肝的存活时间.%Objective To investigate the effect of blockade of OX40-OX40L co-stimulatory signal on the survival time of rat liver allograft. Methods siRNA-expression vectors were constructed to target OX40. Heterotopic liver transplantation models in rats were established. Liver allografts were infected by in situ peffusion of viral particle (5 x 109 pfu of pLVTHM- OX40siRNA) perioperatively. Histological examination was done. Serum IL-2 and IFN-γ levels were assayed by ELISA, and mix lymphocyte response(MLR) was tested by 3 H-thymidine. Results The survival time of recipients in siRNA treatment group(74.00±3.79) days was significantly longer than that in control group (7.33±0.21 ) days, P <0. 01.The inflammatory cell infiltration and liver tissue structure destruction were very milder in siRNA treatment group than in control group. The concentrations of serum IL-2 and IFN-γ were (46±8.4) ng/L and(202.7±14

  19. Mouse kidney transplantation: models of allograft rejection.

    Science.gov (United States)

    Tse, George H; Hesketh, Emily E; Clay, Michael; Borthwick, Gary; Hughes, Jeremy; Marson, Lorna P

    2014-01-01

    Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

  20. Breast Cancer Laterality Does Not Influence Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality

    International Nuclear Information System (INIS)

    Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed for noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does

  1. Breast Cancer Laterality Does Not Influence Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality

    Energy Technology Data Exchange (ETDEWEB)

    Rutter, Charles E., E-mail: charles.rutter@yale.edu [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Chagpar, Anees B. [Department of Surgery, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut (United States); Evans, Suzanne B. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut (United States)

    2014-10-01

    Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed for noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does

  2. Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is associated with long-term survival in patients after cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Risum, Niels; Williams, Eric S; Khouri, Michel G;

    2013-01-01

    Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac resynchroniz...

  3. High-dose stabilized chlorite matrix WF10 prolongs cardiac xenograft survival in the hamster-to-rat model without inducing ultrastructural or biochemical signs of cardiotoxicity

    DEFF Research Database (Denmark)

    Hansen, A; Kemp, K; Kemp, E;

    2001-01-01

    of high dose WF10 as a single drug regimen in the hamster-to-rat xenotransplantation model and searched for possible cardiotoxic side effects. WF10 prolonged cardiac xenograft survival, but did not induce tolerence or inhibit pathological signs of acute rejection. Hamsters from the donor population...

  4. Correlation of human leucocyte antigen matching to acute rejection and allograft survival after renal allograft%肾移植患者抗人类白细胞抗体配型与术后急性排斥反应及移植肾存活的关系

    Institute of Scientific and Technical Information of China (English)

    李留洋; 赵明; 陈剑荣; 钱俊; 李民; 孙尔维; 郭颖; 岳良升; 范礼佩; 陈桦

    2008-01-01

    BACKGROUND: Panel reactive antibody (PRA) can mediate hyperacute rejection, and lead to decrease in success rate of transplantation and survival rate of renal graft in highly sensitized recipients compared to non-sensitized recipients.OBJECTIVE: According to human leucocyte antigen (HLA) cross-matching standards to select suitable donors for sensitized recipients and to evaluate the incidence of acute rejection and survival rate of renal allografts.DESIGN: Case observation.SETTING: Zhujiang Hospital of Southern Medical University.PARTICIPANTS: 136 sensitized recipients with positive PRA underwent renal transplantation in Department of Organ Transplantation, Zhujiang Hospital of Southern Medical University between January 1997 and December 2003 were selected, including 41 males and 95 females, aged (45±9) years. Recipients of first, second, third, and fourth transplant were 115, 18, 2 and 1 case, respectively. The informed consent was obtained from all patients. The protocol was approved by Hospital Ethics Committee. Lambda antigen tray (LAT) and LAT-Mix were purchased from One Lambda, Inc, USA. Special monoclonal tray -Asian HLA class Ⅰ (SMT72R) and Micro SSP Generic HLA Class Ⅱ (DRB/DQB) were also purchased from One Lambda, Inc, USA.METHODS: Pre-operative PRA levels and specificity of recipients were detected by ELISA test with Lambda antigen tray (LAT). Donor and recipient HLA class Ⅰ typing was performed with special tray - Asian HLA class Ⅰ (SMT72R), and HLA class Ⅱ gene typing with Micro SSP Generic HLA Class Ⅱ (DRB/DQB) (Micro-SSP). HLA-matching between donor and recipient was performed according to HLA cross-reactive group (CREG) standards by UNOS and class Ⅱ antigen permissible mismatch. The incidence of acute rejection and survival rate of renal allografts were evaluated within 1, 3 and 5 years.MAIN OUTCOME MEASURES: ①PRA levels and specificity of sensitized recipients before and after transplantation; ②HLA-matching between donor and

  5. Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival.

    Science.gov (United States)

    Malard, Florent; Labopin, Myriam; Chevallier, Patrice; Guillaume, Thierry; Duquesne, Alix; Rialland, Fanny; Derenne, Sophie; Peterlin, Pierre; Leauté, Anne-Gaelle; Brissot, Eolia; Gregoire, Marc; Moreau, Philippe; Saas, Philippe; Gaugler, Béatrice; Mohty, Mohamad

    2016-04-01

    We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27-0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome.

  6. CD20 antigen expression by lymphoma cells in lung allograft recipients is associated with higher remission rate and superior survival: A study on heart and lung transplant recipients

    Directory of Open Access Journals (Sweden)

    Aghil Gholipour-Shoiili

    2014-01-01

    Full Text Available Post-transplant lymphoproliferative disorders (PTLD are one of the fatal complications of transplantation, and there is scarcity of data on the relevance of antigen expression by tumor cells in PTLD. In the current study, we aimed to investigate the potential effects of CD20 antigen expression by PTLD lesions developing in heart/lung transplant recipients. A comprehensive search was performed for reports indicating CD20 antigen tests in PTLD lesions developing in heart and/or lung transplant recipients. For data accumulation, we developed a standard questionnaire and data of patients presented in different published reports were entered into it. Finally, data from 26 previously published reports from different centers around the world were included in the analysis. CD20-positive PTLD lesions are significantly more likely to be of the B cell type (P = 0.006. PTLD in patients with a CD20-positive test represented relevantly shorter time from transplantation to PTLD, although it did not reach a significance level (P = 0.08. At the last follow-up, 53% patients were dead. Survival analysis showed no prognosis difference regarding CD20 test. When data were reanalyzed separately for heart and lung transplant recipients, lung recipients developing PTLD with a CD20-positive test were significantly more likely to represent remission episodes (P = 0.03, and also represented a significantly better outcome than CD20-negative PTLD patients (P = 0.04. CD20-positive PTLD lesions in heart/lung recipients are more likely of the B cell type and develop PTLD lesions earlier than their CD20-negative counterparts. Lung recipients developing CD20-positive PTLD lesions represented higher remission rates and better outcome. Further studies with prospective follow-up of patients are needed for confirming our findings.

  7. c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling.

    Directory of Open Access Journals (Sweden)

    Nanako Kawaguchi

    Full Text Available BACKGROUND: Resident c-kit positive (c-kitpos cardiac stem cells (CSCs could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential. METHODOLOGY/PRINCIPAL FINDINGS: We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs. CONCLUSION/SIGNIFICANCE: c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

  8. Protein Kinase G1 α Overexpression Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction

    OpenAIRE

    Linlin Wang; Zeeshan Pasha; Shuyun Wang; Ning Li; Yuliang Feng; Gang Lu; Millard, Ronald W.; Muhammad Ashraf

    2013-01-01

    BACKGROUND: We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α) could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs) contributing to regeneration of the ischemic heart. METHODS AND RESULTS: MSCs from male rats were transduced with adenoviral vector encoding for PKG1α ((PKG1α)MSCs).Controls included native MSCs ((Nat)MSCs) and MSCs transduced with an empty vector ((Null)MSCs). PKG1α activity was increased appr...

  9. Predictive value of assessing diastolic strain rate on survival in cardiac amyloidosis patients with preserved ejection fraction.

    Directory of Open Access Journals (Sweden)

    Dan Liu

    Full Text Available Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA, we hypothesized that speckle-tracking-imaging (STI derived longitudinal early diastolic strain rate (LSRdias could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%.Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients.Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years. Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views.Nineteen (46% out of 41 CA patients died during a median of 16 months (quartiles 5-35 months follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6 ± 2 vs. 8 ± 3 mm, global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p < 0.05. NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.17-3.26, P = 0.010, global LSRdias (HR = 7.30, 95% CI 2.08-25.65, P = 0.002, and E/LSRdias (HR = 2.98, 95% CI 1.54-5.79, P = 0.001 remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S-1 (sensitivity 68%, specificity 67%. Global LSRdias < 0.85 S-1 predicted a 4-fold increased mortality in CA patients with preserved LVEF.STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.

  10. Activity and Life After Survival of a Cardiac Arrest (ALASCA and the effectiveness of an early intervention service: design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bakx Wilbert GM

    2007-08-01

    Full Text Available Abstract Background Cardiac arrest survivors may experience hypoxic brain injury that results in cognitive impairments which frequently remain unrecognised. This may lead to limitations in daily activities and participation in society, a decreased quality of life for the patient, and a high strain for the caregiver. Publications about interventions directed at improving quality of life after survival of a cardiac arrest are scarce. Therefore, evidence about effective rehabilitation programmes for cardiac arrest survivors is urgently needed. This paper presents the design of the ALASCA (Activity and Life After Survival of a Cardiac Arrest trial, a randomised, controlled clinical trial to evaluate the effects of a new early intervention service for survivors of a cardiac arrest and their caregivers. Methods/design The study population comprises all people who survive two weeks after a cardiac arrest and are admitted to one of the participating hospitals in the Southern part of the Netherlands. In a two-group randomised, controlled clinical trial, half of the participants will receive an early intervention service. The early intervention service consists of several consultations with a specialised nurse for the patient and their caregiver during the first three months after the cardiac arrest. The intervention is directed at screening for cognitive problems, provision of informational, emotional and practical support, and stimulating self-management. If necessary, referral to specialised care can take place. Persons in the control group will receive the care as usual. The primary outcome measures are the extent of participation in society and quality of life of the patient one year after a cardiac arrest. Secondary outcome measures are the level of cognitive, emotional and cardiovascular impairment and daily functioning of the patient, as well as the strain for and quality of life of the caregiver. Participants and their caregivers will be followed

  11. Oral hydrogen water prevents chronic allograft nephropathy in rats.

    Science.gov (United States)

    Cardinal, Jon S; Zhan, Jianghua; Wang, Yinna; Sugimoto, Ryujiro; Tsung, Allan; McCurry, Kenneth R; Billiar, Timothy R; Nakao, Atsunori

    2010-01-01

    Reactive oxygen species (ROS) contribute to the development of interstitial fibrosis and tubular atrophy seen in chronic allograft nephropathy (CAN). As molecular hydrogen gas can act as a scavenger of ROS, we tested the effect of treatment with hydrogen water (HW) in a model of kidney transplantation, in which allografts from Lewis rats were orthotopically transplanted into Brown Norway recipients that had undergone bilateral nephrectomy. Molecular hydrogen was dissolved in water and recipients were given HW from day 0 until day 150. Rats that were treated with regular water (RW) gradually developed proteinuria and their creatinine clearance declined, ultimately leading to graft failure secondary to CAN. In contrast, treatment with HW improved allograft function, slowed the progression of CAN, reduced oxidant injury and inflammatory mediator production, and improved overall survival. Inflammatory signaling pathways, such as mitogen-activated protein kinases, were less activated in renal allografts from HW-treated rats as compared with RW-treated rats. Hence, oral HW is an effective antioxidant and antiinflammatory agent that prevented CAN, improved survival of rat renal allografts, and may be of therapeutic value in the setting of transplantation. PMID:19907413

  12. Prognostic factors for death and survival with or without complications in cardiac arrest patients receiving CPR within 24 hours of anesthesia for emergency surgery

    Directory of Open Access Journals (Sweden)

    Siriphuwanun V

    2014-10-01

    Full Text Available Visith Siriphuwanun,1 Yodying Punjasawadwong,1 Worawut Lapisatepun,1 Somrat Charuluxananan,2 Ketchada Uerpairojkit2 1Department of Anesthesiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Purpose: To determine prognostic factors for death and survival with or without complications in cardiac arrest patients who received cardiopulmonary resuscitation (CPR within 24 hours of receiving anesthesia for emergency surgery. Patients and methods: A retrospective cohort study approved by the Maharaj Nakorn Chiang Mai University Hospital Ethical Committee. Data used were taken from records of 751 cardiac arrest patients who received their first CPR within 24 hours of anesthesia for emergency surgery between January 1, 2003 and October 31, 2011. The reviewed data included patient characteristics, surgical procedures, American Society of Anesthesiologist (ASA physical status classification, anesthesia information, the timing of cardiac arrest, CPR details, and outcomes at 24 hours after CPR. Univariate and polytomous logistic regression analyses were used to determine prognostic factors associated with the outcome variable. P-values of less than 0.05 were considered statistically significant. Results: The outcomes at 24 hours were death (638/751, 85.0%, survival with complications (73/751, 9.7%, and survival without complications (40/751, 5.3%. The prognostic factors associated with death were: age between 13–34 years (OR =3.08, 95% CI =1.03–9.19; ASA physical status three and higher (OR =6.60, 95% CI =2.17–20.13; precardiopulmonary comorbidity (OR =3.28, 95% CI =1.09–9.90; the condition of patients who were on mechanical ventilation prior to receiving anesthesia (OR =4.11, 95% CI =1.17–14.38; surgery in the upper abdominal site (OR =14.64, 95% CI =2.83–75.82; shock prior to cardiac arrest (OR =6.24, 95% CI =2.53–15

  13. Uremic escape of renal allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-10-01

    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.

  14. The Effect of Xin Mai Tong Capsules in Protecting Survival Cardiac Muscles of the Patients with Acute Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    Qiu Ruixiang; Feng Jun; Meng Jun

    2005-01-01

    To study the effect of Composite Xin Mai Tong capsules (复方心脉通胶囊 CXMT) in protecting survival cardiac muscles in patients with acute myocardial infarction (AMI) after percutaneous transluminal coronary angioplasty (PTCA) operation. The treatment with Composite XMT capsules started 3 days prior to the operation and continued for a period of 4 weeks; and its effect on the number of segments of nuclide resting ventricular myocardial imaging, the nuclide defect extension score (ES) and nuclide defect severity score (SS),and the level of vascular endothelial growth factor (VEGF) of circulatory blood were determined and compared with that of the control group. More segments originally scored 1 turning to be scored 2 in nuclide imaging were seen in the treatment group than in the control group; and smaller ES and less SS seen in the former than in the latter group (P<0.05). Composite XMT capsules play an active role in myocardial salvage by promoting its metabolism and expression of circulatory VEGF. Its angiogenesis-like action helps establish collateral flow and has a positive role in myocardial salvage.

  15. Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

    Energy Technology Data Exchange (ETDEWEB)

    Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.

    1987-02-01

    Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA.

  16. Patient-reported health status prior to cardiac resynchronisation therapy identifies patients at risk for poor survival and prolonged hospital stays

    DEFF Research Database (Denmark)

    Versteeg, H.; Denollet, J.; Meine, M.;

    2016-01-01

    BACKGROUND: Patient-reported factors have largely been neglected in search of predictors of response to cardiac resynchronisation therapy (CRT). The current study aimed to examine the independent value of pre-implantation patient-reported health status in predicting four-year survival and cardiac......-related hospitalisation of CRT patients. METHODS: Consecutive patients (N = 139) indicated to receive a first-time CRT-defibrillator at the University Medical Center Utrecht were asked to complete a set of questionnaires prior to implantation. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to assess heart...... % CI 1.88-5.44). CONCLUSIONS: Patient-reported health status assessed prior to CRT identifies patients at risk for poor survival and prolonged hospital stays, independent of traditional risk factors. These results emphasise the importance of incorporating health status measures in cardiovascular...

  17. Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.

    Science.gov (United States)

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

  18. Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells.

    Science.gov (United States)

    Matsuo, Takehiko; Masumoto, Hidetoshi; Tajima, Shuhei; Ikuno, Takeshi; Katayama, Shiori; Minakata, Kenji; Ikeda, Tadashi; Yamamizu, Kohei; Tabata, Yasuhiko; Sakata, Ryuzo; Yamashita, Jun K

    2015-11-20

    Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1 mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2 × 10(6) of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8 mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart.

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

    Directory of Open Access Journals (Sweden)

    Bueno V.

    2002-01-01

    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.

  20. Physician presence in an ambulance car is associated with increased survival in out-of-hospital cardiac arrest: a prospective cohort analysis.

    Directory of Open Access Journals (Sweden)

    Akihito Hagihara

    Full Text Available The presence of a physician seems to be beneficial for pre-hospital cardiopulmonary resuscitation (CPR of patients with out-of-hospital cardiac arrest. However, the effectiveness of a physician's presence during CPR before hospital arrival has not been established. We conducted a prospective, non-randomized, observational study using national data from out-of-hospital cardiac arrests between 2005 and 2010 in Japan. We performed a propensity analysis and examined the association between a physician's presence during an ambulance car ride and short- and long-term survival from out-of-hospital cardiac arrest. Specifically, a full non-parsimonious logistic regression model was fitted with the physician presence in the ambulance as the dependent variable; the independent variables included all study variables except for endpoint variables plus dummy variables for the 47 prefectures in Japan (i.e., 46 variables. In total, 619,928 out-of-hospital cardiac arrest cases that met the inclusion criteria were analyzed. Among propensity-matched patients, a positive association was observed between a physician's presence during an ambulance car ride and return of spontaneous circulation (ROSC before hospital arrival, 1-month survival, and 1-month survival with minimal neurological or physical impairment (ROSC: OR = 1.84, 95% CI 1.63-2.07, p = 0.00 in adjusted for propensity and all covariates; 1-month survival: OR = 1.29, 95% CI 1.04-1.61, p = 0.02 in adjusted for propensity and all covariates; cerebral performance category (1 or 2: OR = 1.54, 95% CI 1.03-2.29, p = 0.04 in adjusted for propensity and all covariates; and overall performance category (1 or 2: OR = 1.50, 95% CI 1.01-2.24, p = 0.05 in adjusted for propensity and all covariates. A prospective observational study using national data from out-of-hospital cardiac arrests shows that a physician's presence during an ambulance car ride was independently associated with

  1. FTY720, a new immunosuppressant,as rescue therapy in mouse cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    WANGMing-Hui; VitaliyMILEKHIN; ZHANGHua; HUANGHong-Zheng

    2003-01-01

    AIM: FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induceslong-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present studyinvestigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a mouseheterotopic cardiac transplantation model. METHODS: BALB/c hearts were heterotopically grafted in C57BL/6mice. FTY720, at the doses of 0.5, 1, and 5 mg.kg-l.d-1 or vehicle was administered to recipients once daily by oralgavage from d 3 to d 7 after transplantation. Histological changes of grafts, and the lymphocyte number in theperipheral blood and the peripheral lymph nodes were determined on d 5 after transplantation. RESULTS: FTY720prolonged the median graft survival time dose-dependently and significantly. Histological evaluation revealed lesslymphocytic infiltration in cardiac allografts treated with FTY720. Moreover, FTY720 remarkably lowered thenumber of peripheral blood lymphocytes but significantly increased the lymphocyte number in the mesentericlymph nodes and the peripheral lymph nodes. CONCLUSION: FTY720 used orally as rescue therapy significantlyextended allograft survival in mouse heterotopic cardiac transplantation.

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

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2013-01-15

    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.

  3. Radionuclide diagnosis of allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    George, E.A.

    1982-10-01

    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.

  4. Emphysematous pyelonephritis in failed renal allograft: Case report and review of literature.

    Science.gov (United States)

    Bansal, Rahul Kumar; Lambe, Shahid; Kapoor, Anil

    2016-01-01

    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.

  5. Skin allograft and vascularized composite allograft: potential for long-term efficacy in the context of lymphatic modulation.

    Science.gov (United States)

    Rinkinen, Jacob; Selley, Ryan; Agarwal, Shailesh; Loder, Shawn; Levi, Benjamin

    2014-01-01

    Tissue transplantation restores form and function in burn patients. The treatment of burn injuries is influenced by severity, location, and the percentage of total body surface area. There have been a number of different techniques developed to temporize and repair the destroyed tissue. However, in patients with large wound burden, sufficient donor site tissue may not be available for autograft harvesting. Such extensive burns necessitate other temporary and permanent options for wound coverage such as skin or vascularized composite allografts (VCA). Rejection of these tissues presents an ongoing problem which is currently managed using a host of systemic immunosuppressive medications. This article discusses the mechanism behind the innate and adaptive immune systems rejection of the allografts. By understanding these pathways, various techniques using immunomodulatory protocols have led to increased allograft survival. However, our primary interest lies in the initial recognition of the graft. We tailor this article to have a specific emphasis on lymphatic modulation as a potential adjunctive therapy. Reviews of the studies evaluating the effect of lymph node modulation on graft survival are described with future implications to allograft transplant research. PMID:25051523

  6. Ação do soro de cabra anti-soro de coelho imunizado ou não com células linfóides do doador sobre o alotransplante cardíaco em ratos: immunosupression of goat antiserum against rabbit serum immunized or not with donor lymphoid cells Cardiac allograft in rats

    Directory of Open Access Journals (Sweden)

    Haylton Jorge Suaid

    2002-01-01

    rejeição aguda dos corações transplantados não apresentaram anticorpos citotóxicos circulantes. O fator causador do bloqueio parace n��o estar vinculado aos bloqueios de citotoxicidade "in vitro" e do teor de precepitinas do SAL.OBJECTIVE: To study the immunosupression efficacy an specific anti-antilymphocytic serum prepared in goats in a model of cardiac allografts in rats. METHODS: Three rabbits were immunized with lymphoid cells obtained from mesenteric lymphatic nodes of Wistar rats. Each one received subcutaneously 3x10(9 cells mixed with Freund's adjuvant. After 2 weeks, they were injected with the same amount of cells at weekly intervals for 4 additional times. In the 5th week they were bled and their serum were mixed. This serum, which had a cytotoxic titer of 1:1024, was used to immunize 2 goats that gave rise to the anti-antilymphocytic serum (AAS-1 and AAS-2. As control we immunized 1 additional goat with normal rabbit serum (ANS. The gel diffusion technique (AAS x rabbit serum showed precipitation bands against till the following dilution: AAS-1 - 1/64, AAS-2 - 1/128 and ANS 1/124. Both AAS were able to block the in vitro lymphocytotoxity of goat antilymphocytic serum till dilution of 1:2 while ANS did not. The hearts from Wistar rats (donors were transplanted in Holtzman rats. The transplanted rats were divide in groups: C1 - 11 animals (control that received no serum; C2 - 5 animals (control that received 1ml of goat normal serum; A- 19 animals - A1 with 5 rats injected intravenously in the day of surgery with 0.5ml of AAS-1, A2 with 7 rats injected with 1ml of AAS-1 only in the of surgery, and A3 with 7 rats that received 1ml of AAS-1 in days 0, 1 and 2 postoperatively; and group B with 19 rats (B1, B2 and B3 treated as group A except with the AAS-2 serum. RESULTS: Mean heart survival in groups C1 and C2 was respectively 11.9 and 14.6 days Survival range in the subgroups A1 and A2 were respectively 9 to 230 days and 23 to 230 days. In subgroup A

  7. Neutrophil mediated smooth muscle cell loss precedes allograft vasculopathy

    Directory of Open Access Journals (Sweden)

    Lee Timothy DG

    2010-06-01

    Full Text Available Abstract Background Cardiac allograft vasculopathy (AV is a pathological process of vascular remodeling leading to late graft loss following cardiac transplantation. While there is consensus that AV is alloimmune mediated, and evidence that the most important alloimmune target is medial smooth muscle cells (SMC, the role of the innate immune response in the initiation of this disease is still being elucidated. As ischemia reperfusion (IR injury plays a pivotal role in the initiation of AV, we hypothesize that IR enhances the early innate response to cardiac allografts. Methods Aortic transplants were performed between fully disparate mouse strains (C3H/HeJ and C57BL/6, in the presence of therapeutic levels of Cyclosporine A, as a model for cardiac AV. Neutrophils were depleted from some recipients using anti-PMN serum. Grafts were harvested at 1,2,3,5d and 1,2wk post-transplant. Ultrastructural integrity was examined by transmission electron microscopy. SMC and neutrophils were quantified from histological sections in a blinded manner. Results Grafts exposed to cold ischemia, but not transplanted, showed no medial SMC loss and normal ultrastructural integrity. In comparison, allografts harvested 1d post-transplant exhibited > 90% loss of SMC (p Conclusions These novel data show that there is extensive damage to medial SMC at 1d post-transplant. By depleting neutrophils from recipients it was demonstrated that a portion of the SMC loss was mediated by neutrophils. These results provide evidence that IR activation of early innate events contributes to the etiology of AV.

  8. Predictors of survival and favorable functional outcomes after an out-of-hospital cardiac arrest in patients systematically brought to a dedicated heart attack center (from the Harefield Cardiac Arrest Study).

    Science.gov (United States)

    Iqbal, M Bilal; Al-Hussaini, Abtehale; Rosser, Gareth; Salehi, Saleem; Phylactou, Maria; Rajakulasingham, Ramyah; Patel, Jayna; Elliott, Katharine; Mohan, Poornima; Green, Rebecca; Whitbread, Mark; Smith, Robert; Ilsley, Charles

    2015-03-15

    Despite advances in cardiopulmonary resuscitation (CPR), survival remains low after out-of-hospital cardiac arrest (OOHCA). Acute coronary ischemia is the predominating precipitant, and prompt delivery of patients to dedicated facilities may improve outcomes. Since 2011, all patients experiencing OOHCA in London, where a cardiac etiology is suspected, are systematically brought to heart attack centers (HACs). We determined the predictors for survival and favorable functional outcomes in this setting. We analyzed 174 consecutive patients experiencing OOHCA from 2011 to 2013 brought to Harefield Hospital-a designated HAC in London. We analyzed (1) all-cause mortality and (2) functional status using a modified Rankin scale (mRS 0 to 6, where mRS0-3(+) = favorable functional status). The overall survival rates were 66.7% (30 days) and 62.1% (1 year); and 54.5% had mRS0-3(+) at discharge. Patients with mRS0-3(+) had reduced mortality compared to mRS0-3(-): 30 days (1.2% vs 72.2%, p <0.001) and 1 year (5.3% vs 77.2%, p <0.001). Multivariate analyses identified lower patient comorbidity, absence of cardiogenic shock, bystander CPR, ventricular tachycardia/ventricullar fibrillation as initial rhythm, shorter duration of resuscitation, prehospital advanced airway, absence of adrenaline and inotrope use, and intra-aortic balloon pump use as predictors of mRS0-3(+). Consistent predictors of increased mortality were the presence of cardiogenic shock, advanced airway use, increased duration of resuscitation, and absence of therapeutic hypothermia. A streamlined delivery of patients experiencing OOHCA to dedicated facilities is associated with improved functional status and survival. Our study supports the standardization of care for such patients with the widespread adoption of HACs.

  9. Factors Associated With Successful Resuscitation After Out-of-Hospital Cardiac Arrest and Temporal Trends in Survival and Comorbidity

    DEFF Research Database (Denmark)

    Søholm, Helle; Hassager, Christian; Lippert, Freddy;

    2015-01-01

    associated with outcome. RESULTS: Of a total of 2,527 attempted resuscitations in out-of-hospital cardiac arrest patients, 40% (n=1,015) were successfully resuscitated and admitted to the hospital. The strongest independent factors associated with successful resuscitation were shockable primary rhythm...... (multivariate OR=1.14; 95% CI 0.91 to 1.44), and employment status (multivariate OR=1.17; 95% CI 0.89 to 1.56) were not independently associated with outcome. The number of patients with a high comorbidity burden (Charlson comorbidity index ≥3) increased during the study period (P trend ...STUDY OBJECTIVE: Out-of-hospital cardiac arrest has an overall poor prognosis. We sought to identify what temporal trends and influencing factors existed for this condition in one region. METHODS: We studied consecutive out-of-hospital cardiac arrest patients from 2007 to 2011 with attempted...

  10. Regulatory Allospecific T Cell Clones Abrogate Chronic Allograft Rejection

    OpenAIRE

    Waaga-Gasser, Ana Maria; Grimm, Martin R.; Lutz, Jens; Lange, Volkmar; Lenhard, Susanne M.; Aviles, Beatriz; Kist-van Holthe, Joana E; Lebedeva, Tatiana; Samsonov, Dimitry; Meyer, Detlef; Hancock, Wayne W.; Heemann, Uwe; Gasser, Martin; Chandraker, Anil

    2009-01-01

    True alloantigen-specific tolerance is the ultimate goal of solid organ transplantation, eliminating the need for long-term immunosuppression. Recent evidence suggests that Th1-derived cytokines are associated with rejection and Th2-derived cytokines with long-term allograft survival, but the roles of these subsets in rejection and tolerance are incompletely understood. Here, we analyzed the functional and regulatory capacities of T cell clones derived from tolerant and rejecting rats (Wistar...

  11. Left versus right deceased donor renal allograft outcome.

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2009-12-01

    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.

  12. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

  13. Emphysema in the renal allograft

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-04-01

    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.

  14. Autophagy in allografts rejection: A new direction?

    Science.gov (United States)

    Sun, Hukui; Cheng, Dayan; Ma, Yuanyuan; Wang, Huaiquan; Liang, Ting; Hou, Guihua

    2016-03-18

    Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation.

  15. Does Pre-hospital Endotracheal Intubation Improve Survival in Adults with Non-traumatic Out-of-hospital Cardiac Arrest? A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ling Tiah

    2014-11-01

    Full Text Available Introduction: Endotracheal intubation (ETI is currently considered superior to supraglottic airway devices (SGA for survival and other outcomes among adults with non-traumatic out-of-hospital cardiac arrest (OHCA. We aimed to determine if the research supports this conclusion by conducting a systematic review. Methods: We searched the MEDLINE, Scopus and CINAHL databases for studies published between January 1, 1980, and 30 April 30, 2013, which compared pre-hospital use of ETI with SGA for outcomes of return of spontaneous circulation (ROSC; survival to hospital admission; survival to hospital discharge; and favorable neurological or functional status. We selected studies using pre-specified criteria. Included studies were independently screened for quality using the Newcastle-Ottawa scale. We did not pool results because of study variability. Study outcomes were extracted and results presented as summed odds ratios with 95% CI. Results: We identified five eligible studies: one quasi-randomized controlled trial and four cohort studies, involving 303,348 patients in total. Only three of the five studies reported a higher proportion of ROSC with ETI versus SGA with no difference reported in the remaining two. None found significant differences between ETI and SGA for survival to hospital admission or discharge. One study reported better functional status at discharge for ETI versus SGA. Two studies reported no significant difference for favorable neurological status between ETI and SGA. Conclusion: Current evidence does not conclusively support the superiority of ETI over SGA for multiple outcomes among adults with OHCA. [West J Emerg Med. 2014;15(7:-0.

  16. Predictive factors of graft dysfunction and long-term kidney allograft failure

    OpenAIRE

    Fonseca, Isabel

    2015-01-01

    Kidney transplantation is considered the treatment of choice for many patients with endstage chronic kidney disease; however, despite advancements in short-term allograft survival, long-term survival has not paralleled this improvement. Due to the inevitable ischemic damage and associated reperfusion injury, delayed graft function (DGF) is a common complication after kidney transplantation, which may negatively affect graft survival. Because serum creatinine (SCr) and other traditional marker...

  17. SPECT- and PET-Based Approaches for Noninvasive Diagnosis of Acute Renal Allograft Rejection

    Directory of Open Access Journals (Sweden)

    Helga Pawelski

    2014-01-01

    photon emission computed tomography (SPECT or positron emission tomography are promising tools for noninvasive diagnosis of acute allograft rejection (AR. Given the importance of renal transplantation and the limitation of available donors, detailed analysis of factors that affect transplant survival is important. Episodes of acute allograft rejection are a negative prognostic factor for long-term graft survival. Invasive core needle biopsies are still the “goldstandard” in rejection diagnostics. Nevertheless, they are cumbersome to the patient and carry the risk of significant graft injury. Notably, they cannot be performed on patients taking anticoagulant drugs. Therefore, a noninvasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review SPECT- and PET-based approaches for noninvasive molecular imaging-based diagnostics of acute transplant rejection.

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

    Science.gov (United States)

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

    2004-01-01

    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.

  19. Anterior cruciate ligament reconstruction with allograft tendons.

    Science.gov (United States)

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

    2003-01-01

    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.

  20. Anterior cruciate ligament reconstruction with allograft tendons.

    Science.gov (United States)

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

    2003-01-01

    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. PMID:12735200

  1. Tertiary centres have improved survival compared to other hospitals in the Copenhagen area after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Søholm, Helle; Wachtell, Kristian; Nielsen, Søren Loumann;

    2013-01-01

    AIMS: Out-of-hospital cardiac arrest (OHCA) has been reported to carry very varying morbidity and mortality. However, it remains unclear whether this is caused by intrinsic factors of the OHCA or due to the level of in-hospital care. The aim of this study is to compare 30-day and long......-term mortality after OHCA at tertiary heart centres and non-tertiary university hospitals. METHODS AND RESULTS: Data from the Copenhagen OHCA registry from June 2002 through December 2010 included a total of 1218 consecutive patients treated by the same mobile emergency care unit (MECU) with either return...... angiography. Therefore, patients with ST-elevation myocardial infarction (n=198) were excluded from the analysis. 30-day mortality was 56% vs. 76% and long term (up to 8years) mortality was 78% vs. 94% for tertiary and non-tertiary hospitals, respectively, both p...

  2. Urinary calprotectin and posttransplant renal allograft injury

    DEFF Research Database (Denmark)

    Tepel, Martin; Borst, Christoffer; Bistrup, Claus;

    2014-01-01

    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...... 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....

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

    Directory of Open Access Journals (Sweden)

    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

  4. Pathological changes after bone marrow and skin allograft transplantation in rats inflicted with severe combined radiation-burn injury

    International Nuclear Information System (INIS)

    Bone marrow and skin allografts from the same donor were transplanted to rats inflicted with 8 Gy γ-radiation combined with third degree burns of 15% body surface area within 6 hr post injury. Pathological changes of hematopoietic tissues and skin allografts were studied. All injured controls died within 7 days post injury without bone marrow regeneration; 50% of treated rats survived with living skin allografts on 50th day post injury. On days 100 and 480 post operation, grafted skin still survived well on recipients with normal ultrastructure. Epidermic cells of skin allografts proliferated on day 5, developed and repaired on day 10. Histological structure of the skin returned to normal on day 30 post operation. The regeneration of bone marrow appeared on 5th day, increased markedly on day 10, and almost completed on day 15 after bone marrow transplantation. However, the regeneration of lymphocytes in cortex of spleen and lymph nodes did not appear until day 15 of BMT. The results show that bone marrow and skin allograft transplantation at early time post injury in most severe combined radiation-burn injury have tremendous beneficial effects, and the skin allograft can survive for a long time

  5. Mucormycosis (zygomycosis) of renal allograft.

    Science.gov (United States)

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

    2012-12-01

    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.

  6. Leiomyoma in a Renal Allograft

    Directory of Open Access Journals (Sweden)

    Yan Jun Li

    2016-01-01

    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.

  7. Laparoscopic cholecystectomy in a cardiac transplant recipient

    OpenAIRE

    Pandya, Seema R.; Saloni Paranjape

    2014-01-01

    An increasing number of cardiac transplants are being carried out around the world. With increasing longevity, these patients present a unique challenge to non-transplant anesthesiologists for a variety of transplant related or incidental surgeries. The general considerations related to a cardiac transplant recipient are the physiological and pharmacological problems of allograft denervation, the side-effects of immunosuppression, the risk of infection and the potential for rejection. A thoro...

  8. Clinical Outcomes of Cryopreserved Arterial Allograft Used as a Vascular Conduit for Hemodialysis.

    Science.gov (United States)

    Ha, Tae-Yong; Kim, Young Hoon; Chang, Jai Won; Park, Yangsoon; Han, Youngjin; Kwon, Hyunwook; Kwon, Tae-Won; Han, Duck Jong; Cho, Yong-Pil; Lee, Sung-Gyu

    2016-08-01

    This single center cohort study aimed to test the hypothesis that use of a cryopreserved arterial allograft could avoid the maturation or healing process of a new vascular access and to evaluate the patency of this technique compared with that of vascular access using a prosthetic graft. Between April 2012 and March 2013, 20 patients underwent an upper arm vascular access using a cryopreserved arterial allograft for failed or failing vascular accesses and 53 using a prosthetic graft were included in this study. The mean duration of catheter dependence, calculated as the time interval from upper arm access placement to removal of the tunneled central catheter after successful cannulation of the access, was significantly longer for accesses using a prosthetic graft than a cryopreserved arterial allograft (34.4 ± 11.39 days vs. 4.9 ± 8.5 days, P unassisted; P = 0.314) and cumulative (assisted; P = 0.673) access survivals were similar in the two groups. There were no postoperative complications related to the use of a cryopreserved iliac arterial allograft except for one patient who experienced wound hematoma. In conclusion, upper arm vascular access using a cryopreserved arterial allograft may permit immediate hemodialysis without the maturation or healing process, resulting in access survival comparable to that of an access using a prosthetic graft. PMID:27478338

  9. Clinical Outcomes of Cryopreserved Arterial Allograft Used as a Vascular Conduit for Hemodialysis

    Science.gov (United States)

    Ha, Tae-Yong; Kim, Young Hoon; Chang, Jai Won; Park, Yangsoon; Han, Youngjin; Kwon, Hyunwook; Kwon, Tae-Won; Han, Duck Jong; Lee, Sung-Gyu

    2016-01-01

    This single center cohort study aimed to test the hypothesis that use of a cryopreserved arterial allograft could avoid the maturation or healing process of a new vascular access and to evaluate the patency of this technique compared with that of vascular access using a prosthetic graft. Between April 2012 and March 2013, 20 patients underwent an upper arm vascular access using a cryopreserved arterial allograft for failed or failing vascular accesses and 53 using a prosthetic graft were included in this study. The mean duration of catheter dependence, calculated as the time interval from upper arm access placement to removal of the tunneled central catheter after successful cannulation of the access, was significantly longer for accesses using a prosthetic graft than a cryopreserved arterial allograft (34.4 ± 11.39 days vs. 4.9 ± 8.5 days, P unassisted; P = 0.314) and cumulative (assisted; P = 0.673) access survivals were similar in the two groups. There were no postoperative complications related to the use of a cryopreserved iliac arterial allograft except for one patient who experienced wound hematoma. In conclusion, upper arm vascular access using a cryopreserved arterial allograft may permit immediate hemodialysis without the maturation or healing process, resulting in access survival comparable to that of an access using a prosthetic graft.

  10. Clinical Outcomes of Cryopreserved Arterial Allograft Used as a Vascular Conduit for Hemodialysis.

    Science.gov (United States)

    Ha, Tae-Yong; Kim, Young Hoon; Chang, Jai Won; Park, Yangsoon; Han, Youngjin; Kwon, Hyunwook; Kwon, Tae-Won; Han, Duck Jong; Cho, Yong-Pil; Lee, Sung-Gyu

    2016-08-01

    This single center cohort study aimed to test the hypothesis that use of a cryopreserved arterial allograft could avoid the maturation or healing process of a new vascular access and to evaluate the patency of this technique compared with that of vascular access using a prosthetic graft. Between April 2012 and March 2013, 20 patients underwent an upper arm vascular access using a cryopreserved arterial allograft for failed or failing vascular accesses and 53 using a prosthetic graft were included in this study. The mean duration of catheter dependence, calculated as the time interval from upper arm access placement to removal of the tunneled central catheter after successful cannulation of the access, was significantly longer for accesses using a prosthetic graft than a cryopreserved arterial allograft (34.4 ± 11.39 days vs. 4.9 ± 8.5 days, P unassisted; P = 0.314) and cumulative (assisted; P = 0.673) access survivals were similar in the two groups. There were no postoperative complications related to the use of a cryopreserved iliac arterial allograft except for one patient who experienced wound hematoma. In conclusion, upper arm vascular access using a cryopreserved arterial allograft may permit immediate hemodialysis without the maturation or healing process, resulting in access survival comparable to that of an access using a prosthetic graft.

  11. Renal allografts from pediatric donors after cardiac death:One case report%儿童心脏死亡器官捐献与肾脏移植1例报告★

    Institute of Scientific and Technical Information of China (English)

    杨顺良; 郭君其; 张伟; 吴晓智; 高霞; 蔡锦全; 谭建明

    2013-01-01

    death legislation and diagnostic criteria, the Ministry of Health and the Red Cross Society of China have jointly promote the cardiac death organ donation. OBJECTIVE: To investigate the feasibility of organ donation from pediatric donors after cardiac death. METHODS: One case of organ donation from a pediatric donor at Fuzhou General Hospital of Nanjing Military Command of PLA was retrospectively analyzed combined with the analysis of the literatures. RESULTS AND CONCLUSION: A 4-year-old boy was independently diagnosed with brain death after cardiopulmonary resuscitation by two groups of specialists at an interval of 24 hours. The criteria included the Diagnostic Criteria for Brain Death (for adults), the Technological Specification for Brain Death (for adults) and atropine test results. The donor parents should be informed and consent with the donor programs and ful y expressed the donation wil ingness, and the program should be approved by the hospital ethics committee. The fol owing steps including donation application, approval, transportation, organ maintaining, mechanical support removal and organ recovery were conducted according to the organ donation guidelines in China after cardiac death. The warm ischemia time was 13 minutes. Two renal grafts were transplanted to two uremic recipients selected by age, weight and human leukocyte antigen matching. The left kidney recipient was a 13-year-old female patient and the right kidney recipient was a 35-year-old female patient. No complications such as delayed graft function, renal graft vascular thrombosis, urinary fistula or ureteral obstruction were observed. The graft length was increased from 7 cm postoperation to 10 cm at 1 year after operation, with negative proteinuria, serum creatinine of 60 μmol/L and estimated glomerular filtration rate was ranged from 70 to 150 mL/min. No long term complications such as serious infections, hypertension, diabetes, hyperlipidemia or liver dysfunction were observed. The

  12. Effect of α-GalCer-activated natural killer T cell on survival of allograft with high-risk rejection after retrobubar injection%α-GalCer活化的自然杀伤T细胞对高危角膜移植后排斥反应的防治作用

    Institute of Scientific and Technical Information of China (English)

    宫妍; 宋丽艳; 孙海成

    2012-01-01

    活时间,为角膜移植排斥反应的防治提供了新的手段.%Background Corneal graft reject is a major cause of corneal transplantation failure.Although many immune-suppressing drugs have been utilized to reduce the reject response,their adverse effects on organ and tissue are still insoluble.The tolerance induction of natural killer T (NKT) cells is currently under investigation.However,the study on the application of NKT cells in high risk corneal transplantation is seldom. Objective The present study was to explore the effects of α-GalCer-activated NKT cella on allografts survival after high-risk corneal transplantation surgery via retro-bubar injection. Methods The lymphocytes were picked up from the spleen of SPF Lewis rats and cultured in RPMI 1640 medium with 100 mg/L α-GalCer.After one week,NKT cells were sorted by the FACSVantage system as CD161+ TCR-α+ cell from the lymphocytes with the cell densities 5×106/ml.Ten SPF Fisher344 rats were used to prepare the donor corneas,and 20 Lewis rats served as recipients.The high risk corneal transplantation models were created by corneal suturing in 20 recipient rats.Penetrating keratoplasty (PKP) was performed in the model rats.0.1 ml NKT cells or the same volume of normal saline solution were retro-bubarly injected at the end of surgery respectively.The corneal allografts were observed and scored based on Holland criteria at the three-day interval under the slit lamp for 30 days.Two weeks after surgery,three rats from each group were sacrificed by excessive anesthesia method and the eyeballs were obtained for histopathological examination.The inflammatory cell infiltration ( CD4+ and CD8+ ) in grafts was evaluated by immunochemistry and flow cytometry.The use of the animals complied with the Statement of ARVO. Results The mean survival time of the allografts was (7.90± 1.37) days in normal saline solution group and (14.70± 1.49) days in NKT cell group,showing a statistically significant difference

  13. Chronic lung allograft dysfunction after lung transplantation: novel insights into immunological mechanisms

    NARCIS (Netherlands)

    Budding, K.

    2016-01-01

    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

  14. Significance and suppression of redundant IL17 responses in acute allograft rejection by bioinformatics based drug repositioning of fenofibrate.

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    Full Text Available Despite advanced immunosuppression, redundancy in the molecular diversity of acute rejection (AR often results in incomplete resolution of the injury response. We present a bioinformatics based approach for identification of these redundant molecular pathways in AR and a drug repositioning approach to suppress these using FDA approved drugs currently available for non-transplant indications. Two independent microarray data-sets from human renal allograft biopsies (n = 101 from patients on majorly Th1/IFN-y immune response targeted immunosuppression, with and without AR, were profiled. Using gene-set analysis across 3305 biological pathways, significant enrichment was found for the IL17 pathway in AR in both data-sets. Recent evidence suggests IL17 pathway as an important escape mechanism when Th1/IFN-y mediated responses are suppressed. As current immunosuppressions do not specifically target the IL17 axis, 7200 molecular compounds were interrogated for FDA approved drugs with specific inhibition of this axis. A combined IL17/IFN-y suppressive role was predicted for the antilipidemic drug Fenofibrate. To assess the immunregulatory action of Fenofibrate, we conducted in-vitro treatment of anti-CD3/CD28 stimulated human peripheral blood cells (PBMC, and, as predicted, Fenofibrate reduced IL17 and IFN-γ gene expression in stimulated PMBC. In-vivo Fenofibrate treatment of an experimental rodent model of cardiac AR reduced infiltration of total leukocytes, reduced expression of IL17/IFN-y and their pathway related genes in allografts and recipients' spleens, and extended graft survival by 21 days (p<0.007. In conclusion, this study provides important proof of concept that meta-analyses of genomic data and drug databases can provide new insights into the redundancy of the rejection response and presents an economic methodology to reposition FDA approved drugs in organ transplantation.

  15. Generation of suppressive blood cells for control of allograft rejection.

    Science.gov (United States)

    Kleist, Christian; Sandra-Petrescu, Flavius; Jiga, Lucian; Dittmar, Laura; Mohr, Elisabeth; Greil, Johann; Mier, Walter; Becker, Luis E; Lang, Peter; Opelz, Gerhard; Terness, Peter

    2015-05-01

    Our previous studies in rats showed that incubation of monocytic dendritic cells (DCs) with the chemotherapeutic drug mitomycin C (MMC) renders the cells immunosuppressive. Donor-derived MMC-DCs injected into the recipient prior to transplantation prolonged heart allograft survival. Although the generation of DCs is labour-intensive and time-consuming, peripheral blood mononuclear cells (PBMCs) can be easily harvested. In the present study, we analyse under which conditions DCs can be replaced by PBMCs and examine their mode of action. When injected into rats, MMC-incubated donor PBMCs (MICs) strongly prolonged heart allograft survival. Removal of monocytes from PBMCs completely abrogated their suppressive effect, indicating that monocytes are the active cell population. Suppression of rejection was donor-specific. The injected MICs migrated into peripheral lymphoid organs and led to an increased number of regulatory T-cells (Tregs) expressing cluster of differentiation (CD) markers CD4 and CD25 and forkhead box protein 3 (FoxP3). Tolerance could be transferred to syngeneic recipients with blood or spleen cells. Depletion of Tregs from tolerogenic cells abrogated their suppressive effect, arguing for mediation of immunosuppression by CD4⁺CD25⁺FoxP3⁺ Tregs. Donor-derived MICs also prolonged kidney allograft survival in pigs. MICs generated from donor monocytes were applied for the first time in humans in a patient suffering from therapy-resistant rejection of a haploidentical stem cell transplant. We describe, in the present paper, a simple method for in vitro generation of suppressor blood cells for potential use in clinical organ transplantation. Although the case report does not allow us to draw any conclusion about their therapeutic effectiveness, it shows that MICs can be easily generated and applied in humans.

  16. Use of CTLA4Ig for induction of mixed chimerism and renal allograft tolerance in nonhuman primates.

    Science.gov (United States)

    Yamada, Y; Ochiai, T; Boskovic, S; Nadazdin, O; Oura, T; Schoenfeld, D; Cappetta, K; Smith, R-N; Colvin, R B; Madsen, J C; Sachs, D H; Benichou, G; Cosimi, A B; Kawai, T

    2014-12-01

    We have previously reported successful induction of renal allograft tolerance via a mixed chimerism approach in nonhuman primates. In those studies, we found that costimulatory blockade with anti-CD154 mAb was an effective adjunctive therapy for induction of renal allograft tolerance. However, since anti-CD154 mAb is not clinically available, we have evaluated CTLA4Ig as an alternative agent for effecting costimulation blockade in this treatment protocol. Two CTLA4Igs, abatacept and belatacept, were substituted for anti-CD154 mAb in the conditioning regimen (low dose total body irradiation, thymic irradiation, anti-thymocyte globulin and a 1-month posttransplant course of cyclosporine [CyA]). Three recipients treated with the abatacept regimen failed to develop comparable lymphoid chimerism to that achieved with anti-CD154 mAb treatment and these recipients rejected their kidney allografts early. With the belatacept regimen, four of five recipients developed chimerism and three of these achieved long-term renal allograft survival (>861, >796 and >378 days) without maintenance immunosuppression. Neither chimerism nor long-term allograft survival were achieved in two recipients treated with the belatacept regimen but with a lower, subtherapeutic dose of CyA. This study indicates that CD28/B7 blockade with belatacept can provide a clinically applicable alternative to anti-CD154 mAb for promoting chimerism and renal allograft tolerance.

  17. Heart Allograft Tolerance Induced and Maintained by Vascularized Hind-Limb Transplant in Rats

    Directory of Open Access Journals (Sweden)

    Quan Liu

    2013-01-01

    Full Text Available Organ/tissue transplantation has become an effective therapy for end-stage diseases. However, immunosuppression after transplantation may cause severe side effects. Donor-specific transplant tolerance was proposed to solve this problem. In this study, we report a novel method for inducing and maintaining heart allograft tolerance rats. First, we induced indefinite vascularized hind-limb allograft survival with a short-term antilymphocyte serum + Cyclosporine A treatment. Peripheral blood chimerism disappeared 6-7 weeks after immunosuppression was withdrawn. Then the recipients accepted secondary donor-strain skin and heart transplantation 200 days following vascularized hind-limb transplantation without any immunosuppression, but rejected third party skin allografts, a status of donor-specific tolerance. The ELISPOT results suggested a mechanism of clone deletion. These findings open new perspectives for the role of vascularized hind-limb transplant in the induction and maintenance of organ transplantation tolerance.

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

    International Nuclear Information System (INIS)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-12-01

    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).

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

    Science.gov (United States)

    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

    2009-01-01

    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. (http://ClinicalTrials.gov; NCT-00702247.) PMID:19064724

  1. Pilot study exploring lung allograft surfactant protein A (SP-A) expression in association with lung transplant outcome.

    Science.gov (United States)

    D'Ovidio, F; Kaneda, H; Chaparro, C; Mura, M; Lederer, D; Di Angelo, S; Takahashi, H; Gutierrez, C; Hutcheon, M; Singer, L G; Waddell, T K; Floros, J; Liu, M; Keshavjee, S

    2013-10-01

    Primary graft failure and chronic lung allograft dysfunction (CLAD) limit lung transplant long-term outcomes. Various lung diseases have been correlated with surfactant protein (SP) expression and polymorphisms. We sought to investigate the role of SP expression in lung allografts prior to implantation, in relation to posttransplant outcomes. The expression of SP-(A, B, C, D) mRNA was assayed in 42 allografts. Posttransplant assessments include pulmonary function tests, bronchoscopy, broncho-alveolar lavage fluid (BALF) and biopsies to determine allograft rejection. BALF was assayed for SP-A, SP-D in addition to cytokines IL-8, IL-12 and IL-2. The diagnosis of CLAD was evaluated 6 months after transplantation. Lung allografts with low SP-A mRNA expression prior to implantation reduced survival (Log-rank p < 0.0001). No association was noted for the other SPs. Allografts with low SP-A mRNA had greater IL-2 (p = 0.03) and IL-12 (p < 0.0001) in the BALF and a greater incidence of rejection episodes (p = 0.003). Levels of SP-A mRNA expression were associated with the SP-A2 polymorphisms (p = 0.015). Specifically, genotype 1A1A(0) was associated with lower SP-A mRNA expression (p < 0.05). Lung allografts with low levels of SP-A mRNA expression are associated with reduced survival. Lung allograft SP-A mRNA expression appears to be associated with SP-A gene polymorphisms.

  2. Enzymes for Pancreatic Islet Isolation Impact Chemokine-Production and Polarization of Insulin-Producing β-Cells with Reduced Functional Survival of Immunoisolated Rat Islet-Allografts as a Consequence.

    Science.gov (United States)

    de Vos, Paul; Smink, Alexandra M; Paredes, Genaro; Lakey, Jonathan R T; Kuipers, Jeroen; Giepmans, Ben N G; de Haan, Bart J; Faas, Marijke M

    2016-01-01

    The primary aim of this study was to determine whether normal variations in enzyme-activities of collagenases applied for rat-islet isolation impact longevity of encapsulated islet grafts. Also we studied the functional and immunological properties of rat islets isolated with different enzyme preparations to determine whether this impacts these parameters. Rat-islets were isolated from the pancreas with two different collagenases with commonly accepted collagenase, neutral protease, and clostripain activities. Islets had a similar and acceptable glucose-induced insulin-release profile but a profound statistical significant difference in production of the chemokines IP-10 and Gro-α. The islets were studied with nanotomy which is an EM-based technology for unbiased study of ultrastructural features of islets such as cell-cell contacts, endocrine-cell condition, ER stress, mitochondrial conditions, and cell polarization. The islet-batch with higher chemokine-production had a lower amount of polarized insulin-producing β-cells. All islets had more intercellular spaces and less interconnected areas with tight cell-cell junctions when compared to islets in the pancreas. Islet-graft function was studied by implanting encapsulated and free islet grafts in rat recipients. Alginate-based encapsulated grafts isolated with the enzyme-lot inducing higher chemokine production and lower polarization survived for a two-fold shorter period of time. The lower survival-time of the encapsulated grafts was correlated with a higher influx of inflammatory cells at 7 days after implantation. Islets from the same two batches transplanted as free unencapsulated-graft, did not show any difference in survival or function in vivo. Lack of insight in factors contributing to the current lab-to-lab variation in longevity of encapsulated islet-grafts is considered to be a threat for clinical application. Our data suggest that seemingly minor variations in activity of enzymes applied for islet

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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.

  4. 腺病毒介导的hCTLA4-Ig和FasL基因转移诱导大鼠同种异体肾移植长期存活的作用%Adenovirus-mediated CTLA4-Ig and FasL gene transfer induces long-term survival of renal allografts in rats

    Institute of Scientific and Technical Information of China (English)

    平季根; 温端改; 侯建全; 吕金星; 严春寅

    2009-01-01

    Objective To investigate the potential role of adenovirus-CTLA4-Ig and adenovirus-FasL recombinant in inducing transplantation tolerance using renal-graft model and its related mecha-nisms. Methods Allogeneic kidney transplants were performed between SD donors and Wistar recipients. The experimental rats were divided into 4 groups. In Ad-CTLA4-Ig group and Ad-CTLA4-Ig + Ad-FasL group, the donor kidney of the SD rats was locally transfected by Ad-CTLA4-Ig and Ad-CTLA4-Ig + Ad-FasL with the dose of 1 × 10~9-5 × 10~9 PFUml respectively and then transplanted to the recipient Wistar rats. In control group, the kidneys of the SD rats were directly transplanted to Wistar rats without any thera-py. The rats treated with Ad-EGFP served as empty vector group. After kidney transplantation, the survival time and the kidney function in each group were observed. Kidney allografts were evaluated by HE staining and immunohistochemical staining. The pathological features and ultrastructures of the grafts were ob-served. Results The survival time of allografts were prolonged significantly in recipients receiving Ad-CT-LA4-Ig + Ad-FasL with a mean survival time of (64.67 ± 6.41) days ,significantly longer than that in Ad-CTLA4-Ig treated group (31.33±6.77) days,control group (8.17 ± 1.17) days and empty vector group (8.00 ± 1.55) days (P < 0.01). After transplantation, the levels of creatinine in serum were significantly higher in control group and empety vector group than in Ad-CTLA4-Ig + Ad-FasL treated group and Ad-CTLA4-Ig treated group. Conclusion Adenoviral vectors can be successfully transduced into rat kidneys with the CTLA4-Ig and FasL cDNA. Ad-mediated transduction of the CTLA4-Ig and FasL gene can signifi-cantly prolong the survival of rat renal allograft. The induced tolerance is donor specific, and may result from regulatory T cells and the deletion of alloreactive T cells.%目的 探讨腺病毒介导hCTLA4-Ig和FasL基因转移延长异基因大鼠肾移植物

  5. Future of allografts in sports medicine.

    Science.gov (United States)

    Harner, Christopher D; Lo, Marvin Y

    2009-04-01

    Allografts play a prominent role in sports medicine, and their usage has increased dramatically over the past few decades, but the role of allograft in the future of sports medicine largely depends on several factors: (1) the ability of the tissue banking industry to convince both surgeons and the general population that tissue procurement is safe and nearly disease-free, (2) the ability to sterilize tissue with minimal compromise to tissue integrity, (3) successful clinical outcomes with allograft, and (4) the advent of artificial scaffolds and ligaments that function as well. PMID:19306738

  6. Allograft safety in anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Cohen, Steven B; Sekiya, Jon K

    2007-10-01

    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.

  7. Allograft safety in anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Cohen, Steven B; Sekiya, Jon K

    2007-10-01

    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. PMID:17920955

  8. Histidine-tryptophan-ketoglutarate for pancreas allograft preservation: the Indiana University experience.

    Science.gov (United States)

    Fridell, J A; Mangus, R S; Powelson, J A

    2010-05-01

    Histidine-tryptophan-ketoglutarate solution (HTK) has been scrutinized for use in pancreas transplantation. A recent case series and a United Network for Organ Sharing data base review have suggested an increased incidence of allograft pancreatitis and graft loss with HTK compared to the University of Wisconsin solution (UW). Conversely, a recent randomized, controlled study failed to show any significant difference between HTK and UW for pancreas allograft preservation. This study was a retrospective review of all pancreas transplants performed at Indiana University between 2003 and 2009 comparing preservation with HTK or UW. Data included recipient and donor demographics, 7-day, 90-day and 1-year graft survival, peak 30-day serum amylase and lipase, HbA1c and C-peptide levels. Of the 308 pancreas transplants, 84% used HTK and 16% UW. There were more SPK compared to pancreas after kidney and pancreas transplant alone in the HTK group. Donor and recipient demographics were similar. There was no significant difference in 7-day, 90-day or 1-year graft survival, 30-day peak serum amylase and lipase, HbA1c or C-peptide. No clinically significant difference between HTK and UW for pancreas allograft preservation was identified. Specifically, in the context of low-to-moderate flush volume and short cold ischemia time (allograft pancreatitis or graft loss was observed. PMID:20353471

  9. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    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)

  10. Graft enhancement and antiidiotypic antibody. Lymphocytes from long-term rat renal allograft recipients have normal responsiveness in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Fitch, F.W.; Weiss, A.; McKearn, T.J.; Stuart, F.P.

    1978-06-01

    Treatment of allograft recipients with antigen Ag and antibody Ab causes a transient appearance of anti-Id antibody, and kidneys transplanted at the time of peak anti-Id response fare better than those transplanted earlier or later. Since these observations suggested a role for anti-Id Ab in rat renal allograft enhancement, the immunologic reactivity of lymphocytes from animals bearing long-term, enhanced renal allografts was studied. The survival of long-term enhanced renal allografts remains an enigma. Although anti-Id Ab is produced as a result of the initial treatment used for induction of enhancement, such Ab is not detected in long-term recipients. The reactivity of cells from such recipients is not that reported for animals actively producing anti-Id Ab. The responsiveness of lymphocytes in vitro from long-term allograft recipients appears to be normal, not increased as observed in sensitized rats or absent as observed in neonatally tolerant rats. It is not known why these cells fail to respond to graft antigens in the enhanced allograft recipient. Inhibitory processes that function in the intact animal seem to be inactive in the experimental systems used for measurement of lymphocyte responsiveness in culture.

  11. Renal allograft rejection: sonography and scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; Cohen, W.N.

    1980-07-01

    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.

  12. Computational Biology: Modeling Chronic Renal Allograft Injury.

    Science.gov (United States)

    Stegall, Mark D; Borrows, Richard

    2015-01-01

    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.

  13. 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

    Directory of Open Access Journals (Sweden)

    Camila T. Lopes

    2008-01-01

    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

  14. Collaborative effects of bystander-initiated cardiopulmonary resuscitation and prehospital advanced cardiac life support by physicians on survival of out-of-hospital cardiac arrest: a nationwide population-based observational study

    OpenAIRE

    Yasunaga, Hideo; Horiguchi, Hiromasa; Tanabe, Seizan; Akahane, Manabu; OGAWA, Toshio; Koike, Soichi; Imamura, Tomoaki

    2010-01-01

    Introduction There are inconsistent data about the effectiveness of prehospital physician-staffed advanced cardiac life support (ACLS) on the outcomes of out-of-hospital cardiac arrest (OHCA). Furthermore, the relative importance of bystander-initiated cardiopulmonary resuscitation (BCPR) and ACLS and the effectiveness of their combination have not been clearly demonstrated. Methods Using a prospective, nationwide, population-based registry of all OHCA patients in Japan, we enrolled 95,072 pa...

  15. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  16. Donation after cardiac death in abdominal organ transplantation.

    Science.gov (United States)

    Reich, David J; Guy, Stephen R

    2012-01-01

    This article reviews the field of donation after cardiac death, focusing on the history, ethicolegal issues, clinical outcomes, best practices, operative techniques, and emerging strategies to optimize utilization of this resource. Donation after cardiac death is one effective way to decrease the organ shortage and has contributed the largest recent increase in abdominal organ allografts. Currently, donation after cardiac death organs confer an increased risk of ischemic cholangiopathy after liver transplant and of delayed graft function after kidney transplant. As this field matures, risk factors for donation after cardiac death organ transplant will be further identified and clinical outcomes will improve as a result of protocol standardization and ongoing research. PMID:22678860

  17. Ipsilateral Lymphadenectomy to Inhibit Corneal Allograft Rejection in Rats

    Institute of Scientific and Technical Information of China (English)

    LING Shiqi; HU Yanhua

    2005-01-01

    In order to investigate the ipsilateral lymphadenectomy for inhibiting rejection in rat corneal transplantation, corneal allogenic transplantation models were established in rats. Eighteen female Wister rats were used as donors, and 36 Sprague Dawley rats as recipients. After penetrating corneal transplantation, recipients were randomly divided into 3 groups: group A (control group);group B, the ipsilateral lymphadenectomy group; group C, the bilateral lymphadenectomy group.Among 12 rats in each group, the corneas of 2 rats in each group were used for pathological study at day 14 after the transplantation, and the remaining 10 rats were used for studying corneal rejection by a slit lamp. The time points when allograft rejection occurred were recorded and mean survival time (MST) was compared. The results showed that MST in groups B and C was 46.30±9.464 days and 44.43 ± 7. 604 days, respectively, which was significantly prolonged as compared with that in group A (10.71±1. 567 days, P<0.01). There was no significant difference in MST between groups B and C (P>0.05). Itwas concluded that both bilateral and ipsilateral lymphadenectomy therapies could effectively inhibit the corneal allograft rejection. Ipsilateral lymphadenectomy is a less complex surgical procedure and is just as effective in preventing rejection.

  18. Down regulation of genes involved in T cell polarity and motility during the induction of heart allograft tolerance by allochimeric MHC I.

    Directory of Open Access Journals (Sweden)

    Wojciech Lisik

    Full Text Available BACKGROUND: The allochimeric MHC class I molecule [alpha1h1/u]-RT1.Aa that contains donor-type (Wistar Furth, WF; RT1u epitopes displayed on recipient-type (ACI, RT1a administered in conjunction with sub-therapeutic dose of cyclosporine (CsA induces indefinite survival of heterotopic cardiac allografts in rat model. In vascularized transplantation models, the spleen contributes to graft rejection by generating alloantigen reactive T cells. The immune response in allograft rejection involves a cascade of molecular events leading to the formation of immunological synapses between T cells and the antigen-presenting cells. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the molecular pathways involved in the immunosuppressive function of allochimeric molecule we performed microarray and quantitative RTPCR analyses of gene expression profile of splenic T cells from untreated, CsA treated, and allochimeric molecule + subtherapeutic dose of CsA treated animals at day 1, 3 and 7 of post transplantation. Allochimeric molecule treatment caused down regulation of genes involved in actin filament polymerization (RhoA and Rac1, cell adhesion (Catna1, Vcam and CD9, vacuolar transport (RhoB, Cln8 and ATP6v1b2, and MAPK pathway (Spred1 and Dusp6 involved in tubulin cytoskeleton reorganization and interaction between actin and microtubule cytoskeleton. All these genes are involved in T cell polarity and motility, i.e., their ability to move, scan and to form functional immunological synapse with antigen presenting cells (APCs. CONCLUSIONS: These results indicate that the immunosuppressive function of allochimeric molecule may depend on the impairment of T cells' movement and scanning ability, and possibly also the formation of immunological synapse. We believe that these novel findings may have important clinical implications for organ transplantation.

  19. Radionuclide surveillance of the allografted pancreas

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-04-01

    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

  20. Application of anti-CD103 immunotoxin for saving islet allograft in context of transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lei; Gregg A. Hadley

    2010-01-01

    Background Previous studies using knockout mice document a key role for the integrin CD103 in promoting organ allograft rejection and graft-versus-host disease. However, a determination of whether blockade of the CD103 pathway represents a viable therapeutic strategy for intervention in these processes has proven problematic due to the lack of reagents that efficiently deplete CD103+ cells from wild type hosts. To circumvent this problem, in the present study, we invented an anti-CD103 immunotoxin (M290-SAP). We investigated whether M290-SAP has capacity to eliminate CD103-expressing cells in vivo and protect transplanted islets from destroying by host immune cells.Methods Flow cytometry was used to analyze the efficacy of M290-SAP in depleting CD103-expressing cells in vivo.Then using allogenic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, the therapeutic efficacy of CD103-expressing cell depletion was addressed.Results M290-SAP dramatically reduces the frequency and absolute numbers of CD103-expressing leukocytes in peripheral lymphatic tissues of treated mice. Balb/c islets transplanted into streptozotocin-induced diabetic C57BL/6 mice under single M290-SAP treatment showed an indefinite survival time compared with untreated mice, M290-treated mice and IgG-SAP treated mice (mean survival time, >100 days vs. <20 days). C57BL/6 islets transplanted into hyperglycemic NOD mice under single M290-SAP treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time 12-13 days vs. <7 days). Immunological analysis of mice with long-term islet allograft survival revealed an obvious atrophy thymus and severe downregulation of alloimmunity of CD8 subpopulation response to allogenic stimulation.Conclusion Regardless of the underlying mechanisms, these data document that depletion of CD103-expressing cells represents a viable strategy for therapeutic intervention in islet allograft

  1. Cutting edge: membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection.

    Science.gov (United States)

    Guo, Z; Wang, J; Meng, L; Wu, Q; Kim, O; Hart, J; He, G; Zhou, P; Thistlethwaite, J R; Alegre, M L; Fu, Y X; Newell, K A

    2001-11-01

    Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4(+) T cells are necessary for rejection. When CD8(+) T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8(+) T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8(+) T cells. This effect was associated with decreased monokine induced by IFN-gamma (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4(+) T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8(+) T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection. PMID:11673481

  2. Intercalary Reconstructions with Vascularised Fibula and Allograft after Tumour Resection in the Lower Limb

    Directory of Open Access Journals (Sweden)

    Katharina Rabitsch

    2013-01-01

    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.

  3. Chronic Kidney Isograft and Allograft Rejection

    Institute of Scientific and Technical Information of China (English)

    严群; 张鹏; 杨传永

    2002-01-01

    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.

  4. Prolonged rat liver allograft survival by in vivo targeting OX40-siRNA OX40-OX40L co-stimulatory cascade blockade%靶向OX40基因的siRNA抑制大鼠肝脏移植排斥反应的研究

    Institute of Scientific and Technical Information of China (English)

    武聚山; 夏仁品; 卢实春; 张毅; 娄金丽; 李宁

    2008-01-01

    目的 探讨RNA干扰阻断OX40-OX40L共刺激通路对大鼠移植肝存活时间的影响.方法 制作原位肝脏移植物大鼠模型,供体DA大鼠,受体Lewis大鼠.移植术毕时将5 ml含5×109pfu的pLVTHM-OX40-siRNA重组慢病毒经阴茎背静脉在10秒内注射受鼠体内,术后观察受鼠存活时间,移植肝脏进行组织病理学检查,采用ELISA法检测大鼠外周血IL-2、IFN-γ的水平,并进行受者大鼠脾细胞对供者大鼠脾细胞的混和淋巴细胞反应(MLR). 结果转染组大鼠肝脏移植物的存活时间为(74.0±9.3)d,明显长于对照组(7.3±0.5)d和未转染组(7.5±0.5)d;转染组移植肝组织炎细胞浸润、间质水肿、肝组织坏死程度较对照组和未转染组减轻;耐受组大鼠脾脏中T淋巴细胞刺激T淋巴细胞增殖的能力较对照组降低(t=25.1,P<0.01);移植术后第7 d,转染组血清IL-2浓度为(46±8.4)pg/ml,IFN-γ浓度为(202.7±14.6)pg/ml,均显著低于对照组和未转染组(分别t=176.4,45.5,P<0.01).结论 转染靶向OX40的siRNA,可通过阻断OX40-OX40L共刺激通路,抑制大鼠肝脏移植后的排斥反应,延长大鼠移植肝的存活时间.%Objective To investigate the effect of blockading OX40-OX40L co-stimulatory signaling on the survival time of liver allograft in rat.Methods siRNA-expression vectors were constructed to targeting OX40.3~5 minutes before DA to Lewis orthotopic liver transplantation was performed,5×109 pfu of targeting OX40 siRNA plasmid DNA were diluted in 5 ml of phosphate buffered saline(PBS)and inlected intravenously into recipient Lewis rat over a period of 10 seconds.Serum IL-2 and IFN-γ levels were assayed by ELISA,and mix lymphocyte response(MLR)were tested by 3H-thymidine.Results The survival time of recipients in siRNA treatment group(74.0±9.3)was significantly longer than that in control group[(7.3±0.5)days].In experiment group,the inflammatory cell infihration and liver tissue structure destruction were very slight

  5. 移植肾平滑肌瘤1例%Leiomyoma in renal allograft in one case

    Institute of Scientific and Technical Information of China (English)

    王志文; 陈桦; 刘永光; 李民; 赵明

    2011-01-01

    背景:移植肾平滑肌瘤的发生将对移植肾有不同程度的影响,甚至威胁移植肾的长期存活.目的:报告1例移植肾平滑肌瘤的诊治经验.方法:回顾性分析1例患者为男性,53岁,11年前因"尿毒症"在外院行右同种异体肾移植,移植后肾功能恢复正常,长期口服免疫抑制剂抗排斥治疗,患者的临床资料.结果与结论:移植肾平滑肌瘤确诊主要依靠病理检查,影像学无明显特异性.移植肾平滑肌瘤的治疗以单纯手术切除肿瘤为主.%BACKGROUND: Leiomyoma in renal allograft would influence the renal allograft 10 different extents and even threaten thelong-term survival of renal allograft.OBJECTIVE: To summarize the diagnosis and treatment experience of leiomyoma in renal allograft from one case.METHODS: To retrospectively analyze one 53-year-old male case. The case received renal allograft in other hospitals becauseof uremia 11 years ago. After surgery, renal function recovered to normal, and he orally took immunosuppressive agent for longterm. The clinical data of this case were analyzed.RESULTS AND CONCLUSION: The leiomyoma in renal allograft was diagnosed primarily according to pathological examination,and imaging examination had no obvious specificity. Simple surgical resection of tumor body is the primary means for treatmentof leiomyoma in renal allograft.

  6. TLR2单克隆抗体对大鼠角膜移植术后植片存活的保护作用%Protective role of anti-TLR2 monoclonal antibody to corneal graft survival after allograft corneal transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    白浪; 郑艳华; 梁伟怡

    2015-01-01

    Background The effects of Toll-like receptor 2 (TLR2) in grafting-related immune diseases have attracted more and more attention.Blocking TLR2 signal pathway can extend the survival time of heart and kidney grafts.However, the effects of anti-TLR2 monoclonal antibody on corneal graft have not been confirmed.Objective This study was to investigate the influence of anti-TLR2 monoclonal antibody on corneal graft survival in the rats received penetrating keratoplasty (PKP).Methods Allograft corneal transplantation was performed on the right eyes of 24 SPF female Wistar rats to establish PKP models,with 12 SD rats as donors.The model eyes were randomized into the TLR2 monoclonal antibody group and the model group.Anti-TLR2 monoclonal antibody of 15 μg/30 μl was subconjunctivally injected on day 0,2,4,6 and 8 following the modeling in the TLR2 monoclonal antibody group,and equal amount of normal saline was injected in the same way in the model group.The edema,transparency and neovascularization were observed under the slit lamp microscope after surgery, and rejection index (RI) was scored based on the criteria of Holland.Corneal tissue sections of the rats were prepared for the histopathological examination on day 9 and 15 after operation.The research protocol was approved by the Southern Medical University Ethics Committee.Results Mild corneal edema was found in the two groups 1-4 days after operation.A lot of new blood vessels, edema and opacification of corneas were seen in the model group 9-14 days after operation,but in the TLR2 monoclonal antibody group,corneal opacification was found 15 days after operation.The RI scores were significantly higher in the model group than those in the TLR2 monoclonal antibody group 5,9,15 days after operation (t=4.183,4.954,13.506;all at P<0.05).The survival time in the TLR2 monoclonal antibody group was 15.5 days,with the 95% confidence interval (CI) 14.9-16.1;while that in the model group was 9.5 days,with the 95% CI 8

  7. Bone Allografts: What Is the Risk of Disease Transmission with Bone Allografts?

    Science.gov (United States)

    ... calculated to be one in 2.8 billion [Russo 1995]. Therefore, the established exclusionary criteria combined with ... bone allograft. J Periodontol 1992;12:979–983. Russo R, Scarborough N. Inactivation of viruses in demineralized ...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    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.

  9. Renal Allograft in a Professional Boxer

    Directory of Open Access Journals (Sweden)

    Einollahi Behzad

    2008-01-01

    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.

  10. Renal allograft rejection. Unusual scintigraphic findings

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-11-01

    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.

  11. Liver transplantation with donation after cardiac death donors: risk factors for recipient survival%心脏死亡器官捐赠供受者术前及术后早期临床指标对肝移植预后的影响

    Institute of Scientific and Technical Information of China (English)

    李飞; 王东平; 何晓顺; 朱晓峰; 鞠卫强; 巫林伟

    2013-01-01

    Objective To analyze the risk factors for the outcomes of recipients after orthotopic liver transplantation using donation after cardiac death (DCD) donors.Method A retrospective study was performed to observe the available clinical data of 60 patients who had receiced hepatic allografts of DCD donors from July 2007 to December 2012 in our hospital and a 3-year follow-up was conducted to investigate outcome.In the patients whose ALT and/or AST levels were more than 1500 U/L within 72 h following surgery,early allograft dysfunction (EAD) was defined.Potential risk fators right before surgery included donor and recipient age,donor ALT AST,TBIL and WIT,and recipient creatine,TBIL,INR,albumin,MELD,BMI and recipient CIT.Kaplan-meier method was used to calculate the cumulative survival rate.Log-rank test and Cox regression model were performed to analyze donors and recipients related risk factors by univariate and multivariate analysis respectively.All statistical data were analyzed by using SPSS 19.0.Results The overall cumulative survival rate of 1 and 3 years was 76% and 62% respectively.Donor ALT,AST and WIT,and recipient Cre,MELD,CIT and EAD were significant risk fators in univariate analysis.However,the multivariate analysis revealed that donor WIT was the only independent risk factor affecting survival in our study.Conclusion By identifying and controlling certain characteristics,the outcomes of DCD liver transplant recipients could be dramaticly improved.%目的 探讨心脏死亡器官捐赠(DCD)供受者术前及术后早期各项临床指标对受者预后的影响.方法 回顾性分析60例DCD肝移植供受者的临床资料.术前指标包括:供者年龄、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST);受者年龄、血肌酐、胆红素总量(TBil)、国际标准化比值(INR)、白蛋白、终末期肝病模型(MELD)评分、体质量指数;供肝热缺血时间和冷缺血时间.将术后72 h内ALT或(和)AST> 1500 U/L定义为术后

  12. Arthroscopic meniscal allograft transplantation without bone plugs.

    Science.gov (United States)

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

    2011-02-01

    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.

  13. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

    Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

  14. Cardiac power index, mean arterial pressure, and Simplified Acute Physiology Score II are strong predictors of survival and response to revascularization in cardiogenic shock.

    Science.gov (United States)

    Popovic, Batric; Fay, Renaud; Cravoisy-Popovic, Aurelie; Levy, Bruno

    2014-07-01

    Short-term prognostic factors in patients with cardiogenic shock (CS) have previously been established using only hemodynamic parameters without taking into account classic intensive care unit (ICU) severity score or organ failure/support. The aim of this study was to assess early predictors of in-hospital mortality of a monocentric cohort of patients with ST-elevation myocardial infarction complicated by early CS. We retrospectively studied 85 consecutive patients with CS complicating acute myocardial infarction and Thrombolysis in Myocardial Infarction flow grade 3 after percutaneous coronary revascularization. All patients were managed according to the following algorithm: initial resuscitation by a mobile medical unit or in-hospital critical care physician unit followed by percutaneous coronary revascularization and CS management in the ICU. Prehospital CS was diagnosed in 69% of cases, initially complicated by an out-of-hospital cardiac arrest in 64% of cases. All patients were treated with vasopressors, 82% were ventilated, and 22% underwent extrarenal epuration. The 28-day mortality rate was 39%. Under multivariate analysis, initial cardiac power index, mean arterial pressure of less than 75 mmHg at hour 6 of ICU management, and Simplified Acute Physiology Score II were independent predictive factors of in-hospital mortality. In conclusion, parameters directly related to cardiac performance and vascular response to vasopressors and admission Simplified Acute Physiology Score II are strong predictors of in-hospital mortality.

  15. Regulation of Cardiac Hypertrophy: the nuclear option

    NARCIS (Netherlands)

    D.W.D. Kuster (Diederik)

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, c

  16. Transplant allograft vasculopathy: Role of multimodality imaging in surveillance and diagnosis.

    Science.gov (United States)

    Payne, Gregory A; Hage, Fadi G; Acharya, Deepak

    2016-08-01

    Cardiac allograft vasculopathy (CAV) is a challenging long-term complication of cardiac transplantation and remains a leading long-term cause of graft failure, re-transplantation, and death. CAV is an inflammatory vasculopathy distinct from traditional atherosclerotic coronary artery disease. Historically, the surveillance and diagnosis of CAV has been dependent on serial invasive coronary angiography with intravascular imaging. Although commonly practiced, angiography is not without significant limitations. Technological advances have provided sophisticated imaging techniques for CAV assessment. It is now possible to assess the vascular lumen, vessel wall characteristics, absolute blood flow, perfusion reserve, myocardial contractile function, and myocardial metabolism and injury in a noninvasive, expeditious manner with little risk. The current article will review key imaging modalities for the surveillance, diagnosis, and prognosis of CAV and discuss coronary physiology of transplanted hearts with emphasis on the clinical implications for provocative and vasodilator stress testing. PMID:26711101

  17. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  18. Cardiac-specific over-expression of epidermal growth factor receptor 2 (ErbB2 induces pro-survival pathways and hypertrophic cardiomyopathy in mice.

    Directory of Open Access Journals (Sweden)

    Polina Sysa-Shah

    Full Text Available BACKGROUND: Emerging evidence shows that ErbB2 signaling has a critical role in cardiomyocyte physiology, based mainly on findings that blocking ErbB2 for cancer therapy is toxic to cardiac cells. However, consequences of high levels of ErbB2 activity in the heart have not been previously explored. METHODOLOGY/PRINCIPAL FINDINGS: We investigated consequences of cardiac-restricted over-expression of ErbB2 in two novel lines of transgenic mice. Both lines develop striking concentric cardiac hypertrophy, without heart failure or decreased life span. ErbB2 transgenic mice display electrocardiographic characteristics similar to those found in patients with Hypertrophic Cardiomyopathy, with susceptibility to adrenergic-induced arrhythmias. The hypertrophic hearts, which are 2-3 times larger than those of control littermates, express increased atrial natriuretic peptide and β-myosin heavy chain mRNA, consistent with a hypertrophic phenotype. Cardiomyocytes in these hearts are significantly larger than wild type cardiomyocytes, with enlarged nuclei and distinctive myocardial disarray. Interestingly, the over-expression of ErbB2 induces a concurrent up-regulation of multiple proteins associated with this signaling pathway, including EGFR, ErbB3, ErbB4, PI3K subunits p110 and p85, bcl-2 and multiple protective heat shock proteins. Additionally, ErbB2 up-regulation leads to an anti-apoptotic shift in the ratio of bcl-xS/xL in the heart. Finally, ErbB2 over-expression results in increased activation of the translation machinery involving S6, 4E-BP1 and eIF4E. The dependence of this hypertrophic phenotype on ErbB family signaling is confirmed by reduction in heart mass and cardiomyocyte size, and inactivation of pro-hypertrophic signaling in transgenic animals treated with the ErbB1/2 inhibitor, lapatinib. CONCLUSIONS/SIGNIFICANCE: These studies are the first to demonstrate that increased ErbB2 over-expression in the heart can activate protective signaling

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

    Directory of Open Access Journals (Sweden)

    Madhan Krishan

    2009-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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))

    1994-01-01

    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.).

  1. Urinary Calprotectin and Posttransplant Renal Allograft Injury

    Science.gov (United States)

    Bistrup, Claus; Marcussen, Niels; Pagonas, Nikolaos; Seibert, Felix S.; Arndt, Robert; Zidek, Walter; Westhoff, Timm H.

    2014-01-01

    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 m2 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. PMID:25402277

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

    Directory of Open Access Journals (Sweden)

    Yan Qiang

    2012-01-01

    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

  3. Regulation of Cardiac Hypertrophy: the nuclear option

    OpenAIRE

    Kuster, Diederik

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, cardiac hypertrophy is an independent risk factor for the development of heart failure and is therefore called pathological hypertrophy. That hypertrophy is not bad per se, is illustrated by the hyp...

  4. Surgical technique and clinical results for scapular allograft reconstruction following resection of scapular tumors

    Directory of Open Access Journals (Sweden)

    Xiang Zhou

    2009-04-01

    Full Text Available Abstract Background Progress in developing effective surgical techniques, such as scapular allograft reconstruction, enhance shoulder stability and extremity function, in patients following scapular tumor resection. Methods Case details from seven patients who underwent scapular allograft reconstruction following scapular tumor resection were reviewed. A wide marginal resection (partial scapulectomy was performed in all patients and all affected soft tissues were resected to achieve a clean surgical margin. The glenoid-resected and glenoid-saved reconstructions were performed in three and four patients, respectively. The residual host scapula were fixed to the size-matched scapular allografts with plates and screws. The rotator cuff was affected frequently and was mostly resected. The deltoid and articular capsule were infrequently involved, but reconstructed preferentially. The remaining muscles were reattached to the allografts. Results The median follow-up was 26 months (range, 14–50 months. The average function scores were 24 points (80% according to the International Society of Limb Salvage criteria. The range of active shoulder abduction and forward flexion motion were 40°–110° and 30°–90°, respectively. There was no difference between the glenoid-saved and glenoid-resected reconstructions in the total scores (mean, 24.5 points/81% versus 24 points/79%, but the glenoid-saved procedure was superior to the later in terms of abduction/flexion motion (mean, 72°/61° versus 55°/43°. During the study follow-up period, one patient died following a relapse, one patient lived despite of local recurrence, and five patients survived with no evidence of recurrence of the original cancer. Post-surgical complications such as shoulder dislocations, non-unions, and articular degeneration were not noted during this study period. Conclusion Scapular allograft reconstruction had a satisfactory functional, cosmetic, and oncological outcome in

  5. Manual vs. integrated automatic load-distributing band CPR with equal survival after out of hospital cardiac arrest. The randomized CIRC trial

    NARCIS (Netherlands)

    Wik, L.; Olsen, J.A.; Persse, D.; Sterz, F.; Lozano Jr, M.; Brouwer, M.A.; Westfall, M.; Souders, C.M.; Malzer, R.; Grunsven, P.M. van; Travis, D.T.; Whitehead, A.; Herken, U.R.; Lerner, E.B.

    2014-01-01

    OBJECTIVE: To compare integrated automated load distributing band CPR (iA-CPR) with high-quality manual CPR (M-CPR) to determine equivalence, superiority, or inferiority in survival to hospital discharge. METHODS: Between March 5, 2009 and January 11, 2011 a randomized, unblinded, controlled group s

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-08-01

    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.

  7. Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome

    NARCIS (Netherlands)

    Damman, Jeffrey; Bloks, Vincent W.; Daha, Mohamed R.; van der Most, Peter J.; Sanjabi, Bahram; van der Vlies, Pieter; Snieder, Harold; Ploeg, Rutger J.; Krikke, Christina; Leuvenink, Henri G. D.; Seelen, Marc A.

    2015-01-01

    Background. In the last few decades, strategies to improve allograft survival after kidney transplantation have been directed to recipient-dependent mechanisms of renal injury. In contrast, no such efforts have been made to optimize organ quality in the donor. Optimizing deceased donor kidney qualit

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

    Directory of Open Access Journals (Sweden)

    Basil Leodoro

    2014-11-01

    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.

  9. Renal-sparing strategies in cardiac transplantation

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Ross, Heather J

    2009-01-01

    PURPOSE OF REVIEW: Renal dysfunction due to calcineurin inhibitor (CNI) toxicity is a major clinical problem in cardiac transplantation. The aim of the article is to review the efficacy and safety of various renal sparing strategies in cardiac transplantation. RECENT FINDINGS: Small studies have...... documented that late initiation of CNI is safe in patients treated with induction therapy at the time of transplantation. Use of mycophenolate is superior when compared with azathioprine to allow for CNI reduction. More substantial reduction in CNI levels is safe and effective with the introduction...... of sirolimus or everolimus. However, studies that use very early CNI discontinuation have found an increased risk of allograft rejection, and this strategy requires further study before it can be routinely recommended. CNI discontinuation late after cardiac transplantation seems more effective than CNI...

  10. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  11. Use of local allograft irradiation following renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-07-01

    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.

  12. Adenosine triphosphate-competitive mTOR inhibitors: a new class of immunosuppressive agents that inhibit allograft rejection.

    Science.gov (United States)

    Rosborough, B R; Raïch-Regué, D; Liu, Q; Venkataramanan, R; Turnquist, H R; Thomson, A W

    2014-09-01

    The mechanistic/mammalian target of rapamycin (mTOR) is inhibited clinically to suppress T cell function and prevent allograft rejection. mTOR is the kinase subunit of two mTOR-containing complexes, mTOR complex (mTORC) 1 and 2. Although mTORC1 is inhibited by the macrolide immunosuppressant rapamycin (RAPA), its efficacy may be limited by its inability to block mTORC1 completely and its limited effect on mTORC2. Adenosine triphosphate (ATP)-competitive mTOR inhibitors are an emerging class of mTOR inhibitors that compete with ATP at the mTOR active site and inhibit any mTOR-containing complex. Since this class of compounds has not been investigated for their immunosuppressive potential, our goal was to determine the influence of a prototypic ATP-competitive mTOR inhibitor on allograft survival. AZD8055 proved to be a potent suppressor of T cell proliferation. Moreover, a short, 10-day course of the agent successfully prolonged murine MHC-mismatched, vascularized heart transplant survival. This therapeutic effect was associated with increased graft-infiltrating regulatory T cells and reduced CD4(+) and CD8(+) T cell interferon-γ production. These studies establish for the first time, that ATP-competitive mTOR inhibition can prolong organ allograft survival and warrant further investigation of this next generation mTOR inhibitors. PMID:25307040

  13. Surgical techniques and radiological findings of meniscus allograft transplantation.

    Science.gov (United States)

    Lee, Hoseok; Lee, Sang Yub; Na, Young Gon; Kim, Sung Kwan; Yi, Jae Hyuck; Lim, Jae Kwang; Lee, So Mi

    2016-08-01

    Meniscus allograft transplantation has been performed over the past 25 years to relieve knee pain and improve knee function in patients with an irreparable meniscus injury. The efficacy and safety of meniscus allograft transplantation have been established in numerous experimental and clinical researches. However, there is a lack of reviews to aid radiologists who are routinely interpreting images and evaluating the outcome of the procedures, and also meniscus allograft transplantation is not widely performed in most hospitals. This review focuses on the indications of the procedure, the different surgical techniques used for meniscus allograft transplantation according to the involvement of the lateral and medial meniscus, and the associated procedures. The postoperative radiological findings and surgical complications of the meniscus allograft transplantation are also described in detail. PMID:27423673

  14. EARLY ALLOGRAFT DYSFUNCTION AND ACUTE KIDNEY INJURY AFTER LIVER TRANSPLANTATION: DEFINITIONS, RISK FACTORS AND CLINICAL SIGNIFICANCE

    Directory of Open Access Journals (Sweden)

    L. Y. Moysyuk

    2012-01-01

    Full Text Available This review discusses issues related to intensive care in recipients of transplanted liver in the early postoperative period, with an emphasis on contemporary conditions and attitudes that are specific for this group of patients. Early allograft dysfunction (EAD requires immediate diagnosis and appropriate treatment in case. The causes of the EAD and therapeutic tactics are discussed. Acute kidney injury (AKI and renal failure are common in patients after transplantation. We consider etiology, risk factors, diagnosis and treatment guidelines for AKI. The negative impact of EAD and AKI on the grafts survival and recipients is demonstrated. 

  15. Complications of massive allograft reconstruction for bone tumors

    Directory of Open Access Journals (Sweden)

    Abolhasan Borjian

    2006-11-01

    Full Text Available BACKGROUND: Since the evolution of multi-drug chemotherapy and radiotherapy and new sophisticated surgical techniques, limb salvage and reconstruction, rather than amputation, has become the preferred treatment for patients with bone tumors. One option is allograft replacement. Although allograft has several advantages, it is not without complications. This study was performed to observe these complications in a group of patients treated with allograft replacement for bone tumor resection. The purpose was to gain an overview of the factors predisposing to these complications to minimize their occurrence. METHODS: This retrospective study was performed on patients with benign aggressive and malignant bone tumors undergoing limb reconstruction with allograft between 1997 and 2005 in Al-Zahra and Kashani Hospitals in Isfahan, Iran. Data was collected from patient files, clinical notes, radiographs and a recent physical examination. Complications including local recurrence, fracture of allograft, fixation failure, nonunion, infection, skin necrosis and neurological damage were recorded. RESULTS: Sixty patients including 39 males and 21 females were studied. The mean age of patients was 23 ± 11.7 years. The mean follow-up interval was 28.1 ± 12.4 months (mean ± SD. Complications were allograft fracture in 20%, local recurrence in 16%, fixation failure in 11%, nonunion in 6%, infection in 6%, skin necrosis in 6%, and peroneal nerve palsy in 1% of cases. Most local recurrences (60% were those with a mal-performed biopsy. Most allograft fractures occurred when a short plate was used. CONCLUSIONS: Allograft replacement for bone tumors remains a valid option. To avoid complications, biopsy should be done by a trained surgeon in bone oncology. A long plate is recommended for fixation. Sterility and graft processing must be optimal. Autogenous bone graft must be added at host-allograft junction. KEY WORDS: Bone tumors, bone allograft, limb

  16. Adding the implantable cardioverter-defibrillator to cardiac resynchronization therapy is associated with improved long-term survival in ischaemic, but not in non-ischaemic cardiomyopathy

    DEFF Research Database (Denmark)

    Witt, Christoffer Tobias; Kronborg, Mads Brix; Nohr, Ellen Aagaard;

    2015-01-01

    Hospital, Denmark from 2000 to 2010 were included. Baseline characteristics were retrieved from patient files and survival data were obtained from the Danish Civil Registration System. The primary outcome was all-cause mortality. The effect of ICD backup was estimated using Cox proportional hazards model...... to ischaemic cardiomyopathy (ICM) or non-ischaemic cardiomyopathy (NICM) treated with a CRT device with or without defibrillator backup. METHODS AND RESULTS: In this observational study, consecutive patients with an ejection fraction ≤35% and QRS width ≥120 ms receiving a CRT device at Aarhus University...

  17. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

    Directory of Open Access Journals (Sweden)

    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  18. Graft vasculopathy in the skin of a human hand allograft: implications for diagnosis of rejection of vascularized composite allografts.

    Science.gov (United States)

    Kanitakis, Jean; Karayannopoulou, Georgia; Lanzetta, Marco; Petruzzo, Palmina

    2014-11-01

    Whereas vascularized composite allografts often undergo acute rejections early in the postgraft period, rejection manifesting with severe vascular changes (graft vasculopathy) has only been observed on three occasions in humans. We report a hand-allografted patient who developed severe rejection following discontinuation of the immunosuppressive treatment. It manifested clinically with erythematous maculopapules on the skin and pathologically with graft vasculopathy that affected both large vessels and smaller cutaneous ones. The observation that graft vasculopathy can affect skin vessels shows that it is amenable to diagnosis with usual skin biopsy as recommended for the follow-up of these allografts. Graft vasculopathy developing in the setting of vascularized composite allografts likely represents chronic rejection due to under-immunosuppression and, if confirmed, should be included in a future update of the Banff classification of vascularized composite allograft rejection. PMID:25041139

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

    Science.gov (United States)

    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

    2016-01-01

    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

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

    Science.gov (United States)

    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

    2016-01-01

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    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

  2. Minimizing the risk of chronic allograft nephropathy.

    Science.gov (United States)

    Weir, Matthew R; Wali, Ravinder K

    2009-04-27

    Chronic allograft nephropathy, now defined as interstital fibrosis and tubular atrophy not otherwise specified, is a near universal finding in transplant kidney biopsies by the end of the first decade posttransplantation. After excluding death with functioning graft, caused by cardiovascular disease or malignancy, chronic allograft nephropathy is the leading cause of graft failure. Original assumptions were that this was not a modifiable process but inexorable, likely due to past kidney injuries. However, newer understandings suggest that acute or subacute processes are involved, and with proper diagnosis, appropriate interventions can be instituted. Our method involved a review of the primary and secondary prevention trials in calcineurin inhibitor withdrawal. Some of the more important causes of progressive graft deterioration include subclinical cellular or humoral rejection, and chronic calcineurin inhibitor toxicity. Early graft biopsy, assessment of histology, and changes in immunosuppression may be some of the most important measures available to protect graft function. The avoidance of clinical inertia in pursuing subtle changes in graft function is critical. Modification in maintenance immunosuppression may benefit many patients with early evidence of graft deterioration. PMID:19384181

  3. Autograft versus allograft in anterior cruciate ligament reconstruction

    Science.gov (United States)

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

    2016-01-01

    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

  4. Percutaneous fusion of lumbar facet with bone allograft

    Directory of Open Access Journals (Sweden)

    Félix Dolorit Verdecia

    2015-03-01

    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.

  5. Bidimensional measurements of right ventricular function for prediction of survival in patients with pulmonary hypertension: comparison of reproducibility and time of analysis with volumetric cardiac magnetic resonance imaging analysis.

    Science.gov (United States)

    Corona-Villalobos, Celia P; Kamel, Ihab R; Rastegar, Neda; Damico, Rachel; Kolb, Todd M; Boyce, Danielle M; Sager, Ala-Eddin S; Skrok, Jan; Shehata, Monda L; Vogel-Claussen, Jens; Bluemke, David A; Girgis, Reda E; Mathai, Stephen C; Hassoun, Paul M; Zimmerman, Stefan L

    2015-09-01

    We tested the hypothesis that bidimensional measurements of right ventricular (RV) function obtained by cardiac magnetic resonance imaging (CMR) in patients with pulmonary arterial hypertension (PAH) are faster than volumetric measures and highly reproducible, with comparable ability to predict patient survival. CMR-derived tricuspid annular plane systolic excursion (TAPSE), RV fractional shortening (RVFS), RV fractional area change (RVFAC), standard functional and volumetric measures, and ventricular mass index (VMI) were compared with right heart catheterization data. CMR analysis time was recorded. Receiver operating characteristic curves, Kaplan-Meier, Cox proportional hazard (CPH), and Bland-Altman test were used for analysis. Forty-nine subjects with PAH and 18 control subjects were included. TAPSE, RVFS, RVFAC, RV ejection fraction, and VMI correlated significantly with pulmonary vascular resistance and mean pulmonary artery pressure (all P < 0.05). Patients were followed up for a mean (± standard deviation) of 2.5 ± 1.6 years. Kaplan-Meier curves showed that death was strongly associated with TAPSE <18 mm, RVFS <16.7%, and RVFAC <18.8%. In CPH models with TAPSE as dichotomized at 18 mm, TAPSE was significantly associated with risk of death in both unadjusted and adjusted models (hazard ratio, 4.8; 95% confidence interval, 2.0-11.3; P = 0.005 for TAPSE <18 mm). There was high intra- and interobserver agreement. Bidimensional measurements were faster (1.5 ± 0.3 min) than volumetric measures (25 ± 6 min). In conclusion, TAPSE, RVFS, and RVFAC measures are efficient measures of RV function by CMR that demonstrate significant correlation with invasive measures of PAH severity. In patients with PAH, TAPSE, RVFS, and RVFAC have high intra- and interobserver reproducibility and are more rapidly obtained than volumetric measures. TAPSE <18 mm by CMR was strongly and independently associated with survival in PAH. PMID:26401254

  6. Cell therapy to induce allograft tolerance: Time to switch to plan B?

    Directory of Open Access Journals (Sweden)

    Antoine eSicard

    2015-04-01

    Full Text Available Organ transplantation is widely acknowledged as the best option for end stage failure of vital organs. Long-term graft survival is however limited by graft rejection, a destructive process resulting from the response of recipient’s immune system against donor-specific alloantigens. Prevention of rejection currently relies exclusively on immunosuppressive drugs that lack antigen specificity and therefore increase the risk for infections and cancers. Induction of donor-specific tolerance would provide indefinite graft survival without morbidity and therefore represents the Grail of transplant immunologists.Progresses in the comprehension of immunoregulatory mechanisms over the last decades have paved the way for cell therapies to induce allograft tolerance. The first part of the present article reviews the promising results obtained in experimental models with adoptive transfer of ex vivo-expanded regulatory CD4+ T cells (CD4+ Tregs and discuss which source and specificity should be preferred for transferred CD4+ Tregs. Interestingly, B cells have recently emerged as potent regulatory cells, able to establish a privileged crosstalk with CD4+ T cells. The second part of the present article reviews the evidences demonstrating the crucial role of regulatory B cells in transplantation tolerance. We propose the possibility to harness B cell regulatory functions to improve cell-based therapies aiming at inducing allograft tolerance.

  7. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  8. Renalase Gene Polymorphism in Patients After Renal Allograft Transplantation

    Directory of Open Access Journals (Sweden)

    Andrzej Pawlik

    2014-06-01

    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.

  9. Osteochondral Allograft Transplantation in the Knee.

    Science.gov (United States)

    Zouzias, Ioannis C; Bugbee, William D

    2016-06-01

    The technique of osteochondral allograft (OCA) transplantation has been used to treat a wide spectrum of cartilage deficiencies in the knee. Its use has been supported by basic science and clinical studies that show it is a safe and effective treatment option. What sets fresh OCA transplantation apart from other cartilage procedures in the knee, is the ability to treat large defects with mature hyaline cartilage. Studies looking at transplantation of fresh OCAs in the general population have shown reliable pain relief and return to activities of daily living. Reports of cartilage injuries in athletes have risen over the years and more research is needed in evaluating the successfulness of OCA transplantation in the athletic population. PMID:27135291

  10. Preventing Allograft Rejection by Targeting Immune Metabolism

    Directory of Open Access Journals (Sweden)

    Chen-Fang Lee

    2015-10-01

    Full Text Available Upon antigen recognition and co-stimulation, T lymphocytes upregulate the metabolic machinery necessary to proliferate and sustain effector function. This metabolic reprogramming in T cells regulates T cell activation and differentiation but is not just a consequence of antigen recognition. Although such metabolic reprogramming promotes the differentiation and function of T effector cells, the differentiation of regulatory T cells employs different metabolic reprogramming. Therefore, we hypothesized that inhibition of glycolysis and glutamine metabolism might prevent graft rejection by inhibiting effector generation and function and promoting regulatory T cell generation. We devised an anti-rejection regimen involving the glycolytic inhibitor 2-deoxyglucose (2-DG, the anti-type II diabetes drug metformin, and the inhibitor of glutamine metabolism 6-diazo-5-oxo-L-norleucine (DON. Using this triple-drug regimen, we were able to prevent or delay graft rejection in fully mismatched skin and heart allograft transplantation models.

  11. THE DIAGNOSIS OF LIVER ALLOGRAFT ACUTE REJECTION IN LIVER BIOPSIES

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    L. V. Shkalova

    2011-01-01

    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. 

  12. Leukocytic acetylcholine in chronic rejection of renal allografts

    OpenAIRE

    Wilczynska, Joanna

    2011-01-01

    Leukocytes, which accumulate in graft blood vessels during fatal acute rejection of experimental renal allografts, synthesise and release acetylcholine (ACh). In this study, I tested the hypothesis that ACh produced by leukocytes accumulating in graft blood vessels contributes to the pathogenesis of chronic renal allograft vasculopathy (CAV). Kidneys were transplanted in the allogeneic Fischer 344 to Lewis rat strain combination. Isogeneic transplantations were performed in Lew...

  13. Nox-2 Is a Modulator of Fibrogenesis in Kidney Allografts

    OpenAIRE

    Djamali, A; A Vidyasagar; Adulla, M.; Hullett, D.; Reese, S.

    2008-01-01

    We studied the role of classical phagocytic NADPH oxidase (Nox) in the pathogenesis of kidney allograft tubulointerstitial fibrosis. Immunofluorescence studies showed that Nox-2 and p22phox (electron transfer subunits of Nox) colocalized in the tubulointerstitium of human kidney allografts. Tubular Nox-2 also colocalized with α -SMA in areas of injury, suggestive of epithelial-to-mesenchymal transition (EMT). Interstitial macrophages (CD68+) and myofibroblasts (α -SMA+) expressed Nox-2 while ...

  14. Deceased donor skin allograft banking: Response and utilization

    Directory of Open Access Journals (Sweden)

    Gore Madhuri

    2010-10-01

    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.

  15. De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

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    Kanodia K

    2008-01-01

    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.

  16. The Spectrum of Renal Allograft Failure

    Science.gov (United States)

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

    2016-01-01

    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

  17. 延长非协调性异种心脏移植存活时间的研究%Study of prolonging graft survival of discordant cardiac xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    区景松; 孙培吾

    2000-01-01

    Objective To search the way of prolonging xenograft survival of discordant cardiac xenotransplantation.Methods All animals were divided into groups A,B,C and D receiving the following combined therapies respectively:cobra venom factor (CVF) in group A,CVF and pentoxifylline (FTX) in group B,CVF and CCS (CsA,CTX,MP)in group C,CVF,PTX and CCS in group D.The recipients were given CVF 150 μg/kg(i.P) twice daily 1,4 days before transplantation;PTX 50 mg/kg daily(i.P)1 h before transplamtation,then 25 mg/kg(i.P)in an interval of 6 h until rejection thereafter;CsA 10mg/kg(i.p) daily one day and 1 h before transplantation until rejection;CTX 40 mg/kg(i.p) one day before transplantation,then 10 mg/kg(i.P)daily 1 h before transplantation until rejection thereafter;MP 10 mg/kg(i.v)1 h before transplantation,then 1 mg/kg(i.m) daily until rejection thereafter.The expression of vascular cell adhesion molecular-1 (VCAM-1) of vascular endothelial cells (EC) in cardiac xenografts was detected by using immunohistochemical staining method.Results The mean survival time of cardiac xenografts was 57.5 h (group A),77.38 h(group B),79.13 h (group C) and 98.75 h(group D),respectively.Twenty-four h after transplantation.VCAM-1 expression in the groups B and D was not upregulated,but slightly up-regulated in group C and obvious in group A.At rejection,the up-regulation of VCAM-1 expression was mildest in group D and most obvious in group A.and VCAM-1 expression in group B was milder than that in group C (P<0.05).Conclusions CVF combined with PTX and CCS could significantly prolong the survival time of cardiac xenograft.PTX mainly protected EC and CCS mainly inhibit inflammatory cell infiltration.Combined use of them could complement and reinforce mutually.%目的 寻找延长非协调性异种心脏移植存活时间的方法.方法 实验分A、B、C、D 4组,将异种心脏(豚鼠-大鼠)移植于颈部.A组:移植前受体用眼镜蛇蛇毒因子(CVF)150 μg·kg-1·d-1,腹膜

  18. Musculoskeletal allograft risks and recalls in the United States.

    Science.gov (United States)

    Mroz, Thomas E; Joyce, Michael J; Steinmetz, Michael P; Lieberman, Isador H; Wang, Jeffrey C

    2008-10-01

    There have been several improvements to the US tissue banking industry over the past decade. Tissue banks had limited active government regulation until 1993, at which time the US Food and Drug Administration began regulatory oversight because of reports of disease transmission from allograft tissues. Reports in recent years of disease transmission associated with the use of allografts have further raised concerns about the safety of such implants. A retrospective review of allograft recall data was performed to analyze allograft recall by tissue type, reason, and year during the period from January 1994 to June 30, 2007. During the study period, more than 96.5% of all allograft tissues recalled were musculoskeletal. The reasons underlying recent musculoskeletal tissue recalls include insufficient or improper donor evaluation, contamination, recipient infection, and positive serologic tests. Infectious disease transmission following allograft implantation may occur if potential donors are not adequately evaluated or screened serologically during the prerecovery phase and if the implant is not sterilized before implantation. PMID:18832599

  19. Meniscal Allograft Transplantation Does Not Prevent or Delay Progression of Knee Osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Catherine Van Der Straeten

    Full Text Available Meniscal tears are common knee injuries. Meniscal allograft transplantation (MAT has been advocated to alleviate symptoms and delay osteoarthritis (OA after meniscectomy. We investigated (1 the long-term outcome of MAT as a treatment of symptomatic meniscectomy, (2 most important factors affecting survivorship and (3 OA progression.From 1989 till 2013, 329 MAT were performed in 313 patients. Clinical and radiographic results and MAT survival were evaluated retrospectively. Failure was defined as conversion to knee arthroplasty (KA or total removal of the MAT.Mean age at surgery was 33 years (15-57; 60% were males. No-to-mild cartilage damage was found in 156 cases, moderate-to-severe damage in 130. Simultaneous procedures in 118 patients included cartilage procedures, osteotomy or ACL-reconstruction. At a mean follow-up of 6.8 years (0.2-24.3years, 5 patients were deceased and 48 lost (14.6%, 186 MAT were in situ (56.5% whilst 90 (27.4% had been removed, including 63 converted to a KA (19.2%. Cumulative allograft survivorship was 15.1% (95% CI:13.9-16.3 at 24.0 years. In patients <35 years at surgery, survival was significantly better (24.1% compared to ≥35 years (8.0% (p = 0.017. In knees with no-to-mild cartilage damage more allografts survived (43.0% compared to moderate-to-severe damage (6.6% (p = 0.003. Simultaneous osteotomy significantly deteriorated survival (0% at 24.0 years (p = 0.010. 61% of patients underwent at least one additional surgery (1-11 for clinical symptoms after MAT. Consecutive radiographs showed significant OA progression at a mean of 3.8 years (p<0.0001. Incremental Kellgren-Lawrence grade was +1,1 grade per 1000 days (2,7yrs.MAT did not delay or prevent tibiofemoral OA progression. 19.2% were converted to a knee prosthesis at a mean of 10.3 years. Patients younger than 35 with no-to-mild cartilage damage may benefit from MAT for relief of symptoms (survivorship 51.9% at 20.2 years, but patients and healthcare payers

  20. Chronic rejection in DLA identical dogs after orthotopic cardiac transplantation

    NARCIS (Netherlands)

    O.C.K.M. Penn

    1979-01-01

    textabstractThe justification for clinical cardiac transplantation is that it should solve end-stage cardiac disease when no other medical or surgical treatment is available (76). However, after cardiac transplantation the main barriers to long-term survival and complete rehabilitation include the m

  1. 心脏穿透伤后生存过程:类型演变和分类救治的研究%Injury evolution and classified treatment in survival process of penetrating cardiac trauma

    Institute of Scientific and Technical Information of China (English)

    杨波; 杨建

    2013-01-01

    time point by survival analysis.Impacts of medical interventions on prognosis of those patients were analyzed,such as pericardial space exploration,emergency room thoracotomy (ERT),operating room thoracotomy (ORT).Results Some patients at sub-clinical phase were aggravated into clinical phase or agonal phase,as well as some patients at clinical phase were aggravated into agonal phase during in-hospital treatment.There were significance differences of posttraumatic suvival course among the four groups,namely sub-clinical type,cardiac tamponade type,hemorrhagic shock type and agonal type (P < 0.01).The differences of posttraumatic survival course were also significant among the three groups,namely sub-clinical phase,clinical phase and agonal phase (P < 0.01).Conclusion Clinical symptom classification (or pathogenesis phase) of PCT may not be always unchangeable,thus it is recommended that PCT patients should be treated based on their clinical symptom classification or patbogenesis phase at consultation.

  2. B-cell-mediated strategies to fight chronic allograft rejection

    Directory of Open Access Journals (Sweden)

    Ali H Dalloul

    2013-12-01

    Full Text Available Solid organs have been transplanted for decades. Since the improvement in graft selection and in medical and surgical procedures, the likelihood of graft function after one year is now close to 90%. Nonetheless even well-matched recipients continue to need medications for the rest of their lives hence adverse side effects and enhanced morbidity. Understanding Immune rejection mechanisms, is of increasing importance since the greater use of living-unrelated donors and genetically unmatched individuals. Chronic rejection is devoted to T-cells, however the role of B-cells in rejection has been appreciated recently by the observation that B-cell depletion improve graft survival. By contrast however, B-cells can be beneficial to the grafted tissue. This protective effect is secondary to either the secretion of protective antibodies or the induction of B-cells that restrain excessive inflammatory responses, chiefly by local provision of IL-10, or inhibit effector T-cells by direct cellular interactions. As a proof of concept B-cell-mediated infectious transplantation tolerance could be achieved in animal models, and evidence emerged that the presence of such B-cells in transplanted patients correlate with a favorable outcome. Among these populations, regulatory B-cells constitute a recently described population. These cells may develop as a feedback mechanism to prevent uncontrolled reactivity to antigens and inflammatory stimuli. The difficult task for the clinician, is to quantify the respective ratios and functions of tolerant vs effector B-cells within a transplanted organ, at a given time point in order to modulate B-cell-directed therapy. Several receptors at the B-cell membrane as well as signaling molecules, can now be targeted for this purpose. Understanding the temporal expansion of regulatory B-cells in grafted patients and the stimuli that activate them will help in the future to implement specific strategies aimed at fighting chronic

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

    Institute of Scientific and Technical Information of China (English)

    ZhijieLi; ChenLi

    1995-01-01

    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.

  4. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    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.

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

    Science.gov (United States)

    Mabe, Isaac; Hunter, Shawn

    2014-12-01

    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. PMID:24414293

  7. Role of Biological Sex in Normal Cardiac Function and in its Disease Outcome – A Review

    OpenAIRE

    Prabhavathi, K.; Selvi, K.Tamarai; Poornima, K.N.; Sarvanan, A.

    2014-01-01

    Biological sex plays an important role in normal cardiac physiology as well as in the heart‘s response to cardiac disease. Women generally have better cardiac function and survival than do men in the face of cardiac disease; however, this is progressively lost when comparing postmenopausal women with age matched men. Animal model of cardiac disease mirror what is seen in humans. Sex hormones contribute significantly to sex based difference in cardiac functioning and in its disease outcome. Es...

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

    Directory of Open Access Journals (Sweden)

    Li Min

    2014-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Yu-Hua Jia

    2015-01-01

    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.

  10. Mannan binding lectin : a two-faced regulator of renal allograft injury?

    NARCIS (Netherlands)

    Damman, Jeffrey; Seelen, Marc A.

    2013-01-01

    Complement activation plays an important role in the pathogenesis of renal allograft injury after kidney transplantation. There are three known pathways of complement activation, namely, classical, alternative, and lectin pathways. In renal allograft injury, contradictory results were reported about

  11. Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.

    Directory of Open Access Journals (Sweden)

    Aric L Gregson

    Full Text Available Bronchiolitis obliterans syndrome (BOS is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-, and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+ and CD103(- and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+ Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+ Treg frequency and inversely with BOS. Higher frequencies of CCR7(+ CD3(+CD4(+CD25(hiFoxp3(+CD45RA(- lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.

  12. Colonisation with methicillin-resistant Staphylococcus aureus prior to renal transplantation is associated with long-term renal allograft failure.

    Science.gov (United States)

    Moore, Carmel; Davis, Niall F; Burke, John P; Power, Richard; Mohan, Ponnusamy; Hickey, David; Smyth, Gordon; Eng, Molly; Little, Dilly M

    2014-09-01

    Renal transplant recipients are at an increased risk of developing Methicillin-resistant Staphylococcus aureus due to their immunosuppressed status. Herein, we investigate the incidence of MRSA infection in patients undergoing renal transplantation and determine the effect of MRSA colonisation on renal allograft function and overall mortality. Between January 1st 2007 and December 31st 2012, 1499 consecutive kidney transplants performed in our transplant unit and a retrospective 1:2 matched case-control study was performed on this patient cohort. The 1-, 3- and 5-year overall graft survival rates were 100%, 86% and 78%, respectively, in MRSA positive recipients compared with 100%, 100% and 93%, respectively, in the control group (P renal allograft failure at 5 years (hazard ratio: 4.6, 95% confidence interval: 1-30.7, P = 0.048). These findings demonstrate that the incidence of long-term renal allograft failure is significantly greater in this patient cohort compared with a matched control population.

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

    Science.gov (United States)

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

    2016-01-01

    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.

  14. KIDNEY TRANSPLANTATION FROM DONORS AFTER CARDIAC DEATH

    Directory of Open Access Journals (Sweden)

    R.L. Rozental

    2012-01-01

    Full Text Available From 668 kidney transplantations performed during the period 2000–2005 68 grafts were recovered from donors after cardiac death and 176 from donors with confirmed brain death. Early results (number of primarily non-functioning grafts, rates of delayed graft function and acute rejections were similar in both groups. 5-year patient survival was 85% from donors after cardiac death and 88% from donors with confirmed brain death. 5-year graft survival was 77% and 85%, respectively. Results showed that the use of kidney grafts recovered from donors after cardiac death is valuable additional source of donor organs. 

  15. Banking of massive osteoarticular and intercalary bone allografts--12 years' experience.

    Science.gov (United States)

    Malinin, T I; Martinez, O V; Brown, M D

    1985-01-01

    Preparation and banking of massive osteoarticular allografts and intercalary bone allografts have been performed for the past 12 years. Careful selection of donors as well as extensive laboratory studies of the donor and the allograft have virtually eliminated the danger of transmitting disease from the donor to the recipient. The availability of a variety of allografts in the Tissue Bank allows for the selection, on an anatomic basis, of an allograft best suited for a particular recipient. The authors have supplied several hundred allografts to recipients in many institutions on the premise that excision, preparation, banking, and implantation of bone allografts constitute a clinical service. Thus, the surgeon who excises and prepares the allograft assumes a joint responsibility for the care of the recipient with the surgeon who implants the allograft. This establishes a close working relationship, which encourages frequent consultation between the parties concerned. This relationship is of particular importance in the initial evaluation of the patient and in determining which particular allograft will best serve a given patient. The experience at the authors' institution provides a model for a multiinstitutional facility that may serve as a base for discussion of the methodology involved in the excision, preparation, and storage of bone allografts. The costs associated with the operation of such a facility are not inconsiderable, but the cost of individual osteoarticular and intercalary allografts can be brought down by an increase in the efficiency of operation inherent in the processing of allografts from over 100 donors per year. During the past several years, the cost of excising and preparing intercalary allografts has been $600 per implant, while the cost for osteochondral allografts varied between $900 and $1,200. Such a large multiinstitutional facility offers the advantages of readily available allografts and quality control. However, because of the

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

    Science.gov (United States)

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

    1992-01-01

    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.

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

    Science.gov (United States)

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

    1992-01-01

    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. PMID:1389780

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

    Science.gov (United States)

    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

    2016-09-01

    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.

  19. Graft-infiltrating cells expressing a CD200 transgene prolong allogeneic skin graft survival in association with local increases in Foxp3(+)Treg and mast cells.

    Science.gov (United States)

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

    2011-12-01

    Expression of the molecule CD200 has been reported to increase allograft survival by suppression of inflammation and acquired immunity. In previous studies we have shown that increased skin and cardiac allograft survival in transgenic mice over-expressing CD200 (CD200(tg)) occurs in association with increased intra-graft expression of mRNAs for genes associated with altered T cell subset differentiation. We investigated changes in graft-infiltrating cells, Treg and mast cells in skin grafts post transplantation into control or CD200(tg) mice, using focused gene array and real-time PCR to assess altered gene expression, and FACS, immunohistology and MLC to determine numbers/function of those cells. Graft-infiltrating cells isolated from CD200(tg) recipients suppressed induction of CTL from control lymph node cells in vitro, and contained increased numbers of infiltrating, non-degranulating, mast cells and Foxp3(+)Treg. Mast cells were also evident in graft tissue of control animals, but there these cells showed evidence for degranulation, and fewer Foxp3(+)Treg were present than was the case of CD200(tg) mice. The infusion of a competitive inhibitor of CD200:CD200R interactions, CD200(tr), at high concentrations (50μg/mouse iv) caused rapid rejection of grafts in CD200(tg) mice, mast cell degranulation within graft tissue, and a decrease in Treg infiltrates. These effects were attenuated by simultaneous infusion of the mast cell stabilizer, sodium cromoglycate. We conclude that CD200 expression contributes to graft prolongation through local suppression of mast cell degranulation, attraction/expansion of Treg, and attenuation of T cell effector activation. PMID:21801836

  20. Nutritional Status and Cardiac Autophagy

    Directory of Open Access Journals (Sweden)

    Jihyun Ahn

    2013-02-01

    Full Text Available Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.

  1. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  2. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  3. Nebulized Pentamidine-Induced Acute Renal Allograft Dysfunction

    Directory of Open Access Journals (Sweden)

    Siddhesh Prabhavalkar

    2013-01-01

    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.

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

    DEFF Research Database (Denmark)

    Jacobsen, I M; Claesson, Mogens Helweg

    1998-01-01

    tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.......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...... on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft...

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

    Directory of Open Access Journals (Sweden)

    Fernando Vázquez Alonso

    2012-01-01

    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.

  6. Prevention of allograft rejection in heart transplantation through concurrent gene silencing of TLR and Kinase signaling pathways

    Science.gov (United States)

    Wang, Hongmei; Zhang, Xusheng; Zheng, Xiufen; Lan, Zhu; Shi, Jun; Jiang, Jifu; Zwiep, Terry; Li, Qing; Quan, Douglas; Zhang, Zhu-Xu; Min, Weiping

    2016-01-01

    Toll-like receptors (TLRs) act as initiators and conductors responsible for both innate and adaptive immune responses in organ transplantation. The mammalian target of rapamycin (mTOR) is one of the most critical signaling kinases that affects broad aspects of cellular functions including metabolism, growth, and survival. Recipients (BALB/c) were treated with MyD88, TRIF and mTOR siRNA vectors, 3 and 7 days prior to heart transplantation and 7, 14 and 21 days after transplantation. After siRNA treatment, recipients received a fully MHC-mismatched C57BL/6 heart. Treatment with mTOR siRNA significantly prolonged allograft survival in heart transplantation. Moreover, the combination of mTOR siRNA with MyD88 and TRIF siRNA further extended the allograft survival; Flow cytometric analysis showed an upregulation of FoxP3 expression in spleen lymphocytes and a concurrent downregulation of CD40, CD86 expression, upregulation of PD-L1 expression in splenic dendritic cells in MyD88, TRIF and mTOR treated mice. There is significantly upregulated T cell exhaustion in T cells isolated from tolerant recipients. This study is the first demonstration of preventing immune rejection of allogeneic heart grafts through concurrent gene silencing of TLR and kinase signaling pathways, highlighting the therapeutic potential of siRNA in clinical transplantation. PMID:27659428

  7. Transplante experimental cardíaco heterotópico e cutâneo em camundongos Experimental heterotopic cardiac and cutaneous transplantation in mice

    Directory of Open Access Journals (Sweden)

    Patrícia Sestrheim

    2005-06-01

    Full Text Available OBJETIVO: Estudo experimental com o objetivo de desenvolver e avaliar a viabilidade das técnicas de transplante experimental cardíaco heterotópico abdominal vascularizado e cutâneo em camundongos, criando um instrumento para investigação da eficácia de soluções de preservação, novas drogas imunossupressoras, agentes biológicos, terapia gênica e indução de tolerância imunológica. MÉTODO: Para este estudo, as técnicas utilizadas foram descritas previamente por Corry et al. e Billingham et al. RESULTADOS: O tempo cirúrgico total para a realização dos transplantes cardíacos (n=20 foi, em média, 60,3±6,3 minutos e para os transplantes cutâneos (n=20, 17,75±0,71 minutos. A média de sobrevida dos aloenxertos cutâneos (n=34 e cardíacos (n=24 foi, respectivamente, 7 e 11 dias, enquanto que os isoenxertos sobreviveram por mais de 100 dias. CONCLUSÕES: Ambas as técnicas se caracterizaram pela fácil reprodutibilidade dos modelos experimentais. As diferenças entre as técnicas não se limitaram às peculiaridades metodológicas ou ao tempo de sobrevida e vascularização, mas principalmente à sua imunogenicidade e suscetibilidade à rejeição.OBJECTIVE: This is an experimental study which aims at developing and evaluating the feasibility of experimental techniques of vascularized and cutaneous abdominal heterotopic heart transplant in mice, creating an instrument of investigation for the effectiveness of prservation solutions, new immunosuppressive drugs, biological agents, genetic therapy and induction of immunological tolerance. METHOD: The techniques used in this work were previously described by Corry et al. and Billingham et al. RESULTS: The total surgical time to perform the cardiac transplants (n=20 was on average 60.3+6.3 minutes and the time of cutaneous transplants (n= 20 17.75+0.71 minutes. The average survival of the cutaneous allografts (n=34 and cardiac (n=24 allografts was 7 and 11 days, respectively, while

  8. EXPRESSION OF ICAM-1 AND LFA-1 MOLECULES IN RELATION TO RENAL ALLOGRAFT REJECTION IN RATSA

    Institute of Scientific and Technical Information of China (English)

    黄孝伦; 沈文律; 李幼平; 周泽清; 谭建三

    1999-01-01

    Objective. The purpose of this study was to assess the renal graft expression of ICAM-I (intercellular adhesion moleculeq) and LFA l(lymphocyte function-aa.soziated antigen-1)molecule with relation to graft rejection. Methods. Rat kidney traansplantation was performed according to the procedure of Kamada with some modification. Experimental rats were dividod into 5 groups. The survival time of recipient rats and function of grafts after renal transplantation were observed. The sections of renal graft were mined forantibody ICAM-1 and LFA-1, and then quantification of ICAM-1 and LFA-1 expression was accomplished by computer image analysis. Results. ICAM-1 and LFA-1 increased significantly in the renal allograft rejection group as compared with the non-rejection groups(P<0. 05). Conclustion. Both biopsy of renal graft and monitoring of ICAM-1 and LFA-1 are useful tools in diagnosing and treating acute rejection.

  9. Immune responses on allograft heart transplantation in inbred rats infected with Echinococcosis multilocularis

    Institute of Scientific and Technical Information of China (English)

    Mai Hepiretihan·Ai Erken; ZHAO Jin-ming; GUAN Xiao-yan; WEN Hao; WANG Yun-hai

    2012-01-01

    Background Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis (E.multilocularis) and is a rare but life-threatening disease.This disease commonly is characterized by an infiltrative,tumor-like growth of the E.multilocularis metacestode in the liver of human.Liver transplantation is an effective therapy for end-stage of hepatic AE,but the characteristics of host immunity associated with E.multilocularis infection with organ transplantation are poorly defined.We hereby aimed to study the immunological status and allograft heart survival in inbred rats with E.multilocularis infection.Methods Rat models of AE were established by injecting the E.multilocularis suspension made from E.multilocularis infected tissues into the abdomen of Lewis (LEW) rats.Three months later,in the experimental group,allograft heart transplantation was performed from Brown-Norway (BN) rats to the E.multilocularis infected LEW rats.In the control group,we transplanted hearts from BN rats to healthy LEW rats.The influence of the disturbed immune system in E.multilocularis infected rats on the heart transplantation was assessed,including observation of allograft heart survival time,histopathological examination of grafts and immunohistochemical examination of infiltrating cells (CD4+ T cells,CD8+ T cells and eosinophile granulocytes),measurement of interleukin (IL)-4 and interferon (IFN)-Y in the serum by enzyme-linked immunosorbent assay (ELISA) and analysis of CD4+CD25+ regulatory T cells in peripheral blood by fluorescence activated cell sorting (FACS) flow cytometric analysis.Results The survival time of recipients in the experimental group was prolonged compared with those in the control group.The numbers of graft infiltrating CD8+ T cells were decreased whereas the graft infiltrating eosinophil granulocytes (CD15+) were increased in grafts in the experimental group (P <0.05).Furthermore,the proportion of CD4+CD25+ regulatory T cells in the

  10. EXPRESSION OF ICAM-1 AND LFA-1 MOLECULES IN RELATION TO RENAL ALLOGRAFT REJECTION IN RATS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective.The purpose of this study was to assess the renal graft expression of ICAM-1(intercellular adhesion molecule-1) nd LFA-1(lymphocyte function-associated antigen-1)molecule with relation to graft rejection.Methods.Rat kiney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM-1 and LFA-1, and then quantification of ICAM-1 and LFA-1 expression was accomplished by computer image analysis.Results.ICAM-1 and LFA-1 increased significantly in the renal allograft rejection group as compared with the non-rejection groups(P<0.05).Conluson.Both biopsy of renal graft and monitoring of ICAM-1 and LFA-1 are useful tools in diagnosing and treating acute rejection.

  11. Soaking morselized allograft in bisphosphonate can impair implant fixation

    DEFF Research Database (Denmark)

    Jakobsen, Thomas; Baas, Jørgen; Bechtold, Joan E;

    2007-01-01

    biomechanical implant fixation and graft incorporation. In 10 dogs, a pair of titanium implants surrounded by a 2.5-mm gap was inserted into the proximal part of each humerus during two separate surgeries to allow two observation periods. The gap was filled with impacted, morselized allograft soaked in either...... implants was observed for 12 weeks and the second pair for 4 weeks. Implants were evaluated by histomorphometry and biomechanical pushout test. We found substantially decreased biomechanical implant fixation for all implants surrounded by impacted, morselized allograft that had been soaked in alendronate...

  12. Lateral Meniscal Allograft Transplantation: The Bone Trough Technique.

    Science.gov (United States)

    Chahla, Jorge; Olivetto, Javier; Dean, Chase S; Serra Cruz, Raphael; LaPrade, Robert F

    2016-04-01

    The lateral meniscus plays a critical role in the stability and health of the knee. Treating patients who have undergone a total lateral meniscectomy or functional equivalent is challenging, especially young and active patients. Current literature regarding meniscal tears supports that repair should be the first surgical option. Moreover, it is recommended to preserve as much meniscal tissue as possible. In cases in which a total or functional meniscectomy is a pre-existing condition, a lateral meniscal allograft transplantation is a possible option. The purpose of this surgical technique description was to detail the method of lateral meniscal allograft transplantation using a bone trough. PMID:27462536

  13. A Case of Intraparenchymal Pseudoaneurysms in Kidney Allograft

    Science.gov (United States)

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

    2016-01-01

    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

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

    Science.gov (United States)

    Ardalan, Mohammadreza

    2012-01-01

    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.

  15. Isolated heart transplantation for familial transthyretin (TTR) V122I cardiac amyloidosis.

    Science.gov (United States)

    Thenappan, Thenappan; Fedson, Savitri; Rich, Jonathan; Murks, Catherine; Husain, Aliya; Pogoriler, Jennifer; Anderson, Allen S

    2014-06-01

    Transthyretin (TTR) cardiac amyloidosis is characterized by deposition of either mutant or wild type TTR amyloid protein in the myocardium ultimately leading to progressive cardiomyopathy and heart failure. The most common TTR gene mutation that leads to TTR cardiac amyloidosis is the valine-to-isoleucine substitution at position 122 (V122I or Ile122). Currently, the only definitive treatment suggested for mutant TTR cardiac amyloidosis is the combined or sequential liver-heart transplantation in eligible patients, since liver is the source of TTR production. Here, we report a case of heterozygous Val122L mutated TTR-related cardiac amyloidosis treated with isolated heart transplantation with no recurrence of amyloid in the cardiac allograft and no systemic abnormalities 5 years after heart transplantation. Abbreviations MMF mycophenolate mofetil NYHA New York Heart Association TTR transthyretin VE minute ventilation. PMID:24818650

  16. [Cardiac amyloidosis].

    Science.gov (United States)

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  17. Honey preserved cortical allografts in the repair of diaphyseal femoral defect in dogs: clinical and radiographic

    International Nuclear Information System (INIS)

    Fourteen adult mongrel dogs were used to evaluate the honey preserved cortical allografts in the repair of diaphyseal femoral defect. The allografts were inserted into a 5cm segmental defect created in the mid-diaphysis of the right femur in each dog. The bones were stabilized with a dynamic compression plate and eight bone screws. Healing was followed clinically and femora were evaluated radiographically, periodically. Nineteen (79.2%) of the twenty-four host-graft interfaces were radiographically incorporated. Average time to allograft incorporation was 67.1 days (range 45 days to 90 days). There was no statistical difference in the allograft incorporation time between proximal and distal host-graft interfaces. Complications observed were nonunion, allograft fracture, and allograft resorption. The conclusion is that despite the complications, honey preserved cortical allografts are a viable option to bone reconstruction

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...

  19. Tolerability of sirolimus: a decade of experience at a single cardiac transplant center.

    Science.gov (United States)

    Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, William Steves; Peltz, Matthias; Drazner, Mark H

    2013-01-01

    Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. PMID:24304376

  20. Fetal cardiac interventions: clinical and experimental research.

    Science.gov (United States)

    Yuan, Shi-Min; Humuruola, Gulimila

    2016-01-01

    Fetal cardiac interventions for congenital heart diseases may alleviate heart dysfunction, prevent them evolving into hypoplastic left heart syndrome, achieve biventricular outcome and improve fetal survival. Candidates for clinical fetal cardiac interventions are now restricted to cases of critical aortic valve stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic left heart syndrome with an intact or highly restrictive atrial septum as well as fetal heart block. The therapeutic options are advocated as prenatal aortic valvuloplasty, pulmonary valvuloplasty, creation of interatrial communication and fetal cardiac pacing. Experimental research on fetal cardiac intervention involves technical modifications of catheter-based cardiac clinical interventions and open fetal cardiac bypass that cannot be applied in human fetuses for the time being. Clinical fetal cardiac interventions are plausible for midgestation fetuses with the above-mentioned congenital heart defects. The technical success, biventricular outcome and fetal survival are continuously being improved in the conditions of the sophisticated multidisciplinary team, equipment, techniques and postnatal care. Experimental research is laying the foundations and may open new fields for catheter-based clinical techniques. In the present article, the clinical therapeutic options and experimental fetal cardiac interventions are described. PMID:27279868

  1. Trichloroethylene Exposure during Cardiac Valvuloseptal Morphogenesis Alters Cushion Formation and Cardiac Hemodynamics in the Avian Embryo

    OpenAIRE

    Drake, Victoria J.; Koprowski, Stacy L.; Lough, John; Hu, Norman; Susan M. Smith

    2006-01-01

    It is controversial whether trichloroethylene (TCE) is a cardiac teratogen. We exposed chick embryos to 0, 0.4, 8, or 400 ppb TCE/egg during the period of cardiac valvuloseptal morphogenesis (2–3.3 days’ incubation). Embryo survival, valvuloseptal cellularity, and cardiac hemodynamics were evaluated at times thereafter. TCE at 8 and 400 ppb/egg reduced embryo survival to day 6.25 incubation by 40–50%. At day 4.25, increased proliferation and hypercellularity were observed within the atriovent...

  2. Successful Management of Sequential Pulmonary Infections in a Cardiac Transplant Recipient

    OpenAIRE

    Galbraith, John; Preiksaitis, Jutta K.; Czekanski, Sandra; Poznansky, Mark J; Hirji, Mohamed

    1990-01-01

    A case of a cardiac allograft recipient who had an initial combined pulmonary infection with cytomegalovirus, Aspergillus fumigatus and Nocardia asteroides, successfully treated with liposomal amphotericin B and sulfisoxazole and followed by an episode of respiratory syncytial virus pneumonitis, is presented. This case illustrates the role of computed tomographic imaging in the recognition, diagnosis and monitoring of complex opportunistic pulmonary infections and the benefits of liposomal am...

  3. IL-6 Promotes Cardiac Graft Rejection Mediated by CD4+ Cells1

    OpenAIRE

    Booth, Adam Jared; Grabauskiene, Svetlana; Wood, Sherri Chan; Lu, Guanyi; Burrell, Bryna E.; Bishop, D. Keith

    2011-01-01

    IL-6 mediates numerous immunologic effects relevant to transplant rejection; however its specific contributions to these processes are not fully understood. To this end, we neutralized IL-6 in settings of acute cardiac allograft rejection associated with either CD8+ or CD4+ cell dominant responses. In a setting of CD8+ cell dominant graft rejection, IL-6 neutralization delayed the onset of acute rejection while decreasing graft infiltrate and inverting anti-graft Th1/Th2 priming dominance in ...

  4. Coronary artery bypass with glycerol-preserved saphenous vein allografts

    OpenAIRE

    Bortolotti, Uberto; Casarotto, Dino; Frugoni, Carlo; De Mozzi, Pierluigi; Thiene, Gaetano; Gallucci, Vincenzo

    1981-01-01

    Over a 2-year period, 19 patients whose autologous saphenous veins were either unsuitable or unavailable underwent myocardial revascularization with saphenous vein allografts (SVAs) at our institution. All SVAs had been preserved in 98% glycerol at room temperature for at least 3 weeks (average, 7 weeks); before use, they were rinsed with saline and antibiotic solution.

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

    Science.gov (United States)

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Rajan Kapoor

    2016-01-01

    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.

  7. Effect of allograft compound vertebra on vertebral reconstruction in rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHOU Pang-hu; LIU Shi-qing; MING Jiang-hua

    2007-01-01

    Objective: To study the effect of allograft compound vertebra on vertebral reconstruction in rabbits so as to provide biomechanical direction for manufacturing and selecting vertebral reconstruction materials.Methods: Twenty-five healthy New Zealand white rabbits were divided randomly into three groups: normal group ( Group A, n = 5), iliac bone graft group ( Group B,n = 10) and allograft compound vertebra group ( Group C,n = 10). After C4 was resected, iliac bone implantation and allograft bone cage transplantation were fulfilled in Group B and Group C, respectively. Every 5 rabbits from Group B and Group C were selected to test the biomechanical strength and biological activity one and two months postoperatively.Results: No significant statistical difference was found between Group A and Group C one and two months postoperatively (P > 0.05). The biomechanical strength of Group B was much weaker than that of Group A and Group C one month postoperatively ( P < 0.05 ), but at two months postoperatively, no statistical difference was found among the three groups. The biological activity and vertebral moulding ability of Group C were better than those of Group B at one and two months postoperatively.Conclusions: Compound vertebra, which is made up of allograft cortical bone cage and autogenous cancellous bone, shows instantaneous and permanent biomechanical stability and biological activity, therefore, it is an ideal material for vertebral reconstruction.

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

    Science.gov (United States)

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

    2012-01-01

    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.

  9. Identification and treatment of cyclosporine-associated allograft thrombosis

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-08-01

    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.

  10. TGF-β1转基因对大鼠心脏移植物缺血-再灌注损伤的影响%Effect of Ad. mTGF-β1-gene transfection on ischemia-reperfusion injury to the cardiac allografts of rat in vitro

    Institute of Scientific and Technical Information of China (English)

    崔广晖; 赵松; 王铁栓; 廖崇先

    2010-01-01

    Objective Isohemia-reperfusion injury oecurred during heart transplantation may result in failure of grafts and the death of receivers perioperatively. Over expression of TGF-β1 in the myocardium therapeutically was shown to be help-ful in limiting the reperfusion injury to the grafts. The study was designed to investigate the role of Ad. mTGF-β1 gene transfec-tion during ischemia-reperfusion injury in vitro after heart transplantation in rats and the possible mechanisms. Methods The model of heterotopic cardiac transplantation was established by Heron's technique with cuff vessel anastomosis. Animals were divided into 3 groups: in group A ( n =6, control group), the donor hearts were perfusod with 6 ml of Stanford University cardio-plegic solution via coronary arteries at 4℃ for about 40 minutes; in group B ( n =6, vector alone group), the donor hearts were perfused with 6 ml of Stanford University cardioplegic solution containing 5 × 10~9 plaque-forming units( pfu)/gram of the vec-tor, and in group C (study group), the donor hearts were perfused with the solution containing 5 × 10~9 pfu/gram vector with mTGF-β1. The donor hearts were observed with an electro-microscope. The expression of mTGF-β1 in the grafts was identified with immunohistochemical staining. Gene products expressed in tissues were quantified by one step RT-PCR. Activities of SOD ,MDA ,MPO in the grafts were measured. Results At 8 hours after transplantation, mTGF-β1 and its expression were de-tected by means of RT-PCR and immunohistochemical staining in the rats of group C. Expression scores of foreign gene were significantly higher in groups A and B. The apoptotic index of the myocardial cells in group C was lower than those in groups A and B. The activity of SOD was higher in group C than those in groups A and B, though the activities of MDA and MPO were decreased. Conclusion The study demonstrated that gent transfer in vitro via coronary artery was effective. Ad. mTGF-β1 gene

  11. ACL graft failure location differs between allografts and autografts

    Directory of Open Access Journals (Sweden)

    Magnussen Robert A

    2012-06-01

    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

  12. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  13. Patient selection for cardiac transplant in 2012.

    Science.gov (United States)

    Kinkhabwala, Mona Parikh; Mancini, Donna

    2013-02-01

    Heart transplantation is the treatment of choice for many patients with advanced heart failure who remain symptomatic despite optimal medical therapy. Although heart transplantation results have improved over the past 10 years, careful patient selection and risk stratification of patients with advanced heart failure is paramount given limited allograft resources. Moreover, as alternative therapies to heart transplant, such as mechanical circulatory support, continue to improve in terms of patient outcomes, the selection strategy for those patients who would benefit from device support as destination therapy or bridge-to-transplant versus those patients who should proceed directly to transplant will continue to evolve. This review focuses on the optimal timing for heart transplant, risk stratification models for patient selection, as well as examining factors that continue to provoke controversy during the candidate selection process and factors that have changed from absolute to relative contraindications as the authors experience with cardiac transplantation continues to increase. PMID:23405839

  14. Combined HLA matched limbal stem cells allograft with amniotic membrane transplantation as a prophylactic surgical procedure to prevent corneal graft rejection after penetrating keratoplasty: case report

    Directory of Open Access Journals (Sweden)

    Paolo Capozzi

    2014-09-01

    Full Text Available Purpose. To determine if the use of combined HLA matched limbal stem cells allograft with amniotic membrane transplantation (AMT is a safe and effective prophylactic surgical procedure to prevent corneal graft after penetrating keratoplasty (PK. Methods. We report the case of a 17 years old patient with a history of congenital glaucoma, trabeculectomy and multiple corneal graft rejections, presenting total limbal cell deficiency. To reduce the possibility of graft rejection in the left eye after a new PK, a two step procedure was performed. At first the patient underwent a combined HLA matched limbal stem cells allograft (LAT and AMT and then, 10 months later, a new PK. Results. During 12 months of follow-up, the corneal graft remained stable and smooth, with no sign of graft rejection. Conclusions. In our patient, the prophylactic use of LAT from HLA-matched donors and AMT before PK, may result in a better prognosis of corneal graft survival.

  15. [Cardiac support and replacement therapies].

    Science.gov (United States)

    Lotz, Christopher; Roewer, Norbert; Muellenbach, Ralf M

    2016-09-01

    Circulatory support represents an integral part within the treatment of the critically ill patient. Sophisticated pharmacologic regimens help to maintain systemic perfusion pressure by increasing vascular tone as well as mediating positive inotropic effects. Besides the administration of catecholamines and phosphodiesterase-III-inhibitors, in particular the administration of levosimendan represents a promising alternative during low-cardiac-output. Nevertheless, sufficient evidence demonstrating a survival benefit for any pharmacologic regimen is nonexistent. In case pharmacological measures do not suffice mechanical cardiopulmonary support (MCS) may be used. MCS may be used during cardiopulmonary resuscitation or a "low-cardiac-output-syndrome" as bridging towards decision, recovery or long-term support. Venoarterial extracorporeal membrane oxygenation (vaECMO) may take over cardiopulmonary function and may improve survival as well as neurological outcome after cardiogenic shock or cardiopulmonary resuscitation. PMID:27631451

  16. MANAGEMENT OF ALLOSENSITIZED CARDIAC TRANSPLANT CANDIDATES

    OpenAIRE

    Velez, Mauricio; Johnson, Maryl R.

    2009-01-01

    Cardiac transplantation remains the best treatment in advanced heart failure patients with a high risk of death. However, an inadequate supply of donor hearts decreases the likelihood of transplantation for many patients. Ventricular assist devices (VAD) are being increasingly used as a bridge to transplant in patients who may not survive long enough to receive a heart. This expansion in VAD use has been associated with increasing rates of allosensitization in cardiac transplant candidates. A...

  17. Across all solid organs, adolescent age recipients have worse transplant organ survival than younger age children: A US national registry analysis.

    Science.gov (United States)

    Dharnidharka, Vikas R; Lamb, Kenneth E; Zheng, Jie; Schechtman, Kenneth B; Meier-Kriesche, Herwig-Ulf

    2015-08-01

    Univariate analyses suggest that adolescents have worse long-term allograft survival versus younger children across different SOT. This study's objective was to determine whether multivariate analyses of a large national database recording all deceased SOT (KI; LI; HR; LU) also show worse adolescent allograft survival in the different organs. Using data from the national Scientific Registry for Transplant Recipients in the USA for pediatric primary SOT from 1989 to 2010, we calculated median half-lives and constructed K-M graft survival curves. Recipient age at transplant (organs will be a defining issue in the future.

  18. Cardiac Penetrating Injuries and Pseudoaneurysm

    Institute of Scientific and Technical Information of China (English)

    CHEN Shifeng

    2002-01-01

    Objective To discuss the early diagnosis and treatment of cardiac penetrating injuries and pseudoaneurysm. Methods 18 cases of cardiac penetrating injuries, in which 2 cases were complicated with pseudoaneurysm, were diagnosed by emergency operation and color Doppler echocardiography between May 1973 and Dec. 2001 in our hospital. The basis for emergency operation is the injured path locating in cardiac dangerous zone, severe shock or pericardial tamponade. ResultsAmong 18 cases of this study, 17 cases underwent emergency operation. During the operation, 11 cases were found injured in right ventricle, 2 cases were found injured in right atrium, 1 case was found injured in pulmonary artery,4 cases were found injured in left ventricle, 2 cases were found complicated with pseudoaneurysm. 17cases underwent cardiac repair including 1 case of rupture of aneurysm. 1 case underwent elective aneurysm resection. In whole group, 15 cases survived(83.33% ), 3 cases died( 16.67%). The cause of death is mainly hemorrhagic shock. Conclusion Highly suspicious cardiac penetrating injuries or hemopericaridium should undergo direct operative exploration. Pseudoaneurysm should be resected early,which can prevent severe complications.

  19. Study on donor-specific splenocyte combined with anti-splenocyte serum inducing cardiac xenograft survival in rat%延长大鼠异种心脏移植后存活时间的实验研究

    Institute of Scientific and Technical Information of China (English)

    杜成友; 姚榛祥; 郑军; 董蒲江; 周洪伟

    2000-01-01

    Objective To study the effect of donor-specific splenocyte combined with antisplenocyte serum to be given i.v.to rats 12 days before transplantation on both IgG production and cardiac xenograft survival.Methods All rats were divided into groups A,B,C and D,recieving the following combined therapies respectively:splenocytes and anit-serum(group A);splenocyte,anti-serum and CCV(group B);splenocyte,anti-serum,CCV,CsA and Cy(group C);splenocytes,anti-serum,CCV,CsA,Cy,anti-MΦmAb and anti-NK mAb(group D).The rats were given i.v.splenocytes(1 time in groups A,B,C and D were(0.32±0.12)h,(25.6±9.6)h,(48.6±10.4)h(P<0.05,vs group B)and(72.4±21.7)h(P<0.05,vs groups B and C)respectively.The serum IgG values in groups A,B,C and D on the day 0 were decreased significantly (P<0.05,groups B,C and D vs A;P<0.05 vs those of groups A,B,C and D on the day-6);The pathologic and immunohistochemical examination of rejected hearts in group A revealed the lesion of hyperacute rejection with C3 deposition,and in groups B,C and D monocyte infiltration,hemorrhage and a little IgG deposition.Conclusion The donor-spectific splenocytes combined with anti-splenocyte serum to be given i.v.to recipients 12 days pretransplantation,especially with CCV,CsA,Cy combination therapies can effectively suppress the IgG production and prolong the graft survival.%目的 研究如何延长大鼠异种心脏移植后的存活时间.方法 实验分为A、B、C、D四组.A组:移植术前12、8、4、0 d及10、6、2、0 d分别将脾细胞1 x 108个,抗血清0.2 ml静脉注入受体大鼠;B组:在A组的基础上,加用中华眼镜蛇毒(CCV)0.2 mg·kg-1·d-1,术前3 d至术日腹腔注射.C组:在B组的基础上,加用环孢素A(CsA)10 mg·kg-1·d-1、环磷酰胺(Cy)20 mg·kg-1·d-1,术前12d开始至术日腹腔注射.D组:在C组的基础上,加用抗巨噬细胞和抗自然杀伤细胞单克隆抗体250μg穔g-1穌-1,术前12 d开始至术日腹腔注射.结果 A、B、C、D

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-11-01

    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.

  1. Freeze-dried fibular allograft in anterior spinal surgery: cervical and lumbar applications.

    OpenAIRE

    Wetzel, F.T.; Hoffman, M. A.; Arcieri, R. R.

    1993-01-01

    Fifty-six patients who underwent anterior fusion utilizing fibular allograft are reviewed. Thirty-two patients underwent multiple-level anterior cervical discectomy and fusion utilizing fibular strut allograft, and 24 underwent anterior lumbar discectomy and fusion using fibular strut allograft. Cervical surgery was performed via the strut technique of Whitecloud and LaRocca and lumbar surgery was performed via a transperitoneal or retroperitoneal approach. Postoperatively, patients were assi...

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

    Science.gov (United States)

    2001-12-01

    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.

  3. Healing properties of allograft from alendronate-treated animal in lumbar spine interbody cage fusion

    OpenAIRE

    Xue, Qingyun; Li, Haisheng; Zou, Xuenong; Bünger, Mathias; Egund, Niels; Lind, Martin; Christensen, Finn Bjarke; Bünger, Cody

    2004-01-01

    This study investigated the healing potential of allograft from bisphosphonate-treated animals in anterior lumbar spine interbody fusion. Three levels of anterior lumbar interbody fusion with Brantigan cages were performed in two groups of five landrace pigs. Empty Brantigan cages or cages filled with either autograft or allograft were located randomly at different levels. The allograft materials for the treatment group were taken from the pigs that had been fed with alendronate, 10 mg daily ...

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

    Science.gov (United States)

    2001-12-01

    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. PMID:11770503

  5. Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues.

    Science.gov (United States)

    Kant, Cavit D; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Yamada, Yohei; Connolly, Sarah E; Marino, Jose; Tocco, Georges; Benichou, Gilles

    2015-02-01

    In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs.

  6. Management of post-biopsy renal allograft arteriovenous fistulas with selective arterial embolization: immediate and long-term outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Loffroy, R. [Department of Diagnostic and Interventional Radiology, University of Dijon School of Medicine, Bocage Teaching Hospital, Dijon (France)], E-mail: loffroy.romaric@neuf.fr; Guiu, B.; Lambert, A. [Department of Diagnostic and Interventional Radiology, University of Dijon School of Medicine, Bocage Teaching Hospital, Dijon (France); Mousson, C.; Tanter, Y. [Department of Nephrology and Renal Transplantation (France); Martin, L. [Department of Pathology, University of Dijon School of Medicine, Bocage Teaching Hospital, Dijon (France); Cercueil, J.-P.; Krause, D. [Department of Diagnostic and Interventional Radiology, University of Dijon School of Medicine, Bocage Teaching Hospital, Dijon (France)

    2008-06-15

    Aim: To evaluate the outcomes after transcatheter embolization of percutaneous biopsy-related arteriovenous fistulas in renal allografts. Materials and methods: All post-biopsy renal-transplant vascular injuries referred for embolization between June 1999 and October 2006 were reviewed retrospectively. There were six male and six female patients with a mean age of 49.8 years (range 25-67 years); nine patients were symptomatic, three asymptomatic. Colour Doppler ultrasound (CDUS) and angiography showed one intra-renal arteriovenous fistula in 10 patients and two in two patients, combined with a pseudoaneurysm in six patients. Superselective embolization using a single catheter or coaxial microcatheter was performed with 0.035'' coils or 0.018''microcoils, respectively, in all 12 cases. 24-h creatinine clearance values before (the day of biopsy) and after (7-14 days; 3 months) the procedure were compared using the Wilcoxon signed-rank test. Physical examination and CDUS were performed after 1, 6, and 12 months, and yearly thereafter. Mean follow-up was 33.6 months. Results: Complete definitive occlusion of the fistula was achieved consistently with a single procedure. No procedure-related complications occurred. Renal infarction was minor in all patients (0-10% in nine and 10-20% in three). Symptoms resolved completely. Creatinine clearance values obtained before and after embolization were not statistically different (p = 0.168;.889 respectively). No late recurrences were reported. Conclusion: Transcatheter embolization with coaxial or single-catheter techniques was effective and safe for treating post-biopsy arteriovenous fistulas in renal transplants. The loss of renal parenchyma was minimal and no mid-term deterioration of allograft function was noted. The long-term survival of the renal allograft seemed to be not affected by embolization.

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

    DEFF Research Database (Denmark)

    Ito, Hiromu; Koefoed, Mette; Tiyapatanaputi, Prarop;

    2005-01-01

    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...

  8. Healing properties of allograft from alendronate-treated animal in lumbar spine interbody cage fusion.

    Science.gov (United States)

    Xue, Qingyun; Li, Haisheng; Zou, Xuenong; Bünger, Mathias; Egund, Niels; Lind, Martin; Christensen, Finn Bjarke; Bünger, Cody

    2005-04-01

    This study investigated the healing potential of allograft from bisphosphonate-treated animals in anterior lumbar spine interbody fusion. Three levels of anterior lumbar interbody fusion with Brantigan cages were performed in two groups of five landrace pigs. Empty Brantigan cages or cages filled with either autograft or allograft were located randomly at different levels. The allograft materials for the treatment group were taken from the pigs that had been fed with alendronate, 10 mg daily for 3 months. The histological fusion rate was 2/5 in alendronate-treated allograft and 3/5 in non-treated allograft. The mean bone volume was 39% and 37.2% in alendronate-treated or non-treated allograft (NS), respectively. No statistical difference was found between the same grafted cage comparing two groups. The histological fusion rate was 7/10 in all autograft cage levels and 5/10 in combined allograft cage levels. No fusion was found at all in empty cage levels. With the numbers available, no statistically significant difference was found in histological fusion between autograft and allograft applications. There was a significant difference of mean bone volume between autograft (49.2%) and empty cage (27.5%) (P<0.01). In conclusion, this study did not demonstrate different healing properties of alendronate-treated and non-treated allograft for anterior lumbar interbody fusion in pigs. PMID:15248057

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-12-31

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

    2010-06-15

    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.)

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    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....

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

    DEFF Research Database (Denmark)

    Koefoed, Mette; Ito, Hiromu; Gromov, Kirill;

    2005-01-01

    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...... coating induced endochondral bone formation directly on the cortical surface of the allograft by day 14. By day 28 there was evidence of remodeling of the new woven bone and massive osteoclastic resorption of the cortical surface of the rAAV-caAlk2-coated allografts only. Micro-CT analysis of rAAV-Lac...

  13. Cold Ischemia Induces Isograft Arteriopathy, but Does Not Augment Allograft Arteriopathy in Non-Immunosuppressed Hosts

    OpenAIRE

    Furukawa, Yutaka; Libby, Peter; Stinn, Jennifer L.; Becker, Gerold; Mitchell, Richard N

    2002-01-01

    Prolonged cold ischemia has been suggested as a factor that will exacerbate later graft arterial disease (GAD), a major limiting factor for long-term transplant survival. We therefore examined the effects of cold ischemia on GAD as well as adhesion molecule and cytokine expression in murine cardiac grafts. Mild GAD developed in isografts undergoing 4-hour cold ischemia. Relative to control isografts, cold ischemia induced transiently enhanced endothelial expression of intercellular adhesion m...

  14. Raman-based detection of hydroxyethyl starch in kidney allograft biopsies as a potential marker of allograft quality in kidney transplant recipients

    Science.gov (United States)

    Vuiblet, Vincent; Fere, Michael; Bankole, Ezechiel; Wynckel, Alain; Gobinet, Cyril; Birembaut, Philippe; Piot, Olivier; Rieu, Philippe

    2016-01-01

    In brain-dead donor resuscitation, hydroxyethyl starch (HES) use has been associated with presence of osmotic-nephrosis-like lesions in kidney transplant recipients. Our aim was to determine whether the presence of HES in protocol renal graft biopsies at three months (M3) after transplantation is associated with renal graft quality. According to the HES administered to the donor during the procurement procedure, two groups of patients were defined according graft exposition to HES: HES group, (N = 20) and control group (N = 6). Detection and relative quantification of HES was performed by Raman spectroscopy microimaging on M3 protocol renal graft biopsies. Statistical analyses were used to investigate the association between Raman data and graft characteristics. HES spectral signal was revealed negative in the control group, whereas it was positive in 40% of biopsies from the HES group. In the HES group, a stronger HES signal was associated with a lower risk of graft failure measured by the Kidney Donor Risk Index (KDRI) and was correlated with the allograft kidney function. Thus, HES accumulation in donor kidney, as probed by Raman biophotonic technique, is correlated with the quality of donor kidney and consequently the graft renal function and graft survival. PMID:27608775

  15. Regulatory oversight in the United States of vascularized composite allografts.

    Science.gov (United States)

    Glazier, Alexandra K

    2016-06-01

    Vascularized composite allograft (VCA) transplantation is a medically acceptable treatment for the reconstruction of major tissue loss. The advent of VCA transplantation has spurred regulatory and policy development in the United States to address the multiple clinical, ethical and legal issues that must be considered for the practice of VCA donation and transplantation to develop within the existing framework of public trust and transparency vital to the success of donation and transplantation. PMID:26284312

  16. Lumbar intervertebral disc allografting in a goat model

    OpenAIRE

    Hung, Y; Xiao, J; Luk, K.; Leung, V.; Lu, W.

    2012-01-01

    Preliminary study in humans indicated that whole fresh-frozen intervertebral disc (IVD) transplantation may be an effective treatment for disc degenerative diseases, but signs of degenerative change in the allograft were noted after the transplantation. The underlying mechanisms are not fully understood and remain a series of ongoing research in large animal model. Because of the ethically and economically accessible issues as well as anatomical similarity with human disc, the goats were used...

  17. Mechanisms involved in antibody- and complement-mediated allograft rejection

    OpenAIRE

    Wasowska, Barbara A.

    2010-01-01

    Antibody-mediated rejection has become critical clinically because this form of rejection is usually unresponsive to conventional anti-rejection therapy, and therefore, it has been recognized as a major cause of allograft loss. Our group developed experimental animal models of vascularized organ transplantation to study pathogenesis of antibody- and complement-mediated endothelial cell injury leading to graft rejection. In this review, we discuss mechanisms of antibody-mediated graft rejectio...

  18. SOCS3基因转染对小鼠同种异体移植心脏存活时间的影响%Suppressors of cytokine signaling 3 gene transfer prolongs the survival time of cardiac allograft in mice

    Institute of Scientific and Technical Information of China (English)

    宋少华; 傅志仁; 沈筱芸; 刘芳; 郭闻渊; 王正昕; 丁国善

    2010-01-01

    目的 研究腺病毒载体介导的细胞因子信号抑制因子3(suppressors of cytokine sig-naling 3,SOCS3)基因转染对小鼠同种异体移植心脏存活时间的影响.方法 以Balb/c小鼠为供体,以C5781/6小鼠为受体,行同种异体心脏移植.C57BL/6同种异体小鼠心脏移植受体分为3组(21只/组): (1)埘照组,单纯同种异体心脏移植;(2)Ad-SOCS3组,供体术前24 h转染2×109pfu编码SOCS3基闪的腺病毒载体; (3)Ad-GFP组,供体术前24 h转染2×109pfu空病毒载体.每组10只受体用于观察生存期;每组5只受体分别于术后第1、3、5、7、9日处死,获取移植物,采用实时定量逆转录酶聚合酶链反应检测SOCS3 mRNA表达的变化:每组6只受体于术后第6 日处死,获取移植物和脾脏用于组织学检查及Foxp3 mRNA、白介素(IL)-17 mRNA表达的检测,同时检测脾脏的混合淋巴细胞反应(mixed lymphocyte reaction,MLR)强度,采用流式细胞仪分析调节性T细胞(Treg)及Th17细胞的比例.结果 供体术前SOCS3基因转染可明显增加术后移植物内SOCS3 mRNA表达;Ad-SOCS3组的移植心脏存活时间明显长于对照组、Ad-GFP组(P0.05).但IL-17 mRNA水平及脾脏内CD4+IL-17+Th17比例较其他两组明显降低(均为P<0.05).结论 腺病毒载体介导的供体SOCS3基凶转染能够延长移植心脏存活时间,其机制可能与抑制淋巴细胞浸润、抑制T淋巴细胞同种抗原反应性以及抑制Th17免疫反应等有关,与Treg的产生及功能无关.

  19. Pathological spectrum of cytomegalovirus infection of renal allograft recipients-an autopsy study from north India.

    Science.gov (United States)

    Joshi, Kusum; Nada, Ritambhra; Radotra, Bishan Das; Jha, Vivekanand; Sakhuja, Vinay

    2004-07-01

    This is a retrospective study of autopsy material to highlight the histo-morphological changes in cytomegalovirus (CMV) infection amongst renal allograft recipients. Nineteen out of 80 patients (23.75%) autopsied during a seventeen-year period (1985-2001) had CMV infection. Pulmonary infection was present in 14 out of 19 cases of which four had isolated lung involvement. Likewise, there were two cases each of isolated oesophageal and renal involvement; one case with isolated colonic involvement. The other 10 cases had multi-organ involvement and the organs involved were kidneys (4), esophagus (6), stomach (1), colon (5), adrenals (3), pancreas (3), liver (1) and spleen (1). Pulmonary infection with CMV was associated with acute pneumonitis in 3 cases and lymphocytic interstitial pneumonitis in 9 instances. Four out of 6 cases had acute tubulo-interstitial nephritis induced by CMV and only two cases had no significant inflammatory response. Glomerular involvement in the form of CMV inclusions in the glomeruli was present in only one case. Gastrointestinal CMV infection (15) presented as acute necrotizing ulceration because of predominant endothelial involvement. Post transplant survival period varied from one month to three years, with majority (14) of the patients having survived for less than one year.

  20. Treatment of chronic osteomyelitis with one-stage allograft

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

    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.

  1. Significance of Urinary Proteome Pattern in Renal Allograft Recipients

    Directory of Open Access Journals (Sweden)

    Sufi M. Suhail

    2014-01-01

    Full Text Available 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.

  2. Multidetector computed tomography findings of spontaneous renal allograft ruptures

    Energy Technology Data Exchange (ETDEWEB)

    Basaran, C. [Department of Radiology, Baskent University Faculty of Medicine, Ankara (Turkey)], E-mail: ceylab@baskent-ank.edu.tr; 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)

    2009-05-15

    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.

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

    Science.gov (United States)

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

    2014-03-01

    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.

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

    Science.gov (United States)

    Suhail, Sufi M

    2014-01-01

    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.

  5. Advances in cardiac magnetic resonance imaging of congenital heart disease

    NARCIS (Netherlands)

    Driessen, Mieke M P; Breur, Johannes M. P. J.; Budde, Ricardo P J; van Oorschot, Joep W M; van Kimmenade, Roland R J; Sieswerda, Gertjan Tj.; Meijboom, Folkert J; Leiner, Tim

    2015-01-01

    Due to advances in cardiac surgery, survival of patients with congenital heart disease has increased considerably during the past decades. Many of these patients require repeated cardiovascular magnetic resonance imaging to assess cardiac anatomy and function. In the past decade, technological advan

  6. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  7. Impact of cytokine expression in the pre-implanted donor lung on the development of chronic lung allograft dysfunction subtypes.

    Science.gov (United States)

    Saito, T; Takahashi, H; Kaneda, H; Binnie, M; Azad, S; Sato, M; Waddell, T K; Cypel, M; Liu, M; Keshavjee, S

    2013-12-01

    The long-term success of lung transplantation continues to be challenged by the development of chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the relationship between cytokine expression levels in pre-implanted donor lungs and the posttransplant development of CLAD and its subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Of 109 patients who underwent bilateral lung or heart-lung transplantation and survived for more than 3 months, 50 BOS, 21 RAS and 38 patients with No CLAD were identified by pulmonary function test results. Using donor lung tissue biopsies sampled from each patient, expression levels of IL-6, IL-1β, IL-8, IL-10, interferon-γ and tumor necrosis factor-α mRNA were measured. IL-6 expression levels were significantly higher in pre-implanted lungs of patients that ultimately developed BOS compared to RAS and No CLAD (p = 0.025 and 0.011, respectively). Cox regression analysis demonstrated an association between high IL-6 expression levels and BOS development (hazard ratio = 4.98; 95% confidence interval = 2.42-10.2, p < 0.001). In conclusion, high IL-6 mRNA expression levels in pre-implanted donor lungs were associated with the development of BOS, not RAS. This association further supports the contention that early graft injury impacts on both late graft function and early graft function. PMID:24164971

  8. Anaesthesia for non-cardiac surgery in a cardiac transplant recipient

    OpenAIRE

    Adarsh C Swami; Amit Kumar; Sunny Rupal; Sneh Lata

    2011-01-01

    Cardiac transplantation has become the standard therapy for idiopathic dilated cardiomyopathy and end-stage ischaemic heart disease. With the introduction of newer immunosuppressants, together with better patient selection, improved perioperative monitoring and care, the overall survival of recipients has improved. An increasing number of patients who received a transplant present for either elective or emergency non-cardiac surgery. We hereby discuss the perioperative management of such a pa...

  9. Recipient origin of neointimal vascular smooth muscle cells in cardiac allografts with transplant arteriosclerosis

    NARCIS (Netherlands)

    Hillebrands, JL; van den Hurk, BMH; Klatter, FA; Popa, ER; Nieuwenhuis, P; Rozing, J

    2000-01-01

    Background: Coronary artery disease is today's most important post-heart transplantation problem after the first perioperative year. Histologically, coronary artery disease is characterized by transplant arteriosclerosis. The current view on this vasculopathy is that vascular smooth muscle (VSM) cel

  10. Role of the spleen in cell-mediated cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Hall, B.M.

    1982-04-01

    A quantitative adoptive transfer assay was used to investigate the role of the spleen in cell-mediated rejection of directly vascularized heart grafts. In this assay, the cell-mediated rejection response can be examined directly by testing the capacity of inocula of T cells to effect rejection of DA heart grafts in PVG rats whose own lymphocytes have been destroyed by whole body irradiation. The capacity of a variety of inocula, including lymph node cells (LNCs), spleen cells, and T cells from lymph node and spleen, to restore rejection were compared in groups of splenectomized and nonsplenectomized hosts. In both groups all inocula restored rejection toward normal. Only in experiments testing inocula equivalent to a small fraction of the naive peripheral lymphocyte pool was rejection delayed in the splenectomized hosts, and this was only a delay of a few days. These results showed that in the absence of the spleen, the primary rejection responses can be generated. In addition, it was demonstrated that the normal spleen contains only a small fraction of the T cell pool with the capacity to effect rejection. Memory T cells were also shown to mediate rejection in splenectomized hosts. It is concluded that with strongly incompatible grafts, splenectomy has only a trivial immunosuppressive effect; it removes neither a sigificant proportion of the alloreactive T cell pool nor the essential site for activation of proliferation of these cells.

  11. Review Article of Cardiac Amyloidosis

    Directory of Open Access Journals (Sweden)

    Jittiporn PURATTANAMAL

    2010-06-01

    Full Text Available Cardiac amyloidosis is a term that means the deposit of abnormal proteins in the myocardium leading to global thickening of the heart walls. The clinical character is that of infiltrative cardiomyopathy. AL amyloidosis is the most common type that involves cardiac failure. Cardiac amyloid precedes clinical congestive heart failure, especially right-sided heart failure. Laboratory investigations have identified the amyloid fibril proteins deposited in the organ tissues. Immunofixation tests are the most sensitive that recognize the paraprotein mean light chain protein or immunoglobulin subtype deposit. Prognosis is poor if AL amyloidosis is untreated. Treatment of systemic involvement in AL amyloidosis is via chemotherapy such as melphalan and prednisolone. UK experts have reported the results of treatment in AL amyloidosis. Regardless of the use of adjunctive chemotherapy, the five-year survival after heart transplantation was generally poorer for AL (20 % at five years, but similar for non-AL amyloidosis (64 % at five years, than heart transplants in other cases. Progression of the systemic disease contributed to increased mortality. A specific treatment that increases the chances of survival is unknown.

  12. The challenge to detect heart transplant rejection and transplant vasculopathy non-invasively - a pilot study

    OpenAIRE

    Helber Uwe; Schroeder Stephen; Aebert Hermann; Burgstahler Christof; Usta Engin; Kopp Andreas F; Ziemer Gerhard

    2009-01-01

    Abstract Background Cardiac allograft rejection and vasculopathy are the main factors limiting long-term survival after heart transplantation. In this pilot study we investigated whether non-invasive methods are beneficial to detect cardiac allograft rejection (Grade 03 R) and cardiac allograft vasculopathy. Thus we compared multi-slice computed tomography and magnetic resonance imaging with invasive methods like coronary angiography and left endomyocardial biopsy. Methods 10 asymptomatic lon...

  13. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    Directory of Open Access Journals (Sweden)

    A. O. Shevchenko

    2015-01-01

    Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

  14. Cognitive and Functional Consequence of Cardiac Arrest.

    Science.gov (United States)

    Perez, Claudia A; Samudra, Niyatee; Aiyagari, Venkatesh

    2016-08-01

    Cardiac arrest is associated with high morbidity and mortality. Better-quality bystander cardiopulmonary resuscitation training, cardiocerebral resuscitation principles, and intensive post-resuscitation hospital care have improved survival. However, cognitive and functional impairment after cardiac arrest remain areas of concern. Research focus has shifted beyond prognostication in the immediate post-arrest period to identification of mechanisms for long-term brain injury and implementation of promising protocols to reduce neuronal injury. These include therapeutic temperature management (TTM), as well as pharmacologic and psychological interventions which also improve overall neurological function. Comprehensive assessment of cognitive function post-arrest is hampered by heterogeneous measures among studies. However, the domains of attention, long-term memory, spatial memory, and executive function appear to be affected. As more patients survive cardiac arrest for longer periods of time, there needs to be a greater focus on interventions that can enhance cognitive and psychosocial function post-arrest. PMID:27311306

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

    Science.gov (United States)

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

    2009-01-01

    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.

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

    NARCIS (Netherlands)

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

    2015-01-01

    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 t

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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....

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

    Science.gov (United States)

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

    2015-02-01

    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.

  19. A Systematic Review of Anterior Cruciate Ligament Reconstruction with Autograft Compared with Allograft

    OpenAIRE

    Carey, James L.; Dunn, Warren R.; Dahm, Diane L.; Zeger, Scott L.; Spindler, Kurt P.

    2009-01-01

    Background: Anterior cruciate ligament reconstruction can be performed with use of either autograft or allograft tissue. It is currently unclear if the outcomes of these two methods differ significantly. This systematic review and meta-analysis investigated whether the short-term clinical outcomes of anterior cruciate reconstruction with allograft were significantly different from those with autograft.

  20. Predictors for outcome among cardiac arrest patients

    DEFF Research Database (Denmark)

    Wibrandt-Johansen, Ida Maria; Norsted, Kristine; Schmidt, Henrik;

    2015-01-01

    BackgroundIn the past decade, early treatment of cardiac arrest (CA) victims has been improved in several ways, leading to more optimistic over all prognoses. However, the global survival rate after out-of-hospital CA (OHCA) is still not more than 5-10%. With a better knowledge of the predictors...

  1. Efecto de la pentoxifilina en la supervivencia, la función cardiaca y en la hemodinámica portal y sistémica de la cirrosis alcohólica avanzada: a randomized double-blind placebo-controlled trial Effect of pentoxiphylline on survival, cardiac function, and portal and systemic hemodynamics in advanced alcoholic cirrhosis

    Directory of Open Access Journals (Sweden)

    C. M. Fernández-Rodríguez

    2008-08-01

    Full Text Available Objetivo: valorar el efecto de la pentoxifilina (un potente inhibidor del factor de necrosis tumoral alfa en la supervivencia, en la hemodinámica sistémica y portal y en la función cardiaca en la cirrosis alcohólica avanzada. Diseño: estudio aleatorizado, doble-ciego, controlado con placebo. Contexto: estudio unicéntrico utilizando grupos de pacientes en paralelo para comparar pentoxifilina y placebo. Pacientes: se incluyeron 24 pacientes con cirrosis alcohólica (8 en estadio B de Child-Pugh y 16 en estadio C de Child-Pugh. Intervención: los pacientes fueron aleatorizados a recibir pentoxifilina (400 mg, 3 veces al día, n = 12 o placebo (n = 12 durante 4 semanas. Determinaciones: el objetivo principal fue la supervivencia a corto/largo plazo. Los objetivos secundarios fueron observar beneficios hemodinámicos (mejoría en la función cardiaca y/o en el índice de resistencias vasculares sistémicas o disminución de la presión portal. Resultados: la presión portal y la función cardiaca no se modificaron y no hubo diferencias en la supervivencia a corto y largo plazo entre los grupos tratados y placebo. Los índices de resistencia vascular sistémica y cardiaco cambiaron en el grupo de pentoxifilina (de 1.721 ± 567 a 2.082 ± 622 Din.seg ¹ cm-5 m-2 y de 4,17 ± 1,4 a 3,4 ± 0,9 lm-2, p = 0,05. Conclusiones: aunque la pentoxifilina parece producir algún beneficio hemodinámico a corto plazo en pacientes con cirrosis alcohólica avanzada, no tiene efecto sobre la tasa de supervivencia, la función cardiaca ni sobre la presión portal en estos pacientes.Objective: to assess the effect of pentoxiphylline (a potent inhibitor of tumor necrosis factor alpha on survival, on systemic and portal hemodynamics, and on cardiac function in patients with alcoholic cirrhosis. Design: a randomized double-blind placebo-controlled trial. Setting: a single center using parallel groups of patients to compare pentoxiphylline with placebo. Patients: we

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

    1995-12-15

    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

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

    Science.gov (United States)

    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

    2016-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fawwaz, R.A.

    1984-07-01

    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.

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

    Science.gov (United States)

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

    2009-02-01

    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.

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

    Science.gov (United States)

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

    2013-01-01

    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.

  7. Quantitative assessment of myocardial blush grade in patients with coronary artery disease and in cardiac transplant recipients

    Institute of Scientific and Technical Information of China (English)

    Nina; Patricia; Hofmann; Hartmut; Dickhaus; Hugo; A; Katus; Grigorios; Korosoglou

    2014-01-01

    Quantitative assessment of myocardial perfusion by myocardial blush grade(MBG) is an angiographic computer-assisted method to assess myocardial tissue-level reperfusion in patients with acute coronary syndromes and microvascular integrity in heart transplant recipients with suspected cardiac allograft vasculopathy. This review describes the ability of quantitative MBG as a simple, fast and cost effective modality for the prompt diagnosis of impaired microvascular integrity during routine cardiac catheterization. Herein, we summarize the existing evidence, its usefulness in the clinical routine, and compare this method to other techniques which can be used for the assessment of myocardial perfusion.

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

    Directory of Open Access Journals (Sweden)

    Tatomirović Željka

    2003-01-01

    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

  9. Out-of-Hospital Cardiac Arrest in Denmark

    DEFF Research Database (Denmark)

    Wissenberg Jørgensen, Mads

    challenges, due to the victim’s physical location, which brings an inherent risk of delay (or altogether absence) of recognition and treatment of cardiac arrest. A low frequency of bystander cardiopulmonary resuscitation and low 30-day survival after out-of-hospital cardiac arrest were identified nearly ten......BACK COVER TEXT Cardiac arrest is an emergency medical condition characterized by the cessation of cardiac mechanical activity; without immediate and decisive treatment, a victim’s chances of survival are minimal. Out-of-hospital cardiac arrest is a particular arrest subgroup that poses additional...... years ago in Denmark. These findings led to several national initiatives to strengthen bystander resuscitation attempts and advance care. Despite these nationwide efforts, it was unknown prior to this project whether these efforts resulted in changes in resuscitation attempts by bystanders and changes...

  10. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  11. Ankle and shoulder joint reconstruction using soft tissue allografts

    International Nuclear Information System (INIS)

    Full text: Lateral Collateral Ligament Insufficiency is a common complication of injury to the ankle joint. This needs reconstruction of the torn ligament as the joint instability gives rise to frequent giving way at the ankle joint. It can be reconstructed using autologous peroneus brevis tendon. The authors prefer to reconstruct using deep frozen (-80 degree C) non-gamma irradiated tibialis anterior or tibialis posterior tendon allograft procured by NUH Tissue Bank. The graft must be at least between 18-22 cm long. The procedure employed is a first stage Brostrom Procedure repairing the anterior talo-fibula ligament using Mitek sutures. In the second stage the Calcaneofibular ligament is reconstructed using a figure of eight tendon reconstruction via drill holes in the fibular above and the calcaneum below. Twelve cases have been reconstructed this way with good results. When injury is sustained to the Acromia-clavicular (AC) Joint, for type 3 to 5 AC Joint Dislocation and in manual labourers, reconstruction is needed. The author's preferred method is a 2 stage procedure using deep frozen (-80 degree C), non gamma-irradiated fascia lata allografts procured by NUH Tissue Bank. In the first stage the dislocated AC Joint is reduced and held in position by transfixation using 2 baby Steinmann Pins and repair of torn corac clavicular ligaments. The second stage consisted of reconstruction with rolled-up fascia lata figure of eight allograft tendon between the clavicle and the coracoid process. The 2 pins are removed after 6 weeks and the shoulder mobilised. 10 cases have been done with good results. Two cases showed mild subluxation of the AC joint due to slight loss of the reduction performed during the operation. (Author)

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

    Science.gov (United States)

    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

    2016-02-01

    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.

  13. 1. Predictors of cardio pulmonary resuscitation outcome in post-operative cardiac children

    OpenAIRE

    Nasser, B.

    2016-01-01

    Outcome of cardiopulmonary resuscitation (CPR) in children with congenital heart disease has improved and many children survived after in hospital cardiac arrestthe purpose of this study is to determine predictor of poor outcome after CPR in critical children undergoing cardiac surgerywe conducted a retrospective chart review and data analysis of all CPR records and charts of all postoperative cardiac children who had cardiac arrest and required resuscitation from 2012 till 2015. Demographic,...

  14. Stem cell death and survival in heart regeneration and repair.

    Science.gov (United States)

    Abdelwahid, Eltyeb; Kalvelyte, Audrone; Stulpinas, Aurimas; de Carvalho, Katherine Athayde Teixeira; Guarita-Souza, Luiz Cesar; Foldes, Gabor

    2016-03-01

    Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

  15. Diagnosis and management of late hepatic allograft dysfunction

    Institute of Scientific and Technical Information of China (English)

    MEI Jian-min; YU Cong-hui

    2005-01-01

    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.

  16. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    Institute of Scientific and Technical Information of China (English)

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan

    2010-01-01

    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  17. Surviving Cancer

    Science.gov (United States)

    ... his or her health status, when diagnosed with cancer may have an effect on their survival and recovery. Older adults are more likely to have other health conditions such as diabetes and heart disease. Managing these conditions can complicate ...

  18. Survival of allografts from bone marrow donors in temporary dog radiation chimeras

    International Nuclear Information System (INIS)

    Complete radiation chimeras accept indefinitely a skin or a kidney graft from the bone marrow (BM) donor. The advantages of this method of inducing graft acceptance are that it does not require the use of toxic post-operative immunosuppressive agents and that the immune reactivity against antigens other than the ones carried by the BM donor remains intact. The disadvantages of this approach are that supralethal total body irradiation (TBI) causes toxicity and that allogeneic BM cells can cause lethal Graft versus Host reactions. Attempts were made to diminish the significance of these disadvantages by using lower dose TBI and giving fewer BM cells. It is shown that, in dogs, 7.5 Gy TBI followed by 4 X 108 BM cells.kg-1 body weight of a DLA identical sibling leads to the development of complete radiation chimeras. The exclusive presence of donor type haemopoiesis can be demonstrated by determinations of 'informative' genetic markers, i.e., markers that show different genotypes in donor and recipient. (Auth.)

  19. INADEQUATE ANTIBODY-RESPONSE AGAINST RESPIRATORY VIRAL-INFECTION IN LONG-SURVIVING RAT LUNG ALLOGRAFTS

    NARCIS (Netherlands)

    WINTER, JB; GROEN, M; VANDERLOGT, K; WILDEVUUR, CRH; PROP, J

    1995-01-01

    Lung transplant recipients suffer from a high number of viral infections. It has been suggested that the defense against viral infections is impaired in lung transplants, Therefore, we investigated in rat lung transplants whether antibody responses against an intrapulmonary viral infection were impa

  20. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  1. Abrogation of the immunosuppressive effect of donor spleen cells on renal allografts in the rat by irradiation or heat treatment

    Energy Technology Data Exchange (ETDEWEB)

    Cranston, D.; Wood, K.J.; Morris, P.J.

    1986-09-01

    In the donor-recipient strain combination Lewis (RT1l) to Dark Agouti (RT1a), indefinite renal allograft survival (MST greater than 100 days) was induced by pretreating recipient animals i.v. with 10(6) to 10(8) viable spleen lymphocytes, seven days before transplantation. Pretreatment with 10(4) or 10(5) cells was ineffective (MST 10 days). However when 10(7) live, but heat-treated (55 degrees C for 10 min) or irradiated (1000 rads) cells were used, all the animals rejected the allograft in a normal fashion (MST 10 and 11 days, respectively). Median survival time of third-party controls was 10 days. The relative amount of cell surface major histocompatibility antigens (class I and class II) expressed by the three spleen cell preparations was investigated using monoclonal antibodies and fluorescence activated cell sorter analysis and found to be similar. After 24 hr in culture, only 1% of heat-treated and 10% of irradiated cells were viable, in contrast to 75% of untreated splenocytes. Trafficking of these lymphocytes in recipient animals was investigated by 51chromium labeling of the cells: 30% of lymphocytes had localized in the liver within 3 hr with little difference in localization among the different cell preparations. But, although 20% of normal and irradiated cells localized in the spleen within 3 hr, at no stage were more than 5% of the heat-treated cells found in the spleen. It is suggested that the length of time viable donor lymphocytes remain in the recipient circulation is important in the induction of specific immunosuppression by spleen lymphocytes.

  2. Physical activity increases survival after heart valve surgery

    DEFF Research Database (Denmark)

    Lund, K.; Sibilitz, Kirstine Lærum; Kikkenborg berg, Selina;

    2016-01-01

    OBJECTIVES: Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between...... physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient...... of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation....

  3. Elevated urine heparanase levels are associated with proteinuria and decreased renal allograft function.

    Directory of Open Access Journals (Sweden)

    Itay Shafat

    Full Text Available Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains, leading to structural modifications that loosen the extracellular matrix barrier and associated with tumor metastasis, inflammation and angiogenesis. In addition, the highly sulfated heparan sulfate proteoglycans are important constituents of the glomerular basement membrane and its permselective properties. Recent studies suggest a role for heparanase in several experimental and human glomerular diseases associated with proteinuria such as diabetes, minimal change disease, and membranous nephropathy. Here, we quantified blood and urine heparanase levels in renal transplant recipients and patients with chronic kidney disease (CKD, and assessed whether alterations in heparanase levels correlate with proteinuria and renal function. We report that in transplanted patients, urinary heparanase was markedly elevated, inversely associated with estimated glomerular filtration rate (eGFR, suggesting a relationship between heparanase and graft function. In CKD patients, urinary heparanase was markedly elevated and associated with proteinuria, but not with eGFR. In addition, urinary heparanase correlated significantly with plasma heparanase in transplanted patients. Such a systemic spread of heparanase may lead to damage of cells and tissues alongside the kidney.The newly described association between heparanase, proteinuria and decreased renal function is expected to pave the way for new therapeutic options aimed at attenuating chronic renal allograft nephropathy, leading to improved graft survival and patient outcome.

  4. Systemic Venous Inflow to the Liver Allograft to Overcome Diffuse Splanchnic Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Cristian Lupascu

    2015-01-01

    Full Text Available Diffuse splanchnic venous thrombosis (DSVT, formerly defined as contraindication for liver transplantation (LT, is a serious challenge to the liver transplant surgeon. Portal vein arterialisation, cavoportal hemitransposition and renoportal anastomosis, and finally combined liver and small bowel transplantation are all possible alternatives to deal with this condition. Five patients with preoperatively confirmed extensive splanchnic venous thrombosis were transplanted using cavoportal hemitransposition (4x and renoportal anastomosis (1x. Median follow-up was 58 months (range: 0,5 to 130 months. Two patients with previous radiation-induced peritoneal injury died, respectively, 18 days and 2 months after transplantation. The three other patients had excellent long-term survival, despite the fact that two of them needed a surgical reintervention for severe gastrointestinal bleeding. Extensive splanchnic venous thrombosis is no longer an absolute contraindication to liver transplantation. Although cavoportal hemitransposition and renoportal anastomosis undoubtedly are life-saving procedures allowing for ensuring adequate allograft portal flow, careful follow-up of these patients remains necessary as both methods are unable to completely eliminate the complications of (segmental portal hypertension.

  5. Systemic Venous Inflow to the Liver Allograft to Overcome Diffuse Splanchnic Venous Thrombosis.

    Science.gov (United States)

    Lupascu, Cristian; Darius, Tom; Goffette, Pierre; Lerut, Jan

    2015-01-01

    Diffuse splanchnic venous thrombosis (DSVT), formerly defined as contraindication for liver transplantation (LT), is a serious challenge to the liver transplant surgeon. Portal vein arterialisation, cavoportal hemitransposition and renoportal anastomosis, and finally combined liver and small bowel transplantation are all possible alternatives to deal with this condition. Five patients with preoperatively confirmed extensive splanchnic venous thrombosis were transplanted using cavoportal hemitransposition (4x) and renoportal anastomosis (1x). Median follow-up was 58 months (range: 0,5 to 130 months). Two patients with previous radiation-induced peritoneal injury died, respectively, 18 days and 2 months after transplantation. The three other patients had excellent long-term survival, despite the fact that two of them needed a surgical reintervention for severe gastrointestinal bleeding. Extensive splanchnic venous thrombosis is no longer an absolute contraindication to liver transplantation. Although cavoportal hemitransposition and renoportal anastomosis undoubtedly are life-saving procedures allowing for ensuring adequate allograft portal flow, careful follow-up of these patients remains necessary as both methods are unable to completely eliminate the complications of (segmental) portal hypertension. PMID:26539214

  6. Hearing Benefit in Allograft Tympanoplasty Using Tutoplast Processed Malleus

    Directory of Open Access Journals (Sweden)

    Anja Lieder

    2014-01-01

    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.

  7. B cells mediate chronic allograft rejection independently of antibody production.

    Science.gov (United States)

    Zeng, Qiang; Ng, Yue-Harn; Singh, Tripti; Jiang, Ke; Sheriff, Khaleefathullah A; Ippolito, Renee; Zahalka, Salwa; Li, Qi; Randhawa, Parmjeet; Hoffman, Rosemary A; Ramaswami, Balathiripurasundari; Lund, Frances E; Chalasani, Geetha

    2014-03-01

    Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture.

  8. De novo C3 glomerulonephritis in a renal allograft.

    Science.gov (United States)

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

    2016-01-01

    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. PMID:26986539

  9. B cells mediate chronic allograft rejection independently of antibody production.

    Science.gov (United States)

    Zeng, Qiang; Ng, Yue-Harn; Singh, Tripti; Jiang, Ke; Sheriff, Khaleefathullah A; Ippolito, Renee; Zahalka, Salwa; Li, Qi; Randhawa, Parmjeet; Hoffman, Rosemary A; Ramaswami, Balathiripurasundari; Lund, Frances E; Chalasani, Geetha

    2014-03-01

    Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture. PMID:24509079

  10. De novo C3 glomerulonephritis in a renal allograft.

    Science.gov (United States)

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

    2016-01-01

    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.

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

    Science.gov (United States)

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

    2015-05-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-11-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Rohit Dewan

    2016-01-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

    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.

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

    Science.gov (United States)

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

    2015-05-01

    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. PMID:25950536

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    Hu F

    2015-07-01

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    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.

  19. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    A.S. Amin; A. Asghari-Roodsari; H.L. Tan

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  20. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  1. Surface Electrocardiogram Predictors of Sudden Cardiac Arrest

    Science.gov (United States)

    Abdelghani, Samy A.; Rosenthal, Todd M.; Morin, Daniel P.

    2016-01-01

    Background: Heart disease is a major cause of death in industrialized nations, with approximately 50% of these deaths attributable to sudden cardiac arrest. If patients at high risk for sudden cardiac arrest can be identified, their odds of surviving fatal arrhythmias can be significantly improved through prophylactic implantable cardioverter defibrillator placement. This review summarizes the current knowledge pertaining to surface electrocardiogram (ECG) predictors of sudden cardiac arrest. Methods: We conducted a literature review focused on methods of predicting sudden cardiac arrest through noninvasive electrocardiographic testing. Results: Several electrocardiographic-based methods of risk stratification of sudden cardiac arrest have been studied, including QT prolongation, QRS duration, fragmented QRS complexes, early repolarization, Holter monitoring, heart rate variability, heart rate turbulence, signal-averaged ECG, T wave alternans, and T-peak to T-end. These ECG findings have shown variable effectiveness as screening tools. Conclusion: At this time, no individual ECG finding has been found to be able to adequately stratify patients with regard to risk for sudden cardiac arrest. However, one or more of these candidate surface ECG parameters may become useful components of future multifactorial risk stratification calculators. PMID:27660578

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

    Science.gov (United States)

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

    2014-01-01

    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. PMID:25548701

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

    Science.gov (United States)

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

    2014-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Judd Fitzgerald

    2014-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-08-01

    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.

  6. VITAL COMPUTER MORPHOMETRY OF LIMPHOCYTES IN DIAGNOSIS OF ACUTE RENAL ALLOGRAFT REJECTION

    Directory of Open Access Journals (Sweden)

    A. V. Vatazin

    2009-01-01

    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. 

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

    Science.gov (United States)

    Gupta, Pallav; Sharma, Amit; Khullar, Dinesh

    2014-08-01

    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.

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

    Science.gov (United States)

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

    2004-12-31

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

    Background OX40/OX40 ligand (OX40/OX40L) and programmed death-1/programmed death ligand-1 (PD-1/PD-L1) costimulatory signals play important roles in T cell-induced immune responses.The aim of this study was to investigate the roles of OX40/OX40L and PD-1/PD-L1 costimulatory pathways in mouse islet allograft rejection.Methods Lentiviral vectors containing OX40L siRNA sequences and an adenovirus vector containing the PD-L1 gene were constructed.The streptozotocin-induced model of diabetes was established in C57BL/6 (H-2b) mice.Diabetic C57BL/6 mice were randomly allocated into five groups:group 1,untreated control; group 2,Ad-EGFP treatment; group 3,Ad-PD-L1 treatment; group 4,OX40L-RNAi-LV treatment; group 5,OX40L-RNAi-LV combined with Ad-PD-L1 treatment.Lentiviral vector and the adenovirus vector were injected,singly or combined,into the caudal vein one day before islet transplantation.The islets of DBA/2 (H-2d) mice were transplanted into the renal subcapsular space of the diabetic recipients.Recipient blood glucose and the survival time of the allografts were monitored.Antigen-specific mixed lymphocyte reaction was also evaluated.Results The recombinant lentiviral RNA interference vector OX40L-RNAi-LV reduced OX40L protein expression by 70%.The recombinant adenovirus vector Ad-PD-L1 increased PD-L1 protein expression in vivo in C57BL/6 recipient mice.Combined OX40L-RNAi-LV/Ad-PD-L1 treatment induced a synergistic protective effect in pancreatic islet allografts.Allograft survival time in the combined treatment group was (92.27±9.65) days,not only longer than that of the control ((6.51±0.27) days) and Ad-EGFP groups ((7.09±0.13) days) (P <0.01),but also significantly longer than that of Ad-PD-L1 and OX40L-RNAi-LV single treatment groups ((40.64±3.95) days and (55.14±5.48) days respectively,P <0.01).The blood glucose concentration of recipient mice in the combined treatment group was also stable and kept within the normal range.Flow cytometry analysis

  10. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  11. The use of osteochondral allograft with bone marrow-derived mesenchymal cells and hinge joint distraction in the treatment of post-collapse stage of osteonecrosis of the femoral head.

    Science.gov (United States)

    Gagala, J; Tarczynska, M; Gaweda, K; Matuszewski, L

    2014-09-01

    Osteonecrosis of the femoral head is an entity which occurs mainly in young and active patients aged between 20 and 50. The success of hip joint preserving treatments ranges from 15% to 50% depending on the stage and amount of osteonecrotic lesion. Total hip replacement is indicated in late post-collapse hips but it has unsatisfactory survival because of the wear and osteolysis in young and active patients. Osteochondral allografts have been reported in the treatment of large articular lesions with defects in underlying bone in knee, talus and shoulder. By combining osteoconductive properties of osteochondral allograft with osteogenic abilities of bone marrow-derived mesenchymal cells it has a potential to be an alternative to an autologous graft. The adjunct of hinged joint distraction should minimize stresses in subchondral bone to promote creeping substitution and prevent femoral head collapse. Unlike current treatment modalities, it would provide both structural support and allow bony and articular substitution.

  12. Survival after in-hospital Cardiopulmonary Resuscitation

    Directory of Open Access Journals (Sweden)

    M Adib Hajbaghery

    2005-05-01

    Full Text Available Background: During recent years, cardiopulmonary resuscitation (CPR in hospital has received much attention. However, the survival rate of CPR in Iran’s hospitals is unknown. This study was designed to evaluate outcome of in-hospital CPR in Kashan. Methods: A longitudinal case registry study was conducted on all cases of in-hospital CPR during 6 months at 2002. Necessary data including; age, sex, underlying disease, working shift, time from cardiac arrest until initiating of CPR and until defibrillation, duration and result of CPR, frequency of tracheal intubations and time served for it were collected in a checklist. Results: In six months study, 206 cases of cardiopulmonary resuscitation attempted. The survival rate was similar for both sexes. Short-term survival observed in19.9% of cases and only 5.3% survived to discharge. Conclusions: Duration of CPR, time of the first defibrillation, response time and the location of cardiac arrest are the key predictors of survival to hospital discharge and in-hospital CPR strategies require improvement. This study promotes a national study on post CPR survival for accurate data on our performance in attention to chain of survival. KeyWords: Cardiopulmonary Resuscitation (CPR, Survival rate, Iran

  13. Allograftic bone marrow-derived mesenchymal stem cells transplanted into heart infarcted model of rabbit to renovate infarcted heart

    Institute of Scientific and Technical Information of China (English)

    王建安; 李长岭; 樊友启; 何红; 孙勇

    2004-01-01

    Objective: To investigate the directed transplantation of allograftic bone marrow-derived mesenchymal stem cells (MSCs) in myocardial infarcted (MI) model rabbits. Materials and Methods: Rabbits were divided into 3 groups, heart infarcted model with MSCs transplanted treatment (MSCs group, n=12), heart infarcted model with PBS injection (control group, n=20), sham operation with PBS injection (sham group, n=17). MSCs labelled by BrdUrd were injected into the MI area of the MSCs group. The same volume of PBS was injected into the MI area of the control group and sham group. The mortality, LVIDd, LVIDs and LVEF of the two groups were compared 4 weeks later. Tropomyosin inhibitory component (Tn Ⅰ) and BrdUrd immunohistochemistry identified the engrafted cells 4 weeks after transplantation. Result: The mortality of the MSCs group was 16.7% (2/12), and remarkably lower than the control group's mortality [35% (7/20) (P<0.05)]. Among the animals that survived for 4 weeks, the LVIDd and LVIDs of the MSCs group after operation were 1.17±0.21cm and 0.74±0.13cm, and remarkably lower than those of the model group, which were 1.64±0.14cm and 1.19±0.12cm (P<0.05); the LVEF of the MSCs group after operation was 63±6%, and remarkably higher than that of the model group, which was 53±6% (P<0.05). Among the 10 cases of animals that survived for 4 weeks in the MSCs group, in 8 cases (80%), the transplanted cells survived in the non MI, MI region and its periphery, and even farther away; part of them differentiated into cardiomyocytes; in 7 cases (70%), the transplanted cells participated in the formation of blood vessel tissue in the MI region. Conclusion: Transplanted allograftic MSCs can survive and differentiate into cardiomyocytes, form the blood vessels in the MI region. MSCs transplantation could improve the heart function after MI.

  14. Allograftic bone marrow-derived mesenchymal stem cells transplanted into heart infarcted model of rabbit to renovate infarcted heart

    Institute of Scientific and Technical Information of China (English)

    王建安; 李长岭; 樊友启; 何红; 孙勇

    2004-01-01

    Objective: To investigate the directed transplantation of allograftic bone marrow-derived mesenchymal stem cells (MSCs) in myocardial infarcted (MI) model rabbits. Materials and Methods: Rabbits were divided into 3 groups, heart infarcted model with MSCs transplanted treatment (MSCs group, n=12), heart infarcted model with PBS injection (control group, n=20), sham operation with PBS injection (sham group, n=l 7). MSCs labelled by BrdUrd were injected into the MI area of the MSCs group. The same volume of PBS was injected into the MI area of the control group and sham group. The mortality, LVIDd, LVIDs and LVEF Of the two groups were compared 4 weeks later. Tropomyosin inhibitory component (Tn I) and BrdUrd immunohistochemistry identified the engrafted cells 4 weeks after transplantation. Result: The mortality of the MSCs group was 16.7% (2/12), and remarkably lower than the control group's mortality [35% (7/20) (P<0.05)].Among the animals that survived for 4 weeks, the LVIDd and LVIDs of the MSCs group after operation were 1.17±0.21 cm and 0.74±0.13 cm, and remarkably lower than those of the model group, which were 1.64±0.14 cm and 1.19±0.12 cm (P<0.05); the LVEF of the MSCs group after operation was 63±6%, and remarkably higher than that of the model group,which was 53±6% (P<0.05). Among the 10 cases of animals that survived for 4 weeks in the MSCs group, in 8 cases (80%),the transplanted cells survived in the non MI, MI region and its periphery, and even farther away; part of them differentiated into cardiomyocytes; in 7 cases (70%), the transplanted cells participated in the formation of blood vessel tissue in the MI region. Conclusion: Transplanted allograftic MSCs can survive and differentiate into cardiomyocytes, form the blood vessels in the MI region. MSCs transplantation could improve the heart function after MI.

  15. Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs

    DEFF Research Database (Denmark)

    Baad-Hansen, Thomas Einer; Overgaard, S; Lind, M;

    2007-01-01

    weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own. ProOsteon alone cannot be recommended as a......Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules...... surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three...

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

    NARCIS (Netherlands)

    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.

    2008-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1979-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Bin Liu

    2013-01-01

    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.

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

    LENUS (Irish Health Repository)

    Johnston, Olwyn

    2011-08-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Brett D. Crist

    2016-04-01

    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.

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

    Science.gov (United States)

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

    2015-02-01

    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.

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

    Science.gov (United States)

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

    2015-02-01

    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. PMID:25973378

  3. Distal Femur Allograft Selection Using a Spectral Shape Descriptor

    International Nuclear Information System (INIS)

    The automatic selection of bone allografts in a virtual bone databank is an active line of research. This work presents a new approach to solve this problem, based on a recently published image descriptor, called Volumetric Heat Kernel Signature. This descriptor is used to compare the size and shape of three dimensional thresholded computed tomography volumes. This approach is compared to a published method that uses the Iterative Closest Points algorithm to register a segmented search template to different candidates present in the databank. Statistical testing of the agreement between the two methods show that both approaches render similar results in the relevant clinical context. The proposed method avoids incorrect registrations due to local minima and does not require lengthly manual image segmentation and positioning before its use. The new method is conceptually simple and its mathematical basis is sound

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

    Directory of Open Access Journals (Sweden)

    Rizzuti A

    2014-12-01

    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

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

    Directory of Open Access Journals (Sweden)

    CARVALHO Maria Fernanda C.

    1997-01-01

    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

  6. Focal segmental glomerulosclerosis recurrence in the renal allograft.

    Science.gov (United States)

    Leca, Nicolae

    2014-09-01

    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.

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

    Science.gov (United States)

    Rossi, Michael J

    2016-01-01

    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.

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

    Science.gov (United States)

    Rossi, Michael J

    2016-01-01

    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. PMID:26743407

  9. Processing of gamma irradiated bone allografts for treatment of injuries in a nuclear scenario

    International Nuclear Information System (INIS)

    Bone allografts fill an important void in the surgical practice of orthopaedic surgery, and their use to replace and reconstruct musculoskeletal structures following injury or disease has gained increasing acceptance by orthopaedic surgeons. Serious mechanical injuries in a nuclear scenario involving compression, displacement and missile hit will lead to high incidence of various kinds of bone fractures, spinal injuries and joint injuries apart from lethality, lung damage and eardrum rupture. Bone allografts can be employed for repairing fracture defects, filling in destroyed regions of bone, management of open fractures and joint injuries. Autologous bone grafts, though ideal, have the drawback of secondary surgery for autograft retrieval, complications of infection and donor site morbidity. Bone allografts eliminate additional incision necessary for acquiring an autograft and consequently reduce operating time, blood loss as well as hospital and medical costs. However, disease transmission and bacterial infection in bone allograft transplantation is of significant concern. Sterilization by gamma irradiation is a definitive method for eliminating microorganisms and can prevent life-threatening allograft associated infections. The present study was carried out with the aim of bioburden assessment, radiation sterilization and clinical evaluation of bone allografts processed from femoral heads obtained from living donors. Femoral heads were obtained during surgery at Department of Orthopaedic Surgery, SN Medical College, Jodhpur and processed as freeze-dried bone allografts. Bioburden of bone allografts was found to be in the range of 2.26 to 3.59 log CFU/g. Verification dose for different batches of processing was 7.24±1.27 kGy. Radiological data of processed gamma irradiated bone grafts used in clinical cases of trauma surgery was recorded and has shown successful graft incorporation in allogenic recipients. (author)

  10. Microparticulate Cortical Allograft: An Alternative to Autograft in the Treatment of Osseous Defects

    OpenAIRE

    Temple, H. Thomas; Malinin, Theodore I

    2008-01-01

    Benign bone tumors are commonly diagnosed and treated. Following tumor removal, the defect in the bone can be filled with auto- or allografts, (degradable) bone substitutes or non-degradable polymethylmethacrylate. The ideal substitute for this purpose should provide immediate structural support and readily incorporate into bone over a short period of time. Experimentally, microparticulate allograft has been shown to incorporate quickly in metaphyseal and metadiaphyseal cortico-cancellous def...

  11. Consolidation of massive bone allografts in limb-preserving operations for bone tumours

    OpenAIRE

    San-Julian, M.; Leyes, M.; Mora, G. (Gonzalo); Cañadell, J.M. (J. M.)

    1995-01-01

    This study analysed the influence of several factors affecting the consolidation time of 83 massive bone allografts in 79 patients with malignant bone tumours: osteosarcoma 57; Ewing's sarcoma 8; malignant fibrous histiocytoma 3; chondrosarcoma 4; fibrosarcoma 5; and giant cell tumours 2. The mean age of the patients was 19 years and the mean length of the allografts was 18 cm. The minimum follow up was for 12 months. The mean consolidation time for metaphyseal and diaphyseal osteotomies was ...

  12. Is Duplex-Ultrasound a useful tool in defining rejection episodes in composite tissue allograft transplants?

    Science.gov (United States)

    Loizides, Alexander; Kronberger, Irmgard-Elisabeth; Plaikner, Michaela; Gruber, Hannes

    2015-12-01

    Immunologic reactions in transplanted organs are in more or less all allograft patients detectable: clear parameters exist as e.g. in renal transplants where the clearance power reduces by rejection. On the contrary, in composite tissue allografts clear and objective indicators stating a rejection episode lack. We present the case of a hand-transplanted subject with signs of acute transplant rejection diagnosed by means of Duplex Ultrasound and confirmed by biopsy.

  13. Cutting Edge: Acute Lung Allograft Rejection Is Independent of Secondary Lymphoid Organs1

    OpenAIRE

    Gelman, Andrew E.; Li, Wenjun; Richardson, Steven B.; Zinselmeyer, Bernd H.; Lai, Jiaming; Okazaki, Mikio; Kornfeld, Christopher G.; Kreisel, Friederike H.; Sugimoto, Seiichiro; Tietjens, Jeremy R.; Dempster, John; Patterson, G. Alexander; Krupnick, Alexander S.; Miller, Mark J.; Kreisel, Daniel

    2009-01-01

    It is the prevailing view that adaptive immune responses are initiated in secondary lymphoid organs. Studies using alymphoplastic mice have shown that secondary lymphoid organs are essential to initiate allograft rejection of skin, heart, and small bowel. The high immunogenicity of lungs is well recognized and allograft rejection remains a major contributing factor to poor outcomes after lung transplantation. We show in this study that alloreactive T cells are initially primed within lung all...

  14. Human Split-Thickness Skin Allograft: Skin Substitute in the Treatment of Burn

    OpenAIRE

    Mahdavi-Mazdeh, M.; Nozary Heshmati, B.; Tavakoli, S. A. H.; Ayaz, M.; F. Azmoudeh Ardalan; M. Momeni

    2013-01-01

    Background: Human skin allograft has been used as wound coverage for a long time; it is one of the most successful and widely used dressings for burn wounds in the world. Objective: To prepare a freeze-dried human split-thickness skin allograft and evaluate its cytotoxicity, the structure and physical properties after processing methods and clinical efficacy in burn patients. Methods: After ensuring tissue safety, we lyophilized human cadaveric partial thickness skin and exposed it to gamma r...

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

    Directory of Open Access Journals (Sweden)

    Hilary Cassidy

    2013-09-01

    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. Prospective Comparative Study of ACL Reconstruction Between Using Hamstring Autograft and Soft Tissue Allograft

    OpenAIRE

    Song, Eun Kyoo; Seon, Jong Keun; Kim, Hasung

    2014-01-01

    Objectives: Nowadays, two most commonly used grafts in the anterior cruciate ligament reconstruction are hamstring autograft and soft tissue allograft. Although the short-term clinical outcomes between two grafts were similar, only a few studies reported mid-term clinical outcomes. The purpose of this prospective study was to compare clinical outcomes of ACL reconstruction between using hamstring autograft and soft tissue allograft after mid-term follow-up. Methods: One-hundred sixty-one pati...

  17. Characterization of ionizing radiation effects on human skin allografts

    International Nuclear Information System (INIS)

    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 60Co 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)

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

    Science.gov (United States)

    Kiberd, B A

    1989-12-01

    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.

  19. Sirolimus use and incidence of venous thromboembolism in cardiac transplant recipients.

    Science.gov (United States)

    Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, W Steves; Peltz, Matthias; Drazner, Mark H

    2012-01-01

    Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism (VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log-rank statistic: 4.66, p=0.03). Lower body mass index (BMI) and total cholesterol levels were also associated with VTE (p<0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p=0.03) but not when adjusting for total cholesterol (p=0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted. PMID:22775970

  20. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.