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Sample records for cardiac allograft survival

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

    Science.gov (United States)

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

    2015-09-01

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

  2. Risk factors of cardiac allograft vasculopathy.

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

    2015-12-01

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

  3. 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

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

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    Uchiyama Masateru

    2012-03-01

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

  5. Cardiac allograft immune activation: current perspectives

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    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

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

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    Xiaofei Shen

    2016-11-01

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

  7. Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure

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    Acker Michael A

    2008-05-01

    Full Text Available Abstract Background Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated. Methods 709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%. A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function. Results Etiology of primary graft failure included transplant arteriopathy (n = 10, acute rejection (n = 3, hyperacute rejection (n = 1, and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1. Mean age at retransplantation was 45.5 ± 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 ± 12.2% at a mean follow-up of 32.6 ± 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 ± 95.7 mos post-transplant. Conclusion Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.

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

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    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.

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

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    Francesca D'Addio

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

  10. 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....

  11. Inflammatory mediators and cytotoxins in cardiac allograft rejection

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

    1986-03-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  13. 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.

  14. 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.

  15. 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.

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

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

    2016-01-01

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

  17. Effect of blood transfusions on canine renal allograft survival

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    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.

  18. Effect of blood transfusions on canine renal allograft survival

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    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.

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

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    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.

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

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

    1987-03-01

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

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

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    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.

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

    DEFF Research Database (Denmark)

    Wassilew, Katharina

    2017-01-01

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

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

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    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.

  4. Cardiac allograft acceptance after localized bone marrow transplantation by isolated limb perfusion in nonmyeloablated recipients.

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    Askenasy, Nadir; Yolcu, Esma S; Shirwan, Haval; Wang, Zhiliang; Farkas, Daniel L; Yoleuk, Esma S

    2003-01-01

    Donor-specific tolerance to cardiac grafts may be induced by hematopoietic chimerism. This study evaluates the potential of localized bone marrow transplantation (BMT) performed by isolated limb (IL) perfusion to induce tolerance to secondary cardiac grafts without myeloablative conditioning. BALB/c recipients (H2d) preconditioned with lethal and sublethal doses of busulfan were injected i.v. and IL with 10(7) whole bone marrow cells (wBMCs) from B10 donors (H2(b)). Two hours after IL infusion of PKH-labeled wBMCs into myeloablated hosts, there were few labeled cells in the host peripheral blood (p < 0.001 versus i.v.) and femurs of the infused limb contained 57% +/- 7% PKH-labeled blasts (p < 0.001 versus 8% +/- 0.6% after i.v.). Femurs of the noninfused limbs contained 60-70 PKH-labeled blasts (p < 0.001 versus i.v.-BMT) after 2 days and 47% +/- 5% of 0.32 x 10(7) donor cells (p < 0.001 versus 78% +/- 4% of 1.2 x 10(7) donor cells in infused femurs) after 4 weeks. The survival rates of myeloablated hosts were 90% and 80% after i.v. and IL infusion, respectively, and the chimeras had 78%-84% donor peripheral blood cells. In recipients conditioned with 35 mg/g busulfan, the levels of donor chimerism in peripheral blood were 33% +/- 4% and 21% +/- 4% at 3 weeks after i.v.- and IL-BMT, respectively. Transplantation of donor-matched (H2(b)) secondary vascularized hearts in these chimeras after 3 weeks resulted in graft survival for periods exceeding 8 weeks, while third-party (H2(k)) allografts were acutely rejected (p < 0.001 versus H2(b)). These data indicate that IL perfusion is a reliable alternative procedure for establishment of hematopoietic chimerism and donor-specific tolerance without myeloablative conditioning.

  5. 高频超声心动图评估Bax基因转染对大鼠异位移植心脏存活的影响%Assessment of Bax gene transfer influence on survival of heterotopic cardiac allograft in rats by high-frequency echocardiography

    Institute of Scientific and Technical Information of China (English)

    金佳美; 张宇辉; 陈明; 朱烨; 曹浩

    2013-01-01

    目的 探讨高频超声心动图在评估Bax基因转染对大鼠异位移植心脏存活影响中的价值.方法 建立30只腹腔同种异体心脏移植大鼠模型,分为3组,每组10只:A组,单纯移植组;B组,供心移植+抗排异反应药物组;C组,供心移植+ Bax-shRNA+超声微泡组.大鼠分别于心脏移植手术后第1、3、6d,采用高频超声心动图测量大鼠左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、左室射血分数(LVEF)、左室心肌厚度(LVT)、左室心肌增厚率(LVTR)等参数,于术后第6d超声测量完毕后处死5只大鼠取心肌组织行病理检查,其余5只大鼠用于观察移植心脏存活时间.结果 ①高频超声心动图能清晰显示大鼠移植心脏常规切面;②C组移植心脏存活时间为(16.21±5.01)d,明显长于B组[(11.14±1.72)d,P<0.05]及A组[(7.26±1.57)d,P<0.01].③移植术后,三组大鼠左室心肌厚度逐渐增加;术后第6d,A组LVEF明显低于B组及C组(P<0.05),而B组与C组间差异无统计学意义(P>0.05);术后第3、6d,A组及B组LVT高于C组(P<0.05),LVTR低于C组(P<0.05).结论 高频超声心动图能准确评价Bax基因转染对大鼠移植心脏存活的影响,判断移植心脏结构和功能,其中LVT及LVTR较LVEF更为敏感,可作为早期评估指标.%Objective To evaluate the value of high-frequency echocardiography in assessing Bax gene transfer influence on survival of heterotopic cardiac allograft in rats.Methods Thirty rat models of heterotopic heart transplantation were established.Group A received heart transplantation only; Group B received cyclosporin (CsA) after operatiom Group C received ultrasound targeted microbubble destruction (UTMD) combined with Bax-shRNA.All rats were tested by high-frequency echocardiography at day 1,3,6 after transplantation.The ultrasound parameters included left ventricular internal dimension diastole (LVIDd),left ventricular internal dimension systole(LVIDs),left ventricular

  6. RNA干扰技术阻断CD40/CD40L共刺激通路对小鼠移植心存活时间的影响%Effects of blocking CD40/CD40L costimulatory pathway by RNA interference on the survival of mouse cardiac allograft

    Institute of Scientific and Technical Information of China (English)

    朱杰昌; 付蔚华; 朱理玮

    2010-01-01

    Objective To investigate the effect of blocking CD40/CD40L costimulatory pathway by the lentiviral vector-mediated RNA interference on the survival of mouse cardiac allograft. Methods Mouse bone marrow-derived dendritic cells (DCs) were infected by CD40-RNAi lentiviral vector in vitro, and tolerogenic DCs (Tol-DCs) with decreased CD40 expression were prepared. Fluorescence real-time quantitative PCR and flow cytometry were used to analyze the expression of CD40 mRNA and DC surface antigens CD40, CD11c, MHC Ⅱ before and after infection. Mouse model of heterotropic abdominal heart transplantation was established. Seven days prior to heart transplantation, Tol-DCs with decreased CD40 expression were transfused into recipient mice intravenously (lentivirus infected DC group). Control group and non-infected DC group were assigned simultaneously. The survival of cardiac allograft was monitored and pathological grade of acute rejection 7 days after heterotropic abdominal heart transplantation was determined. Results The transcription of CD40 mRNA of DCs was down-regulated significantly at 48 h after CD40-RNAi lentiviral vector infection, and the inhibition rate was 80. 9%. The expression of CD40 protein was also significantly decreased as compared with control group (40. 07% ± 4. 03% ) ( P < 0. 05 ).Compared to control group (8 ± 2 days) and non-infected DC group (9 ± 1 days), the survival time of cardiac allograft in CD40-RNAi lentivirus infected DC group (14 ± 4 days) was significantly prolonged (P< 0. 05 ), and the pathological grade of acute rejection decreased significantly ( P < 0. 05 ).Conclusion Blocking CD40/CD40L costimulatory pathway could hamper the activation of allogeneic T lymphocyte, inhibit the acute rejection and prolong the survival of mouse cardiac allograft.%目的 探讨慢病毒介导RNA干扰(RNAi)技术阻断CD40/CD40L共刺激通路对小鼠移植心存活时间的影响.方法 以针对小鼠CD40基因的RNAi慢病毒载体在体外

  7. 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.

  8. Induction of tolerance to cardiac allografts using donor splenocytes engineered to display on their surface an exogenous fas ligand protein.

    Science.gov (United States)

    Yolcu, Esma S; Gu, Xiao; Lacelle, Chantale; Zhao, Hong; Bandura-Morgan, Laura; Askenasy, Nadir; Shirwan, Haval

    2008-07-15

    The critical role played by Fas ligand (FasL) in immune homeostasis renders this molecule an attractive target for immunomodulation to achieve tolerance to auto- and transplantation Ags. Immunomodulation with genetically modified cells expressing FasL was shown to induce tolerance to alloantigens. However, genetic modification of primary cells in a rapid, efficient, and clinically applicable manner proved challenging. Therefore, we tested the efficacy of donor splenocytes rapidly and efficiently engineered to display on their surface a chimeric form of FasL protein (SA-FasL) for tolerance induction to cardiac allografts. The i.p. injection of ACI rats with Wistar-Furth rat splenocytes displaying SA-FasL on their surface resulted in tolerance to donor, but not F344 third-party cardiac allografts. Tolerance was associated with apoptosis of donor reactive T effector cells and induction/expansion of CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells. Treg cells played a critical role in the observed tolerance as adoptive transfer of sorted Treg cells from long-term graft recipients into naive unmanipulated ACI rats resulted in indefinite survival of secondary Wistar-Furth grafts. Immunomodulation with allogeneic cells rapidly and efficiently engineered to display on their surface SA-FasL protein provides an effective and clinically applicable means of cell-based therapy with potential application to regenerative medicine, transplantation, and autoimmunity.

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

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  12. 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.

  13. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-07-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

  14. Immunological aspects of clinical and experimental cardiac valve allograft implantation

    NARCIS (Netherlands)

    F.B.S. Oei (Frank)

    2001-01-01

    textabstractThe documented history of allogeneic cardiac valve implantation began in 1952. In that year, the first successful implantation of an canine aortic valve in the descendlng aorta of another dog, was carried out by Conrad Lam etal. Driven by the succes seen in this animal model Murray et al

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Morphologic and immunohistochemical findings in antibody-mediated rejection of the cardiac allograft.

    Science.gov (United States)

    Fishbein, Gregory A; Fishbein, Michael C

    2012-12-01

    The recognition and acceptance of the entity of antibody-mediated rejection (AMR) of solid organs has been slow to develop. Greatest acceptance and most information relates to cardiac transplantation. AMR is thought to represent antibody/complement mediated injury to the microvasculature of the graft that can result in allograft dysfunction, allograft loss, accelerated graft vasculopathy, and increased mortality. The morphologic hallmark is microvascular injury with immunoglobulin and complement deposition in capillaries, accumulation of intravascular macrophages, and in more severe cases, microvascular hemorrhage and thrombosis, with inflammation and edema of the affected organ. Understanding of the pathogenesis of AMR, criteria and methods for diagnosis, and treatment strategies are still in evolution, and will be addressed in this review.

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

    Institute of Scientific and Technical Information of China (English)

    梁晓燕; 陈宗佑; 钱诗光; 李树浓

    2000-01-01

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

  1. Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study.

    Science.gov (United States)

    Pighi, Michele; Tomai, Fabrizio; Petrolini, Alessandro; de Luca, Leonardo; Tarantini, Giuseppe; Barioli, Alberto; Colombo, Paola; Klugmann, Silvio; Ferlini, Marco; Ormezzano, Maurizio Ferrario; Loi, Bruno; Calabrò, Paolo; Bianchi, Renato Maria; Faggian, Giuseppe; Forni, Alberto; Vassanelli, Corrado; Valgimigli, Marco; Ribichini, Flavio

    2016-02-01

    Cardiac allograft vasculopathy (CAV) is a form of accelerated atherosclerosis, which represents the leading cause of late morbidity and mortality after heart transplantation. The recent bioresorbable vascular scaffold (BVS) technology represents a potential novel therapeutic tool, in the context of CAV, by allowing transient scaffolding and concomitant vessel healing. Eligible subjects will be treated by using the Absorb Everolimus-Eluting BVS (Abbott Vascular, Santa Clara, CA, USA), and evaluated at pre-determined time points, up to 3 years since the index procedure. Both clinical and imaging data will be collected in dedicated case report forms (CRF). All imaging data will be analyzed in an independent core laboratory. The primary aim of the study is to evaluate the angiographic performance at 1 year of second-generation Absorb BVS, in heart transplant recipients affected by CAV.

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

    Science.gov (United States)

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

    2006-12-20

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Noninvasive assessment of treatment of cardiac allograft rejection with indium-111-labeled lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Rosenbloom, M.; Eisen, H.J.; Laschinger, J.; Saffitz, J.E.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. III

    1988-09-01

    We have shown previously that cardiac allograft rejection can be detected noninvasively with gamma scintigraphy after administration of indium-111 (111In)-labeled lymphocytes. To determine whether this technique could be used to monitor salvage immunosuppressive therapy in reversing rejection, 5 dogs were studied after thoracic heterotopic cardiac transplantation. Initial postoperative immunosuppression was maintained with cyclosporine (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 7 days after transplantation and then discontinued. Scintigraphy after administration of labeled lymphocytes was performed during initial immunosuppression and every 3 days after its termination. Endomyocardial biopsies were obtained on each day scintigraphy was performed. Once scintigraphic criteria for rejection were met (111In-lymphocyte uptake greater than mean +/- 2SD of normal myocardium), animals were treated with high dose methylprednisolone and cyclosporine. Myocardial 111In-lymphocyte activity compared with that in blood was 0.7 +/- 0.8 during initial immunosuppression, increased to 5.7 +/- 3.5 after termination of therapy (P less than 0.01), and diminished with salvage immunosuppressive therapy to 0.5 +/- 0.8 (P = NS compared with native hearts or allografts during initial immunosuppression). Scintigraphy accurately predicted all but one episode of biopsy-documented rejection and accurately detected reversal of rejection during salvage. Thus, scintigraphy with 111In-labeled lymphocytes should facilitate noninvasive monitoring of antirejection therapy in patients.

  5. 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.

  6. 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.

  7. Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival.

    Science.gov (United States)

    Batal, Ibrahim; De Serres, Sacha A; Safa, Kassem; Bijol, Vanesa; Ueno, Takuya; Onozato, Maristela L; Iafrate, A John; Herter, Jan M; Lichtman, Andrew H; Mayadas, Tanya N; Guleria, Indira; Rennke, Helmut G; Najafian, Nader; Chandraker, Anil

    2015-12-01

    Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.

  8. Chronic cardiac allograft rejection: critical role of ED-A(+) fibronectin and implications for targeted therapy strategies.

    Science.gov (United States)

    Franz, Marcus; Neri, Dario; Berndt, Alexander

    2012-03-01

    Chronic cardiac allograft rejection is characterized by cardiac allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) causing severe long-term complications after heart transplantation and determining allograft function and patients' prognosis. Until now, there have been no sufficient preventive or therapeutic strategies. CAV and CIF are accompanied by changes in the extracellular matrix, including re-expression of the fetal fibronectin splice variant known as ED-A(+) fibronectin. This molecule has been shown to be crucial for the development of myofibroblasts (MyoFbs) as the main cell type in CIF and for the activation of vascular smooth muscle cells (VSMCs) as the main cell type in CAV. Relevant re-expression and protein deposition of ED-A(+) fibronectin has been demonstrated in animal models of chronic rejection, with spatial association to CAV and CIF, and a quantitative correlation to the rejection grade. The paper by Booth et al published in this issue of The Journal of Pathology could prove for the first time the functional importance of ED-A(+) fibronectin for the development of CIF as a main component of chronic cardiac rejection. Thus, promising conclusions for the development of new diagnostic, preventive, and therapeutic strategies for chronic cardiac rejection focusing on ED-A(+) fibronectin can be suggested.

  9. 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

  10. 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.

  11. Induction of Tolerance to Cardiac Allografts Using Donor Splenocytes Engineered to Display on Their Surface an Exogenous FasL Protein1

    Science.gov (United States)

    Yolcu, Esma S.; Gu, Xiao; Lacelle, Chantale; Zhao, Hong; Bandura-Morgan, Laura; Askenasy, Nadir; Shirwan, Haval

    2008-01-01

    The critical role played by FasL in immune homeostasis renders this molecule as an attractive target for immunomodulation to achieve tolerance to auto and transplantation antigens. Immunomodulation with genetically modified cells expressing FasL was shown to induce tolerance to alloantigens. However, genetic modification of primary cells in a rapid, efficient, and clinically applicable manner proved challenging. Therefore, we tested the efficacy of donor splenocytes rapidly and efficiently engineered to display on their surface a chimeric form of FasL protein (SA-FasL) for tolerance induction to cardiac allografts. Intraperitoneal injection of ACI rats with WF splenocytes displaying SA-FasL on their surface resulted in tolerance to donor, but not F344 third party, cardiac allografts. Tolerance was associated with apoptosis of donor reactive T effector cells and induction/expansion of CD4+CD25+FoxP3+ T regulatory (Treg) cells. Treg cells played a critical role in the observed tolerance as adoptive transfer of sorted Treg cells from long-term graft recipients into naïve unmanipulated ACI rats resulted in indefinite survival of secondary WF grafts. Immunomodulation with allogeneic cells rapidly and efficiently engineered to display on their surface SA-FasL protein provides an effective and clinically applicable means of cell-based therapy with potential application to regenerative medicine, transplantation, and autoimmunity. PMID:18606644

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Host-derived smooth muscle cells accumulate in cardiac allografts: role of inflammation and monocyte chemoattractant protein 1.

    Directory of Open Access Journals (Sweden)

    Piotr Religa

    Full Text Available Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35+/-2.3% of cells in arterioles (range, 0.08-12.51%. As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41+/-1.03, p = 0.034 and the number of leukocytes (19.1+/-12.7 per 20 high-power fields, p = 0.01. The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1 released from leukocytes was crucial for SMC migration. After heart allotransplantation, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts.

  17. Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

    Science.gov (United States)

    Bojakowski, Krzysztof; Soin, Joanna; Nozynski, Jerzy; Zakliczynski, Michal; Gaciong, Zbigniew; Zembala, Marian; Söderberg-Nauclér, Cecilia

    2009-01-01

    Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs) both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35±2.3% of cells in arterioles (range, 0.08–12.51%). As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41±1.03, p = 0.034) and the number of leukocytes (19.1±12.7 per 20 high-power fields, p = 0.01). The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1) released from leukocytes was crucial for SMC migration. After heart allotransplantion, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts. PMID:19142231

  18. 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.

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

    OpenAIRE

    V. Y. Abramov; Y. G. Moysyuk; N. N. Kaluzhina; N. B. Bogdanova; V. V. Morozova; N. V. Apanasenko

    2012-01-01

    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 n...

  20. Optimizing Survival Outcomes For Adult Patients With Nontraumatic Cardiac Arrest.

    Science.gov (United States)

    Jung, Julianna

    2016-10-01

    Patient survival after cardiac arrest can be improved significantly with prompt and effective resuscitative care. This systematic review analyzes the basic life support factors that improve survival outcome, including chest compression technique and rapid defibrillation of shockable rhythms. For patients who are successfully resuscitated, comprehensive postresuscitation care is essential. Targeted temperature management is recommended for all patients who remain comatose, in addition to careful monitoring of oxygenation, hemodynamics, and cardiac rhythm. Management of cardiac arrest in circumstances such as pregnancy, pulmonary embolism, opioid overdose and other toxicologic causes, hypothermia, and coronary ischemia are also reviewed.

  1. 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

  2. Early Inflammatory Markers Are Independent Predictors of Cardiac Allograft Vasculopathy in Heart-Transplant Recipients

    Science.gov (United States)

    Labarrere, Carlos A.; Woods, John R.; Hardin, James W.; Jaeger, Beate R.; Zembala, Marian; Deng, Mario C.; Kassab, Ghassan S.

    2014-01-01

    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 improves

  3. 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.

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

    Science.gov (United States)

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

    2013-11-01

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

  5. 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.

  6. 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. 

  7. Improved renal allograft survival using the mixed lymphocyte culture for selection of nonidentical living related donors.

    Science.gov (United States)

    Riggio, R R; Saal, S D; Katz, E B; Tapia, L; White, R; Chami, J; Sheigh, J S; Sullivan, J F; Stenzel, K H; Stubenbord, W T; Whitsell, J C; Rubin, A L

    1975-01-01

    Our results concur with earlier published work, by other groups, showing that LRD-recipient pairs with low MLC stimulation usually have better and more prolonged graft success than do those with higher stimulation. Specific HL-A compatibilities or incompatibilities did not seem to affect these results, nor did the presence of an increased number of common loci, short of increasing the apparent chromosome compatibility. The presence of pre-transplant cytotoxic antibodies, in patients with a high MI, however, may unfavorably affect the LRD transplant. The overall results of our LRD transplant experience is shown in Figure 1, and superimposed upon Figure 2, is the current extrapolation of data showing MLC stimulation and haplotype success. Thus, it appears that graft survival may be improved and more closely approach the levels seen in a full-house, diplotype match, by using the MLC results in considering patients for transplantation. Not all patients with a high MLC, however, (see table) reject their grafts and it is impossible to predict pre-transplant who will develop specific allograft enhancement. Before the MI becomes a specific criteria for transplant selection, additional studies of patient stimulation in MLC should be done. Suppression of stimulation by donor cells in autologous serum, as compared to the response to unrelated controls, might provide pre-transplant clues to the presence of enhancing factors. Such studies could provide an index that would be more meaningful than the MI in AB sera alone. Since overall results from both our series and from the Transplant Registry continue to indicate better long term graft survival for LRD than for cadaver transplants, and since the evidence suggests that a successful transplant offers a patient a better quality of life, as well as decreased morbidity and mortality compared to concomitant time spent on hemodialysis, continued LRD transplants with high MI is warranted in some circumstances with the patient

  8. Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.

    Science.gov (United States)

    Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun

    2014-10-01

    Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

  9. 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.

  10. 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.

  11. 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...

  12. 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

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

    Science.gov (United States)

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

    2001-01-01

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

  14. The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors.

    Directory of Open Access Journals (Sweden)

    Jin Xu

    Full Text Available The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD. The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD, we aimed to understand how ischemia/reperfusion (I/R injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13 and DBD (n = 10 livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22 and DBD (n = 13 livers.When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05 and C22 ceramide (p<0.05 were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST of DCD allografts had significantly increased.These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.

  15. Evolution in functional complexity of heart rate dynamics: a measure of cardiac allograft adaptability.

    Science.gov (United States)

    Kresh, J Y; Izrailtyan, I

    1998-09-01

    The capacity of self-organized systems to adapt is embodied in the functional organization of intrinsic control mechanisms. Evolution in functional complexity of heart rate variability (HRV) was used as measure of the capacity of the transplanted heart to express newly emergent regulatory order. In a cross-sectional study of 100 patients after (0-10 yr) heart transplantation (HTX), heart rate dynamics were assessed using pointwise correlation dimension (PD2) analysis. A new observation is that, commencing with the acute event of allograft transplantation, the dynamics of rhythm formation proceed through complex phase transitions. At implantation, the donor heart manifested metronome-like chronotropic behavior (PD2 approximately 1.0). At 11-100 days, dimensional complexity of HRV reached a peak (PD2 approximately 2.0) associated with resurgence in the high-frequency component (0.15-0.5 Hz) of the power spectral density. Subsequent dimensional loss to PD2 approximately 1.0 at 20-30 mo after HTX was followed by a progressive near-linear gain in system complexity, reaching PD2 approximately 3.0 7-10 yr after HTX. The "dynamic reorganization" in the allograft rhythm-generating system, seen in the first 100 days, is a manifestation of the adaptive capacity of intrinsic control mechanisms. The loss of HRV 2 yr after HTX implies a withdrawal of intrinsic autonomic control and/or development of an entrained dynamic pattern characteristic of extrinsic sympathetic input. The subsequent long-term progressive rise in dimensional complexity of HRV can be attributed to the restoration of a functional order patterning parasympathetic control. The recognition that the decentralized heart can restitute the multidimensional state space of HR generator dynamics independent of external autonomic signaling may provide a new perspective on principles that constitute homeodynamic regulation.

  16. 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.

  17. 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.

  18. Evaluation of the updated deifnition of early allograftdysfunctionindonationafterbraindeath and donation after cardiac death liver allografts

    Institute of Scientific and Technical Information of China (English)

    Kris P Croome; William Wall; Douglas Quan; Sai Vangala; Vivian McAlister; Paul Marotta; Roberto Hernandez-Alejandro

    2012-01-01

    BACKGROUND: An  updated  deifnition  of  early  allograft dysfunction (EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients. This analysis did not differentiate between donation after brain death (DBD) and donation after cardiac death (DCD) allograft recipients. METHODS: We reviewed our prospectively entered database for all DBD (n=377) and DCD (n=38) liver transplantations between January 1, 2006 and October 30, 2011. The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups. RESULTS: EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients, but in DCD allograft recipients there was no signiifcant difference in the rate of graft failure in those with EAD (11.5%) compared with those without EAD (16.7%) (P=0.664) or in the rate of death in recipients with EAD (3.8%) compared with those without EAD (8.3%) (P=0.565). The graft failure rate in the ifrst 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio  CONCLUSIONS: The recently validated deifnition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts. On initial assessment, it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts, however a study with a larger sample size of DCD

  19. 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...

  20. 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.

  1. 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.

  2. Similar patient survival following kidney allograft failure compared with non-transplanted patients.

    Science.gov (United States)

    Mourad, Georges; Minguet, Johanna; Pernin, Vincent; Garrigue, Valérie; Peraldi, Marie-Noelle; Kessler, Michèle; Jacquelinet, Christian; Couchoud, Cécile; Duny, Yohan; Daurès, Jean-Pierre

    2014-07-01

    Data from the national French Renal Epidemiology and Information Network (REIN) registry were used to compare survival between transplant recipients under age 65 who resumed dialysis after graft failure during 2007-2009 and transplant-naïve incident dialysis patients matched for age, gender, diabetes mellitus, and year of starting dialysis. Among 911 transplant patients who returned to dialysis, 103 had died by 1 January 2011. Multivariate analysis showed that age over 48 years, coronary artery disease, peripheral artery disease, and inability to walk unassisted were significant predictors of death. In the case-control analysis, the observed mortality rates in 778 transplant failure and 778 transplant-naïve dialysis patients were 11.8 and 10.8%, respectively. Kaplan-Meier estimates of survival after transplant failure vs. the transplant-naïve controls were 95.2 vs. 94.1% at 1 year, 90.3 vs. 88.8% at 2 years, and 84.2 vs. 80.2% at 3 years (log rank P=0.197 overall). Dialysis in transplant failure vs. transplant-naïve patients was not associated with significantly increased mortality. At the start of dialysis, the serum creatinine levels and the rate of unplanned dialysis were significantly lower in transplant failure patients compared with transplant-naïve controls. Thus, in patients under 65 years of age in France, survival of dialysis patients after graft loss is similar to that of incident dialysis patients who have not undergone transplantation.

  3. 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.

  4. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Mihai Onofriescu

    Full Text Available Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered.A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE, by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup. Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO: 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort.In the entire study population, patients considered overhydrated (using both cut-offs had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3

  5. 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.

  6. Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

    Science.gov (United States)

    Guberina, Hana; Rebmann, Vera; Wagner, Bettina; da Silva Nardi, Fabiola; Dziallas, Phillip; Dolff, Sebastian; Bienholz, Anja; Wohlschlaeger, Jeremias; Bankfalvi, Agnes; Heinemann, Falko M; Witzke, Oliver; Zoet, Yvonne M; Claas, Frans H J; Horn, Peter A; Kribben, Andreas; Doxiadis, Ilias I N

    2017-03-01

    Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (pE-mediated immune activation. Moreover, HLA-E expression correlated with deterioration in renal allograft function (pE along with high numbers of mismatched HLA-class I leader peptides might represent additional targets for immune-activating responses.

  7. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites

    DEFF Research Database (Denmark)

    Krag, A; Bendtsen, F; Henriksen, J H;

    2010-01-01

    OBJECTIVES: Recent studies suggest that cardiac dysfunction precedes development of the hepatorenal syndrome. In this follow-up study, we aimed to investigate the relation between cardiac and renal function in patients with cirrhosis and ascites and the impact of cardiac systolic function...... on survival. Patients and DESIGN: Twenty-four patients with cirrhosis and ascites were included. Cardiac function was investigated by gated myocardial perfusion imaging (MPI) for assessment of cardiac index (CI) and cardiac volumes. The renal function was assessed by determination of glomerular filtration...... (130 (SD 46) vs 78 (SD 29) mumol/l, pdeveloped hepatorenal syndrome type 1 within 3 months was higher in the group with low CI than in the high CI group (43% vs 5%, p = 0.04). Patients with the lowest CI (N = 8) had significantly poorer survival at 3, 9, and 12 months...

  8. Proximal tubular dysfunction is associated with chronic allograft nephropathy and decreased long-term renal-graft survival

    NARCIS (Netherlands)

    Camara, N.O.S.; Silva, M.S.; Nishida, S.; Pereira, A.B.; Pacheco-Silva, A.

    2004-01-01

    Background: Chronic allograft nephropathy is the major cause of graft loss after the first year of transplantation. Although many conditions are associated with its development, there is no method that can anticipate its risk in patients with good renal function. Methods: We prospectively studied 92

  9. 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...

  10. 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

    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.......13 (95% CI=0.99-1.29). CONCLUSION: In this large population-based observational study, we found prehospital physician involvement after OHCA associated with better 30-day survival. This association was also found for ROSC, but with less certainty for 1-year survival....... 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...

  11. 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...

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Survival after blunt left ventricular rupture with cardiac tamponade

    Directory of Open Access Journals (Sweden)

    Yu-Jang Su

    2013-01-01

    Full Text Available A 34-year-old man was drunk and drove to hit a traffic island. Cold sweating and unconscious status were found on arrival. Vital signs revealed BP 42/25, and heart rate 121/min. There was massive pericardial effusion with cardiac tamponade found by CT. Immediate surgical intervention and rupture of left ventricular (LV free wall was found. He was discharged after 2 d intensive care unit (ICU observation and 5-day regular ward care. There is high mortality rate in traumatic heart rupture although timely repair, over all mortality is around 20%-36% in recent 3 years.

  17. Experimental Study of IL-17 on Cardiac Allograft Rejection in Mice%IL-17参与小鼠心脏移植排斥反应的实验研究

    Institute of Scientific and Technical Information of China (English)

    雷钧; 何凡; 吴敏; 郑翔; 李舒媛; 陈知水

    2009-01-01

    Objective To investigate the role of Thl7 cells and their cytokines in cardiac allograft rejection in mice. Methods The heterotopic cardiac transplantation models were divided into two groups:rejection group and isograft group. Mean survival time(MST)was measured. The mouse hearts in each group were harvested on the day 1,2,3,4 ,5,6,7,and 8 post-transplantation. The mRNA expression of IL-17, RORγt and IFN-γ was detected by semiquantitative RT-PCR. The expression of IL-17 in CD4~+ or CD8~+ T cells was observed on the postoperative day 4 by immunofluorescence technique. Results RT-PCR revealed that IL-17 and RORγt mRNA was expressed earlier than IFN-γ, their expression was detected on the second day after transplantation, the expression quantity reached the peak on the postoperative day 4,then gradually reduced,and on the postoperative day 6 and 7,no expression was detectable. Immunofluorescence staining demonstrated that both CD4~+ and CD8~+ T cells were present,but the majority of the graft-infiltrating lymphocytes in rejection group were IL-17-producing CD4~+ T cells. Conclusion Thl7 cells may play an important role in the development of cardiac transplant rejection. IL-17 could serve as a predictive parameter for allograft rejection in the future.%目的 研究Th17细胞相关因子白细胞介素17(IL-17)在小鼠心脏移植排斥反应中的表达及意义.方法 建立小鼠颈部异位心脏移植模型,实验动物随机分为同系移植组和急性排斥反应组.观察2组供心存活时间,应用RT-PCR检测移植心脏IL-17、核孤独受体γt(RORγt)、干扰素-γ(IFN-γ)mRNA在移植术后1、2、3、4、5、6、7、8 d的动态表达水平.免疫荧光法观察移植术后第4天移植心脏内CD4~+、CD8~+T细胞中IL-17的表达情况.结果 RT-PCR检测显示,在急性排斥反应组中,IL-17和RORγt mRNA的表达都早于IFN-γ,在移植术后第2天即可于移植心脏中检测到,其表达量在术后第4天均达到高峰,随后逐

  18. 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].

  19. Initial outcomes of using allografts from donation after cardiac death donors for liver transplantation in New South Wales

    NARCIS (Netherlands)

    van der Stelt, Jorieke M.; Verran, Deborah J.; deRoo, Ronald A.; Christine, Hazel; Crawford, Michael

    2013-01-01

    Objectives: To report the early outcomes of the initial selection and use of donation after cardiac death (DCD) donor livers for transplantation in New South Wales, following a guidelines implementation process. Design and setting: Review of database and medical records from the Australian National

  20. Factors affecting survival in pediatric cardiac tamponade caused by central venous catheters.

    Science.gov (United States)

    Kayashima, Kenji

    2015-12-01

    Pediatric central venous catheter (CVC) placement is useful but associated with complications such as cardiac tamponade. We aimed to identify risk factors for death in cardiac tamponade. Published articles on pediatric CVC-associated cardiac tamponade were obtained by searching PubMed and Google and retrospectively reviewed to analyze risk factors for death. Factors examined for their effect on mortality risk included patient age, weight, CVC size, days from CVC insertion to tamponade occurrence, substances administered, insertion site, treatment, CVC material, and initial CVC tip position. Of 110 patients reported in 62 articles, 69 survived and 41 died. Among survivors, 55 of 69 patients were treated; among deaths, only 7 of 38 (OR 537.9, 95% CI 29.3-9,877, p tamponade survival. Past studies have mainly discussed how to avoid pediatric cardiac tamponade; by contrast, the present study focused on how to avoid deaths. The findings of this review suggest that cardiac tamponade survival is better when tamponade is detected early and treated promptly and might be affected by initial CVC tip position.

  1. 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

  2. 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

  3. Role of the Galectin-7 expression in cardiac allografts in human and mouse%Galectin-7在人和鼠同种异体心脏移植物中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    雒真龙; 周鸿敏; 黄霞; 方静; 徐洪来; 高义; 杨超; 潘铁成; 陈忠华

    2013-01-01

    Objective To explore the function of galectin-7 in acute rejection through detecting the expression galectin-7 in cardiac allografts in human and mouse.Methods Mouse models of cardiac allografts and isografts were constructed.Western blot and Immunohistochemistry (IHC) were used for detecting galectin-7 expression in the grafts.IHC was used for detecting galectin-7 expression in nyocardial tissues of 15 heart transplant patients with acute rejection and 10 normal individuals.Results The expression of galectin-7 in mouse allografts was significantly higher than that in isografts (1.34 ± 0.18,0.77 ± 0.03,P < 0.01).Galectin-7 mainly located in lymphocytes and vascular endothelial cells in human allografts.Conclusion Galectin-7 is related to the acute rejection in human and mouse cardiac allografts.%目的:通过检测发生急性排斥反应的小鼠及人移植心脏的galectin-7表达,进而分析galectin-7在急排发生过程中的作用.方法:建立小鼠心脏移植模型,分为鼠急排组和鼠对照组.Western blot法和免疫组化法检测小鼠移植心脏galectin-7的表达情况.选择15例心脏移植急排患者(人急排组)和10例正常人(人对照组),免疫组化法检测心肌组织galectin-7的表达.结果:鼠急排组gatectin-7表达明显高于鼠对照组(1.34±0.18,0.77±0.03,P< 0.01).人急排组心脏galectin-7表达明显高于人对照组,且galectin-7主要定位于人急排心脏的浸润淋巴细胞及血管内皮细胞.结论:Galectin-7与人和鼠同种异体心脏移植急性排斥反应有相关性.

  4. Out-of-hospital cardiac arrest: determinant factors for immediate survival after cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Daniela Aparecida Morais

    2014-08-01

    Full Text Available OBJECTIVE: to analyze determinant factors for the immediate survival of persons who receive cardiopulmonary resuscitation from the advanced support units of the Mobile Emergency Medical Services (SAMU of Belo Horizonte.METHOD: this is a retrospective, epidemiological study which analyzed 1,165 assistance forms, from the period 2008 - 2010. The collected data followed the Utstein style, being submitted to descriptive and analytical statistics with tests with levels of significance of 5%.RESULTS: the majority were male, the median age was 64 years, and the ambulance response time, nine minutes. Immediate survival was observed in 239 persons. An association was ascertained of this outcome with "cardiac arrest witnessed by persons trained in basic life support" (OR=3.49; p<0.05; CI 95%, "cardiac arrest witnessed by Mobile Emergency Medical Services teams" (OR=2.99; p<0.05; CI95%, "only the carry out of basic life support" (OR=0.142; p<0.05; CI95%, and "initial cardiac rhythm of asystole" (OR=0.33; p<0.05; CI 95%.CONCLUSION: early access to cardiopulmonary resuscitation was related to a favorable outcome, and the non-undertaking of advanced support, and asystole, were associated with worse outcomes. Basic and advanced life support techniques can alter survival in the event of cardiac arrest.

  5. Does Glucagon Improve Survival in a Porcine (Sus Scrofa) of Adult Asphyxial Cardiac Arrest in Addition to Standard Epinephrine Therapy?

    Science.gov (United States)

    2012-01-17

    UDIIILI: oa. I..UN I ItA!.. I NUMDI:It Does Glucagon improve survival in a porcine (Sus Scrofa ) of adult asphyxial cardiac arrest in addition to...EXPIRATION DATE: 25 Mar 13 PROTOCOL TITLE: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial Cardiac Arrest in Addition...Additions: Deletions: 2 Protocol No: A-2007-03 Protocol Title: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial

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

    Directory of Open Access Journals (Sweden)

    Diva Novy Barbosa Chaves

    2008-02-01

    effects of cyclosporine, as an immunosuppressor model, and thalidomide and dyclofenac as anti-inflammatory drugs on an experimental skin allograft research. METHODS: Forty-two rabbits were divided in the following groups (n=6: Group 1 - autografting control; Group 2 - allografting control; Group 3 - allografts under thalidomide effect (100 mg/kg/day; Group 4 - allografts under sodium dyclofenac effect (2 mg/kg/day; - Group 5 -allografts under cyclosporine effect (10 mg/kg/day; Group 6 - allografts under cyclosporine effect (5 mg/kg/day; Group 7- allografts under cyclosporine (5 mg/kg/day plus thalidomide (100 mg/kg/day effect. Drugs were given via orogastric tube since the day before transplantation and daily during the postoperative period. Circular total skin grafts of the ear were exchanged between California and White New Zealand rabbits. RESULTS: Cyclosporine 10 mg/kg/day increased allograft survival and this effect was comparable to the association of cyclosporine 5 mg/kg/day with thalidomide 100 mg/kg/day. Thalidomide as an isolated drug and dyclofenac had a minimum effect on the average survival of the skin allografts. The number of eosinophils around the necrotic skin was higher in the dyclofenac group and lower in the group receiving cyclosporine associated with thalidomide. CONCLUSION: This study showed that thalidomide may be an useful drug when associated with subtherapeutic doses of cyclosporine for treatment of skin allografts.

  7. 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.

  8. Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest.

    Science.gov (United States)

    Miao, Fen; Cai, Yun-Peng; Zhang, Yu-Xiao; Li, Ye; Zhang, Yuan-Ting

    2015-01-01

    Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH) often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF), a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model). Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis.

  9. Divine Love and Deep Connections: A Long-Term Followup of Patients Surviving Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Amy L. Ai

    2011-01-01

    Full Text Available We examined experiencing divine love as an indicator of affective spiritual growth in a prospective cohort of 200 patients surviving cardiac surgery. These patients previously completed two-wave preoperative interviews when standardized cardiac surgery data were also collected. The information included left ventricular ejection fraction, New York Heart Association Classification, baseline health (physical and mental, optimism, hope, religiousness, prayer coping, religious/spiritual coping, and demographics. We then measured divine love at 900 days postoperatively. Hierarchical linear regression indicated the direct effect of positive religious coping on experiences of divine love, controlling for other key variables. Postoperatively perceived spiritual support was entered at the final step as an explanatory factor, which appeared to mediate the coping effect. None of the other faith factors predicted divine love. Further research regarding divine love and spiritual support may eventually guide clinical attempts to support patients' spiritual growth as an independently relevant outcome of cardiac surgery.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. Avaliação da doença vascular do enxerto no transplante cardíaco: experiência de um centro brasileiro Assessment of cardiac allograft vasculopathy in cardiac transplantation: experience of a Brazilian center

    Directory of Open Access Journals (Sweden)

    Elide Sbardellotto Mariano da Costa

    2012-10-01

    Full Text Available FUNDAMENTO: O transplante cardíaco continua sendo o tratamento de escolha para a insuficiência cardíaca refratária ao tratamento otimizado. Dois métodos diagnósticos apresentam elevada sensibilidade no diagnóstico de episódios de rejeição ao enxerto e Doença Vascular do Enxerto (DVE, causas importantes de mortalidade no pós-transplante. OBJETIVO: Avaliar a relação entre os resultados do ultrassom intracoronariano (USIV e os laudos das biópsias endomiocárdicas (BX no seguimento de pacientes submetidos a transplante cardíaco em um serviço de referência brasileiro. MÉTODOS: Foi realizado um ensaio epidemiológico retrospectivo observacional, com pacientes submetidos a transplante cardíaco ortotópico, no período de 2000 a 2009. Foram analisados os prontuários desses pacientes e os resultados dos USIV e BX realizados rotineiramente no seguimento clínico pós-transplante e terapêutica em uso. RESULTADOS: Dos 77 pacientes analisados, 63,63% são do sexo masculino, nas faixas etárias de 22 a 69 anos. Quanto aos resultados dos USIV, 33,96% foram classificados em Stanford classe I, e 32,08%, como Stanford IV. Dos 143 laudos das biópsias, 51,08% tiveram resultado 1R, 3R em 0,69% dos laudos, e 14,48% apresentaram a descrição de efeito Quilty. Todos usaram antiproliferativos, 80,51% usaram inibidores da calcineurina e 19,48% usaram inibidores do sinal de proliferação (ISP. CONCLUSÃO: A avaliação dos pacientes pós-transplante cardíaco por meio do USIV incorpora informações detalhadas para o diagnóstico precoce e sensível da DVE, que são complementadas pelas informações histológicas fornecidas pelas BX, estabelecendo uma possível relação causal entre a DVE e os episódios de rejeição humoral.BACKGROUND: Cardiac transplantation continues to be the treatment of choice for heart failure refractory to optimized treatment. Two methods have high sensitivity for diagnosing allograft rejection episodes and cardiac

  18. 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.

  19. 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.

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

    Science.gov (United States)

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

    2008-08-01

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

  2. β-Adrenergic Regulation of Cardiac Progenitor Cell Death Versus Survival and Proliferation

    Science.gov (United States)

    Khan, Mohsin; Mohsin, Sadia; Avitabile, Daniele; Siddiqi, Sailay; Nguyen, Jonathan; Wallach, Kathleen; Quijada, Pearl; McGregor, Michael; Gude, Natalie; Alvarez, Roberto; Tilley, Douglas G.; Koch, Walter J.; Sussman, Mark A.

    2013-01-01

    Rationale Short-term β-adrenergic stimulation promotes contractility in response to stress but is ultimately detrimental in the failing heart because of accrual of cardiomyocyte death. Endogenous cardiac progenitor cell (CPC) activation may partially offset cardiomyocyte losses, but consequences of long-term β-adrenergic drive on CPC survival and proliferation are unknown. Objective We sought to determine the relationship between β-adrenergic activity and regulation of CPC function. Methods and Results Mouse and human CPCs express only β2 adrenergic receptor (β2-AR) in conjunction with stem cell marker c-kit. Activation of β2-AR signaling promotes proliferation associated with increased AKT, extracellular signal-regulated kinase 1/2, and endothelial NO synthase phosphorylation, upregulation of cyclin D1, and decreased levels of G protein–coupled receptor kinase 2. Conversely, silencing of β2-AR expression or treatment with β2-antagonist ICI 118, 551 impairs CPC proliferation and survival. β1-AR expression in CPC is induced by differentiation stimuli, sensitizing CPC to isoproterenol-induced cell death that is abrogated by metoprolol. Efficacy of β1-AR blockade by metoprolol to increase CPC survival and proliferation was confirmed in vivo by adoptive transfer of CPC into failing mouse myocardium. Conclusions β-adrenergic stimulation promotes expansion and survival of CPCs through β2-AR, but acquisition of β1-AR on commitment to the myocyte lineage results in loss of CPCs and early myocyte precursors. PMID:23243208

  3. 阻断ICOS/B7h信号的供体特异性输血对移植受体CD4+CD25+调节性T细胞的影响%Influence of donor specific transfusion with impaired ICOS/B7h allorecognition on CD4 + CD25+regulatory T cells of cardiac allograft recipient

    Institute of Scientific and Technical Information of China (English)

    杜峻峰; 李世拥; 于波; 白雪; 左富义

    2010-01-01

    transplanted in the neck of C57BL/6, without treatment. In treatment group, a combination of 5 × 106 ICOS-Fcrecipient C57BL/6 mice following a heterotopic cardiac allograft transplantation. Graft function was assessed daily by palpation, with rejection defined as the absence of detectable beating, then survival of grafts was recorded. CD4 + CD25 + Treg subsets in the peripheral blood of allograft recipients were analyzed by flow cytometry. The expression of FOXP3 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). To assess the suppressive activity of CD4 + CD25 + Treg from tolerant C57BL/6 mice on CD4 + CD25- Teff from naive BALB/C mice, suppression allogeneic MLR assays were performed in vitro.Results In comparison with allogenic group, the survival of cardiac grafts could be prolonged by the comICOS-Fc on the day 0-6 [(84.38 ± 29. 14) days vs (7.00 ± 0. 76) days, P < 0. 01]. Among 3 groups, a considerable proportion of CD4 + CD25 + Treg could be observed in treatment group [(15.60 ± 5.69 )% ,P <0. 01], meanwhile, high expression of FOXP3 mRNA was also detected within allografts in treatment group.Furthermore, in contrast to naive C57BL/6 mice, CD4+ CD25 + Treg harvested from tolerant C57BL/6 mice showed more potent suppressive effect on the proliferation of CD4 + CD25 - Teff. Conclusion Allograft tolerance can be induced by donor specific transfusion with impaired ICOS/B7h allorecognition. CD4 + CD25 + Treg played a critical role in the establishment and the maintenance of this allograft tolerance.

  4. 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.

  5. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  6. Specific unresponsiveness to skin allografts in burns.

    Science.gov (United States)

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

    1989-05-01

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

  7. 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.

  8. 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

  9. 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.

  10. Evaluation of kidney allograft status using novel ultrasonic technologies

    Directory of Open Access Journals (Sweden)

    Cheng Yang

    2015-07-01

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

  11. Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1α-CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Fengdi Yan

    Full Text Available BACKGROUND: Cardiac progenitor cells (CPCs have been shown to be suitable in stem cell therapy for resurrecting damaged myocardium, but poor retention of transplanted cells in the ischemic myocardium causes ineffective cell therapy. Hypoxic preconditioning of cells can increase the expression of CXCR4 and pro-survival genes to promote better cell survival; however, it is unknown whether hypoxia preconditioning will influence the survival and retention of CPCs via the SDF-1α/CXCR4 axis. METHODS AND RESULTS: CPCs were isolated from adult mouse hearts and purified by magnetic activated cell sorting using c-kit magnetic beads. These cells were cultured at various times in either normoxic or hypoxic conditions, and cell survival was analyzed using flow cytometry and the expression of hypoxia-inducible factor-1α (HIF-1α, CXCR4, phosphorylated Akt and Bcl-2 were measured by Western blot. Results showed that the expression of pro-survival genes significantly increased after hypoxia treatment, especially in cells cultured in hypoxic conditions for six hours. Upon completion of hypoxia preconditioning from c-kit+ CPCs for six hours, the anti-apoptosis, migration and cardiac repair potential were evaluated. Results showed a significant enhancement in anti-apoptosis and migration in vitro, and better survival and cardiac function after being transplanted into acute myocardial infarction (MI mice in vivo. The beneficial effects induced by hypoxia preconditioning of c-kit+ CPCs could largely be blocked by the addition of CXCR4 selective antagonist AMD3100. CONCLUSIONS: Hypoxic preconditioning may improve the survival and retention of c-kit+ CPCs in the ischemic heart tissue through activating the SDF-1α/CXCR4 axis and the downstream anti-apoptosis pathway. Strategies targeting this aspect may enhance the effectiveness of cell-based cardiac regenerative therapy.

  12. Significance of Anti-HLA Antibodies on Adult and Pediatric Heart Allograft Outcomes

    Science.gov (United States)

    Mangiola, Massimo; Marrari, Marilyn; Feingold, Brian; Zeevi, Adriana

    2017-01-01

    As methods for human leukocyte antigens (HLA) antibody detection have evolved and newer solid phase assays are much more sensitive, the last 15 years has seen a renewed focus on the importance of HLA antibodies in solid organ transplant rejection. However, there is still much controversy regarding the clinical significance of antibody level as depicted by the mean fluorescence intensity of a patient’s neat serum. Emerging techniques, including those that identify antibody level and function, show promise for the detection of individuals at risk of allograft rejection, determination of the effectiveness of desensitization prior to transplant, and for monitoring treatment of rejection. Here, we review current publications regarding the relevance of donor-specific HLA antibodies (DSA) in adult and pediatric heart transplantation (HT) with graft survival, development of antibody-mediated rejection and cardiac allograft vasculopathy (CAV). The negative impact of DSA on patient and allograft survival is evident in adult and pediatric HT recipients. Many questions remain regarding the most appropriate frequency of assessment of pre- and posttransplant DSA as well as the phenotype of DSA memory vs. true de novo antibody using large multicenter adult and pediatric cohorts and state-of-the-art methodologies for DSA detection and characterization. PMID:28191005

  13. 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

  14. 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.

  15. Pet ownership, social support, and one-year survival after acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial (CAST).

    Science.gov (United States)

    Friedmann, E; Thomas, S A

    1995-12-15

    Social support and pet ownership, a nonhuman form of social support, have both been associated with increased coronary artery disease survival. The independent effects of pet ownership, social support, disease severity, and other psychosocial factors on 1-year survival after acute myocardial infarction are examined prospectively. The Cardiac Arrhythmia Suppression Trial provided physiologic data on a group of post-myocardial infarction patients with asymptomatic ventricular arrhythmias. An ancillary study provided psychosocial data, including pet ownership, social support, recent life events, future life events, anxiety, depression, coronary prone behavior, and expression of anger. Subjects (n = 424) were randomly selected from patients attending participating Cardiac Arrhythmia Suppression Trial sites and completed baseline psychosocial questionnaires. One year survival data were obtained from 369 patients (87%), of whom 112 (30.4%) owned pets and 20 (5.4%) died. Logistic regression indicates that high social support (p owning a pet (p = 0.085) tend to predict survival independent of physiologic severity and demographic and other psychosocial factors. Dog owners (n = 87, 1 died) are significantly less likely to die within 1 year than those who did not own dogs (n = 282, 19 died; p pet ownership and social support are significant predictors of survival, independent of the effects of the other psychosocial factors and physiologic status. These data confirm and extend previous findings relating pet ownership and social support to survival among patients with coronary artery disease.

  16. Study regarding the survival of patients suffering a traumatic cardiac arrest.

    Science.gov (United States)

    Georgescu, V; Tudorache, O; Nicolau, M; Strambu, V

    2015-01-01

    Severe trauma is the most frequent cause of death in young people, in civilized countries with major social and vital costs. The speed of diagnostic decision making and the precocity of treatment approaches are both essential and depend on the specialists' colaboration. The present study aims to emphasize the actual situation of medical interventions in case of cardiorespiratory arrest due to trauma. 1387 patients who suffered a cardio respiratory arrest both traumatic and non-traumatic were included in order to point out the place of traumatic arrest. Resuscitation of such patients is considered useless and resource consumer by many trauma practitioners who are reporting survival rates of 0%-3.5%. As the determinant of lesions, trauma etiology was as it follows car accidents - 43%, high falls - 30%, suicidal attempts - 3%, domestic violence - 3%, other causes - 21%. Hypovolemia remains the major cause of cardiac arrest and death and that is why the efforts of emergency providers (trauma team) must be oriented towards "hidden death" in order to avoid it. This condition could be revealed and solved easier with minimal diagnostic and therapeutic maneuvers in the emergency department.

  17. OSTEOARTICULAR ALLOGRAFTS IN PAEDIATRIC BONE TUMOR RECONSTRUCTION OF THE KNEE.

    Science.gov (United States)

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

    2015-01-01

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

  18. 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....

  19. 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.

  20. Immediate retransplantation for pancreas allograft thrombosis.

    Science.gov (United States)

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

    2009-04-01

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

  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...... the first 6 h after arrest. Primary outcome was mortality at the end of trial. A Cox proportional hazard model was created to estimate hazard of death, adjusting for covariates. In addition, a propensity score matched analysis was performed. RESULTS: A total of 252 patients (46 %) received early CAG...

  2. 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...

  3. Clinical and functional outcomes of tibial intercalary allograft reconstructions

    Directory of Open Access Journals (Sweden)

    Lucas López Millán

    2012-12-01

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

  4. 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.

  5. 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...

  6. Modulation of excitability, membrane currents and survival of cardiac myocytes by N-acylethanolamines.

    Science.gov (United States)

    Voitychuk, Oleg I; Asmolkova, Valentyna S; Gula, Nadiya M; Sotkis, Ganna V; Galadari, Sehamuddin; Howarth, Frank C; Oz, Murat; Shuba, Yaroslav M

    2012-09-01

    N-acylethanolamines (NAE) are endogenously produced lipids playing important roles in a diverse range of physiological and pathological conditions. In the present study, using whole-cell patch clamp technique, we have for the first time investigated the effects of the most abundantly produced NAEs, N-stearoylethanolamine (SEA) and N-oleoylethanolamine (OEA), on electric excitability and membrane currents in cardiomyocytes isolated from endocardial, epicardial, and atrial regions of neonatal rat heart. SEA and OEA (1-10μM) attenuated electrical activity of the myocytes from all regions of the cardiac muscle by hyperpolarizing resting potential, reducing amplitude, and shortening the duration of the action potential. However, the magnitudes of these effects varied significantly depending on the type of cardiac myocyte (i.e., endocardial, epicardial, atrial) with OEA being generally more potent. OEA and to a lesser extent SEA suppressed in a concentration-dependent manner currents through voltage-gated Na(+) (VGSC) and L-type Ca(2+) (VGCC) channels, but induced variable cardiac myocyte type-dependent effects on background K(+) and Cl(-) conductance. The mechanisms of inhibitory action of OEA on cardiac VGSCs and VGCCs involved influence on channels' activation/inactivation gating and partial blockade of ion permeation. OEA also enhanced the viability of cardiac myocytes by reducing necrosis without a significant effect on apoptosis. We conclude that SEA and OEA attenuate the excitability of cardiac myocytes mainly through inhibition of VGSCs and VGCC-mediated Ca(2+) entry. Since NAEs are known to increase during tissue ischemia and infarction, these effects of NAEs may mediate some of their cardioprotective actions during these pathological conditions.

  7. Blockade of CD40-CD154 at the time of donor-specific blood transfusion does not lead to prolonged kidney allograft survival in nonhuman primates

    NARCIS (Netherlands)

    Ringers, J; Haanstra, KG; Kroczek, RA; Kliem, K; Kuhn, EM; Wubben, J; Ossevoort, MA; Volk, HD; Jonker, M

    2002-01-01

    Background. In rodents it has been demonstrated that blockade of the CD40-CD154 (CD40L) pathway at the time of donor-specific blood transfusion (DST) can result in indefinite graft survival. Because it has been reported in the past that DST in monkeys can have a favorable effect on graft outcome and

  8. 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

  9. 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...

  10. 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

  11. Posttraumatic growth in patients who survived cardiac surgery: the predictive and mediating roles of faith-based factors.

    Science.gov (United States)

    Ai, Amy L; Hall, Daniel; Pargament, Kenneth; Tice, Terrence N

    2013-04-01

    Despite the growing knowledge of posttraumatic growth, only a few studies have examined personal growth in the context of cardiac health. Similarly, longitudinal research is lacking on the implications of religion/spirituality for patients with advanced cardiac diseases. This paper aims to explore the effect of preoperative religious coping on long-term postoperative personal growth and potential mediation in this effect. Analyses capitalized on a preoperative survey and medical indices from the Society of Thoracic Surgeons' National Database of patients undergoing cardiac surgery. Participants in the current follow-up study completed a mailed survey 30 months after surgery. Hierarchical regression analysis was performed to evaluate the extent to which preoperative use of religious coping predicted growth at follow-up, after controlling for key demographics, medical indices, mental health, and protective factors. Predictors of posttraumatic growth at follow-up were positive religious coping and a living status without a partner. Medical indices, optimistic expectations, social support, and other religious factors were unrelated to posttraumatic growth. Including religious factors diminished effects of gender, age, and race. Including perceived spiritual support completely eliminated the role of positive religious coping, indicating mediation. Preoperative positive religious coping may have a long-term effect on postoperative personal growth, explainable by higher spiritual connections as a part of significance-making. These results suggest that spirituality may play a favorable role in cardiac patients' posttraumatic growth after surviving a life-altering operation. The elimination of demographic effects may help explain previously mixed findings concerning the association between these factors and personal growth.

  12. 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

  13. 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...

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

    Science.gov (United States)

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

    2017-01-01

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

  15. Cardiac Recurrence in a Patient with Long-Term Survival from Metastatic Colon Cancer

    Directory of Open Access Journals (Sweden)

    Annabelle Butler

    2012-04-01

    Full Text Available Metastatic colorectal cancer represents a major health problem in the US and worldwide. Forty percent of patients undergoing resection of the primary tumor will experience relapse. In this brief review, we describe a case of a woman with metastatic disease and long-term survival culminating with an unusual myocardial recurrence. Over three decades, a multimodality approach has evolved to allow for long-term survival in selected patients with metastatic colorectal cancer. In this case report, the role of multiple aggressive surgical resections is emphasized.

  16. EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival

    Directory of Open Access Journals (Sweden)

    Monica Jara-Avaca

    2017-02-01

    Full Text Available Subtype-specific human cardiomyocytes (CMs are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs in response to 1-ethyl-2-benzimidazolinone (EBIO, a chemical modulator of small-/intermediate-conductance Ca2+-activated potassium channels (SKs 1–4. Investigating EBIO in human pluripotent stem cells (PSCs, we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency. Equivalent to mPSCs, timed EBIO supplementation during hPSC differentiation resulted in dose-dependent enrichment of up to 80% CMs, including an increase in nodal- and atrial-like phenotypes. However, our study revealed extensive EBIO-triggered cell loss favoring cardiac progenitor preservation and, subsequently, CMs with shortened action potentials. Proliferative cells were generally more sensitive to EBIO, presumably via an SK-independent mechanism. Together, EBIO did not promote cardiogenic differentiation of PSCs, opposing previous findings, but triggered lineage-selective survival at a cardiac progenitor stage, which we propose as a pharmacological strategy to modulate CM subtype composition.

  17. 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.

  18. Anomalous expression of heat shock protein 27 and glucose regulated protein 78 contributed to cardiac allograft vasculopathy%热休克蛋白27和糖调节蛋白78分布异常对心脏移植后血管病变的影响

    Institute of Scientific and Technical Information of China (English)

    雷虹; 尹海辉; 章庆春; 严中亚

    2013-01-01

    目的 观察移植后心脏组织中热休克蛋白27(HSP27)和糖调节蛋白78(GRP78)的组织分布,探讨移植后心脏血管病变(CAV)的发病机制.方法 建立大鼠同基因(n=8)和异基因(n=8)心脏移植的Ono模型,采用免疫组织化学法[链霉菌抗生物素蛋白-过氧化物酶(SP)法]验证移植后心脏组织中HSP27和GRP78的组织分布.结果 同基因植组,HSP27和GRP78在心脏组织内均匀分布;异基因移植组,HSP27和GRP78在环血管周围心肌组织中高表达(2.24±0.36比1.04±0.10,P<0.01;1.51±0.12比0.85±0.30,P<0.05),而在增生的冠状动脉组织内几乎不表达(2.24±0.36比0.25±0.08,P<0.01;1.51±0.12比0.16±0.10,P<0.01).结论 HSP27和GRP78在异基因移植后心脏组织中分布不均,导致冠状动脉组织无力对抗免疫损伤,诱发血管平滑肌细胞过度增殖可能是CAV发生、发展的重要原因.%Objective To observe the protein expression of heat shock protein 27 (HSP27) and glucose regulated protein 78 (GRP78) in rats transplanted hearts,and provide some clues to elucidate the pathogenesis of cardiac allograft vasculopathy (CAV).Methods The hearts were transplanted from Lewis to Sprague-Dawely rats as allograft (n =8) and from Lewis to Lewis rats as isograft (n =8) based on Ono' s model.The protein expression of HSP27 and GRP78 was detected by using immunohistochemistry [streptavid-inperoxidase (SP) method].Results The expression of HSP27 and GRP78 was stained uniformly in cardiac isografts,but that was anomalous in cardiac allografts,which showed higher expression on cardiac muscle (2.24 ± 0.36 vs.1.04 ± 0.10,P < 0.01 ; 1.51 ± 0.12 vs.0.85 ± 0.30,P < 0.05) and lower expression on blood vessels in biopsies with CAV (2.24 ±0.36 vs.0.25 ±0.08,P <0.01 ; 1.51 ±0.12 vs.0.16 ± 0.10,P < 0.01).Conclusion The less expression of HSP27 and GRP78 on blood vessels decreased the defense to immunologic injury,which stimulated the over-proliferation of vascular

  19. 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.

  20. 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

  1. 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...

  2. 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...

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Effect of sirolimus on the expression of integrin ανβ3 mRNA in cardiac allograft in rats%西罗莫司对大鼠移植心脏组织中整合素ανβ3mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    胡名松; 胡建国; 郑宝石

    2011-01-01

    Objective To investigate the effect of sirolimus (SRL) on the expression of integrin ανβ3 mRNA in vascular smooth muscle cells of cardiac allografts in rats, and the possible mechanism of SRL in the prevention of cardiac allograft vasculopathy. Methods Heterotopic heart transplantation models were established. Hearts from Wistar rats were heterotopically transplanted to SD rats (allograft) or Wistar rats (isograft). All rats were randomly divided into four groups:SRL group, SRL 1.25 mg/kg every day,oral intubation after cardiac transplantation; cyclosporine (CsA) group,CsA 10mg/kg every day, subcutaneous administration ; isograft group, no immunosuppressant administration;control group, normal hearts of Wistar rats. All of the animals were killed at 60 day after transplantation. Angiostenosis degree was analyzed by Mias system 4.1 after the cardiac tissues were stained with Van Gieson stain. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the expression of integrin ανβ3 mRNA in cardiac allografts. The relationship between the expression of integrin ανβ3 mRNA and the area of vascular stenosis was analyzed. ResultsIn control group, there was no thickened vascular intima and no vascular stenosis. In allograft group,the thickness of vascular intima was slightly increased but no vascular stenosis was detected. In CsA group, the vascular intima was obviously thickened, the lumen was narrowed, and some small arteries had obstruction. In SRL group, vascular intima proliferation and angiostenosis degree were obviously milder than in CsA group. Semiquantitative RT-PCR analysis revealed that the relative expression of integrin ανβ3 mRNA in CsA and SRL groups was increased significantly as compared with control group and isograft group (2.51±0.43 or 1.17±0.12 vs 0.28±0.08 or 0. 38 ± 0. 05, P<0. 01). The relative expression of integrin ανβ3 mRNA in SRL group was decreased significantly as compared with CsA group (1.17±0

  10. 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...

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

    Science.gov (United States)

    Gracon, Adam S A; Wilkes, David S

    2014-08-01

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

  12. Developing an analytical tool for evaluating EMS system design changes and their impact on cardiac arrest outcomes: combining geographic information systems with register data on survival rates

    Directory of Open Access Journals (Sweden)

    Sund Björn

    2013-02-01

    Full Text Available Abstract Background Out-of-hospital cardiac arrest (OHCA is a frequent and acute medical condition that requires immediate care. We estimate survival rates from OHCA in the area of Stockholm, through developing an analytical tool for evaluating Emergency Medical Services (EMS system design changes. The study also is an attempt to validate the proposed model used to generate the outcome measures for the study. Methods and results This was done by combining a geographic information systems (GIS simulation of driving times with register data on survival rates. The emergency resources comprised ambulance alone and ambulance plus fire services. The simulation model predicted a baseline survival rate of 3.9 per cent, and reducing the ambulance response time by one minute increased survival to 4.6 per cent. Adding the fire services as first responders (dual dispatch increased survival to 6.2 per cent from the baseline level. The model predictions were validated using empirical data. Conclusion We have presented an analytical tool that easily can be generalized to other regions or countries. The model can be used to predict outcomes of cardiac arrest prior to investment in EMS design changes that affect the alarm process, e.g. (1 static changes such as trimming the emergency call handling time or (2 dynamic changes such as location of emergency resources or which resources should carry a defibrillator.

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

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    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.

  14. 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.

  15. 大鼠心脏移植后心肌组织内支链氨基酸代谢对移植物血管病变的影响%Dysfunction of branded-chain amino acids catabolism in rat cardiac allograft

    Institute of Scientific and Technical Information of China (English)

    章庆春; 尹海辉; 严中亚; 吴岳恒; 朱正艳; 雷虹; 卢中

    2011-01-01

    Sprague-Dawely rats served as allografts and those from Lewis to Lewis rats as isografts based on Ono 's model. The differential proteins in transplanted hearts were separated by comparative proteomic technique, and some enzymes which regulated the metabolism of BCAA were identified and validated.Results All transplanted hearts at second week postoperation were characterized by lumen loss (total area-luminal area/total area) in coronary artery, but more predominant at 8th week. All samples from the left ventricles were analyzed by proteomic techniques and the subunits E1 a, E1β and E3 of branched-chain α-ketoacid dehydrogenase (BCKDH) complex were decreased in the heart allografts.Immunohistological detection also showed the expression of BCKDH was reduced not only in the cardiac muscle but also more significantly in blool vessels with cardiac allograft vasculopathy (CAV).BCAA concentrations were increased in the cardiac allografts, but there was no difference in the serum. Conclusion These findings suggest that the catabolic pathways of the BCAA may be inhibited owing to the reduced expression of BCKDH complex, and elevated intracellular concentrations of leucine. The vascular smooth muscle cell and cardiac muscle cell proliferation is stimulated via mTOR-dependent and mTOR-independent pathways, which is associated with the formation of myocardial hypertrophy and AV in the heart allografts.

  16. 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

  17. 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.

  18. 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.

  19. Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Polizzi Clara

    2010-11-01

    Full Text Available Abstract Background Accumulating evidence suggests glucagon-like peptide-1 (GLP-1 exerts cardioprotective effects in animal models of myocardial infarction (MI. We hypothesized that chronic treatment with GLP-1 or the exenatide analog AC3174 would improve cardiac function, cardiac remodeling, insulin sensitivity, and exercise capacity (EC in rats with MI-induced chronic heart failure (CHF caused by coronary artery ligation. Methods Two weeks post-MI, male Sprague-Dawley rats were treated with GLP-1 (2.5 or 25 pmol/kg/min, AC3174 (1.7 or 5 pmol/kg/min or vehicle via subcutaneous infusion for 11 weeks. Cardiac function and morphology were assessed by echocardiography during treatment. Metabolic, hemodynamic, exercise-capacity, and body composition measurements were made at study end. Results Compared with vehicle-treated rats with CHF, GLP-1 or AC3174 significantly improved cardiac function, including left ventricular (LV ejection fraction, and end diastolic pressure. Cardiac dimensions also improved as evidenced by reduced LV end diastolic and systolic volumes and reduced left atrial volume. Vehicle-treated CHF rats exhibited fasting hyperglycemia and hyperinsulinemia. In contrast, GLP-1 or AC3174 normalized fasting plasma insulin and glucose levels. GLP-1 or AC3174 also significantly reduced body fat and fluid mass and improved exercise capacity and respiratory efficiency. Four of 16 vehicle control CHF rats died during the study compared with 1 of 44 rats treated with GLP-1 or AC3174. The cellular mechanism by which GLP-1 or AC3174 exert cardioprotective effects appears unrelated to changes in GLUT1 or GLUT4 translocation or expression. Conclusions Chronic treatment with either GLP-1 or AC3174 showed promising cardioprotective effects in a rat model of CHF. Hence, GLP-1 receptor agonists may represent a novel approach for the treatment of patients with CHF or cardiovascular disease associated with type 2 diabetes.

  20. 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.

  1. 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

    .7%, 30.3%, and 23.4%; and prehospital shock from a defibrillator in 54.7%, 45.0%, and 33.8% (all P... survival if they met 2 criteria: had not achieved return of spontaneous circulation on hospital arrival and had not received a prehospital shock from a defibrillator. CONCLUSIONS: All age groups experienced a large temporal increase in survival on hospital arrival, but the increase in 30-day survival...

  2. 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.

  3. Sarcomatoid Type Primary Pericardial Mesothelioma with a Long-term Survival after the Onset of Cardiac Tamponade

    OpenAIRE

    Saisho, Chika; Ishii, Hidenobu; Edakuni, Nobutaka; Imamura, Yohei; Tokito, Takaaki; Kinoshita, Takashi; Azuma, Koichi; Yamada, Kazuhiko; Hoshino, Tomoaki

    2016-01-01

    Primary pericardial malignant mesothelioma is a very rare clinical entity and its prognosis is very poor. We herein report a 67-year-old man who presented with pericardial mesothelioma that was diagnosed 21 months after the onset of cardiac tamponade as the initial manifestation. Despite undergoing pericardiocentesis and surgical pericardial fenestration at the onset of cardiac tamponade, we were unable to make a conclusive diagnosis of mesothelioma based on the cytological and histological f...

  4. 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

  5. Modifying cyclosporine associated renal allograft dysfunction

    Directory of Open Access Journals (Sweden)

    Mohapatra N

    2009-01-01

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

  6. 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.

  7. 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.

  8. Survival rate in patients after sudden cardiac arrest at the university hospital of northern Norway treated with or without opioids: A retrospective evaluation

    Directory of Open Access Journals (Sweden)

    Vladimir Kuklin

    2013-01-01

    Full Text Available Background: Experimental studies both in vivo and in vitro show significantly increased survival rate in animals and in cortical neurons respectively exposed to acute hypoxia and pre-treated with opioids compared to non-treated counterparts. Thus, the main aim of the study was to examine survival rates in patients after sudden cardiac arrest (SCA in the hospital who were or were not treated with opioids before and/or during cardiac pulmonary resuscitation (CPR. Methods: The registry SCA database at the University Hospital of Northern Norway (UNN for the period of January 2006-December 2009 was used to obtain data for the evaluation. Inclusion criteria were observed SCA at UNN for patients with American Society of Anesthesiologists (ASA 1-3. Exclusion criteria included ASA four to five patients and unobserved SCA. Study patients were divided into two groups: Those not treated with opioids and those treated with opioids not more then 3 h before and/or during CPR. Survival rate 1, 2, 3 and 28 days post CPR were compared for the two groups. Results: A total of 117 patients were registered in the SCA database at UNN for the period from January 2006 to December 2009. Sixty seven patients were excluded from the study: 17 patients had an unknown time of SCA dιbut, two patients had only syncope and 48 were ASA four to five patients. A total of 50 ASA one to three patients were included in the study, 33 and 17 patients respectively in the control and opioid-treated groups. The patients who were treated with opioids before or during CPR had a significantly higher 1, 2, 3 and 28 days survival rate as compared to those receiving only conventional CPR. The model was adjusted for duration of CPR (P=0.047 and treatment with adrenaline (P=0.779 in the groups. Adjusted Odds ratio was 0.075 (95% confidence interval (CI: 0.015-0.387. Relative risk of fatal outcome in the opioids group was 0.2944 (95% CI: 0.1549-0.5594. Conclusion: Significantly higher 1, 2, 3 and

  9. Association of bystander cardiopulmonary resuscitation and survival according to ambulance response-times after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Rajan, Shahzleen; Wissenberg, Mads; Folke, Fredrik;

    2016-01-01

    chances decreased both for patients with bystander CPR and those without. However, the contrast between the survival chances of patients with vs. without bystander CPR increased over time: within 5 minutes, 30-day survival was 14.5% (95% CI: 12.8-16.4) vs. 6.3% (95% CI: 5.1-7.6), corresponding to 2.......3 times higher chances of survival associated with bystander CPR; within 10 minutes, 30-day survival chances were 6.7% (95% CI: 5.4-8.1) vs. 2.2% (95% CI: 1.5-3.1), corresponding to 3.0 times higher chances of 30-day survival associated with bystander CPR. The contrast in 30-day survival became...... statistically insignificant when response time exceeded 13 minutes (bystander CPR vs. no bystander CPR: 3.7% [95% CI: 2.2-5.4] vs. 1.5% [95% CI: 0.6-2.7]) but 30-day survival was still 2.5 times higher associated with bystander CPR. Based on the model and Danish OHCA Statistics, an additional of 233 patients...

  10. Effects of culture of parathyroid in atmosphere of 95% air-5% CO2 and 95%2-5%CO2 on the survival of parathyroid allografts in rats%空气和高氧培养对大鼠甲状旁腺移植物存活期的影响及比较

    Institute of Scientific and Technical Information of China (English)

    温浙盛; 许太武; 陈国锐; 张步振; 黄雪玲; 丁玉兴; 周汉城; 李晓亮; 董发团; 王慧明; 张秀琼

    1997-01-01

    以成年纯系雌性Wistar大鼠作供体,成年纯系雌性SD大鼠作受体,以子宫内膜下为受区,在完全同等的实验条件下,将甲状旁腺(PTG)分别在空气(95%空气和5%CO2)和高氧(95%O2和5%CO2)两种环境下进行培养,以观察不同培养条件对PTG移植物存活期的影响,并就两种培养效果及优缺点进行比较.培养液均为RPMI 1640,移植后都不用免疫抑制剂.结果证实,两种条件下培养14天的PTG在移植术后1~2周,受体大鼠血钙值均恢复正常或接近正常值,移植物平均存活期分别为:空气组164.70±19.09天,高氧组180±12.02天,两组比较,差异无统计学意义(P>0.05).鉴于空气培养较高氧培养简单易行,不易污染,移植后存活率高,因此,空气培养法更易在临床推广.%The effects of cultures in atmosphere of 95% air-5%O2 and 95% O2-5% CO2 on the survival of parathyroid allografts in rats were compared.Female adult rats of Wistar and SD strains were used as donors and recipients.The parathyroid glands after culture for 14 days in medium of RPMI 1640 were implanted under uterus mucosa.No immunosuppressant was used in the procedure.The results showed that serum calcium of all the recipients returned tO normal within 1 to 2 weeks.The mean survival time of allografts cultured in atmosphere of 95% air-5% CO2 was 164.70±19.00 days while that of 95% O2-5%CO2 was 180±12.02 days.No significant difference was fcund between two groups but the technique of former was simple,had less contamination and higher survival rate.

  11. 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

    (multivariate odds ratio [OR]=3.9; 95% confidence interval [CI] 3.1 to 5.0), witnessed arrest (multivariate OR=3.5; 95% CI 2.7 to 4.6), and out-of-hospital cardiac arrest in a public area (multivariate OR=2.1; 95% CI 1.6 to 2.8), whereas no comorbidity (multivariate OR=1.1; 95% CI 0.8 to 1.45), sex...

  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. Influence of dendritic cells modified with costimulatory blocker cytotoxic T lymphocyte associated antigen-4 immunoglobulin on the survival of renal allografts%共刺激阻断剂细胞毒性T淋巴细胞相关抗原4Ig基因修饰树突状细胞对移植肾存活的影响

    Institute of Scientific and Technical Information of China (English)

    黄赤兵; 李健; 张艮甫; 范明齐; 王琦

    2008-01-01

    BACKGROUND: Previous studies showed that donor systemic injection of B7/CD28 costimulatory blocker cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA-4Ig) needed in T cell activation can markedly prolong the survival time of rat renal allografts, which, however, has limitations, such as high dose, extensive influence, poor specificity, systemic adverse reactions.OBJECTIVE: In order to improve the targeting of CTLA-4Ig, we modified the dendritic cells of donors and recipients in vitro with CTLA- 4Ig and observed the influence of two kinds of dendritic cells applied alone or together on the survival of renal allografis in rats.DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed between April 2003 and July 2004 at Laboratory of Department of Urinary Surgery, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.MATERIALS: Kidney donor: inbred Brown-Norway rats, kidney recipient: inbred Lewis rats, unrelated lymphocyte donor: Wistar rats.METHODS: Bone marrow derived dendritic cells of Lewis and Brown Norway rats were modified with CTLA- 4Ig gene recombinant adenovirus in vitro. Animal models of kidney transplantation were built with Brown Norway rats as donors while Lewis rats as recipients. The modified dendritic cells were injected into Lewis rats through femoral vein 24 hours before kidney transplantation alone (group 1 (n=8), donor dendritic cells; group 2 (n=8), recipient dendritic cells) and in combination (group 3 (n=8), donor and recipient dendritic cells). While the recipients without injection were used as control (group 4 (n=6)).MAIN OUTCOME MEASURES: Survival time of renal allografts; the reaction degrees of splenocytes to donor and unrelated antigen determined by MTT method on day 20 postoperation.RESULTS: Survival time of renal allografts in group 2 was not prolonged compared with group 4 while the survival time was markedly prolonged in group 3 (P < 0.01). The response of rat splenocytes

  14. 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.

  15. Expression of the Cardiac Maintenance and Survival Factor FGF-16 Gene Is Regulated by Csx/Nkx2.5 and Is an Early Target of Doxorubicin Cardiotoxicity.

    Science.gov (United States)

    Wang, Jie; Jin, Yan; Cattini, Peter A

    2017-02-01

    The fibroblast growth factor (FGF) 16 gene (Fgf-16) is preferentially expressed by neonatal cardiomyocytes after birth, with levels increasing into adulthood. Null mice and isolated heart studies suggest a role for FGF-16 in cardiac maintenance and survival, including increased resistance to doxorubicin (DOX)-induced injury. However, the effect of DOX on endogenous FGF-16 synthesis and specifically regulation of cardiac Fgf-16 expression has not been reported. Here we assess the effect of DOX on FGF-16 RNA levels and stability as well as promoter activity and use sequence analysis, knockdown, and overexpression to investigate the role of cardiac transcription factor(s) implicated in the response. Endogenous FGF-16 RNA levels were reduced >70% in 8-week-old rats treated with 15 mg DOX/kg for 6 h. This was modeled in neonatal rat cardiomyocyte cultures, where an equivalent decrease was also seen within 6 h of 1 μM DOX treatment. Six kilobases of mouse Fgf-16 upstream flanking and promoter DNA was also assessed for DOX responsiveness in transfected cardiomyocytes. A decrease in FGF-16 promoter activity was seen with only 747 base pairs containing the Fgf-16 TATA box that includes a putative and highly conserved binding site for the cardiac transcription factor Csx/Nkx2.5. There was also no effect of DOX on FGF-16 RNA stability, consistent with transcriptional control. Levels and binding of Csx/Nkx2.5 to the FGF-16 promoter were reduced with DOX treatment. Knockdown of Csx/Nkx2.5 specifically decreased endogenous FGF-16 RNA and protein levels, whereas Csx/Nkx2.5 overexpression stimulated levels, and increased resistance to the rapid DOX-induced depletion of FGF-16. These observations indicate that Fgf-16 expression is directly regulated by Csx/Nkx2.5 in neonatal cardiomyocytes, and a negative effect of DOX on Csx/Nkx2.5 and, thus, endogenous FGF-16 synthesis may contribute indirectly to its cardiotoxic effects. Targeting FGF-16 levels could, however, offer

  16. Mechanism of arterial remodeling in chronic allograft vasculopathy

    Institute of Scientific and Technical Information of China (English)

    Qichang Zheng; Shanglong Liu; Zifang Song

    2011-01-01

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

  17. Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival

    DEFF Research Database (Denmark)

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

    2015-01-01

    after CRT implantation, long-term adherence to this treatment, and its association with patient survival. METHODS AND RESULTS: This observational study included 826 consecutive patients who received a CRT device at a tertiary centre. Data were obtained from patient files and prescription data from...... the Danish National Prescription Registry. Doses are expressed as percentages of target doses. We used Cox proportional hazard model to compute adjusted hazard ratios (aHRs) for survival with 95% confidence intervals (CIs), adjusted for potential confounders. During the median (quartiles) follow-up of 4.4 (3......HR 0.55 (0.38-0.80); P = 0.002). CONCLUSION: After CRT implantation, optimization of HF treatment is possible, and long-term adherence to HF medication remains high. Higher doses of BB and ACEi/ARB were associated with prolonged survival....

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

    Science.gov (United States)

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

    2012-04-17

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

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

    Institute of Scientific and Technical Information of China (English)

    XU Zheng-jian; HE Rong-xin

    2010-01-01

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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  5. 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

  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. 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

  8. Influence of St. Jude medical valve in patients with aortic stenosis and small aortic annulus on cardiac function and late survival result.

    Science.gov (United States)

    Natsuaki, Masafumi; Itoh, Tsuyoshi; Okazaki, Yukio; Takarabe, Kyoumi; Furukawa, Koujirou; Rikitake, Kazuhisa; Ohtubo, Satoshi

    2002-10-01

    This clinical study analyzes our experience of postoperative cardiac function and long-term survival rate in patients with aortic stenosis and small-size St. Jude Medical (SJM) valve. Sixty-eight patients who underwent aortic valve replacement by SJM valve were divided into two groups by preoperative aortic annulus diameter. Group 1 consisted of 44 patients with small aortic annulus and small-size SJM valve (19 mm or 21 mm). In Group 1, small SJM standard valves were implanted in 16 patients, and small SJM Hemodynamic Plus (HP) valves were implanted in 28 patients. Group 2 consisted of 24 patients with large-size SJM standard valve (23 mm or larger). Preoperative left ventricular mass index, left ventricular dimension, the dimension of ascending aorta, and body surface area were significantly smaller in Group 1 than in Group 2. Average age at surgery was older in Group 1 than in Group 2. Effective orifice area index of the SJM valve measured by the manufacturer's data was smaller in Group 1 than in Group 2. Postoperative left ventricular mass indexes of Group 1 (standard valve or HP valve) and Group 2 significantly decreased in comparison with the preoperative mass indexes. Postoperative left ventricular ejection fraction and the peak ejection rate of Group 1 were not different from those of Group 2. The 10 year survival rate of Group 1 was 79%, and the rate of Group 2 was 77%. At 10 years after surgery, freedom from valve-related complication of Group 1 was 80%, and freedom from complication of Group 2 was 81%. Our results demonstrated that small-size SJM valve afforded satisfactory long-term survival rate and valve-related event-free rate for elderly patients with small body surface area and small aortic annulus.

  9. 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

  10. 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.

  11. Acellular nerve allograft promotes selective regeneration

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  12. 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.

  13. Immunosuppression with FTY720 Reverses Cardiac Dysfunction in Hypomorphic ApoE Mice Deficient in SR-BI Expression that Survive

    Science.gov (United States)

    Luk, Fu Sang; Kim, Roy Y.; Li, Kang; Ching, Daniel; Wong, David K.; Joshi, Sunil K.; Imhof, Isabella; Honbo, Norman; Hoover, Holly; Zhu, Bo-Qing; Lovett, David H.; Karliner, Joel S.; Raffai, Robert L.

    2015-01-01

    Aims We recently reported that immunosuppression with FTY720 improves cardiac function and extends longevity in Hypomorphic ApoE mice deficient in scavenger receptor Type-BI expression, also known as the HypoE/SR-BI−/− mouse model of diet-induced coronary atherosclerosis and myocardial infarction (MI). In this study we tested the impact of FTY720 on cardiac dysfunction in HypoE/SR-BI−/− mice that survive MI and subsequently develop chronic heart failure. Methods/Results HypoE/SR-BI−/− mice were bred to Mx1-Cre transgenic mice and offspring were fed a high fat diet (HFD) for 3.5 weeks to provoke hyperlipidemia, coronary atherosclerosis and recurrent MIs. In contrast to our previous study, hyperlipidemia was rapidly reversed by inducible Cre-mediated gene repair of the HypoE allele and switching mice to a normal chow diet. Mice that survived the period of HFD were subsequently given oral FTY720 in drinking water or not, and left ventricular (LV) function was monitored using serial echocardiography for up to 15 weeks. In untreated mice, LV performance progressively deteriorated. Although FTY720 treatment did not initially prevent a decline of heart function among mice six weeks after Cre-mediated gene repair, it almost completely restored normal LV function in these mice by 15 weeks. Reversal of heart failure did not result from reduced atherosclerosis as the burden of aortic and coronary atherosclerosis actually increased to similar levels in both groups of mice. Rather, FTY720 caused systemic immunosuppression as assessed by reduced numbers of circulating T and B lymphocytes. In contrast, FTY720 did not enhance the loss of T cells or macrophages that accumulated in the heart during the HFD feeding period, but it did enhance the loss of B cells soon after plasma lipid lowering. Moreover, FTY720 potently reduced the expression of matrix metalloproteinase-2 and genes involved in innate immunity-associated inflammation in the heart. Conclusions Our data

  14. 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).

  15. 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

  16. 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.

  17. 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

  18. 一种新的免疫抑制剂FTY720对小鼠心脏移植的救治作用%FTY720, a new immunosuppressant,as rescue therapy in mouse cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    王铭辉; Vitaliy MILEKHIN; 张华; 黄洪铮

    2003-01-01

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

  19. 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

  20. 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.

  1. Radiation sterilization of skin allograft

    Science.gov (United States)

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

    2009-07-01

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

  2. 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.

  3. 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.

  4. 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)

  5. 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.

  6. 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.

  7. Interleukin-12 (IL-12p70 promotes induction of highly potent Th1-like CD4+CD25+T regulatory cells that inhibit allograft rejection in unmodified recipients.

    Directory of Open Access Journals (Sweden)

    Nirupama Darshan Verma

    2014-05-01

    Full Text Available In rat models, CD4+CD25+T regulatory cells (Treg play a key role in the induction and maintenance of antigen specific transplant tolerance, especially in DA rats with PVG cardiac allografts(1, 2. We have previously described generation of alloantigen specific Treg (Ts1, by culture of naïve natural CD4+CD25+ Treg (nTreg with specific alloantigen and IL-2 for 4 days. These cells express mRNA for IFN-γ receptor (ifngr and suppress donor but not third party cardiac allograft rejection mediated by alloreactive CD4+T cells at ratios of We induced highly suppressive Th1-like Treg from naïve nTreg in 7 days by culture with alloantigen, first with rIL-2 then with rIL-12p70. These Th1-like Treg delayed specific-donor allograft rejection demonstrating therapeutic potential

  8. Impaired elastin deposition in Fstl1-/- lung allograft under the renal capsule.

    Directory of Open Access Journals (Sweden)

    Yan Geng

    Full Text Available Lung alveolar development in late gestation is a process important to postnatal survival. Follistatin-like 1 (Fstl1 is a matricellular protein of the Bmp antagonist class, which is involved in the differentiation/maturation of alveolar epithelial cells during saccular stage of lung development. This study investigates the role of Fstl1 on elastin deposition in mesenchyme and subsequent secondary septation in the late gestation stage of terminal saccular formation. To this aim, we modified the renal capsule allograft model for lung organ culture by grafting diced E15.5 distal lung underneath the renal capsule of syngeneic host and cultured up to 7 days. The saccular development of the diced lung allografts, as indicated by the morphology, epithelial and vascular developments, occurred in a manner similar to that in utero. Fstl1 deficiency caused atelectatic phenotype companied by impaired epithelial differentiation in D3 Fstl1(-/- lung allografts, which is similar to that of E18.5 Fstl1(-/- lungs, supporting the role of Fstl1 during saccular stage. Inhibition of Bmp signaling by intraperitoneal injection of dorsomorphin in the host mice rescued the pulmonary atelectasis of D3 Fstl1(-/- allografts. Furthermore, a marked reduction in elastin expression and deposition was observed in walls of air sacs of E18.5 Fstl1(-/- lungs and at the tips of the developing alveolar septae of D7 Fstl1(-/- allografts. Thus, in addition to its role on alveolar epithelium, Fstl1 is crucial for elastin expression and deposition in mesenchyme during lung alveologenesis. Our data demonstrates that the modified renal capsule allograft model for lung organ culture is a robust and efficient technique to increase our understanding of saccular stage of lung development.

  9. Bortezomib for refractory antibody-mediated cardiac allograft rejection.

    Science.gov (United States)

    Eckman, Peter M; Thorsgard, Marit; Maurer, David; Kim, Youngki; Alloway, Rita R; Woodle, E Steve

    2009-01-01

    This experience demonstrates that a bortezomib-based regimen provided effective therapy for late, refractory AMR in an adult heart transplant recipient and was well tolerated. This remarkably positive experience despite the refractory nature of the AMR episode argues strongly for continued evaluation of bortezomib use in this patient population.

  10.  Liver transplantation in the critically ill: donation after cardiac death compared to donation after brain death grafts.

    Science.gov (United States)

    Taner, C Burcin; Bulatao, Ilynn G; Arasi, Lisa C; Perry, Dana K; Willingham, Darrin L; Sibulesky, Lena; Rosser, Barry G; Canabal, Juan M; Nguyen, Justin H; Kramer, David J

    2012-01-01

     Patients with end stage liver disease may become critically ill prior to LT requiring admission to the intensive care unit (ICU). The high acuity patients may be thought too ill to transplant; however, often LT is the only therapeutic option. Choosing the correct liver allograft for these patients is often difficult and it is imperative that the allograft work immediately. Donation after cardiac death (DCD) donors provide an important source of livers, however, DCD graft allocation remains a controversial topic, in critically ill patients. Between January 2003-December 2008, 1215 LTs were performed: 85 patients at the time of LT were in the ICU. Twelve patients received DCD grafts and 73 received donation after brain dead (DBD) grafts. After retransplant cases and multiorgan transplants were excluded, 8 recipients of DCD grafts and 42 recipients of DBD grafts were included in this study. Post-transplant outcomes of DCD and DBD liver grafts were compared. While there were differences in graft and survival between DCD and DBD groups at 4 month and 1 year time points, the differences did not reach statistical significance. The graft and patient survival rates were similar among the groups at 3-year time point. There is need for other large liver transplant programs to report their outcomes using liver grafts from DCD and DBD donors. We believe that the experience of the surgical, medical and critical care team is important for successfully using DCD grafts for critically ill patients.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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

  13. Mesenchymal stem cells with overexpression of midkine enhance cell survival and attenuate cardiac dysfunction in a rat model of myocardial infarction

    NARCIS (Netherlands)

    S.-L. Zhao (Shu-Li); Y. Zhang (Yaojun); M.-H. Li (Ming-Hui); X.-L. Zhang (Xin-Lei); S.-L. Chen (Shao-Liang)

    2014-01-01

    textabstractIntroduction. Elevated midkine (MK) expression may contribute to ventricular remodeling and ameliorate cardiac dysfunction after myocardial infarction (MI). Ex vivo modification of signaling mechanisms in mesenchymal stem cells (MSCs) with MK overexpression may improve the efficacy of ce

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  15. 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

  16. 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.

  17. 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...... incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. RESULTS: We observed a significant inverse association of urinary calprotectin...... regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. CONCLUSIONS: Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation....

  18. 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.

  19. 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.

  20. 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

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

    Science.gov (United States)

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

    2004-07-01

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

  2. 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.

  3. Renal Structural Changes after Kidney Allograft Transplantation

    NARCIS (Netherlands)

    Bakker, R.C.

    2005-01-01

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

  4. Ultrastructural basis of acute renal allograft rejection

    NARCIS (Netherlands)

    V.D. Vuzevski (Vojislav)

    1976-01-01

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

  5. 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.

  6. 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.

  7. 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.

  8. Probiotic-fermented purple sweet potato yogurt activates compensatory IGF‑IR/PI3K/Akt survival pathways and attenuates cardiac apoptosis in the hearts of spontaneously hypertensive rats.

    Science.gov (United States)

    Lin, Pei-Pei; Hsieh, You-Miin; Kuo, Wei-Wen; Lin, Yueh-Min; Yeh, Yu-Lan; Lin, Chien-Chung; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang; Tsai, Cheng-Chih

    2013-12-01

    Apoptosis is recognized as a predictor of adverse outcomes in subjects with cardiac diseases. The aim of this study was to explore the effects of probiotic-fermented purple sweet potato yogurt (PSPY) with high γ-aminobutyric acid (GABA) content on cardiac apoptosis in spontaneously hypertensive rat (SHR) hearts. The rats were orally adminsitered with 2 different concentrations of PSPY (10 and 100%) or captopril, 15.6 mg/kg, body weight (BW)/day. The control group was administered distilled water. DAPI and TUNEL staining were used to detect the numbers of apoptotic cells. A decrease in the number of TUNEL-positive cardiac myocytes was observed in the SHR-PSPY (10 and 100%) groups. In addition, the levels of key components of the Fas receptor- and mitochondrial-dependent apoptotic pathways were determined by western blot analysis. The results revealed that the levels of the key components of the Fas receptor- and mitochondrial-dependent apoptotic pathway were significantly decreased in the SHR-captopril, and 10 and 100% PSPY groups. Additionally, the levels of phosphorylated insulin-like growth factor‑I receptor (p-IGF‑IR) were increased in SHR hearts from the SHR-control group; however, no recovery in the levels of downstream signaling components was observed. In addition, the levels of components of the compensatory IGF-IR-dependent survival pathway (p-PI3K and p-Akt) were all highly enhanced in the left ventricles in the hearts form the SHR-10 and 100% PSPY groups. Therefore, the oral administration of PSPY may attenuate cardiomyocyte apoptosis in SHR hearts by activating IGF‑IR-dependent survival signaling pathways.

  9. Improved neurologically intact survival with the use of an automated, load-distributing band chest compression device for cardiac arrest presenting to the emergency department

    OpenAIRE

    2012-01-01

    Introduction It has been unclear if mechanical cardiopulmonary resuscitation (CPR) is a viable alternative to manual CPR. We aimed to compare resuscitation outcomes before and after switching from manual CPR to load-distributing band (LDB) CPR in a multi-center emergency department (ED) trial. Methods We conducted a phased, prospective cohort evaluation with intention-to-treat analysis of adults with non-traumatic cardiac arrest. At these two urban EDs, systems were changed from manual CPR to...

  10. 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.

  11. Laminins affect T cell trafficking and allograft fate.

    Science.gov (United States)

    Warren, Kristi J; Iwami, Daiki; Harris, Donald G; Bromberg, Jonathan S; Burrell, Bryna E

    2014-05-01

    Lymph nodes (LNs) are integral sites for the generation of immune tolerance, migration of CD4⁺ T cells, and induction of Tregs. Despite the importance of LNs in regulation of inflammatory responses, the LN-specific factors that regulate T cell migration and the precise LN structural domains in which differentiation occurs remain undefined. Using intravital and fluorescent microscopy, we found that alloreactive T cells traffic distinctly into the tolerant LN and colocalize in exclusive regions with alloantigen-presenting cells, a process required for Treg induction. Extracellular matrix proteins, including those of the laminin family, formed regions within the LN that were permissive for colocalization of alloantigen-presenting cells, alloreactive T cells, and Tregs. We identified unique expression patterns of laminin proteins in high endothelial venule basement membranes and the cortical ridge that correlated with alloantigen-specific immunity or immune tolerance. The ratio of laminin α4 to laminin α5 was greater in domains within tolerant LNs, compared with immune LNs, and blocking laminin α4 function or inducing laminin α5 overexpression disrupted T cell and DC localization and transmigration through tolerant LNs. Furthermore, reducing α4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation.

  12. 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.

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

    Science.gov (United States)

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

    2009-03-01

    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.

  14. 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

  15. 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.).

  16. Urinary calprotectin and posttransplant renal allograft injury.

    Directory of Open Access Journals (Sweden)

    Martin Tepel

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

  17. [Tubulointerstitial rejection of renal allografts].

    Science.gov (United States)

    Malušková, Jana; Honsová, Eva

    2015-01-01

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

  18. Extensor mechanism allograft in total knee arthroplasty

    Science.gov (United States)

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

    2013-01-01

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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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. 

  7. 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: ...

  8. 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

  9. 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...

  10. 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

  11. 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

  12. Interleukin-6, A Cytokine Critical to Mediation of Inflammation, Autoimmunity and Allograft Rejection: Therapeutic Implications of IL-6 Receptor Blockade.

    Science.gov (United States)

    Jordan, Stanley C; Choi, Jua; Kim, Irene; Wu, Gordon; Toyoda, Mieko; Shin, Bonga; Vo, Ashley

    2017-01-01

    The success of kidney transplants is limited by the lack of robust improvements in long-term survival. It is now recognized that alloimmune responses are responsible for the majority of allograft failures. Development of novel therapies to decrease allosensitization is critical. The lack of new drug development in kidney transplantation necessitated repurposing drugs initially developed in oncology and autoimmunity. Among these is tocilizumab (anti-IL-6 receptor [IL-6R]) which holds promise for modulating multiple immune pathways responsible for allograft injury and loss. Interleukin-6 is a cytokine critical to proinflammatory and immune regulatory cascades. Emerging data have identified important roles for IL-6 in innate immune responses and adaptive immunity. Excessive IL-6 production is associated with activation of T-helper 17 cell and inhibition of regulatory T cell with attendant inflammation. Plasmablast production of IL-6 is critical for initiation of T follicular helper cells and production of high-affinity IgG. Tocilizumab is the first-in-class drug developed to treat diseases mediated by IL-6. Data are emerging from animal and human studies indicating a critical role for IL-6 in mediation of cell-mediated rejection, antibody-mediated rejection, and chronic allograft vasculopathy. This suggests that anti-IL-6/IL-6R blockade could be effective in modifying T- and B-cell responses to allografts. Initial data from our group suggest anti-IL-6R therapy is of value in desensitization and prevention and treatment of antibody-mediated rejection. In addition, human trials have shown benefits in treatment of graft versus host disease in matched or mismatched stem cell transplants. Here, we explore the biology of IL-6/IL-6R interactions and the evidence for an important role of IL-6 in mediating allograft rejection.

  13. [Long-term survival of a breast cancer patient with carcinomatous pleuritis and carcinomatous cardiac tamponade successfully treated by multimodality therapy].

    Science.gov (United States)

    Tanaka, Yosuke; Tsuboi, Kaori; Yamamoto, Akira; Tsuda, Shoichi; Tsujii, Shigehiro; Yagi, Ken; Kitamura, Tatsuhiko

    2015-04-01

    A 69-year old woman was admitted to our hospital because of dyspnea and pain in her left breast. Computed tomography revealed a massive quantity of left pleural effusion, a tumor in the left breast(5 cm in diameter), left cervical and supraclavicular lymph node metastasis, and a large left axillary metastatic mass. Based on a core needle biopsy, her breast tumor was diagnosed pathologically as scirrhous carcinoma, which was positive for estrogen receptor/progesterone receptor and negative for HER2 using the FISH assay, and left pleural metastasis was diagnosed cytologically. The carcinomatous pleural effusion was successfully controlled using pleural instillations of pirarubicin HCl and OK-432 after pleural drainage. A near clinical complete response was achieved by EC systemic chemotherapy(6 months)followed by endocrine therapy(letrozole), but 3 months later she was diagnosed cytologically with carcinomatous cardiac tamponade. After operative pericardial drainage, intrapericardial instillations of cisplatin and OK-432 successfully prevented re-accumulation of pericardial effusion. Systemic chemotherapy(weekly paclitaxel)for 11 months and endocrine therapy(letrozole)resulted in a clinical complete response. One year and 10 months after pericardial drainage, she underwent surgery(mastectomy and axillary lymph node dissection level II)because of two small tumors in the left breast which were found to be malignant using PET-CT. One tumor(diameter 1.6 cm)was found pathologically to consist of degenerated cancer cells, and another tumor(diameter 2 cm)was diagnosed as recurrent cancer. There was no lymph node metastasis in the axilla except for a single mass(1.4×0.7×0.3 cm), which was composed of extremely degenerative and necrotic non-lymphoid cancerous tissue. Since having the surgery, she has not experienced recurrence on hormone therapy with fulvestrant, and to date she is still alive, 3 years and 5 months since the left pleural metastasis episode.

  14. A score model for the continuous grading of early allograft dysfunction severity.

    Science.gov (United States)

    Pareja, Eugenia; Cortes, Miriam; Hervás, David; Mir, José; Valdivieso, Andrés; Castell, José V; Lahoz, Agustín

    2015-01-01

    Early allograft dysfunction (EAD) dramatically influences graft and patient outcomes. A lack of consensus on an EAD definition hinders comparisons of liver transplant outcomes and management of recipients among and within centers. We sought to develop a model for the quantitative assessment of early allograft function [Model for Early Allograft Function Scoring (MEAF)] after transplantation. A retrospective study including 1026 consecutive liver transplants was performed for MEAF score development. Multivariate data analysis was used to select a small number of postoperative variables that adequately describe EAD. Then, the distribution of these variables was mathematically modeled to assign a score for each actual variable value. A model, based on easily obtainable clinical parameters (ie, alanine aminotransferase, international normalized ratio, and bilirubin) and scoring liver function from 0 to 10, was built. The MEAF score showed a significant association with patient and graft survival at 3-, 6- and 12-month follow-ups. Hepatic steatosis and age for donors; cold/warm ischemia times and postreperfusion syndrome for surgery; and intensive care unit and hospital stays, Model for End-Stage Liver Disease and Child-Pugh scores, body mass index, and fresh frozen plasma transfusions for recipients were factors associated significantly with EAD. The model was satisfactorily validated by its application to an independent set of 200 patients who underwent liver transplantation at a different center. In conclusion, a model for the quantitative assessment of EAD severity has been developed and validated for the first time. The MEAF provides a more accurate graft function assessment than current categorical classifications and may help clinicians to make early enough decisions on retransplantation benefits. Furthermore, the MEAF score is a predictor of recipient and graft survival. The standardization of the criteria used to define EAD may allow reliable comparisons of

  15. 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

  16. 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.

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

    Science.gov (United States)

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

    2001-02-01

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

  18. Cardiac Sarcoidosis.

    Science.gov (United States)

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  19. 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.

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

    Science.gov (United States)

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

    2014-05-01

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

  1. 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

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

    OpenAIRE

    Madhan Krishan; Temple-Camp Cynric

    2009-01-01

    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...

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 

  5. Cortical and medullary vascularity in renal allograft biopsies

    OpenAIRE

    2012-01-01

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

  6. De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

    Directory of Open Access Journals (Sweden)

    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.

  7. Proximal femur reconstruction by an allograft prosthesis composite.

    Science.gov (United States)

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

    2002-01-01

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

  8. Molecular Aspects of Exercise-induced Cardiac Remodeling.

    Science.gov (United States)

    Bernardo, Bianca C; McMullen, Julie R

    2016-11-01

    Exercise-induced cardiac remodeling is typically an adaptive response associated with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers of cardiac remodeling include increased hemodynamic load, increased sympathetic activity, and the release of hormones and growth factors. Prolonged and strenuous exercise may lead to maladaptive exercise-induced cardiac remodeling including cardiac dysfunction and arrhythmia. In addition, this article describes novel therapeutic approaches for the treatment of heart failure that target mechanisms responsible for adaptive exercise-induced cardiac remodeling, which are being developed and tested in preclinical models.

  9. 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.

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

    Science.gov (United States)

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

    2008-01-01

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

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

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    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

  12. Outcome of pregnancy in renal allograft recipients: SIUT experience.

    Science.gov (United States)

    Naqvi, R; Noor, H; Ambareen, S; Khan, H; Haider, A; Jafri, N; Alam, A; Aziz, R; Manzoor, K; Aziz, T; Ahmed, E; Akhtar, F; Naqvi, A; Rizvi, A

    2006-09-01

    The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

    Science.gov (United States)

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

    2012-09-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

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    Doh Kyoung Chan

    2014-06-01

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

  3. 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.

  4. 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.

    2016-01-01

    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. PMID:27352120

  5. 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.

  6. Cardiac cameras.

    Science.gov (United States)

    Travin, Mark I

    2011-05-01

    Cardiac imaging with radiotracers plays an important role in patient evaluation, and the development of suitable imaging instruments has been crucial. While initially performed with the rectilinear scanner that slowly transmitted, in a row-by-row fashion, cardiac count distributions onto various printing media, the Anger scintillation camera allowed electronic determination of tracer energies and of the distribution of radioactive counts in 2D space. Increased sophistication of cardiac cameras and development of powerful computers to analyze, display, and quantify data has been essential to making radionuclide cardiac imaging a key component of the cardiac work-up. Newer processing algorithms and solid state cameras, fundamentally different from the Anger camera, show promise to provide higher counting efficiency and resolution, leading to better image quality, more patient comfort and potentially lower radiation exposure. While the focus has been on myocardial perfusion imaging with single-photon emission computed tomography, increased use of positron emission tomography is broadening the field to include molecular imaging of the myocardium and of the coronary vasculature. Further advances may require integrating cardiac nuclear cameras with other imaging devices, ie, hybrid imaging cameras. The goal is to image the heart and its physiological processes as accurately as possible, to prevent and cure disease processes.

  7. Synergistic effect of mycophenolate mofetil and angiotensin-converting enzyme inhibitor in patients with chronic allograft nephropathy

    Directory of Open Access Journals (Sweden)

    G.T. Moscoso-Solorzano

    2009-05-01

    Full Text Available Experimental data and few clinical non-randomized studies have shown that inhibition of the renin-angiotensin system by angiotensin-converting enzyme (ACE associated or not with the use of mycophenolate mofetil (MMF could delay or even halt the progression of chronic allograft nephropathy (CAN. In this retrospective historical study, we investigated whether ACE inhibition (ACEI associated or not with the use of MMF has the same effect in humans as in experimental studies and what factors are associated with a clinical response. A total of 160 transplant patients with biopsy-proven CAN were enrolled. Eighty-one of them were on ACE therapy (G1 and 80 on ACEI_free therapy (G2. Patients were further stratified for the use of MMF. G1 patients showed a marked decrease in proteinuria and stabilized serum creatinine with time. Five-year graft survival after CAN diagnosis was more frequent in G1 (86.9 vs 67.7%; P < 0.05. In patients on ACEI-free therapy, the use of MMF was associated with better graft survival. The use of ACEI therapy protected 79% of the patients against graft loss (OR = 0.079, 95%CI = 0.015-0.426; P = 0.003. ACEI and MMF or the use of MMF alone after CAN diagnosis conferred protection against graft loss. This finding is well correlated with experimental studies in which ACEI and MMF interrupt the progression of chronic allograft dysfunction and injury. The use of ACEI alone or in combination with MMF significantly reduced proteinuria and stabilized serum creatinine, consequently improving renal allograft survival.

  8. Cardiac arrhythmias in pregnancy.

    Science.gov (United States)

    Knotts, Robert J; Garan, Hasan

    2014-08-01

    As more women with repaired congenital heart disease survive to their reproductive years and many other women are delaying pregnancy until later in life, a rising concern is the risk of cardiac arrhythmias during pregnancy. Naturally occurring cardiovascular changes during pregnancy increase the likelihood that a recurrence of a previously experienced cardiac arrhythmia or a de novo arrhythmia will occur. Arrhythmias should be thoroughly investigated to determine if there is a reversible etiology, and risks/benefits of treatment options should be fully explored. We discuss the approach to working up and treating various arrhythmias during pregnancy with attention to fetal and maternal risks as well as treatment of fetal arrhythmias. Acute management in stable patients includes close monitoring and intravenous pharmacologic therapy, while DC cardioversion should be used to terminate arrhythmias in hemodynamically unstable patients. Long-term management may require continued oral antiarrhythmic therapy, with particular attention to fetal safety, to prevent complications associated with arrhythmias.

  9. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2004-03-01

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

  12. 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.

  13. 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...

  14. Cardiac arrest: comparison of paramedic and conventional ambulance services.

    OpenAIRE

    1983-01-01

    A prospective study conducted in the Greater Vancouver area compared survival rates in prehospital cardiac arrest managed by an advanced life support (paramedic) service with those in cardiac arrest managed by conventional ambulance service. Management by the paramedic service was associated with higher survival rates for patients found in cardiac arrest but not for patients who suffered the arrest while the ambulance was present. Cardiopulmonary resuscitation by bystanders was associated wit...

  15. Postoperative cardiac arrest in children with congenital heart abnormalities

    OpenAIRE

    2013-01-01

    BACKGROUND The exact survival rates and markers of survival after postoperative cardiac arrest in children with congenital heart abnormalities are unknown. METHODS In this one-year study, we identified children younger than seven years of age with postoperative cardiac arrest in our pediatric cardiac intensive care unit database. Parameters from perioperative, pre-arrest, and resuscitation periods were analyzed for these patients. Comparisons were made between survivors and non-survivors afte...

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

    Directory of Open Access Journals (Sweden)

    P. P. Yablonsky

    2015-01-01

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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Porous allograft bone scaffolds: doping with strontium.

    Directory of Open Access Journals (Sweden)

    Yantao Zhao

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

  2. 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.

  3. An Update on Cardiac Transplantation in the United States.

    Science.gov (United States)

    Everly, Matthew J

    2014-01-01

    Heart transplantation in the United States remains an important option for those with heart failure. Survival rates over the last 25 years have improved with the advent of newer immunosuppressive agents, innovation, and a better understanding of managing risk. However, many patients continue to experience allograft failure after transplantation. Innovations in modalities to reduce acute and chronic rejection are needed to improve the long-term success of heart transplantation.

  4. 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

  5. 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.

  6. 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...

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

    Science.gov (United States)

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

    2009-01-05

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

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

    Science.gov (United States)

    Hirn, M; Laitinen, M; Vuento, R

    2003-01-01

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

  9. Efficacy of isoniazid prophylaxis in renal allograft recipients.

    Science.gov (United States)

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

    2006-09-01

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

  10. 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

  11. 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.

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

    Science.gov (United States)

    Kapoor, Rajan; 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.

  13. 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.

  14. 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.

  15. Cardiac Rehabilitation

    Science.gov (United States)

    ... your risk of future heart problems, and to improve your health and quality of life. Cardiac rehabilitation programs increase ... exercise routine at home or at a local gym. You may also continue to ... health concerns. Education about nutrition, lifestyle and weight loss ...

  16. Cardiac surgery 2015 reviewed.

    Science.gov (United States)

    Doenst, Torsten; Strüning, Constanze; Moschovas, Alexandros; Gonzalez-Lopez, David; Essa, Yasin; Kirov, Hristo; Diab, Mahmoud; Faerber, Gloria

    2016-10-01

    For the year 2015, almost 19,000 published references can be found in PubMed when entering the search term "cardiac surgery". The last year has been again characterized by lively discussions in the fields where classic cardiac surgery and modern interventional techniques overlap. Lacking evidence in the field of coronary revascularization with either percutaneous coronary intervention or bypass surgery has been added. As in the years before, CABG remains the gold standard for the revascularization of complex stable triple-vessel disease. Plenty of new information has been presented comparing the conventional to transcatheter aortic valve implantation (TAVI) demonstrating similar short- and mid-term outcomes at high and low risk, but even a survival advantage with transfemoral TAVI at intermediate risk. In addition, there were many relevant and interesting other contributions from the purely operative arena. This review article will summarize the most pertinent publications in the fields of coronary revascularization, surgical treatment of valve disease, heart failure (i.e., transplantation and ventricular assist devices), and aortic surgery. While the article does not have the expectation of being complete and cannot be free of individual interpretation, it provides a condensed summary that is intended to give the reader "solid ground" for up-to-date decision-making in cardiac surgery.

  17. [Cardiopulmonary resuscitation in cardiac arrest following trauma].

    Science.gov (United States)

    Leidel, B A; Kanz, K-G

    2016-11-01

    For decades, survival rates of cardiac arrest following trauma were reported between 0 and 2 %. Since 2005, survival rates have increased with a wide range up to 39 % and good neurological recovery in every second person injured for unknown reasons. Especially in children, high survival rates with good neurologic outcomes are published. Resuscitation following traumatic cardiac arrest differs significantly from nontraumatic causes. Paramount is treatment of reversible causes, which include massive bleeding, hypoxia, tension pneumothorax, and pericardial tamponade. Treatment of reversible causes should be simultaneous. Chest compression is inferior following traumatic cardiac arrest and should never delay treatment of reversible causes of the traumatic cardiac arrest. In massive bleeding, bleeding control has priority. Damage control resuscitation with permissive hypotension, aggressive coagulation therapy, and damage control surgery represent the pillars of initial treatment. Cardiac arrest due to hypoxia should be resolved by airway management and ventilation. Tension pneumothorax should be decompressed by finger thoracostomy, pericardial tamponade by resuscitative thoracotomy. In addition, resuscitative thoracotomy allows direct and indirect bleeding control. Untreated impact brain apnea may rapidly lead to cardiac arrest and requires quick opening of the airway and effective oxygenation. Established algorithms for treatment of cardiac arrest following trauma enable a safe, structured, and effective management.

  18. Metabolomic Profiling in Individuals with a Failing Kidney Allograft

    Science.gov (United States)

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

    2017-01-01

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

  19. 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

  20. 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

  1. Early experience with lung transplantation using donors after cardiac death.

    Science.gov (United States)

    Mason, David P; Murthy, Sudish C; Gonzalez-Stawinski, Gonzalo V; Budev, Marie M; Mehta, Atul C; McNeill, Ann M; Pettersson, Gösta B

    2008-05-01

    Lung transplantations that utilize donor organs after cardiac death (DCD) can substantially increase the number of available allografts for waiting recipients. Unfortunately, reported clinical outcomes are limited and widespread acceptance is slow. To further examine the potential of this modality, the results of 4 patients transplanted with DCD organs, implementing a protocol of controlled organ retrieval (Maastricht Classification III), were reviewed. There were no operative deaths; extracorporeal membrane oxygenation was required in 1 patient secondary to severe primary graft dysfunction. Three patients are alive and well at 4, 15 and 21 months; 1 patient died at 34 months with bronchiolitis obliterans syndrome, in part attributable to medication non-compliance.

  2. 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.

  3. B cells and plasma cells in coronaries of chronically rejected cardiac transplants.

    Science.gov (United States)

    Wehner, Jennifer R; Fox-Talbot, Karen; Halushka, Marc K; Ellis, Carla; Zachary, Andrea A; Baldwin, William M

    2010-05-15

    BACKGROUND.: Previously, we reported that transcripts of immunoglobulins were increased in coronary arteries dissected from cardiac transplants with arteriopathy, but the prevelance and patterns of B cell and plasma cell infiltration in cardiac allografts has not been documented. METHODS.: In this study, we documented the frequency and distribution of B cells and plasma cells in 16 cardiac transplants with advanced chronic rejection that were explanted during a second transplant procedure. Coronary arteries with pathologically confirmed allograft vasculopathy and controls with native atherosclerosis were immunohistologically stained for markers of T cells, B cells, plasma cells, IgG subclasses, C4d, CD21, and CXCL13. RESULTS.: We found that B cells and plasma cells were prevalent in most of the samples analyzed (14 of 16) and were distributed in three patterns: adventitial nodules, diffuse adventitial infiltrates, and neointimal infiltrates. These cells were found most frequently in nodules, some of which had distinct compartmentalization and granular C4d deposits on follicular dendritic cells (FDCs) that typify tertiary lymphoid nodules. FDCs also stained for CD21 and CXCL13. Diffuse infiltrates of B cells and plasma cells were found in fibrotic areas of the neointima and adventitia. Only a minority of control coronaries with atherosclerosis contained B cells. CONCLUSIONS.: B cells and plasma cell infiltrates are consistent findings in and around coronary arteries with allograft vasculopathy and are significantly more frequent than in coronaries with native atherosclerosis. The presence of C4d on FDCs in tertiary lymphoid nodules suggests active antigen presentation.

  4. Clinical Significance of HLA-DQ Antibodies in the Development of Chronic Antibody-Mediated Rejection and Allograft Failure in Kidney Transplant Recipients.

    Science.gov (United States)

    Lee, Hyeyoung; Min, Ji Won; Kim, Ji-Il; Moon, In-Sung; Park, Ki-Hyun; Yang, Chul Woo; Chung, Byung Ha; Oh, Eun-Jee

    2016-03-01

    With the development of the single antigen beads assay, the role of donor specific alloantibody (DSA) against human leukocyte antigens in kidney transplantation (KT) has been highlighted. This study aimed to investigate the clinical significance of DQ-DSA detected at renal allograft biopsy. We evaluated 263 KT recipients who underwent allograft biopsy and DSA detection at the same time. Among them, 155 patients who were nonsensitized before transplantation were selected to investigate the role of de-novo DQ-DSA. Both the total and nonsensitized subgroup was categorized into 4 groups each according to DSA results as: DQ only, DQ + non-DQ, non-DQ, and no DSA. In the total patient group, post-KT DSA was positive in 79 (30.0%) patients and DQ-DSA was most prevalent (64.6%). In the nonsensitized subgroup, de-novo DSAs were detected in 45 (29.0%) patients and DQ-DSA was also most prevalent (73.3%). The DQ only group showed a significantly longer post-KT duration compared to the other groups (P chronic AMR, only DQ-DSA showed significance in both the total and the nonsensitized subgroup (P chronic tissue injury were more frequently detected in the groups with DQ-DSA. The worst postbiopsy survival was seen in the DQ + non-DQ group of the total patient group, and patients with de-novo DQ-DSA showed poorer graft survival in the nonsensitized subgroup compared to the no DSA group (P failure (P chronic AMR. These findings suggest that the detection of DQ-DSA in nonsensitized patients is significantly associated with the development of chronic AMR and late allograft failure. Therefore monitoring of DQ-DSA not only in sensitized patients, but also nonsensitized patients may be necessary to improve long-term allograft outcomes.

  5. Treatment strategies to minimize or prevent chronic allograft dysfunction in pediatric renal transplant recipients: an overview.

    Science.gov (United States)

    Höcker, Britta; Tönshoff, Burkhard

    2009-01-01

    Long-term allograft survival poses a major problem in pediatric renal transplantation, with allograft nephropathy being the principal cause of graft failure after the first post-transplant year. The mechanisms of nephron loss resulting in graft dysfunction are multiple, comprising both immunologic factors such as acute and chronic antibody- or T-cell-mediated rejection and non-immunologic components. The latter include peri-transplant injuries and renovascular lesions (renal artery stenosis, thrombosis) as well as cardiovascular risk factors such as arterial hypertension and hyperlipidemia. Another relevant issue leading to progressive nephron loss and declining kidney transplant function is acute and chronic nephrotoxicity induced by the calcineurin inhibitors (CNIs) ciclosporin (cyclosporine microemulsion) and tacrolimus. Furthermore, the presence of an abnormal lower urinary tract as well as bacterial (recurrent pyelonephritis) and viral (cytomegalovirus [CMV], polyomavirus [BK virus; BKV]) infections are crucial factors involved in the incidence of chronic allograft dysfunction and graft failure. Renovascular lesions and lower urinary tract obstruction are typical indicators for surgical intervention. The aim of treatment in pediatric patients with renal failure secondary to a dysfunctional lower urinary tract is to create a sterile, continent, and nonrefluxive reservoir. Surgical techniques such as bladder augmentation and the introduction of intermittent catheterization and anticholinergic therapy have significantly improved graft outcome. Arterial hypertension, another factor responsible for graft function deterioration in pediatric renal transplant recipients, is controlled preferably by the use of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists, which are known to possess nephroprotective properties in addition to their potent antihypertensive effects. Although treatment of subclinical rejection with augmented

  6. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian

    2011-05-01

    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  7. Influence of mycophenolate mofetil (MMF) upon the maturation and allo-stimulatory activity of cultured progenitors of dendritic cells and the effects on the tolerance induction in allograft recipients

    Institute of Scientific and Technical Information of China (English)

    CONGHUIHAN; YUXINWANG; QINGLIANG; MINGZHANG; YINGWANG; MINGYIN; ZHILIANMING; KELIZHENG

    2005-01-01

    To investigate the influence of mycophenolate mofetil (MMF) upon the maturation and the allo-stimulatory activity of cultured progenitors of dendritic cells (DCp), and to evaluate the effects of the pre-treated dentritic cells of recipients with MMF on the tolerance induction as well as its possible mechanism, GM-CSF and MMF were added to the in vitro cultured progenitor cells, and the immuno-phenotypical analysis was performed by means of flow cytometry. The secretion of IL-12 was detected by ELISA and the stimulatory activities of DCp on allogeneic T cells were observed by mixed lymphocyte reaction.Twenty-four C57BL/6 mice were divided into 3 groups (each with 8 mice), in which group A of mice accepted allografts of heart from BALB/c mice, group B of mice had received untreated DCp from donors of BALB/c mice 7 days before transplantation, and C57BL/6 mice in group C were treated by injection with MMF-treated allografts of heart from BALB/c mice 7 days before transplantation. The survival times of allografts and the changes of the cytokine levels in sere of the recipient mice were observed after transplantation. The experimental results showed that MMF could significantly inhibit the expressions of the costimulatory molecules CD80 and CD86 on DCs and the secretion of IL-12 and the allo-stimulatory activities of DCs were also markedly inhibited. The survival times of allografts in group B of mice were longer than those in group A, while the group C showed the longest survival times of allografts, with a marked reduction in the production of the Thl type cytokines. It is evident that MMF has a suppressive effect on the maturation and allo-stimulatory activities of the cultured dendritic cell progenitors, thus leading to a donor specific tolerance in heart-transplanted recipients.

  8. A severe penetrating cardiac injury in the absence of cardiac tamponade.

    Science.gov (United States)

    Connelly, Tara M; Kolcow, Walenty; Veerasingam, Dave; DaCosta, Mark

    2016-10-26

    Penetrating cardiac injury is rare and frequently not survivable. Significant haemorrhage resulting in cardiac tamponade commonly ensues. Such cardiac tamponade is a clear clinical, radiological and sonographic indicator of significant underlying injury. In the absence of cardiac tamponade, diagnosis can be more challenging. In this case of a 26-year old sailor stabbed at sea, a significant pericardial effusion and cardiac tamponade did not occur despite an injury transversing the pericardium. Instead, the pericardial haemorrhage drained into the left pleural cavity resulting in a haemothorax. This case is notable due to a favourable outcome despite a delay in diagnosis due to a lack of pericardial effusion, a concomitant cerebrovascular event and a long delay from injury to appropriate medical treatment in the presence of a penetrating cardiac wound deep enough to cause a muscular ventricular septal defect and lacerate a primary chordae of the anterior mitral leaflet.

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

    DEFF Research Database (Denmark)

    Koefoed, Mette; Ito, Hiromu; Gromov, Kirill

    2005-01-01

    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 r......Structural bone allografts often fracture due to their lack of osteogenic and remodeling potential. To overcome these limitations, we utilized allografts coated with recombinant adeno-associated virus (rAAV) that mediate in vivo gene transfer. Using beta-galactosidase as a reporter gene, we show...... 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...

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

    Science.gov (United States)

    Varettas, Kerry

    2013-12-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

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    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.

  13. Long-term renal allograft function on a tacrolimus-based, pred-free maintenance immunosuppression comparing sirolimus vs. MMF.

    Science.gov (United States)

    Gallon, L; Perico, N; Dimitrov, B D; Winoto, J; Remuzzi, G; Leventhal, J; Gaspari, F; Kaufman, D

    2006-07-01

    It is not known how different steroid-free immunosuppressive combinations affect renal graft survival and long-term kidney transplant function. Here we sought to compare the impact on graft survival and long-term graft function of two tacrolimus (Tac)-based, prednisone-free maintenance immunosuppressive protocols: Tac/Mycophenolate Mofetil (MMF) vs. Tac/Sirolimus (SRL). Renal transplant patients given induction therapy with IL2-RA and methylprednisolone on days 0, 1 and 2 post-transplant were prospectively randomized to two maintenance immunosuppressive regimens with Tac/MMF (n = 45) or Tac/SRL (n = 37). During the 3-year follow-up the following data were collected: patient survival, renal allograft survival, incidence of acute rejection and glomerular filtration rate (GFR) at different time-points post-transplant. Cumulative graft survival was significantly different in the two groups: one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL (log-rank test p = 0.04). GFR at different time-points post-transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group. The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group. This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF.

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

    Science.gov (United States)

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

    2015-12-04

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

  15. Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D.

    Directory of Open Access Journals (Sweden)

    Abdallah Fayssoil

    Full Text Available Type 2C and 2D limb girdle muscular dystrophies (LGMD are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.We reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax, cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke and mortality as outcomes of interest for the present analysis.A total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24-38]. At baseline, median pulmonary vital capacity (VC was 31% of predicted value [20-40]. Median maximal inspiratory pressure (MIP was 31 cmH2O [IQR 20.25-39.75]. Median maximal expiratory pressure (MEP was 30 cm H2O [20-36]. Median left ventricular ejection fraction (LVEF was 55% [45-64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD were associated with mortality, whilst respiratory parameters (VC, MIP, MEP and the need for home mechanical ventilation (HMV were associated with respiratory events.In our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality.ClinicalTrials.gov NCT02501083.

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

    Science.gov (United States)

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

    2017-02-16

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

  17. 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.

  18. Effect of immune protection of heart allograft in mice induced by immune escape mechanism of trichinella spiralis%旋毛虫免疫逃避机制对诱导小鼠移植心脏免疫保护作用的影响

    Institute of Scientific and Technical Information of China (English)

    邓庚国; 卢新军; 马毅; 廖冰; 陈颖华; 王国栋; 何晓顺

    2015-01-01

    Objective To observe the effect of immune protection of heart allograft in mice induced by immune escape mechanism of trichinella spiralis,and explore new and potential ways against acute rejection in clinic.Methods The heterotopic cardiac transplantation models were divided into three groups:rejection group,treatment group,and isograft group.Mean survival time was measured.Twenty-eight days before transplantation,recipients (C57BL/6) of rejection group were orally infected with 300 muscle larvae,and donors were untreated.Hearts in each group were harvested on the day 7 post-transplantation for pathological observation.Proportion of CD4 +,CD8 + T cells and regulatory T cells (Tregs) was detected by flow cytometry.Results As compared with rejection group (11 days),survival of allografts was significantly prolonged in treatment group (24 days) (P < 0.01),alleviated pathologic signd were observed,and proportion of CD8 + T cells (36.6%) was reduced (48.8%,P < 0.01),but there was no significant difference in CD4 + T cells between treatment group and rejection group.Meanwhile,proportion of Tregs in treatment group (16.9%) was significantly higher than in rejection group (10.8%,P < 0.05).Conclusion Trichinella spiralis infection lowered the proportion of CD8 + T cells,augmented Tregs frequency,and alleviated acute rejection of heterotopic cardiac transplantation in mice,which immunologically protected mice heart allograft.%目的 观察旋毛虫免疫逃避机制对诱导小鼠移植心脏免疫保护作用的影响,探讨可应用于临床的新抗排斥途径.方法 小鼠心脏移植术前28 d,实验组每只受体小鼠(C57 BL/6)以300条旋毛虫肌幼虫经口感染,供体小鼠(BALB/c)未感染,同时设立急性排斥反应组以及同系移植对照组,观察各组移植心脏的存活时间.术后第7天获取供心并观察移植物排斥病理学改变,流式细胞术检测受体脾脏淋巴细胞中CD4+、CD8+T淋巴细胞和调

  19. 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.

  20. 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.

  1. 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.)

  2. 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...

  3. 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

  4. 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....

  5. Late Acute Rejection Occuring in Liver Allograft Recipients

    Directory of Open Access Journals (Sweden)

    Eric M Yoshida

    1996-01-01

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

  6. 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

    2016-09-01

    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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Cardiac sarcoidosis and heart transplantation: a report of four consecutive patients

    DEFF Research Database (Denmark)

    Milman, N.; Andersen, Claus Bøgelund; Mortensen, Sven Aage;

    2008-01-01

    Heart transplantation (HTx) is a well-established treatment for severe cardiac failure. However, HTx for cardiac sarcoidosis is rare; less than 80 patients have been reported worldwide. In many patients, the diagnosis was not made prior to HTx. The aim of this study was to describe the use of HTx...... to HTx. In three patients, all with dilated cardiomyopathy due to myocardial sarcoidosis, the final diagnosis was obtained by examination of the explanted heart. Arrythmias (supraventricular and ventricular), heart block, mitral valve insufficiency and dilated cardiomyopathy were prominent clinical...... features. None of the patients had recurrence of sarcoid disease in the allograft. Two patients are long-term survivors and two are deceased, one of primary graft failure, the other from Cytomegalovirus myocarditis. In conclusion, HTx is a viable treatment for cardiac sarcoidosis with end stage cardiac...

  13. Genome-wide transcription profile of endothelial cells after cardiac transplantation in the rat.

    Science.gov (United States)

    Mikalsen, B; Fosby, B; Wang, J; Hammarström, C; Bjaerke, H; Lundström, M; Kasprzycka, M; Scott, H; Line, P-D; Haraldsen, G

    2010-07-01

    Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on days 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-gamma-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin, which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection.

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

    Directory of Open Access Journals (Sweden)

    Tatomirović Željka

    2003-01-01

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

  15. Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies

    Science.gov (United States)

    Guo, Xuli; Hu, Juan; Luo, Weiguang; Luo, Qizhi; Guo, Jing; Tian, Fang; Ming, Yingzi

    2017-01-01

    Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1) was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%, p = 0.002). Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120 μmol/L), 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77) versus 16.9% (30/178), p = 0.0187). A better understanding of this antigenic target will improve long-term allograft survival.

  16. Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.

    Science.gov (United States)

    Bombas, A; Stein-Oakley, A N; Baxter, K; Thomson, N M; Jablonski, P

    1999-01-01

    Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.

  17. 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

  18. 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.

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

    Science.gov (United States)

    Stiehl, J B

    1991-04-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  2. 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....

  3. 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.

  4. 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

  5. The effect of blood transfusion and immunosuppression on organ graft survival : a study in dogs and rats

    NARCIS (Netherlands)

    G.J.C.M. Niessen

    1982-01-01

    textabstractSince the first preliminary report by Opelz et al. (1973a) on the beneficial effect of blood transfusions, it has gradually become evident that blood transfusions do have such an effect on renal allograft survival. Nevertheless, some physicians are still reluctant to adopt a deliberate b

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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. 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

  13. The experimental study of inhibitory effect on the rejection of rat cardiac allo graft and the expression of intercellular adhesion molecule-1 by mycophenolate mofetil%大鼠心脏移植排斥反应时细胞间粘附分子-1的表达及霉酚酸酯对其的抑制作用

    Institute of Scientific and Technical Information of China (English)

    龙刚; 王西墨; 陈实; 陈刚

    2001-01-01

    Objectives To investigate the expression of intercellular adhesion molecule-1 (ICAM-1) in heart tissues during the course of the rejection and the inhibitory effects of mycophenolate mofetil (MMF) on the rejection of cardiac allograft as well as the expression of ICAM-1.Methods The rat model of heterotopic cardiac allograft was developed. The rats were divided into following groups: control group of car diac isograft of Wistar to Wistar rats, group of cardiac allograft of SD to Wist ar rats and MMF-treated group of cardiac allograft. The grafts were collected t o receive immunohistochemical and histopathological examinations. Quantitative m easurement of ICAM-1 expression in the grafts was done with multimedia patholog y imaging analysis system.Results Faint ICAM-1 expression was observed both in the control group and MMF-treated groups. Also in the latter, rare infiltration of lymphocytes was found. Controv ersially, in the allotransplantation groups, capillary endothelial cells of the grafts strongly expressed ICAM-1 during the episode of rejection, which occurred two or three days earlier than the ordinary histological study. Conclusions The expression level of ICAM-1 was related t o the occurrence and development of rejection. MMF could reduce the expressi on of intercellular adhesion molecule and the infiltration of lymphocytes in the grafts obviously and prolong grafts survival greatly.%目的探讨大鼠同种异位心脏移植排斥反应期间移植心组织细胞间粘附分子-1(ICAM-1)的表达及霉酚酸酯(MMF)对移植心ICAM-1表达和排斥反应的抑制作用。方法建立大鼠心脏腹腔移植模型,设Wistar到Wistar大鼠的同系心脏移植对照组、SD大鼠到Wi s tar大鼠的同种移植组和同种移植MMF治疗组。采集移植心组织标本行免疫组织化学和组织病理学检查,应用多媒体彩色图文分析系统对移植心组织ICAM-1的表达进行定量检测。

  14. 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

  15. 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.

  16. 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.

  17. Stem cell autograft and allograft in autoimmune diseases.

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

    Issa, Fadi

    2016-06-01

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

  19. 调节性T细胞对输注树突状细胞后小鼠移植心脏的保护作用%The protective effects of CD4+ CD25+ Treg cell on the allograft after infusion of dendritic cells with low expression of CD40 from donor in mouse heart transplantation

    Institute of Scientific and Technical Information of China (English)

    朱杰昌; 付蔚华; 许翼麟; 朱理玮

    2013-01-01

    Objective To explore the effects of CD4+CD25+Treg cell on the allograft after infusion of dendritic cells (DCs) with low expression of CD40 from donor in mouse heart transplantation.Methods In vitro,mouse bone marrow-derived DCs were infected by CD40-RNAi lentiviral vector,and tolerogenic DCs (Tol-DCs) with low expression of CD40 were prepared.A heterotopic abdominal heart transplantation model was established in mice,and the other three groups that were control group,noninfected DC group and lentivirus infected DC group were designed correspondingly.Cardiac allograft survival time was recorded and pathological grading for acute rejection was assessed on the 7 d after heterotopic abdominal heart transplantation.Concentrations of CD4+CD25+Treg cells in peripheral blood were analyzed before and after transplantation by flow cytometry.Results After 48 h infection of DCs by CD40-RNAi lentiviral vector in vitro,the expression of CD40 mRNA was down-regulated significantly,whose inhibition rate was 80.9%.The expression of CD40 was decreased from 74.37% ±4.08% to 40.07% ± 4.03% (P<0.05) after 48 h infection.Compared with the control group and the noninfected DC group,the cardiac allograft survival time was significantly prolonged in the CD40-RNAi lentivirus infected DC group,which was (14 ± 4) d(P<0.01) ; concentrations of CD4+CD25+Treg cells in peripheral blood were increased both on the 3 d and the 7 d after transplantation (P<0.05) ; the pathological grading for acute rejection was decreased on the 7 d after transplantation (P<0.05).Conclusion The CD4+CD25+Treg cell in peripheral blood was protective to cardiac allograft in prolonging its survival time in mouse heart transplantation.%目的 探讨在输注供者低表达CD40的树突状细胞(dendritic cells,DC)后,调节性T细胞(regulatory T cell,Treg)对小鼠移植心脏的保护作用.方法 以针对小鼠CD40基因的RNA干扰(RNA interference,RNAi)慢病毒载体在体外感染供者骨髓

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Fast and slow methylators: do racial differences influence risk of allograft rejection?

    Science.gov (United States)

    Chocair, P R; Duley, J A; Sabbaga, E; Arap, S; Simmonds, H A; Cameron, J S

    1993-06-01

    A catabolic route for azathioprine involving methylation by thiopurine methyltransferase has been directly implicated in the drug's immunosuppressive efficacy. Since ethnic differences in thiopurine methyltransferase activity have been reported in a study of Lapps, this study compared the distribution of thiopurine methyltransferase activity in erythrocyte lysates from 134 healthy, randomly selected subjects living in Brazil, comprising 39 blacks (i.e. Afro-Brazilians), 33 white subjects, 30 mixed-race subjects, and 32 Brazilian-residing Japanese subjects. The results demonstrated bimodality of thiopurine methyltransferase activity compatible with genetic polymorphism in the white, black and mixed-race groups, but not in the Japanese, who were homogeneously 'fast methylators' (high thiopurine methyltransferase activity). Thiopurine methyltransferase activity was generally higher in Brazilian males than females, and some individuals in the black and mixed-race groups had very high activity. Azathioprine-immunosuppressed transplant patients with thiopurine methyltransferase activity above 35 pmol/h/mgHb have previously been shown to have significantly poorer outcomes. Using this thiopurine methyltransferase value as the cut-off point between 'poor responders' and 'good responders' to azathioprine, 65% of the Japanese, 59% of the black subjects, and 63% of the mixed-race subjects fell into the 'poor responder' category, compared with only 42% of the white group. Interestingly, this approximately 20% difference in azathioprine response corresponds to the racial differences seen in allograft survival.

  5. 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.

  6. 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...

  7. 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....

  8. 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.

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

    Science.gov (United States)

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

    2007-06-01

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

  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. 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

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

    Science.gov (United States)

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

    2017-01-01

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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  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. 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.

  19. 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.

  20. 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.

  1. 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. 

  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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Cardiac tamponade (image)

    Science.gov (United States)

    Cardiac tamponade is a condition involving compression of the heart caused by blood or fluid accumulation in the space ... they cannot adequately fill or pump blood. Cardiac tamponade is an emergency condition that requires hospitalization.

  8. What Is Cardiac Rehabilitation?

    Science.gov (United States)

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  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. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    Amin, A.S.; Asghari-Roodsari, A.; Tan, H.L.

    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

  12. 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.

  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=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.

  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=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.

  15. 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

  16. Biomimetic materials design for cardiac tissue regeneration.

    Science.gov (United States)

    Dunn, David A; Hodge, Alexander J; Lipke, Elizabeth A

    2014-01-01

    Cardiovascular disease is the leading cause of death worldwide. In the absence of sufficient numbers of organs for heart transplant, alternate approaches for healing or replacing diseased heart tissue are under investigation. Designing biomimetic materials to support these approaches will be essential to their overall success. Strategies for cardiac tissue engineering include injection of cells, implantation of three-dimensional tissue constructs or patches, injection of acellular materials, and replacement of valves. To replicate physiological function and facilitate engraftment into native tissue, materials used in these approaches should have properties that mimic those of the natural cardiac environment. Multiple aspects of the cardiac microenvironment have been emulated using biomimetic materials including delivery of bioactive factors, presentation of cell-specific adhesion sites, design of surface topography to guide tissue alignment and dictate cell shape, modulation of mechanical stiffness and electrical conductivity, and fabrication of three-dimensional structures to guide tissue formation and function. Biomaterials can be engineered to assist in stem cell expansion and differentiation, to protect cells during injection and facilitate their retention and survival in vivo, and to provide mechanical support and guidance for engineered tissue formation. Numerous studies have investigated the use of biomimetic materials for cardiac regeneration. Biomimetic material design will continue to exploit advances in nanotechnology to better recreate the cellular environment and advance cardiac regeneration. Overall, biomimetic materials are moving the field of cardiac regenerative medicine forward and promise to deliver new therapies in combating heart disease.

  17. 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

  18. 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.

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2016-12-01

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

  2. 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

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

    OpenAIRE

    Conklin, L D; Reardon, M J

    1999-01-01

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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Acute pulmonary embolism: prediction of cor pulmonale and short-term patient survival from assessment of cardiac dimensions in routine multidetector-row CT; Mehrschicht-Spiral-CT bei vermuteter und inzidenteller akuter Lungenembolie: prognostischer Wert morpholoqischer Herzparameter

    Energy Technology Data Exchange (ETDEWEB)

    Engeike, C. [Radiologie, Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany); Rummeny, E.; Marten, K. [Inst. fuer Roentgendiagnostik, Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany)

    2006-10-15

    Purpose: evaluation of the prognostic value of morphological cardiac parameters in patients with suspected and incidental acute pulmonary embolism (PE) using multidetector-row chest CT (MSCT). Materials and methods: 2335 consecutive MSCT scans were evaluated for the presence of PE. The arterial enhancement and analysability of pulmonary arteries and the heart were assessed as parameters of the scan quality. The diastolic right and left ventricular short axes (RV{sub D}, LV{sub D}) and the interventricular septal deviation (ISD) were measured in all PE-positive patients and the echocardiography reports were reviewed. The clinical data assessment included cardio-respiratory and other co-morbidities, systemic anticoagulant therapy (ACT), and the 30-day outcome. Predictors of acute cor pulmonale and the short-term outcome were calculated by univariate and multivariate logistic regressions including odds ratios (OR) and ROC analyses using positive (PPV) and negative predictive values (NPV). Results: 90 patients with acute PE were included (36 with clinically suspected PE, 54 with incidental PE). 26 patients had cardio-respiratory co-morbidities. Four patients underwent systemic thrombolysis, 43 underwent anticoagulation in therapeutic doses, 19 underwent anticoagulation in prophylactic doses, and 24 patients did not undergo ACT. 15 of 41 patients had echocardiographic evidence of acute cor pulmonale. 8 patients died within 30 days. The RV{sub D} was the best independent predictor of acute cor pulmonale (p = 0,002, OR = 9.16, PPV = 0.68, NPV=1 at 4.49 cm cut off) and short-term outcome (p= 0,0005, OR = 2.82, PPV = 0.23, NPV = 0.98 at 4.75 cm cut off). The RV{sub D}/LV{sub D} ratio had a PPV of 0.85 for cor pulmonale. (orig.)

  10. 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.

  11. 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.

  12. 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.

  13. Long-term outcome in patients treated with combined heart and liver transplantation for familial amyloidotic cardiomyopathy

    DEFF Research Database (Denmark)

    Nelson, Laerke M; Penninga, Luit; Sander, Kaare

    2013-01-01

    allograft vasculopathy or neuropathy after transplantation. No recurrence of cardiac amyloid was found. CONCLUSIONS: CHLTx in selected patients with FAC due to Leu111Met mutation offers acceptable long-term survival, almost comparable with isolated cardiac transplantation. Allograft rejection was rare....

  14. Mechanisms of cardiac pain.

    Science.gov (United States)

    Foreman, Robert D; Garrett, Kennon M; Blair, Robert W

    2015-04-01

    Angina pectoris is cardiac pain that typically is manifested as referred pain to the chest and upper left arm. Atypical pain to describe localization of the perception, generally experienced more by women, is referred to the back, neck, and/or jaw. This article summarizes the neurophysiological and pharmacological mechanisms for referred cardiac pain. Spinal cardiac afferent fibers mediate typical anginal pain via pathways from the spinal cord to the thalamus and ultimately cerebral cortex. Spinal neurotransmission involves substance P, glutamate, and transient receptor potential vanilloid-1 (TRPV1) receptors; release of neurokinins such as nuclear factor kappa b (NF-kb) in the spinal cord can modulate neurotransmission. Vagal cardiac afferent fibers likely mediate atypical anginal pain and contribute to cardiac ischemia without accompanying pain via relays through the nucleus of the solitary tract and the C1-C2 spinal segments. The psychological state of an individual can modulate cardiac nociception via pathways involving the amygdala. Descending pathways originating from nucleus raphe magnus and the pons also can modulate cardiac nociception. Sensory input from other visceral organs can mimic cardiac pain due to convergence of this input with cardiac input onto spinothalamic tract neurons. Reduction of converging nociceptive input from the gallbladder and gastrointestinal tract can diminish cardiac pain. Much work remains to be performed to discern the interactions among complex neural pathways that ultimately produce or do not produce the sensations associated with cardiac pain.

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

    Directory of Open Access Journals (Sweden)

    S. R. Alam

    2015-01-01

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

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

    Science.gov (United States)

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

    2002-08-01

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

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

    Science.gov (United States)

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

    2012-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-04

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

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

    Directory of Open Access Journals (Sweden)

    J.R. Olmos-Zúãiga

    2016-01-01

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

  1. Postoperative Cardiac Arrest after Heart Surgery: Does Extracorporeal Perfusion Support a Paradigm Change in Management?

    Directory of Open Access Journals (Sweden)

    Edward Gologorsky

    2010-01-01

    Full Text Available Early institution of extracorporeal perfusion support (ECPS may improve survival after cardiac arrest. Two patients sustained unexpected cardiac arrest in the Intensive Care Unit (ICU following cardiac interventions. ECPS was initiated due to failure to restore hemodynamics after prolonged (over 60 minutes advanced cardiac life support (ACLS protocol-guided cardiopulmonary resuscitation. Despite relatively late institution of ECPS, both patients survived with preserved neurological function. This communication focuses on the utility of ECPS in the ICU as a part of resuscitative efforts.

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

    Science.gov (United States)

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

    2016-04-01

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

  3. A novel cardioprotective agent in cardiac transplantation: metformin activation of AMP-activated protein kinase decreases acute ischemia-reperfusion injury and chronic rejection.

    Science.gov (United States)

    Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P

    2011-12-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.

  4. Extracorporeal life support in pediatric cardiac patients

    Directory of Open Access Journals (Sweden)

    Matteo Di NARDO

    2016-10-01

    Full Text Available Extracorporeal Life Support (ECLS is a valuable tool in the management of neonates and older children with severe cardiac or respiratory failure. In this review, we focus on ECLS when used for neonatal and pediatric cardiac disease. Strict selection of patients and timely deployment are necessary to optimize outcomes. Although every attempt should be made to deploy ECLS urgently rather than emergently, extracorporeal cardiopulmonary resuscitation (ECPR is being increasingly used and reasonable survival rates have been achieved after initiation of ECLS during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS are falling over time, although lethal chromosomal abnormalities, severe irreversible brain injury, and extremely low gestational age and weight (<32 weeks gestation or <1.5 kg remain firm contraindications.

  5. Surviving Objects

    OpenAIRE

    Murjas, Teresa

    2012-01-01

    Surviving Objects (2012) is a devised multi-media practice-as-research performance based on extensive interviews conducted with my elderly mother and recorded on a hand-held device. Our conversations concern her experiences as a child refugee following violent deportation by the Soviet Army from Eastern Poland to Siberia (1941), and her subsequent route, via Persia, to a British-run refugee camp in Northern Rhodesia, where she remained for 6 years before arriving in the UK. In order to aid my...

  6. Stimulating endogenous cardiac regeneration

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    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.

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

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    Mascarenhas, Randy; McConkey, Mark O; Forsythe, Brian; Harner, Christopher D

    2015-04-01

    Revision anterior cruciate ligament (ACL) reconstruction is a technically demanding procedure with outcomes that generally fail to reach those seen with primary ACL reconstruction. With most index procedures using autograft tissue, it is not uncommon for allograft tissue to be required for revision ACL reconstruction. Compared with autografts, allografts take longer to incorporate and lead to more episodes of instability. In this article, we describe ipsilateral iliotibial band tenodesis performed to augment use of bone-patellar tendon-bone allograft in revision ACL reconstruction. This technique adds rotational stability to protect the allograft tissue while it incorporates.

  8. Anterior cruciate ligament reconstruction with BPTB autograft, irradiated versus non-irradiated allograft: a prospective randomized clinical study.

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    Sun, Kang; Tian, Shaoqi; Zhang, Jihua; Xia, Changsuo; Zhang, Cailong; Yu, Tengbo

    2009-05-01

    The effect of using gamma irradiation to sterilize bone-patellar tendon-bone (BPTB) allograft on the clinical outcomes of anterior cruciate ligament (ACL) reconstruction with irradiated allograft remains controversial. Our study was aimed to analyze the clinical outcomes of arthroscopic ACL reconstruction with irradiated BPTB allograft compared with non-irradiated allograft and autograft. All BPTB allografts were obtained from a single tissue bank and the irradiated allografts were sterilized with 2.5 Mrad of irradiation prior to distribution. A total of 102 patients undergoing arthroscopic ACL reconstruction were prospectively randomized consecutively into three groups. The same surgical technique was used in all operations done by the same senior surgeon. Before surgery and at the average of 31 months follow-up (range 24-47 months) patients were evaluated by the same observer according to objective and subjective clinical evaluations. Of these patients, 99 (autograft 33, non-irradiated allograft 34, irradiated allograft 32) were available for full evaluation. When compared the irradiated allograft group to non-irradiated allograft group or autograft group at 31 months follow-up by the Lachman test, ADT, pivot shift test and KT-2000 arthrometer testing, statistically significant differences were found. Most importantly, 87.8% of patients in the Auto group, 85.3% in the Non-Ir-Auto group and just only 31.3% in the Ir-Allo group had a side-to-side difference of less than 3 mm according to KT-2000. The failure rate of the ACL reconstruction with irradiated allograft (34.4%) was higher than that with autograft (6.1%) and non-irradiated allograft (8.8%). The anterior and rotational stability decreased significantly in the irradiated allograft group. According to the overall IKDC, functional, subjective evaluations and activity level testing, no statistically significant differences were found between the three groups. However, there was a trend that the functional and

  9. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  10. Comparative study of the role of professional versus semiprofessional or nonprofessional antigen presenting cells in the rejection of vascularized organ allografts.

    Science.gov (United States)

    Sundstrom, J B; Ansari, A A

    1995-12-01

    The immune systems of transplant recipients are progressively challenged with exposure to the multiple lineages of donor cells that comprise the vascularized organ allograft. Each lineage of such donor tissue constitutively expresses or can be induced to express varying densities of MHC antigens ranging from no expression of MHC to MHC class I only to both MHC class I and class II. In addition, the cell surface expression of a diverse assortment of costimulatory and cell adhesion molecules also varies in density in a tissue specific fashion within the allograft. The MHC class I/II molecules displayed on the donor cells contain within their clefts a constellation of processed protein antigens in the form of peptides derived from intracellular and to some extent extracellular sources. Therefore, the potential for each cell lineage to induce alloactivation and serve as a target for allospecific immune responses is dependent on the diversity and density of peptide-bearing MHC molecules, costimulatory molecules, and cell adhesion molecules. In addition, the T cell receptor repertoire of the recipient also contributes to the magnitude of the allogeneic response. Consequently, the variety of clinical outcomes following organ transplantation even with the institution of potent immunosuppressive (drug) therapies is not surprising, as it appears reasonable for such therapies to influence the allogeneic response against distinct lineages differentially. Our failure to prevent chronic human allograft rejection may therefore be due to our limited appreciation of the full spectrum of alloactivating experiences encountered by host T cells as they interact with donor cells of diverse tissue lineages. Investigations by our laboratory of the immunopathogenesis of chronic cardiac allograft rejection have revealed an intrinsic inability of human cardiac myocytes to process and present antigens, not only for primary but also for secondary alloimmune responses. One obvious explanation

  11. Transgenic expression of CD95 ligand on thyroid follicular cells confers immune privilege upon thyroid allografts.

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    Tourneur, L; Malassagne, B; Batteux, F; Fabre, M; Mistou, S; Lallemand, E; Lores, P; Chiocchia, G

    2001-08-01

    Constitutive Fas ligand (FasL) expression by specialized cells in the body participates in the immune privilege status of tissues containing these cells. This property has been used to prevent rejection of allogeneic grafts. Nevertheless, the mechanism responsible for such protection has not been fully elucidated. Unfortunately, grafting of FasL transgenic (TG) tissues has been unsuccessful. We have generated TG mice expressing FasL (soluble + membrane bound) on thyroid follicular cells (TFC), and used them to show that ectopic FasL expression prevents thyroid allograft rejection. FasL expression on TFC led to markedly decreased anti-allogeneic, cytotoxic, and helper T lymphocyte activities. The alloantibody response in TG thyroid recipients was either completely inhibited or switched toward a T2-Ab response. Surprisingly, the beneficial effect of FasL on TG thyroid grafts was abolished by host CD4(+) T cell depletion. Host CD8(+) T cell depletion improved nontransgenic (NTG), but not TG graft survival. Altogether, our results suggest that FasL-induced tolerance is concomitant with a move away from a T1 type response, and a CD4 T cell-mediated regulation of the allocytotoxic T cell response. These results were dependent upon the level of FasL expression on TFC, in that low expression of FasL led to a less marked effect compared with the effect observed with high expression of FasL. These results provide some insight into the role of FasL in regulating destructive alloimmune responses in the case of whole organ grafting, and they have important implications for the development of FasL-based immunotherapy in organ transplantation.

  12. A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism.

    Science.gov (United States)

    Cruzado, Josep M; Moreno, Pablo; Torregrosa, José V; Taco, Omar; Mast, Richard; Gómez-Vaquero, Carmen; Polo, Carolina; Revuelta, Ignacio; Francos, José; Torras, Joan; García-Barrasa, Arantxa; Bestard, Oriol; Grinyó, Josep M

    2016-08-01

    Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m(2) The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

  13. [Sudden cardiac death in individuals with normal hearts: an update].

    Science.gov (United States)

    González-Melchor, Laila; Villarreal-Molina, Teresa; Iturralde-Torres, Pedro; Medeiros-Domingo, Argelia

    2014-01-01

    Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1h after the onset of symptoms in a person without previous signs of fatality. It can be named "recovered SD" when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event.

  14. An audit of consent for allograft use in elective orthopaedic surgery.

    Science.gov (United States)

    Mullan, C J; Pagoti, R; Davison, H; McAlinden, M G

    2016-04-01

    Introduction Patients receiving musculoskeletal allografts may be at risk of postoperative infection. The General Medical Council guidelines on consent highlight the importance of providing patients with the information they want or need on any proposed investigation or treatment, including any potential adverse outcomes. With the increased cost of defending medicolegal claims, it is paramount that adequate, clear informed patient consent be documented. Methods We retrospectively examined the patterns of informed consent for allograft bone use during elective orthopaedic procedures in a large unit with an onsite bone bank. The initial audit included patients operated over the course of 1 year. Following a feedback session, a re-audit was performed to identify improvements in practice. Results The case mix of both studies was very similar. Revision hip arthroplasty surgery constituted the major subgroup requiring allograft (48%), followed by foot and ankle surgery (16.3%) and revision knee arthroplasty surgery (11.4%) .On the initial audit, 17/45 cases (38%) had either adequate preoperative documentation of the outpatient discussion or an appropriately completed consent form on the planned use of allograft. On the re-audit, 44/78 cases (56%) had adequate pre-operative documentation. There was little correlation between how frequently a surgeon used allograft and the adequacy of consent (Correlation coefficient -0.12). Conclusions Although the risk of disease transmission with allograft may be variable, informed consent for allograft should be a routine part of preoperative discussions in elective orthopaedic surgery. Regular audit and feedback sessions may further improve consent documentation, alongside the targeting of high volume/low compliance surgeons.

  15. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason