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Sample records for resist cardiac allograft

  1. Cardiac allograft immune activation: current perspectives

    Directory of Open Access Journals (Sweden)

    Chang D

    2014-12-01

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

  2. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    International Nuclear Information System (INIS)

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B.

    1991-01-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Pretransplant portal venous administration of donor antigen and portal venous allograft drainage synergistically prolong rat cardiac allograft survival

    International Nuclear Information System (INIS)

    Kamei, T.; Callery, M.P.; Flye, M.W.

    1990-01-01

    The effect of antigen given through the portal vein (PV) before transplantation or continuous drainage of a graft into the PV results in moderate prolongation of allograft survival. This study examines these treatment modalities further. Pretransplant donor antigen as 25 x 10(6) ultraviolet B-irradiated (12,000 joules/m2) donor spleen cells was given 7 days before heart transplantation through either the PV or systemic venous (IV) routes. On day 0, Lewis-to-Buffalo rat cardiac allografts were drained either into the PV or IV. Pretransplant PV donor antigen administration (p less than 0.005), but not by IV administration, significantly prolonged cardiac allograft survival across the strong RT 1 rat histoincompatibility barrier. Similarly PV, but not IV, drainage of the graft prolonged graft survival (p less than 0.005). Pretransplant IV antigen administration had no additive effect on PV drainage graft survival. In contrast, when pretransplant PV donor antigen was combined with PV drainage, 11 of 14 allografts (p less than 0.001) continued to function, free of rejection, after 150 days. Therefore for rat cardiac transplants a clearly synergistic graft-prolonging effect results when pretransplant PV donor antigen is combined with PV drainage of the allografts. These data clarify the potent tolerogenic effects of alloantigen not only administered into the PV but also continuously shed intraportally so that it is first processed by the liver

  5. Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization

    Science.gov (United States)

    Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.

    2012-01-01

    Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for transplantation. PMID:22615333

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

    International Nuclear Information System (INIS)

    Li Lusheng; Zhao Xin; Song Guangmin; Yang Xixiu; Song Huimin

    2001-01-01

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

  7. Early aspirin use and the development of cardiac allograft vasculopathy.

    Science.gov (United States)

    Kim, Miae; Bergmark, Brian A; Zelniker, Thomas A; Mehra, Mandeep R; Stewart, Garrick C; Page, Deborah S; Woodcome, Erica L; Smallwood, Jennifer A; Gabardi, Steven; Givertz, Michael M

    2017-12-01

    Cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Little is known about the influence of aspirin on clinical expression of CAV. We followed 120 patients with OHT at a single center for a median of 7 years and categorized them by the presence or absence of early aspirin therapy post-transplant (aspirin treatment ≥6 months in the first year). The association between aspirin use and time to the primary end-point of angiographic moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) was investigated. Propensity scores for aspirin treatment were estimated using boosting models and applied by inverse probability of treatment weighting (IPTW). Despite a preponderance of risk factors for CAV among patients receiving aspirin (male sex, ischemic heart disease as the etiology of heart failure, and smoking), aspirin therapy was associated with a lower rate of moderate or severe CAV at 5 years. Event-free survival was 95.9% for patients exposed to aspirin compared with 79.6% for patients without aspirin exposure (log-rank p = 0.005). IPTW-weighted Cox regression revealed a powerful inverse association between aspirin use and moderate to severe CAV (adjusted hazard ratio 0.13; 95% confidence interval 0.03-0.59), which was directionally consistent for CAV of any severity (adjusted hazard ratio 0.50; 95% confidence interval 0.23-1.08). This propensity score-based comparative observational analysis suggests that early aspirin exposure may be associated with a reduced risk of development of moderate to severe CAV. These findings warrant prospective validation in controlled investigations. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Cellular basis for accumulation of 111In-labeled leukocytes and platelets in rejecting cardiac allografts: concise communication

    International Nuclear Information System (INIS)

    Wang, T.S.; Oluwole, S.; Fawwaz, R.A.; Wolff, M.; Kuromoto, N.; Satake, K.; Hardy, M.A.; Alderson, P.O.

    1982-01-01

    Biodistribution and imaging studies in rats showed that 111 In-labeled leukocytes and platelets accumulate progressively with time after transplantation in cardiac allografts undergoing rejection, but do not accumulate in normal syngeneic heart grafts. Maximum heart allograft-to-blood ratios of 9:1 were obtained, and allograft-to-native heart ratios of 17:1. Microscopic studies of the rejecting cardiac allografts showed that histologic findings paralleled the cellular changes predicted by the radionuclide studies. Intravenously administered 67 Ga citrate and /sup 99m/Tc sulfur colloid failed to show significant accumulation in rejecting grafts. The findings suggest that cellular rejection, rather than nonspecific inflammatory changes, is the primary basis for accumulation of 111 In leukocytes and platelets in rejecting cardiac allografts

  9. Cellular basis for accumulation of In-111-labeled leukocytes and platelets in rejecting cardiac allografts: concise communication

    International Nuclear Information System (INIS)

    Wang, T.S.T.; Oluwole, S.; Fawwaz, R.A.; Wolff, M.; Kuromoto, N.; Satake, K.; Hardy, M.A.; Alderson, P.O.

    1982-01-01

    Biodistribution and imaging studies in rats showed that In-111-labeled leukocytes and platelets accumulate progressively with time after transplantation in cardiac allografts undergoing rejection, but do not accumulate in normal syngeneic heart grafts. Maximum heart allograft-to-blood ratios of 9:1 were obtained, and allograft-to-native heart ratios of 17:1. Microscopic studies of the rejecting cardiac allografts showed that histologic findings paralleled the cellular changes predicted by the radionuclide studies. Intravenously administered Ga-67 citrate and Tc-99m sulfur colloid failed to show significant accumulation in rejecting grafts. The findings suggest that cellular rejection, rather than nonspecific inflammatory changes, is the primary basis for accumulation of In-111 leukocytes and platelets in rejecting cardiac allografts

  10. Sensitivity of scintigraphy with 111In-lymphocytes for detection of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. III

    1988-01-01

    We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively

  11. Diagnosis of cardiac allograft rejection with indium-111 labeled platelets in cyclosporin treated rats

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1984-01-01

    Rejection of heart transplants remains difficult to diagnose. Indium-111 (In-111) labeled lymphocytes accumulate in rat cardiac allografts when recipients are treated with Cyclosporin (Cy), even in the absence of clinical rejection. This presumably occurs because of the non-specific 'interstitial infiltration' caused by Cy. This study examines the usefulness of In-111 labeled platelets in differentiating experimental cardiac allograft rejection from Cy-induced tissue changes. The authors initially examined the migration patterns of syngeneic In-111 labeled platelets in groups of Lewis recipients of ACI cardiac allografts treated with IM Cy (10mg/kg) for 6-14 days. In addition, 10 control animals were not immunosuppressed, and 10 were treated with Cy but received Lewis cardiac isografts. Syngeneic In-111 platelets were injected IV into each animal 24 hours prior to sacrifice. Three to five rats from each group were killed at 3 ,7, 14, 21 and 28 days after transplantation and the % ID/gm in the transplanted hearts and native hearts were determined and correlated with histopathology. Untreated Lewis recipients rejected ACI hearts in 6.5 +- 0.4 days while Cy prolonged allograft survival in a variable fashion. In-111 platelet accumulation correlated well with the degree of rejection determined independently by histopathology. No significant In-111 platelet accumulation was detected in non-rejecting cardiac transplants or in native hearts in Cy treated or control animals. The results suggest that In-111 labeled platelets will be an effective agent for diagnosis of cardiac rejection, even in the presence of Cy treatment

  12. Identification of capillary rarefaction using intracoronary wave intensity analysis with resultant prognostic implications for cardiac allograft patients.

    Science.gov (United States)

    Broyd, Christopher J; Hernández-Pérez, Francisco; Segovia, Javier; Echavarría-Pinto, Mauro; Quirós-Carretero, Alicia; Salas, Clara; Gonzalo, Nieves; Jiménez-Quevedo, Pilar; Nombela-Franco, Luis; Salinas, Pablo; Núñez-Gil, Ivan; Del Trigo, Maria; Goicolea, Javier; Alonso-Pulpón, Luis; Fernández-Ortiz, Antonio; Parker, Kim; Hughes, Alun; Mayet, Jamil; Davies, Justin; Escaned, Javier

    2018-05-21

    Techniques for identifying specific microcirculatory structural changes are desirable. As such, capillary rarefaction constitutes one of the earliest changes of cardiac allograft vasculopathy (CAV) in cardiac allograft recipients, but its identification with coronary flow reserve (CFR) or intracoronary resistance measurements is hampered because of non-selective interrogation of the capillary bed. We therefore investigated the potential of wave intensity analysis (WIA) to assess capillary rarefaction and thereby predict CAV. Fifty-two allograft patients with unobstructed coronary arteries and normal left ventricular (LV) function were assessed. Adequate aortic pressure and left anterior descending artery flow measurements at rest and with intracoronary adenosine were obtained in 46 of which 2 were lost to follow-up. In a subgroup of 15 patients, simultaneous RV biopsies were obtained and analysed for capillary density. Patients were followed up with 1-3 yearly screening angiography. A significant relationship with capillary density was noted with CFR (r = 0.52, P = 0.048) and the backward decompression wave (BDW) (r = -0.65, P < 0.01). Over a mean follow-up of 9.3 ± 5.2 years patients with a smaller BDW had an increased risk of developing angiographic CAV (hazard ratio 2.89, 95% CI 1.12-7.39; P = 0.03). Additionally, the index BDW was lower in those who went on to have a clinical CAV-events (P = 0.04) as well as more severe disease (P = 0.01). Within cardiac transplant patients, WIA is able to quantify the earliest histological changes of CAV and can predict clinical and angiographic outcomes. This proof-of-concept for WIA also lends weight to its use in the assessment of other disease processes in which capillary rarefaction is involved.

  13. 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....

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

    DEFF Research Database (Denmark)

    Wassilew, Katharina

    2017-01-01

    . 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...... allograft dysfunction, as MCS patients show a higher frequency of antibody-mediated rejection (AMR) episodes. We aimed to analyze the effects of MCS on cardiac AMR with regards to capillary C3d and C4d depositions. Regarding the functional parameters, both acute cellular rejection (ACR) and an increase...... of interstitial fibrosis (IF) often correlate with impaired ventricular function. The innate immune system, in particular macrophages, plays an important role in the resorptive process of ACR and is, on the other hand, known to promote IF. In this study we aimed to analyze the effect of ACR and specifically...

  15. Isatis tinctoria L. combined with co-stimulatory molecules blockade prolongs survival of cardiac allografts in alloantigen-primed mice.

    Science.gov (United States)

    Kang, Xiangpeng; Chen, Jibing; Qin, Qing; Wang, Feng; Wang, Yongzhi; Lan, Tianshu; Xu, Shuo; Wang, Feiyu; Xia, Junjie; Ekberg, Henrik; Qi, Zhongquan; Liu, Zhongchen

    2010-05-01

    Memory T cells present a unique challenge in transplantation. Although memory T cells express robust immune responses to invading pathogens, they may be resistant to the effects of immunosuppressive therapies used to prolong graft survival. In previous studies, we found that compound K, the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., reduced acute cardiac allograft rejection in mice (Wang et al., 2009 [1]). Here, we further investigated the effect of compound K on cardiac allograft rejection in alloantigen-primed mice. We found that compound K significantly inhibited CD4(+) and CD8(+) memory T cells proliferation in a mixed lymphocyte reaction (MLR). In vivo, compound K combined with anti-CD154 and anti-LFA-1 monoclonal antibodies (mAbs) significantly extended the survival time of heart grafts in alloantigen-primed mice with no obvious toxic side effects. Furthermore, our data suggests that compound K works by reducing the expression of both IL-2 and IFN-gamma within the graft rather than enhancing expression of regulatory T cells (Tregs). Compound K can also inhibit the alloresponses of memory T cells, while increasing the proportion of CD4(+) memory T cells in the spleen of the recipients and significantly reducing the level of alloantibodies in the serum. Our study highlights the unique immune effects of compound K that may be further explored for clinical use in extending the survival of transplant grafts. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  16. Effect of 34 kinds of traditional Japanese herbal medicines on prolongation of cardiac allograft survival.

    Science.gov (United States)

    Jin, X; Uchiyama, M; Zhang, Q; Harada, T; Otsuka, K; Shimokawa, T; Niimi, M

    2014-05-01

    Herbal medicines have been used for over 3,000 years in Asian as alternative therapy for their variety effects and have recently become popular in Europe and the United States. In the last 30 years, Japanese herbal medicines were widely used for treatment of diseases after been recognized officially by Japanese government. In this study, we investigated the effect of 34 kinds of traditional Japanese herbal medicines on alloimmune responses in a murine model of cardiac allograft transplantation. CBA mice (H2(k)) underwent transplantation of a C57BL/6 (H2(b)) heart and received oral administration of 2 g/kg/d of the 34 kinds of herbal medicines from the day of transplantation until 7 days afterward. Naïve CBA mice rejected B6 cardiac grafts acutely (median survival time [MST], 7 days). CBA transplant recipients given 2 g/kg/d of Sairei-to (TJ-114) and Tokishakuyaku-san (TJ-23) had prolonged C57BL/6 allograft survival indefinitely (both MSTs > 100 days). Moreover, CBA transplant recipients given Seisinrensiin (TJ-111), Tokishigyakukagoshuyushokyoto (TJ-38), Rikkunshito (TJ-43), Maobushisaishinto (TJ-127), Ninjin-yoei-to (TJ-108), Ryokan-kyomi-shinge-nin-to (TJ-119), Inchingorei-san (TJ-117), Hochuekkito (TJ-41), Kihi-to (TJ-65), and Sinbu-to (TJ-30) had also prolonged C57BL/6 allograft survival significantly (MSTs of 28, 22, 16, 14, 14, 13, 12, 9.5, 9 and 9 days, respectively). However, none of other 22 kinds of herbal medicines could prolong the allograft survival. Furthermore, oral administration of 2 g/kg/d of Daikenchuto (TJ-100) induced sudden death (within 1 minute) in CBA mice. In conclusion, 12 kinds of Japanese herbal medicines prolonged allograft survival and one showed toxic effect in mice. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  18. Prevalence of polyreactive innate clones among graft--infiltrating B cells in human cardiac allograft vasculopathy.

    Science.gov (United States)

    Chatterjee, Debanjana; Moore, Carolina; Gao, Baoshan; Clerkin, Kevin J; See, Sarah B; Shaked, David; Rogers, Kortney; Nunez, Sarah; Veras, Yokarla; Addonizio, Linda; Givertz, Michael M; Naka, Yoshifumi; Mancini, Donna; Vasilescu, Rodica; Marboe, Charles; Restaino, Susan; Madsen, Joren C; Zorn, Emmanuel

    2018-03-01

    Cardiac allograft vasculopathy (CAV) has been associated with graft-infiltrating B cells, although their characteristics are still unclear. In this study we examined the frequency, localization and reactivity profile of graft-infiltrating B cells to determine their contribution to the pathophysiology of CAV. B cells, plasma cells and macrophages were examined by immunohistochemistry in 56 allografts with CAV, 49 native failed hearts and 25 autopsy specimens. A total of 102 B-cell clones were immortalized directly from the infiltrates of 3 fresh cardiac samples with CAV. Their secreted antibodies were assessed using enzyme-linked immunoassay and flow cytometry. B-cell infiltration was observed around coronary arteries in 93% of allograft explants with CAV. Comparatively, intragraft B cells were less frequent and less dense in the intraventricular myocardium from where routine biopsies are obtained. Plasma cells and macrophages were also detected in 85% and 95% of explants, respectively. Remarkably, B-cell infiltrates were not associated with circulating donor-specific antibodies (DSA) or prior episodes of antibody-mediated rejection (AMR). Among all B-cell clones generated from 3 explants with CAV, a majority secreted natural antibodies reactive to multiple autoantigens and apoptotic cells, a characteristic of innate B cells. Our study reveals a high frequency of infiltrating B cells around the coronary arteries of allografts with CAV, independent of DSA or AMR. These cells are enriched for innate B cells with a polyreactive profile. The findings shift the focus from conventional DSA-producing B cells to the potentially pathogenic polyreactive B cells in the development of clinical CAV. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Diagnosis of cardiac allograft rejection with MR imaging

    International Nuclear Information System (INIS)

    Soulen, R.L.; Fraser, C.D.; Hutchins, G.M.; Baumgartner, W.A.; Reitz, B.A.

    1987-01-01

    Serial MR images and endomyocardial biopsy specimens of heterotopic cervical cardiac allotransplants were obtained in six dogs during 2 weeks of immunosuppression followed by 1 week without such therapy. A surface coil and gated spin-echo technique were used. Myocardial intensity (MI) measurements and histopathologic interpretations were performed independently. All six dogs showed a decrease in MI between their first and second MR studies, while showing no rejection. One dog had no rejection and died; in five dogs studies gated to every other beat showed progressive increase in MI that correlated significantly with increasing rejection, though absolute MI values did not correlated with a specific biopsy score. Severe rejection also caused overt increase in myocardial mass. The MI in the early postoperative period may reflect reperfusion injury. Absolute intensity values cannot predict rejection. Serial studies in transplant patients may prove clinically useful

  20. Induction of transplantation tolerance to fully mismatched cardiac allografts by T cell mediated delivery of alloantigen

    Science.gov (United States)

    Tian, Chaorui; Yuan, Xueli; Jindra, Peter T.; Bagley, Jessamyn; Sayegh, Mohamed H.; Iacomini, John

    2010-01-01

    Induction of transplantation tolerance has the potential to allow for allograft acceptance without the need for life-long immunosuppression. Here we describe a novel approach that uses delivery of alloantigen by mature T cells to induce tolerance to fully allogeneic cardiac grafts. Adoptive transfer of mature alloantigen-expressing T cells into myeloablatively conditioned mice results in long-term acceptance of fully allogeneic heart transplants without evidence of chronic rejection. Since myeloablative conditioning is clinically undesirable we further demonstrated that adoptive transfer of mature alloantigen-expressing T cells alone into mice receiving non-myeloablative conditioning resulted in long-term acceptance of fully allogeneic heart allografts with minimal evidence of chronic rejection. Mechanistically, tolerance induction involved both deletion of donor-reactive host T cells and the development of regulatory T cells. Thus, delivery of alloantigen by mature T cells induces tolerance to fully allogeneic organ allografts in non-myeloablatively conditioned recipients, representing a novel approach for tolerance induction in transplantation. PMID:20452826

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

    NARCIS (Netherlands)

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

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

  2. Coronary Allograft Vasculopathy after Cardiac Transplantation: Prevalence, Prognostic and Risk Factors.

    Science.gov (United States)

    Antunes, André; Prieto, David; Pinto, Carlos; Branco, Carlos; Correia, Pedro; Batista, Manuel; Antunes, Manuel

    2017-01-01

    Coronary allograft vasculopathy (CAV) is still a serious long-term complication after cardiac transplantation. To evaluate the prevalence of CAV in a single institution, its impact on survival and to explore associated risk factors. From November-2003 through June-2016, 316 patients were submitted to cardiac transplantation. After excluding those with paediatric age (n=8), those with previous renal or hepatic transplantation (n=2) and those who didn't survive the first year after cardiac transplantation (n=40), the study population resulted in 266 patients. Forty two patients (15.8%) with CAV, diagnosed by a new >50% coronary artery stenosis in any vessel during follow-up, were compared with a non-CAV group. Both groups share de same median age (54+10years). Recipient male sex predominated in the CAV group (93% vs. 74%), as did ischemic etiology (52% vs. 37%). Although not reaching statistical significance, CAV patients also had more dyslipidemia (60% vs. 50%), history of smoking (52% vs. 44%) and peripheral vascular disease (45% vs. 29%). The incidence of celular acute rejection 1R is more frequent in CAV group (69% vs. 60%) such as 2R or 3R (29% vs. 27%). Prolonged use of inotropic support and mechanical assistance after cardiac transplantation were comparable between both groups. The survival of this patients, who were submitted to cardiac transplantation and had lived at least 1 year, between CAV and non-CAV group was comparable at 5-year (91% vs. 85%), but tended to be lower for CAV patients in 10-year interval (52% vs. 73%). This data confirms CAV as a common long-term complication following cardiac transplantation. Although short to mid-term survival seems not to be affected by CAV, long-term survival appears lower, hence a longer follow-up is needed.

  3. Relationship between natriuretic peptides and inflammation: proteomic evidence obtained during acute cellular cardiac allograft rejection in humans.

    Science.gov (United States)

    Meirovich, Yael F; Veinot, John P; de Bold, Mercedes L Kuroski; Haddad, Haissam; Davies, Ross A; Masters, Roy G; Hendry, Paul J; de Bold, Adolfo J

    2008-01-01

    Cardiac natriuretic peptides (NPs) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are polypeptide hormones secreted by the heart. Previously, we found that BNP, but not ANF, plasma levels may increase during an acute cellular cardiac allograft rejection episode. In vitro, the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) produced a selective increase of BNP gene expression and secretion. Other pro-inflammatory cytokines had no such effects. We identified cytokines associated with the selective upregulation of BNP during cardiac allograft rejection using a proteomics approach to measure 120 cytokines and related substances in the plasma of 16 transplant patients before, during and after an acute rejection episode. The values obtained were correlated with BNP plasma levels. Cytokines identified as being significantly related to BNP plasma levels were tested in neonatal rat ventricular cardiocytes in culture for their ability to selectively promote BNP secretion. The signaling pathway related to this phenomenon was pharmacologically characterized. Regulated-on-activation, normal T-expressed and secreted (RANTES), neutrophil-activating protein-2 (NAP-2) and insulin growth factor binding protein-1 (IGFBP-1) had significant correlations with BNP plasma levels during Grade 3A (Grade 2 revised [2R]) or above rejection as diagnosed by endomyocardial biopsy score according to the International Society for Heart and Lung Transplantation (ISHLT) grading system. In rat neonatal ventricular cardiocyte cultures, IGFBP-1 and RANTES were capable of promoting BNP, but not ANF secretion, as observed in rejecting patients. The BNP-promoting secretion activity of the identified cytokines was abolished by SB203580, a specific p38 MAP kinase inhibitor. This work shows that cytokines other than pro-inflammatory cytokines correlate with BNP plasma levels observed during acute cardiac allograft rejection, and that

  4. Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study

    NARCIS (Netherlands)

    Hoogen, M.W.F. van den; Kho, M.M.; Abrahams, A.C.; Zuilen, A.D. van; Sanders, J.S.; Dijk, M.; Hilbrands, L.B.; Weimar, W.; Hoitsma, A.J.

    2013-01-01

    OBJECTIVES: Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting

  5. Effect of a Single Intraoperative High-Dose ATG-Fresenius on Delayed Graft Function in Donation After Cardiac-Death Donor Renal Allograft Recipients : A Randomized Study

    NARCIS (Netherlands)

    van den Hoogen, Martijn W. F.; Kho, Marcia M. L.; Abrahams, Alferso C.; van Zuilen, Arjan D.; Sanders, Jan Stephan; van Dijk, Marja; Hilbrands, Luuk B.; Weimar, Willem; Hoitsma, Andries J.

    Objectives: Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting

  6. Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

    Science.gov (United States)

    Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

    2013-01-01

    Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

  7. The predictive value of renal vascular resistance for late renal allograft loss

    NARCIS (Netherlands)

    de Vries, APJ; van Son, WJ; van der Heide, JJH; Ploeg, RJ; Navis, G; de Jong, PE; Gans, ROB; Bakker, SJL; Gansevoort, RT

    The renal artery resistance index (RI), assessed by Doppler ultrasonography, was recently identified as a new risk marker for late renal allograft loss. This finding requires confirmation since RI in that study was not measured at predetermined time points and ultrasonography is operator-dependent.

  8. The predictive value of renal vascular resistance for late renal allograft loss

    NARCIS (Netherlands)

    de Vries, A. P. J.; van Son, W. J.; Homan van der Heide, J. J.; Ploeg, R. J.; Navis, G.; de Jong, P. E.; Gans, R. O. B.; Bakker, S. J. L.; Gansevoort, R. T.

    2006-01-01

    The renal artery resistance index (RI), assessed by Doppler ultrasonography, was recently identified as a new risk marker for late renal allograft loss. This finding requires confirmation since RI in that study was not measured at predetermined time points and ultrasonography is operator-dependent.

  9. Long term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1996-01-01

    Purpose: To evaluate the short and long term effects of total lymphoid irradiation (TLI) in the treatment of allograft rejection in cardiac transplant patients. Materials and Methods: From 1986 to 1995, 48 courses of TLI were delivered to 47 patients who had received cardiac transplants at Stanford University. In 38 cases, TLI was administered for chronic, intractable allograft rejection despite conventional anti-rejection therapy, including corticosteroids, azathioprine, cyclosporine, OKT3, DHPG, RATG, and methotrexate. Ten patients received TLI prophylactically, beginning radiation between 5 and 16 days after heart transplantation. The prescribed radiation dose was 800 cGy given in 80 cGy fractions twice weekly to all major lymph node regions using mantle and inverted Y fields. Patients continued to receive all medications except azathioprine which was held during TLI to prevent severe marrow suppression. All patients were closely monitored for episodes of rejection, infection, prednisone requirements, blood counts, and complications of treatment. Post-irradiation follow up ranged from 6 months to 9.1 years with a mean of 3.1 years. Results: The actual mean dose of radiation was 730 cGy delivered over a mean of 39 calendar days. Fifty six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, the frequency of rejection dropped from 0.46 episodes/patient/month before radiation to 0.14 episodes/patient/month during TLI (p 3 during TLI (p = 0.01) and remained low at 167.6 cells/mm 3 2-4 months after treatment (p = 0.05). CD8+ lymphocytes also decreased during treatment from 233.2 to 65.8 cells/mm 3 (p = 0.003) but rose significantly above normal to 381.3 cells/mm 3 2-4 months after TLI (p 0.05). Thus, the ratio of helper/suppresser T-cells was chronically decreased. Infection rates were not significantly different before, during or after

  10. Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1997-01-01

    Purpose: To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection. Methods and Materials: Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years. Results: The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort. Conclusion: TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not

  11. Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model.

    Science.gov (United States)

    Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

    2012-01-01

    The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of

  12. Music exposure induced prolongation of cardiac allograft survival and generated regulatory CD4⁺ cells in mice.

    Science.gov (United States)

    Uchiyama, M; Jin, X; Zhang, Q; Amano, A; Watanabe, T; Niimi, M

    2012-05-01

    In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts.

    Science.gov (United States)

    Yun, K L; Fann, J I; Sokoloff, M H; Fong, L G; Sarris, G E; Billingham, M E; Miller, D C

    1991-01-01

    With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7

  14. Effect of a single intraoperative high-dose ATG-fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: A randomized study

    NARCIS (Netherlands)

    M.W.F. van den Hoogen (M. W F); M.M.L. Kho (Marcia); A.C. Abrahams (Alferso); A.D. van Zuilen (Arjan); J.-S. Sanders (Jan-Stephan); M. van Dijk (Marja); L.B. Hilbrands (Luuk); W. Weimar (Willem); A.J. Hoitsma (Andries)

    2013-01-01

    textabstractObjectives: Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with

  15. Selective lymphoid irradiation: III. Prolongation of cardiac xenografts and allografts in presensitized rats

    International Nuclear Information System (INIS)

    Hardy, M.A.; Oluwole, S.; Fawwaz, R.; Satake, K.; Nowygrod, R.; Reemtsma, K.

    1982-01-01

    Selective lymphoid irradiation (SLI) with palladium-109-hematoporphyrin (Pd-H) combined with antilymphocyte globulin (ALG) induces either donor-specific permanent rat heart allograft acceptance or significant allograft prolongation depending on the degree of donor-recipient matching. The purpose of this study was to determine if SLI combined with ALG can affect ACI heart allograft survival in Lewis recipients presensitized to ACI, and of hamster heart xenografts of Lewis rats. SLI combined with ALG delays allograft and xenograft rejection in the presence of induced or preformed antidonor antibodies, and converts primarily a humoral rejection into a cellular rejection by mechanisms as yet uncertain. Such peritransplant treatment had significant effect on the levels of antidonor complement-dependent cytotoxic antibody titers but did not correlate directly with graft survival. Histological analysis of rejected hearts in all groups demonstrated primarily a humoral hyperacute rejection in control animals and in recipients treated with ALG alone, while peritransplant treatment with Pd-H and ALG resulted not only in prolonged graft survival but histologically, primarily a cellular rejection of the graft

  16. 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.

  17. Intra and interobserver variability of renal allograft ultrasound volume and resistive index measurements

    International Nuclear Information System (INIS)

    Mancini, Marcello; Liuzzi, Raffaele; Daniele, Stefania; Raffio, Teresa; Salvatore, Marco; Sabbatini, Massimo; Cianciaruso, Bruno; Ferrara, Liberato Aldo

    2005-01-01

    Purpose: Aim of the presents study was to evaluate the repeatability and reproducibility of the Doppler Resistive Index (R.I.) and the Ultrasound renal volume measurement in renal transplants. Materials and methods: Twenty -six consecutive patients (18 men, 8 women) mean age of 42,8±12,4 years (M±SD)(range 22-65 years) were studied twice by each of two trained sonographers using a color Doppler ultrasound scanner. Twelve of them had a normal allograft function (defined as stable serum creatinine levels ≤123,76 μmol/L), whilst the remaining 14 had decreased allograft function (serum creatinine 132.6-265.2 μmol/L). Results were given as mean of 6 measurements performed at upper, middle and lower pole of the kidney. Intra- and interobserver variability was assessed by the repeatability coefficient and coefficient of variation (CV). Results: Regarding Resistive Index measurement, repeatability coefficient was between 0.04 and 0.06 and the coefficient of variation was [it

  18. Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial

    DEFF Research Database (Denmark)

    Arora, Stina Jørgensen; Erikstad, I; Ueland, T

    2012-01-01

    of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However...... with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal...

  19. Circulating endothelial progenitor cell numbers are not associated with donor organ age or allograft vasculopathy in cardiac transplant recipients.

    Science.gov (United States)

    Thomas, H E; Parry, G; Dark, J H; Arthur, H M; Keavney, B D

    2009-02-01

    Increasing age is associated with reduced numbers of circulating endothelial progenitor cells (EPCs). It is unclear whether this relates to depletion or impairment of bone marrow progenitors, or to deficient mobilization signals from aging tissues. In cardiac transplant patients, one previous study has reported an association between circulating EPCs and the risk of cardiac allograft vasculopathy (CAV). We investigated whether increased donor heart age, a strong risk factor for CAV, was associated with reduced circulating EPC numbers in a group of cardiac transplant recipients matched for factors which influence EPC numbers, but with maximally discordant donor heart ages. We identified 32 patient pairs, matched for factors known to influence EPC numbers, but who had discordant donor heart ages by at least 20 years. EPCs were quantified using flow cytometry for absolute counts of cells expressing all the combinations of CD45, CD34, CD133 and the kinase domain receptor (KDR). There were no significant differences in the numbers of circulating EPCs between patients with old or young donor heart age. There was no association between the presence of CAV and circulating EPC numbers. We suggest that the increased susceptibility to CAV of older donor hearts is not mediated via circulating EPCs. Our results are consistent with the theory that the normal age-related decline in EPC numbers relates to bone marrow aging rather than failure of target tissues to induce EPC mobilization.

  20. Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft

    Science.gov (United States)

    Qiu, Ying; Yun, Mark M; Han, Xia; Zhao, Ruidong; Zhou, Erxia; Yun, Sheng

    2014-01-01

    Background: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. Methods: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. Results: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. Conclusions: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID:25126177

  1. The potential of cardiac allografts from donors after cardiac death at the University of Wisconsin Organ Procurement Organization.

    Science.gov (United States)

    Osaki, Satoru; Anderson, James E; Johnson, Maryl R; Edwards, Niloo M; Kohmoto, Takushi

    2010-01-01

    The purpose of this study is to investigate the potential availability of hearts from adult donation after cardiac death (DCD) donors within an acceptable hypoxic period. We retrospectively reviewed a donor database from the University of Wisconsin Organ Procurement Organization Donor Tracking System between 2004 and 2006. The DCD population (n=78) was screened using our inclusion criteria for DCD cardiac donor suitability, including warm ischaemic time (WIT) limit of 30 min. In the same period, 70 hearts were donated from brain-dead donors. Of 78 DCD donors, 12 (15%) met our proposed DCD cardiac donor criteria. The mean WIT of these 12 DCD donors was 21 min (range 14-29 min). When inclusion criteria are further narrowed to (1) age Based on our proposed DCD cardiac donor criteria, the potential application of DCD cardiac donors would represent an increase in cardiac donation of 17% (12/70) during the 3-year period. When the criteria were narrowed to the initial 'ideal' case, only two donors met such criteria, suggesting that such 'ideal' DCD donors are rare but they do exist. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  2. 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.

  3. 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

    International Nuclear Information System (INIS)

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

    1980-01-01

    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

  4. Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

    Science.gov (United States)

    van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

    2013-04-01

    Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

  5. Impact of Leukocyte Function-Associated Antigen-1 Blockade on Endogenous Allospecific T Cells to Multiple Minor Histocompatibility Antigen Mismatched Cardiac Allograft.

    Science.gov (United States)

    Kwun, Jean; Farris, Alton B; Song, Hyunjin; Mahle, William T; Burlingham, William J; Knechtle, Stuart J

    2015-12-01

    Blocking leukocyte function-associated antigen (LFA)-1 in organ transplant recipients prolongs allograft survival. However, the precise mechanisms underlying the therapeutic potential of LFA-1 blockade in preventing chronic rejection are not fully elucidated. Cardiac allograft vasculopathy (CAV) is the preeminent cause of late cardiac allograft failure characterized histologically by concentric intimal hyperplasia. Anti-LFA-1 monoclonal antibody was used in a multiple minor antigen-mismatched, BALB.B (H-2B) to C57BL/6 (H-2B), cardiac allograft model. Endogenous donor-specific CD8 T cells were tracked down using major histocompatibility complex multimers against the immunodominant H4, H7, H13, H28, and H60 minor Ags. The LFA-1 blockade prevented acute rejection and preserved palpable beating quality with reduced CD8 T-cell graft infiltration. Interestingly, less CD8 T cell infiltration was secondary to reduction of T-cell expansion rather than less trafficking. The LFA-1 blockade significantly suppressed the clonal expansion of minor histocompatibility antigen-specific CD8 T cells during the expansion and contraction phase. The CAV development was evaluated with morphometric analysis at postoperation day 100. The LFA-1 blockade profoundly attenuated neointimal hyperplasia (61.6 vs 23.8%; P < 0.05), CAV-affected vessel number (55.3 vs 15.9%; P < 0.05), and myocardial fibrosis (grade 3.29 vs 1.8; P < 0.05). Finally, short-term LFA-1 blockade promoted long-term donor-specific regulation, which resulted in attenuated transplant arteriosclerosis. Taken together, LFA-1 blockade inhibits initial endogenous alloreactive T-cell expansion and induces more regulation. Such a mechanism supports a pulse tolerance induction strategy with anti-LFA-1 rather than long-term treatment.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with cyclosporine on rat cardiac allograft survival

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Lau, H.T.; Reemtsma, K.; Hardy, M.A.

    1988-01-01

    We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by CsA treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with CsA, graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant CsA, the MST was increased to 68.83 +/- 16.1 days as compared to an MST of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA

  8. Effect of blood transfusion and cyclophosphamide on cardiac allograft survival in sensitized mice

    International Nuclear Information System (INIS)

    Lasek, Witold; Sora, Magdalena; Jakobisiak, Marek

    1994-01-01

    In the H-2-incompatible donor-recipient model in mice (BALB/c → CBA/H), combination of donor-specific blood transfusion (DST) on the day -9 before transplantation with both pre- and post transplant immunosuppression with cyclophosphamide (CY) interacted beneficially to produce significant donor-specific prolongation of cardiac graft survival. However, in recipients presensitized with donor-specific blood on the day -21, combination of DST with pre- and post transplant CY immunosuppression did not act synergistically and graft survival in this group did not differ from that in presentized mice treated with 2 doses of CY alone. (author). 21 refs, 1 fig., 3 tabs

  9. Aspirin resistance following pediatric cardiac surgery.

    Science.gov (United States)

    Cholette, Jill M; Mamikonian, Lara; Alfieris, George M; Blumberg, Neil; Lerner, Norma B

    2010-09-01

    Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels. This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained. 101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (pchildren with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  10. The Impact of Timing and Graft Dysfunction on Survival and Cardiac Allograft Vasculopathy in Antibody Mediated Rejection

    Science.gov (United States)

    Clerkin, Kevin J.; Restaino, Susan W.; Zorn, Emmanuel; Vasilescu, Elena R.; Marboe, Charles C.; Mancini, Donna M.

    2017-01-01

    Background Antibody mediated rejection (AMR) has been associated with increased mortality and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction while recent reports have demonstrated an association with increased mortality. We sought to investigate the timing of AMR and its association with graft dysfunction, mortality, and CAV. Methods This retrospective cohort study identified all adult heart transplant recipients at Columbia University Medical Center from 2004–2013 (689 patients). There were 68 primary cases of AMR, which were stratified by early (1-year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression. Results From January 1, 2004 through October 1, 2015 43 patients had early AMR (median 23 days post-OHT) and 25 had late AMR (median 1084 days post-OHT). Graft dysfunction was less common with early compared with late AMR (25.6% vs. 56%, p=0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1-year 80% vs. 93%, 5-year 51% vs. 73%, p<0.05). When stratified by graft dysfunction, only those with late AMR and graft dysfunction had worse survival (30-day 79%, 1-year 64%, and 5-year 36%, p<0.006). The association remained irrespective of age, sex, DSA, LVAD use, reason for OHT, and recovery of graft function. Similarly, those with late AMR and graft dysfunction had accelerated development of de-novo CAV (50% at 1 year, HR 5.42, p=0.009), while all other groups were all similar to the general transplant population. Conclusion Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR there is an early and sustained increased risk of mortality and rapid development of de-novo CAV despite aggressive treatment. PMID:27423693

  11. Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients.

    Science.gov (United States)

    Pampaloni, Miguel Hernandez; Shrestha, Uttam M; Sciammarella, Maria; Seo, Youngho; Gullberg, Grant T; Botvinick, Elias H

    2017-08-01

    Risk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. Twelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 years) with no history of post OHT myocardial ischemia were enrolled 5.4 ± 2.0 years after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 years) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic 13 N-NH 3 PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. Mean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33 ± 0.31 and 1.01 ± 0.21 mL/min/g for Groups 1 and 2, respectively, P < .001), while mean hyperemic MBF values were similar in both Groups (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P = .018). Both mean and median CFR values demonstrated a significant reduction for Group 1 compared to Group 2 patients (2.07 ± 0.74 vs 2.63 ± 0.48, P = .025). This study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV.

  12. The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection.

    Science.gov (United States)

    Clerkin, Kevin J; Restaino, Susan W; Zorn, Emmanuel; Vasilescu, Elena R; Marboe, Charles C; Mancini, Donna M

    2016-09-01

    Antibody-mediated rejection (AMR) has been associated with increased death and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction, whereas recent reports have demonstrated an association with increased mortality. We investigated the timing of AMR and its association with graft dysfunction, death, and CAV. This retrospective cohort study identified all adult orthotopic heart transplant (OHT) recipients (N = 689) at Columbia University Medical Center from 2004 to 2013. There were 68 primary cases of AMR, which were stratified by early ( 1 year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression. From January 1, 2004, through October 1, 2015, early AMR (median 23 days post-OHT) occurred in 43 patients and late AMR (median 1,084 days post-OHT) occurred in 25. Graft dysfunction was less common with early compared with late AMR (25.6% vs 56%, p = 0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1 year: 80% vs 93%, 5 years: 51% vs 73%, p < 0.05). When stratified by graft dysfunction, only those with late AMR and graft dysfunction had worse survival (30 days: 79%, 1 year: 64%, 5 years: 36%; p < 0.006). The association remained irrespective of age, sex, donor-specific antibodies, left ventricular assist device use, reason for OHT, and recovery of graft function. Similarly, those with late AMR and graft dysfunction had accelerated development of de novo CAV (50% at 1 year; hazard ratio, 5.42; p = 0.009), whereas all other groups were all similar to the general transplant population. Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR, there is an early and sustained increased risk of death and rapid development of de novo CAV despite aggressive treatment. Copyright © 2016 International Society for Heart and Lung

  13. Osteochondral allograft.

    Science.gov (United States)

    Torrie, Arissa M; Kesler, William W; Elkin, Joshua; Gallo, Robert A

    2015-12-01

    Over the past decade, osteochondral allograft transplantation has soared in popularity. Advances in storage techniques have demonstrated improved chondrocyte viability at longer intervals and allowed for potential of increased graft availability. Recent studies have stratified outcomes according to location and etiology of the chondral or osteochondral defect. Unipolar lesions generally have favorable outcomes with promising 10-year survival rates. Though those undergoing osteochondral allograft transplantation often require reoperation, patient satisfaction remains high.

  14. Does Resistance Training Stimulate Cardiac Muscle Hypertrophy?

    Science.gov (United States)

    Bloomer, Richard J.

    2003-01-01

    Reviews the literature on the left ventricular structural adaptations induced by resistance/strength exercise, focusing on human work, particularly well-trained strength athletes engaged in regular, moderate- to high-intensity resistance training (RT). The article discusses both genders and examines the use of anabolic-androgenic steroids in…

  15. Cardiac Insulin Resistance and MicroRNA Modulators

    Directory of Open Access Journals (Sweden)

    Lakshmi Pulakat

    2012-01-01

    Full Text Available Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS, and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS and angiotensin II (Ang II activate mammalian target for rapamycin (mTOR/p70 S6 kinase (S6K1 signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2, it also renders cardioprotection via increased Ang II receptor 2 (AT2R upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...

  17. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  19. 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

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

    International Nuclear Information System (INIS)

    Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong; Shi, Bing-Yi

    2010-01-01

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

  2. Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease

    Science.gov (United States)

    Govindsamy, Annelene; Naidoo, Strinivasen

    2018-01-01

    Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors. Disrupted cardiac insulin signalling contributes to cardiac insulin resistance. Intrauterine under- or overnutrition alters offspring cardiac structure and function, notably cardiac hypertrophy, systolic and diastolic dysfunction, and hypertension that precede the onset of cardiovascular disease. Optimal intrauterine nutrition and oxygen saturation are required for normal cardiac development in offspring and the maintenance of their cardiovascular physiology. PMID:29484207

  3. Insulin resistance and circadian rhythm of cardiac autonomic modulation

    Directory of Open Access Journals (Sweden)

    Cai Jianwen

    2010-12-01

    Full Text Available Abstract Background Insulin resistance (IR has been associated with cardiovascular diseases (CVD. Heart rate variability (HRV, an index of cardiac autonomic modulation (CAM, is also associated with CVD mortality and CVD morbidity. Currently, there are limited data about the impairment of IR on the circadian pattern of CAM. Therefore, we conducted this investigation to exam the association between IR and the circadian oscillations of CAM in a community-dwelling middle-aged sample. Method Homeostasis models of IR (HOMA-IR, insulin, and glucose were used to assess IR. CAM was measured by HRV analysis from a 24-hour electrocardiogram. Two stage modeling was used in the analysis. In stage one, for each individual we fit a cosine periodic model based on the 48 segments of HRV data. We obtained three individual-level cosine parameters that quantity the circadian pattern: mean (M, measures the overall average of a HRV index; amplitude (Â, measures the amplitude of the oscillation of a HRV index; and acrophase time (θ, measures the timing of the highest oscillation. At the second stage, we used a random-effects-meta-analysis to summarize the effects of IR variables on the three circadian parameters of HRV indices obtained in stage one of the analysis. Results In persons without type diabetes, the multivariate adjusted β (SE of log HOMA-IR and M variable for HRV were -0.251 (0.093, -0.245 (0.078, -0.19 (0.06, -4.89 (1.76, -3.35 (1.31, and 2.14 (0.995, for log HF, log LF, log VLF, SDNN, RMSSD and HR, respectively (all P Conclusion Elevated IR, among non-diabetics significantly impairs the overall mean levels of CAM. However, the  or θ of CAM were not significantly affected by IR, suggesting that the circadian mechanisms of CAM are not impaired. However, among persons with type 2 diabetes, a group clinically has more severe form of IR, the adverse effects of increased IR on all three HRV circadian parameters are much larger.

  4. Multidrug Resistant Pseudomonas Mycotic Pseudoaneurysm following Cardiac Transplant Bridged by Ventricular Assistant Device

    Directory of Open Access Journals (Sweden)

    C. Aye

    2017-01-01

    Full Text Available Mycotic pseudoaneurysm of aorta following cardiac surgery is rare but is highly fatal if it is unrecognized and untreated. Here, we report a case of a 45-year-old male patient who presented with rapidly progressive multiple pseudoaneurysms of the ascending aorta infected with multidrug resistant (MDR Pseudomonas aeruginosa at 5 weeks after cardiac transplantation, on a background of prior bridging therapy with left ventricular assistant device (LVAD. The patient was successfully treated with the newer cephalosporin, Ceftolozane/Tazobactam, in combination with surgery. This is the first reported case of mycotic pseudoaneurysm infected with MDR Pseudomonas. This case also highlights the importance of high vigilance and timely multimodality treatment in the diagnosis and management of mycotic pseudoaneurysm following cardiac transplant, especially in patients who had LVAD.

  5. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    International Nuclear Information System (INIS)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats

  6. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

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    Camilla Figueiredo Grans

    2014-07-01

    Full Text Available Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week. At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32% and trained infarcted (+46% in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%, myocardial performance index (-39% and systolic blood pressure (+6% improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%, as well as in the low frequency band of systolic blood pressure (-46% in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  7. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Energy Technology Data Exchange (ETDEWEB)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

    2014-07-15

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  8. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Science.gov (United States)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Background Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats. PMID:25014059

  9. Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin-resistant rats

    Science.gov (United States)

    Apaijai, Nattayaporn; Pintana, Hiranya; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2013-01-01

    Background and Purpose Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance. Experimental Approach Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined. Key Results Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV. Conclusions and Implications Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats. PMID:23488656

  10. Influence of glutamine on the effect of resistance exercise on cardiac ANP in rats

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    Romeu Rodrigues de Souza

    2015-03-01

    Full Text Available Various nutritional supplements (herbs, vitamins, and micronutrients improve responses and adaptations to resistance exercise. ANP is a heart hormone that contributes to fluid, electrolyte and blood pressure homeostasis through its natriuretic and vasodilative actions. In the present study, the adaptation of ANP in response to resistance exercise was investigated in rats supplemented with glutamine for five weeks. The results showed that supplementation with glutamine did not influence the number of ANP granules per atrial cardiocyte in sedentary animals. In exercised-trained rats, the number and diameter of the granules was significantly higher in comparison with the control group and in exercised animals supplemented with glutamine there was significant increase in the number and diameter of ANP granules compared with controls. Altogether, these data indicated that in resistance exercise rats, glutamine significantly enhances cardiac ANP thus implicating the beneficial effects of glutamine supplementation to the ANP system.

  11. Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

    Science.gov (United States)

    Paolillo, S; Rengo, G; Pellegrino, T; Formisano, R; Pagano, G; Gargiulo, P; Savarese, G; Carotenuto, R; Petraglia, L; Rapacciuolo, A; Perrino, C; Piscitelli, S; Attena, E; Del Guercio, L; Leosco, D; Trimarco, B; Cuocolo, A; Perrone-Filardi, P

    2015-10-01

    Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  12. Body Size Predicts Cardiac and Vascular Resistance Effects on Men's and Women's Blood Pressure

    Directory of Open Access Journals (Sweden)

    Joyce M. Evans

    2017-08-01

    Full Text Available Key Points SummaryWe report how blood pressure, cardiac output and vascular resistance are related to height, weight, body surface area (BSA, and body mass index (BMI in healthy young adults at supine rest and standing.Much inter-subject variability in young adult's blood pressure, currently attributed to health status, may actually result from inter-individual body size differences.Each cardiovascular variable is linearly related to height, weight and/or BSA (more than to BMI.When supine, cardiac output is positively related, while vascular resistance is negatively related, to body size. Upon standing, the change in vascular resistance is positively related to size.The height/weight relationships of cardiac output and vascular resistance to body size are responsible for blood pressure relationships to body size.These basic components of blood pressure could help distinguish normal from abnormal blood pressures in young adults by providing a more effective scaling mechanism.Introduction: Effects of body size on inter-subject blood pressure (BP variability are not well established in adults. We hypothesized that relationships linking stroke volume (SV, cardiac output (CO, and total peripheral resistance (TPR with body size would account for a significant fraction of inter-subject BP variability.Methods: Thirty-four young, healthy adults (19 men, 15 women participated in 38 stand tests during which brachial artery BP, heart rate, SV, CO, TPR, and indexes of body size were measured/calculated.Results: Steady state diastolic arterial BP was not significantly correlated with any index of body size when subjects were supine. However, upon standing, the more the subject weighed, or the taller s/he was, the greater the increase in diastolic pressure. Systolic pressure strongly correlated with body weight and height both supine and standing. Diastolic and systolic BP were more strongly related to height, weight and body surface area than to body mass

  13. Bone allografting in children

    Science.gov (United States)

    Sadovoy, M. A.; Kirilova, I. A.; Podorognaya, V. T.; Matsuk, S. A.; Novoselov, V. P.; Moskalev, A. V.; Bondarenko, A. V.; Afanasev, L. M.; Gubina, E. V.

    2017-09-01

    A total of 522 patients with benign and intermediate bone tumors of various locations, aged 1 to 15 years, were operated in the period from 1996 to 2016. To diagnose skeleton tumors, we used clinical observation, X-ray, and, if indicated, tomography and tumor site biopsy. In the extensive bone resection, we performed bone reconstruction with the replacement of a defect with an allograft (bone strips, deproteinized and spongy grafts), sometimes in the combination with bone autografting. After segmental resection, the defects were filled with bone strips in the form of matchstick grafts; the allografts were received from the Laboratory for Tissue Preparation and Preservation of the Novosibirsk Research Institute of Traumatology and Orthopedics. According to the X-ray data, a complete reorganization of bone grafts occurred within 1.5 to 3 years. The long-term result was assessed as good.

  14. Allograft Pancreatectomy: Indications and Outcomes.

    Science.gov (United States)

    Nagai, S; Powelson, J A; Taber, T E; Goble, M L; Mangus, R S; Fridell, J A

    2015-09-01

    This study evaluated the indications, surgical techniques, and outcomes of allograft pancreatectomy based on a single center experience. Between 2003 and 2013, 47 patients developed pancreas allograft failure, excluding mortality with a functioning pancreas allograft. Early graft loss (within 14 days) occurred in 16, and late graft loss in 31. All patients with early graft loss eventually required allograft pancreatectomy. Nineteen of 31 patients (61%) with late graft loss underwent allograft pancreatectomy. The main indication for early allograft pancreatectomy included vascular thrombosis with or without severe pancreatitis, whereas one recipient required urgent allograft pancreatectomy for gastrointestinal hemorrhage secondary to an arterioenteric fistula. In cases of late allograft pancreatectomy, graft failure with clinical symptoms such as abdominal discomfort, pain, and nausea were the main indications (13/19 [68%]), simultaneous retransplantation without clinical symptoms in 3 (16%), and vascular catastrophes including pseudoaneurysm and enteric arterial fistula in 3 (16%). Postoperative morbidity included one case each of pulmonary embolism leading to mortality, formation of pseudoaneurysm requiring placement of covered stent, and postoperative bleeding requiring relaparotomy eventually leading to femoro-femoral bypass surgery 2 years after allograftectomy. Allograft pancreatectomy can be performed safely, does not preclude subsequent retransplantation, and may be lifesaving in certain instances. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Electro-resistive bands for non-invasive cardiac and respiration monitoring, a feasibility study

    International Nuclear Information System (INIS)

    Gargiulo, Gaetano D; Breen, Paul P; O’Loughlin, Aiden

    2015-01-01

    Continuous unobtrusive monitoring of tidal volume, particularly for critical care patients (i.e. neonates and patients in intensive care) during sleep studies and during daily activities, is still an unresolved monitoring need. Also a successful monitoring solution is yet to be proposed for continuous non-invasive cardiac stroke volume monitoring that is a novel clinical need. In this paper we present the feasibility study for a wearable, non-invasive, non-contact and unobtrusive sensor (embedded in a standard T-shirt) based on four electro-resistive bands that simultaneously monitors tidal volume and cardiac stroke volume changes. This low power sensor system (requires only 100 mW and accepts a wide power supply range up to ±18 V); thus the sensor can be easily embedded in existing wearable solutions (i.e. Holter monitors). Moreover, being contactless, it can be worn over bandages or electrodes, and as it does not rely over the integrity of the garment to work, it allows practitioners to perform procedures during monitoring. For this preliminary evaluation, one subject has worn the sensor over the period of 24 h (removing it only to shower); the accuracy of the tidal volume tested against a portable spirometer reported a precision of ±10% also during physical activity; accuracy tests for cardiac output (as it may require invasive procedure) have not been carried out in this preliminary trial. (note)

  16. Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

    Science.gov (United States)

    Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

    2016-01-01

    The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

  17. Ca(2+) mishandling and cardiac dysfunction in obesity and insulin resistance: role of oxidative stress.

    Science.gov (United States)

    Carvajal, Karla; Balderas-Villalobos, Jaime; Bello-Sanchez, Ma Dolores; Phillips-Farfán, Bryan; Molina-Muñoz, Tzindilu; Aldana-Quintero, Hugo; Gómez-Viquez, Norma L

    2014-11-01

    Obesity and insulin resistance (IR) are strongly connected to the development of subclinical cardiac dysfunction and eventually can lead to heart failure, which is the main cause of morbidity and death in patients having these metabolic diseases. It has been considered that excessive fat tissue may play a critical role in producing systemic IR and enhancing reactive oxygen species (ROS) generation. This oxidative stress (OS) may elicit or exacerbate IR. On the other hand, evidence suggests that some of the cellular mechanisms involved in the pathophysiology of obesity and IR-related cardiomyopathy are excessive myocardial ROS production and abnormal Ca(2+) homeostasis. In addition, emerging evidence suggests that augmented ROS production may contribute to Ca(2+) mishandling by affecting the redox state of key proteins implicated in this process. In this review, we focus on the role of Ca(2+) mishandling in the development of cardiac dysfunction in obesity and IR and address the evidence suggesting that OS might also contribute to cardiac dysfunction by affecting Ca(2+) handling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Junqueira, Adriana, E-mail: francispacagnelli@unoeste.br [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Cicogna, Antônio Carlos [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Engel, Letícia Estevam; Aldá, Maiara Almeida [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Tomasi, Loreta Casquel de [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Giuffrida, Rogério; Giometti, Inês Cristina [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Freire, Ana Paula Coelho Figueira [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Universidade Estadual Paulista (UNESP), Campus Presidente Prudente, SP (Brazil); Aguiar, Andreo Fernando [Universidade do Norte do Paraná, UNOPAR, Londrina, PR (Brazil); Pacagnelli, Francis Lopes [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil)

    2016-01-15

    Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca{sup 2+} transport.

  19. Immediate changes in estimated cardiac output and vascular resistance after 60Co exposure in monkeys: implication for performance decrement

    International Nuclear Information System (INIS)

    Bruner, A.

    1977-01-01

    Aortic blood flow velocity, blood pressure, and heart rate were recorded in 12 unanesthetized, nonperforming monkeys during exposure to 1000 rad 60 Co at 129--164 rad/min. The first postradiation changes were seen within 3--4 min of the exposure's start and included tachycardia, a transient hypotension secondary to a loss in peripheral resistance, and a brief increase followed by a decrease to subnormal levels in cardiac output. The lowest cardiac output occurred between 10 and 20 min postexposure while blood pressure and peripheral resistance were recovering. It was proposed that the concurrent combination of low cardiac output, low blood pressure, and supranormal peripheral resistance might sufficiently attenuate cerebral perfusion temporarily to account for the transient behavioral decrements often seen during this time. Histamine release was postulated as responsible for this vascular shock syndrome

  20. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  1. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    International Nuclear Information System (INIS)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-01-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [ 3 H]glucose and 2-deoxy[ 14 C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

  2. Intra and interobserver variability of renal allograft ultrasound volume and resistive index measurements; Variabilita' intra- ed interoperatore delle misure ecografiche del volume e dell'indice di resistenza del rene trapiantato

    Energy Technology Data Exchange (ETDEWEB)

    Mancini, Marcello; Liuzzi, Raffaele [CNR, Napoli (Italy). Istituto di biostrutture e bioimmagini; Daniele, Stefania; Raffio, Teresa; Salvatore, Marco [Napoli Univ., Napoli (Italy). Dipartimento di diagnostica per immagini; Sabbatini, Massimo; Cianciaruso, Bruno [Napoli Univ., Napoli (Italy). Istituto di nefrologia medica; Ferrara, Liberato Aldo [Napoli Univ., Napoli (Italy). Dipartimento di medicina clinica e sperimentale

    2005-04-01

    Purpose: Aim of the presents study was to evaluate the repeatability and reproducibility of the Doppler Resistive Index (R.I.) and the Ultrasound renal volume measurement in renal transplants. Materials and methods: Twenty -six consecutive patients (18 men, 8 women) mean age of 42,8{+-}12,4 years (M{+-}SD)(range 22-65 years) were studied twice by each of two trained sonographers using a color Doppler ultrasound scanner. Twelve of them had a normal allograft function (defined as stable serum creatinine levels {<=}123,76 {mu}mol/L), whilst the remaining 14 had decreased allograft function (serum creatinine 132.6-265.2 {mu}mol/L). Results were given as mean of 6 measurements performed at upper, middle and lower pole of the kidney. Intra- and interobserver variability was assessed by the repeatability coefficient and coefficient of variation (CV). Results: Regarding Resistive Index measurement, repeatability coefficient was between 0.04 and 0.06 and the coefficient of variation was <5%. The analysis of the Student's test did not show any significant difference between the measurements (t=0.15; p=0.87 n.s.). A good reproducibility was also detected in US measurements of renal length and volume. Conclusions: These results suggest that Color Doppler Resistive Index measurements of renal allograft and Ultrasound renal volume measurements are repeatable and reproducible. [Italian] Scopo: Valutare la ripetibilit� e la riproducibilit� delle misurazioni ecografiche dell'Indice di Resistenza (I.R.) e del volume del rene trapiantato. Materiale e metodi: Ventisei pazienti (18 uomini, 8 donne) con et� media di 42,8{+-}12,4 anni (M{+-}SD)(range 22-65 anni) sono stati studiati consecutivamente due volte con eco-color-Doppler da due ecografisti esperti. Dodici pazienti avevano funzione renale normale (livello serico di creatina stabilmente {<=}123,76 {mu}mol/L, i rimanenti 14 avevano una lieve e stabile disfunzione del rene trapiantato (creatina serica 132.6-265.2 {mu

  3. Time-dependent changes in B-type natriuretic peptide after heart transplantation: correlation with allograft rejection and function.

    Science.gov (United States)

    Bader, Feras M; Rogers, R Kevin; Kfoury, Abdallah G; Gilbert, Edward M; Horne, Ben D; Stehlik, Josef; Renlund, Dale G

    2009-01-01

    Endomyocardial biopsy is the gold standard to diagnose cardiac allograft rejection, although a noninvasive modality such as brain natriuretic peptide (BNP) is attractive. The authors examined the correlation of BNP levels with rejection patterns and allograft function in cardiac allograft recipients followed up to 8 years. One hundred forty-four consecutive patients underwent endomyocardial biopsy, right heart catheterization, and blood sampling. BNP levels decreased during the first 6 months after transplant but then reached a plateau. Time-dependent correlations were made between BNP levels and allograft rejection, left ventricular ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, and serum creatinine. BNP levels were not different between patients with any rejection pattern and no rejection prior to or after 6 months following transplant. BNP levels did not correlate with ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, or creatinine in the first 6 months after transplant. Statistically significant correlations existed between BNP and these parameters after 6 months following transplant. In cardiac transplant recipients, BNP levels decrease in the first 6 months following transplant and then reach a plateau regardless of the presence, type, or severity of allograft rejection. BNP levels do predict allograft rejection but correlate with allograft function after 6 months following transplant.

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

    Directory of Open Access Journals (Sweden)

    V. Bueno

    2002-11-01

    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.

  5. Radionuclide diagnosis of allograft rejection

    International Nuclear Information System (INIS)

    George, E.A.

    1982-01-01

    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 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 111 In labeled autologous leukocytes and platelets are presently under investigation

  6. Allograft in bone tumour surgery

    International Nuclear Information System (INIS)

    Sengupta, S.

    1999-01-01

    In the last twenty years, there has been a vast improvement in the prognosis of primary malignant tumours of bone. This is due to many factors including early detection, staging and classification of tumours as a result of better staining and imaging techniques, better surgical technology, e.g. endoprosthesis and most importantly adjuvant treatment with cytotoxic drugs. As a result of long term survival, amputation of limb has more or less been replaced by limb salvage surgery. This procedure consists of two parts. Primary objective is of course complete removal of the tumour by adequate soft tissue cover and secondarily by reconstruction of the locomotor system, If possible with retention of the function of the limb. These procedures include endo-prosthetic replacement or arthroplasty and arthrodesis using autologus grafts, allograft or combination. With the development of bone banks and assured safety of preserved bones, reconstructive limb salvage surgery using massive allograft is gradually replacing prosthetic implants. The advantages include replacement of articular surfaces, incorporation of the graft to the host bone, attachment of bone tissue and increased probably permanent survival. Allograft can be used for intercalary replacement, osteo-articular arthroplasty arthrodesis or filling large cavities. Inherent complication of massive allograft are disease transmission, infection, delayed and non-union, pathological fractures, mechanical failure and joint destruction. Several limb salvage procedures using allografts have been carried out in our institution with one failure due to infection. Paucity of available allograft has restricted more such procedures to be carried out

  7. Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors

    International Nuclear Information System (INIS)

    Schwartz, E.; Lapidot, T.; Gozes, D.; Singer, T.S.; Reisner, Y.

    1987-01-01

    Host-vs-graft activity presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C 3 H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of 125 IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected

  8. Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

    Science.gov (United States)

    Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

    2016-04-01

    To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

  9. Adefovir nephrotoxicity in a renal allograft recipient

    Directory of Open Access Journals (Sweden)

    N George

    2015-01-01

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

  10. Freeze-dried microarterial allografts

    International Nuclear Information System (INIS)

    Raman, J.; Hargrave, J.C.

    1990-01-01

    Rehydrated freeze-dried microarterial allografts were implanted to bridge arterial defects using New Zealand White rabbits as the experimental model. Segments of artery from the rabbit ear and thigh were harvested and preserved for a minimum of 2 weeks after freeze-drying. These allografts, approximately 1 mm in diameter and ranging from 1.5 to 2.5 cm in length, were rehydrated and then implanted in low-pressure and high-pressure arterial systems. Poor patency was noted in low-pressure systems in both allografts and autografts, tested in 12 rabbits. In the high-pressure arterial systems, allografts that were freeze-dried and reconstituted failed in a group of 10 rabbits with an 8-week patency rate of 30 percent. Gamma irradiation in an effort to reduce infection and antigenicity of grafts after freeze-drying was associated with a patency rate of 10 percent at 8 weeks in this system in another group of 10 rabbits. Postoperative cyclosporin A therapy was associated with a patency rate of 22.2 percent in the high-pressure arterial system in a 9-rabbit group. Control autografts in this system in a group of 10 rabbits showed a 100 percent patency at 8 weeks. Microarterial grafts depend on perfusion pressure of the vascular bed for long-term patency. Rehydrated freeze-dried microarterial allografts do not seem to function well in lengths of 1 to 2.5 cm when implanted in a high-pressure arterial system. Freeze-dried arterial allografts are probably not antigenic

  11. Biomechanical properties of bone allografts

    International Nuclear Information System (INIS)

    Pelker, R.R.; Friedlaender, G.E.; Markham, T.C.

    1983-01-01

    The biomechanical properties of allograft bone can be altered by the methods chosen for its preservation and storage. These effects are minimal with deep-freezing or low-level radiation. Freeze-drying, however, markedly diminishes the torsional and bending strength of bone allografts but does not deleteriously affect the compressive or tensile strength. Irradiation of bone with more than 3.0 megarad or irradiation combined with freeze-drying appears to cause a significant reduction in breaking strength. These factors should be considered when choosing freeze-dried or irradiated allogeneic bone that will be subjected to significant loads following implantation

  12. In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport

    International Nuclear Information System (INIS)

    Briat, Arnaud; Slimani, Lotfi; Perret, Pascale; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine; Halimi, Serge; Demongeot, Jacques

    2007-01-01

    Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [ 123 I]6-deoxy-6-iodo-D-glucose (6DIG). We investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45 min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the heart. These coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16 ± 0.06 vs 2.28 ± 0.18 (p < 0.001) for the fructose-fed group, 0.92 ± 0.05 vs 1.62 ± 0.25 (p < 0.01) for the Zucker group and 1.34 ± 0.06 vs 2.01 ± 0.26 (p < 0.05) for the ZDF group. These results show that 6DIG could be a useful tracer to image cardiac insulin resistance. (orig.)

  13. In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport

    Energy Technology Data Exchange (ETDEWEB)

    Briat, Arnaud; Slimani, Lotfi; Perret, Pascale; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine [INSERM, E0340, Radiopharmaceutiques Biocliniques, Grenoble (France); Univ Grenoble, Grenoble (France); Halimi, Serge [Univ Grenoble, Grenoble (France); Hopital Michallon, Service de Diabetologie, CHRU Grenoble, Grenoble (France); Demongeot, Jacques [Univ Grenoble, Grenoble (France); CNRS, UMR 5525, Grenoble (France)

    2007-11-15

    Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [{sup 123}I]6-deoxy-6-iodo-D-glucose (6DIG). We investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45 min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the heart. These coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16 {+-} 0.06 vs 2.28 {+-} 0.18 (p < 0.001) for the fructose-fed group, 0.92 {+-} 0.05 vs 1.62 {+-} 0.25 (p < 0.01) for the Zucker group and 1.34 {+-} 0.06 vs 2.01 {+-} 0.26 (p < 0.05) for the ZDF group. These results show that 6DIG could be a useful tracer to image cardiac insulin resistance. (orig.)

  14. Incidence, microbiological profile of nosocomial infections, and their antibiotic resistance patterns in a high volume Cardiac Surgical Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Sahu

    2016-01-01

    Full Text Available Background: Nosocomial infections (NIs in the postoperative period not only increase morbidity and mortality, but also impose a significant economic burden on the health care infrastructure. This retrospective study was undertaken to (a evaluate the incidence, characteristics, risk factors and outcomes of NIs and (b identify common microorganisms responsible for infection and their antibiotic resistance profile in our Cardiac Surgical Intensive Care Unit (CSICU. Patients and Methods: After ethics committee approval, the CSICU records of all patients who underwent cardiovascular surgery between January 2013 and December 2014 were reviewed retrospectively. The incidence of NI, distribution of NI sites, types of microorganisms and their antibiotic resistance, length of CSICU stay, and patient-outcome were determined. Results: Three hundred and nineteen of 6864 patients (4.6% developed NI after cardiac surgery. Lower respiratory tract infections (LRTIs accounted for most of the infections (44.2% followed by surgical-site infection (SSI, 11.6%, bloodstream infection (BSI, 7.5%, urinary tract infection (UTI, 6.9% and infections from combined sources (29.8%. Acinetobacter, Klebsiella, Escherichia coli, and Staphylococcus were the most frequent pathogens isolated in patients with LRTI, BSI, UTI, and SSI, respectively. The Gram-negative bacteria isolated from different sources were found to be highly resistant to commonly used antibiotics. Conclusion: The incidence of NI and sepsis-related mortality, in our CSICU, was 4.6% and 1.9%, respectively. Lower respiratory tract was the most common site of infection and Gram-negative bacilli, the most common pathogens after cardiac surgery. Antibiotic resistance was maximum with Acinetobacter spp.

  15. Role of allografts in spinal surgery

    International Nuclear Information System (INIS)

    Aziz Nather

    1999-01-01

    With development of more tissue banks in the region and internationally, allografts are increasingly being used in orthopaedic surgery including spinal surgery. Two groups of patients will particularly benefit from the use of allografts. The first group is young children in whom iliac crest is cartilaginous and cannot provide sufficient quantity of autografts. The second is the elderly where bones from iliac crest are porotic and fatty. Allografts are used to fulfill two distinct functions in Spinal Surgery. One is to act as a buttress for anterior spinal surgery using cortical allografts. The other is to enhance fusion for posterior spinal surgery. Up to December 1997, 71 transplantations have been performed using allografts from NUH Tissue Bank. Anterior Spinal Surgery has been performed in 15 cases. The indications are mainly Trauma-Burst Fractures and Spinal Secondaries to the Spine. All cases are in thoracic and thoracolumbar region. Allografts used are deep frozen and freeze-dried cortical allografts. Femur is used for thoraco-lumbar region and humerus for upper thoracic region. Instrumentation used ranged from anterior devices (Canada, DCP, Synergy etc) to posterior devices (ISOLA). Deep frozen allografts and more recently freeze-dried allografts are preferred especially for osteoporotic spines. Cortical allografts are packed with autografts from ribs in the medullary canal. Allograft-autograft composites are always used to ensure better incorporation. Postero-lateral fusion has been performed for 56 cases. The indications include congenital and idiopathic scoliosis, degenerative stenosis, degenerative spondylolisthesis, spondylolytic spondylolisthesis, fracture-dislocation, osteoporotic burst fracture, spinal secondaries with cord compression and traumatic spondylolisthesis. Deep frozen bone allografts are used in combination with patient's own autografts from spinous processes to provide a 50% mix. Instrumentation used include Hartshill, Steffee, Isola

  16. 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

  17. Resistance in gram-negative bacilli in a cardiac intensive care unit in India: Risk factors and outcome

    Directory of Open Access Journals (Sweden)

    Pawar Mandakini

    2008-01-01

    Full Text Available The objective of this study was to compare the risk factors and outcome of patients with preexisting resistant gram-negative bacilli (GNB with those who develop sensitive GNB in the cardiac intensive care unit (ICU. Of the 3161 patients ( n = 3,161 admitted to the ICU during the study period, 130 (4.11% developed health care-associated infections (HAIs with GNB and were included in the cohort study. Pseudomonas aeruginosa (37.8% was the most common organism isolated followed by Klebsiella species (24.2%, E. coli (22.0%, Enterobacter species (6.1%, Stenotrophomonas maltophilia (5.7%, Acinetobacter species (1.3%, Serratia marcescens (0.8%, Weeksella virosa (0.4% and Burkholderia cepacia (0.4%. Univariate analysis revealed that the following variables were significantly associated with the antibiotic-resistant GNB: females ( P = 0.018, re-exploration ( P = 0.004, valve surgery ( P = 0.003, duration of central venous catheter ( P < 0.001, duration of mechanical ventilation ( P < 0.001, duration of intra-aortic balloon counter-pulsation ( P = 0.018, duration of urinary catheter ( P < 0.001, total number of antibiotic exposures prior to the development of resistance ( P < 0.001, duration of antibiotic use prior to the development of resistance ( P = 0.014, acute physiology and age chronic health evaluation score (APACHE II, receipt of anti-pseudomonal penicillins (piperacillin-tazobactam ( P = 0.002 and carbapenems ( P < 0.001. On multivariate analysis, valve surgery (adjusted OR = 2.033; 95% CI = 1.052-3.928; P = 0.035, duration of mechanical ventilation (adjusted OR = 1.265; 95% CI = 1.055-1.517; P = 0.011 and total number of antibiotic exposure prior to the development of resistance (adjusted OR = 1.381; 95% CI = 1.030-1.853; P = 0.031 were identified as independent risk factors for HAIs in resistant GNB. The mortality rate in patients with resistant GNB was significantly higher than those with sensitive GNB (13.9% vs. 1.8%; P = 0.03. HAI with

  18. History of osteochondral allograft transplantation.

    Science.gov (United States)

    Nikolaou, V S; Giannoudis, P V

    2017-07-01

    Osteochondral defects or injuries represent the most challenging entities to treat, especially when occur to young and active patients. For centuries, it has been recognized that such defects are almost impossible to treat. However, surgeons have never stopped the effort to develop reliable methods to restore articular cartilage and salvage the endangered joint function. Osteochondral allograft transplantation in human was first introduced by Eric Lexer in 1908. Since that era, several pioneers have been worked in the field of osteochondral allotransplantation, presenting and developing the basic research, the methodology and the surgical techniques. Herein we present in brief, the history and the early clinical results of osteochondral allograft transplantation in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Mucormycosis (zygomycosis) of renal allograft

    Science.gov (United States)

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

    2012-01-01

    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. PMID:26069793

  20. Renal allograft rupture: US diagnosis

    International Nuclear Information System (INIS)

    Maklad, N.F.

    1987-01-01

    The US appearances in seven pathologically and/or surgically proved cases of renal allograft rupture are presented. These include a triangular or amorphous echogenic area in the cortex and medulla in a polar location, an echogenic band or wavy, branching anechoic lines in the hyperechoic region, a subcapsular hematoma, and an extrarenal hematoma in direct continuity with the echogenic area. Duplex Doppler examination in renal allograft rupture shows marked reduction of absence of the diastolic component of the velocity waveform in the arcuate and interlobar arteries, with reduction in amplitude of the systolic wave form. Correlation of the US appearances with gross and microscopic pathologic findings indicates that the echogenic area is due to an intrarenal hematoma, while the echogenic band represents the cortical laceration with adherent blood clots. The US-duplex Doppler examination should be the primary diagnostic modality in this life-threatening condition

  1. 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.

  2. Prolongation of islet allograft survival

    International Nuclear Information System (INIS)

    Lacy, P.E.; Davie, J.M.; Finke, E.H.; Scharp, D.W.

    1979-01-01

    Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if hand-picked, clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier

  3. Upper-body progressive resistance training improves strength and household physical activity performance in women attending cardiac rehabilitation.

    Science.gov (United States)

    Coke, Lola A; Staffileno, Beth A; Braun, Lynne T; Gulanick, Meg

    2008-01-01

    The purpose of this study was to examine the impact of moderate-intensity, progressive, upper-body resistance training (RT) on muscle strength and perceived performance of household physical activities (HPA) among women in cardiac rehabilitation. The 10-week, pretest-posttest, experiment randomized women to either usual care (UC) aerobic exercise or RT. Muscle strength for 5 upper-body RT exercises (chest press, shoulder press, biceps curl, lateral row, and triceps extension) was measured using the 1-Repetition Maximum Assessment. The RT group progressively increased weight lifted using 40%, 50%, and 60% of obtained 1-Repetition Maximum Assessment at 3-week intervals. Perceived performance of HPA was measured with the Kimble Household Activities Scale. The RT group (n = 16, mean age 64 +/- 11) significantly increased muscle strength in all 5 exercises in comparison with the UC group (n = 14, mean age 65 +/- 10) (chest press, 18% vs 11%; shoulder press, 24% vs 14%; biceps curl, 21% vs 12%; lateral row, 32% vs 9%; and triceps extension, 28% vs 20%, respectively). By study end, Household Activities Scale scores significantly increased (F = 13.878, P = .001) in the RT group (8.75 +/- 3.19 vs 11.25 +/- 2.14), whereas scores in the UC group decreased (8.60 +/- 3.11 vs 6.86 +/- 4.13). Progressive upper-body RT in women shows promise as an effective tool to increase muscle strength and improve the ability to perform HPA after a cardiac event. Beginning RT early after a cardiac event in a monitored cardiac rehabilitation environment can maximize the strengthening benefit.

  4. Aerobic exercise training promotes additional cardiac benefits better than resistance exercise training in postmenopausal rats with diabetes.

    Science.gov (United States)

    Quinteiro, Hugo; Buzin, Morgana; Conti, Filipe Fernandes; Dias, Danielle da Silva; Figueroa, Diego; Llesuy, Susana; Irigoyen, Maria-Cláudia; Sanches, Iris Callado; De Angelis, Kátia

    2015-05-01

    The aim of this study was to evaluate the effects of aerobic exercise training or resistance exercise training on cardiac morphometric, functional, and oxidative stress parameters in rats with ovarian hormone deprivation and diabetes. Female Wistar rats (200-220 g) were divided into a sham-operated group (euglycemic sham-operated sedentary [ES]; n = 8) and three ovariectomized (bilateral removal of ovaries) and diabetic (streptozotocin 50 mg/kg IV) groups as follows: diabetic ovariectomized sedentary (DOS; n = 8), diabetic ovariectomized undergoing aerobic exercise training (DOTA; n = 8), and diabetic ovariectomized undergoing resistance exercise training (DOTR; n = 8). After 8 weeks of resistance (ladder) or aerobic (treadmill) exercise training, left ventricle function and morphometry were evaluated by echocardiography, whereas oxidative stress was evaluated at the left ventricle. The DOS group presented with increased left ventricle cavity in diastole and relative wall thickness (RWT), and these changes were attenuated in both DOTA and DOTR groups. Systolic and diastolic function was impaired in the DOS group compared with the ES group, and only the DOTA group was able to reverse this dysfunction. Lipoperoxidation and glutathione redox balance were improved in both trained groups compared with the DOS group. Glutathione peroxidase and superoxide dismutase were higher in the DOTA group than in the other studied groups. Correlations were observed between lipoperoxidation and left ventricle cavity in diastole (r = 0.55), between redox balance and RWT (r = 0.62), and between lipoperoxidation and RWT (r = -0.60). Aerobic exercise training and resistance exercise training promote attenuation of cardiac morphometric dysfunction associated with a reduction in oxidative stress in an experimental model of diabetes and menopause. However, only dynamic aerobic exercise training is able to attenuate systolic and diastolic dysfunction under this condition.

  5. Correlation between nuclear perfusion parameters and duplex US indices in the diagnosis of renal allograft rejection

    International Nuclear Information System (INIS)

    Kim, E.E.; Maklad, N.F.; Pjura, G.A.; Lowry, P.A.

    1986-01-01

    Fifty nuclear perfusion and duplex US studies in 30 patients who had received renal allografts were prospectively analyzed to evaluate their respective measures of blood flow as indicators of rejection. The nuclear study (Tc-99m DTPA) generated three parameters, and a real-time, pulsed Doppler sector scanner generated resistance and pulsatility indices. In nine cases with a greater than 70% resistance index and 1.4 pulsatility index on US, the US findings correlated well with changes in nuclear perfusion parameters, indication rejection. The authors conclude that the combination of decreasing nuclear perfusion parameters and positive US indices may obviate the need for biopsy in the diagnosis of allograft rejection

  6. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis.

    Science.gov (United States)

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P; De Geest, Bart

    2017-07-18

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher ( p coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold ( p coconut oil mice than in standard chow mice. Myocardial capillary density ( p coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold ( p coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower ( p coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  7. Pulse methylprednisolone therapy for impending cardiac tamponade in immunoglobulin-resistant Kawasaki disease

    NARCIS (Netherlands)

    Dahlem, P. G.; von Rosenstiel, I. A.; Lam, J.; Kuijpers, T. W.

    1999-01-01

    We describe a boy with Kawasaki disease (KD) whose clinical course was marked by a rapid improvement upon treatment with intravenous immunoglobulin (IVIG) and oral aspirin, which - within 14 days - was followed by the development of a large pericardial effusion with symptoms of impending cardiac

  8. Skin allografts in lethally irradiated animals repopulated with syngeneic hemopoietic cells

    International Nuclear Information System (INIS)

    Schwadron, R.B.

    1983-01-01

    Total body irradiation and repopulation with syngeneic hemopoietic cells can be used to induce tolerance to major histocompatibility complex (MHC) mismatched heart and kidney grafts in rats and mice. However, this protocol does not work for MHC mismatched skin grafts in rats or mice. Furthermore, LEW rats that accept WF cardiac allografts after irradiation and repopulation reject subsequent WF skin grafts. Treatment of skin allograft donors with methotrexate prior to grafting onto irradiated and reconstituted mice resulted in doubling of the mean survival time. Analysis of which antigens provoked skin graft rejection by irradiation and reconstituted animals revealed the importance of I region antigens. Cardiac allograft acceptance by irradiated and reconstituted animals is mediated by suppressor cells found in the spleen. Adoptively tolerant LEW rats accepted WF skin grafts in 50% of grafted animals. Analysis of this phenomenon revealed that the adoptive transfer procedure itself was important in achieving skin allograft acceptance by these animals. In general, it seems that the lack of ability of irradiated and reconstituted animals to accept fully MHC disparate skin grafts results from the inability of these animals to suppress lymph node effector cells against I region antigen seen on highly immunogenic allogeneic Langerhans cells in the skin

  9. Mandibular reconstruction using bone allografts

    International Nuclear Information System (INIS)

    Chang Joon Yim

    1999-01-01

    Further understanding of bone healing mechanisms, bone physiology and bone biology, transplantation immunology, and development of Tissue Banking procedures has enabled oral and maxillofacial surgeons to reconstruct even the most difficult bony defects successfully with the preserved allogeneic bone implant. Although it had been known that bone allografts were clinically effective, its application has not been widespread until the reports of Inclan (I 942), Hyatt and Butler (I 950), and Wilson (I 95 1). Tissue Banking provides the surgeon with a readily available, relatively inexpensive, and relatively safe selection of allogeneic bone for clinical use. Now autogenous bone and allogeneic bone implants present a wide variety of surgical options to surgeons, whether used separately or in combination. The surgeons are able to make judicious and fruitful choices, only with a thorough knowledge of the above-mentioned biological principles and skillful techniques. Many kinds of bone grafting techniques have been tried for reconstructing defective osseous tissues of the oral and maxillofacial region, though they have varying degrees of success. The osseous defects which require grafting include those of various size, shape, position, or amount. Unlike autogenous grafts, whose function is to provide osteogenic cells, allografts are purely passive, offering only a matrix for the inductive phase of bone healing. The condition of the recipient bed is of primary importance, because the host must produce all of the essential elements for the bone allograft to become incorporated. Depending on the processing methods of the allogeneic bone, the bone graft materials have different qualities, different healing potentials and different indications. Proper selection of grafts and surgical techniques requires an understanding of graft immunology and the mechanisms of graft healing. The surgeons should know about the biological principles to raise the clinical success rate

  10. The Higher the Insulin Resistance the Lower the Cardiac Output in Men with Type 1 Diabetes During the Maximal Exercise Test.

    Science.gov (United States)

    Niedzwiecki, Pawel; Naskret, Dariusz; Pilacinski, Stanislaw; Pempera, Maciej; Uruska, Aleksandra; Adamska, Anna; Zozulinska-Ziolkiewicz, Dorota

    2017-06-01

    The aim of this study was to assess the hemodynamic parameters analyzed in bioimpedance cardiography during maximal exercise in patients with type 1 diabetes differing in insulin resistance. The study group consisted of 40 men with type 1 diabetes. Tissue sensitivity to insulin was assessed on the basis of the glucose disposal rate (GDR) analyzed during hyperinsulinemic-euglycemic clamp. Patients were divided into groups with GDR insulin sensitivity) and GDR ≥4.5 mg/kg/min (G2 group-higher insulin sensitivity). During the exercise test, the heart rate, systolic volume, cardiac output, cardiac index were measured by the impedance meter (PhysioFlow). Compared with the G2 group, the G1 group had a lower cardiac output (CO): during exercise 8.6 (IQR 7.7-10.0) versus 12.8 (IQR 10.8-13.7) L/min; P insulin resistance is associated with cardiac hemodynamic parameters assessed during and after exercise. The higher the insulin resistance the lower the cardiac output during maximal exercise in men with type 1 diabetes.

  11. MCP-1 Levels are Associated with Cardiac Remodeling but not with Resistant Hypertension.

    Science.gov (United States)

    Ritter, Alessandra Mileni Versuti; Faria, Ana Paula Cabral de; Sabbatini, Andrea; Corrêa, Nathalia Batista; Brunelli, Veridiana; Modolo, Rodrigo; Moreno, Heitor

    2017-04-01

    Hypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood. This study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects. We enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography. We found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population. Since MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata. A hipertensão arterial é um processo crônico de baixo grau inflamatório, associado com liberação de citocinas e desenvolvimento de lesão em órgãos-alvo. A desregulação dos níveis de proteína quimiotática de monócitos-1 (MCP-1) tem sido associada com elevação da press

  12. 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.

  13. Radiation sterilization of skin allograft

    International Nuclear Information System (INIS)

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

    2009-01-01

    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.

  14. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

    Directory of Open Access Journals (Sweden)

    Ilayaraja Muthuramu

    2017-07-01

    Full Text Available Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05 in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64 during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p < 0.01 higher in coconut oil mice than in standard chow mice. Myocardial capillary density (p < 0.001 was decreased, interstitial fibrosis was 1.88-fold (p < 0.001 higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p < 0.001 higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p < 0.05 in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  15. Successful treatment of verruca vulgaris with Thuja occidentalis in a renal allograft recipient

    Directory of Open Access Journals (Sweden)

    R Joseph

    2013-01-01

    Full Text Available Human papillomavirus-driven verruca vulgaris infection is common in solid organ transplant recipients and increases the risk for squamous cell carcinoma. The available treatment modalities have limited response. We report a renal allograft recipient who presented with multiple warts not responding to cryotherapy and radiosurgery with one turning malignant, needing amputation of the finger. An extract from Thuja occidentalis (White cedar tree cured the resistant warts on the other fingers, leaving only superficial scars and without affecting allograft function. We have reviewed the pharmacological and clinical properties of T. occidentalis.

  16. [Attitude towards organ and tissue donation in Europe : Prerequisite for osteochondral allograft treatment].

    Science.gov (United States)

    Schmidt, S; Schulte, A; Schwarz, S; Hofmann, N; Tietz, S; Boergel, M; Sixt, S U

    2017-11-01

    The biggest obstacle to overcome for routine treatment of various pathologies with fresh osteochondral allograft is the availability of tissue for transplantation. Large fresh osteochondral allografts are usually harvested from organ donors, but in contrast to organs, tissues can be procured after cardiac arrest. Medical staff as well the general public are much less aware of the possibilities and requirements of tissue donation compared to organ donation. This review aims to highlight the current situation of organ and tissue donation in Europe and to raise this much needed awareness. For this research, PubMed database was scanned using the terms "tissue/organ donation", "bone donation/transplantation", "cartilage transplantation/allografts" and "osteochrondral allografts". Relatives of potential donors are often not approached because physicians and nurses do not feel sufficiently prepared for this task and, thus, are reluctant to address this topic. Different options could alleviate the pressure medical staff is feeling. Furthermore, there are different factors influencing consent that can be addressed to increase donation rates. Currently, a lot of potential concerning musculoskeletal tissue grafts remains unused. Most importantly, families should be encouraged to speak about their potenzial will to donate and educational programs should be established to increase trust in organ and tissue donation and the allocation system and to increase knowledge about the importance of transplantation medicine. But joined efforts of different parts of the medical systems and different organizations involved in tissue transplantation should improve the situation for patients waiting for much needed transplants.

  17. Angiotensin receptor blockade improves cardiac mitochondrial activity in response to an acute glucose load in obese insulin resistant rats

    Directory of Open Access Journals (Sweden)

    Max Thorwald

    2018-04-01

    Full Text Available Hyperglycemia increases the risk of oxidant overproduction in the heart through activation of a multitude of pathways. Oxidation of mitochondrial enzymes may impair their function resulting in accumulation of intermediates and reverse electron transfer, contributing to mitochondrial dysfunction. Furthermore, the renin-angiotensin system (RAS becomes inappropriately activated during metabolic syndrome, increasing oxidant production. To combat excess oxidant production, the transcription factor, nuclear factor erythriod-2- related factor 2 (Nrf2, induces expression of many antioxidant genes. We hypothesized that angiotensin II receptor type 1 (AT1 blockade improves mitochondrial function in response to an acute glucose load via upregulation of Nrf2. To address this hypothesis, an oral glucose challenge was performed in three groups prior to dissection (n = 5–8 animals/group/time point of adult male rats: 1 Long Evans Tokushima Otsuka (LETO; lean strain-control, 2 insulin resistant, obese Otsuka Long Evans Tokushima Fatty (OLETF, and 3 OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 6 weeks. Hearts were collected at T0, T60, and T120 minutes post-glucose infusion. ARB increased Nrf2 binding 32% compared to OLETF at T60. Total superoxide dismutase (SOD and catalase (CAT activities were increased 45% and 66% respectively in ARB treated animals compared to OLETF. Mitochondrial enzyme activities of aconitase, complex I, and complex II increased by 135%, 33% and 66%, respectively in ARB compared to OLETF. These data demonstrate the protective effects of AT1 blockade on mitochondrial function during the manifestation of insulin resistance suggesting that the inappropriate activation of AT1 during insulin resistance may impair Nrf2 translocation and subsequent antioxidant activities and mitochondrial function. Keywords: Angiotensin II, Mitochondria, Cardiac, Antioxidant enzymes, TCA cycle

  18. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    International Nuclear Information System (INIS)

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A.

    1990-01-01

    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms

  19. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    Energy Technology Data Exchange (ETDEWEB)

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A. (Columbia Univ. College of Physicians and Surgeons, New York, NY (USA))

    1990-05-01

    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

  20. Cardiac autonomic regulation in response to a mixed meal is impaired in obese children and adolescents: the role played by insulin resistance.

    Science.gov (United States)

    Cozzolino, Domenico; Esposito, Katherine; Palmiero, Giuseppe; De Bellis, Annamaria; Furlan, Raffaello; Perrotta, Silverio; Perrone, Laura; Torella, Daniele; Miraglia del Giudice, Emanuele

    2014-09-01

    Obesity in children/adolescents has been associated with subtle cardiac abnormalities, including myocardial dysfunction and cardiac autonomic dysregulation at rest, both likely responsible for a higher mortality in adulthood. Food intake induces remarkable adjustments of cardiovascular autonomic activity in healthy subjects. The objective of the study was to evaluate in obese children/adolescents meal-induced cardiac autonomic response and the role played by insulin resistance. Sixty-eight obese and 30 matched normal-weight children/adolescents underwent blood sampling and cardiovascular autonomic analysis while recumbent and 20 minutes after a mixed meal ingestion. Spectrum analysis of the R-R interval and systolic blood pressure (SBP) variability provided the indices of sympathetic [low frequency (LFRR)] and vagal [high frequency (HFRR)] modulation of the sinoatrial node and the low frequency component of SBP. The homeostasis model assessment of insulin resistance served to separate insulin resistant (n = 35) from non insulin resistant (n = 33) obese children/adolescents. At baseline, C-reactive protein, the LFRR to HFRR ratio, SBP, and low frequency oscillatory component of SBP variability in obese children/adolescents were significantly (P meal-induced increase in the LFRR to HFRR ratio was significantly less than in controls and exaggeratedly scanty (or opposite) among insulin resistant subjects. The homeostasis model assessment of insulin resistance index strongly and inversely correlated (r = -0.871; P meal-induced changes in the LFRR to HFRR ratio among obese subjects. Autonomic modulation of the heart was impaired after eating in obese children/adolescents. This abnormality was exaggerated among insulin resistant subjects and strongly correlated with the degree of insulin resistance.

  1. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

    Science.gov (United States)

    Young, Lawrence H; Viscoli, Catherine M; Curtis, Jeptha P; Inzucchi, Silvio E; Schwartz, Gregory G; Lovejoy, Anne M; Furie, Karen L; Gorman, Mark J; Conwit, Robin; Abbott, J Dawn; Jacoby, Daniel L; Kolansky, Daniel M; Pfau, Steven E; Ling, Frederick S; Kernan, Walter N

    2017-05-16

    Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P =0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P =0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P =0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P =0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus

  2. Magnetic resonance imaging of massive bone allografts with histologic correlation

    International Nuclear Information System (INIS)

    Hoeffner, E.G.; Soulen, R.L.; Ryan, J.R.; Qureshi, F.

    1996-01-01

    The objective of this study was to better understand the MRI appearance of massive bone allografts. The MRI findings of three massive bone allografts imaged in vivo were correlated with the histologic findings following removal of the allografts. A fourth allograft, never implanted, was imaged and evaluated histologically. Allografts were placed for the treatment of primary or recurrent osteosarcoma. The in-vivo allografts have a heterogeneous appearance on MRI which we attribute to the revascularization process. Fibrovascular connective tissue grows into the graft in a patchy, focal fashion, down the medullary canal from the graft-host junction and adjacent to the periosteum. The marrow spaces are initially devoid of normal cellular elements and occupied by fat and gelatinous material. This normal postoperative appearance of massive bone allografts must not be interpreted as recurrent neoplasm or infection in the allograft. Recognition of these complications rests on features outside the marrow. (orig./MG)

  3. Aortic allografts in treatment of aortic valve and ascending aorta prosthetic endocarditis

    Directory of Open Access Journals (Sweden)

    S.V. Spiridonov

    2017-03-01

    Full Text Available The aim – to assess short- and long-term results of aortic root replacement using aortic allografts in patients with prosthetic endocarditis. Materials and methods. Since February 2009 until June 2016 aortic valve and ascending aorta replacement using aortic allografts was performed in 26 patients with prosthetic endocarditis. In 50 % of cases at initial operation aortic valve replacement was performed, in another 50 % of cases – aortic valve and ascending aorta replacement. Echocardiography was performed 10 days, 3, 6 and 12 months, 2, 3 and 5 years after surgery. Analysis of long-term results included all cases of deaths, prosthesis-related complications and recurrence of endocarditis. Results. 30-day mortality was 23.1 %. Extracorporeal membranous oxygenation (ECMO was used only in 5 patients (19.2 %. Four patients were weaned from ECMO. We did not observe any allograft-related complications. During follow-up period there were no cases of reoperation due to structural allograft failure. Relapse of infection occurred in 1 patient (3.8 % four years after the operation and led to lethal outcome. Conclusion. Reoperations using allografts are an effective surgical treatment of prosthetic endocarditis. In majority of cases prosthetic endocarditis was caused by gram-positive cocci (Staphylococcus. In 84.6 % of cases it was associated with destruction of paravalvular structures and abscesses formation. Heart failure was a causative factor of different complications in these patients, which required ECMO in 19.2 % of patients. In 80 % of cases patients were weaned from ECMO. Allografts using for the treatment of prosthetic endocarditis is associated with high resistance to infection and with a significant rate of freedom from recurrence of endocarditis within 3 years after surgery.

  4. Allograft materials in phalloplasty: a comparative analysis.

    Science.gov (United States)

    Solomon, Mark P; Komlo, Caroline; Defrain, Molly

    2013-09-01

    Allograft use has increased recently with the rising use of allograft materials in breast surgery. There are few data that compare the performance of the various allograft materials in this application, despite marketing efforts by the manufacturers to present one allograft material as superior to another. Phalloplasty is a procedure that uses allografts for penis girth augmentation. Preparation of these grafts differs with each manufacturer. We report our experience with 3 different types of allografts for this procedure. This allows for the comparison of these materials in their performance with a single model. Forty-seven patients who underwent penis girth enhancement with allograft material were reviewed. All patients underwent circumferential grafting to the shaft of the penis at the level of Buck's fascia. Graft materials included AlloDerm (n = 9), Belladerm (n = 20), and Repriza (n = 21). Charts were reviewed for material type, presence and type of infection, wound exposure, and graft loss with attention to the type of allograft material that was used. Follow-up ranged from 1 to 120 months with an average of 11.25 months. Infection, defined as an open wound with graft exposure, occurred in 20 (42%) of 47 patients. Of these, graft exposure only occurred in 17 (36%) patients, whereas 3 (6%) patients sustained total graft loss. Graft exposure or loss occurred in 3 patients who had AlloDerm, 9 patients with Belladerm, and 8 patients with Repriza. No patients with AlloDerm sustained graft loss, whereas 2 patients with Belladerm and 1 patient with Repriza sustained graft loss. There were no statistical differences among these graft types with regard to infection or graft loss. Three different brands of allograft material were used in 1 surgical procedure and followed up for their performance with regard to exposure and infection. In this model, there is no difference in the rate of infection in these materials despite their different methods of preparation

  5. Application of radiation sterilization to bone allografts

    International Nuclear Information System (INIS)

    Li Youchen; Li Baoxing; Sun Shiquan

    2003-01-01

    With prominent features of high penetration, no temperature increases, no harm residues and easy dose control, radiation sterilization technology is widely used in the sterilization of bone allografts. During the radiation sterilization of bone allografts, the irradiation dose should be optimized to ensure sterilization of grafts and preservation of biological properties of bone. The immunogenicity of allografts is decreased by irradiation. IAEA devoted great efforts to generalization of the radiation sterilization of tissue allografts in developing countries since 1986. Tissue Bank of China Institute for Radiation Protection (CIRP) was initially established in 1988 with the support of IAEA, afterwards restructured into Shanxi Provincial Tissue Bank (SPTB). The SPTB, as the first manufacturer of the irradiated bone allografts in the country, was granted production license by the State Food and Drug Administration of China. The SPTB sponsored IAEA/RCA Training Courses, National Symposium on Bone Grafting, and National Training Course on Bone Banking. Technique of radiation sterilization for bone grafts has become popularized in China after these activities. (authors)

  6. Radionuclide surveillance of the allografted pancreas

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  7. Antimyosin monoclonal antibodies for early detection of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Schuetz, A.; Fritsch, S.; Kemkes, B.M.; Kugler, C.; Angermann, C.; Spes, C.; Anthuber, M.; Weiler, A.; Wenke, K.; Gokel, J.M.

    1990-01-01

    Sixty-eight indium 111-labeled antimyosin Fab-DTPA imaging studies (0.5 mg intravenously with a radioactivity of 65 to 75 MBq) were executed on 37 of 116 patients undergoing heart transplantation to assess diagnostic accuracy and clinical utility. As controls, 21 patients with cardiomyopathy (n = 8), unstable angina (n = 9), and myocardial infarction (n = 4) were selected. After 48 hours, single photon emission computed tomographic images were evaluated visually, and heart/lung ratios were measured, using the region of interest technique. They were compared with echocardiographic and endomyocardial biopsy results. In 40 studies a heart/lung ratio less than or equal to 1.6 corresponded to a negative biopsy result in 98% (40/41). Echocardiography enabled correct identification of 95% of the patients with normal biopsy findings. In 91% (22/24) a positive biopsy finding correlated with a heart/lung ratio greater than 1.6 including 20 mild rejections, but in only 64%, with an increase in wall thickness and/or decrease of fractional diameter shortening seen on echocardiogram. In addition, the various stages of rejection episodes determined the amount of the heart-lung ratio. There was a significant relationship between the histologic findings and the antimyosin uptake. In 13 patients a second investigation was performed after rejection therapy. All patients had a negative biopsy result, and the heart/lung ratio decreased to normal ranges (less than or equal to 1.6). Five antimyosin antibody studies were excluded, as in these cases, negative uptake results were found during rejection therapy with high-dose steroids. The overall sensitivity was calculated at 93% and the specificity at 98%

  8. Combined osteochondral allograft and meniscal allograft transplantation: a survivorship analysis.

    Science.gov (United States)

    Getgood, Alan; Gelber, Jonathon; Gortz, Simon; De Young, Alison; Bugbee, William

    2015-04-01

    The efficacy of meniscal allograft transplantation (MAT) and osteochondral allografting (OCA) as individual treatment modalities for select applications is well established. MAT and OCA are considered symbiotic procedures due to a complementary spectrum of indications and reciprocal contraindications. However, few outcomes of concomitant MAT and OCA have been reported. This study is a retrospective review of patients who received simultaneous MAT and OCA between 1983 and 2011. Forty-eight (twenty-nine male: nineteen female) patients with a median age of 35.8 years (15-66) received combined MAT and OCA procedures between 1983 and 2011. Forty-three patients had received previous surgery with a median of 3 procedures (1-11 procedures). The underlying diagnosis was trauma (tibial plateau fracture) in 33 % with osteoarthritis predominating in 54.2 % of cases. Thirty-one patients received a lateral meniscus, 16 received a medial meniscus and one patient received bilateral MAT. The median number of OCAs was two per patient (1-5 grafts), with a median graft area of 15 cm(2) (0.7-41 cm(2)). There were 21 unipolar, 24 bipolar (tibiofemoral) and three multifocal lesions. Thirty-six MATs constituted a compound tibial plateau OCA with native meniscus attached. At follow-up, failure was defined as any procedure resulting in removal or revision of one or more of the grafts. Patients completed the modified Merle d'Aubigné and Postel (18-point) scale, Knee Society Function (KS-F) score, and subjective International Knee Documentation Committee (IKDC) scores. Patient satisfaction was also captured. Twenty-six of 48 patients (54.2 %) required reoperation, but only 11 patients (22.9 %) were noted to have failed (10 MAT and 11 OCA). The mean time to failure was 3.2 years (95 % CI 1.5-4.9 years) and 2.7 years (95 % CI 1.3-4.2 years) for MAT and OCA, respectively. The 5-year survivorship was 78 and 73 % for MAT and OCA respectively, and 69 and 68 % at 10 years. Six of

  9. Factors associated with methicillin-resistant coagulase-negative staphylococci as causing organisms in deep sternal wound infections after cardiac surgery

    Directory of Open Access Journals (Sweden)

    R. Sommerstein

    2015-07-01

    Full Text Available Established preoperative antibiotic prophylaxis in cardiac surgery is ineffective against methicillin-resistant coagulase-negative staphylococci (CoNS. This case–control study aimed to determine factors predicting deep sternal wound infections due to methicillin-resistant CoNS. All cardiac surgery patients undergoing sternotomy between June 2009 and March 2013 prospectively documented in a Swiss tertiary care center were included. Among 1999 patients, 82 (4.1% developed deep sternal wound infection. CoNS were causal in 36 (44% patients, with 25/36 (69% being methicillin resistant. Early reintervention for noninfectious causes (odds ratio (OR 4.3; 95% confidence interval (CI 1.9–9.5 was associated with methicillin-resistant CoNS deep sternal wound infection. Among CoNS deep sternal wound infection, perioperative antimicrobial therapy (p 0.002, early reintervention for noninfectious causes (OR 7.9; 95% CI 0.9–71.1 and time between surgery and diagnosis of infection over 21 days (OR 10.8; 95% CI 1.2–97.8 were associated with methicillin resistance. These findings may help to better tailor preoperative antimicrobial prophylaxis.

  10. A ten years experience with allograft implantation

    International Nuclear Information System (INIS)

    Thanya Subhadrabandha; Sommart Keorochana; Yongyudh Vajaradul

    1999-01-01

    Since 1986 the Department of Orthopaedics, Ramathibodi Hospital has performed 30 resections and fresh frozen allograft implantations for the management of tumourous bone conditions. All allografts were provided by Bangkok Biomaterial Center, Siriraj Hospital. Following resection of the tumor, the selected part was implanted and held with plates and screws, intramedullary rods or prostheses and the patients were observed closely for alterations suggestive of rejection, relationship of complications to outcome, functional status of the part and presence of recurrences or metastases. Thirty patients were followed up for two or more years, the graft performed acceptably (excellent or good function result) in 70%. The results were better when the allografts were used in upper extremities or combined with prostheses. Local recurrence and severe infection were the major factors in determining outcome

  11. Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension

    NARCIS (Netherlands)

    van Brussel, Peter M.; Eeftinck Schattenkerk, Daan W.; Dobrowolski, Linn C.; de Winter, Robbert J.; Reekers, Jim A.; Verberne, Hein J.; Vogt, Liffert; van den Born, Bert-Jan H.

    2016-01-01

    Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity

  12. 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...... concentrations and eGFR 4 weeks after transplantation (Spearman r = -0.33; Prelative risk, 4.3; P

  13. Treatment with low-dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats.

    Science.gov (United States)

    Louis, Xavier L; Thandapilly, Sijo J; MohanKumar, Suresh K; Yu, Liping; Taylor, Carla G; Zahradka, Peter; Netticadan, Thomas

    2012-09-01

    We hypothesized that a low-dose resveratrol will reverse cardiovascular abnormalities in rats fed a high-fat (HF) diet. Obese prone (OP) and obese resistant (OR) rats were fed an HF diet for 17 weeks; Sprague-Dawley rats fed laboratory chow served as control animals. During the last 5 weeks of study, treatment group received resveratrol daily by oral gavage at a dosage of 2.5 mg/kg body weight. Assessments included echocardiography, blood pressure, adiposity, glycemia, insulinemia, lipidemia, and inflammatory and oxidative stress markers. Body weight and adiposity were significantly higher in OP rats when compared to OR rats. Echocardiographic measurements showed prolonged isovolumic relaxation time in HF-fed OP and OR rats. Treatment with resveratrol significantly improved diastolic function in OP but not in OR rats without affecting adiposity. OP and OR rats had increased blood pressure which remained unchanged with treatment. OP rats had elevated fasting serum glucose and insulin, whereas OR rats had increased serum glucose and normal insulin concentrations. Resveratrol treatment significantly reduced serum glucose while increasing serum insulin in both OP and OR rats. Inflammatory and oxidative stress markers, serum triglycerides and low-density lipoprotein were higher in OP rats, which were significantly reduced with treatment. In conclusion, HF induced cardiac dysfunction in both OP and OR rats. Treatment reversed abnormalities in diastolic heart function associated with HF feeding in OP rats, but not in OR rats. The beneficial effects of resveratrol may be mediated through regression of hyperglycemia, oxidative stress and inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    ... HIV virus in freeze-dried bone allografts. Pract Periodontics Aesthet Dent 1995;7:13–22. Mellonig JT, ... source: Division of Oral Health , National Center for Chronic Disease Prevention and Health Promotion Follow CDC Email ...

  15. Orthotopic Transplantation of Achilles Tendon Allograft in Rats

    Science.gov (United States)

    Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

    2018-01-01

    The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

  16. Bone allograft banking in South Australia.

    Science.gov (United States)

    Campbell, D G; Oakeshott, R D

    1995-12-01

    The South Australian Bone Bank had expanded to meet an increased demand for allograft bone. During a 5 year period from 1988 to 1992, 2361 allografts were harvested from 2146 living donors and 30 cadaveric donors. The allografts were screened by contemporary banking techniques which include a social history, donor serum tests for HIV-1, HIV-2, hepatitis B and C, syphilis serology, graft microbiology and histology. Grafts were irradiated with 25 kGy. The majority of grafts were used for arthroplasty or spinal surgery and 99 were used for tumour reconstruction. Of the donated grafts 336 were rejected by the bank. One donor was HIV-positive and two had false positive screens. There were seven donors with positive serology for hepatitis B, eight for hepatitis C and nine for syphilis. Twenty-seven grafts had positive cultures. Bone transplantation is the most frequent non-haematogenous allograft in South Australia and probably nationally. The low incidence of infectious viral disease in the donor population combined with an aggressive discard policy has ensured relative safety of the grafts. The frequency of graft rejection was similar to other bone banks but the incidence of HIV was lower.

  17. Meniscal Allograft Transplantation: State of the Art.

    Science.gov (United States)

    Trentacosta, Natasha; Graham, William C; Gersoff, Wayne K

    2016-06-01

    Meniscal allograft transplantation has evolved over the years to provide a state-of-the-art technique for the sports medicine surgeon to utilize in preserving contact mechanics and function of the knee in irreparable meniscal pathology. However, this procedure continues to spark considerable debate on proper tissue processing techniques, acceptable indications, methods of implantation, and potential long-term outcomes.

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

    International Nuclear Information System (INIS)

    Boyd, A.D.; Spencer, F.C.; Hirose, H.; Engelman, R.M.; Cannon, F.D.; Ferrebee, J.W.; Rapaport, F.T.

    1975-01-01

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

  19. 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

  20. Characterization of skin allograft use in thermal injury.

    Science.gov (United States)

    Fletcher, John L; Caterson, E J; Hale, Robert G; Cancio, Leopoldo C; Renz, Evan M; Chan, Rodney K

    2013-01-01

    This study provides objective data on the practice of allograft usage in severely burned patients. Furthermore, gaps in our knowledge are identified, and areas for further research are delineated. Using an institutional review board-approved protocol, active duty military patients injured while deployed in support of overseas contingency operations and treated at our burn center between March 2003 and December 2010 were identified. Their electronic medical records were reviewed for allograft use, TBSA burned, injury severity score, anatomic distribution of burns, operative burden, length of stay, transfusions, and outcome. Among 844 patients, 112 (13.3%) received allograft and 732 (86.7%) did not. The amount of allograft used per patient varied and was not normally distributed (median, 23.5; interquartile range, 69.5). Patients received allograft skin an average of 12.75 times during their admission. Allografted patients sustained severe burns (μ, 53.8% TBSA); most were transfused (71.2%) and grafted frequently, averaging every 7.45 days. Most commonly, allograft was placed on the extremities (66.5%) followed by the trunk (44.2%); however, the vast majority of allografted patients also had concomitant burns of the head (91.1%) and hands (87.5%). All-cause mortality among the allografted patients was 19.1%. In conclusion, allograft is commonly used in the surgical treatment of severe burns. Although there are no anatomic limitations to allograft placement, there are distinct patterns of use. Given the role of allograft in the acute management of large burns, there is need for further investigation of its effect on mortality, morbidity, and antigenicity.

  1. Mechanisms of allograft rejection of corneal endothelium

    International Nuclear Information System (INIS)

    Tagawa, Y.; Silverstein, A.M.; Prendergast, R.A.

    1982-01-01

    The local intraocular graft-vs.-host (GVH) reaction, involving the destruction of the corneal endothelial cells of the rabbit host by sensitized donor lymphoid cells, has been used to study the mechanism of corneal allograft rejection. Pretreatment of donor cells with a specific mouse monoclonal hybridoma anti-T cell antibody and complement suppresses the destructive reaction, suggesting that a cellular-immune mechanism is primarily involved. Pretreatment of donor cells with mitomycin-C completely abolishes the local GVH reaction, indicating that the effector lymphocytes must undergo mitosis within the eye before they can engage in target cell destruction. Finally, studies of the local GVH reaction in irradiated leukopenic recipients or in preinflamed rabbit eyes suggest that host leukocytes may contribute nonspecifically to enhance the destructive process. These studies show that the local ocular GVH reaction may provide a useful model for the study of the mechanisms involved in the rejection of corneal allografts

  2. Papillary renal cell carcinoma in allograft kidney

    International Nuclear Information System (INIS)

    Roy, Catherine; El Ghali, Sofiane; Buy, Xavier; Gangi, Afshin; Lindner, Veronique

    2005-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. Its occurrence in allograft transplanted kidney has not been debated in the literature. We report two pathologically proven cases and discuss the clinical hypothesis for such neoplasms and the aspect on MR images. The paramagnetic effect of the iron associated with an absence of signal coming from calcifications is a plausible explanation for this unusual hypointense appearance on T2-weighted sequence. (orig.)

  3. Should fractures in massive intercalary bone allografts of the lower limb be treated with ORIF or with a new allograft?

    Science.gov (United States)

    Aponte-Tinao, Luis A; Ayerza, Miguel A; Muscolo, D Luis; Farfalli, Germán L

    2015-03-01

    Massive bone allografts have been used for limb salvage of bone tumor resections as an alternative to endoprostheses, although they have different outcomes and risks. There is no general consensus about when to use these alternatives, but when it is possible to save the native joints after the resection of a long bone tumor, intercalary allografts offer some advantages despite complications, such as fracture. The management and outcomes of this complication deserve more study. The purposes of this study were to (1) analyze the fracture frequency in a group of patients treated with massive intercalary bone allografts of the femur and tibia; (2) compare the results of allografts treated with open reduction and internal fixation (ORIF) with those treated with resection and repeat allograft reconstruction; and (3) determine the likelihood that treatment of a fracture resulted in a healed intercalary reconstruction. We reviewed patients treated with intercalary bone allografts between 1991 and 2011. During this period, patients were generally treated with intercalary allografts when after tumor resection at least 1 cm of residual epiphysis remained to allow fixation of the osteotomy junction. To obtain a homogeneous group of patients, we excluded allograft-prosthesis composites and osteoarticular and hemicylindrical intercalary allografts from this study. We analyzed the fracture rate of 135 patients reconstructed with segmental intercalary bone allografts of the lower extremities (98 femurs and 37 tibias). In patients whose grafts fractured were treated either by internal fixation or a second allograft, ORIF generally was attempted but after early failures in femur fractures, these fractures were treated with a second allograft. Using a chart review, we ascertained the frequency of osseous union, complications, and reoperations after the treatment of fractured intercalary allografts. Followup was at a mean of 101 months (range, 24-260 months); of the original 135

  4. Extensive tumor reconstruction with massive allograft

    International Nuclear Information System (INIS)

    Zulmi Wan

    1999-01-01

    Massive deep-frozen bone allografts were implanted in four patients after wide tumor resection. Two cases were solitary proximal femur metastases, secondary to Thyroid cancer and breast cancer respectively; while the other two cases were primary in nature i.e. Chondrosarcoma proximal humerus and Osteosarcoma proximal femur. All were treated with a cemented alloprosthesis except in the upper limb where shoulder fusion was performed. Augmentation of these techniques were done with a segment 1 free vascularised fibular composite graft to the proximal femur of breast secondaries and proximal humerus Chondrosarcoma. Coverage of the wound of the latter was also contributed by lattisimus dorsi flap. The present investigations demonstrated the massive bone allografts were intimately anchored by host bone and there had been no evidence of aseptic loosening at the graft-cement interface. This study showed that with good effective tumor control, reconstructive surgery with massive allografts represented a good alternative to prosthetic implants in tumors of the limbs. No infection was seen in all four cases

  5. Renal denervation in a patient with Alport syndrome and rejected renal allograft

    Directory of Open Access Journals (Sweden)

    Narayana Raju

    2015-12-01

    Full Text Available Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation.

  6. 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

  7. Irradiated strut allografts for reconstructing tumour defects: how effective?

    International Nuclear Information System (INIS)

    Astrid Lobo Gajiwala; Manish Agarwal; Ajay Puri; Cynthia D Lima

    2008-01-01

    Full text: Allografts are biological options for reconstructing large bone defects. We report our experience with 87 irradiated (25 kGy of gamma radiation) strut allografts used in various defects following tumour surgery. Reconstruction in 35 full segment defects involved 22 full segment allografts used alone, 4 allograft prosthetic composites (APC) and 9 allografts combined with a vascularized fibula. Twelve partial segment defects were reconstructed with allograft struts (including 2 APC). Full segment allograft struts (mainly fibulae) were used in 40 contained post-curettage defects. The cases were studied for time to incorporation and complications. The follow-up ranged from 12 to 72 months. Of the 26 full segment defects where allograft alone or APC was used, 2 were lost to follow-up, 5 died before incorporation and 3 grafts were removed (2 infection and 1 local recurrence). Six united primarily at 2-4 years. Seven patients with non union were autografted at both junctions resulting in 6 unions. One patient had early plate breakage and refused further treatment. One allograft fractured after union after autografting. Two of 4 APC also united. In contrast, the 9 allograft-vascularized fibula combinations showed unambiguous incorporation between 5-9 months with only one junction requiring bone grafting. Of the 12 partial segment struts, barring one removed for infection, 11 have completely incorporated. Thirty one out of 40 struts placed within contained post curettage defects have incorporated (2 removed for infection and seven lost to follow-up). There were total 6 infections (7%) 4 of which occurred 1-2 years after surgery. Irradiated full segment struts alone incorporate poorly and are best used combined with a live fibula. Irradiated full and partial segment allografts used inside contained defects give consistently good results. Frozen grafts seem to incorporate faster and better than lyophilised grafts. (Author)

  8. 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.

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

    International Nuclear Information System (INIS)

    Olmos-Zúãiga, J.R.; Jasso-Victoria, R.; Díaz-Martínez, N.E.; Gaxiola-Gaxiola, M.O.; Sotres-Vega, A.; Heras-Romero, Y.; Baltazares-Lipp, M.; Baltazares-Lipp, M.E.; Santillán-Doherty, P.; Hernández-Jiménez, C.

    2015-01-01

    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

  10. 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.

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

    Science.gov (United States)

    Olmos-Zúñiga, J R; Jasso-Victoria, R; Díaz-Martínez, N E; Gaxiola-Gaxiola, M O; Sotres-Vega, A; Heras-Romero, Y; Baltazares-Lipp, M; Baltazares-Lipp, M E; Santillán-Doherty, P; Hernández-Jiménez, C

    2016-02-01

    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.

  12. Selective lymphoid irradiation. V. Synergism with pretransplant thymectomy or thymic irradiation in cardiac transplantation in rats

    International Nuclear Information System (INIS)

    Iga, C.; Fawwaz, R.; Nowygrod, R.; Reemtsma, K.; Hardy, M.A.

    1985-01-01

    Selective lymphoid irradiation (SLI) using palladium-109-hematoporphyrin (Pd-H), given four days prior to transplantation, combined with two doses of antilymphocyte globulin (ALG) (10 mg, days -2 and -1), was evaluated as a method of induction of permanent heterotopic cardiac allograft survival in the highly histoincompatible rat strain combination of ACI (RT1(1))-to-Lewis (RT1a). Both Pd-H and ALG localize poorly in the thymus, so this study evaluated whether thymic irradiation (TI) or thymectomy (TX) of the adult recipient results in indefinite allograft survival. Immunosuppression with Pd-H or ALG alone gave a mean survival time (MST) of 6.7 +/- 0.6 days, but the combination of the two agents led to an MST of 17.6 +/- 3.4 days. When TI was combined with Pd-H and ALG, cardiac allograft survival was prolonged to 50.2 +/- 13.9 days, but TI alone showed an MST of 10.3 +/- 1.8 days. Permanent cardiac allograft survival (greater than 250 days) was achieved in all thymectomized recipients treated with the combination of Pd-H and a brief course of ALG. These animals also accepted second-set skin grafts and rejected third-party skin grafts following more than 150 days of ACI cardiac allograft survival. Thymic irradiation, although effective in acting synergistically with SLI and ALG, led to prolonged, but limited allograft survival, although thymectomy with SLI and ALG is synergistic in prolonging allograft survival permanently without chronic immunosuppression

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

    Science.gov (United States)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Jacobsen, I M; Claesson, Mogens Helweg

    1998-01-01

    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....

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

    Science.gov (United States)

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

    2016-08-01

    Meniscus allograft transplantation has been performed over the past 25 years to relieve knee pain and improve knee function in patients with an irreparable meniscus injury. The efficacy and safety of meniscus allograft transplantation have been established in numerous experimental and clinical researches. However, there is a lack of reviews to aid radiologists who are routinely interpreting images and evaluating the outcome of the procedures, and also meniscus allograft transplantation is not widely performed in most hospitals. This review focuses on the indications of the procedure, the different surgical techniques used for meniscus allograft transplantation according to the involvement of the lateral and medial meniscus, and the associated procedures. The postoperative radiological findings and surgical complications of the meniscus allograft transplantation are also described in detail. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Revision allograft reconstruction of the lateral collateral ligament complex in elbows with previous failed reconstruction and persistent posterolateral rotatory instability.

    Science.gov (United States)

    Baghdadi, Yaser M K; Morrey, Bernard F; O'Driscoll, Shawn W; Steinmann, Scott P; Sanchez-Sotelo, Joaquin

    2014-07-01

    six elbows were rated with a good or excellent result. All patients with persistent instability had some degree of preoperative bone loss. Revision allograft reconstruction of the LCLC is an option for treating recurrent PLRI, although this is a complex and resistant problem, and nearly ½ of the patients in this cohort either had persistent instability and/or had a fair or poor elbow score. Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

  17. Complications of massive allograft reconstruction for bone tumors

    Directory of Open Access Journals (Sweden)

    Abolhasan Borjian

    2006-11-01

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

  18. Elevated cranial ultrasound resistive indices are associated with improved neurodevelopmental outcomes one year after pediatric cardiac surgery: A single center pilot study.

    Science.gov (United States)

    Jenks, Christopher L; Hernandez, Ana; Stavinoha, Peter L; Morris, Michael C; Tian, Fenghua; Liu, Hanli; Garg, Parvesh; Forbess, Joseph M; Koch, Joshua

    To determine if a non-invasive, repeatable test can be used to predict neurodevelopmental outcomes in patients with congenital heart disease. This was a prospective study of pediatric patients less than two months of age undergoing congenital heart surgery at the Children's Health Children's Medical Center at Dallas. Multichannel near-infrared spectroscopy (NIRS) was utilized during the surgery, and ultrasound (US) resistive indices (RI) of the major cranial vessels were obtained prior to surgery, immediately post-operatively, and prior to discharge. Pearson's correlation, Fischer exact t test, and Fischer r to z transformation were used where appropriate. A total of 16 patients were enrolled. All had US data. Of the sixteen patients, two died prior to the neurodevelopmental testing, six did not return for the neurodevelopmental testing, and eight patients completed the neurodevelopmental testing. There were no significant correlations between the prior to surgery and prior to discharge US RI and neurodevelopmental outcomes. The immediate post-operative US RI demonstrated a strong positive correlation with standardized neurodevelopmental outcome measures. We were able to demonstrate qualitative differences using multichannel NIRS during surgery, but experienced significant technical difficulties implementing consistent monitoring. A higher resistive index in the major cerebral blood vessels following cardiac surgery in the neonatal period is associated with improved neurological outcomes one year after surgery. Obtaining an ultrasound with resistive indices of the major cerebral vessels prior to and after surgery may yield information that is predictive of neurodevelopmental outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. A review: HIV inactivation in allografts

    International Nuclear Information System (INIS)

    Astrid Lobo Gajiwala

    1999-01-01

    This review focuses on the use of 70% ethanol as a virucidal agent with particular reference to human immunodeficiency virus (HIV). The transmission of this virus through allografts is of particular to tissue banks since the screening for HIV antibody of potential donors of tissues does not eliminate the risk of HIV transmission. Seronegetive donors who were in the 'window' period i.e. the time between infection and seroconversion, have been known to transmit HIV. It is suggested that exposure to 70% ethanol be included as a routine step in the banking of tissues whether fresh frozen or freeze-dried

  20. Vascularized Composite Allografts: Procurement, Allocation, and Implementation.

    Science.gov (United States)

    Rahmel, Axel

    Vascularized composite allotransplantation is a continuously evolving area of modern transplant medicine. Recently, vascularized composite allografts (VCAs) have been formally classified as 'organs'. In this review, key aspects of VCA procurement are discussed, with a special focus on interaction with the procurement of classical solid organs. In addition, options for a matching and allocation system that ensures VCA donor organs are allocated to the best-suited recipients are looked at. Finally, the different steps needed to promote VCA transplantation in society in general and in the medical community in particular are highlighted.

  1. Meniscal allograft transplantation: a meta-analysis

    Directory of Open Access Journals (Sweden)

    De Bruycker Manolito

    2017-01-01

    Full Text Available Purpose: This meta-analysis evaluates the mid- to long-term survival outcome of MAT (meniscal allograft transplantation. Potential prognosticators, with particular focus on chondral status and age of the patient at the time of transplantation, were also analysed. Study design: Meta-analysis. Methods: An online database search was performed using following search string: “meniscal allograft transplantation” and “outcome”. A total of 65 articles were analysed for a total of 3157 performed MAT with a mean follow-up of 5.4 years. Subjective and clinical data was analysed. Results: The subjective and objective results of 2977 patients (3157 allografts were analysed; 70% were male, 30% were female. Thirty-eight percent received an isolated MAT. All other patients underwent at least one concomitant procedure. Lysholm, Knee injury and Osteoarthritis Outcome (KOOS, International Knee Documentation Committee (IKDC and Visual Analogue Scale (VAS scores were analysed. All scores showed a good patient satisfaction at long-term follow-up. The mean overall survival rate was 80.9%. Complication rates were comparable to standard meniscal repair surgery. There was a degenerative evolution in osteoarthritis with at least one grade in 1760 radiographically analysed patients. Concomitant procedures seem to have no effect on the outcome. Age at transplantation is a negative prognosticator. The body mass index (BMI of the patient shows a slightly negative correlation with the outcome of MAT. Conclusions: MAT is a viable solution for the younger patient with chronic pain in the meniscectomised knee joint. The complications are not severe and comparable to meniscal repair. The overall failure rate at final follow-up is acceptable and the allograft heals well in most cases, but MAT cannot be seen as a definitive solution for post-meniscectomy pain. The correct approach to the chronic painful total meniscectomised knee joint thus requires consideration of all

  2. AICAR Protects against High Palmitate/High Insulin-Induced Intramyocellular Lipid Accumulation and Insulin Resistance in HL-1 Cardiac Cells by Inducing PPAR-Target Gene Expression

    Directory of Open Access Journals (Sweden)

    Ricardo Rodríguez-Calvo

    2015-01-01

    Full Text Available Here we studied the impact of 5-aminoimidazole-4-carboxamide riboside (AICAR, a well-known AMPK activator, on cardiac metabolic adaptation. AMPK activation by AICAR was confirmed by increased phospho-Thr172-AMPK and phospho-Ser79-ACC protein levels in HL-1 cardiomyocytes. Then, cells were exposed to AICAR stimulation for 24 h in the presence or absence of the AMPK inhibitor Compound C, and the mRNA levels of the three PPARs were analyzed by real-time RT-PCR. Treatment with AICAR induced gene expression of all three PPARs, but only the Ppara and Pparg regulation were dependent on AMPK. Next, we exposed HL-1 cells to high palmitate/high insulin (HP/HI conditions either in presence or in absence of AICAR, and we evaluated the expression of selected PPAR-targets genes. HP/HI induced insulin resistance and lipid storage was accompanied by increased Cd36, Acot1, and Ucp3 mRNA levels. AICAR treatment induced the expression of Acadvl and Glut4, which correlated to prevention of the HP/HI-induced intramyocellular lipid build-up, and attenuation of the HP/HI-induced impairment of glucose uptake. These data support the hypothesis that AICAR contributes to cardiac metabolic adaptation via regulation of transcriptional mechanisms.

  3. Histomorphological Assessment of Phlebitis in Renal Allografts

    Science.gov (United States)

    Jurčić, Vesna; Jeruc, Jera; Marić, Stela; Ferluga, Dušan

    2007-01-01

    Aim To evaluate the histomorphological features of veins in normal and transplanted kidneys. Methods Between 1992 and 1997 at the Institute of Pathology in Ljubljana, we semiquantitatively evaluated histomorphological changes in veins in nephrectomy specimens of 29 renal allografts with rejection and in 31 control kidneys. The structure of different segments of renal veins was additionally analyzed. Results Small interlobular veins were composed of endothelium and basement membrane, similar to capillaries, while the walls of large interlobular and arcuate veins had smooth muscle cell bundles forming the medial layer, similar to large extrarenal veins. In the control group, only focal mononuclear infiltration around small interlobular veins was found (8/31). In rejected kidney allografts, the veins were frequently infiltrated with inflammatory cells, predominantly T lymphocytes and macrophages (29/29). Other changes included thrombosis (16/29), fibrinoid necrosis (7/29), and sclerosis (9/29), and in one case an intimal lipid deposition. Conclusion This study, performed on whole explanted kidney specimens, revealed that rejection vasculitis often involved extrarenal and intrarenal veins, showing a whole spectrum of histopathological changes similar to those in arteries. Since large intrarenal veins have a muscle wall, we believe that the term »rejection phlebitis« could be used in renal transplant pathology. PMID:17589975

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

    Science.gov (United States)

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

    2015-01-01

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

  5. The safety of bone allografts used in dentistry: a review.

    Science.gov (United States)

    Holtzclaw, Dan; Toscano, Nicholas; Eisenlohr, Lisa; Callan, Don

    2008-09-01

    Recent media reports concerning "stolen body parts" have shaken the public's trust in the safety of and the use of ethical practices involving human allografts. The authors provide a comprehensive review of the safety aspects of human bone allografts. The authors reviewed U.S. government regulations, industry standards, independent industry association guidelines, company guidelines and scientific articles related to the use of human bone allografts in the practice of dentistry published in the English language. The use of human bone allografts in the practice of dentistry involves the steps of procurement, processing, use and tracking. Rigorous donor screening and aseptic proprietary processing programs have rendered the use of human bone allografts safe and effective as a treatment option. When purchasing human bone allografts for the practice of dentistry, one should choose products accredited by the American Association of Tissue Banks for meeting uniformly high safety and quality control measures. Knowledge of human bone allograft procurement, processing, use and tracking procedures may allow dental clinicians to better educate their patients and address concerns about this valuable treatment option.

  6. Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.

    Science.gov (United States)

    Losman, J G

    1977-09-24

    Cardiovascular disease is the chief cause of death in technologically advanced countries and accounts for more than 50% of all deaths in the USA. For a patient with end-stage cardiac failure the only treatment presently available is organ replacement, either by transplantation or by the use of a mechanical heart. Transplantation has demonstrated its value: survival of more than 8 years and restoration of a normal quality of life to patients who were in end-stage cardiac decompensation. However, the prospect of routine clinical application of an artificial heart remains distant. The development of a totally implantable artificial heart still presents a series of challenging engineering problems with regard to strict constraints of size, weight, blood-material compatibility, adaptability of output to demand, efficiency and reliability of the power supply, and safety if nuclear fuel is used. The totally artificial heart is presently not an alternative to the cardiac allograft, but could provide short-term support for patients awaiting cardiac transplantation.

  7. Regulatory dendritic cell infusion prolongs kidney allograft survival in non-human primates

    OpenAIRE

    Ezzelarab, M.; Zahorchak, A.F.; Lu, L.; Morelli, A.E.; Chalasani, G.; Demetris, A.J.; Lakkis, F.G.; Wijkstrom, M.; Murase, N.; Humar, A.; Shapiro, R.; Cooper, D.K.C.; Thomson, A.W.

    2013-01-01

    We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 cos...

  8. Dual growth factor delivery from biofunctionalized allografts: Sequential VEGF and BMP-2 release to stimulate allograft remodeling.

    Science.gov (United States)

    Sharmin, Farzana; McDermott, Casey; Lieberman, Jay; Sanjay, Archana; Khan, Yusuf

    2017-05-01

    Autografts have been shown to stimulate osteogenesis, osteoclastogenesis, and angiogenesis, and subsequent rapid graft incorporation. Large structural allografts, however, suffer from limited new bone formation and remodeling, both of which are directly associated with clinical failure due to non-unions, late graft fractures, and infections, making it a priority to improve large structural allograft healing. We have previously shown the osteogenic ability of a polymer-coated allograft that delivers bone morphogenetic protein-2 both in vitro and in vivo through both burst release and sustained release kinetics. In this study, we have demonstrated largely sequential delivery of bone morphogenetic protein-2 and vascular endothelial growth factor from the same coated allograft. Release data showed that loading both growth factors onto a polymeric coating with two different techniques resulted in short-term (95% release within 2 weeks) and long-term (95% release within 5 weeks) delivery kinetics. We have also demonstrated how released VEGF, traditionally associated with angiogenesis, can also provide a stimulus for allograft remodeling via resorption. Bone marrow derived mononuclear cells were co-cultured with VEGF released from the coated allograft and showed a statistically significant (p exposed to VEGF released from the allografts over controls (p < 0.05). These results indicate that by using different loading protocols temporal control can be achieved when delivering multiple growth factors from a polymer-coated allograft. Further, released VEGF can also stimulate osteoclastogenesis that may enhance allograft incorporation, and thus mitigate long-term clinical complications. © 2017 Orthopedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1086-1095, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. Vav1 GEF activity is required for T cell mediated allograft rejection.

    Science.gov (United States)

    Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert

    2012-06-01

    The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    Science.gov (United States)

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (PHIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; PHIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Novel All-Extremity High-Intensity Interval Training Improves Aerobic Fitness, Cardiac Function and Insulin Resistance in Healthy Older Adults

    Science.gov (United States)

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M.; Petersen, John W.; Christou, Demetra D.

    2016-01-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1 years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4 minutes 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4x/week for 8 weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (PHIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; PHIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. PMID:27346646

  12. Preventing Allograft Rejection by Targeting Immune Metabolism

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    Chen-Fang Lee

    2015-10-01

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

  13. Inhibition of WISE preserves renal allograft function.

    Science.gov (United States)

    Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

    2013-01-01

    Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

  14. Risk of renal allograft rejection following angiography

    International Nuclear Information System (INIS)

    Heideman, M.; Claes, G.; Nilson, A.E.

    1976-01-01

    In a retrospective study of 173 immediately functioning primary kidney transplants, correlation between angiography and renal allograft rejection was studied during the first 14 days. It was found that rejection was more frequent in kidneys undergoing angiography than in those not undergoing angiography. It was also found that in kidneys undergoing angiography an overwhelming number of the rejections started the day after angiography. These differences in rejection frequency could not be explained by differences in HLA matching or the origin of the kidneys. These findings suggest a possible connection indicating that the angiography might elicit an acute rejection episode. A possible mechanism for starting this reaction might be activation of the complement system which was found in 50 percent of the patients undergoing angiography in peripheral blood and in 100 percent when studied in vitro

  15. Surgical revascularization induces angiogenesis in orthotopic bone allograft

    NARCIS (Netherlands)

    Willems, Wouter F.; Kremer, Thomas; Friedrich, Patricia; Bishop, Allen T.

    2012-01-01

    Remodeling of structural bone allografts relies on adequate revascularization, which can theoretically be induced by surgical revascularization. We developed a new orthotopic animal model to determine the technical feasibility of axial arteriovenous bundle implantation and resultant angiogenesis. We

  16. The Spectrum of Renal Allograft Failure.

    Directory of Open Access Journals (Sweden)

    Sourabh Chand

    Full Text Available Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum.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.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%.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 individualised patient care.

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

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    L. V. Shkalova

    2011-01-01

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

  18. De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

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    Kanodia K

    2008-01-01

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

  19. Deceased donor skin allograft banking: Response and utilization

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    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.

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

    Science.gov (United States)

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

    2008-10-01

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

  1. Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

    Science.gov (United States)

    Haisheng, Han; Songjie, Zuo; Xin, Li

    2008-01-01

    Although regeneration of nerve allotransplant is a major concern in the clinic, there have been few papers quantitatively assessing functional recovery of animals' nerve allografts in the long term. In this study, functional recovery, histopathological study, and immunohistochemistry changes of rat nerve allograft with FK506 were investigated up to 12 weeks without slaughtering. C57 and SD rats were used for transplantation. The donor's nerve was sliced and transplanted into the recipient. The sciatic nerve was epineurally sutured with 10-0 nylon. In total, 30 models of transplantation were performed and divided into 3 groups that were either treated with FK506 or not. Functional recovery of the grafted nerve was serially assessed by the pin click test, walking track analysis and electrophysiological evaluations. A histopathological study and immunohistochemistry study were done in the all of the models. Nerve allografts treated with FK506 have no immune rejection through 12 weeks. Sensibility had similarly improved in both isografts and allografts. There has been no difference in each graft. Walk track analysis demonstrates significant recovery of motor function of the nerve graft. No histological results of difference were found up to 12 weeks in each graft. In the rodent nerve graft model, FK506 prevented nerve allograft rejection across a major histocompatibility barrier. Sensory recovery seems to be superior to motor function. Nerve isograft and allograft treated with FK506 have no significant difference in function recovery, histopathological result, and immunohistochemistry changes.

  2. Cardiac rehabilitation

    Science.gov (United States)

    ... rehab; Heart failure - cardiac rehab References Anderson L, Taylor RS. Cardiac rehabilitation for people with heart disease: ... of Medicine, Division of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed ...

  3. Human breast tumor cells are more resistant to cardiac glycoside toxicity than non-tumorigenic breast cells.

    Directory of Open Access Journals (Sweden)

    Rebecca J Clifford

    Full Text Available Cardiotonic steroids (CTS, specific inhibitors of Na,K-ATPase activity, have been widely used for treating cardiac insufficiency. Recent studies suggest that low levels of endogenous CTS do not inhibit Na,K-ATPase activity but play a role in regulating blood pressure, inducing cellular kinase activity, and promoting cell viability. Higher CTS concentrations inhibit Na,K-ATPase activity and can induce reactive oxygen species, growth arrest, and cell death. CTS are being considered as potential novel therapies in cancer treatment, as they have been shown to limit tumor cell growth. However, there is a lack of information on the relative toxicity of tumor cells and comparable non-tumor cells. We have investigated the effects of CTS compounds, ouabain, digitoxin, and bufalin, on cell growth and survival in cell lines exhibiting the full spectrum of non-cancerous to malignant phenotypes. We show that CTS inhibit membrane Na,K-ATPase activity equally well in all cell lines tested regardless of metastatic potential. In contrast, the cellular responses to the drugs are different in non-tumor and tumor cells. Ouabain causes greater inhibition of proliferation and more extensive apoptosis in non-tumor breast cells compared to malignant or oncogene-transfected cells. In tumor cells, the effects of ouabain are accompanied by activation of anti-apoptotic ERK1/2. However, ERK1/2 or Src inhibition does not sensitize tumor cells to CTS cytotoxicity, suggesting that other mechanisms provide protection to the tumor cells. Reduced CTS-sensitivity in breast tumor cells compared to non-tumor cells indicates that CTS are not good candidates as cancer therapies.

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

    Science.gov (United States)

    2013-01-01

    Background The spleen is an active lymphoid organ. The effect of splenectomy on the immune response remains unclear. This study investigated whether splenectomy can induce immune tolerance and has a beneficial role in cardiac allograft. Methods Wistar rats were used for heart donors. The Sprague–Dawley (SD) rats designated as the recipients of heart transplantation (HT) were randomly assigned into four groups: sham, splenectomy, HT, splenectomy + HT. The survival of transplanted hearts was assessed by daily checking of abdominal palpation. At various time points after transplantation, the transplanted hearts were collected and histologically examined; the level of CD4+CD25+ T regulatory lymphocytes (Tregs) and rate of lymphocyte apoptosis (annexin-v+ PI+ cells) in the blood were analyzed by using flow cytometric method. Results 1) Splenectomy significantly prolonged the mean survival time of heart allografts (7 ± 1.1 days and 27 ± 1.5 days for HT and splenectomy + HT, respectively; n = 12-14/group, HT vs. splenectomy + HT, p Splenectomy delayed pathological changes (inflammatory cell infiltration, myocardial damage) of the transplanted hearts in splenectomy + HT rats; 3) The level of CD4+CD25+ Tregs in the blood of splenectomized rats was significantly increased within 7 days (2.4 ± 0.5%, 4.9 ± 1.3% and 5.3 ± 1.0% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p splenectomy surgery and gradually decreased to baseline level; 4) Splenectomy increased the rate of lymphocyte apoptosis (day 7: 0.3 ± 0.05%, 3.9 ± 0.9% and 4.1 ± 0.9% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p Splenectomy inhibits the development of pathology and prolongs the survival time of cardiac allograft. The responsible mechanism is associated with induction of immune

  5. Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

    International Nuclear Information System (INIS)

    Crescioli, Clara; Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

    2008-01-01

    CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFNγ and TNFαα; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNFα-induced up-regulation of IFNγR. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor γ agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFNγ-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants

  6. Outcome of organs procured from donors on extracorporeal membrane oxygenation support: an analysis of kidney and liver allograft data.

    Science.gov (United States)

    Carter, Timothy; Bodzin, Adam S; Hirose, Hitoshi; West, Sharon; Hasz, Richard; Maley, Warren R; Cavarocchi, Nicholas C

    2014-07-01

    Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. 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.

  8. Significant prolongation of segmental pancreatic allograft survival in two species

    Energy Technology Data Exchange (ETDEWEB)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-06-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

  9. Significant prolongation of segmental pancreatic allograft survival in two species

    International Nuclear Information System (INIS)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-01-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival

  10. Use of massive structural allograft in revision septic hip arthroplasty

    International Nuclear Information System (INIS)

    Imran Ilyas; Morgan, F.; David, A.

    1999-01-01

    The reconstruction of failed septic hip arthroplasty with the use of massive osseous allograft segments is reported in ten patients. All of these patients had a two-stage procedure with an interval Girdlestone arthroplasty separating the initial demolition from the subsequent reconstruction. The mean follow-up was 58 months (range 36 to 98 months) and the most common pathogen isolated was Staphylococcus epidermidis. The mean preoperative modified Harris hip score was 27 points (range 9 to 58) and the mean postoperative score was 73 points (range 53 to 92). There was one patient who required an additional procedure not related to allograft use. There has been no case of recurrence of infection. We conclude that the revision of septic hip arthroplasty in the use of massive allografts do not have to be mutually exclusive events

  11. Allografts versus Equine Xenografts in Calcaneal Fracture Repair.

    Science.gov (United States)

    Sonmez, Mehmet Mesut; Armagan, Raffi; Ugurlar, Meric; Eren, Tugrul

    Displaced intra-articular calcaneal fractures are difficult to treat. We determined the functional results and complications of using allografts or equine xenografts in treating these fractures. We reviewed patients seen at our center from May 2011 to December 2014 with Sanders type III or IV unilateral calcaneal fractures treated with locking plates and an additional bone allograft or equine xenograft. A minimum of 1 year after surgery, a history of infection and functional outcomes were assessed using the American Orthopaedic Foot and Ankle Society clinical rating system. Changes in the Gissane angle (GA) and Böhler angle were assessed from radiographs. Of the 91 eligible patients, 15 were lost to follow-up, leaving a sample of 76 patients (42 males): 45 received allografts (19 for type III and 26 for type IV fractures) and 31 received xenografts (20 for type III and 11 for type IV fractures). The mean age was about 40 years in both groups. After ≥1 year of follow-up, the proportion of patients in the American Orthopaedic Foot and Ankle Society scoring categories did not differ significantly between the 2 groups (mean ankle score, 86.5 in the allograft group and 85.1 in the xenograft group), and the American Orthopaedic Foot and Ankle Society functional outcomes were good or excellent in 69% and 68%, respectively (p = .986). The groups did not differ in the incidence of superficial or deep infection (p = 1.000). The Böhler angles were significantly decreased in the xenograft group. Xenografts might be preferred for repairing intra-articular calcaneal fractures because they can perform as well as allografts, avoid donor site morbidities, and are more available and less expensive than allografts. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Laparoscopic cholecystectomy in a cardiac transplant recipient.

    Science.gov (United States)

    Pandya, Seema R; Paranjape, Saloni

    2014-04-01

    An increasing number of cardiac transplants are being carried out around the world. With increasing longevity, these patients present a unique challenge to non-transplant anesthesiologists for a variety of transplant related or incidental surgeries. The general considerations related to a cardiac transplant recipient are the physiological and pharmacological problems of allograft denervation, the side-effects of immunosuppression, the risk of infection and the potential for rejection. A thorough understanding of the physiology of a denervated heart, need for direct vasoactive agents and post-transplant morbidities is essential in anesthetic management of such a patient. Here, we describe a case of a heart transplant recipient who presented for a cholecystectomy at our center.

  13. Renal denervation in a patient with Alport syndrome and rejected renal allograft.

    Science.gov (United States)

    Raju, Narayana; Lloyd, Vincent; Yalagudri, Sachin; Das, Bharati; Ravikishore, A G

    2015-12-01

    Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  14. Regulatory dendritic cell infusion prolongs kidney allograft survival in non-human primates

    Science.gov (United States)

    Ezzelarab, M.; Zahorchak, A.F.; Lu, L.; Morelli, A.E.; Chalasani, G.; Demetris, A.J.; Lakkis, F.G.; Wijkstrom, M.; Murase, N.; Humar, A.; Shapiro, R.; Cooper, D.K.C.; Thomson, A.W.

    2014-01-01

    We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on day −2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n=6) and 113.5 days (pDCreg-treated animals (n=6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95+ T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further pre-clinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. PMID:23758811

  15. 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.

  16. Soaking morselized allograft in bisphosphonate can impair implant fixation

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  17. Characterization of Skin Allograft Use in Thermal Injury

    Science.gov (United States)

    2013-01-01

    of burn surgery. New York: Marcel Dekker; 2004. 6. Burd A, Lam PK, Lau H. Allogenic skin: transplant or dressing? Burns 2002;28:358–66. 7...with CPA, and the feet (1.4%) and groin (0.5%) together have CPA placed at ɚ% of all engraftments (Figure 5). When propensity matched for TBSA ( N = 72...nonallografted and allografted patients propensity matched on TBSA Variable No. Nonallograft N Allograft P TBSA 36 34.83 ± 18.74 (0.5–90) 36 35.14

  18. Early kidney allograft loss - is there scope for improvement?

    Science.gov (United States)

    Ferrari, Paolo

    2018-02-17

    Increased longevity matching using Kidney Donor Profile Index (KDPI) to optimize long-term kidney allograft survival has been central to the effort of appropriate allocation of deceased donor kidneys. The data by Helenterä and co-workers in this issue, who looked at predictors of early allograft loss, should prompt an analysis of whether predictors of short-term graft survival can improve KDPI-based decisions when considering whether to accept or decline a deceased donor kidney offer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Use of bone allograft in Kuala Lumpur Hospital

    International Nuclear Information System (INIS)

    Ruslan Nazaruddin

    1999-01-01

    We have revived twenty two patients who underwent surgery requiring allograft in Hospital Kuala Lumpur between 1994-1997. There were 12 females and 10 males with mean age of 49. 8 year old. The surgery was done for various reason namely revision total hip replacement (THR), traumatic fracture with bone gap, lower limb tumour excision and spine tumour excision. The reason for using allograft, are mainly to reconstruct the acetabulum and femoral bone defects, as a gap filler following excision of tumour, also prosthesis and as on lay. The progress of these patients will be mentioned

  20. Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion

    International Nuclear Information System (INIS)

    Bair, H.J.; Platsch, G.; Wolf, F.; Guenter, E.; Becker, D.; Rupprecht, H.; Neumayer, H.H.

    1997-01-01

    Aim: The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery. Methods: From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts. Results: Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up. Conclusion: In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and colorcoded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion. (orig.) [de

  1. An osteophyte in the tibial plateau is a risk factor for allograft extrusion after meniscus allograft transplantation.

    Science.gov (United States)

    Jeon, Byeongsam; Kim, Jong-Min; Kim, Jong-Min; Lee, Chang-Rack; Kim, Kyung-Ah; Bin, Seong-Il

    2015-05-01

    Osteophytes can be observed on the tibial plateau during meniscus allograft transplantation (MAT). However, no studies to date have evaluated the effect of these osteophytes on meniscus allograft extrusion. Osteophyte excision in the tibial plateau could reduce extrusion of the transplanted meniscus and improve short-term clinical outcomes with meniscus allograft transplantation. Cohort study; Level of evidence, 3. Between October 2004 and July 2012, a total of 323 patients underwent MAT at a single institution. Of these, 88 patients had a peripheral osteophyte in their tibial plateau, and they were enrolled in the study retrospectively. The mean age of the patients was 35.3 years (range, 15-56 years); there were 57 male and 31 female patients. Forty-four patients underwent osteophyte excision concomitantly with MAT and 44 patients underwent MAT only. The 2 groups showed no difference in terms of age, body mass index, time after meniscectomy, and preoperative knee scores. A medial meniscus allograft was transplanted in 13 cases (15%) and a lateral meniscus in 75 (85%). The absolute extrusion and relative percentage of extrusion were measured to evaluate allograft extrusion 12 months after MAT. The modified Lysholm scoring system and the Hospital for Special Surgery score at 2 years after MAT were used to evaluate clinical outcomes. The mean absolute extrusions at 1 year postoperatively in the excision and nonexcision groups were 3.5±1.5 and 5.5±1.6 mm, respectively. The mean relative percentages of extrusion were 34.1%±15.9% and 54.7%±20.7%, respectively. The rates of allograft extrusion (>3 mm) were 28 of 44 (63.6%) and 41 of 44 (93.2%) in the excision and nonexcision groups, respectively. The intergroup differences in absolute extrusion, relative percentage of extrusion, and rate of allograft extrusion were statistically significant (P<.001 for all 3 parameters). There were no significant differences in the clinical outcomes (modified Lysholm or Hospital of

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

    International Nuclear Information System (INIS)

    Alievi, Marcelo Meller; Wallau Schossler, João Eduardo; Christo de Oliveira, Ana Néri; Almeida Ferreira, Carolina Kist TraeslelIV Patrícia; Dambrósio Guimarães, Luciana

    2007-01-01

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

  3. 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

  4. Primary Nonfunction of Renal Allograft Secondary to Acute Oxalate Nephropathy

    Directory of Open Access Journals (Sweden)

    Ravi Parasuraman

    2011-01-01

    Full Text Available Primary nonfunction (PNF accounts for 0.6 to 8% of renal allograft failure, and the focus on causes of PNF has changed from rejection to other causes. Calcium oxalate (CaOx deposition is common in early allograft biopsies, and it contributes in moderate intensity to higher incidence of acute tubular necrosis and poor graft survival. A-49-year old male with ESRD secondary to polycystic kidney disease underwent extended criteria donor kidney transplantation. Posttransplant, patient developed delayed graft function (DGF, and the biopsy showed moderately intense CaOx deposition that persisted on subsequent biopsies for 16 weeks, eventually resulting in PNF. The serum oxalate level was 3 times more than normal at 85 μmol/L (normal <27 μmol/L. Allograft nephrectomy showed massive aggregates of CaOx crystal deposition in renal collecting system. In conclusion, acute oxalate nephropathy should be considered in the differential diagnosis of DGF since optimal management could change the outcome of the allograft.

  5. Could Uric acid have a Pathogenic Role in Chronic Allograft ...

    African Journals Online (AJOL)

    Introduction: Chronic allograft dysfunction (CAD) is the primary cause of chronic graft failure after kidney transplantation. The pathogenesis of CAD involves both antigen-dependent and antigen-independent mechanisms. Serum uric acid could have a role in both mechanisms. Review: Hyperuricemia in subjects with renal ...

  6. Kidney allograft survival in dogs treated with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-01-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients

  7. 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.

  8. Noninvasive diagnosis of allograft vascular disease after heart transplantation

    Directory of Open Access Journals (Sweden)

    Fernando Bacal

    2001-01-01

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

  9. 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.

  10. Inhibition of the immune response to experimental fresh osteoarticular allografts

    International Nuclear Information System (INIS)

    Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. III; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M.

    1989-01-01

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed

  11. Introducing banked allograft skin to burn surgery in South Africa

    African Journals Online (AJOL)

    Burn injury remains a severely neglected epidemic in South Africa. (SA), despite the magnitude of the problem. This has been described by a number of authors, and there is a shift towards addressing the deficits.[1-6] The recent establishment of the first allograft skin bank in SA is potentially a tremendous stride towards ...

  12. Apoptosis of acinar cells in pancreas allograft rejection

    NARCIS (Netherlands)

    Boonstra, J. G.; Wever, P. C.; Laterveer, J. C.; Bruijn, J. A.; van der Woude, F. J.; ten Berge, I. J.; Daha, M. R.

    1997-01-01

    BACKGROUND: Recently it has been recognized that apoptosis of target cells may occur during liver and kidney allograft rejection and is probably induced by infiltrating cells. Pancreas rejection is also characterized by a cellular infiltrate, however, the occurrence of apoptosis has not been

  13. Cell-Free DNA and Active Rejection in Kidney Allografts.

    Science.gov (United States)

    Bloom, Roy D; Bromberg, Jonathan S; Poggio, Emilio D; Bunnapradist, Suphamai; Langone, Anthony J; Sood, Puneet; Matas, Arthur J; Mehta, Shikha; Mannon, Roslyn B; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C; Cohen, David; Weir, Matthew R; Hiller, David; Prasad, Preethi; Woodward, Robert N; Grskovic, Marica; Sninsky, John J; Yee, James P; Brennan, Daniel C

    2017-07-01

    Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls ( P =0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection. Copyright © 2017 by the American Society of Nephrology.

  14. Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

    Directory of Open Access Journals (Sweden)

    Roberto Bassi

    Full Text Available Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.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.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.We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

  15. Splenic microenvironment and self recognition as factors in allograft rejection in rats. A study using indium-111-labeled cells

    International Nuclear Information System (INIS)

    Pollak, R.; Blanchard, J.M.; Lazda, V.A.

    1986-01-01

    Splenectomy facilitates organ allograft survival in some rat strains, and in weak donor-recipient histoincompatible pairs. We have found using a heart spleen twin graft model, using ACI rats as recipients and Lewis rats as donors, that the transplanted heart will survive in most recipients after delayed host splenectomy. The presence of a viable mass of splenic tissue will allow rejection to proceed only when the transplanted spleen is of host origin, and not when it comes from the donor (i.e., when it is allogeneic). The use of 111In-labeled cells has allowed us to show that lymphocyte traffic and trapping is markedly altered in the transplanted allogeneic spleens, when compared with control transplanted syngeneic spleens. Thus, despite the presence of the splenic ''microenvironment,'' cardiac allograft rejection does not occur in the absence of syngeneic splenic tissue. We conclude that the role of the spleen in the immune response is to facilitate the recognition of self and the acquisition of alloreactivity in weak responder rat strains and donor-recipient pairs

  16. Cardiac arrest

    Science.gov (United States)

    ... magnesium. These minerals help your heart's electrical system work. Abnormally high or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your ...

  17. Cardiac Ochronosis

    Science.gov (United States)

    Erek, Ersin; Casselman, Filip P.A.; Vanermen, Hugo

    2004-01-01

    We report the case of 67-year-old woman who underwent aortic valve replacement and mitral valve repair due to ochronotic valvular disease (alkaptonuria), which was diagnosed incidentally during cardiac surgery. PMID:15745303

  18. Cardiac catheterization

    Science.gov (United States)

    ... tests. However, it is very safe when done by an experienced team. The risks include: Cardiac tamponade Heart attack Injury to a coronary artery Irregular heartbeat Low blood pressure Reaction to the contrast dye Stroke Possible complications ...

  19. Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection.

    Science.gov (United States)

    Lejay, Anne; Delay, Charline; Girsowicz, Elie; Chenesseau, Bettina; Bonnin, Emilie; Ghariani, Mohamed-Zied; Thaveau, Fabien; Georg, Yannick; Geny, Bernard; Chakfe, Nabil

    2017-11-01

    The aim of this study was to report outcomes of cryopreserved arterial allografts used as a vascular substitute in the setting of prosthetic material infection. A retrospective analysis of prospectively collected data was conducted including all consecutive interventions performed with cryopreserved arterial allografts used for vascular reconstruction in the setting of prosthetic material infection between January 2005 and December 2014. Five year outcomes included allograft related re-interventions, survival, primary patency, and limb salvage rates. Fifty-three procedures were performed using cryopreserved allografts for vascular prosthetic infection: 25 procedures (47%) were performed at aorto-iliac level (Group 1) and 28 procedures (53%) at peripheral level (Group 2). The mean follow-up was 52 months. Five year allograft related re-intervention was 55% in Group 1 (6 allograft ruptures and 5 allograft aneurysm degenerations) and 33% in Group 2 (2 allograft ruptures and 7 allograft aneurysm degenerations). Five year survival was 40% and 68%, primary patency was 89% and 59% and limb salvage was 100% and 89% for Group 1 and 2 respectively. Use of cryopreserved arterial allografts provides acceptable results but is tempered by suboptimal 5 year outcomes with high re-intervention rates. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  20. Nuclear cardiac

    International Nuclear Information System (INIS)

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques

  1. The effect of pregnancy on paternal skin allograft survival

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

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

  2. Efficacy of prophylactic irradiation in altering renal allograft survival

    International Nuclear Information System (INIS)

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

    1974-01-01

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

  3. Cardiac CT

    International Nuclear Information System (INIS)

    Dewey, Marc

    2011-01-01

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

  4. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

  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. Pancreas Allograft Transplantation in Dogs with Experimental Diabetes Mellitus

    OpenAIRE

    Mendívil Zapata, Rolando; Garmendia, Fausto; Yerén, Cecilia; Torres, William

    2014-01-01

    OBJETIVE : To evaluate the efficacy of pancreatic allograft transplantation (TAP ) in dogs with diabetes mellitus ( DME ) induced by alloxan . METHODS : 63 mongrel dogs were used , of which 33 for the very best experimental conditions , the other 30 were divided into 3 groups of 10 each : a) controls, were only produced DME b ) receptors with DME, the who underwent TAP and c) pancreas donors . RESULTS : The glycemic control was complete in 50% of recipients and partial in 30% , giving an over...

  7. Acute Hepatic Allograft Rejection in Pediatric Recipients: Independent Factors

    OpenAIRE

    Dehghani, S. M.; Shahramian, I.; Afshari, M.; Bahmanyar, M.; Ataollahi, M.; Sargazi, A.

    2017-01-01

    Background: Acute cellular rejection (ACR) has a reversible effect on graft and its survival. Objective: To evaluate the relation between ACR and clinical factors in recipients of liver transplant allografts. Methods: 47 consecutive liver recipients were retrospectively studied. Their data were extracted from records and analyzed. Results: 38 (81%) of the 47 recipients experienced ACR during a 24-month follow-up. The rate of rejection was associated with none of the studied factors—recipient’...

  8. Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

    Directory of Open Access Journals (Sweden)

    Hanbo Hu

    Full Text Available Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression. Donor lungs were primed with Trx at 4°C for 4 hr prior to transplantation. After up to 37 days post-transplantation, allograft lung morphology, recipient T cell and humoral alloantigen-specific immune responses were examined. We found that Trx-primed lungs exhibited much reduced acute rejection and associated lung injuries resulting in loss of graft functional area at 5-37 days post-transplant in contrast to the control groups. CD4+ T cells from the recipients with Trx-primed grafts responded to the stimulation of dendritic cells (DCs of donor origin, in contrast to DCs from the third party, with significantly reduced proliferation. Consistent with above findings, we observed that CD4+Foxp3+ regulatory T cells in spleen cells from the recipients with Trx-primed grafts were significantly increased compared to controls, and CD4+ T cells from the recipients with Trx-primed grafts produced much higher levels of immunosuppressive cytokine, IL-10 when stimulated with allogeneic donor DCs. In addition, humoral immune tolerance was also induced as there was no significant increase levels of serum antibodies against donor antigens in Trx-lung recipients when re-challenged with allogeneic donor antigens. Our results demonstrate that one-time Trx-priming of donor lung grafts prior to transplantation significantly prolongs the survival of the grafts through inducing or promoting cellular and humoral alloantigen-specific immune tolerance, which might be associated with the induction of

  9. Lateral column lengthening using allograft interposition and cervical plate fixation.

    Science.gov (United States)

    Philbin, Terrence M; Pokabla, Christopher; Berlet, Gregory C

    2008-10-01

    Lateral column lengthening has been used successfully in the treatment of stage II adult-acquired pes planovalgus deformity. The purpose of this study is to review the union rate when allograft material is used and the osteotomy stabilized with a cervical plate. A retrospective review was performed on 28 feet in 26 patients who underwent correction of stage II pes planovalgus deformity using a lateral column lengthening with allograft tricortical iliac crest stabilized with a cervical plate. Patients were evaluated preoperatively and postoperatively using a modified American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and the Short Form-12 health survey, as well as radiographically by assessing the talonavicular coverage angle. At a mean follow-up of 9 months, the mean total modified AOFAS score and pain subscore were significantly higher (45.6 and 25.0, respectively) versus preoperatively (27.3 and 11.2, respectively). Graft incorporation occurred in all but one case, and the average length of time to union was 10.06 weeks. Complications included 4 hardware removals, 1 nonunion, 1 graft penetration of the calcaneocuboid joint, and 2 cases of calcaneocuboid joint arthritis. Lateral column lengthening using allograft tricortical iliac crest bone graft with cervical plate fixation is a viable option for the correction of acquired pes planovalgus deformity. Allograft bone avoids donor site morbidity of autogenous iliac crest grafts and was not shown to increase rates of nonunion. Cervical plate fixation avoids the necessity of penetrating the graft with a screw and is associated with high patient satisfaction and radiographic union.

  10. 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.

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

    Science.gov (United States)

    Lanzman, Rotem S; Wittsack, Hans-Jörg; Martirosian, Petros; Zgoura, Panagiota; Bilk, Philip; Kröpil, Patric; Schick, Fritz; Voiculescu, Adina; Blondin, Dirk

    2010-06-01

    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.

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

    International Nuclear Information System (INIS)

    Lanzman, Rotem S.; Wittsack, Hans-Joerg; Bilk, Philip; Kroepil, Patric; Blondin, Dirk; Martirosian, Petros; Schick, Fritz; Zgoura, Panagiota; Voiculescu, Adina

    2010-01-01

    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.)

  13. Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine

    Energy Technology Data Exchange (ETDEWEB)

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Els, D.; Du Toit, L.B.; Weideman, A.; Davids, H.; van der Merwe, E.

    1987-09-01

    The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum.

  14. Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine

    International Nuclear Information System (INIS)

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.

    1987-01-01

    The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum

  15. Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone

    Science.gov (United States)

    Culpepper, Bonnie K.; Bonvallet, Paul P.; Reddy, Michael S.; Ponnazhagan, Selvarangan; Bellis, Susan L.

    2012-01-01

    Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments. PMID:23182349

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

    Science.gov (United States)

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

    2013-01-01

    Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Macrophages: contributors to allograft dysfunction, repair, or innocent bystanders?

    Science.gov (United States)

    Mannon, Roslyn B

    2012-02-01

    Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury, while more recent studies indicate that they may play a reparative role, depending on phenotype - M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid-organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage-mediated injury, explore their potential reparative role, and determine if they or their functional products are biomarkers of poor graft outcomes.

  18. Remodeling of ACL Allografts is Inhibited by Peracetic Acid Sterilization

    Science.gov (United States)

    Gonnermann, Johannes; Kamp, Julia; Przybilla, Dorothea; Pruss, Axel

    2008-01-01

    Sterilization of allografts for anterior cruciate ligament (ACL) reconstruction has become an important prerequisite to prevent disease transmission. However, current sterilization techniques impair the biological or mechanical properties of such treated grafts. Peracetic acid (PAA) has been successfully used to sterilize bone allografts without these disadvantages and does not impair the mechanical properties of soft tissue grafts in vitro. We asked whether PAA sterilization would influence recellularization, restoration of crimp length and pattern, and revascularization of ACL grafts during early healing. We used an in vivo sheep model for open ACL reconstruction. We also correlated the histologic findings with the restoration of anteroposterior stability and structural properties during load-to-failure testing. PAA slowed remodeling activity at 6 and 12 weeks compared to nonsterilized allografts and autografts. The mechanical properties of PAA grafts were also reduced compared to these control groups at both time points. We conclude PAA sterilization currently should not be used to sterilize soft tissue grafts typically used in ACL reconstruction. PMID:18491201

  19. STAT4 gene polymorphism in patients after renal allograft transplantation.

    Science.gov (United States)

    Dąbrowska-Żamojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Domański, Leszek; Słuczanowska-Głabowska, Sylwia; Pawlik, Andrzej

    2016-01-01

    STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allografts. A total of 270 recipients of first renal transplants were included in the study. Single nucleotide polymorphisms (SNPs) within the STAT4 gene were genotyped using TaqMan genotyping assays. There were no statistically significant associations between the STAT4 gene rs7574865 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction, post-transplant diabetes mellitus, or creatinine serum concentrations after transplantation. Our results suggest a lack of association between the STAT4 rs7574865 SNP and kidney allograft function in the Polish population.

  20. Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates.

    Science.gov (United States)

    Ezzelarab, M B; Zahorchak, A F; Lu, L; Morelli, A E; Chalasani, G; Demetris, A J; Lakkis, F G; Wijkstrom, M; Murase, N; Humar, A; Shapiro, R; Cooper, D K C; Thomson, A W

    2013-08-01

    We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5-10 × 10(6) /kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on Day -2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n = 6) and 113.5 days (p DCreg-treated animals (n = 6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95(+) T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further preclinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. New developments for the detection and treatment of cardiac vasculopathy.

    Science.gov (United States)

    Clerkin, Kevin J; Ali, Ziad A; Mancini, Donna M

    2017-02-15

    Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Innovative new techniques to diagnose CAV have been applied to detect disease. This review will examine the current diagnostic and treatment options available to clinicians for CAV. Diagnostic modalities addressing the pathophysiology underlying CAV (arterial wall thickening and decreased coronary blood flow) improve diagnostic sensitivity when compared to traditional (angiography and dobutamine stress echocardiography) techniques. Limited options are available to prevent and treat CAV; however, progress has been made in making an earlier and more accurate diagnosis. Future research is needed to identify the optimal time to modify immunosuppression and investigate novel treatments for CAV.

  2. [Cardiac cachexia].

    Science.gov (United States)

    Miján, Alberto; Martín, Elvira; de Mateo, Beatriz

    2006-05-01

    Chronic heart failure (CHF), especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular) mass and adipose and bone tissue osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

  3. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    Fiandra, O.; Espasandin, W.; Fiandra, H.

    1984-01-01

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  4. Inability to determine tissue health is main indication of allograft use in intermediate extent burns.

    Science.gov (United States)

    Fletcher, John L; Cancio, Leopoldo C; Sinha, Indranil; Leung, Kai P; Renz, Evan M; Chan, Rodney K

    2015-12-01

    Cutaneous allograft is commonly used in the early coverage of excised burns when autograft is unavailable. However, allograft is also applied in intermediate-extent burns (25-50%), during cases in which it is possible to autograft. In this population, there is a paucity of data on the indications for allograft use. This study explores the indications for allograft usage in moderate size burns. Under an IRB-approved protocol, patients admitted to our burn unit between March 2003 and December 2010 were identified through a review of the burn registry. Data on allograft use, total burn surface area, operation performed, operative intent, number of operations, intensive care unit length of stay, and overall length of stay were collected and analyzed. Data are presented as means±standard deviations, except where noted. In the study period, 146 patients received allograft during their acute hospitalization. Twenty-five percent of allograft recipients sustained intermediate-extent burns. Patients with intermediate-extent burns received allograft later in their hospitalization than those with large-extent (50-75% TBSA) burns (6.8 days vs. 3.4 days, p=0.01). Allografted patients with intermediate-extent burns underwent more operations (10.8 vs. 6.1, p=0.002) and had longer hospitalizations (78.3 days vs. 40.9 days, ppatients, when controlled for TBSA. Clinical rationale for placement of allograft in this population included autograft failure, uncertain depth of excision, lack of autograft donor site, and wound complexity. When uncertain depth of excision was the indication, allograft was universally applied onto the face. In half of allografted intermediate-extent burn patients the inability to identify a viable recipient bed was the ultimate reason for allograft use. Unlike large body surface area burns, allograft skin use in intermediate-extent injury occurs later in the hospitalization and is driven by the inability to determine wound bed suitability for autograft

  5. Tendon allograft sterilized by peracetic acid/ethanol combined with gamma irradiation.

    Science.gov (United States)

    Zhou, Mo; Zhang, Naili; Liu, Xiaoming; Li, Youchen; Zhang, Yumin; Wang, Xusheng; Li, Baoming; Li, Baoxing

    2014-07-01

    Research and clinical applications have demonstrated that the effects of tendon allografts are comparable to those of autografts when reconstructing injured tendons or ligaments, but allograft safety remains problematic. Sterilisation could eliminate or decrease the possibility of disease transmission, but current methods seldom achieve satisfactory sterilisation without affecting the mechanical properties of the tendon. Peracetic acid-ethanol in combination with low-dose gamma irradiation (PE-R) would inactivate potential deleterious microorganisms without affecting mechanical and biocompatible properties of tendon allograft. Controlled laboratory design. HIV, PPV, PRV and BVDV inactivation was evaluated. After verifying viral inactivation, the treated tendon allografts were characterised by optical microscopy, scanning electron microscopy and tensile testing, and the cytocompatibility was assessed with an MTT assay and by subcutaneous implantation. Effective and efficient inactivation of HIV, PPV, PRV and BVDV was observed. Histological structure and ultrastructure were unchanged in the treated tendon allograft, which also exhibited comparable biomechanical properties and good biocompatibility. The preliminary results confirmed our hypothesis and demonstrated that the PE-R tendon allograft has significant potential as an alternative to ligament/tendon reconstruction. Tendon allografts have been extensively used in ligament reconstruction and tendon repair. However, current sterilisation methods have various shortcomings, so PE-R has been proposed. This study suggests that PE-R tendon allograft has great potential as an alternative for ligament/tendon reconstruction. Sterilisation has been a great concern for tendon allografts. However, most sterilisation methods cannot inactivate viruses and bacteria without impairing the mechanical properties of the tendon allograft. Peracetic acid/ethanol with gamma irradiation can effectively inactivate viruses and bacteria

  6. Radiation therapy treatment of acute refractory renal allograft rejection

    International Nuclear Information System (INIS)

    Godinez, J.; Thisted, R.A.; Woodle, E.S.; Thistlethwaite, J.R.; Powers, C.; Haraf, D.

    1996-01-01

    Purpose: To evaluate the impact of the use of radiotherapy to preserve the renal graft in patients with recurrent graft rejection that failed to respond to medical treatment and identify risk factors to predict the probability of graft loss. Material and Methods: Between June 1989 and December 1995, 53 renal graft recipients were treated at our institution after experiencing several episodes of rejection. Rejection was defined as an unexplained, consecutive, daily rise in serum creatinine. Each episode was confirmed with renal biopsy. Patients who experienced rejection were initially treated with solu medrol bolus and prednisone. Patients with steroid-resistant or recurrent rejection received OKT3, polyclonal antilymphocyte antibody, FK506, or mycophenolate mofetil. Those who failed to respond to medical treatment were referred for radiotherapy. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, AP or AP/PA. All patients underwent ultrasound kidney localization; a 2 cm margin was given around the kidney. Results: Median follow-up from the date of transplant to the last follow-up was 22 months (range 1-83 months), the median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow up was 10 months (range 0.1 to 64 months). Of these 34 men and 19 women, median age of 3), Ninety-one percent were cadaveric transplant recipients., human leukocyte antigen matching on HLA-A and HLA-B (zero antigens in 26 patients/one or two shared antigens in 27 patients), HLA-DR locus (zero antigens in 34 patients/one or two shared antigens in 19 patients), transplant panel-reactive antibodies at transplantation (median PRA-Curr of 3% and median PRA-Max of 8%), number of acute rejection episodes, interval from the date of the transplant to the first rejection (median 1 month, range 5 days to 68 months), serum creatinine levels at the time of the first

  7. 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...

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

    DEFF Research Database (Denmark)

    Ito, H; Koefoed, M; Tiyapatanaputi, P

    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 ...

  9. Automatic allograft bone selection through band registration and its application to distal femur.

    Science.gov (United States)

    Zhang, Yu; Qiu, Lei; Li, Fengzan; Zhang, Qing; Zhang, Li; Niu, Xiaohui

    2017-09-01

    Clinical reports suggest that large bone defects could be effectively restored by allograft bone transplantation, where allograft bone selection acts an important role. Besides, there is a huge demand for developing the automatic allograft bone selection methods, as the automatic methods could greatly improve the management efficiency of the large bone banks. Although several automatic methods have been presented to select the most suitable allograft bone from the massive allograft bone bank, these methods still suffer from inaccuracy. In this paper, we propose an effective allograft bone selection method without using the contralateral bones. Firstly, the allograft bone is globally aligned to the recipient bone by surface registration. Then, the global alignment is further refined through band registration. The band, defined as the recipient points within the lifted and lowered cutting planes, could involve more local structure of the defected segment. Therefore, our method could achieve robust alignment and high registration accuracy of the allograft and recipient. Moreover, the existing contour method and surface method could be unified into one framework under our method by adjusting the lift and lower distances of the cutting planes. Finally, our method has been validated on the database of distal femurs. The experimental results indicate that our method outperforms the surface method and contour method.

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

    DEFF Research Database (Denmark)

    Koefoed, Mette; Ito, Hiromu; Gromov, Kirill

    2005-01-01

    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...

  11. Cardiac ablation

    Directory of Open Access Journals (Sweden)

    Kelly Ratheal

    2016-01-01

    Full Text Available Cardiac ablation is a procedure that uses either radiofrequency or cryothermal energy to destroy cells in the heart to terminate and/or prevent arrhythmias. The indications for cardiac catheter ablation include refractory, symptomatic arrhythmias, with more specific guidelines for atrial fibrillation in particular. The ablation procedure itself involves mapping the arrhythmia and destruction of the aberrant pathway in an effort to permanently prevent the arrhythmia. There are many types of arrhythmias, and they require individualized approaches to ablation based on their innately different electrical pathways. Ablation of arrhythmias, such as Wolff-Parkinson-White syndrome, AV nodal reentrant tachycardia, and atrial-fibrillation, is discussed in this review. Ablation has a high success rate overall and minimal complication rates, leading to improved quality of life in many patients.

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

    International Nuclear Information System (INIS)

    Fawwaz, R.A.

    1984-01-01

    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

  13. A single administration of LFA-1 antibody confers prolonged allograft survival.

    Science.gov (United States)

    Talento, A; Nguyen, M; Blake, T; Sirotina, A; Fioravanti, C; Burkholder, D; Gibson, R; Sigal, N H; Springer, M S; Koo, G C

    1993-02-01

    C57BL/6 (B6) thyroid gland transplanted to the left kidney capsule of an allogeneic (BALB/c) host was typically rejected in 14 days. A single administration of 500 micrograms of an antibody to the adhesion molecule, leucocyte function-associated antigen (LFA-1, CD11a), prevented all thyroid allograft rejection for at least 70 days. Fifty percent of the treated recipients retained intact allografts for 470 days. However, the same treatment with anti-CD11a could not protect a sensitized BALB/c mouse from rejecting a second B6 thyroid allograft. Production of donor-specific alloantibodies elicited by allograft rejection was also inhibited in this system. In this transplant model, the Ab therapy is more efficacious than that of FK506, administered daily for 14 days at 15 mg/kg. These results demonstrate the remarkable effect of an anti-LFA-1 antibody in promotion of allograft survival.

  14. Recipient origin of neointimal vascular smooth muscle cells in cardiac allografts with transplant arteriosclerosis

    NARCIS (Netherlands)

    Hillebrands, JL; van den Hurk, BMH; Klatter, FA; Popa, ER; Nieuwenhuis, P; Rozing, J

    2000-01-01

    Background: Coronary artery disease is today's most important post-heart transplantation problem after the first perioperative year. Histologically, coronary artery disease is characterized by transplant arteriosclerosis. The current view on this vasculopathy is that vascular smooth muscle (VSM)

  15. Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing.

    Science.gov (United States)

    Sun, Kai; Alvarez, Maite; Ames, Erik; Barao, Isabel; Chen, Mingyi; Longo, Dan L; Redelman, Doug; Murphy, William J

    2012-02-09

    Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.

  16. Femoral revision with impaction allografting and an uncemented femoral component

    DEFF Research Database (Denmark)

    Nickelsen, T N; Erenbjerg, M; Retpen, J B

    2008-01-01

    A technique for uncemented revision of the femoral component which combines impaction allografting and the use of a long-stemmed proximally coated titanium prostheses (Bimetric, Biomet Inc.) is described. The results after a mean follow-up of 112 months are reported. From 1991 to 1995 femoral...... implants 88% had no pain, 10% had slight pain and only 2% had severe pain. Thirty-eight patients had radiographic signs of remodelling of the graft and/or cortical repair. In cases with a successful outcome, the results have been encouraging in relation to clinical performance, regeneration of bone...

  17. Fresh osteochondral allograft transplantation for isolated patellar cartilage injury.

    Science.gov (United States)

    Gracitelli, Guilherme C; Meric, Gokhan; Pulido, Pamela A; Görtz, Simon; De Young, Allison J; Bugbee, William D

    2015-04-01

    The treatment of patellofemoral cartilage injuries can be challenging. Osteochondral allograft (OCA) transplantation has been used as a treatment option for a range of cartilage disorders. To evaluate functional outcomes and survivorship of the grafts among patients who underwent OCA for patellar cartilage injuries. Case series; Level of evidence, 4. An institutional review board-approved OCA database was used to identify 27 patients (28 knees) who underwent isolated OCA transplantation of the patella between 1983 and 2010. All patients had a minimum 2-year follow-up. The mean age of the patients was 33.7 years (range, 14-64 years); 54% were female. Twenty-six (92.9%) knees had previous surgery (mean, 3.2 procedures; range, 1-10 procedures). The mean allograft area was 10.1 cm(2) (range, 4.0-18.0 cm(2)). Patients returned for clinical evaluation or were contacted via telephone for follow-up. The number and type of reoperations were assessed. Any reoperation resulting in removal of the allograft was considered a failure of the OCA transplantation. Patients were evaluated pre- and postoperatively using the modified Merle d'Aubigné-Postel (18-point) scale, the International Knee Documentation Committee (IKDC) pain, function, and total scores, and the Knee Society function (KS-F) score. Patient satisfaction was assessed at latest follow-up. Seventeen of the 28 knees (60.7%) had further surgery after the OCA transplantation; 8 of the 28 knees (28.6%) were considered OCA failures (4 conversions to total knee arthroplasty, 2 conversions to patellofemoral knee arthroplasty, 1 revision OCA, 1 patellectomy). Patellar allografting survivorship was 78.1% at 5 and 10 years and 55.8% at 15 years. Among the 20 knees (71.4%) with grafts in situ, the mean follow-up duration was 9.7 years (range, 1.8-30.1 years). Pain and function improved from the preoperative visit to latest follow-up, and 89% of patients were extremely satisfied or satisfied with the results of the OCA

  18. The outcomes of simultaneous liver and kidney transplantation using donation after cardiac death organs.

    Science.gov (United States)

    Alhamad, Tarek; Spatz, Christin; Uemura, Tadahiro; Lehman, Eric; Farooq, Umar

    2014-12-15

    There has been a remarkable increase in simultaneous liver and kidney transplantations (SLK). As organ demand has increased, so has the use of donation after cardiac death (DCD). However, little is known about the outcomes of DCD in SLK. We performed a retrospective analysis using the United Network for Organ Sharing database to compare the outcomes of DCD SLK to donation after brain death (DBD) and determine the impact of donor and recipient factors on allograft and patient survival. Between 2002 and 2011, a total of 3,026 subjects received SLK from DBD and 98 from DCD. Kidney, liver, and patient survival from DCD donors were inferior to DBD at 1, 3, and 5 years (P=0.0056, P=0.0035, and P=0.0205, respectively). With the use of the Cox model, DCD was a significant risk factor for kidney and liver allograft failure and patient mortality. Recipient factors that were associated with worse allograft and patient outcomes included black race, diabetes, being on a ventilator, hospitalization, delayed graft function, hepatocellular carcinoma, and intensive care unit stay. Older age of the donor was also associated with worse outcomes. Despite the decreased allograft and patient survival compared with DBD, DCD SLK provides an acceptable option for SLK, with a survival probability of more than 50% at 5 years.

  19. Yogurt Feeding Induced the Prolongation of Fully Major Histocompatibility Complex-Mismatched Murine Cardiac Graft Survival by Induction of CD4+Foxp3+ Cells.

    Science.gov (United States)

    Uchiyama, M; Yin, E; Yanagisawa, T; Jin, X; Hara, M; Matsuyama, S; Imazuru, T; Uchida, K; Kawamura, M; Niimi, M

    Yogurt is a nutrient-rich food and the beneficial effects of yogurt on both health and immunomodulatory effects are well documented. In this pilot study, we investigated the effects of commercially produced yogurt R-1 on alloimmune responses in a murine cardiac transplantation model. The R-1 is produced by Meiji Co., Ltd., and contains live and active lactic acid bacteria (lactobacillus bulgaricus OLL1073R-1) mainly. CBA (H2 k ) mice underwent transplantation of a C57BL/6 (H2 b ; B6) heart and received oral administration of 1 mL, 0.1 mL, and 0.01 mL of R-1 from the day of transplantation until 7 days afterward. Additionally, we prepared one group of CBA recipients given 1 mL of R-1 sterilized by microwave for 7 days. Histological and immunohistochemical studies were performed. Naïve CBA mice rejected B6 cardiac graft acutely (median survival time [MST]: 7 days). CBA recipients given of 1 mL of R-1 had significantly prolonged B6 allograft survival (MST, 27 days). However, other doses of 0.1 mL and 0.01 mL of R-1 did not prolonged allograft survival (MSTs, 9 days and 8.5 days, respectively). Also, CBA recipients administered microwaved R-1 had no prolongation of B6 allograft (MST, 9 days). Histological and immunohistochemical studies showed the cardiac allograft from R-1-exposed CBA recipients had preserved graft and vessel structure and the number of infiltrated CD4 + , CD8 + , and Foxp3 + cells in R-1-exposed CBA recipients increased, respectively. In conclusion, our findings imply that yogurt containing active lactic acid bacteria could change alloimmune responses partially and induce the prolongation of cardiac allograft survival via CD4 + Foxp3 + regulatory cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Radiation sterilisation of tissue allografts for transplant surgery

    International Nuclear Information System (INIS)

    Phillips, G.O.

    1994-01-01

    The application of ionising radiation to sterilise biological tissues is an extension of their use for the sterilisation of other medical products and pharmaceuticals. This paper describes the effects of radiation on biological tissues, both at the macro- and molecular level. Changes in mechanical and other physical properties can accompany irradiation. These are shown to be due to the glycosamino-glycan component (hyaluronic acid), rather than to the collagen fibrils. Fast reaction methods are used to identify the mechanism of the radiation degradation processes. Methods by which tissues can be protected from these undesirable effects are discussed. The application of radiation sterilisation to human tissues used in transplant surgery is described, and the practical methods of processing given. Such radiation sterilised allografts now have wide application, with more than 500,000 used each year. The IAEA programme in this field has extended the application to 13 countries of the Asia and Pacific Region. Such Tissue Banks are also established with the support of IAEA in Africa and South America. The allografts can now be produced in developing countries in a readily available form, at low cost, and reduce the need for costly imported alternatives. (author). 45 refs., 19 figs., 3 tabs

  1. Nocturnal polyuria and saluresis in renal allograft recipients.

    Science.gov (United States)

    Chan, M K; Varghese, Z; Fernando, O N; Moorhead, J F

    1980-01-01

    The evolution of nocturnal polyuria and saluresis in renal allograft recipients was studied by comparing the day to night (D:N) ratios of urine volume and sodium excretion in 15 patients who had undergone transplantation less than one year previously (recent-transplant group) with those in 11 patients who had undergone transplantation at least one year previously. Eleven patients with chronic renal failure and 12 normal subjects served as controls. Patients in the recent-transplant group had significantly lower D:N ratios of urine volume and sodium excretion than the patients who had undergone transplantation at least a year before, while the ratios in this last group did not differ significantly from those in the normal subjects. Nocturnal polyuria and saluresis gradually subsided in five patients studied for three months. Chronic renal failure and uraemic autonomic neuropathy were unlikely causes of the nocturia. The patients in the recent-transplant group had significantly lower D:N ratios of urine volume than the controls with chronic renal failure, and the mean Valsalva ratio in eight of them was not significantly different from that in the normal subjects. An undue sensitivity of renal allografts to postural influences was proposed. PMID:6986946

  2. Femoral head allograft disinfection system using moderate heat

    International Nuclear Information System (INIS)

    Knaepler, H.; Von Garrel, T.

    1999-01-01

    The employment of a reliable thermal viral inactivation process, which minimally manipulates tissues, for surgically retrieved femoral head allografts addresses the increased concerns with virus transmissibility while minimizing the loss of biological properties. The newest European and German surgical bone banking guidelines have incorporated the use of independently validated then-nal viral inactivation methods in place of repeat serological testing of donor. Our investigations have shown that heat treatment at 80 degree C for a minimum of 10 minutes provides safe, good quality cancellous bone allografts and increases the cost-effectiveness and simplicity of managing a hospital frozen femoral head bone bank. Human femoral head centers were contaminated with different vegetative bacterial and viral suspensions. A core temperature of 80 degree C for 10 minutes was sufficient to fully inactivate 3 x 106 ml Staphylococcus aureus and Streptococcus faecalis, and >5 loglo steps of cytomeglia (herpes group), polio (enterovirus), and yellow fever (arbovirus) viruses. A one hour treatment in a water bath set at 80 degree sufficient to fully inactivate E. coli, proteus vulgaris, and Pseudomonas aerog. vegetative suspensions; 20 minutes was sufficient to fully inactivate the D antigen (rhesus factor) but had no effect on A or B antigens. Several biomechanical and biological properties of bone following a one hour treatment in a water bath set at 80 degree C were investigated. Employing compression and tension tests, 80 degree C treated human and porcine cancellous bone blocks showed reductions in properties ranging from 8-19% compared to untreated control groups. Osteointegration at 3 months following treatment of explanted and then reimplanted autograft rat diaphyseal segment was 15% less than untreated controls. Subsequently, a thermal disinfection system for femoral heads from living donors (Lobator Marburg Bone Bank System, Telos GmbH, Hungen, Germany) was developed. A

  3. Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without Incorporation of Autologous Mesenchymal Stem Cells.

    Science.gov (United States)

    Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

    2018-02-01

    The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at -80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

  4. 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.

  5. Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

    Science.gov (United States)

    Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

    2013-01-01

    Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

  6. 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. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. Allograft pretreatment for the repair of sciatic nerve defects: green tea polyphenols versus radiation

    Directory of Open Access Journals (Sweden)

    Sheng-hu Zhou

    2015-01-01

    Full Text Available Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can eliminate 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-pretreated 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-pretreated 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 fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to transplanting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation

  8. Cost effectiveness of meniscal allograft for torn discoid lateral meniscus in young women.

    Science.gov (United States)

    Ramme, Austin J; Strauss, Eric J; Jazrawi, Laith; Gold, Heather T

    2016-09-01

    A discoid meniscus is more prone to tears than a normal meniscus. Patients with a torn discoid lateral meniscus are at increased risk for early onset osteoarthritis requiring total knee arthroplasty (TKA). Optimal management for this condition is controversial given the up-front cost difference between the two treatment options: the more expensive meniscal allograft transplantation compared with standard partial meniscectomy. We hypothesize that meniscal allograft transplantation following excision of a torn discoid lateral meniscus is more cost-effective compared with partial meniscectomy alone because allografts will extend the time to TKA. A decision analytic Markov model was created to compare the cost effectiveness of two treatments for symptomatic, torn discoid lateral meniscus: meniscal allograft and partial meniscectomy. Probability estimates and event rates were derived from the scientific literature, and costs and benefits were discounted by 3%. One-way sensitivity analyses were performed to test model robustness. Over 25 years, the partial meniscectomy strategy cost $10,430, whereas meniscal allograft cost on average $4040 more, at $14,470. Partial meniscectomy postponed TKA an average of 12.5 years, compared with 17.30 years for meniscal allograft, an increase of 4.8 years. Allograft cost $842 per-year-gained in time to TKA. Meniscal allografts have been shown to reduce pain and improve function in patients with discoid lateral meniscus tears. Though more costly, meniscal allografts may be more effective than partial meniscectomy in delaying TKA in this model. Additional future long term clinical studies will provide more insight into optimal surgical options.

  9. Daptomycin as a possible new treatment option for surgical management of Methicillin-Resistant Staphylococcus aureus sternal wound infection after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Emmert Alexander

    2010-08-01

    Full Text Available Abstract We present a case of a 77-year old female who had undergone a coronary artery bypass grafting with an aortic valve replacement and developed three month later a Methicillin-Resistant Staphylococcus aureus (MRSA sternal wound infection which was successful treated with Daptomycin combined with vacuum-assisted closure (VAC.

  10. 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.

  11. The use of allograft bone in reconstruction of the acetabulum during hip revision arthroplasty

    International Nuclear Information System (INIS)

    David, A.; Morgan, F.; Imran Ilyas

    1999-01-01

    We have reviewed 80 patients who underwent an allograft acetabular reconstruction between 1987 and 1995. This group had a mean age of 66 years with a mean follow-up of 5.2 years. A mean preoperative Harris hip score of 32 points was improved to a mean postoperative score of 72 points. There was a 16.5% rerevision rate. Acetabular defects were classified according to the American Academy of Orthopaedic Surgeons system. Subgroup classification categories were analysed and reconstruction methodologies have been devised. This paper deals with the relative indications for the use of morsellised bone, block allografts, anatomic specific allografts and reconstruction shells according to type of acetabular defects

  12. Complete recovery of renal allograft function after six days of delay following living related transplantation

    International Nuclear Information System (INIS)

    Arogundade, F.A.; Sanusi, A.A.; Badmus, T.A.

    2008-01-01

    Delayed graft function (DGF), a term employed when a newly transplanted organ does not function efficiently is commonly observed following cadaveric renal transplantation but is very rare after living related transplants. We present a 31-year-old female recipient of a related donor kidney (mother) who had DGF following transplantation due to acute tubular necrosis, probably caused by partial allograft arterial thrombosis, which recovered function after 60 days. Appropriate use of allograft biopsy should be encouraged even in resource-limited settings lest the allograft be assumed to have failed irreversibly. (author)

  13. 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. 

  14. Cardiac pacemaker

    International Nuclear Information System (INIS)

    Kolenik, S.A.

    1976-01-01

    The construction of a cardiac pacemaker is described which is characterized by particularly small dimensions, small weight and long life duration. The weight is under 100g, the specific weight under 1.7. Mass inertia forces which occur through acceleration and retardation processes, thus remain below the threshold values, above which one would have to reckon with considerable damaging of the surrounding body tissue. The maintaining of small size and slight weight is achieved by using an oscillator on COSMOS basis, where by considerably lower energy consumption, amongst others the lifetimes of the batteries used - a lithium anode with thionyl chloride electrolyte - is extended to over 5 years. The reliability can be increased by the use of 2 or more batteries. The designed dimension are 20x60x60 mm 3 . (ORU/LH) [de

  15. Cardiac ventriculography

    International Nuclear Information System (INIS)

    Hillis, L.D.; Grossman, W.

    1986-01-01

    Cardiac ventriculography has been used extensively to define the anatomy of the ventricles and related structures in patients with congenital, valvular, coronary, and cardiomyopathic heart disease. Specifically, left ventriculography may provide valuable information about global and segmental left ventricular function, mitral valvular incompetence, and the presence, location, and severity of a number of other abnormalities, including ventricular septal defect and hypertrophic cardiomyopathy. As a result, it should be a routine part of catheterization in patients being evaluated for coronary artery disease, aortic or mitral valvular disease, unexplained left ventricular failure, or congenital heart disease. Similarly, right ventriculography may provide information about global and segmental right ventricular function and can be especially helpful in patients with congenital heart disease

  16. Impact of post-kidney transplant parathyroidectomy on allograft function

    Science.gov (United States)

    Parikh, Samir; Nagaraja, Haikady; Agarwal, Anil; Samavedi, Srinivas; Von Visger, Jon; Nori, Uday; Andreoni, Kenneth; Pesavento, Todd; Singh, Neeraj

    2013-01-01

    Background The impact of parathyroidectomy on allograft function in kidney transplant patients is unclear. Methods We conducted a retrospective, observational study of all kidney transplant recipients from 1988 to 2008 who underwent parathyroidectomy for uncontrolled hyperparathyroidism (n = 32). Post-parathyroidectomy, changes in estimated glomerular filtration rate (eGFR) and graft loss were recorded. Cross-sectional associations at baseline between eGFR and serum calcium, phosphate, and parathyroid hormone (PTH), and associations between their changes within subjects during the first two months post-parathyroidectomy were assessed. Results Post-parathyroidectomy, the mean eGFR declined from 51.19 mL/min/1.73 m2 at parathyroidectomy to 44.78 mL/min/1.73 m2 at two months (p < 0.0001). Subsequently, graft function improved, and by 12 months, mean eGFR recovered to 49.76 mL/min/1.73 m2 (p = 0.035). Decrease in serum PTH was accompanied by a decrease in eGFR (p = 0.0127) in the first two months post-parathyroidectomy. Patients whose eGFR declined by ≥ 20% (group 1) in the first two months post-parathyroidectomy were distinguished from the patients whose eGFR declined by <20% (group 2). The two groups were similar except that group 1 had a higher baseline mean serum PTH compared with group 2, although not significant (1046.7 ± 1034.2 vs. 476.6 ± 444.9, p = 0.14). In group 1, eGFR declined at an average rate of 32% (p < 0.0001) during the first month post-parathyroidectomy compared with 7% (p = 0.1399) in group 2, and the difference between these two groups was significant (p = 0.0003). The graft function recovered in both groups by one yr. During median follow-up of 66.00 ± 49.45 months, 6 (18%) patients lost their graft with a mean time to graft loss from parathyroidectomy of 37.2 ± 21.6 months. The causes of graft loss were rejection (n = 2), pyelonephritis (n = 1) and chronic allograft nephropathy (n = 3). No graft loss occurred during the first-year post

  17. Quality control processes in allografting: A twenty-year retrospective review of a hospital-based bone bank in Taiwan.

    Science.gov (United States)

    Fu, Shau-Huai; Liu, Jyh-You; Huang, Chuan-Ching; Lin, Feng-Ling; Yang, Rong-Sen; Hou, Chun-Han

    2017-01-01

    Musculoskeletal allografts are now commonly used. To decrease the potential risks of transmission of pathogenic bacteria, fungi, or viruses to the transplant recipients, certain issues regarding the management of patients who receive contaminated allografts need to be addressed. We aimed to clarify the incidence and extent of disease transmission from allografts by analyzing the allografting procedures performed in the bone bank of our hospital over the past 20 years. We retrospectively reviewed the data from our allograft registry center on 3979 allografts that were implanted in 3193 recipients throughout a period of two decades, from July 1991 to June 2011. The source of the allografts, results of all screening tests, dates of harvesting and implantation, and recipients of all allografts were checked. With the help of the Center for Infection Control of our hospital, a strict prospective, hospital-wide, on-site surveillance was conducted, and every patient with healthcare-associated infection was identified. Fisher's exact test was used to compare the infection rate between recipients with sterile allografts and those with contaminated allografts. The overall discard and infection rates were, respectively, 23% and 1.3% in the first decade (1991-2001); and 18.4% and 1.25% in the second decade (2001-2011). The infection rate of contaminated allograft recipients was significantly higher than that of sterile allograft recipients (10% vs. 1.15%, P bank are comparable with those of international bone banks. Strict allograft processing and adequate prophylactic use of antibiotics are critical to prevent infection and disease transmission in such cases.

  18. Quality control processes in allografting: A twenty-year retrospective review of a hospital-based bone bank in Taiwan.

    Directory of Open Access Journals (Sweden)

    Shau-Huai Fu

    Full Text Available Musculoskeletal allografts are now commonly used. To decrease the potential risks of transmission of pathogenic bacteria, fungi, or viruses to the transplant recipients, certain issues regarding the management of patients who receive contaminated allografts need to be addressed. We aimed to clarify the incidence and extent of disease transmission from allografts by analyzing the allografting procedures performed in the bone bank of our hospital over the past 20 years. We retrospectively reviewed the data from our allograft registry center on 3979 allografts that were implanted in 3193 recipients throughout a period of two decades, from July 1991 to June 2011. The source of the allografts, results of all screening tests, dates of harvesting and implantation, and recipients of all allografts were checked. With the help of the Center for Infection Control of our hospital, a strict prospective, hospital-wide, on-site surveillance was conducted, and every patient with healthcare-associated infection was identified. Fisher's exact test was used to compare the infection rate between recipients with sterile allografts and those with contaminated allografts. The overall discard and infection rates were, respectively, 23% and 1.3% in the first decade (1991-2001; and 18.4% and 1.25% in the second decade (2001-2011. The infection rate of contaminated allograft recipients was significantly higher than that of sterile allograft recipients (10% vs. 1.15%, P < 0.01 in the second decade. Both infection and discard rates of our bone bank are comparable with those of international bone banks. Strict allograft processing and adequate prophylactic use of antibiotics are critical to prevent infection and disease transmission in such cases.

  19. Acute Hepatic Allograft Rejection in Pediatric Recipients: Effective Factors.

    Science.gov (United States)

    Dehghani, S M; Shahramian, I; Afshari, M; Bahmanyar, M; Ataollahi, M; Sargazi, A

    2018-01-01

    Acute cellular rejection (ACR), a reversible process, can affect the graft survival. To evaluate the relation between ACR and clinical factors in recipients of allograft liver transplantation. 47 recipients of liver were consecutively enrolled in a retrospective study. Their information were retrieved from their medical records and analyzed. Of the 47 recipients, 38 (81%) experienced acute rejection during 24 months of the transplantation. None of the studied factors for occurring transplant rejection, i.e ., blood groups, sex, age, familial history of disease, receiving drugs and blood products, type of donor, Child score, and Child class, was not found to be significant. During a limited follow-up period, we did not find any association between ACR and suspected risk factors.

  20. 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

  1. Platelet deposition in rat heart allografts and the effect of a thromboxane receptor antagonist

    International Nuclear Information System (INIS)

    Foegh, M.L.; Khirabadi, B.S.; Ramwell, P.W.

    1986-01-01

    The effect of a thromboxane antagonist, L640,035 on platelet deposition in heart allografts was studied. Twenty Lewis rats received heterotopic allografts from Lewis x Brown-Norway F1 hybrid. All recipients received azathioprine (5 mg/kg/day). The rats were divided into three groups. Groups II and III were also treated daily with either the vehicle for L640,035 or L640,035 respectively. Syngeneic indium-111-labeled platelet deposition was determined in the allograft and the native heart at 6, 9, and 13 days after transplantation; group III was studied on the sixth and ninth day only. A rapidly increasing platelet deposition was seen in allografts from rats given azathioprine; whereas the thromboxane antagonist prevented the increase in platelet deposition on the ninth day

  2. 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.

  3. 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.

  4. RNA-seq analysis of clinical-grade osteochondral allografts reveals activation of early response genes

    NARCIS (Netherlands)

    Lin, Yang; Lewallen, Eric A.; Camilleri, Emily T.; Bonin, Carolina A.; Jones, Dakota L.; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J.; Larson, Annalise N.; Dahm, Diane L.; Stuart, Michael J.; Levy, Bruce A.; Smith, Jay; Ryssman, Daniel B.; Westendorf, Jennifer J.; Im, Hee-Jeong; van Wijnen, Andre J.; Riester, Scott M.; Krych, Aaron J.

    2016-01-01

    Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression

  5. The use of allograft bone during the course of femoral reconstruction in hip revision arthroplasty

    International Nuclear Information System (INIS)

    David, A.; Morgan, F.; Imran Ilyas

    1999-01-01

    We have studied 61 patients who underwent femoral revision surgery requiring allograft reconstruction of the skeleton between 1987 and 1995. The group had a mean age of 68 years with a mean follow-up of 5.1 years. The preoperative Harris hip score was increased from 30 points to a postoperative score of 69 points. A rerevision rate of 20% was noted. Segmental anomalies were classified according to the American Academy of Orthopaedic Surgeons system. Subgroups were analysed according to the classification and relative indications for the use of impaction allografting, corticocancellous strut grafting, anatomic specific allografts and calcar allografts were devised. This paper details the results of those subgroups and outlines pitfalls and problems associated with complex surgery of this type

  6. 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.

  7. Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance

    NARCIS (Netherlands)

    Brouard, Sophie; Mansfield, Elaine; Braud, Christophe; Li, Li; Giral, Magali; Hsieh, Szu-Chuan; Baeten, Dominique; Zhang, Meixia; Ashton-Chess, Joanna; Braudeau, Cecile; Hsieh, Frank; Dupont, Alexandre; Pallier, Annaik; Moreau, Anne; Louis, Stephanie; Ruiz, Catherine; Salvatierra, Oscar; Soulillou, Jean-Paul; Sarwal, Minnie

    2007-01-01

    Long-term allograft survival generally requires lifelong immunosuppression (IS). Rarely, recipients display spontaneous "operational tolerance" with stable graft function in the absence of IS. The lack of biological markers of this phenomenon precludes identification of potentially tolerant patients

  8. 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

  9. Characterization of ionizing radiation effects on human skin allografts

    International Nuclear Information System (INIS)

    Bourroul, Selma Cecilia

    2004-01-01

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

  10. Outcomes of Renal Allograft Recipients With Hepatitis C.

    Science.gov (United States)

    Carpio, R; Pamugas, G E; Danguilan, R; Que, E

    2016-04-01

    Studies on the effect of hepatitis C virus (HCV) infection showed decreased graft survival compared to HCV-negative matched patients. It was also identified as an independent risk factor for graft loss and mortality in kidney transplantation patients. This study was designed to evaluate the 10-year graft and patient outcomes of renal allograft recipients with HCV infection at the National Kidney and Transplant Institute. This is a retrospective study of patients who underwent renal transplantation with HCV infection and a group who were HCV-negative in the same post-transplantation period. Data were gathered from the in-patient and out-patient clinic records. Patient survival was significantly lower in the HCV-positive than in the HCV-negative group. The mean duration of patient survival was 154.95 (+4.95) months (12 years and 10 months) in HCV-negative patients compared to 141 (+6.52) months (11 years and 9 months) in the HCV-positive group (P = .05). Graft survival did not differ significantly between HCV-positive and HCV-negative recipients (P = .734). The mean duration of graft survival was 137 (+7.68) months (11 years and 5 months) in HCV-negative patients compared to 130 (+6.84) months (10 years and 10 months) in HCV-positive patients. Short- and long-term outcomes including biopsy-proven acute rejection, transplant glomerulopathy, chronic allograft nephropathy, renal function, and proteinuria were similar in both groups. Rejection, glomerulopathy, and renal function were similar in both groups. HCV progression was also observed in patients with detectable HCV-RNA 6 months before transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Effect of cold nerve allograft preservation on antigen presentation and rejection

    Science.gov (United States)

    Ray, Wilson Z.; Kale, Santosh S.; Kasukurthi, Rahul; Papp, Esther M.; Johnson, Philip J.; Santosa, Katherine B.; Yan, Ying; Hunter, Daniel A.; Mackinnon, Susan E.; Tung, Thomas H.

    2010-01-01

    Object Nerve allotransplantation provides a temporary scaffold for host nerve regeneration and allows for the reconstruction of significant segmental nerve injuries. The need for systemic the current clinical utilization of nerve allografts, although this need is reduced by the practice of cold nerve allograft preservation. Activation of T cells in response to alloantigen presentation occurs in the context of donor antigen presenting cells (direct pathway) or host antigen-presenting cells (indirect pathway). The relative role of each pathway in eliciting an alloimmune response and its potential for rejection of the nerve allograft model has not previously been investigated. The objective of this investigation was to study the effect of progressive periods of cold nerve allograft preservation on antigen presentation and the alloimmune response. Methods The authors used wild type C57Bl/6 (B6), BALB/c, and major histocompatibility Class II–deficient (MHC−/−) C57Bl/6 mice as both nerve allograft recipients and donors. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap. Progressive cold preservation of donor nerve allografts was used. Quantitative assessment was made after 3 weeks using nerve histomorphometry. Results The donor-recipient combination lacking a functional direct pathway (BALB/c host with MHC−/− graft) rejected nerve allografts as vigorously as wild-type animals. Without an intact indirect pathway (MHC−/− host with BALB/c graft), axonal regeneration was improved (p < 0.052). One week of cold allograft preservation did not improve regeneration to any significant degree in any of the donor-recipient preservation did improve regeneration significantly (p < 0.05) for all combinations compared with wild-type animals without pretreatment. However, only in the presence of an intact indirect pathway (no direct pathway) did 4 weeks of cold preservation improve regeneration significantly compared with 1 week and no

  12. A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection

    OpenAIRE

    Shi, Ming; Liu, Zhenwen; Wang, Ying; Xu, Rounan; Sun, Yanling; Zhang, Min; Yu, Xi; Wang, Hongbo; Meng, Lingzhan; Su, Haibin; Jin, Lei; Wang, Fu‐Sheng

    2017-01-01

    Abstract Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned int...

  13. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection

    OpenAIRE

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-01-01

    Background Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. Methods The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules inc...

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

    OpenAIRE

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

    2014-01-01

    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 6,216 incident, pediatric End Stage Renal Disease patients in the United States Renal Data System (kidney transplant fr...

  15. Processing of gamma irradiated bone allografts for treatment of injuries in a nuclear scenario

    International Nuclear Information System (INIS)

    Singh, Durgeshwer; Singh, Antaryami; Singh, Rita; Shah, Om

    2014-01-01

    Bone allografts fill an important void in the surgical practice of orthopaedic surgery, and their use to replace and reconstruct musculoskeletal structures following injury or disease has gained increasing acceptance by orthopaedic surgeons. Serious mechanical injuries in a nuclear scenario involving compression, displacement and missile hit will lead to high incidence of various kinds of bone fractures, spinal injuries and joint injuries apart from lethality, lung damage and eardrum rupture. Bone allografts can be employed for repairing fracture defects, filling in destroyed regions of bone, management of open fractures and joint injuries. Autologous bone grafts, though ideal, have the drawback of secondary surgery for autograft retrieval, complications of infection and donor site morbidity. Bone allografts eliminate additional incision necessary for acquiring an autograft and consequently reduce operating time, blood loss as well as hospital and medical costs. However, disease transmission and bacterial infection in bone allograft transplantation is of significant concern. Sterilization by gamma irradiation is a definitive method for eliminating microorganisms and can prevent life-threatening allograft associated infections. The present study was carried out with the aim of bioburden assessment, radiation sterilization and clinical evaluation of bone allografts processed from femoral heads obtained from living donors. Femoral heads were obtained during surgery at Department of Orthopaedic Surgery, SN Medical College, Jodhpur and processed as freeze-dried bone allografts. Bioburden of bone allografts was found to be in the range of 2.26 to 3.59 log CFU/g. Verification dose for different batches of processing was 7.24±1.27 kGy. Radiological data of processed gamma irradiated bone grafts used in clinical cases of trauma surgery was recorded and has shown successful graft incorporation in allogenic recipients. (author)

  16. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection.

    Science.gov (United States)

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-11-03

    Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules including chemokine receptor type 5 (CXCR5), inducible T cell co-stimulator (ICOS), programmed death-1 (PD-1), ICOSL, PDL-1 and interleukin-21 (IL-21), of peripheral blood were comparatively measured in 42 primary renal allograft recipients within 1-3 years after transplantation. Among them, 24 patients had definite chronic rejection, while other 18 patients had normal renal function. Tfh-cell ratio was significantly increased with PD-1 down-regulation in the patients with chronic renal allograft rejection, while B cells and the alloimmune-regulating molecules studied did not show any appreciable change in parallel. The patients with chronic renal allograft rejection have a characteristic increase in circulating Tfh cells with a decrease in PD-1 expression. These pathological changes may be a therapeutic target for the treatment of chronic renal allograft rejection and can be useful as a clinical index for monitoring conditions of renal transplant.

  17. Soluble CD30 correlates with clinical but not subclinical renal allograft rejection.

    Science.gov (United States)

    Hirt-Minkowski, Patricia; Roth, Michèle; Hönger, Gideon; Amico, Patrizia; Hopfer, Helmut; Schaub, Stefan

    2013-01-01

    Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate-based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post-transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus-mycophenolate-based immunosuppression. © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.

  18. Injury to Allografts: innate immune pathways to acute and chronic rejection

    International Nuclear Information System (INIS)

    Land, W. G.

    2005-01-01

    An emerging body of evidence suggests that innate immunity, as the first line of host defense against invading pathogens or their components [pathogen-associated molecular patterns, (PAMPs)], plays also a critical role in acute and chronic allograft rejection. Injury to the donor organ induces an inflammatory milieu in the allograft, which appears to be the initial key event for activation of the innate immune system. Injury-induced generation of putative endogenous molecular ligand, in terms of damaged/danger-associated molecular patterns (DAMPs) such as heat shock proteins, are recognized by Toll-like receptors (TLRs), a family of pattern recognition receptors on cells of innate immunity. Acute allograft injury (e.g. oxidative stress during donor brain-death condition, post-ischemic reperfusion injury in the recipient) includes DAMPs which may interact with, and activate, innate TLR-bearing dendritic cells (DCs) which, in turn, via direct allo-recognition through donor-derived DCs and indirect allo-recogntion through recipient-derived DCs, initiate the recipient's adaptive alloimmune response leading to acute allograft rejection. Chronic injurious events in the allograft (e.g. hypertension, hyperlipidemia, CMV infection, administration of cell-toxic drugs [calcineurin-inhibitors]) induce the generation of D AMPs , which may interact with and activate innate TLR-bearing vascular cells (endothelial cells, smooth muscle cells) which, in turn, contribute to the development of atherosclerosis of donor organ vessels (alloatherosclerosis), thus promoting chronic allograft rejection. (author)

  19. Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

    Science.gov (United States)

    Yang, Chun-Hua; Lu, Yi; Chen, Xue-Xia; Xian, Wen-Feng; Tu, Wei-Feng; Li, Hong-Yan

    2015-12-01

    The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association. © The Author(s) 2015.

  20. Evaluation of renal allograft function early after transplantation with diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Eisenberger, Ute; Frey, Felix J.; Thoeny, Harriet C.; Binser, Tobias; Boesch, Chris; Gugger, Mathias; Vermathen, Peter

    2010-01-01

    To determine the inter-patient variability of apparent diffusion coefficients (ADC) and concurrent micro-circulation contributions from diffusion-weighted MR imaging (DW-MRI) in renal allografts early after transplantation, and to obtain initial information on whether these measures are altered in histologically proven acute allograft rejection (AR). DW-MRI was performed in 15 renal allograft recipients 5-19 days after transplantation. Four patients presented with AR and one with acute tubular necrosis (ATN). Total ADC (ADC T ) was determined, which includes diffusion and micro-circulation contributions. Furthermore, diffusion and micro-circulation contributions were separated, yielding the ''perfusion fraction'' (F P ), and ''perfusion-free'' diffusion (ADC D ). Diffusion parameters in the ten allografts with stable function early after transplantation demonstrated low variabilities. Values for ADC T and ADC D were (x 10 -5 mm 2 /s) 228 ± 14 and 203 ± 9, respectively, in cortex and 226 ± 16 and 199 ± 9, respectively, in medulla. F P values were 18 ± 5% in cortex and 19 ± 5% in medulla. F P values were strongly reduced to less than 12% in cortex and medulla of renal transplants with AR and ATN. F P values correlated with creatinine clearance. DW-MRI allows reliable determination of diffusion and micro-circulation contributions in renal allografts shortly after transplantation; deviations in AR indicate potential clinical utility of this method to non-invasively monitor derangements in renal allografts. (orig.)

  1. Pancreatic islet allograft in spleen with immunosuppression with cyclosporine. Experimental model in dogs.

    Science.gov (United States)

    Waisberg, Jaques; Neff, Charles Benjamin; Waisberg, Daniel Reis; Germini, Demetrius; Gonçalves, José Eduardo; Zanotto, Arnaldo; Speranzini, Manlio Basilio

    2011-01-01

    To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. In the animals with immunosuppression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.

  2. Effect of gamma-irradiation on mouse pancreatic islet-allograft survival

    International Nuclear Information System (INIS)

    Kanai, T.; Porter, J.; Gotoh, M.; Monaco, A.P.; Maki, T.

    1989-01-01

    Elimination or inactivation of lymphoid tissue in the pancreatic islet preparation achieves prolongation of islet-allograft survival. In this study we examined the effect of gamma-irradiation on mouse islet-allograft survival. In a B6AF1 isograft model, irradiation up to 2400 rad did not induce deterioration of islet function over 200 days, but greater doses caused cessation of graft function between 83 and 186 days. When DBA/2 crude islets were transplanted into B6AF1 recipients, all nonirradiated allografts were acutely rejected. Marked prolongation of allograft survival was achieved by islet irradiation with doses between 800 and 12,000 rad. With higher doses, significant numbers of allografts survived beyond the controls, but many lost function between 78 and 180 days, with none surviving greater than 200 days. Irradiation with 16,000 rad caused acute radiation damage. Because most secondary islet allografts in recipient mice that lost primary islet-graft function between 84 and 195 days survived greater than 100 days, late functional loss was probably due to the radiation injury. Combined use of recipient treatment with cyclosporin A and graft irradiation (2400 rad) achieved prolongation of DBA/2 islets in B6AF1 mice

  3. Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

    Science.gov (United States)

    Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

    2013-11-01

    Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  4. The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

    Science.gov (United States)

    Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

    2017-08-01

    Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

  5. Serum cortisol concentration with exploratory cut-off values do not predict the effects of hydrocortisone administration in children with low cardiac output after cardiac surgery

    NARCIS (Netherlands)

    Verweij, E. J.; Hogenbirk, Karin; Roest, Arno A. W.; van Brempt, Ronald; Hazekamp, Mark G.; de Jonge, Evert

    2012-01-01

    Low cardiac output syndrome is common after paediatric cardiac surgery. Previous studies suggested that hydrocortisone administration may improve haemodynamic stability in case of resistant low cardiac output syndrome in critically ill children. This study was set up to test the hypothesis that the

  6. Cardiac regeneration therapy: connections to cardiac physiology.

    Science.gov (United States)

    Takehara, Naofumi; Matsubara, Hiroaki

    2011-12-01

    Without heart transplantation, a large number of patients with failing hearts worldwide face poor outcomes. By means of cardiomyocyte regeneration, cardiac regeneration therapy is emerging with great promise as a means for restoring loss of cardiac function. However, the limited success of clinical trials using bone marrow-derived cells and myoblasts with heterogeneous constituents, transplanted at a wide range of cell doses, has led to disagreement on the efficacy of cell therapy. It is therefore essential to reevaluate the evidence for the efficacy of cell-based cardiac regeneration therapy, focusing on targets, materials, and methodologies. Meanwhile, the revolutionary innovation of cardiac regeneration therapy is sorely needed to help the millions of people who suffer heart failure from acquired loss of cardiomyocytes. Cardiac regeneration has been used only in limited species or as a developing process in the rodent heart; now, the possibility of cardiomyocyte turnover in the human heart is being revisited. In the pursuit of this concept, the use of cardiac stem/progenitor stem cells in the cardiac niche must be focused to usher in a second era of cardiac regeneration therapy for the severely injured heart. In addition, tissue engineering and cellular reprogramming will advance the next era of treatment that will enable current cell-based therapy to progress to "real" cardiac regeneration therapy. Although many barriers remain, the prevention of refractory heart failure through cardiac regeneration is now becoming a realistic possibility.

  7. Effects of renal denervation with a standard irrigated cardiac ablation catheter on blood pressure and renal function in patients with chronic kidney disease and resistant hypertension.

    Science.gov (United States)

    Kiuchi, Márcio Galindo; Maia, George Luiz Marques; de Queiroz Carreira, Maria Angela Magalhães; Kiuchi, Tetsuaki; Chen, Shaojie; Andrea, Bruno Rustum; Graciano, Miguel Luis; Lugon, Jocemir Ronaldo

    2013-07-01

    Evaluation of the safety and efficacy of renal denervation with a standard irrigated cardiac ablation catheter (SICAC) in chronic kidney disease (CKD) patients with refractory hypertension. Twenty-four patients were included and treated with a SICAC. Denervation was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n = 16), 3 (n = 4), and 4 (n = 4). Data were obtained at baseline and monthly until 180th day of follow-up. Baseline values of blood pressure (mean ± SD) were 186 ± 19 mmHg/108 ± 13 mmHg in the office, and 151 ± 18 mmHg/92 ± 11 mmHg by 24 h ambulatory blood pressure monitoring (ABPM). Office blood pressure values at 180th day after the procedure were 135 ± 13 mmHg/88 ± 7 mmHg (P < 0.0001, for both comparisons). The mean ABPM decreased to 132 ± 15 mmHg/85 ± 11 mmHg at the 180th day after the procedure (P < 0.0001 for systolic and P = 0.0015 for diastolic). Estimated glomerular filtration (mean ± SD) increased from baseline (64.4 ± 23.9 mL/min/1.73 m(2)) to the 180th day (85.4 ± 34.9 mL/min/1.73 m(2), P < 0.0001) of follow-up. The median urine albumin:creatinine ratio decreased from baseline (48.5, IQR: 35.8-157.2 mg/g) to the 180th day after ablation (ACR = 15.7, IQR: 10.3-34.2 mg/g, P = 0.0017). No major complications were seen. The procedure using SICAC seemed to be feasible, effective, and safe resulting in a better control of BP, a short-term increase in estimated glomerular filtration rate, and reduced albuminuria. Although encouraging, our data are preliminary and need to be validated in the long term.

  8. Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

    OpenAIRE

    Hayam Abdel Meguid El Aggan; Mona Abdel Kader Salem; Nahla Mohamed Gamal Farahat; Ahmad Fathy El-Koraie; Ghaly Abd Al-Rahim Mohammed Kotb

    2013-01-01

    Introduction: Chronic allograft nephropathy (CAN) is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs) and mesenchymal stem cells (MSCs). Char...

  9. Experience with a bone bank operation and allograft bone infection in recipients at a medical centre in southern Taiwan.

    Science.gov (United States)

    Liu, J W; Chao, L H; Su, L H; Wang, J W; Wang, C J

    2002-04-01

    To assess the contamination rate of allograft bones at retrieval and the infection rate of the implanted allograft bone, we audited a bone bank retrospectively and reviewed the medical charts of allograft bone recipients between June 1999 and June 2000 at a medical centre in southern Taiwan. The bone bank did its utmost to minimize allograft contamination with hospital-acquired pathogens by adopting purposefully designed criteria for selection of donors. This protocol included sterilization with soaking of the retrieved allograft in a solution of a first-generation cephalosporin before storage and prophylaxis in recipients with first-generation cephalosporin. The contamination rates at allograft retrieval from living and cadaveric donors were 2.7% and 12.4%, respectively (P<0.001). Culture of 262 specimens taken at allograft implant revealed 12 (4.6%) positive for culture. Of the 12 patients implanted with allograft bones positive for culture, nine (75.0%) had allograft bone infection, while three (25.0%) did not. Among the 250 recipients with sterile allograft bones, four (1.6%) were found to have allograft infection. None of the cases of infection required removal of the allograft bones, and all cases were successfully treated with tailored antimicrobial therapy based on susceptibility tests on isolated bacteria. The overall infection rate was 5.0%, which compared favourably with those in other series. A prospective cohort study is needed to determine which of the varied sterilization methodologies gives the best and/or most cost-effective outcome. Copyright 2002 The Hospital Infection Society.

  10. External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

    Science.gov (United States)

    Hogan, T S

    2012-10-01

    Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient's cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

  11. External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

    LENUS (Irish Health Repository)

    Hogan, T S

    2012-10-01

    Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient\\'s cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

  12. iPSC-Derived Regulatory Dendritic Cells Inhibit Allograft Rejection by Generating Alloantigen-Specific Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Songjie Cai

    2017-05-01

    Full Text Available Regulatory dendritic cell (DCregs-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs, which could remain in a “stable immature stage” even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs, and induced donor-specific allograft acceptance. We immunized naive CBA (H-2Kk mice with B6 (H-2Kb iPS-DCregs and found that Tregs (CD4+CD25+FOXP3+ significantly increased in CBA splenocytes. Moreover, immunized CBA recipients permanently accepted B6 cardiac grafts in a donor-specific pattern. We demonstrated mechanistically that donor-type iPS-DCregs triggered transforming growth factor β1 secretion, under which the donor-antigen peptides directed naive CD4+ T cells to differentiate into donor-specific FOXP3+ Tregs instead of into effector T cells in vivo. These findings highlight the potential of iPS-DCregs as a key cell therapy resource in clinical transplantation.

  13. Species selective resistance of cardiac muscle voltage gated sodium channels: characterization of brevetoxin and ciguatoxin binding sites in rats and fish.

    Science.gov (United States)

    Dechraoui, Marie-Yasmine Bottein; Wacksman, Jeremy J; Ramsdell, John S

    2006-11-01

    Brevetoxins (PbTxs) and ciguatoxins (CTXs) are two suites of dinoflagellate derived marine polyether neurotoxins that target the voltage gated sodium channel (VGSC). PbTxs are commonly responsible for massive fish kills and unusual mortalities in marine mammals. CTXs, more often noted for human intoxication, are suspected causes of fish and marine mammal intoxication, although this has never been reported in the field. VGSCs, present in the membrane of all excitable cells including those found in skeletal muscle, nervous and heart tissues, are found as isoforms with differential expression within species and tissues. To investigate the tissue and species susceptibility to these biotoxins, we determined the relative affinity of PbTx-2 and -3 and P-CTX-1 to native VGSCs in the brain, heart, and skeletal muscle of rat and the marine teleost fish Centropristis striata by competitive binding in the presence of [(3)H]PbTx-3. No differences between rat and fish were observed in the binding of PbTxs and CTX to either brain or skeletal muscle. However, [(3)H]PbTx-3 showed substantial lower affinity to rat heart tissue while in the fish it bound with the same affinity to heart than to brain or skeletal muscle. These new insights into PbTxs and CTXs binding in fish and mammalian excitable tissues indicate a species related resistance of heart VGSC in the rat; yet, with comparable sensitivity between the species for brain and skeletal muscle.

  14. The protective effect of meniscus allograft transplantation on articular cartilage: a systematic review of animal studies.

    Science.gov (United States)

    Rongen, J J; Hannink, G; van Tienen, T G; van Luijk, J; Hooijmans, C R

    2015-08-01

    Despite widespread reporting on clinical results, the effect of meniscus allograft transplantation on the development of osteoarthritis is still unclear. The aim of this study was to systematically review all studies on the effect of meniscus allograft transplantation on articular cartilage in animals. Pubmed and Embase were searched for original articles concerning the effect of meniscus allograft transplantation on articular cartilage compared with both its positive (meniscectomy) and negative (either sham or non-operated) control in healthy animals. Outcome measures related to assessment of damage to articular cartilage were divided in five principal outcome categories. Standardized mean differences (SMD) were calculated and pooled to obtain an overall SMD and 95% confidence interval. 17 articles were identified, representing 14 original animal cohorts with an average timing of data collection of 24 weeks [range 4 weeks; 30 months]. Compared to a negative control, meniscus allograft transplantation caused gross macroscopic (1.45 [0.95; 1.95]), histological (3.43 [2.25; 4.61]) damage to articular cartilage, and osteoarthritic changes on radiographs (3.12 [1.42; 4.82]). Moreover, results on histomorphometrics and cartilage biomechanics are supportive of this detrimental effect on cartilage. On the other hand, meniscus allograft transplantation caused significantly less gross macroscopic (-1.19 [-1.84; -0.54]) and histological (-1.70 [-2.67; -0.74]) damage to articular cartilage when compared to meniscectomy. However, there was no difference in osteoarthritic changes on plain radiographs (0.04 [-0.48; 0.57]), and results on histomorphometrics and biomechanics did neither show a difference in effect between meniscus allograft transplantation and meniscectomy. In conclusion, although meniscus allograft transplantation does not protect articular cartilage from damage, it reduces the extent of it when compared with meniscectomy. Copyright © 2015 Osteoarthritis

  15. Importance of Donor Chondrocyte Viability for Osteochondral Allografts.

    Science.gov (United States)

    Cook, James L; Stannard, James P; Stoker, Aaron M; Bozynski, Chantelle C; Kuroki, Keiichi; Cook, Cristi R; Pfeiffer, Ferris M

    2016-05-01

    Osteochondral allograft (OCA) transplantation provides a biological treatment option for functional restoration of large articular cartilage defects in multiple joints. While successful outcomes after OCA transplantation have been linked to viable donor chondrocytes, the importance of donor cell viability has not been comprehensively validated. To use a canine model to determine the importance of donor chondrocyte viability at the time of implantation with respect to functional success of femoral condylar OCAs based on radiographic, gross, cell viability, histologic, biochemical, and biomechanical outcome measures. Controlled laboratory study. After approval was obtained from the institutional animal care and use committee, adult female dogs (N = 16) were implanted with 8-mm cylindrical OCAs from male dogs in the lateral and medial femoral condyles of 1 knee. OCAs were preserved for 28 or 60 days after procurement, and chondrocyte viability was quantified before implantation. Two different storage media, temperatures, and time points were used to obtain a spectrum of percentage chondrocyte viability at the time of implantation. A successful outcome was defined as an OCA that was associated with graft integration, maintenance of hyaline cartilage, lack of associated cartilage disorder, and lack of fibrillation, fissuring, or fibrous tissue infiltration of the allograft based on subjective radiographic, gross, and histologic assessments at 6 months after implantation. Chondrocyte viability ranged from 23% to 99% at the time of implantation. All successful grafts had >70% chondrocyte viability at the time of implantation, and no graft with chondrocyte viability <70% was associated with a successful outcome. Live-dead stained sections and histologic findings with respect to cell morphological features suggested that successful grafts were consistently composed of viable chondrocytes in lacunae, while grafts that were not successful were composed of nonviable

  16. Quality system and audit of human skin allografts

    International Nuclear Information System (INIS)

    Van Baare, J.

    1999-01-01

    Allograft skin has long been recognised as an important resource in the management of bum wounds. The important issue in skin banking is fust to guarantee safety of human cadaveric donor skin. Second, the quality of the allografts should be assured. The Euro Skin Bank, established in 1976, is located in The Netherlands. Not only in The Netherlands, but in many other (European) countries no specific regulation exists for tissue banking. With respect to skin banking in The Netherlands the Euro Skin Bank requested the government what regulations should be applied on their activities. It was stated in 1994 that human allografl skin should be regarded as a phan-naceutical drug, a magistral preparation. The Euro Skin Bank should therefore be subjected to the guidelines given for the Good Laboraton, Practices and Good Manufacturing Practices to process allogmft skin. Nevertheless, it was in the opinion of the Euro Skin Bank that regulating human tissue as a pharmaceutical drug was not sufficient e.g. no specific regulations for serologic testing of the tissue donor is given, which should be one of the most important issues in tissue banking. Recently the government has published new legislation for tissue banks in The Netherlands: on July I st, 1998, a new legislation was enforced concerning organ and tissue donation and on November I st, 1998, quality requirements for organ and tissue banks are published. The European Community discussed the possibility to bring all animal and human tissues under the Medical Device Directive (MDD). Soon it was proposed not to incorporate viable hw-nan tissue into the MDD. Last year all human tissue was excluded from the MDD. Lack of European regulations has been resulted in national laws, e.g. in The Netherlands, Germany and France. Possibly there might be a more significant role for the European Association of Tissue Banks in the near future for European legislation on tissue banking. In order to have a standard quality system wmch is

  17. Assessment of early renal allograft dysfunction with blood oxygenation level-dependent MRI and diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Yoon [Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Chan Kyo, E-mail: chankyokim@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Byung Kwan [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Sung Ju; Lee, Sanghoon [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Huh, Wooseong [Department of Nephrology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    Highlights: • R2* and ADC in renal allografts are moderately correlated with eGFR. • R2* and ADC are lower in early allograft dysfunction than normal allograft function. • No significant difference between AR and ATN was found in both R2* and ADC. - Abstract: Purpose: To investigate blood oxygenation level-dependent (BOLD) MRI and diffusion-weighted imaging (DWI) at 3 T for assessment of early renal allograft dysfunction. Materials and methods: 34 patients with a renal allograft (early dysfunction, 24; normal, 10) were prospectively enrolled. BOLD MRI and DWI were performed at 3 T. R2* and apparent diffusion coefficient (ADC) values were measured in cortex and medulla of the allografts. Correlation between R2* or ADC values and estimated glomerular filtration rate (eGFR) was investigated. R2* or ADC values were compared among acute rejection (AR), acute tubular necrosis (ATN) and normal function. Results: In all renal allografts, cortical or medullary R2* and ADC values were moderately correlated with eGFR (P < 0.05). Early dysfunction group showed lower R2* and ADC values than normal function group (P < 0.05). AR or ATN had lower R2* values than normal allografts (P < 0.05), and ARs had lower cortical ADC values than normal allografts (P < 0.05). No significant difference of R2* or ADC values was found between AR and ATN (P > 0.05). Conclusion: BOLD MRI and DWI at 3 T may demonstrate early functional state of renal allografts, but may be limited in characterizing a cause of early renal allograft dysfunction. Further studies are needed.

  18. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    Gulati, Gurpreet S; Kothari, Shyam S

    2011-01-01

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  19. Mast cell protease 6 is required for allograft tolerance.

    Science.gov (United States)

    de Vries, V C; Elgueta, R; Lee, D M; Noelle, R J

    2010-09-01

    It has been shown that mast cells (MC) are absolutely required for transplant acceptance. However, only a few of the numerous mediators produced by MC have been proposed as potential mechanisms for the observed immunosuppression. The role of proteases in acquired immune tolerance as such has not yet been addressed. In this study, we have shown the requirement for MC protease 6 (MCP6), an MC-specific tryptase, to establish tolerance toward an allogeneic skin graft. The substrate for MCP6 is interleukin (IL)-6, cytokine generally considered to indicate transplant rejection. Herein we have shown an inverse correlation between MCP6 and IL-6. High expression of MCP6 is accompanied by low levels of IL-6 when the allograft is accepted, whereas low expression of MCP6 in combination with high levels of IL-6 are observed in rejecting grafts. Moreover, tolerance toward an allogeneic graft cannot be induced in MCP6(-/-) mice. Rejection observed in these mice was comparable to that of MC-deficient hosts; it is T-cell mediated. These findings suggest that MCP6 actively depletes the local environment of IL-6 to maintain tolerance. 2010. Published by Elsevier Inc.

  20. Effect of blood transfusions on canine renal allograft survival

    International Nuclear Information System (INIS)

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

    1982-01-01

    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

  1. Effect of blood transfusions on canine renal allograft survival

    International Nuclear Information System (INIS)

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

    1982-01-01

    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

  2. Restrictive allograft syndrome after lung transplantation: new radiological insights

    Energy Technology Data Exchange (ETDEWEB)

    Dubbeldam, Adriana; Barthels, Caroline; Coolen, Johan; Verschakelen, Johny A.; Wever, Walter de [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Verleden, Stijn E.; Vos, Robin; Verleden, Geert M. [University Hospitals Leuven, Department of Pneumology, Leuven (Belgium)

    2017-07-15

    To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities. In 14 patients, non-regressing nodules and reticulations predominantly affecting the upper lobes developed an average of 13.9 months prior to the diagnosis of RAS. Median graft survival after onset of non-regressing abnormalities was 33.5 months, with most patients in follow-up (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly affecting both upper and lower lobes was seen an average of 2.8 months prior to the diagnosis of RAS. Median graft survival was 6.4 months after first onset of non-regressing abnormalities, with graft loss in most patients (6/8). RAS has been previously described as a homogenous group. However, our study shows two different groups of RAS-patients: one with slow progression and one with fast progression. The two groups show different onset and progression patterns of CT abnormalities. (orig.)

  3. Bone marrow-derived T lymphocytes responsible for allograft rejection

    International Nuclear Information System (INIS)

    Senjanovic, M.; Marusic, M.

    1984-01-01

    Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

  4. The effect of donor gender on renal allograft survival.

    Science.gov (United States)

    Neugarten, J; Srinivas, T; Tellis, V; Silbiger, S; Greenstein, S

    1996-02-01

    Donor gender plays a role in the outcome of renal transplantation, but the mechanisms responsible for this effect are unclear. In this study, actuarial graft survival in 1049 recipients transplanted at Montefiore Medical Center between 1979 and 1994 was examined. It was found that donor gender had no influence on graft survival in recipients treated with precyclosporine immunosuppressive agents. In contrast, graft survival time was greater in cyclosporine-treated recipients of male donor kidneys compared with female kidneys (p demand results in hyperfiltration-mediated glomerular injury and that this is responsible for reduced survival time of female allografts. Any hypothesis purporting to explain gender-related differences in graft survival time must take into account this study's observations that the donor-gender effect was observed only in cyclosporine-treated recipients, was not seen in African-American donors, appeared soon after renal transplantation, and did not increase progressively with time. These observations are most consistent with the hypothesis that gender-related differences in graft survival time may reflect differences in susceptibility to cyclosporine nephrotoxicity or differences in the therapeutic response to cyclosporine.

  5. Impact of obesity on development of chronic renal allograft dysfunction

    International Nuclear Information System (INIS)

    Jahromi, Alireza Hamidian; Jalali, Ghanbar Ali Raiss; Roozbeh, Jamshid

    2009-01-01

    Obesity in nontransplant patients has been associated with hypertension, hyperlipidemia, diabetes, and proteinuria. To determine whether renal transplant recipients with an elevated BMI have worse long term graft survival, we prospectively studied 92 patients transplanted between April 1999 and July 2000. Weight (Wt) and height of the patients were recorded prior to transplantation and two weeks, one, two and three years post transplantation. Blood urea nitrogen (BUN), creatinine (Cr) and blood pressure were checked monthly, while triglyceride, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) were obtained 3 monthly for 3 years post transplantation. Graft dysfunction was defined as serum Cr > 1.8 mg/dL. While BMI and Wt of the patients before transplantation did not show any significant correlation with chronic renal allograft dysfunction (CRAD), patients with higher Wt and BMI two weeks after transplantation showed an increased risk of developing CRAD during the three year post transplant independent of other risk factors (P< 0.05). Patients with greater Wt loss in the first two weeks post transplantation showed a decreased risk of developing CRAD in the following 3 years (P< 0.001). Our study suggests that high Wt and BMI are significantly associated with worse graft survival 3 years post renal transplantation. (author)

  6. Outcomes of Osteochondral Allograft Transplantation With and Without Concomitant Meniscus Allograft Transplantation: A Comparative Matched Group Analysis.

    Science.gov (United States)

    Frank, Rachel M; Lee, Simon; Cotter, Eric J; Hannon, Charles P; Leroux, Timothy; Cole, Brian J

    2018-03-01

    Osteochondral allograft transplantation (OCA) is often performed with concomitant meniscus allograft transplantation (MAT) as a strategy for knee joint preservation, although to date, the effect of concomitant MAT on outcomes and failure rates after OCA has not been assessed. To determine clinical outcomes for patients undergoing OCA with MAT as compared with a matched cohort of patients undergoing isolated OCA. Control study; Level of evidence, 3. Patients who underwent OCA of the medial or lateral femoral condyle without concomitant MAT by a single surgeon were compared with a matched group of patients who underwent OCA with concomitant MAT (ipsilateral compartment). The patients were matched per age, sex, body mass index, and number of previous ipsilateral knee operations ±1. Patient-reported outcomes, complications, reoperations, and survival rates were compared between groups. One hundred patients undergoing OCA (50 isolated, 50 with MAT) with a mean ± SD follow-up of 4.9 ± 2.7 years (minimum, 2 years) were included (age, 31.7 ± 9.8 years; 52% male). Significantly more patients underwent OCA to the medial femoral condyle (n = 59) than the lateral femoral condyle (n = 41, P OCA. There were no significant differences between the groups regarding reoperation rate (n = 18 for OCA with MAT, n = 17 for OCA without MAT, P = .834), time to reoperation (2.2 ± 2.4 years for OCA with MAT, 3.4 ± 2.7 years for OCA without MAT, P = .149), or failure rates (n = 7 [14%] for OCA with MAT, n = 7 [14%] for OCA without MAT, P > .999). There were no significant differences in patient-reported clinical outcome scores between the groups at final follow-up. There was no significant difference in failure rates between patients undergoing medial femoral condyle OCA (n = 12, 15.3%) and lateral femoral condyle OCA (n = 5, 12.2%, P = .665). These results imply that with appropriate surgical indications to address meniscus deficiency in patients otherwise indicated for OCA and

  7. Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

    Science.gov (United States)

    Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

    2016-01-01

    We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more

  8. Diffusion tensor imaging and tractography for assessment of renal allograft dysfunction - initial results

    Energy Technology Data Exchange (ETDEWEB)

    Hueper, Katja; Gutberlet, M.; Rodt, T.; Wacker, F.; Galanski, M.; Hartung, D. [Institute for Diagnostic and Interventional Radiology, Hannover Medical School - Germany, Hannover (Germany); Gwinner, W. [Clinic for Nephrology, Hannover Medical School - Germany, Hannover (Germany); Lehner, F. [Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School - Germany, Hannover (Germany)

    2011-11-15

    To evaluate MR diffusion tensor imaging (DTI) as non-invasive diagnostic tool for detection of acute and chronic allograft dysfunction and changes of organ microstructure. 15 kidney transplanted patients with allograft dysfunction and 14 healthy volunteers were examined using a fat-saturated echo-planar DTI-sequence at 1.5 T (6 diffusion directions, b = 0, 600 s/mm{sup 2}). Mean apparent diffusion coefficient (ADC) and mean fractional anisotropy (FA) were calculated separately for the cortex and for the medulla and compared between healthy and transplanted kidneys. Furthermore, the correlation between diffusion parameters and estimated GFR was determined. The ADC in the cortex and in the medulla were lower in transplanted than in healthy kidneys (p < 0.01). Differences were more distinct for FA, especially in the renal medulla, with a significant reduction in allografts (p < 0.001). Furthermore, in transplanted patients a correlation between mean FA in the medulla and estimated GFR was observed (r = 0.72, p < 0.01). Tractography visualized changes in renal microstructure in patients with impaired allograft function. Changes in allograft function and microstructure can be detected and quantified using DTI. However, to prove the value of DTI for standard clinical application especially correlation of imaging findings and biopsy results is necessary. (orig.)

  9. Defining kidney allograft benefit from successful pancreas transplant: separating fact from fiction.

    Science.gov (United States)

    Wiseman, Alexander C; Stites, Erik; Kennealey, Peter

    2018-06-06

    To define the natural history of kidney allograft loss related to recurrent diabetes following transplant, and to understand the potential benefit of pancreas transplantation upon kidney allograft survival. A postulated benefit of simultaneous pancreas kidney transplant is that, unlike kidney transplant alone, euglycemia from the added pancreas allograft may confer a nephroprotective benefit and prevent recurrent diabetic nephropathy in the renal allograft. Recent large database analyses and long-term histological assessments have been published that assist in quantifying the problem of recurrent diabetic nephropathy and answering the question of the potential benefits of euglycemia. Further data may be extrapolated from larger single-center series that follow the prognosis of early posttransplant diabetes mellitus as another barometer of risk from diabetic nephropathy and graft loss. Recurrent diabetic nephropathy following kidney transplant is a relatively rare, late occurrence and its clinical significance is significantly diminished by the competing risks of death and chronic alloimmune injury. Although there are hints of a protective effect upon kidney graft survival with pancreas transplant, these improvements are small and may take decades to appreciate. Clinical decision-making regarding pancreas transplant solely based upon nephroprotective effects of the kidney allograft should be avoided.

  10. Geographic inequities in liver allograft supply and demand: does it affect patient outcomes?

    Science.gov (United States)

    Rana, Abbas; Kaplan, Bruce; Riaz, Irbaz B; Porubsky, Marian; Habib, Shahid; Rilo, Horacio; Gruessner, Angelika C; Gruessner, Rainer W G

    2015-03-01

    Significant geographic inequities mar the distribution of liver allografts for transplantation. We analyzed the effect of geographic inequities on patient outcomes. During our study period (January 1 through December 31, 2010), 11,244 adult candidates were listed for liver transplantation: 5,285 adult liver allografts became available, and 5,471 adult recipients underwent transplantation. We obtained population data from the 2010 United States Census. To determine the effect of regional supply and demand disparities on patient outcomes, we performed linear regression and multivariate Cox regression analyses. Our proposed disparity metric, the ratio of listed candidates to liver allografts available varied from 1.3 (region 11) to 3.4 (region 1). When that ratio was used as the explanatory variable, the R(2) values for outcome measures were as follows: 1-year waitlist mortality, 0.23 and 1-year posttransplant survival, 0.27. According to our multivariate analysis, the ratio of listed candidates to liver allografts available had a significant effect on waitlist survival (hazards ratio, 1.21; 95% confidence interval, 1.04-1.40) but was not a significant risk factor for posttransplant survival. We found significant differences in liver allograft supply and demand--but these differences had only a modest effect on patient outcomes. Redistricting and allocation-sharing schemes should seek to equalize regional supply and demand rather than attempting to equalize patient outcomes.

  11. 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.

  12. Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

    Science.gov (United States)

    Freedman, B I; Julian, B A; Pastan, S O; Israni, A K; Schladt, D; Gautreaux, M D; Hauptfeld, V; Bray, R A; Gebel, H M; Kirk, A D; Gaston, R S; Rogers, J; Farney, A C; Orlando, G; Stratta, R J; Mohan, S; Ma, L; Langefeld, C D; Hicks, P J; Palmer, N D; Adams, P L; Palanisamy, A; Reeves-Daniel, A M; Divers, J

    2015-06-01

    Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Bair, H.J.; Platsch, G.; Wolf, F. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Nuclear Medicine; Guenter, E.; Becker, D. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Internal Medicine 1; Rupprecht, H.; Neumayer, H.H. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Internal Medicine 4

    1997-08-01

    Aim: The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery. Methods: From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts. Results: Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up. Conclusion: In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and colorcoded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion. (orig.) [Deutsch] Ziel der Studie war es, das

  14. Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded allograft

    Directory of Open Access Journals (Sweden)

    J O Eniwumide

    2007-08-01

    Full Text Available Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as controls and the experimental groups comprised autologous bone marrow derived stem cell seeded allograft, biphasic calcium phosphate (BCP and tricalcium phosphate (TCP, respectively. All implants were implanted in the back muscle of adult Dutch milk goats for 12 weeks. Micro-computed tomography (µCT analysis and histomorphometry was performed to evaluate and quantify ectopic bone formation. In good agreement, both µCT and histomorphometric analysis demonstrated a significant increase in bone formation by cell-seeded calcium phosphate scaffolds as compared to the autograft, allograft and cell-seeded allograft implants. An extensive resorption of the autograft, allograft and cell-seeded allograft implants was observed by histology and confirmed by histomorphometry. Cell-seeded TCP implants also showed distinct signs of degradation with histomorphometry and µCT, while the degradation of the cell-seeded BCP implants was negligible. These results indicate that cell-seeded calcium phosphate scaffolds are superior to autograft, allograft or cell-seeded allograft in terms of bone formation at ectopic implantation sites. In addition, the usefulness of µCT for the efficient and non-destructive analysis of mineralised bone and calcium phosphate scaffold was demonstrated.

  15. Respuesta hemodinámica con el entrenamiento en resistencia y fuerza muscular de miembros superiores en rehabilitación cardiaca Hemodynamic response to training in resistance and muscular strength of upper limbs in cardiac rehabilitation

    Directory of Open Access Journals (Sweden)

    Diana M Camargo

    2007-08-01

    de 1,92 ± 2,49 lb (pAntecedentes: training of muscular strength in patients with cardiovascular events was totally contraindicated because of the risk of incrementing the systolic and diastolic arterial pressure values, as well as the submission to a myocardial overload. Objective: evaluate the hemodynamic response (heart rate, arterial pressure during the resistance to muscular strength training in patients assisting to a heart rehabilitation program. Design: quasi experimental prospective study. Setting: resistance training to muscular strength in upper limbs to patients during stage II of cardiac rehabilitation was realized. Subjects: 175 patients were included. 135 men and 40 women with mean age 58.79 years with coronary disease, with or without revascularization procedures, valvular surgery, syncope and surgical correction of congenital heart disease. Procedure: previous aerobic training (treadmill or static bicycle, muscular strength evaluation was realized through maximal repetition and the strength training was initiated at 30%-50% of this, in a three different exercise circuit in upper limbs, 10 repetitions in three series with a twice a week frequency. Besides, monitoring of heart frequency, electrocardiogram by telemetry (V5, arterial pressure recording before, during and after the session, and subjective perception of the effort by the Borg scale were made, and signs and symptoms of intolerance to the activity or decompensation were observed. For the statistical analysis, measures of central tendency with the cardiovascular changes were used and in order to compare the change in muscular strength, a paired t test with significance level 0.05 was utilized. Results: mean muscular strength with maximal repetition evidenced a significant increase of 1.92 ± 2.49 lb (p<0.001 in the general population, with an increment of 2.03 ± 2.57 lb (p<0.001 in men and of 1.46 ± 2.1 lb (p<0.001 in women. The muscular resistance training was realized with a mean load of

  16. Cardiac gated ventilation

    International Nuclear Information System (INIS)

    Hanson, C.W. III; Hoffman, E.A.

    1995-01-01

    There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. The authors evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50 msec scan aperture. Multi slice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. The authors observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a non-failing model of the heart

  17. Sirolimus use and incidence of venous thromboembolism in cardiac transplant recipients.

    Science.gov (United States)

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

    2012-01-01

    Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism (VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log-rank statistic: 4.66, p=0.03). Lower body mass index (BMI) and total cholesterol levels were also associated with VTE (p<0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p=0.03) but not when adjusting for total cholesterol (p=0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted. © 2012 John Wiley & Sons A/S.

  18. Surgical treatment of infective endocarditis with aortic and tricuspid valve involvement using cryopreserved aortic and mitral valve allografts.

    Science.gov (United States)

    Ostrovsky, Yury; Spirydonau, Siarhei; Shchatsinka, Mikalai; Shket, Aliaksandr

    2015-05-01

    Surgical treatment of infective and prosthetic endocarditis using allografts gives good results. Aortic allograft implantation is a common technique, while tricuspid valve replacement with a mitral allograft is very rare. Multiple valve disease in case of infective endocarditis is a surgical challenge as such patients are usually in a grave condition and results of surgical treatment are often unsatisfactory. In this article we describe a clinical case of successful surgical treatment in a patient with active infective endocarditis of aortic and tricuspid valve, complicated by an aortic-right ventricular fistula. The aortic valve and ascending aorta were replaced with a cryopreserved aortic allograft; the tricuspid valve was replaced with a cryopreserved mitral allograft. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  19. What tissue bankers should know about the use of allograft meniscus in orthopaedics.

    Science.gov (United States)

    McDermott, Ian D

    2010-02-01

    The menisci of the knee are two crescent shaped cartilage shock absorbers sitting between the femur and the tibia, which act as load sharers and shock absorbers. Loss of a meniscus leads to a significant increase in the risk of developing arthritis in the knee. Replacement of a missing meniscus with allograft tissue can reduce symptoms and may potentially reduce the risk of future arthritis. Meniscal allograft transplantation is a complex surgical procedure with many outstanding issues, including 'what techniques should be used for processing and storing grafts?', 'how should the allografts be sized?' and 'what surgical implantation techniques might be most appropriate?' Further clinical research is needed and close collaboration between the users (surgeons) and the suppliers (tissue banks) is essential. This review explores the above subject in detail.

  20. 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).

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

    International Nuclear Information System (INIS)

    Sonoda, Kazuhiko; Rapaport, F.T.

    1992-01-01

    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)

  2. Editorial Commentary: The Acellular Osteochondral Allograft, the Emperor Has New Clothes.

    Science.gov (United States)

    Mandelbaum, Bert R; Chahla, Jorge

    2017-12-01

    For larger lesions (>2.5-cm 2 ), clinical evidence and practice have shown that fresh osteochondral allograft have good durability, with 88% return to sport and greater than 75% 10-year survival rates for treatment of large femoral condyle lesions. That said, the use of fresh osteochondral allografts in clinical practice is limited by the availability of acceptable donor tissues for eligible patients in a timely fashion. Significant diminution of chondrocyte viability and density occurs during the preservation and storage period. All osteochondral allografts are not equal in performance and outcome. Chondrocyte density and viability are critical for successful transplantation and outcome in the short and long term. This commentary highlights the high failure rates of tissue when it is acellular. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  3. The Use of Structural Allograft in Primary and Revision Knee Arthroplasty with Bone Loss

    Directory of Open Access Journals (Sweden)

    Raul A. Kuchinad

    2011-01-01

    Full Text Available Bone loss around the knee in the setting of total knee arthroplasty remains a difficult and challenging problem for orthopaedic surgeons. There are a number of options for dealing with smaller and contained bone loss; however, massive segmental bone loss has fewer options. Small, contained defects can be treated with cement, morselized autograft/allograft or metal augments. Segmental bone loss cannot be dealt with through simple addition of cement, morselized autograft/allograft, or metal augments. For younger or higher demand patients, the use of allograft is a good option as it provides a durable construct with high rates of union while restoring bone stock for future revisions. Older patients, or those who are low demand, may be better candidates for a tumour prosthesis, which provides immediate ability to weight bear and mobilize.

  4. Evaluation of renal allograft rejection by Doppler sonography and MR imaging

    International Nuclear Information System (INIS)

    Steinberg, H.V.; Nelson, R.C.; Murphy, F.B.; Baumgartner, B.R.; Bourke, E.; Delaney, V.B.; Whelchel, J.B.; Bernardino, M.E.

    1986-01-01

    The authors prospectively studies the efficacy of Doppler sonography and MR imaging in evaluating renal allografts, with specific attention to transplant rejection. Based on study findings, we were unable to make a statement with respect to the appearance or accuracy of diagnosing cyclosporin toxicity or acute tubular necrosis by either modality due to concomitant rejection in the few patients so afflicted. Moreover, the ability to predict and diagnose the presence or absence of allograft rejection was not affected by different serum creatinine values. Most important, however, Doppler sonography was shown to be superior to MR imaging in evaluating for allograft rejection, as evidenced by its higher sensitivity (100% vs. 71%), specificity (88% vs. 75%), and accuracy (96% vs. 73%). Thus, because of its low cost and ease of accessibility, Doppler sonography should become the primary modality for renal transplant screening

  5. A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease.

    Science.gov (United States)

    Riebold, Mathias; Kozany, Christian; Freiburger, Lee; Sattler, Michael; Buchfelder, Michael; Hausch, Felix; Stalla, Günter K; Paez-Pereda, Marcelo

    2015-03-01

    One function of the glucocorticoid receptor (GR) in corticotroph cells is to suppress the transcription of the gene encoding proopiomelanocortin (POMC), the precursor of the stress hormone adrenocorticotropin (ACTH). Cushing disease is a neuroendocrine condition caused by partially glucocorticoid-resistant corticotroph adenomas that excessively secrete ACTH, which leads to hypercortisolism. Mutations that impair GR function explain glucocorticoid resistance only in sporadic cases. However, the proper folding of GR depends on direct interactions with the chaperone heat shock protein 90 (HSP90, refs. 7,8). We show here that corticotroph adenomas overexpress HSP90 compared to the normal pituitary. N- and C-terminal HSP90 inhibitors act at different steps of the HSP90 catalytic cycle to regulate corticotroph cell proliferation and GR transcriptional activity. C-terminal inhibitors cause the release of mature GR from HSP90, which promotes its exit from the chaperone cycle and potentiates its transcriptional activity in a corticotroph cell line and in primary cultures of human corticotroph adenomas. In an allograft mouse model, the C-terminal HSP90 inhibitor silibinin showed anti-tumorigenic effects, partially reverted hormonal alterations, and alleviated symptoms of Cushing disease. These results suggest that the pathogenesis of Cushing disease caused by overexpression of heat shock proteins and consequently misregulated GR sensitivity may be overcome pharmacologically with an appropriate HSP90 inhibitor.

  6. Evaluation of renal allograft function early after transplantation with diffusion-weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Eisenberger, Ute; Frey, Felix J. [University Hospital of Bern, Department of Nephrology and Hypertension, Bern (Switzerland); Thoeny, Harriet C. [University Hospital of Bern, Department of Radiology, Neuroradiology and Nuclear Medicine, Bern (Switzerland); Binser, Tobias; Boesch, Chris [University Hospital of Bern, Department of Clinical Research, Bern (Switzerland); Gugger, Mathias [University Hospital of Bern, Department of Pathology, Bern (Switzerland); Vermathen, Peter [University Hospital of Bern, Department of Clinical Research, Bern (Switzerland); University Bern, Department of Clinical Research/AMSM, Pavillon 52, Inselspital, P.O. Box 35, Bern (Switzerland)

    2010-06-15

    To determine the inter-patient variability of apparent diffusion coefficients (ADC) and concurrent micro-circulation contributions from diffusion-weighted MR imaging (DW-MRI) in renal allografts early after transplantation, and to obtain initial information on whether these measures are altered in histologically proven acute allograft rejection (AR). DW-MRI was performed in 15 renal allograft recipients 5-19 days after transplantation. Four patients presented with AR and one with acute tubular necrosis (ATN). Total ADC (ADC{sub T}) was determined, which includes diffusion and micro-circulation contributions. Furthermore, diffusion and micro-circulation contributions were separated, yielding the ''perfusion fraction'' (F{sub P}), and ''perfusion-free'' diffusion (ADC{sub D}). Diffusion parameters in the ten allografts with stable function early after transplantation demonstrated low variabilities. Values for ADC{sub T} and ADC{sub D} were (x 10{sup -5} mm{sup 2}/s) 228 {+-} 14 and 203 {+-} 9, respectively, in cortex and 226 {+-} 16 and 199 {+-} 9, respectively, in medulla. F{sub P} values were 18 {+-} 5% in cortex and 19 {+-} 5% in medulla. F{sub P} values were strongly reduced to less than 12% in cortex and medulla of renal transplants with AR and ATN. F{sub P} values correlated with creatinine clearance. DW-MRI allows reliable determination of diffusion and micro-circulation contributions in renal allografts shortly after transplantation; deviations in AR indicate potential clinical utility of this method to non-invasively monitor derangements in renal allografts. (orig.)

  7. 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.

  8. Comparison of allograft and polyetheretherketone (PEEK) cage subsidence rates in anterior cervical discectomy and fusion (ACDF).

    Science.gov (United States)

    Yson, Sharon C; Sembrano, Jonathan N; Santos, Edward Rainier G

    2017-04-01

    Structural allografts and PEEK cages are commonly used interbody fusion devices in ACDF. The subsidence rates of these two spacers have not yet been directly compared. The primary aim of this study was to compare the subsidence rate of allograft and PEEK cage in ACDF. The secondary aim was to determine if the presence of subsidence affects the clinical outcome. We reviewed 67 cases (117 levels) of ACDF with either structural allograft or PEEK cages. There were 85 levels (48 cases) with PEEK and 32 levels (19 cases) with allograft spacers. Anterior and posterior disc heights at each operative level were measured at immediate and 6months post-op. Subsidence was defined as a decrease in anterior or posterior disc heights >2mm. NDI of the subsidence (SG) and non-subsidence group (NSG) were recorded. Chi-square test was used to analyze subsidence rates. T-test was used to analyze clinical outcomes (α=0.05). There was no statistically significant difference between subsidence rates of the PEEK (29%; 25/85) and allograft group (28%; 9/32) (p=0.69). Overall mean subsidence was 2.3±1.7mm anteriorly and 2.6±1.2mm posteriorly. Mean NDI improvement was 11.7 (from 47.1 to 35.4; average follow-up: 12mos) for the SG and 14.0 (from 45.8 to 31.8; average follow-up: 13mos) for the NSG (p=0.74). Subsidence rate does not seem to be affected by the use of either PEEK or allograft as spacers in ACDF. Furthermore, subsidence alone does not seem to be predictive of clinical outcomes of ACDF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Freeze dried bone allografts in dental and maxillofacial reconstructive surgery - experience in Malaysia

    International Nuclear Information System (INIS)

    Abd Rani Samsudin; Meor Zaidi Meor Kamal

    1999-01-01

    The utilisation of vascularised and free bone autografts remain the goal standard in maxillofacial reconstructive surgery in Malaysia, but the use of freeze dried bone allograft is still widely practiced in many centres with variable results. This study evaluate the effectiveness and clinical efficacy of using radiation sterilised freeze dried bone allografts in oral and maxillofacial reconstructive surgery. The bone grafts were prepared at the Malaysian National Tissue Bank. Seventy eight patients who had undergone oral and Maxillofacial surgical procedures with reconstruction using bone allografts were included in this study. 50 patients were male and 28 patients were female and their age ranged from 14 to 75 years. Forty two patients underwent enucleation of benign cystic lesions in the jaws, 15 patients underwent repair of orbital floor fractures, 6 patients of jaw fractures with partial loss of bone while 8 patients underwent augmentation of depressed cheek bone. Another 4 patients had partial resection of the mandible because of cancer and 3 patients had facial osteotomies. A follow up period of 12 months up to 4 years was carried out. The patients were assessed both clinically and radiologically throughout their follow up visits. Clinical assessment showed no evidence of rejection of the implanted freeze dried allografts. Bone allografts implanted as inlay grafts demonstrated a better clinical performance than onlay grafts and the poorest results were obtained following bridging bony defects in the jaws. Radiation sterilised freeze dried bone allografts produced at the Malaysian National Tissue Bank are bio-compatible, functional, and provide predictable results when applied to selected areas of the facial skeleton

  10. T2' imaging of native kidneys and renal allografts. A feasibility study

    International Nuclear Information System (INIS)

    Mathys, C.; Blondin, D.; Wittsack, H.J.; Miese, F.R.; Rybacki, K.; Walther, C.; Holstein, A.; Lanzman, R.S.

    2011-01-01

    Purpose: To evaluate the feasibility of T2' mapping in native kidneys and renal allografts. Materials and Methods: Following approval of the local ethics committee, 24 renal allograft recipients and 10 control subjects (healthy volunteers) were included in this study. Multi-echo T2 and T2 * imaging was performed on a 1.5 Tesla scanner. Allograft recipients were assigned to two groups: group (a), 8 patients with good (glomerular filtration rate of more than 40 ml/min) allograft function and no evidence of transplant rejection, transplant renal artery stenosis or ureteral obstruction; group (b), 16 patients with deterioration of renal graft function (glomerular filtration rate (GFR) of 40 ml/min or less). Two different imaging protocols were tested. Results: The mean T2' relaxation parameters were 108.33 msec ± 13.34, 100.00 msec ± 18.89 and 124.57 msec ± 6.51 for groups (a), (b) and for control subjects, respectively. The reduction of T2' values in patient group (b) was not statistically significant. However, significant correlations could be demonstrated between T2' values and the glomerular filtration rate (GFR) of renal allograft function. The reproducibility was tested and the coefficients of variation of T2' values in the cortex of transplanted kidneys were 11.1 % within subjects and 11.3 % between subjects. Conclusion: Our results indicate that T2' imaging is a promising non-enhanced technique, which seems to reveal information on transplant function. Further studies are required to determine the clinical value of T2' mapping for monitoring renal allograft recipients. (orig.)

  11. 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.

  12. Possibility of using combined treatment of processing and ionizing radiation to eliminate contaminated viruses from non-screened donor of tissue allografts

    International Nuclear Information System (INIS)

    Nazly Hilmy; Paramita Pandansari

    2008-01-01

    Full text: New emerging and re- emerging infectious diseases caused by viruses are outbreak and re- outbreak around the world. Most of the viruses come from animals ( zoonoses) and jump to human beings ( host jumping ) such as corona virus ( SARS), HIV, bird flu/ Avian flu H5N1, hepatitis viruses, Dengue fever virus, West Nile virus/WNV, Hantavirus, Marburg haemorrhagic fever virus, Hendra virus, Nipah virus etc. Transmission of those diseases through transplantation of contaminated tissue allograft to recipient can happened if the donor could not be screened properly. The donor can be well screened from some of those viruses such as HIV, hepatitis viruses and WNV. Processing of tissue allografts by pasteurization, washing and soaking in H 2 O 2 and soap can eliminate contaminated viruses to a certain amount, have been reported by several authors. Viruses are very small microbes, they have DNA/RNA, resistant to radiation but to a certain degree they can be well eliminated by radiation. Their D10 - values vary from 4 to 13 kGy. This paper discribes briefly the possibility of using combined treatment of processing, lyophilization and sterilisation by radiation to overcome problems of non screened donor from some contaminated viruses. (Author)

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

    Directory of Open Access Journals (Sweden)

    Ali H Dalloul

    2013-12-01

    allograft rejection.

  14. Intrapancreatic Splenule in a Pancreas Allograft: Case Report.

    Science.gov (United States)

    Yadav, K; Serrano, O K; Kandaswamy, R

    2016-11-01

    A 16-year-old white man was involved in a motor vehicle collision and suffered head, chest, and abdominal trauma. Despite initial resuscitative efforts, he progressed to brain death and was designated to be an organ donor by his family. He had no earlier medical or surgical history and no high-risk behaviors. Blood work revealed normal creatinine, liver function tests, lipase, and amylase. Viral serologies were negative except for cytomegalovirus IgG and Epstein-Barr virus nucleic acid. Imaging revealed a right kidney contusion, a manubrial fracture, and fractures of right first rib and bilateral scapulae. No other abdominal trauma was identified, specifically to the pancreas, duodenum, or spleen. Our transplant center accepted the pancreas from this donor. During back-table inspection of the pancreas, a 1.5 × 1.5 cm dark purple rubbery mass was identified within the parenchyma of the pancreas in the tail. An incisional biopsy of the lesion was sent for frozen section, which yielded a mixed inflammatory infiltrate consisting of neutrophils and lymphocytes and an overlying fibrous capsule. The diagnosis of lymphoma or another neoplasm could not be definitely ruled out. Owing to uncertainty in diagnosis, the entire lesion was excised along with the distal pancreas with the use of a linear stapler. The staple line was oversewn with running 4-0 polypropylene suture, and the pancreas was transplanted. After surgery, the pancreas allograft functioned well with a small pancreatic leak, which had resolved by the first postoperative outpatient visit. Published by Elsevier Inc.

  15. Multiple Osteochondral Allograft Transplantation with Concomitant Tibial Tubercle Osteotomy for Multifocal Chondral Disease of the Knee.

    Science.gov (United States)

    Cotter, Eric J; Waterman, Brian R; Kelly, Mick P; Wang, Kevin C; Frank, Rachel M; Cole, Brian J

    2017-08-01

    Symptomatic patellofemoral chondral lesions are a challenging clinical entity, as these defects may result from persistent lateral patellar maltracking or repetitive microtrauma. Anteromedializing tibial tubercle osteotomy has been shown to be an effective strategy for primary and adjunctive treatment of focal or diffuse patellofemoral disease to improve the biomechanical loading environment. Similarly, osteochondral allograft transplantation has proven efficacy in physiologically young, high-demand patients with condylar or patellofemoral lesions, particularly without early arthritic progression. The authors present the surgical management of a young athlete with symptomatic tricompartmental focal chondral defects with fresh osteochondral allograft transplantation and anteromedializing tibial tubercle osteotomy.

  16. Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome.

    LENUS (Irish Health Repository)

    Garvey, J P

    2009-11-01

    Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN.

  17. Blockade of Vascular Adhesion Protein-1 Inhibits Lymphocyte Infiltration in Rat Liver Allograft Rejection

    OpenAIRE

    Martelius, Timi; Salaspuro, Ville; Salmi, Marko; Krogerus, Leena; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

    2004-01-01

    Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174–5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/gro...

  18. The influence of vascularization of transplanted processed allograft nerve on return of motor function in rats.

    Science.gov (United States)

    Giusti, Guilherme; Lee, Joo-Yup; Kremer, Thomas; Friedrich, Patricia; Bishop, Allen T; Shin, Alexander Y

    2016-02-01

    Processed nerve allografts have become an alternative to repair segmental nerve defects, with results comparable with autografts regarding sensory recovery; however, they have failed to reproduce comparable motor recovery. The purpose of this study was to determine how revascularizaton of processed nerve allograft would affect motor recovery. Eighty-eight rats were divided in four groups of 22 animals each. A unilateral 10-mm sciatic nerve defect was repaired with allograft (group I), allograft wrapped with silicone conduit (group II), allograft augmented with vascular endothelial growth factor (group III), or autograft (group IV). Eight animals from each group were sacrificed at 3 days, and the remaining animals at 16 weeks. Revascularization was evaluated by measuring the graft capillary density at 3 days and 16 weeks. Measurements of ankle contracture, compound muscle action potential, tibialis anterior muscle weight and force, and nerve histomorphometry were performed at 16 weeks. All results were normalized to the contralateral side. The results of capillary density at 3 days were 0.99% ± 1.3% for group I, 0.33% ± 0.6% for group II, 0.05% ± 0.1% for group III, and 75.6% ± 45.7% for group IV. At 16 weeks, the results were 69.9% ± 22.4% for group I, 37.0% ± 16.6% for group II, 84.6% ± 46.6% for group III, and 108.3% ± 46.8% for group IV. The results of muscle force were 47.5% ± 14.4% for group I, 21.7% ± 13.5% for group II, 47.1% ± 7.9% for group III, and 54.4% ± 10.6% for group IV. The use of vascular endothelial growth factor in the fashion used in this study improved neither the nerve allograft short-term revascularization nor the functional motor recovery after 16 weeks. Blocking allograft vascularization from surrounding tissues was detrimental for motor recovery. The processed nerve allografts used in this study showed similar functional motor recovery compared with that of the autograft. © 2014

  19. Long term follow up of pinna reconstruction by costal cartilagenous allograft

    International Nuclear Information System (INIS)

    Chanida Kanchanalarp; Yongyudh Vajaradul

    1999-01-01

    During 1990 to 1998,15 patients underwent pinna reconstruction using costal cartilagenous allografts,10 males, 5 females aged between 13 to 37 years old. The costal cartilages were implanted beneath the post auricular skin. Three months later, the composite cartilage-skin graft was elevated and the other free skin graft was used to reconstruct the pinna. Thirteen out of 15 patients had satisfactory cosmetic and function as usual. Only one cartilagenous graft had necrosis and the other one had infected necrosis after accidental trauma two weeks postoperatively. In conclusion costal cartilagenous allograft is an alternative pinna reconstruction with a good long-term result

  20. Arthroscopic Meniscal Allograft Transplantation With Soft-Tissue Fixation Through Bone Tunnels.

    Science.gov (United States)

    Spalding, Tim; Parkinson, Ben; Smith, Nick A; Verdonk, Peter

    2015-10-01

    Meniscal allograft transplantation improves clinical outcomes for patients with symptomatic meniscus-deficient knees. We describe an established arthroscopic technique for meniscal allograft transplantation without the need for bone fixation of the meniscal horns. After preparation of the meniscal bed, the meniscus is parachuted into the knee through a silicone cannula and the meniscal horns are fixed with sutures through bone tunnels. The body of the meniscus is then fixed with a combination of all-inside and inside-out sutures. This technique is reliable and reproducible and has clinical outcomes comparable with those of bone plug fixation techniques.

  1. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  2. Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs

    DEFF Research Database (Denmark)

    Jensen, T B; Overgaard, S; Lind, M

    2007-01-01

    Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules...... (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant...... surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three...

  3. Intrinsic cardiac nervous system in tachycardia induced heart failure.

    Science.gov (United States)

    Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

    2003-11-01

    The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to

  4. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  5. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    International Nuclear Information System (INIS)

    Easterling, K.J.; Trumble, T.E.

    1990-01-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal

  6. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    Energy Technology Data Exchange (ETDEWEB)

    Easterling, K.J.; Trumble, T.E. (Yale Univ. School of Medicine, New Haven, CT (USA))

    1990-10-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

  7. Comparison of Techniques for Preimplantation Treatment of Osteochondral Allograft Bone.

    Science.gov (United States)

    Baumann, Charles A; Baumann, John R; Bozynski, Chantelle C; Stoker, Aaron M; Stannard, James P; Cook, James L

    2018-03-07

    Articular defects are a major problem with few effective treatment options. Osteochondral allograft (OCA) transplantation can be an effective treatment; however, lack of OCA bone integration can cause failure. This controlled laboratory study was designed to compare clinically applicable methods for marrow element removal and enhanced delivery of bone marrow aspirate concentrate (BMC) to OCA bone. We hypothesized that compressed carbon dioxide (CO 2 ) treatment of OCA bone would result in significantly better marrow element removal, significantly more retention and distribution of viable osteoprogenitor cells, and significantly higher osteoinductive protein elution from OCAs compared with other preimplantation treatments. Fresh humeral heads ( n  = 24) were harvested and stored for 14 days, then randomly assigned to treatment based on marrow element removal and bone treatment: (standard of care [SOC]) ( n  = 4) - SOC high-pulse saline lavage, no BMC; (BMC) ( n  = 5) - saline lavage then canine BMC; (Drill + BMC) ( n  = 5) - 1.1 mm drill-hole immediately subchondral then saline lavage then BMC injection through drill hole; (Carb + BMC) ( n  = 5) - saline lavage then CO 2 then BMC; or (Saline-Carb + BMC) ( n  = 5) - saline lavage and CO 2 together then BMC. Treated OCAs were cultured for 14 days. On day 3, media were collected, centrifuged to isolate cells, and replaced. Cells were cultured for 11 days for colony forming unit (CFU) determination. OCA media were collected on days 7 and 14 of culture for analysis. On day 14, each graft was assessed for viable cell retention and distribution, and bone marrow element removal. BMC had significantly higher ( p  = 0.001) viable cell distribution compared with the SOC, Drill + BMC, Carb + BMC, and Saline-Carb + BMC groups. BMC and Drill + BMC had significantly higher ( p  BMC, and Saline-Carb + BMC. Drill + BMC and Carb + BMC had the highest media

  8. Early liver allograft dysfunction: risk factors, clinical course and outcomes

    Directory of Open Access Journals (Sweden)

    Ya. G. Moysyuk

    2016-01-01

    Full Text Available Early liver allograft dysfunction (EAD is associated with a high incidence of graft loss and patient mortality in the first 6 weeks after orthotopic liver transplantation (OLT.The aim of this retrospective single-center study is to identify the risk factors of EAD and to compare the short- and long-term results in EAD and non-EAD groups.Materials and methods. The results of 213 consecutive deceased donor liver transplantations performed between December 2004 and February 2015 were included in the analysis. Indications for OLT were non-viral liver cirrhosis in 52% of cases, viral hepatitis C or B in 34 %, hepatocellular carcinoma in 8 %; retransplantations were performed in 6% of cases due to previous liver graft dysfunction. EAD was defined by Olthoff criteria (Olthoff et al., 2010.Results. Overall incidence of EAD was 41.3%, including 5.6% of primary non-function grafts (PNF, i.e. irreversible EAD. No significant differences between EAD and non-EAD groups were seen either among donors in their age, gender, cause of death, bilirubin, plasma sodium level, aminotransferases aktivity, or among the recipients in their age, gender, body mass index, MELD. Retransplantation, donor time on mechanical ventilation in the intensive care unit for more than 2 days, highrisk donor category, transplant surgery duration more than 9.5 hours, and cold ischemia time (CIT > 8 hours were independent significant risk factors of EAD in a multivariate model. A 42-day mortality rates were 18.2% in EAD group (mostly due to PNF without urgent retransplantanion in 9.1%, and 0% in non-EAD group. Long-term results in EAD group were also significantly poorer: 1-, 5-, and 10-year graft survival rates were 74%, 68%, and 64%, respectively, versus 96%, 90%, and 83% in non-EAD group, Log-rank p = 0.0001.Conclusion. EAD significantly (≈ 20% decreases the short-term graft and patient survival rates. Meanwhile, a reversible EAD has no impact on long-term results

  9. Early Subretinal Allograft Rejection Is Characterized by Innate Immune Activity.

    Science.gov (United States)

    Kennelly, Kevin P; Holmes, Toby M; Wallace, Deborah M; O'Farrelly, Cliona; Keegan, David J

    2017-06-09

    Successful subretinal transplantation is limited by considerable early graft loss despite pharmacological suppression of adaptive immunity. We postulated that early innate immune activity is a dominant factor in determining graft survival and chose a nonimmunosuppressed mouse model of retinal pigment epithelial (RPE) cell transplantation to explore this. Expression of almost all measured cytokines by DH01 RPE cells increased significantly following graft preparation, and the neutrophil chemoattractant KC/GRO/CINC was most significantly increased. Subretinal allografts of DH01 cells (C57BL/10 origin) into healthy, nonimmunosuppressed C57BL/6 murine eyes were harvested and fixed at 1, 3, 7, and 28 days postoperatively and subsequently cryosectioned and stained. Graft cells were detected using SV40 large T antigen (SV40T) immunolabeling and apoptosis/necrosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Sections were also immunolabeled for macrophage (CD11b and F4/80), neutrophil (Gr1 Ly-6G), and T-lymphocyte (CD3-ɛ) infiltration. Images captured with an Olympus FV1000 confocal microscope were analyzed using the Imaris software. The proportion of the subretinal bolus comprising graft cells (SV40T+) was significantly (p < 0.001) reduced between postoperative day (POD) 3 (90 ± 4%) and POD 7 (20 ± 7%). CD11b+, F4/80+, and Gr1 Ly-6G+ cells increased significantly (p < 0.05) from POD 1 and predominated over SV40T+ cells by POD 7. Colabeling confocal microscopic analysis demonstrated graft engulfment by neutrophils and macrophages at POD 7, and reconstruction of z-stacked confocal images confirmed SV40T inside Gr1 Ly-6G+ cells. Expression of CD3-ɛ was low and did not differ significantly between time points. By POD 28, no graft cells were detectable and few inflammatory cells remained. These studies reveal, for the first time, a critical role for innate immune mechanisms early in subretinal graft rejection. The future success

  10. CT perfusion technique for assessment of early kidney allograft dysfunction: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Helck, A.; Notohamiprodjo, M.; Schoen, F.; Nikolaou, K.; Clevert, D.A.; Reiser, M.; Becker, C. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, University Hospitals Grosshadern, Munich (Germany); Wessely, M.; Schoenermarck, U.; Fischereder, M. [Ludwig-Maximilians-University of Munich, Department of Internal Medicine IV, Nephrology, University Hospitals Grosshadern, Munich (Germany); Klotz, E. [Siemens Healthcare, Computed Tomography, Forchheim (Germany)

    2013-09-15

    To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 {+-} 21 ml/100 ml/min) compared with those with ATN (77.5 {+-} 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 {+-} 3.1 mg/dl in AR and 5.3 {+-} 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 {+-} 5.2 mSv; the mean amount of contrast media applied was 34.5 {+-} 5.1 ml. All examinations were performed without complications. CT perfusion of kidney allografts may help to differentiate between ATN and rejection. (orig.)

  11. Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction

    NARCIS (Netherlands)

    Slort, Pauline R.; Ozden, Nergiz; Pape, Lars; Offner, Gisela; Tromp, Wilma F.; Wilhelm, Abraham J.; Bokenkamp, Arend

    2012-01-01

    Allograft function following renal transplantation is commonly monitored using serum creatinine. Multiple cross-sectional studies have shown that serum cystatin C is superior to creatinine for detection of mild to moderate chronic kidney dysfunction. Recent data in adults indicate that cystatin C

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

    International Nuclear Information System (INIS)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo

    1996-01-01

    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)

  13. Use of vitamin K to decrease allograft failure and patient mortality after organ transplantation

    NARCIS (Netherlands)

    de Borst, Martin; Vermeer, Cees

    2013-01-01

    Poor vitamin K status is provided as an independent risk factor for allograft failure and mortality in patients who received organ transplantation and who are under immunosuppressive medication. Various forms and recommended dosagesof vitamin K, optionally combined with vitamin D and/or other

  14. One-stage human acellular nerve allograft reconstruction for digital nerve defects

    Directory of Open Access Journals (Sweden)

    Xue-yuan Li

    2015-01-01

    Full Text Available Human acellular nerve allografts have a wide range of donor origin and can effectively avoid nerve injury in the donor area. Very little is known about one-stage reconstruction of digital nerve defects. The present study observed the feasibility and effectiveness of human acellular nerve allograft in the reconstruction of < 5-cm digital nerve defects within 6 hours after injury. A total of 15 cases of nerve injury, combined with nerve defects in 18 digits from the Department of Emergency were enrolled in this study. After debridement, digital nerves were reconstructed using human acellular nerve allografts. The patients were followed up for 6-24 months after reconstruction. Mackinnon-Dellon static two-point discrimination results showed excellent and good rates of 89%. Semmes-Weinstein monofilament test demonstrated that light touch was normal, with an obvious improvement rate of 78%. These findings confirmed that human acellular nerve allograft for one-stage reconstruction of digital nerve defect after hand injury is feasible, which provides a novel trend for peripheral nerve reconstruction.

  15. The immune response to corneal allograft requires a site-specific draininglymph node

    Czech Academy of Sciences Publication Activity Database

    Plšková, Jarmila; Duncan, L.; Holáň, Vladimír; Filipec, M.; Kraal, G.; Forrester, J. V.

    2002-01-01

    Roč. 73, č. 2 (2002), s. 210-215 ISSN 0041-1337 R&D Projects: GA MZd NI6019 Grant - others:NATO CRG(GB) LG972853 Institutional research plan: CEZ:MSM 111100005 Keywords : corneal allograft * lymph nodes Subject RIV: EC - Immunology Impact factor: 3.265, year: 2002

  16. Comparison of nutritional status in hemodialysis patients with and without failed renal allografts.

    Science.gov (United States)

    Yelken, B M; Gorgulu, N; Caliskan, Y; Yazici, H; Turkmen, A; Yildiz, A; Sever, M S

    2010-01-01

    The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aimed to compare the nutritional status and its relation with inflammation in patients on HD with and without previous kidney transplantation. Forty-three patients with failed renal allografts (27 males; mean age 36±9 yr) and 40 never transplanted HD patients (24 males; mean age 39±9 yr) were included in the study. Body weight, triceps (TSF), biceps (BSF), subscapular (SSSF), and suprailiac skinfold thicknesses (SISF); mid-arm, mid-arm muscle, hip and waist circumferences; as well as body mass indices (BMIs) were determined as anthropometric parameters. Moreover, biochemical markers of nutritional status, including serum cholesterol and albumin as well as high-sensitive C-reactive protein (hs-CRP), as a marker of inflammation, were measured. Associations among these variables were analyzed. There were no significant differences considering age, gender or duration of renal replacement therapy between the two groups. The TSF (pfailed renal allografts were significantly lower than those of the never transplanted HD patients. Waist circumference was significantly lower as well (p=0.028). Patients with failed transplants were characterized by lower serum albumin (pfailed allografts may induce chronic inflammation in chronic HD patients which may result in a worse nutritional status. © 2009 John Wiley & Sons A/S.

  17. The effects of low-dose radiotherapy on fresh osteochondral allografts: An experimental study in rabbits

    Directory of Open Access Journals (Sweden)

    Uğur Gönç

    2016-10-01

    Conclusion: In osteochondral massive allograft transplantations, the immune reaction of the host could be precluded with radiotherapy, and the side-effects can be prevented by low-dose fractionated regimen. The total dose of fractionated radiotherapy for an immune suppression should be adjusted not to damage the cartilage tissue, but to avoid articular degeneration in the long term.

  18. Partial trapeziectomy and interposition of fascia lata allograft in the operative treatment of thumb base osteoarthritis

    NARCIS (Netherlands)

    Spaans, Anne J.; Weijns, Marieke E.; Braakenburg, Assa; Van Minnen, Leo Paul; Mink Van Der Molen, Aebele B.

    2016-01-01

    Aim: The purpose of this retrospective cohort study was to evaluate the results of fascia lata allograft interposition after partial trapeziectomy in patients with symptomatic first carpometacarpal joint osteoarthritis. Methods and results: Twenty-one patients (22 thumbs) with Eaton-Glickel stage II

  19. Clinical, Histological, and Molecular Markers Associated With Allograft Loss in Transplant Glomerulopathy Patients.

    Science.gov (United States)

    Kamal, Layla; Broin, Pilib Ó; Bao, Yi; Ajaimy, Maria; Lubetzky, Michelle; Gupta, Anjali; de Boccardo, Graciela; Pullman, James; Golden, Aaron; Akalin, Enver

    2015-09-01

    We aimed to investigate the clinical, histopathological, and molecular factors associated with allograft loss in transplant glomerulopathy (TGP) patients. Of the 525 patients who underwent clinically indicated kidney biopsies, 52 (10%) had diagnosis of TGP. Gene expression profiles of 28 TGP and 11 normal transplant kidney biopsy samples were analyzed by Affymetrix HuGene 1.0 ST expression arrays. Over a median follow up of 23 months (1-46 months) after the diagnosis of TGP by biopsy, 17 patients (32%) lost their allografts at a median of 16 months (1-44 months). There was no difference between the 2 groups in terms of any demographic variables, serum creatinine, panel reactive antibody levels, donor-specific antibody frequency, or mean fluorescence intensity values. Patients who lost their allograft had a significantly higher median spot protein to creatinine ratio 2.81 (1.20-6.00) compared to no graft loss patients 1.16 (0.15-2.53), (P TGP patients with allograft loss.

  20. 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

    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...

  1. Urothelial carcinoma of the allograft kidney developed in a renal transplant patient.

    Science.gov (United States)

    Gökçe, Mehmet İlker; Kocaay, Akın Fırat; Aktürk, Serkan; Tüzüner, Acar

    2016-09-01

    Renal transplantation is the best option in the treatment of end-stage renal disease However these patients are under the risk of developing malignancies particularly due to effects of immune supression. These malignancies tend to be more agressive compared to the general population. Here, we present a case of urothelial carcinoma develoing in the ureter of allograft kidney.

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

    Directory of Open Access Journals (Sweden)

    Dongxia Ma

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

  3. Prolongation of rat islet allograft survival by direct ultraviolet irradiation of the graft

    International Nuclear Information System (INIS)

    Lau, H.; Reemtsma, K.; Hardy, M.A.

    1984-01-01

    Ultraviolet irradiation of rat dendritic cells completely abrogated their allostimulatory capacity in a mixed lymphocyte reaction. Rat islets of Langerhans similarly irradiated remained hormonally functional when transplanted into syngeneic diabetic rats. Allogeneic transplantation across a major histocompatibility barrier of islets initially treated in vitro with ultraviolet irradiation resulted in prolonged allograft survival without the use of any immunosuppressive agents

  4. A new in vitro approach to determine acquired tolerance in long-term kidney allograft recipients

    International Nuclear Information System (INIS)

    Reinsmoen, N.L.; Kaufman, D.; Matas, A.; Sutherland, D.E.; Najarian, J.S.; Bach, F.H.

    1990-01-01

    Previous studies indicate some kidney allograft recipients treated with total lymphoid irradiation, cyclosporine, or conventional immunosuppressive therapy demonstrate specific proliferative unresponsiveness in mixed lymphocyte culture (MLC) to donor cells at various times posttransplant. To investigate possible donor-specific hyporeactivity, we have studied 3 patients treated with TLI whose grafts have survived longer than 10 years; 2 patients given the same immunosuppressive protocol but without TLI whose grafts have survived longer than 10 years; and 27 CsA-treated living-related donor and cadaver-allograft recipients 1 year posttransplant. We confirmed previous observations of hyporeactivity of some patients' cells to stimulation by donor cells. In addition, we identified hyporeactivity to stimulation by homozygous typing cells (HTCs) defining the HLA-Dw specificities of the donor cells for all 3 of the 3 TLI patients, 1 of the 2 non-TLI patients, and 9 of the 27 patients 1 year posttransplant. The LRD recipients with donor-specific hyporeactivity as defined by the HTC analysis demonstrated fewer rejection episodes (25% vs. 57%) and lower mean creatinine levels (1.18 vs 1.78 mg/dL) than patients without donor-specific hyporeactivity. These studies demonstrate the feasibility of monitoring the immune status of allograft recipients posttransplant by means of HTC analysis, eliminating the need for pretransplant specimens. This approach provides a possible means to assess which patients may have acquired donor-specific hyporeactivity to their kidney allograft and thus may require less immunosuppression

  5. 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)

  6. Early post transplantation renal allograft perfusion failure due to intimal dissection of the renal artery

    Directory of Open Access Journals (Sweden)

    Khattab Omar

    2009-01-01

    Full Text Available Transplant renal artery stenosis (TRAS is a recognized and potentially curable cause of post transplant arterial hypertension, allograft dysfunction, and graft loss. It usually occurs 3 months to 2 years after transplantation, but early or later presentations are not uncommon. We present a case of renal artery narrowing due to intimal dissection that was managed medically.

  7. Albumin-coated structural lyophilized bone allografts: a clinical report of 10 cases.

    Science.gov (United States)

    Klára, Tamás; Csönge, Lajos; Janositz, Gábor; Csernátony, Zoltán; Lacza, Zsombor

    2014-03-01

    Bone replacement and the use of bone supplementary biological substances have become widespread in clinical practice. Although autografts have excellent properties, their limited availability, difficulties with shaping and donor site morbidity have made allografts a viable and increasingly preferred alternative. The main drawback of allografts is that the preparation destroys osteogenic cells and results in denaturation of osteoinductive proteins. Serum albumin is a well-known constituent of stem cell culture media and we found that lyophilizing albumin onto bone allografts markedly improves stem-cell attachment and bone healing in animal models thus replacing some of the osteoinductive potential. As a first step in the clinical introduction of albumin coated grafts, we aimed to test surgical handling and early incorporation in aseptic revision arthroplasty in humans. We selected patients who needed large structural allografts and the current operation was the last attempt at preserving a moving joint. In a series of 10 cases of hip and knee revision surgery we did not experience any drawbacks of the albumin-coated grafts during handling and implantation. Twelve months radiographic and SPECT-CT follow-up showed that the graft was well received by the host and active remodelling was observed. The lack of graft-related complications and the good 1-year results indicate that controlled trials may be initiated in more common bone grafting indications where long-term effectiveness can be evaluated.

  8. Hemodilution, kidney dysfunction and cardiac surgery

    Directory of Open Access Journals (Sweden)

    Fabio Papa Taniguchi

    2009-03-01

    Full Text Available Hemodilution has been used in cardiac surgery to reduce blood viscosity and peripheral vascular resistance, decrease the need for blood transfusions, attenuate the risk of transfusions and diminish systemic inflammatory response syndrome and hospital costs. The lowest hematocrit level during cardiopulmonary bypass has been stated as 20%. However, severe hemodilution in cardiopulmonary bypass for patients undergoing cardiac surgery has been recognized as a risk factor for hospital deaths and reduced long-term survival. The introduction of normothermia restarted the debate about the lowest acceptable hematocrit during cardiopulmonary bypass. The objective of this review is to evaluate hemodilution during cardiac surgery as a risk factor for the development of post-operative acute renal failure.

  9. A Comparison of Implants Used in Open-Door Laminoplasty: Structural Rib Allografts Versus Metallic Miniplates.

    Science.gov (United States)

    Tabaraee, Ehsan; Mummaneni, Praveen; Abdul-Jabbar, Amir; Shearer, David; Roy, Esha; Amin, Beejal; Ames, Christopher; Burch, Shane; Deviren, Vedat; Berven, Sigurd; Hu, Serena; Chou, Dean; Tay, Bobby K

    2017-06-01

    A retrospective case-controlled study. Open-door laminoplasty has been successfully used to address cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Two common implants include rib allograft struts and metallic miniplates. The goals of this study were to compare outcomes, complications, and costs associated with these 2 implants. A retrospective review was done on 51 patients with allograft struts and 55 patients with miniplates. Primary outcomes were neck visual analog scale (VAS) pain scores and Nurick scores. Secondary outcomes included length of the procedure, estimated blood loss, rates of complications, and the direct costs associated with the surgery and inpatient hospitalization. There were no differences in demographic characteristics, diagnoses, comorbidities, and preoperative outcome scores between the 2 treatment groups. Mean follow-up was 27 months. The postoperative neck VAS scores and Nurick scores improved significantly from baseline to final follow-up for both groups, but there was no difference between the 2 groups. The average length of operation (161 vs. 136 min) and number of foraminotomies (2.7 vs. 1.3) were higher for the allograft group (P=0.007 and 0.0001, respectively). Among the miniplate group, there was no difference in complications but a trend for less neck pain for patients treated without hard collar at final follow-up (1.8 vs. 2.3, P=0.52). The mean direct costs of hospitalization for the miniplate group were 15% higher. Structural rib allograft struts and metallic miniplates result in similar improvements in pain and functional outcome scores with no difference in the rate of complications in short-term follow-up. Potential benefits of using a plate include shorter procedure length and less need for postoperative immobilization. When costs of bracing and operative time are included, the difference in cost between miniplates and allograft struts is negligible.

  10. Sandwich allografts for long-bone nonunions in patients with osteogenesis imperfecta: a retrospective study.

    Science.gov (United States)

    Puvanesarajah, Varun; Shapiro, Jay R; Sponseller, Paul D

    2015-02-18

    Patients with osteogenesis imperfecta often develop nonunions, as internal fixation has limited applicability in this condition. We report the outcomes of a modified "sandwich technique" in the treatment of long-bone nonunions in patients with osteogenesis imperfecta; this technique brings circumferential stabilization and normal collagen to the nonunion site. From May 2003 through February 2012, twelve patients (eight females, four males; median age, 39.0 years; range, eleven to seventy-eight years) who had osteogenesis imperfecta (Sillence type I [three], type III [eight], and type IV [one]) and a combined total of thirteen nonunions (two humeral, two radial, three femoral, four tibial, and two ulnar; median duration, 15.0 months; range, six to 204 months) were treated at our institution with compressed sandwich allograft cortical struts. The struts were fashioned to be wide enough to allow for increased osteoconductive surface area and to approximate a hemicylindrical shape. Treatment history and demographics data were acquired through retrospective chart review. Follow-up radiographs were analyzed by two attending orthopaedic surgeons to determine radiographic findings. The median follow-up time was 4.6 years (range, 2.1 to 10.3 years). All thirteen nonunions, including one requiring a second graft procedure, healed with abundant, smooth allograft incorporation, resulting in an initial healing rate of 92% because of a refracture in one patient. This patient's nonunion ultimately healed with additional allograft struts and a new intramedullary rod. One patient required removal of prominent screws. The final follow-up examinations revealed no pain or refracture at the original nonunion site. All patients regained their prefracture level of function. Sandwich allograft struts constitute a durable, safe method for the stabilization and healing of persistent long-bone nonunions in patients with osteogenesis imperfecta. All patients showed incorporation of the

  11. Influence of socioeconomic status on allograft and patient survival following kidney transplantation.

    Science.gov (United States)

    Ward, Frank L; O'Kelly, Patrick; Donohue, Fionnuala; ÓhAiseadha, Coilin; Haase, Trutz; Pratschke, Jonathan; deFreitas, Declan G; Johnson, Howard; Conlon, Peter J; O'Seaghdha, Conall M

    2015-06-01

    Whether socioeconomic status confers worse outcomes after kidney transplantation is unknown. Its influence on allograft and patient survival following kidney transplantation in Ireland was examined. A retrospective, observational cohort study of adult deceased-donor first kidney transplant recipients from 1990 to 2009 was performed. Those with a valid Irish postal address were assigned a socioeconomic status score based on the Pobal Hasse-Pratschke deprivation index and compared in quartiles. Cox proportional hazards models and Kaplan-Meier survival analysis were used to investigate any significant association of socioeconomic status with patient and allograft outcomes. A total of 1944 eligible kidney transplant recipients were identified. The median follow-up time was 8.2 years (interquartile range 4.4-13.3 years). Socioeconomic status was not associated with uncensored or death-censored allograft survival (hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.99-1.00, P = 0.33 and HR 1.0, 95% CI 0.99-1.00, P = 0.37, respectively). Patient survival was not associated with socioeconomic status quartile (HR 1.0, 95% CI 0.93-1.08, P = 0.88). There was no significant difference among quartiles for uncensored or death-censored allograft survival at 5 and 10 years. There was no socioeconomic disparity in allograft or patient outcomes following kidney transplantation, which may be partly attributable to the Irish healthcare model. This may give further impetus to calls in other jurisdictions for universal healthcare and medication coverage for kidney transplant recipients. © 2015 Asian Pacific Society of Nephrology.

  12. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

    Science.gov (United States)

    Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

    2016-05-01

    Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

  13. Safety in cardiac surgery

    NARCIS (Netherlands)

    Siregar, S.

    2013-01-01

    The monitoring of safety in cardiac surgery is a complex process, which involves many clinical, practical, methodological and statistical issues. The objective of this thesis was to measure and to compare safety in cardiac surgery in The Netherlands using the Netherlands Association for

  14. Cardiac Catheterization (For Kids)

    Science.gov (United States)

    ... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Cardiac Catheterization KidsHealth / For Kids / Cardiac Catheterization What's in this article? What Is ...

  15. Sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Neeraj Parakh

    2015-01-01

    Full Text Available Sudden cardiac death is one of the most common cause of mortality worldwide. Despite significant advances in the medical science, there is little improvement in the sudden cardiac death related mortality. Coronary artery disease is the most common etiology behind sudden cardiac death, in the above 40 years population. Even in the apparently healthy population, there is a small percentage of patients dying from sudden cardiac death. Given the large denominator, this small percentage contributes to the largest burden of sudden cardiac death. Identification of this at risk group among the apparently healthy individual is a great challenge for the medical fraternity. This article looks into the causes and methods of preventing SCD and at some of the Indian data. Details of Brugada syndrome, Long QT syndrome, Genetics of SCD are discussed. Recent guidelines on many of these causes are summarised.

  16. CARDIAC LYMPHOMA IN DOG

    Directory of Open Access Journals (Sweden)

    G. D. Cruz

    2016-11-01

    Full Text Available Lymphoma is a lymphoid tumor that originates in hematopoietic organs such as lymph node, spleen or liver. In dogs, the overall prevalence of cardiac tumors was estimated to be only 0.19% based on the results of the survey of a large database, and lymphomas accounts for approximately 2% of all cardiac tumors. In general, the involvement of the myocardium is rarely described in canine lymphoma. Currently, there is no evidence of a viral association with primary cardiac lymphoma in dogs, but other types of immunosuppression may contribute to abnormal events, such as involvement primary cardiac. The aim of this study was to analyze a case of sudden death of a bitch, SRD, aged 10, who had the final diagnosis of cardiac lymphoma.

  17. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  18. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  19. Robotic cardiac surgery: an anaesthetic challenge.

    Science.gov (United States)

    Wang, Gang; Gao, Changqing

    2014-08-01

    Robotic cardiac surgery with the da Vinci robotic surgical system offers the benefits of a minimally invasive procedure, including a smaller incision and scar, reduced risk of infection, less pain and trauma, less bleeding and blood transfusion requirements, shorter hospital stay and decreased recovery time. Robotic cardiac surgery includes extracardiac and intracardiac procedures. Extracardiac procedures are often performed on a beating heart. Intracardiac procedures require the aid of peripheral cardiopulmonary bypass via a minithoracotomy. Robotic cardiac surgery, however, poses challenges to the anaesthetist, as the obligatory one-lung ventilation (OLV) and CO2 insufflation may reduce cardiac output and increase pulmonary vascular resistance, potentially resulting in hypoxaemia and haemodynamic compromise. In addition, surgery requires appropriate positioning of specialised cannulae such as an endopulmonary vent, endocoronary sinus catheter, and endoaortic clamp catheter under the guidance of transoesophageal echocardiography. Therefore, cardiac anaesthetists should have a working knowledge of these systems, OLV and haemodynamic support. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Tetrodotoxin Sensitivity of the Vertebrate Cardiac Na+ Current

    Directory of Open Access Journals (Sweden)

    Jaakko Haverinen

    2011-11-01

    Full Text Available Evolutionary origin and physiological significance of the tetrodotoxin (TTX resistance of the vertebrate cardiac Na+ current (INa is still unresolved. To this end, TTX sensitivity of the cardiac INa was examined in cardiac myocytes of a cyclostome (lamprey, three teleost fishes (crucian carp, burbot and rainbow trout, a clawed frog, a snake (viper and a bird (quail. In lamprey, teleost fishes, frog and bird the cardiac INa was highly TTX-sensitive with EC50-values between 1.4 and 6.6 nmol·L−1. In the snake heart, about 80% of the INa was TTX-resistant with EC50 value of 0.65 μmol·L−1, the rest being TTX-sensitive (EC50 = 0.5 nmol·L−1. Although TTX-resistance of the cardiac INa appears to be limited to mammals and reptiles, the presence of TTX-resistant isoform of Na+ channel in the lamprey heart suggest an early evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all vertebrates.

  1. [Cardiac sarcoidosis: diagnostics, treatment and follow-up].

    Science.gov (United States)

    Dudziak, Maria; Jankowska, Hanna; Dorniak, Karolina

    2018-03-27

    Sarcoidosis is a generalised granulomatous disorder of unknown aetiology. Cardiac involvement may affect conduction system, myocardium, valvular apparatus and pericardium. Clinical spectrum ranges from asymptomatic involvement to sudden cardiac death. Patients with biopsy-proven extracardiac sarcoidosis should be screened for cardiac involvement (standard ECG, 24-hour Holter ECG, echocardiography) and in case of any abnormalities found on these tests, more advanced diagnostic methods should be used. Steroid treatment is still the mainstay of therapy in cardiac sarcoidosis. Several immunosuppresive agents are also effective and used in different combinations with steroids, as well as heart failure treatment (including ACE inhibitors, angiotensin receptor blockers, beta-blockers and diuretics). Advanced heart block requires pacemaker implantation, and implantable cardioverterdefibrillator is an effective treatment in primary and secondary prophylaxis of sudden cardiac death. Heart transplantation is considered in advanced, drug-resistant heart failure or incessant ventricular arrhythmias unresponsive to other forms of therapy. © 2018 MEDPRESS.

  2. Comparative study and histomorphometric analysis of bone allografts lyophilized and sterilized by autoclaving, gamma irradiation and ethylene oxide in rats

    Directory of Open Access Journals (Sweden)

    Otavio Machado de Almeida

    2013-01-01

    Full Text Available PURPOSE: To compare three sterilization methods (autoclave, gamma irradiation and ethylene oxide over non demineralized lyophilized bone allografts. METHODS: Bone allografts were implanted on paravertebral muscles of 21 rats. After 30 days animals were sacrificed and grafts underwent comparative analysis regarding histomorphometric and macroscopic parameters. RESULTS: Allografts that underwent the three sterilization methods presents similar weight gain, cortical thickness similar to control group, and less fibrosis than the control group. Grafts that underwent sterilization in autoclave presented less presence of multinucleated giant cells, although not statistically significant. There was also no statistically significant difference regarding mineralization on the three groups. CONCLUSION: The three sterilization methods cause similar effects on bone allografts regarding macroscopic and histomorphometric parameters.

  3. Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

    Science.gov (United States)

    Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

    2017-09-01

    A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaoyou [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Dong, Changgui [Institute of Molecular Ecology and Evolution, East China Normal University, Shanghai 200062 (China); Jiang, Zhengyao [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Wu, William K.K. [Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Chan, Matthew T.V. [Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Zhang, Jie [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Li, Haibin; Qin, Ke [Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People' s Liberation Army, Nanning, Guangxi 530021 (China); Sun, Xuyong, E-mail: sunxuyong0528@163.com [Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People' s Liberation Army, Nanning, Guangxi 530021 (China)

    2015-04-10

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.

  5. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    International Nuclear Information System (INIS)

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao; Wu, William K.K.; Chan, Matthew T.V.; Zhang, Jie; Li, Haibin; Qin, Ke; Sun, Xuyong

    2015-01-01

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11

  6. Efficacy of Psychoeducational Intervention on Allograft Function in Kidney Transplant Patients: 10-Year Results of a Prospective Randomized Study.

    Science.gov (United States)

    Breu-Dejean, Nathalie; Driot, Damien; Dupouy, Julie; Lapeyre-Mestre, Maryse; Rostaing, Lionel

    2016-02-01

    Improving treatment adherence to immunosuppressive agents could have positive effects on the morbidity and mortality of kidney transplant recipients. Our objective was to determine whether psychoeducational intervention aimed at improving treatment adherence also could improve 10-year kidney allograft survival rates. A randomized open-label study compared a group who received psychoeducational intervention (n = 55) with a control group (n = 55), with all patients being kidney transplant recipients in the Department of Nephrology and Organ Transplantation (University Hospital, Toulouse, France). Psychoeducational intervention comprised 8 weekly sessions provided by multidisciplinary teams. Patients were included between 2002 and 2003. The primary endpoint was allograft survival at 10 years (ie, by 2012). A failed allograft or death with a functioning allograft was considered an event. Mean overall allograft survival rate at 10 years was 78.2% (95% confidence interval, 70.5-25.3). In the control group, 48 patients (43.6%) still had a functioning graft at 10 years versus 38 patients (34.5%) in the psychoeducational intervention group (P = .02). However, a log-rank test did not find any significant difference in allograft survival between the groups (P = .06). In multivariate analyses (Cox model), no factor was significantly associated with allograft survival at 10 years. After an initial 6-month observational adherence survey, there was no benefit to kidney allograft survival at 10 years after the psychoeducational intervention, which had aimed to improve patient adherence to treatment with immunosuppressive agents. This might be related to the fact that booster interventions are needed (eg, on a yearly basis).

  7. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide

    OpenAIRE

    Williams, Robert C.; Opelz, Gerhard; Weil, E. Jennifer; McGarvey, Chelsea J.; Chakkera, Harini A.

    2017-01-01

    Background Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Methods Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. ...

  8. Laboratory methods used for testing the effect of radiation sterilization and preservation procedures on bone allografts

    International Nuclear Information System (INIS)

    Dziedzic-Goclawska, A.

    1999-01-01

    Sterilization of tissue allografts with ionizing radiation introduced in the mid of 1950s is more and more frequently used in tissue banking practice. The dose of 25 kGy is currently recommended and commonly used by many tissue banks in the world with the exception of the Central Tissue Bank in Warsaw where the dose of 33 kGy + 10 % has been routinely used since 1963, and from 1997 the dose of 35 kGy + 10 % has been introduced. To study the effect of radiation-sterilization on bone allografts the interdisciplinary investigations have been undertaken and several techniques have been implemented in our tissue bank. The electron paramagnetic resonance (EPR) spectroscopy has been applied to investigate the amount, origin and stability of free radicals and other paramagnetic entities induced in radiation-sterilized bone allografts. This technique has been also utilized for quantitative evaluation of remodeling process of radiation-sterilized bone allografts and for estimation of the absorbed dose of ionizing radiation using bone tissue as a dosimeter. A model of heterotopically induced osteogenesis after transplantation of devitalized bone matrix into the muscle (described by Urist in 1965) is very useful in tissue banking practice. It allows one to determine the contribution the graft itself makes to osteogenesis. This model is routinely used in our tissue bank to evaluate the effect of various sterilization and preservation procedures on osteoinductive properties of bone allografts. The solubility in vitro of collagen - a carrier for bone morphogenetic proteins (BMPS) and a major constituent of bone and the other connective tissue grafts, has been studied by measuring the amount of extracted neutral, acid and total soluble collagen from bone grafts preserved by different methods at irradiated at vanous experimental conditions. A positive correlation between collagen solubility in vitro and the rate of graft resorption in vivo has been observed. The high doses of

  9. Irradiated large segment allografts in limb saving surgery for extremity tumor - Philippine experience

    International Nuclear Information System (INIS)

    Wang, E.H.M.; Agcaoili, N.; Turqueza, M.S.

    1999-01-01

    Limb saving surgery has only recently become an option in the Phillipines. This has given a better comprehension of oncologic principles and from the refinement of bone-reconstruction procedures. Foremost among the latter is the use of large segment bone allografts. Large-segment allografts (LSA) are available from the Tissue and Bone Bank of the University of the Philippines (UP). After harvest, these bones are processed at the Bank, radiation-sterilized at the Philippine Nuclear Research Institute, and then stored in a -80 degree C deep freezer. We present our 4-year experience (Jan 93 - Dec 96) with LSA for limb saving surgery in musculoskeletal tumors. All patients included had: (1) malignant or aggressive extremity tumors; (2) surgery performed by the UP - Musculoskeletal Tumor Unit (UP-MUST Unit); (3) reconstructions utilizing irradiated large-segment allografts from the UP Tissue and Bone Bank; and (4) follow-up of at least one year or until death. Tumors included osteosarcoma (6) giant cell tumors (11), and metastatic lesions (3). Age ranged from 16-64 years old; 13 males and 7 females. Bones involved were the femur (12) tibia (5) and humerus (3). Average defect length was 15 cm and surgeries performed were intercalary replacement (5), resection arthrodesis (11), hemicondylar allograft (3), and allograft-prosthesis-composite (1). Follow-up ranged was from 17- 60 months or until death. Fifteen (1 5) were alive with NED (no evidence of disease), 3 were dead (2 of disease 1 of other causes), and 2 were AWED (alive with evidence of disease). Functional evaluation using the criteria of the International Society of Limb Salvage (ISOLS) was performed on 18 patients. This averaged 27.5 out of 30 points (92%) for 15 patients. Many having returned to their previous work and recreation. The 3 failures were due to infections in 2 cases (both of whom opted for amputations but who have not been fit with prostheses), and a fracture (secondary to a fall) in one case. Limb

  10. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  11. Dual energy cardiac CT.

    Science.gov (United States)

    Carrascosa, Patricia; Deviggiano, Alejandro; Rodriguez-Granillo, Gastón

    2017-06-01

    Conventional single energy CT suffers from technical limitations related to the polychromatic nature of X-rays. Dual energy cardiac CT (DECT) shows promise to attenuate and even overcome some of these limitations, and might broaden the scope of patients eligible for cardiac CT towards the inclusion of higher risk patients. This might be achieved as a result of both safety (contrast reduction) and physiopathological (myocardial perfusion and characterization) issues. In this article, we will review the main clinical cardiac applications of DECT, that can be summarized in two core aspects: coronary artery evaluation, and myocardial evaluation.

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

    Directory of Open Access Journals (Sweden)

    Mat Saad A

    2009-01-01

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

  13. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide.

    Science.gov (United States)

    Williams, Robert C; Opelz, Gerhard; Weil, E Jennifer; McGarvey, Chelsea J; Chakkera, Harini A

    2017-05-01

    Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

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

    International Nuclear Information System (INIS)

    Zheng Huaien; Cheng Tianmin; Yan Yongtang

    1994-01-01

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

  15. A comparative evaluation of freeze dried bone allograft and decalcified freeze dried bone allograft in the treatment of intrabony defects: A clinical and radiographic study

    Directory of Open Access Journals (Sweden)

    Rajat Gothi

    2015-01-01

    Full Text Available Background: Ideal graft material for regenerative procedures is autogenous bone graft but the major disadvantage with this graft is the need for a secondary surgical site to procure donor material and the frequent lack of intraoral donor site to obtain sufficient quantities of autogenous bone for multiple or deep osseous defects. Hence, to overcome these disadvantages, bone allografts were developed as an alternative source of graft material. Materials and Methods: In 10 patients with chronic periodontitis, 20 bilateral infrabony defects were treated with freeze dried bone allograft (FDBA-Group A and decalcified freeze dried bone allograft (DFDBA-Group B. Clinical and radiographic parameters were assessed preoperatively and at 3 months and 6 months postoperatively. Data thus obtained was subjected to statistical analysis. Results: Significant improvement in the reduction in probing depth and relative attachment level (RAL from the baseline to 3 months to baseline to 6 months in group A and group B, which was statistically significant but no statistically significant reduction was seen between 3 months and 6 months. On inter-group comparison, no significant differences were observed at all-time points. In adjunct to the probing depth and RAL, the radiographic area of the defect showed a similar trend in intra-group comparison and no significant difference was seen on inter-group comparison at all-time points. Conclusions: Within the limitations of the current study, it can be concluded that DFDBA did not show any improvement in the clinical and radiographic parameters in the treatment of the intrabony defects as compared to FDBA.

  16. Cardiac Catheterization (For Parents)

    Science.gov (United States)

    ... cases, the doctor might call for a cardiac magnetic resonance imaging (MRI) scan or a CAT scan . ... first couple of days. This means no heavy lifting (more than 10 pounds) and no sports. After ...

  17. Cardiac Catheterization (For Teens)

    Science.gov (United States)

    ... doctor may also call for a cardiac MRI (magnetic resonance imaging) scan or a CT (computerized tomography) ... first couple of days. This means no heavy lifting (nothing over 10 pounds) and no sports. After ...

  18. Autonomic cardiac innervation

    Science.gov (United States)

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  19. Cardiac imaging in adults

    International Nuclear Information System (INIS)

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority

  20. Cardiac imaging in adults

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  1. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  2. Post cardiac injury syndrome

    DEFF Research Database (Denmark)

    Nielsen, S L; Nielsen, F E

    1991-01-01

    The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

  3. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  4. Adiponectin and Cardiac Hypertrophy in Acromegaly.

    Science.gov (United States)

    Gurbulak, Sabriye; Akin, Fulya; Yerlikaya, Emrah; Yaylali, Guzin F; Topsakal, Senay; Tanriverdi, Halil; Akdag, Beyza; Kaptanoglu, Bunyamin

    2016-01-01

    Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be

  5. Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection.

    Science.gov (United States)

    Pelzl, Steffen; Opelz, Gerhard; Daniel, Volker; Wiesel, Manfred; Süsal, Caner

    2003-02-15

    Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, Pacute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.

  6. Histological study on the new bone formation of the implanted bone allograft in sheep

    International Nuclear Information System (INIS)

    Li Youchen; Sun Guiying; Shi Zhancheng

    1999-01-01

    The purpose of this study is to compare the formation of new bone in the implanted frozen irradiated bone allograft with the fresh bone autograft. The work on animal model included resection and implantation of sheep's tibial diaphysis and intramedullary nail fixation, with total number 20. Tibias were harvested at 6, 12, and 24 months after operation. Sheep were fed with tetracycline I week before bone harvesting. Bones were examined with usual and fluorescence microscopes. The results showed that the progress of graft incorporation in allografts were generally similar to that of autografts. Capillaries penetration and callus formation extended from the host end to surround the host-graft junction in 6 months. Incorporation of new bone was nearly completed in 12 months; then the speed of new bone formation was decreased, and the implanted bone graft was almost completely substituted with non-nal bone structure in 24 months

  7. Articular reconstruction of the humeral head with autogenous allograft in the treatment of the osteonecrosis

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    Alberto Naoki Miyazaki

    Full Text Available ABSTRACT The authors describe a surgical biological reconstruction of the humeral head with frozen autogenous allograft technique for the treatment of young patients with focal osteonecrosis of the humeral head. This represents a possible alternative, maybe even definitive for some patients, when compared to hemiarthroplasty or total shoulder arthroplasty. The technique consists of the fixation of a frozen autogenous allograft with previously-molded articular cartilage from the humeral head, after cleansing the osteonecrotic focus. Five patients under 50 years of age were treated, with three very satisfactory results, one patient was lost to follow-up, and one patient had an unsatisfactory result (converted to hemiarthroplasty. The study describes the technique in detail and the three cases with a longer follow-up time.

  8. Experience of using allograft transplantation to reconstruct bone defect at Dr. Soetomo Hospital, Surabaya, Indonesia

    International Nuclear Information System (INIS)

    Ferdiansyah Abdurrahman

    1999-01-01

    To evaluate the result of allograft transplantation to reconstruct bone defect. The study was case series. All of the cases have been evaluated clinically and radiologically. All of the operations were carried out at Dr. Soetomo Hospital as the referral hospital. Twenty one patients with bone defect were caused by tumour (11 patients), injury (7 patients) infection (1 patient), and congenitial anomaly (2 patients). Out of 21 patients, 15 (78.8%) were already radiologically united, and out of 21 patients 14 (73.7%) patients showed an excellent and good limb function, whereas 5 (26.3%) patients showed a fair and poor result respectively. Allograft transplantation gave a good result to reconstruct bone defect

  9. Early Allograft Dysfunction Is Associated With Higher Risk of Renal Nonrecovery After Liver Transplantation

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    Hani M. Wadei, MD

    2018-04-01

    Full Text Available Abstract. Early allograft dysfunction (EAD identifies allografts with marginal function soon after liver transplantation (LT and is associated with poor LT outcomes. The impact of EAD on post-LT renal recovery, however, has not been studied. Data on 69 primary LT recipients (41 with and 28 without history of renal dysfunction who received renal replacement therapy (RRT for a median (range of 9 (13-41 days before LT were retrospectively analyzed. Primary outcome was renal nonrecovery defined as RRT requirement 30 days from LT. Early allograft dysfunction developed in 21 (30% patients, and 22 (32% patients did not recover renal function. Early allograft dysfunction was more common in the renal nonrecovery group (50% vs 21%, P = 0.016. Multivariate logistic regression analysis demonstrated that EAD (odds ratio, 7.25; 95% confidence interval, 2.0-25.8; P = 0.002 and baseline serum creatinine (odds ratio, 3.37; 95% confidence interval, 1.4-8.1; P = 0.007 were independently associated with renal nonrecovery. History of renal dysfunction, duration of renal dysfunction, and duration of RRT were not related to renal recovery (P > 0.2 for all. Patients who had EAD and renal nonrecovery had the worst 1-, 3-, and 5-year patient survival, whereas those without EAD and recovered renal function had the best outcomes (P < 0.001. Post-LT EAD was independently associated with renal nonrecovery in LT recipients on RRT for a short duration before LT. Furthermore, EAD in the setting of renal nonrecovery resulted in the worst long-term survival. Measures to prevent EAD should be undertaken in LT recipients on RRT at time of LT.

  10. Post-transplant Lymphoproliferative Disorder Arising from Renal Allograft Parenchyma: A Case Report

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    Park, Byung Kwan; Kim, Chan Kyo; Kwon, Ghee Young [Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication that occurs in patients undergoing kidney transplantation. PTLD usually manifests as a renal hilar mass comprised of histologically B-lymphocytes. We report our experience of managing a patient with PTLD arising from renal parenchyma. Ultrasonographic and MR imaging features of this unusual PTLD suggested differentiated renal cell carcinoma arising from the renal allograft

  11. Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation.

    Science.gov (United States)

    Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward

    2012-03-01

    Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

  12. Dynamic Quantification of Host Schwann Cell Migration into Peripheral Nerve Allografts

    Science.gov (United States)

    Whitlock, Elizabeth L.; Myckatyn, Terence M.; Tong, Alice Y.; Yee, Andrew; Yan, Ying; Magill, Christina K.; Johnson, Philip J.; Mackinnon, Susan E.

    2010-01-01

    Host Schwann cell (SC) migration into nerve allografts is the limiting factor in the duration of immunosuppression following peripheral nerve allotransplantation, and may be affected by different immunosuppressive regimens. Our objective was to compare SC migration patterns between clinical and experimental immunosuppression regimens both over time and at the harvest endpoint. Eighty mice that express GFP under the control of the Schwann cell specific S100 promoter were engrafted with allogeneic, nonfluorescent sciatic nerve grafts. Mice received immunosuppression with either tacrolimus (FK506), or experimental T-cell triple costimulation blockade (CSB), consisting of CTLA4-immunoglobulin fusion protein, anti-CD40 monoclonal antibody, and anti-inducible costimulator monoclonal antibody. Migration of GFP-expressing host SCs into wild-type allografts was assessed in vivo every 3 weeks until 15 weeks postoperatively, and explanted allografts were evaluated for immunohistochemical staining patterns to differentiate graft from host SCs. Immunosuppression with tacrolimus exhibited a plateau of SC migration, characterized by significant early migration (< 3 weeks) followed by a constant level of host SCs in the graft (15 weeks). At the endpoint, graft fluorescence was decreased relative to surrounding host nerve, and donor SCs persisted within the graft. CSB-treated mice displayed gradually increasing migration of host SCs into the graft, without the plateau noted in tacrolimus-treated mice, and also maintained a population of donor SCs at the 15-week endpoint. SC migration patterns are affected by immunosuppressant choice, particularly in the immediate postoperative period, and the use of a single treatment of CSB may allow for gradual population of nerve allografts with host SCs. PMID:20633557

  13. Application of Minicircle Technology of Self-Reproducing Synthetic Protein Drugs in Preventing Skin Allograft Rejection.

    Science.gov (United States)

    Lim, Sun Woo; Kim, Young Kyun; Park, Narae; Jin, Long; Jin, Jian; Doh, Kyoung Chan; Ju, Ji Hyeon; Yang, Chul Woo

    2015-07-30

    Recently, it has been reported that minicircle vectors could allow the expression of transgenes using the protein synthesis system of the host. Here, we tested a novel strategy to permit the production of synthetic biologics using minicircle technology and evaluated their feasibility as a therapeutic tool in a skin allograft model. We engineered vectors to carry cassette sequences for tocilizumab [anti-soluble interleukin-6 receptor (sIL-6R) antibody] and/or etanercept [tumor necrosis factor receptor 2 (TNFR2)-Fc fusion protein], and then isolated minicircle vectors from the parent vectors. We verified the production of proteins from minicircles and their duration in HEK293T cells and mice. We also evaluated whether these proteins were expressed at levels sufficient to ameliorate skin allograft rejection in mice. Each minicircle transfected into cells was detectable for at least 30 days. In mice, the drugs were mainly expressed in the liver and were detectable for at least 10 days after a single injection. These drugs were also detected in the blood. Treatment of mice with minicircles prolonged skin allograft survival, which was accompanied by a reduction of the number of interferon-γ+ or interleukin-17+ lymphocytes and an induction of forkhead box P3 expression. These findings suggest that blocking of sIL-6R and/or TNF-α using minicircles encoding tocilizumab and/or etanercept was functionally active and relevant for preventing acute allograft rejection. Self-reproducing synthetic protein drugs produced using minicircle technology are potentially powerful tools for preventing acute rejection in transplantation.

  14. Allograft tissue irradiation and failure rate after anterior cruciate ligament reconstruction: A systematic review.

    Science.gov (United States)

    Dashe, Jesse; Parisien, Robert L; Cusano, Antonio; Curry, Emily J; Bedi, Asheesh; Li, Xinning

    2016-06-18

    To evaluate whether anterior cruciate ligament (ACL) allograft irradiation is effective for sterility without compromising graft integrity and increasing failure rate. A literature search was conducted using PubMed, Cochrane, and Google. The following search terms were used: "Gamma irradiation AND anterior cruciate ligament AND allograft" with a return of 30 items. Filters used included: English language, years 1990-2015. There were 6 hits that were not reviewed, as there were only abstracts available. Another 5 hits were discarded, as they did not pertain to the topic of interest. There were 9 more articles that were excluded: Three studies were performed on animals and 6 studies were meta-analyses. Therefore, a total of 10 articles were applicable to review. There is a delicate dosing crossover where gamma irradiation is both effective for sterility without catastrophically compromising the structural integrity of the graft. Of note, low dose irradiation is considered less than 2.0 Mrad, moderate dose is between 2.1-2.4 Mrad, and high dose is greater than or equal to 2.5 Mrad. Based upon the results of the literature search, the optimal threshold for sterilization was found to be sterilization at less than 2.2 Mrad of gamma irradiation with the important caveat of being performed at low temperatures. The graft selection process also must include thorough donor screening and testing as well as harvesting the tissue in a sterile fashion. Utilization of higher dose (≥ 2.5 Mrad) of irradiation causes greater allograft tissue laxity that results in greater graft failure rate clinically in patients after ACL reconstruction. Allograft ACL graft gamma irradiated with less than 2.2 Mrad appears to be a reasonable alternative to autograft for patients above 25 years of age.

  15. Polymorphisms in STAT4 increase the risk of acute renal allograft rejection in the Chinese population.

    Science.gov (United States)

    Yang, H; Zhou, Q; Chen, Z M; Chen, W Q; Wang, M M; Chen, J H

    2011-05-01

    Recently, the signal transducer and activator of transcription 4 (STAT4) gene have been associated with multiple autoimmune diseases. Taking into consideration that the different autoimmune diseases may share some common pathogenetic pathways, the aim of the present study was to evaluate the role of STAT4 rs7574865 polymorphism on acute allograft rejection. The present case-control study included 453 renal allograft recipients and 378 sex matched healthy controls. Genotyping was performed using a PCR based discrimination assay for the rs7574865 STAT4 SNP. No evidence of association was found between health controls and renal transplant recipients for the G/T or T/T genotype and wild type G/G. (p=0.431, two-tailed χ(2); OR=0.894, 95% CI=0.677-1.181). But among the transplant recipients, the G/T or T/T genotype was more common in transplant rejectors (acute allograft rejection) than nonrejectors who had mostly wild-type G/G genotype (p=0.003, two-tailed χ(2); OR=0.542, 95% CI=0.361-0.815). We also found a trend that the frequency of G/T or T/T genotype was also relatively more in the acute cellular mediated rejection than antibody mediated ones (p=0.049, two-tailed χ(2); OR=0.466, 95% CI=0.216-1.003). Thus, our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for acute renal allograft rejection in the Chinese population. Copyright © 2011. Published by Elsevier B.V.

  16. Evaluation of blood flow in Allograft Renal Arteries anastomosed with two different techniques

    International Nuclear Information System (INIS)

    Zomorrodi, A.; Bohluli, A.; Tarzamany, M.K.

    2008-01-01

    Renal artery stenosis in renal transplantation (TRAS) is an avoidable short or long term surgical complication. The etiology is multifactorial, but faulty anastomosis is a major factor. In our transplant center, we evaluated the incidence of TRAS with the use of two different suturing techniques of the anastomosis site between allograft renal and renal and iliac arteries in two groups of renal transplant recipients, group A: 14 patients (6 males and 8 females with age 16 to 59 and mean age of 38 years) in whom allograft arteries were anastomosed with a continuous suture technique and group B: 14 patients (7 males and 7 females with age 32 to 61 and mean age of 46.6 years) in whom the allograft arteries were anastomosed with a combined suture technique (continuous and uninterrupted. Post transplantation, the velocity of blood flow in the renal and iliac arteries at the site of anastomosis was measured by color Doppler ultrasound. The ultrasonographer was blinded to the surgical technique in both study groups. The ratio of the maximum velocity of blood at the site of anastomosis to that in the iliac artery of less than 2.5 was considered as non-significant stenosis, while a ratio of more than 2.5 was considered significant stenosis. In group A there were 9 cases of non-significant stenosis in comparison to 3 cases in group B, while there were no cases of significant stenosis in group A in comparison to 3 cases in group B; the difference was not statistically significant. We conclude that there was no difference in the compared surgical techniques of anastomosis in our study groups. This suggests that other factors such as gentle handling of tissue, enough spatula, margin reversion and comparable diameter of the anastomosed vessels may be more important in the prevention of renal allograft stenosis than the type of suture technique. (author)

  17. The cardiac patient during Ramadan and Hajj.

    Science.gov (United States)

    Chamsi-Pasha, Hassan; Ahmed, Waqar H; Al-Shaibi, Khaled F

    2014-10-01

    The holy month of Ramadan is one of the five pillars of Islam. During this month, fasting Muslims refrain from eating, drinking, smoking, and sex from dawn until sunset. Although the Quran exempts sick people from the duty of fasting, it is not uncommon for many heart disease patients to fast during Ramadan. Despite the fact that more than a billion Muslims worldwide fast during Ramadan, there is no clear consensus on its effects on cardiac disease. Some studies have shown that the effects of fasting on stable patients with cardiac disease are minimal and the majority of patients with stable cardiac illness can endure Ramadan fasting with no clinical deterioration. Fasting during Ramadan does not seem to increase hospitalizations for congestive heart failure. However, patients with decompensated heart failure or those requiring large doses of diuretics are strongly advised not to fast, particularly when Ramadan falls in summer. Patients with controlled hypertension can safely fast. However, patients with resistant hypertension should be advised not to fast until their blood pressure is reasonably controlled. Patients with recent myocardial infarction, unstable angina, recent cardiac intervention or cardiac surgery should avoid fasting. Physician advice should be individualized and patients are encouraged to seek medical advice before fasting in order to adjust their medications, if required. The performance of the Hajj pilgrimage is another pillar of Islam and is obligatory once in the lifetime for all adult Muslims who are in good health and can afford to undertake the journey. Hajj is a physically, mentally, emotionally, and spiritually demanding experience. Medical checkups one or two months before leaving for Hajj is warranted, especially for those with chronic illnesses such as cardiovascular disease. Patients with heart failure, uncontrolled hypertension, serious arrhythmias, unstable angina, recent myocardial infarction, or cardiac surgery should be

  18. Effects of low intensity pulsed ultrasound with and without increased cortical porosity on structural bone allograft incorporation

    Directory of Open Access Journals (Sweden)

    Ehrhart Nicole

    2008-05-01

    Full Text Available Abstract Background Though used for over a century, structural bone allografts suffer from a high rate of mechanical failure due to limited graft revitalization even after extended periods in vivo. Novel strategies that aim to improve graft incorporation are lacking but necessary to improve the long-term clinical outcome of patients receiving bone allografts. The current study evaluated the effect of low-intensity pulsed ultrasound (LIPUS, a potent exogenous biophysical stimulus used clinically to accelerate the course of fresh fracture healing, and longitudinal allograft perforations (LAP as non-invasive therapies to improve revitalization of intercalary allografts in a sheep model. Methods Fifteen skeletally-mature ewes were assigned to five experimental groups based on allograft type and treatment: +CTL, -CTL, LIPUS, LAP, LIPUS+LAP. The +CTL animals (n = 3 received a tibial ostectomy with immediate replacement of the resected autologous graft. The -CTL group (n = 3 received fresh frozen ovine tibial allografts. The +CTL and -CTL groups did not receive LAP or LIPUS treatments. The LIPUS treatment group (n = 3, following grafting with fresh frozen ovine tibial allografts, received ultrasound stimulation for 20 minutes/day, 5 days/week, for the duration of the healing period. The LAP treatment group (n = 3 received fresh frozen ovine allografts with 500 μm longitudinal perforations that extended 10 mm into the graft. The LIPUS+LAP treatment group (n = 3 received both LIPUS and LAP interventions. All animals were humanely euthanized four months following graft transplantation for biomechanical and histological analysis. Results After four months of healing, daily LIPUS stimulation of the host-allograft junctions, alone or in combination with LAP, resulted in 30% increases in reconstruction stiffness, paralleled by significant increases (p Conclusion The current study has demonstrated in a large animal model the potential of both LIPUS and LAP

  19. Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

    Directory of Open Access Journals (Sweden)

    Olivia Chen

    2015-01-01

    Full Text Available Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming.

  20. No prolongation of skin allograft survival by immunoproteasome inhibition in mice.

    Science.gov (United States)

    Mundt, Sarah; Basler, Michael; Sawitzki, Birgit; Groettrup, Marcus

    2017-08-01

    The immunoproteasome, a distinct class of proteasomes, which is inducible under inflammatory conditions and constitutively expressed in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. Moreover, inhibition of the immunoproteasome subunit LMP7 ameliorates clinical symptoms of autoimmune diseases in vivo and was shown to suppress the development of T helper cell (Th) 1 and Th17 cells and to promote regulatory T-cell (Treg) generation independently of its function in antigen processing. Since Th1 and Th17 cells are detrimental and Treg cells are critical for transplant acceptance, we investigated the influence of the LMP7-selective inhibitor ONX 0914 in a mixed lymphocyte reaction (MLR) in vitro as well as on allograft rejection in a MHC-disparate (C57BL/6 to BALB/c) and a multiple minor histocompatibility antigen (miHA)-disparate (B10.Br to C3H) model of skin transplantation in vivo. Although we observed reduced allo-specific IL-17 production of T cells in vitro, we found that selective inhibition of LMP7 had neither an influence on allograft survival in an MHC-mismatch model nor in a multiple minor mismatch skin transplantation model. We conclude that inhibition of the immunoproteasome is not effective in prolonging skin allograft survival in skin allotransplantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Concurrent Hepatic Artery and Portal Vein Thrombosis after Orthotopic Liver Transplantation with Preserved Allografts

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    Arshad Khan

    2014-01-01

    Full Text Available In contrast to early HAT, late HAT has an insidious clinical presentation. Nevertheless, biliary and vascular reconstructions in this late setting are unlikely to improve outcome. Patent portal flow makes an important contribution to the viability of liver in case of late HAT while the allograft reconstitutes intrahepatic arterial flow through neovascularization. Concurrent HAT with PVT without immediate graft necrosis is extremely rare, and allograft and patient survival are seemingly impossible without retransplantation. In fact, hepatopetal arterial and portal venous neovascularization are known albeit obscure phenomena that can preserve posttransplant hepatic function under the extenuating circumstances of complete interruption of blood flow to the graft. We describe two such cases that developed combined HAT and PVT more than six months after OLT with perfect preservation of graft function. The survival of allografts in our cases was due to extensive hepatopetal arterial and portal venous collateralization. Simultaneous HAT and PVT after OLT are rare events and almost uniformly fatal, if they occur early. Due to paucity of such cases, however, underlying mechanisms and etiology remain elusive, and despite radiological diagnosis of these complications, there is no way to predict these events in the wake of stable graft function.

  2. Allograft for maxillary sinus floor augmentation: a retrospective study of 90 cases.

    Science.gov (United States)

    Guerrero, Jaime S; Al-Jandan, Badr A

    2012-04-01

    The aim of this study is to demonstrate the clinical applicability and efficacy of an allograft for maxillary sinus augmentations in patients requiring placement of dental implants. Sixty consecutive patients underwent a total of 90 sinus augmentations. Twenty-nine were women and 31 men, with a mean age of 54 years. Twenty-six patients received a bilateral procedure and 34 unilateral. All cases were treated with the lateral wall technique. Allograft consisted of demineralized freeze-dried blocks in 6 cases, particulate in 82 cases, and a combination of both in 2 cases. In 30 patients, it was combined with platelet-rich plasma. A total of 84 implants were inserted. Bone samples of grafted areas were obtained in two patients for histological examination. Seventy-three implants were clinically successful at the reentry time. Eleven implants in seven patients were removed between 15 days and 6 months after their placement. Seven of these implants were replaced and received prostheses as well, for an overall postloading success rate of 95.2%. Follow-up for all patients after final restoration was between 12 and 96 months. Specimen's histological evaluation revealed bone formation and evidence of inflammatory infiltrate. Based on the findings of this study, it can be suggested that the use of the demineralized freeze-dried bone allograft from the Banco de Huesos y Tejidos Fundación Cosme y Damian for sinus augmentation is effective and constitutes a feasible therapeutic alternative for implant placement.

  3. Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Iga, C.; Lau, H.; Hardy, M.A.

    1985-01-01

    The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators

  4. Disinfection of human musculoskeletal allografts in tissue banking: a systematic review.

    Science.gov (United States)

    Mohr, J; Germain, M; Winters, M; Fraser, S; Duong, A; Garibaldi, A; Simunovic, N; Alsop, D; Dao, D; Bessemer, R; Ayeni, O R

    2016-12-01

    Musculoskeletal allografts are typically disinfected using antibiotics, irradiation or chemical methods but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of microorganism kill; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. A systematic review of three databases found 68 laboratory and clinical studies that analyzed the microbial bioburden or contamination rates of musculoskeletal allografts. The use of peracetic acid-ethanol or ionizing radiation was found to be most effective for disinfection of tissues. The use of irradiation is the most frequently published method for the terminal sterilization of musculoskeletal allografts; it is widely used and its efficacy is well documented in the literature. However, effective disinfection results were still observed using the BioCleanse™ Tissue Sterilization process, pulsatile lavage with antibiotics, ethylene oxide, and chlorhexidine. The variety of effective methods to reduce contamination rate or bioburden, in conjunction with limited high quality evidence provides little support for the recommendation of a single bioburden reduction method.

  5. Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?

    Science.gov (United States)

    Nguyen, Huynh; Morgan, David A F; Forwood, Mark R

    2007-01-01

    For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10(-6). The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks.

  6. New approaches to the prevention of organ allograft rejection and tolerance induction.

    Science.gov (United States)

    Bagley, Jessamyn; Tian, Chaorui; Iacomini, John

    2007-07-15

    The therapeutic use of organ allograft transplantation is dependent on the discovery and clinical application of immunologic strategies to blunt the immune response and prevent graft rejection. It was the discovery of powerful immunotherapeutics such as cyclosporine A and rapamycin that has allowed for the widespread use of organ transplantation to treat organ failure. However, despite the attainment of impressive survival rates 1 year after organ transplantation, a significant number of organ allografts are lost to immune-mediated chronic rejection. Furthermore, significant morbidity and mortality can be associated with the use of currently available immunosuppressive regimens. Thus, the development of novel approaches to prevent of organ allograft rejection remains extremely important. Here we discuss two promising and novel avenues of research. First, the discovery and characterization of naturally occurring immune inhibitory signals have led to recent research aimed at exploiting these pathways to induce peripheral tolerance to alloantigen. Furthermore, we discuss new approaches to the induction of donor-specific tolerance by induction of molecular chimerism and the transfer of alloantigen-expressing mature T cells.

  7. Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection.

    Science.gov (United States)

    Martelius, Timi; Salaspuro, Ville; Salmi, Marko; Krogerus, Leena; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

    2004-12-01

    Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units, respectively) compared to control (6.6 +/- 1.0) (P VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection.

  8. Culture methods of allograft musculoskeletal tissue samples in Australian bacteriology laboratories.

    Science.gov (United States)

    Varettas, Kerry

    2013-12-01

    Samples of allograft musculoskeletal tissue are cultured by bacteriology laboratories to determine the presence of bacteria and fungi. In Australia, this testing is performed by 6 TGA-licensed clinical bacteriology laboratories with samples received from 10 tissue banks. Culture methods of swab and tissue samples employ a combination of solid agar and/or broth media to enhance micro-organism growth and maximise recovery. All six Australian laboratories receive Amies transport swabs and, except for one laboratory, a corresponding biopsy sample for testing. Three of the 6 laboratories culture at least one allograft sample directly onto solid agar. Only one laboratory did not use a broth culture for any sample received. An international literature review found that a similar combination of musculoskeletal tissue samples were cultured onto solid agar and/or broth media. Although variations of allograft musculoskeletal tissue samples, culture media and methods are used in Australian and international bacteriology laboratories, validation studies and method evaluations have challenged and supported their use in recovering fungi and aerobic and anaerobic bacteria.

  9. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    International Nuclear Information System (INIS)

    Park, Charn Il; Han, Man Chung

    1981-01-01

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 ± 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 ± 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers

  10. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Charn Il; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1981-06-15

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 {+-} 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 {+-} 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers.

  11. Allograft Cellular Bone Matrix in Extreme Lateral Interbody Fusion: Preliminary Radiographic and Clinical Outcomes

    Directory of Open Access Journals (Sweden)

    Antoine G. Tohmeh

    2012-01-01

    Full Text Available Introduction. Extreme lateral interbody fusion (XLIF is a minimally disruptive alternative for anterior lumbar interbody fusion. Recently, synthetic and allograft materials have been increasingly used to eliminate donor-site pain and complications secondary to autogenous bone graft harvesting. The clinical use of allograft cellular bone graft has potential advantages over autograft by eliminating the need to harvest autograft while mimicking autograft's biologic function. The objective of this study was to examine 12-month radiographic and clinical outcomes in patients who underwent XLIF with Osteocel Plus, one such allograft cellular bone matrix. Methods. Forty (40 patients were treated at 61 levels with XLIF and Osteocel Plus and included in the analysis. Results. No complications were observed. From preoperative to 12-month postoperative followup, ODI improved 41%, LBP improved 55%, leg pain improved 43.3%, and QOL (SF-36 improved 56%. At 12 months, 92% reported being “very” or “somewhat” satisfied with their outcome and 86% being either “very” or “somewhat likely” to choose to undergo the procedure again. Complete fusion was observed in 90.2% (55/61 of XLIF levels. Conclusions. Complete interbody fusion with Osteocel Plus was shown in 90.2% of XLIF levels, with the remaining 9.8% being partially consolidated and progressing towards fusion at 12 months.

  12. Lung transplantation in the rat. III. Functional studies in iso- and allografts

    International Nuclear Information System (INIS)

    Marck, K.W.; Prop, J.; Wildevuur, C.R.

    1983-01-01

    Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research

  13. Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

    Science.gov (United States)

    Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

    2017-01-01

    We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

  14. Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

    Science.gov (United States)

    Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

    2017-01-01

    Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

  15. Characteristics of histocompatibility barriers in congenis strains of mice. III. Passive enhancement of skin allografts in x-irradiated hosts

    International Nuclear Information System (INIS)

    Cantrell, J.L.; Kaliss, N.; Hildemann, W.H.

    1975-01-01

    Passive immunological enhancement of skin allografts was investigated in three donor-host combinations of congenic mice disparate at non-H-2 loci. Serum against the graft donor was derived from mice that had received donor strain lymphoid cells as neonates, and thereby were rendered specifically tolerant of a skin allograft. We refer to this serum as ''allograft-tolerant'' serum. Each strain combination was chosen to provide only two non-H-2 histoincompatibilities present in the donor and absent in the host. The differences are categorized as immunogenetically strong, moderate, or weak, on the basis of skin allograft survival times. With passively administered allograft-tolerant serum, significantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal x-irradiation and allograft-tolerant serum significantly prolonged graft survival in both the moderate and weak combinations, with the largest effect present in the weakest disparity. A hyperimmune alloantiserum (produced in adults) directed against the graft donor prolonged allograft survival in the strongest disparity when given in combination with irradiation. In this combination, graft survival time was increased in hosts exposed to x-ray alone, but joint treatment with x-ray and the alloantiserum gave the largest increment. In contrast, combined treatment with the serum and an antithymocyte alloantiserum did not affect graft survival times. Treatment with both radiation and antithymocyte serum did not prolong graft survival beyond that in mice given only x-radiation. Immunological enhancement with central inhibition is assumed as the mechanism underlying prolonged graft survival, and it is suggested that a population of thymus-derived killer cells, sensitive to x-irradiation, is required for normal graft rejection. (U.S.)

  16. Cross-correlative 3D micro-structural investigation of human bone processed into bone allografts

    International Nuclear Information System (INIS)

    Singh, Atul Kumar; Gajiwala, Astrid Lobo; Rai, Ratan Kumar; Khan, Mohd Parvez; Singh, Chandan; Barbhuyan, Tarun; Vijayalakshmi, S.; Chattopadhyay, Naibedya; Sinha, Neeraj; Kumar, Ashutosh; Bellare, Jayesh R.

    2016-01-01

    Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS® (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all

  17. Cross-correlative 3D micro-structural investigation of human bone processed into bone allografts

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Atul Kumar [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Gajiwala, Astrid Lobo [Tissue Bank, Tata Memorial Hospital, Parel, Mumbai 400012 (India); Rai, Ratan Kumar [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Khan, Mohd Parvez [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Singh, Chandan [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Barbhuyan, Tarun [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Vijayalakshmi, S. [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Chattopadhyay, Naibedya [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Sinha, Neeraj, E-mail: neerajcbmr@gmail.com [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Kumar, Ashutosh, E-mail: ashutoshk@iitb.ac.in [Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076 (India); Bellare, Jayesh R., E-mail: jb@iitb.ac.in [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076 (India)

    2016-05-01

    Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS® (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all

  18. The donor management algorithm in transplantation of a composite facial tissue allograft.. First experience in Russia

    Directory of Open Access Journals (Sweden)

    V. V. Uyba

    2016-01-01

    Full Text Available In the period from 2005 to December 2015, 37 transplantations of vascularized composite facial tissue allografts (VCAs were performed in the world. A vascularized composite tissue allotransplantation has been recognized as a solid organ transplantation rather than a special kind of tissue transplantation. The recent classification of composite tissue allografts into the category of donor organs gave rise to a number of organizational, ethical, legal, technical, and economic problems. In May 2015, the first successful transplantation of a composite facial tissue allograft was performed in Russia. The article describes our experience of multiple team interactions at donor management stage when involved in the identification, conditioning, harvesting, and delivering donor organs to various hospitals. A man, aged 51 years old, diagnosed with traumatic brain injury became a donor after the diagnosis of brain deathhad been made, his death had been ascertained, and the requested consent for organ donation had been obtained from relatives. At donor management stage, a tracheostomy was performed and a posthumous facial mask was molded. The "face first, concurrent completion" algorithm was chosen for organ harvesting and facial VCA procurement; meanwhile, the facial allograft was procured as the "full face" category. The total surgery duration from the incision to completing the procurement (including that of solid organs made 8 hours 20 minutes. Immediately after the procurement, the facial VCA complex was sent to the St. Petersburg clinic by medical aircraft transportation, and was there transplanted 9 hours later. Donor kidneys were transported to Moscow bycivil aviation and transplanted 17 and 20 hours later. The authors believe that this clinical case report demonstrates the feasibility and safety of multiple harvesting of solid organs and a vascularized composite facial tissue allograft. However, this kind of surgery requires an essential

  19. Cardiac radiology: centenary review.

    Science.gov (United States)

    de Roos, Albert; Higgins, Charles B

    2014-11-01

    During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

  20. Invasive hemodynamic monitoring in the postoperative period of cardiac surgery

    Directory of Open Access Journals (Sweden)

    Desanka Dragosavac

    1999-08-01

    Full Text Available OBJETIVE: To assess the hemodynamic profile of cardiac surgery patients with circulatory instability in the early postoperative period (POP. METHODS: Over a two-year period, 306 patients underwent cardiac surgery. Thirty had hemodynamic instability in the early POP and were monitored with the Swan-Ganz catheter. The following parameters were evaluated: cardiac index (CI, systemic and pulmonary vascular resistance, pulmonary shunt, central venous pressure (CVP, pulmonary capillary wedge pressure (PCWP, oxygen delivery and consumption, use of vasoactive drugs and of circulatory support. RESULTS: Twenty patients had low cardiac index (CI, and 10 had normal or high CI. Systemic vascular resistance was decreased in 11 patients. There was no correlation between oxygen delivery (DO2 and consumption (VO2, p=0.42, and no correlation between CVP and PCWP, p=0.065. Pulmonary vascular resistance was decreased in 15 patients and the pulmonary shunt was increased in 19. Two patients with CI < 2L/min/m² received circulatory support. CONCLUSION: Patients in the POP of cardiac surgery frequently have a mixed shock due to the systemic inflammatory response syndrome (SIRS. Therefore, invasive hemodynamic monitoring is useful in handling blood volume, choice of vasoactive drugs, and indication for circulatory support.

  1. Isolated Cardiac Hydatid Cyst

    International Nuclear Information System (INIS)

    Shakil, U.; Rehman, A. U.; Shahid, R.

    2015-01-01

    Hydatid cyst disease is common in our part of the world. Cardiac hydatid cyst is its rare manifestation. We report this case of 48-year male having isolated cardiac hydatid cyst, incidentally found on computed tomography. This patient presented in medical OPD of Combined Military Hospital, Lahore with one month history of mild retrosternal discomfort. His general physical and systemic examinations as well as ECG were unremarkable. Chest X-ray showed an enlarged cardiac shadow with mildly irregular left heart border. Contrast enhanced CT scan of the chest showed a large well defined multiloculated non-enhancing cystic lesion with multiple daughter cysts involving wall of left ventricle and overlying pericardium. Serology for echinococcus confirmed the diagnosis of hydatid cyst. Patient was offered the surgical treatment but he opted for medical treatment only. Albendezol was prescribed. His follow-up echocardiography after one month showed no significant decrease in size of the cyst. (author)

  2. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

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

    International Nuclear Information System (INIS)

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J.

    1990-01-01

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

  4. Serum level of soluble fibrinogen-like protein 2 in renal allograft recipients with acute rejection: a preliminary study.

    Science.gov (United States)

    Zhao, Z; Yang, C; Tang, Q; Zhao, T; Jia, Y; Ma, Z; Rong, R; Xu, M; Zhu, T

    2012-12-01

    Soluble fibrinogen-like protein 2 (sfgl2), which is mainly secreted by T cells, is a novel effector of regulatory T cells with immunosuppressive functions. The aim of this study was to investigate serum levels of sfgl2 among renal allograft recipients. From November 2010 to August 2011 we retrospectively divided 47 renal allograft recipients into an acute rejection (n = 19) versus a stable group (n = 28) according to allograft biopsy results, using the Banff 2007 classification. The acute rejection group was subdivided into grade I (n = 8) versus grade II T-cell-mediated (n = 6) or antibody-mediated rejection episodes (n = 5). Peripheral blood samples were collected at the time of biopsy. Fourteen healthy volunteers were included as normal group controls. Serum levels of sfgl2 were analyzed by enzyme-linked immunosorbent assay. Serum levels of sfgl2 were increased among renal allograft recipients suffering from biopsy-proven acute rejection episodes (61.91 ± 45.68 ng/mL), versus those with stable allografts (38.59 ± 19.92 ng/mL, P rejection episodes (41.71 ± 16.44 ng/mL, P rejection (34.10 ± 9.26 ng/mL, P rejection episodes to an extent dependent upon the pathological type and severity of the response. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  5. Endoscopic versus transcranial procurement of allograft tympano-ossicular systems: a prospective double-blind randomized controlled audit.

    Science.gov (United States)

    Caremans, Jeroen; Hamans, Evert; Muylle, Ludo; Van de Heyning, Paul; Van Rompaey, Vincent

    2016-06-01

    Allograft tympano-ossicular systems (ATOS) have proven their use over many decades in tympanoplasty and reconstruction after resection of cholesteatoma. The transcranial bone plug technique has been used in the past 50 years to procure en bloc ATOS (tympanic membrane with malleus, incus and stapes attached). Recently, our group reported the feasibility of the endoscopic procurement technique. The aim of this study was to assess whether clinical outcome is equivalent in ATOS acquired by using the endoscopic procurement technique compared to ATOS acquired by using the transcranial technique. A double-blind randomized controlled audit was performed in a tertiary referral center in patients that underwent allograft tympanoplasty because of chronic otitis media with and without cholesteatoma. Allograft epithelialisation was evaluated at the short-term postoperative visit by microscopic examination. Failures were reported if reperforation was observed. Fifty patients underwent allograft tympanoplasty: 34 received endoscopically procured ATOS and 16 received transcranially procured ATOS. One failed case was observed, in the endoscopic procurement group. We did not observe a statistically significant difference between the two groups in failure rate. This study demonstrates equivalence of the clinical outcome of allograft tympanoplasty using either endoscopic or transcranial procured ATOS and therefore indicates that the endoscopic technique can be considered the new standard procurement technique. Especially because the endoscopic procurement technique has several advantages compared to the former transcranial procurement technique: it avoids risk of prion transmission and it is faster while lacking any noticeable incision.

  6. Effects of particle size and porosity on in vivo remodeling of settable allograft bone/polymer composites.

    Science.gov (United States)

    Prieto, Edna M; Talley, Anne D; Gould, Nicholas R; Zienkiewicz, Katarzyna J; Drapeau, Susan J; Kalpakci, Kerem N; Guelcher, Scott A

    2015-11-01

    Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity and high viscosity grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105-500 μm) allograft particles healed at 12 weeks postimplantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. © 2015 Wiley Periodicals, Inc.

  7. [A long-term follow-up of treatment of adult unicameral bone cysts with allograft of lyophilized cancellous bone].

    Science.gov (United States)

    Zhang, Yonggang; Wang, Yan; Cheng, Jiying

    2005-08-01

    To investigate the long-term clinical results of treatment of adult unicameral bone cyst with cancellous allograft. From 1993 to 1998, 15 patients with unicameral bone cyst were treated by allograft with lyophilized cancellous bone. Among 15 patients, there were 5 males and 10 females, aging 19-41 years with an average of 27 years. The average follow-up time was 7.5 years (6-11 years). The X-ray films were taken and the CT scanning were carried out. The X-ray films showed that the allograft particles became vague 2-3 months after operation, that the allograft particles fused and began to form new bone and the bone density increased 5 months after operation, and that new bone formation completed after 7 months of operation. At the end of follow-up, remodelling in new bone occurred. Recurrence was not found in all patients. The symptom of pain disappeared or relieved obviously. Allograft of lyophilized cancellous bone is an effective treatment for adult unicameral bone cysts.

  8. New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection

    International Nuclear Information System (INIS)

    Chen, Luci M.; Godinez, Juan; Thisted, Ronald A.; Woodle, E. Steve; Thistlewaite, J. Richard; Powers, Claire; Haraf, Daniel

    2000-01-01

    Purpose: To evaluate the role of radiation therapy for acute refractory renal rejection after failure of medical intervention, and to identify risk factors that influence graft survival following radiation therapy. Methods: Between June 1989 and December 1995, 53 renal transplant recipients (34 men and 19 women) were treated with localized radiation therapy for acute renal allograft rejection. Graft rejection was defined as an increase in serum creatinine with histologic evidence of rejection on renal biopsy. Ninety-one percent were cadaveric transplant recipients. The majority of patients who experienced acute graft rejection initially received corticosteroid therapy, except for 25% who were referred for radiation therapy and steroids for the first rejection. In more recent years, patients with moderate or severe steroid-resistant or recurrent rejection received OKT3, a polyclonal antilymphocyte antibody (ATGAM), tacrolimus (FK506), or mycophenolate mofetil (MMF). Patients who failed to respond to medical treatment were then referred for radiation therapy. Ultrasound was performed for kidney localization. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, delivered AP or AP/PA. Results: The overall actuarial graft survival from the initiation of RT was 83% at 1 month, 60% at 1 year, and 36% at 5 years. The median follow-up from the date of transplant to the last follow-up was 22 months. The median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow-up was 10 months. Variables evaluated were as follows: human leukocyte antigen matching on HLA-A, HLA-B, and HLA-DR, the transplant panel-reactive antibodies (PRA) at transplantation, number of acute rejection episodes, interval from the date of the transplant to the first rejection, serum creatinine levels at the time of the first radiation treatment, number of transplants, and

  9. Quantitative cardiac computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Thelen, M.; Dueber, C.; Wolff, P.; Erbel, R.; Hoffmann, T.

    1985-06-01

    The scope and limitations of quantitative cardiac CT have been evaluated in a series of experimental and clinical studies. The left ventricular muscle mass was estimated by computed tomography in 19 dogs (using volumetric methods, measurements in two axes and planes and reference volume). There was good correlation with anatomical findings. The enddiastolic volume of the left ventricle was estimated in 22 patients with cardiomyopathies; using angiography as a reference, CT led to systematic under-estimation. It is also shown that ECG-triggered magnetic resonance tomography results in improved visualisation and may be expected to improve measurements of cardiac morphology.

  10. Cardiac output measurement

    Directory of Open Access Journals (Sweden)

    Andreja Möller Petrun

    2014-02-01

    Full Text Available In recent years, developments in the measuring of cardiac output and other haemodynamic variables are focused on the so-called minimally invasive methods. The aim of these methods is to simplify the management of high-risk and haemodynamically unstable patients. Due to the need of invasive approach and the possibility of serious complications the use of pulmonary artery catheter has decreased. This article describes the methods for measuring cardiac output, which are based on volume measurement (Fick method, indicator dilution method, pulse wave analysis, Doppler effect, and electrical bioimpedance.

  11. Factors influencing the cardiac MIBG accumulation

    International Nuclear Information System (INIS)

    Takatsu, Hisato; Fujiwara, Hisayoshi

    1997-01-01

    Following factors possibly influencing the cardiac MIBG accumulation were examined mainly in mice. 1. The specific activity of the MIBG (meta-iodo-benzyl guanidine) on the neuronal and non-neuronal fractions. 2. Motor restriction stress on MIBG accumulation and washout. 3. Loading and restriction of sodium chloride on the accumulation and effect of suppression of renin-angiotensin system. 4. Examinations in Dahl rats. 125I- or 131I-MIBG was intravenously administered to mice at 74 kBq. At 30 min or 4 hr after administration, mice were sacrificed and their left ventricles were dissected out for measurement of radioactivity in a liquid scintillation counter. Salt-sensitive and -resistant Dahl rats were given with 37 MBq of 123I-MIBG and cardiac radioactivity was measured externally for calculation of washout. Factors examined were found highly correlated with the accumulation of MIBG and measurement of its washout was considered useful for evaluating sympathetic activity. (K.H.)

  12. A tale of two cases of pulmonary arteriovenous malformation: How they fared after cardiac transplantation.

    Science.gov (United States)

    Wisotzkey, Bethany L; Magyar, Dari L; Jones, Thomas K; Boucek, Robert J; Permut, Lester C; Kemna, Mariska S; Law, Yuk M

    2018-02-01

    In single ventricle patients, aortopulmonary collaterals (APCs) and pulmonary arteriovenous malformations (PAVMs) following superior cavopulmonary shunt (CPS) can complicate orthotopic heart transplant (OHT) by cyanosis and hemoptysis. Although PAVMs can regress with the restoration of hepatic venous flow to the pulmonary circulation, the effects of hypoxemia on the "unconditioned" allograft are not known. Two patients with significant PAVMs after CPS were cyanotic following OHT. One patient with predominantly unilateral left PAVMs had arterial saturation levels less than 70% despite pulmonary vasodilators and ventilation. A custom flow restrictor-covered stent was deployed in the pulmonary artery of the affected side, redirecting the blood flow to the contralateral lung, immediately improving cyanosis. When the PAVMs regressed, the flow restrictor stent was dilated to eliminate the constriction. The second patient with PAVMs had cyanosis and severe hemoptysis from APCs post-OHT. The APCs required an extensive coil embolization, while the cyanosis responded to oxygen and pulmonary vasodilators. Both recipients did well with gradual resolution of PAVMs within 8 months. Despite cyanosis from right-to-left intrapulmonary shunting, allograft function recovered. Novel transcatheter interventions can play a role in patients with significant APCs or PAVM following cardiac transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    International Nuclear Information System (INIS)

    Pennock, J.L.; Reitz, B.A.; Beiber, C.P.; A